Julie Parsonnet

All Publications

• A modified Michaelis-Menten equation estimates growth from birth to 3 years in healthy babies in the USA. BMC medical research methodology Walters, W. A., Ley, C., Hastie, T., Ley, R. E., Parsonnet, J. 2024; 24 (1): 27

  Abstract

  BACKGROUND: Standard pediatric growth curves cannot be used to impute missing height or weight measurements in individual children. The Michaelis-Menten equation, used for characterizing substrate-enzyme saturation curves, has been shown to model growth in many organisms including nonhuman vertebrates. We investigated whether this equation could be used to interpolate missing growth data in children in the first three years of life and compared this interpolation to several common interpolation methods and pediatric growth models.METHODS: We developed a modified Michaelis-Menten equation and compared expected to actual growth, first in a local birth cohort (N=97) then in a large, outpatient, pediatric sample (N=14,695).RESULTS: The modified Michaelis-Menten equation showed excellent fit for both infant weight (median RMSE: boys: 0.22kg [IQR:0.19; 90%<0.43]; girls: 0.20kg [IQR:0.17; 90%<0.39]) and height (median RMSE: boys: 0.93cm [IQR:0.53; 90%<1.0]; girls: 0.91cm [IQR:0.50;90%<1.0]). Growth data were modeled accurately with as few as four values from routine well-baby visits in year 1 and seven values in years 1-3; birth weight or length was essential for best fit. Interpolation with this equation had comparable (for weight) or lower (for height) mean RMSE compared to the best performing alternative models.CONCLUSIONS: A modified Michaelis-Menten equation accurately describes growth in healthy babies aged 0-36months, allowing interpolation of missing weight and height values in individual longitudinal measurement series. The growth pattern in healthy babies in resource-rich environments mirrors an enzymatic saturation curve.

  View details for DOI 10.1186/s12874-024-02145-1

  View details for PubMedID 38302887

• Defining Usual Oral Temperature Ranges in Outpatients Using an Unsupervised Learning Algorithm. JAMA internal medicine Ley, C., Heath, F., Hastie, T., Gao, Z., Protsiv, M., Parsonnet, J. 2023

  Abstract

  Although oral temperature is commonly assessed in medical examinations, the range of usual or "normal" temperature is poorly defined.To determine normal oral temperature ranges by age, sex, height, weight, and time of day.This cross-sectional study used clinical visit information from the divisions of Internal Medicine and Family Medicine in a single large medical care system. All adult outpatient encounters that included temperature measurements from April 28, 2008, through June 4, 2017, were eligible for inclusion. The LIMIT (Laboratory Information Mining for Individualized Thresholds) filtering algorithm was applied to iteratively remove encounters with primary diagnoses overrepresented in the tails of the temperature distribution, leaving only those diagnoses unrelated to temperature. Mixed-effects modeling was applied to the remaining temperature measurements to identify independent factors associated with normal oral temperature and to generate individualized normal temperature ranges. Data were analyzed from July 5, 2017, to June 23, 2023.Primary diagnoses and medications, age, sex, height, weight, time of day, and month, abstracted from each outpatient encounter.Normal temperature ranges by age, sex, height, weight, and time of day.Of 618 306 patient encounters, 35.92% were removed by LIMIT because they included diagnoses or medications that fell disproportionately in the tails of the temperature distribution. The encounters removed due to overrepresentation in the upper tail were primarily linked to infectious diseases (76.81% of all removed encounters); type 2 diabetes was the only diagnosis removed for overrepresentation in the lower tail (15.71% of all removed encounters). The 396 195 encounters included in the analysis set consisted of 126 705 patients (57.35% women; mean [SD] age, 52.7 [15.9] years). Prior to running LIMIT, the mean (SD) overall oral temperature was 36.71 °C (0.43 °C); following LIMIT, the mean (SD) temperature was 36.64 °C (0.35 °C). Using mixed-effects modeling, age, sex, height, weight, and time of day accounted for 6.86% (overall) and up to 25.52% (per patient) of the observed variability in temperature. Mean normal oral temperature did not reach 37 °C for any subgroup; the upper 99th percentile ranged from 36.81 °C (a tall man with underweight aged 80 years at 8:00 am) to 37.88 °C (a short woman with obesity aged 20 years at 2:00 pm).The findings of this cross-sectional study suggest that normal oral temperature varies in an expected manner based on sex, age, height, weight, and time of day, allowing individualized normal temperature ranges to be established. The clinical significance of a value outside of the usual range is an area for future study.

  View details for DOI 10.1001/jamainternmed.2023.4291

  View details for PubMedID 37669046

• Use of Wastewater Metrics to Track COVID-19 in the US. JAMA network open Varkila, M. R., Montez-Rath, M. E., Salomon, J. A., Yu, X., Block, G. A., Owens, D. K., Chertow, G. M., Parsonnet, J., Anand, S. 2023; 6 (7): e2325591

  Abstract

  Importance: Widespread use of at-home COVID-19 tests hampers determination of community COVID-19 incidence.Objective: To examine the association of county-level wastewater metrics with high case and hospitalization rates nationwide both before and after widespread use of at-home tests.Design, Setting, and Participants: This observational cohort study with a time series analysis was conducted from January to September 2022 in 268 US counties in 22 states participating in the US Centers for Disease Control and Prevention's National Wastewater Surveillance System. Participants included the populations of those US counties.Exposures: County level of circulating SARS-CoV-2 as determined by metrics based on viral wastewater concentration relative to the county maximum (ie, wastewater percentile) and 15-day percentage change in SARS-CoV-2 (ie, percentage change).Main Outcomes and Measures: High county incidence of COVID-19 as evidenced by dichotomized reported cases (current cases ≥200 per 100 000 population) and hospitalization (≥10 per 100 000 population lagged by 2 weeks) rates, stratified by calendar quarter.Results: In the first quarter of 2022, use of the wastewater percentile detected high reported case (area under the curve [AUC], 0.95; 95% CI, 0.94-0.96) and hospitalization (AUC, 0.86; 95% CI, 0.84-0.88) rates. The percentage change metric performed poorly, with AUCs ranging from 0.51 (95% CI, 0.50-0.53) to 0.57 (95% CI, 0.55-0.59) for reported new cases, and from 0.50 (95% CI, 0.48-0.52) to 0.55 (95% CI, 0.53-0.57) for hospitalizations across the first 3 quarters of 2022. The Youden index for detecting high case rates was wastewater percentile of 51% (sensitivity, 0.82; 95% CI, 0.80-0.84; specificity, 0.93; 95% CI, 0.92-0.95). A model inclusive of both metrics performed no better than using wastewater percentile alone. The performance of wastewater percentile declined over time for cases in the second quarter (AUC, 0.84; 95% CI, 0.82-0.86) and third quarter (AUC, 0.72; 95% CI, 0.70-0.75) of 2022.Conclusions and Relevance: In this study, nationwide, county wastewater levels relative to the county maximum were associated with high COVID-19 case and hospitalization rates in the first quarter of 2022, but there was increasing dissociation between wastewater and clinical metrics in subsequent quarters, which may reflect increasing underreporting of cases, reduced testing, and possibly lower virulence of infection due to vaccines and treatments. This study offers a strategy to operationalize county wastewater percentile to improve the accurate assessment of community SARS-CoV-2 infection prevalence when reliability of conventional surveillance data is declining.

  View details for DOI 10.1001/jamanetworkopen.2023.25591

  View details for PubMedID 37494040

• Longitudinal comparison of the developing gut virome in infants and their mothers. Cell host & microbe Walters, W. A., Granados, A. C., Ley, C., Federman, S., Stryke, D., Santos, Y., Haggerty, T., Sotomayor-Gonzalez, A., Servellita, V., Ley, R. E., Parsonnet, J., Chiu, C. Y. 2023; 31 (2): 187

  Abstract

  The human gut virome and its early life development are poorly understood. Prior studies have captured single-point assessments with the evolution of the infant virome remaining largely unexplored. We performed viral metagenomic sequencing on stool samples collected longitudinally from a cohort of 53 infants from age 2weeks to 3 years (80.7 billion reads), and from their mothers (9.8 billion reads) to examine and compare viromes. The asymptomatic infant virome consisted of bacteriophages, nonhuman dietary/environmental viruses, and human-host viruses, predominantly picornaviruses. In contrast, human-host viruses were largely absent from the maternal virome. Previously undescribed, sequence-divergent vertebrate viruses were detected in the maternal but not infant virome. As infants aged, the phage component evolved to resemble the maternal virome, but by age 3, the human-host component remained dissimilar from the maternal virome. Thus, early life virome development is determined predominantly by dietary, infectious, and environmental factors rather than direct maternal acquisition.

  View details for DOI 10.1016/j.chom.2023.01.003

  View details for PubMedID 36758519

• SARS-CoV-2 Vaccine Antibody Response and Breakthrough Infection in Patients Receiving Dialysis. Annals of internal medicine Anand, S., Montez-Rath, M. E., Han, J., Garcia, P., Cadden, L., Hunsader, P., Morgan, C., Kerschmann, R., Beyer, P., Dittrich, M., Block, G. A., Chertow, G. M., Parsonnet, J. 1800

  Abstract

  BACKGROUND: Whether breakthrough SARS-CoV-2 infections after vaccination are related to the level of postvaccine circulating antibody is unclear.OBJECTIVE: To determine longitudinal antibody-based response and risk for breakthrough infection after SARS-CoV-2 vaccination.DESIGN: Prospective study.SETTING: Nationwide sample from dialysis facilities.PATIENTS: 4791 patients receiving dialysis.MEASUREMENTS: Remainder plasma from a laboratory processing routine monthly tests was used to measure qualitative and semiquantitative antibodies to the receptor-binding domain (RBD) of SARS-CoV-2. To evaluate whether peak or prebreakthrough RBD values were associated with breakthrough infection, a nested case-control analysis matched each breakthrough case patient to 5 control patients by age, sex, and vaccination month and adjusted for diabetes status and region of residence.RESULTS: Of the 4791 patients followed with monthly RBD assays, 2563 were vaccinated as of 14 September 2021. Among the vaccinated patients, the estimated proportion with an undetectable RBD response increased from 6.6% (95% CI, 5.5% to 7.8%) 14 to 30 days after vaccination to 20.2% (CI, 17.0% to 23.3%) 5 to 6 months after vaccination. Estimated median index values decreased from 91.9 (CI, 78.6 to 105.2) 14 to 30 days after vaccination to 8.4 (CI, 7.6 to 9.3) 5 to 6 months after vaccination. Breakthrough infections occurred in 56 patients, with samples collected a median of 21 days before breakthrough infection. Compared with prebreakthrough index RBD values of 23 or higher (equivalent to ≥506 binding antibody units per milliliter), prebreakthrough RBD values less than 10 and values from 10 to less than 23 were associated with higher odds for breakthrough infection (rate ratios, 11.6 [CI, 3.4 to 39.5] and 6.0 [CI, 1.5 to 23.6], respectively).LIMITATIONS: Single measure of vaccine response; ascertainment of COVID-19 diagnosis from electronic health records.CONCLUSION: The antibody response to SARS-CoV-2 vaccination wanes rapidly in persons receiving dialysis. In this population, the circulating antibody response is associated with risk for breakthrough infection.PRIMARY FUNDING SOURCE: Ascend Clinical Laboratory.

  View details for DOI 10.7326/M21-4176

  View details for PubMedID 34904856

• Estimated SARS-CoV-2 Seroprevalence in US Patients Receiving Dialysis 1 Year After the Beginning of the COVID-19 Pandemic. JAMA network open Anand, S., Montez-Rath, M., Han, J., Cadden, L., Hunsader, P., Kerschmann, R., Beyer, P., Boyd, S. D., Garcia, P., Dittrich, M., Block, G. A., Parsonnet, J., Chertow, G. M. 2021; 4 (7): e2116572

  Abstract

  Importance: Seroprevalence studies complement data on detected cases and attributed deaths in assessing the cumulative spread of the SARS-CoV-2 virus.Objective: To estimate seroprevalence of SARS-CoV-2 antibodies in patients receiving dialysis and adults in the US in January 2021 before the widespread introduction of COVID-19 vaccines.Design, Setting, and Participants: This cross-sectional study used data from the third largest US dialysis organization (US Renal Care), which has facilities located nationwide, to estimate SARS-CoV-2 seroprevalence among US patients receiving dialysis. Remainder plasma (ie, plasma that would have otherwise been discarded) of all patients receiving dialysis at US Renal Care facilities from January 1 to 31, 2021, was tested for SARS-CoV-2 antibodies. Patients were excluded if they had a documented dose of SARS-CoV-2 vaccination or if a residence zip code was missing from electronic medical records. Crude seroprevalence estimates from this sample (January 2021) were standardized to the US adult population using the 2018 American Community Survey 1-year estimates and stratified by age group, sex, self-reported race/ethnicity, neighborhood race/ethnicity composition, neighborhood income level, and urban or rural status. These data and case detection rates were then compared with data from a July 2020 subsample of patients who received dialysis at the same facilities.Exposures: Age, sex, race/ethnicity, and region of residence as well as neighborhood race/ethnicity composition, poverty, population density, and urban or rural status.Main Outcomes and Measures: The spike protein receptor-binding domain total antibody assay (Siemens Healthineers; manufacturer-reported sensitivity of 100% and specificity of 99.8%) was used to estimate crude SARS-CoV-2 seroprevalence in the unweighted sample, and then the estimated seroprevalence rates for the US dialysis and adult populations were calculated, adjusting for age, sex, and region.Results: A total of 21 464 patients (mean [SD] age, 63.1 [14.2] years; 12 265 men [57%]) were included in the unweighted sample from January 2021. The patients were disproportionately older (aged 65-79 years, 7847 [37%]; aged ≥80 years, 2668 [12%]) and members of racial/ethnic minority groups (Hispanic patients, 2945 [18%]; non-Hispanic Black patients, 4875 [29%]). Seroprevalence of SARS-CoV-2 antibodies was 18.9% (95% CI, 18.3%-19.5%) in the sample, with a seroprevalence of 18.7% (95% CI, 18.1%-19.2%) standardized to the US dialysis population, and 21.3% (95% CI, 20.3%-22.3%) standardized to the US adult population. In the unweighted sample, younger persons (aged 18-44 years, 25.9%; 95% CI, 24.1%-27.8%), those who self-identified as Hispanic or living in Hispanic neighborhoods (25.1%; 95% CI, 23.6%-26.4%), and those living in the lowest-income neighborhoods (24.8%; 95% CI, 23.2%-26.5%) were among the subgroups with the highest seroprevalence. Little variability was observed in seroprevalence by geographic region, population density, and urban or rural status in the January 2021 sample (largest regional difference, 1.2 [95% CI, 1.1-1.3] higher odds of seroprevalence in residents of the Northeast vs West).Conclusions and Relevance: In this cross-sectional study of patients receiving dialysis in the US, fewer than 1 in 4 patients had evidence of SARS-CoV-2 antibodies 1 year after the first case of SARS-CoV-2 infection was detected in the US. Results standardized to the US population indicate similar prevalence of antibodies among US adults. Vaccine introduction to younger individuals, those living in neighborhoods with a large population of racial/ethnic minority residents, and those living in low-income neighborhoods may be critical to disrupting the spread of infection.

  View details for DOI 10.1001/jamanetworkopen.2021.16572

  View details for PubMedID 34251441

• Post-vaccination SARS-CoV-2 infections and incidence of presumptive B.1.427/B.1.429 variant among healthcare personnel at a northern California academic medical center. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America Jacobson, K. B., Pinsky, B. A., Montez Rath, M. E., Wang, H., Miller, J. A., Skhiri, M., Shepard, J., Mathew, R., Lee, G., Bohman, B., Parsonnet, J., Holubar, M. 2021

  Abstract

  BACKGROUND: Although mRNA-based SARS-CoV-2 vaccines report ≥90% efficacy, breakthrough infections occur. Little is known about the effectiveness of these vaccines against SARS-CoV-2 variants, including the highly-prevalent B.1.427/B.1.429 variant in California..METHODS: In this quality improvement project, we collected demographic and clinical information from post-vaccine SARS-CoV-2 cases (PVSCs), defined as health care personnel (HCP) with positive SARS-CoV-2 NAAT after receiving ≥1 vaccine dose. Available specimens were tested for L452R, N501Y and E484K mutations by RT-PCR. Mutation prevalence was compared among unvaccinated, early post-vaccinated (<=14 days after dose 1), partially vaccinated (positive test >14 days after dose 1 and ≤14 days after dose 2) and fully vaccinated (>14 days after dose 2) PVSCs.RESULTS: From December 2020-April 2021, >=23,090 HCPS received at least1 dose of an mRNA-based SARS-CoV-2 vaccine, and 660 HCP cases of SARS-CoV-2 occurred of which 189 were PVSCs. Among the PVSCs, 114 (60.3%), 49 (25.9%) and 26 (13.8%) were early post-vaccination, partially vaccinated, and fully vaccinated, respectively. Of 261 available samples from vaccinated and unvaccinated HCP, 103 (39.5%), including 42 PVSCs (36.5%), had L452R mutation presumed to be B.1.427/B.1.429,. When adjusted for community prevalence of B.1.427/B.1.429, PVSCs did not have significantly elevated risk for infection with B.1.427/B.1.429 compared with unvaccinated HCP.CONCLUSIONS: Most PVSCs occurred prior to expected onset of full, vaccine-derived immunity. Presumptive B.1.427/B.1.429 was not more prevalent in post-vaccine cases than in unvaccinated SARS-CoV-2 HCP. Continued infection control measures, particularly ≤14 days post-vaccination, and continued variant surveillance in PVSCs is imperative to control future SARS-CoV-2 surges.

  View details for DOI 10.1093/cid/ciab554

  View details for PubMedID 34137815

• Serial SARS-CoV-2 Receptor-Binding Domain Antibody Responses in Patients Receiving Dialysis. Annals of internal medicine Anand, S., Montez-Rath, M. E., Han, J., Garcia, P., Cadden, L., Hunsader, P., Kerschmann, R., Beyer, P., Boyd, S. D., Chertow, G. M., Parsonnet, J. 2021

  Abstract

  BACKGROUND: Assessing the evolution of SARS-CoV-2 immune response among patients receiving dialysis can define its durability in a highly clinically relevant context because patients receiving dialysis share the characteristics of persons most susceptible to SARS-CoV-2 infection.OBJECTIVE: To evaluate the persistence of SARS-CoV-2 receptor-binding domain (RBD) IgG in seroprevalent patients receiving dialysis.DESIGN: Prospective.SETTING: Nationwide sample from dialysis facilities.PATIENTS: 2215 patients receiving dialysis who had evidence of SARS-CoV-2 infection as of July 2020.MEASUREMENTS: Remainder plasma from routine monthly laboratories was used to measure semiquantitative RBD IgG index value over 6 months.RESULTS: A total of 2063 (93%) seroprevalent patients reached an assay detectable response (IgG index value ≥1). Most (n = 1323, 60%) had responses in July with index values classified as high (IgG ≥10); 1003 (76%) remained within this stratum. Adjusted median index values declined slowly but continuously (July vs. December values were 21 vs. 13; P < 0.001). The trajectory of the response did not vary by age group, sex, race/ethnicity, or diabetes status. Patients without an assay detectable response (n = 137) were more likely to be White and in the younger (18 to 44 years) or older (≥80 years) age groups and less likely to have diabetes and hypoalbuminemia.LIMITATION: Lack of data on symptoms or reverse transcriptase polymerase chain reaction diagnosis, cohort of persons who survived infection, and use of a semiquantitative assay.CONCLUSION: Despite impaired immunity, most seropositive patients receiving dialysis maintained RBD antibody levels over 6 months. A slow and continual decline in median antibody levels over time was seen, but no indication that subgroups with impaired immunity had a shorter-lived humoral response was found.PRIMARY FUNDING SOURCE: Ascend Clinical Laboratories.

  View details for DOI 10.7326/M21-0256

  View details for PubMedID 34000201

• Shared B cell memory to coronaviruses and other pathogens varies in human age groups and tissues. Science (New York, N.Y.) Yang, F., Nielsen, S. C., Hoh, R. A., Roltgen, K., Wirz, O. F., Haraguchi, E., Jean, G. H., Lee, J., Pham, T. D., Jackson, K. J., Roskin, K. M., Liu, Y., Nguyen, K., Ohgami, R. S., Osborne, E. M., Nadeau, K. C., Niemann, C. U., Parsonnet, J., Boyd, S. D. 2021

  Abstract

  Vaccination and infection promote the formation, tissue distribution, and clonal evolution of B cells, which encode humoral immune memory. We evaluated convergent antigen-specific antibody genes of similar sequences shared between individuals in pediatric and adult blood, and deceased organ donor tissues. B cell memory varied for different pathogens. Polysaccharide antigen-specific clones were not exclusive to the spleen. Adults had higher clone frequencies and greater class-switching in lymphoid tissues than blood, while pediatric blood had abundant class-switched convergent clones. Consistent with reported serology, pre-pandemic children had class-switched convergent clones to SARS-CoV-2 with weak cross-reactivity to other coronaviruses, while adult blood or tissues showed few such clones. The results highlight the prominence of early childhood B cell clonal expansions and cross-reactivity for future responses to novel pathogens.

  View details for DOI 10.1126/science.abf6648

  View details for PubMedID 33846272

• Peginterferon Lambda-1a for treatment of outpatients with uncomplicated COVID-19: a randomized placebo-controlled trial. Nature communications Jagannathan, P. n., Andrews, J. R., Bonilla, H. n., Hedlin, H. n., Jacobson, K. B., Balasubramanian, V. n., Purington, N. n., Kamble, S. n., de Vries, C. R., Quintero, O. n., Feng, K. n., Ley, C. n., Winslow, D. n., Newberry, J. n., Edwards, K. n., Hislop, C. n., Choong, I. n., Maldonado, Y. n., Glenn, J. n., Bhatt, A. n., Blish, C. n., Wang, T. n., Khosla, C. n., Pinsky, B. A., Desai, M. n., Parsonnet, J. n., Singh, U. n. 2021; 12 (1): 1967

  Abstract

  Type III interferons have been touted as promising therapeutics in outpatients with coronavirus disease 2019 (COVID-19). We conducted a randomized, single-blind, placebo-controlled trial (NCT04331899) in 120 outpatients with mild to moderate COVID-19 to determine whether a single, 180 mcg subcutaneous dose of Peginterferon Lambda-1a (Lambda) within 72 hours of diagnosis could shorten the duration of viral shedding (primary endpoint) or symptoms (secondary endpoint). In both the 60 patients receiving Lambda and 60 receiving placebo, the median time to cessation of viral shedding was 7 days (hazard ratio [HR] = 0.81; 95% confidence interval [CI] 0.56 to 1.19). Symptoms resolved in 8 and 9 days in Lambda and placebo, respectively, and symptom duration did not differ significantly between groups (HR 0.94; 95% CI 0.64 to 1.39). Both Lambda and placebo were well-tolerated, though liver transaminase elevations were more common in the Lambda vs. placebo arm (15/60 vs 5/60; p = 0.027). In this study, a single dose of subcutaneous Peginterferon Lambda-1a neither shortened the duration of SARS-CoV-2 viral shedding nor improved symptoms in outpatients with uncomplicated COVID-19.

  View details for DOI 10.1038/s41467-021-22177-1

  View details for PubMedID 33785743

• SARS-CoV-2 vaccine antibody response and breakthrough infection in dialysis. medRxiv : the preprint server for health sciences Anand, S., Montez-Rath, M. E., Han, J., Garcia, P., Cadden, L., Hunsader, P., Morgan, C., Kerschmann, R., Beyer, P., Dittrich, M., Block, G. A., Chertow, G. M., Parsonnet, J. 2021

  Abstract

  Patients receiving dialysis are a sentinel population for groups at high risk for death and disability from COVID-19. Understanding correlates of protection post-vaccination can inform immunization and mitigation strategies.Monthly since January 2021, we tested plasma from 4791 patients receiving dialysis for antibodies to the receptor-binding domain (RBD) of SARS-CoV-2 using a high-throughput assay. We qualitatively assessed the proportion without a detectable RBD response and among those with a response, semiquantitative median IgG index values. Using a nested case-control design, we matched each breakthrough case to five controls by age, sex, and vaccination-month to determine whether peak and pre-breakthrough RBD IgG index values were associated with risk for infection post-vaccination.Among 2563 vaccinated patients, the proportion without a detectable RBD response increased from 6.6% [95% CI 5.5-8.1] in 14-30 days post-vaccination to 20.2% [95% CI 17.1-23.8], and median index values declined from 92.7 (95% CI 77.8-107.5) to 3.7 (95% CI 3.1-4.3) after 5 months. Persons with SARS-CoV-2 infection prior-to-vaccination had higher peak index values than persons without prior infection, but values equalized by 5 months (p=0.230). Breakthrough infections occurred in 56 patients, with samples collected a median of 21 days pre-breakthrough. Peak and pre-breakthrough RBD values <23 (equivalent to <506 WHO BAU/mL) were associated with higher odds for breakthrough infection (OR: 3.7 [95% CI 2.0-6.8] and 9.8 [95% CI 2.9-32.8], respectively).The antibody response to SARS-CoV-2 vaccination wanes rapidly, and in persons receiving dialysis, the persisting antibody response is associated with risk for breakthrough infection.

  View details for DOI 10.1101/2021.10.12.21264860

  View details for PubMedID 34671782

  View details for PubMedCentralID PMC8528091

• Post-vaccination SARS-CoV-2 infections and incidence of the B.1.427/B.1.429 variant among healthcare personnel at a northern California academic medical center. medRxiv : the preprint server for health sciences Jacobson, K. B., Pinsky, B. A., Rath, M. E., Wang, H., Miller, J. A., Skhiri, M., Shepard, J., Mathew, R., Lee, G., Bohman, B., Parsonnet, J., Holubar, M. 2021

  Abstract

  Distribution of mRNA-based SARS-CoV-2 vaccines to healthcare personnel (HCP) in the United States began in December 2020, with efficacy > 90%. However, breakthrough infections in fully vaccinated individuals have been reported. Meanwhile, multiple SARS-CoV-2 variants of concern have emerged worldwide, including the B.1.427/B.1.429 variant first described in California. Little is known about the real-world effectiveness of the mRNA-based SARS-CoV-2 vaccines against novel variants including B.1.427/B.1.429.In this quality improvement project, post-vaccine SARS-CoV-2 cases (PVSCs) were defined as individuals with positive SARS-CoV-2 nucleic acid amplification test (NAAT) after receiving at least one dose of a SARS-CoV-2 vaccine. Chart extraction of demographic and clinical information was performed, and available specimens meeting cycle threshold value criteria were tested for L452R, N501Y and E484K mutations by RT-PCR.From December 2020 to March 2021, 189 PVSCs were identified out of 22,729 healthcare personnel who received at least one dose of an mRNA-based SARS-CoV-2 vaccine. Of these, 114 (60.3%) occurred within 14 days of first vaccine dose (early post-vaccination), 49 (25.9%) within 14 days of the second vaccine dose (partially vaccinated), and 26 (13.8%) > 14 days after the second dose (fully vaccinated). Of 115 samples available for mutation testing, 42 were positive for L452R alone, presumptive of B.1.427/B.1.429; three had N501Y mutation alone and none were found with E484K mutation. Though on univariate analysis partially- and fully-vaccinated PVSCs were more likely than early post-vaccination PVSCs to be infected with presumptive B.1.427/B.1.429, when adjusted for community prevalence of B.1.427/B.1.429 at the time of infection, partially- and fully-vaccinated PVSC did not have statistically significantly elevated risk ratios for infection with this variant (RR 1.40, 95% CI 0.81-2.43 and RR 1.13, 95% CI 0.59-2.16, respectively).The great majority of PVSCs occurred prior to the expected onset of full, vaccine-derived immunity. Although the B.1.427/B.1.429 variant did not represent a significantly higher proportion of PVSCs than expected, numbers were small and there was a trend towards higher representation in the partially- and fully-vaccinated subset. Continued infection control measures in the workplace and in the community including social distancing and masking, particularly in the early days post-vaccination, as well as continued variant surveillance in PVSCs, is imperative in order to anticipate and control future surges of infection.

  View details for DOI 10.1101/2021.04.14.21255431

  View details for PubMedID 33907767

  View details for PubMedCentralID PMC8077590

• Decreasing human body temperature in the United States since the industrial revolution. eLife Protsiv, M., Ley, C., Lankester, J., Hastie, T., Parsonnet, J. 2020; 9

  Abstract

  In the US, the normal, oral temperature of adults is, on average, lower than the canonical 37°C established in the 19th century. We postulated that body temperature has decreased over time. Using measurements from three cohorts--the Union Army Veterans of the Civil War (N = 23,710; measurement years 1860-1940), the National Health and Nutrition Examination Survey I (N = 15,301; 1971-1975), and the Stanford Translational Research Integrated Database Environment (N = 150,280; 2007-2017)--we determined that mean body temperature in men and women, after adjusting for age, height, weight and, in some models date and time of day, has decreased monotonically by 0.03°C per birth decade. A similar decline within the Union Army cohort as between cohorts, makes measurement error an unlikely explanation. This substantive and continuing shift in body temperature-a marker for metabolic rate-provides a framework for understanding changes in human health and longevity over 157 years.

  View details for DOI 10.7554/eLife.49555

  View details for PubMedID 31908267

• Prevalence of SARS-CoV-2 antibodies in a large nationwide sample of patients on dialysis in the USA: a cross-sectional study. Lancet (London, England) Anand, S. n., Montez-Rath, M. n., Han, J. n., Bozeman, J. n., Kerschmann, R. n., Beyer, P. n., Parsonnet, J. n., Chertow, G. M. 2020

  Abstract

  Many patients receiving dialysis in the USA share the socioeconomic characteristics of underserved communities, and undergo routine monthly laboratory testing, facilitating a practical, unbiased, and repeatable assessment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seroprevalence.For this cross-sectional study, in partnership with a central laboratory that receives samples from approximately 1300 dialysis facilities across the USA, we tested the remainder plasma of 28 503 randomly selected adult patients receiving dialysis in July, 2020, using a spike protein receptor binding domain total antibody chemiluminescence assay (100% sensitivity, 99·8% specificity). We extracted data on age, sex, race and ethnicity, and residence and facility ZIP codes from the anonymised electronic health records, linking patient-level residence data with cumulative and daily cases and deaths per 100 000 population and with nasal swab test positivity rates. We standardised prevalence estimates according to the overall US dialysis and adult population, and present estimates for four prespecified strata (age, sex, region, and race and ethnicity).The sampled population had similar age, sex, and race and ethnicity distribution to the US dialysis population, with a higher proportion of older people, men, and people living in majority Black and Hispanic neighbourhoods than in the US adult population. Seroprevalence of SARS-CoV-2 was 8·0% (95% CI 7·7-8·4) in the sample, 8·3% (8·0-8·6) when standardised to the US dialysis population, and 9·3% (8·8-9·9) when standardised to the US adult population. When standardised to the US dialysis population, seroprevalence ranged from 3·5% (3·1-3·9) in the west to 27·2% (25·9-28·5) in the northeast. Comparing seroprevalent and case counts per 100 000 population, we found that 9·2% (8·7-9·8) of seropositive patients were diagnosed. When compared with other measures of SARS-CoV-2 spread, seroprevalence correlated best with deaths per 100 000 population (Spearman's ρ=0·77). Residents of non-Hispanic Black and Hispanic neighbourhoods experienced higher odds of seropositivity (odds ratio 3·9 [95% CI 3·4-4·6] and 2·3 [1·9-2·6], respectively) compared with residents of predominantly non-Hispanic white neighbourhoods. Residents of neighbourhoods in the highest population density quintile experienced increased odds of seropositivity (10·3 [8·7-12·2]) compared with residents of the lowest density quintile. County mobility restrictions that reduced workplace visits by at least 5% in early March, 2020, were associated with lower odds of seropositivity in July, 2020 (0·4 [0·3-0·5]) when compared with a reduction of less than 5%.During the first wave of the COVID-19 pandemic, fewer than 10% of the US adult population formed antibodies against SARS-CoV-2, and fewer than 10% of those with antibodies were diagnosed. Public health efforts to limit SARS-CoV-2 spread need to especially target racial and ethnic minority and densely populated communities.Ascend Clinical Laboratories.

  View details for DOI 10.1016/S0140-6736(20)32009-2

  View details for PubMedID 32987007

• Increased T Cell Differentiation and Cytolytic Function in Bangladeshi Compared to American Children. Frontiers in immunology Wagar, L. E., Bolen, C. R., Sigal, N., Lopez Angel, C. J., Guan, L., Kirkpatrick, B. D., Haque, R., Tibshirani, R. J., Parsonnet, J., Petri, W. A., Davis, M. M. 2019; 10: 2239

  Abstract

  During the first 5 years of life, children are especially vulnerable to infection-related morbidity and mortality. Conversely, the Hygiene Hypothesis suggests that a lack of exposure to infectious agents early in life could explain the increasing incidence of allergies and autoimmunity in high-income countries. Understanding these phenomena, however, is hampered by a lack of comprehensive, direct immune monitoring in children with differing degrees of microbial exposure. Using mass cytometry, we provide an in-depth profile of the peripheral blood mononuclear cells (PBMCs) of children in regions at the extremes of exposure: the San Francisco Bay Area, USA and an economically poor district of Dhaka, Bangladesh. Despite variability in clinical health, functional characteristics of PBMCs were similar in Bangladeshi and American children at 1 year of age. However, by 2-3 years of age, Bangladeshi children's immune cells often demonstrated altered activation and cytokine production profiles upon stimulation with PMA-ionomycin, with an overall immune trajectory more in line with American adults. Conversely, immune responses in children from the US remained steady. Using principal component analysis, donor location, ethnic background, and cytomegalovirus infection status were found to account for some of the variation identified among samples. Within Bangladeshi 1-year-olds, stunting (as measured by height-for-age z-scores) was found to be associated with IL-8 and TGFβ expression in PMA-ionomycin stimulated samples. Combined, these findings provide important insights into the immune systems of children in high vs. low microbial exposure environments and suggest an important role for IL-8 and TGFβ in mitigating the microbial challenges faced by the Bangladeshi children.

  View details for DOI 10.3389/fimmu.2019.02239

  View details for PubMedID 31620139

  View details for PubMedCentralID PMC6763580

• Shaping of infant B cell receptor repertoires by environmental factors and infectious disease. Science translational medicine Nielsen, S. C., Roskin, K. M., Jackson, K. J., Joshi, S. A., Nejad, P., Lee, J., Wagar, L. E., Pham, T. D., Hoh, R. A., Nguyen, K. D., Tsunemoto, H. Y., Patel, S. B., Tibshirani, R., Ley, C., Davis, M. M., Parsonnet, J., Boyd, S. D. 2019; 11 (481)

  Abstract

  Antigenic exposures at epithelial sites in infancy and early childhood are thought to influence the maturation of humoral immunity and modulate the risk of developing immunoglobulin E (IgE)-mediated allergic disease. How different kinds of environmental exposures influence B cell isotype switching to IgE, IgG, or IgA, and the somatic mutation maturation of these antibody pools, is not fully understood. We sequenced antibody repertoires in longitudinal blood samples in a birth cohort from infancy through the first 3 years of life and found that, whereas IgG and IgA show linear increases in mutational maturation with age, IgM and IgD mutations are more closely tied to pathogen exposure. IgE mutation frequencies are primarily increased in children with impaired skin barrier conditions such as eczema, suggesting that IgE affinity maturation could provide a mechanistic link between epithelial barrier failure and allergy development.

  View details for PubMedID 30814336

• Time for Helicobacter pylori eradication. The Lancet. Infectious diseases Parsonnet, J. n. 2019; 19 (10): 1042–43

  View details for DOI 10.1016/S1473-3099(19)30406-2

  View details for PubMedID 31559950

• Household triclosan and triclocarban effects on the infant and maternal microbiome. EMBO molecular medicine Ribado, J. V., Ley, C. n., Haggerty, T. D., Tkachenko, E. n., Bhatt, A. S., Parsonnet, J. n. 2017; 9 (12): 1732–41

  Abstract

  In 2016, the US Food and Drug Administration banned the use of specific microbicides in some household and personal wash products due to concerns that these chemicals might induce antibiotic resistance or disrupt human microbial communities. Triclosan and triclocarban (referred to as TCs) are the most common antimicrobials in household and personal care products, but the extent to which TC exposure perturbs microbial communities in humans, particularly during infant development, was unknown. We conducted a randomized intervention of TC-containing household and personal care products during the first year following birth to characterize whether TC exposure from wash products perturbs microbial communities in mothers and their infants. Longitudinal survey of the gut microbiota using 16S ribosomal RNA amplicon sequencing showed that TC exposure from wash products did not induce global reconstruction or loss of microbial diversity of either infant or maternal gut microbiotas. Broadly antibiotic-resistant species from the phylum Proteobacteria, however, were enriched in stool samples from mothers in TC households after the introduction of triclosan-containing toothpaste. When compared by urinary triclosan level, agnostic to treatment arm, infants with higher triclosan levels also showed an enrichment of Proteobacteria species. Despite the minimal effects of TC exposure from wash products on the gut microbial community of infants and adults, detected taxonomic differences highlight the need for consumer safety testing of antimicrobial self-care products on the human microbiome and on antibiotic resistance.

  View details for PubMedID 29030459

• Crossover Control Study of the Effect of Personal Care Products Containing Triclosan on the Microbiome. mSphere Poole, A. C., Pischel, L., Ley, C., Suh, G., Goodrich, J. K., Haggerty, T. D., Ley, R. E., Parsonnet, J. 2016; 1 (3)

  Abstract

  Commonly prescribed antibiotics are known to alter human microbiota. We hypothesized that triclosan and triclocarban, components of many household and personal care products (HPCPs), may alter the oral and gut microbiota, with potential consequences for metabolic function and weight. In a double-blind, randomized, crossover study, participants were given triclosan- and triclocarban (TCS)-containing or non-triclosan/triclocarban (nTCS)-containing HPCPs for 4 months and then switched to the other products for an additional 4 months. Blood, stool, gingival plaque, and urine samples and weight data were obtained at baseline and at regular intervals throughout the study period. Blood samples were analyzed for metabolic and endocrine markers and urine samples for triclosan. The microbiome in stool and oral samples was then analyzed. Although there was a significant difference in the amount of triclosan in the urine between the TCS and nTCS phases, no differences were found in microbiome composition, metabolic or endocrine markers, or weight. Though this study was limited by the small sample size and imprecise administration of HPCPs, triclosan at physiologic levels from exposure to HPCPs does not appear to have a significant or important impact on human oral or gut microbiome structure or on a panel of metabolic markers. IMPORTANCE Triclosan and triclocarban are commonly used commercial microbicides found in toothpastes and soaps. It is unknown what effects these chemicals have on the human microbiome or on endocrine function. From this randomized crossover study, it appears that routine personal care use of triclosan and triclocarban neither exerts a major influence on microbial communities in the gut and mouth nor alters markers of endocrine function in humans.

  View details for DOI 10.1128/mSphere.00056-15

  View details for PubMedID 27303746

  View details for PubMedCentralID PMC4888890

• Cost-Effectiveness of a Potential Prophylactic Helicobacter pylori Vaccine in the United States JOURNAL OF INFECTIOUS DISEASES Rupnow, M. F., Chang, A. H., Shachter, R. D., Owens, D. K., Parsonnet, J. 2009; 200 (8): 1311-1317

  Abstract

  Helicobacter pylori vaccines are under development to prevent infection. We quantified the cost-effectiveness of such a vaccine in the United States, using a dynamic transmission model.We compartmentalized the population by age, infection status, and clinical disease state and measured effectiveness in quality-adjusted life years (QALYs). We simulated no intervention, vaccination of infants, and vaccination of school-age children. Variables included costs of vaccine, vaccine administration, and gastric cancer treatment (in 2007 US dollars), vaccine efficacy, quality adjustment due to gastric cancer, and discount rate. We evaluated possible outcomes for periods of 10-75 years.H. pylori vaccination of infants would cost $2.9 billion over 10 years; savings from cancer prevention would be realized decades later. Over a long time horizon (75 years), incremental costs of H. pylori vaccination would be $1.8 billion, and incremental QALYs would be 0.5 million, yielding a cost-effectiveness ratio of $3871/QALY. With school-age vaccination, the cost-effectiveness ratio would be $22,137/QALY. With time limited to <40 years, the cost-effectiveness ratio exceeded $50,000/QALY.When evaluated with a time horizon beyond 40 years, the use of a prophylactic H. pylori vaccine was cost-effective in the United States, especially with infant vaccination.

  View details for DOI 10.1086/605845

  View details for PubMedID 19751153

• Fecal and oral shedding of Helicobacter pylori from healthy infected adults JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Parsonnet, J., Shmuely, H., Haggerty, T. 1999; 282 (23): 2240-2245

  Abstract

  Helicobacter pylori commonly infects humans; however, its mode of transmission remains unknown.To determine how humans-the primary host for H pylori-shed the organism into the environment.Controlled clinical experimental study conducted from February through December 1998.Clinical research unit of a hospital in northern California.Sixteen asymptomatic H pylori-infected and 10 uninfected adults.A cathartic (sodium phosphate) and an emetic (ipecac) were given to all infected subjects and an emetic was given to 1 uninfected subject.Confirmed H pylori isolates cultured from stool, air, or saliva before and after catharsis and emesis and from vomitus during emesis. Isolates were fingerprinted using repetitive extragenic palindromic (REP) polymerase chain reaction and species identity was confirmed by sequencing the 16s ribosomal RNA gene.All vomitus samples from infected subjects grew H pylori, often in high quantities. Air sampled during vomiting grew H pylori from 6 (37.5%) of the 16 subjects. Saliva before and after emesis grew low quantities of H pylori in 3 (18.8%) and 9 (56.3%) subjects, respectively. No normal stools and only 22 (21.8%) of 101 induced stools grew the organism, although 7 (50.0%) of 14 subjects had at least 1 positive culture (2 stool culture samples were contaminated by fungus and were not included). Fingerprints of isolates within subjects were identical to one another but differed among subjects. No samples from uninfected subjects yielded H pylori.Helicobacter pylori can be cultivated uniformly from vomitus and, occasionally, from saliva and cathartic stools. The organism is potentially transmissible during episodes of gastrointestinal tract illness, particularly with vomiting.

  View details for Web of Science ID 000084138600032

  View details for PubMedID 10605976

• Modelling cost-effectiveness of Helicobacter pylori screening to prevent gastric cancer: A mandate for clinical trials LANCET Parsonnet, J., Harris, R. A., HACK, H. M., Owens, D. K. 1996; 348 (9021): 150-154

  Abstract

  It is unknown whether eradication of Helicobacter pylori infection prevents development of gastric adenocarcinoma. To determine whether screening and treatment trials are warranted, we conducted a cost-effectiveness analysis to estimate the costs and benefits associated with screening for H pylori at age 50 and treating those individuals infected with antibiotics.We compared two interventions: (1) screen for H pylori and treat those with a positive test, and (2) do not screen and do not treat. Estimates of risks and costs were obtained by review of published reports. Since the efficacy of H pylori therapy in cancer prevention is unknown, we did sensitivity analyses, varying this estimate widely. In our base-case analysis, we assumed that H pylori treatment prevented 30% of attributable gastric cancers.In the base-case analysis, 11,646,000 persons in the US would be screened and 4,658,400 treated, at a cost of $996 million. Cost-effectiveness was $25,000 per year of life saved. Cost-effectiveness was sensitive to the efficacy of the cancer prevention strategy. At low efficacy rates (< 10%), the screening programme was more expensive (> $75,000 per year of life saved). In a high-risk group such as Japanese-Americans, however, screening and treatment required less than $50,000 per year of life saved, even at 5% treatment efficacy.Screening and treatment for H pylori infection is potentially cost-effective in the prevention of gastric cancer, particularly in high-risk populations. Cancer prevention trials are strongly recommended.

  View details for PubMedID 8684154

• HELICOBACTER-PYLORI INFECTION AND GASTRIC LYMPHOMA NEW ENGLAND JOURNAL OF MEDICINE Parsonnet, J., Hansen, S., Rodriguez, L., Gelb, A. B., Warnke, R. A., Jellum, E., Orentreich, N., Vogelman, J. H., Friedman, G. D. 1994; 330 (18): 1267-1271

  Abstract

  Helicobacter pylori infection is a risk factor for gastric adenocarcinoma. We examined whether this infection is also a risk factor for primary gastric non-Hodgkin's lymphoma.This nested case-control study involved two large cohorts (230,593 participants). Serum had been collected from cohort members and stored, and all subjects were followed for cancer. Thirty-three patients with gastric non-Hodgkin's lymphoma were identified, and each was matched to four controls according to cohort, age, sex, and date of serum collection. For comparison, 31 patients with nongastric non-Hodgkin's lymphoma from one of the cohorts were evaluated, each of whom had been previously matched to 2 controls. Pathological reports and specimens were reviewed to confirm the histologic type of the tumor. Serum samples from all subjects were tested for H. pylori IgG by an enzyme-linked immunosorbent assay.Thirty-three cases of gastric non-Hodgkin's lymphoma occurred a median of 14 years after serum collection. Patients with gastric lymphoma were significantly more likely than matched controls to have evidence of previous H. pylori infection (matched odds ratio, 6.3; 95 percent confidence interval, 2.0 to 19.9). The results were similar in both cohorts. Among the 31 patients with nongastric lymphoma, a median of six years had elapsed between serum collection and the development of disease. No association was found between nongastric non-Hodgkin's lymphoma and previous H. pylori infection (matched odds ratio, 1.2; 95 percent confidence interval, 0.5 to 3.0).Non-Hodgkin's lymphoma affecting the stomach, but not other sites, is associated with previous H. pylori infection. A causative role for the organism is plausible, but remains unproved.

  View details for Web of Science ID A1994NJ51200003

  View details for PubMedID 8145781

• HELICOBACTER-PYLORI INFECTION AND THE RISK OF GASTRIC-CARCINOMA NEW ENGLAND JOURNAL OF MEDICINE Parsonnet, J., Friedman, G. D., Vandersteen, D. P., Chang, Y., Vogelman, J. H., Orentreich, N., Sibley, R. K. 1991; 325 (16): 1127-1131

  Abstract

  Infection with Helicobacter pylori has been linked with chronic atrophic gastritis, an inflammatory precursor of gastric adenocarcinoma. In a nested case-control study, we explored whether H. pylori infection increases the risk of gastric carcinoma.From a cohort of 128,992 persons followed since the mid-1960s at a health maintenance organization, 186 patients with gastric carcinoma were selected as case patients and were matched according to age, sex, and race with 186 control subjects without gastric carcinoma. Stored serum samples collected during the 1960s were tested for IgG antibodies to H. pylori by enzyme-linked immunosorbent assay. Data on cigarette use, blood group, ulcer disease, and gastric surgery were obtained from questionnaires administered at enrollment. Tissue sections and pathology reports were reviewed to confirm the histologic results.The mean time between serum collection and the diagnosis of gastric carcinoma was 14.2 years. Of the 109 patients with confirmed gastric adenocarcinoma (excluding tumors of the gastroesophageal junction), 84 percent had been infected previously with H. pylori, as compared with 61 percent of the matched control subjects (odds ratio, 3.6; 95 percent confidence interval, 1.8 to 7.3). Tumors of the gastroesophageal junction were not linked to H. pylori infection, nor were tumors in the gastric cardia. H. pylori was a particularly strong risk factor for stomach cancer in women (odds ratio, 18) and blacks (odds ratio, 9). A history of gastric surgery was independently associated with the development of cancer (odds ratio, 17; P = 0.03), but a history of peptic ulcer disease was negatively associated with subsequent gastric carcinoma (odds ratio, 0.2; P = 0.02). Neither blood group nor smoking history affected risk.Infection with H. pylori is associated with an increased risk of gastric adenocarcinoma and may be a cofactor in the pathogenesis of this malignant condition.

  View details for Web of Science ID A1991GK53800003

  View details for PubMedID 1891020

• Monthly Sulfadoxine-Pyrimethamine During Pregnancy Prevents Febrile Respiratory Illnesses: A Secondary Analysis of a Malaria Chemoprevention Trial in Uganda. Open forum infectious diseases Lee, J. J., Kakuru, A., Jacobson, K. B., Kamya, M. R., Kajubi, R., Ranjit, A., Gaw, S. L., Parsonnet, J., Benjamin-Chung, J., Dorsey, G., Jagannathan, P., Roh, M. E. 2024; 11 (4): ofae143

  Abstract

  Trials evaluating antimalarials for intermittent preventive treatment in pregnancy (IPTp) have shown that dihydroartemisinin-piperaquine (DP) is a more efficacious antimalarial than sulfadoxine-pyrimethamine (SP); however, SP is associated with higher birthweight, suggesting that SP demonstrates "nonmalarial" effects. Chemoprevention of nonmalarial febrile illnesses (NMFIs) was explored as a possible mechanism.In this secondary analysis, we leveraged data from 654 pregnant Ugandan women without HIV infection who participated in a randomized controlled trial comparing monthly IPTp-SP with IPTp-DP. Women were enrolled between 12 and 20 gestational weeks and followed through delivery. NMFIs were measured by active and passive surveillance and defined by the absence of malaria parasitemia. We quantified associations among IPTp regimens, incident NMFIs, antibiotic prescriptions, and birthweight.Mean "birthweight for gestational age" Z scores were 0.189 points (95% CI, .045-.333) higher in women randomized to IPTp-SP vs IPTp-DP. Women randomized to IPTp-SP had fewer incident NMFIs (incidence rate ratio, 0.74; 95% CI, .58-.95), mainly respiratory NMFIs (incidence rate ratio, 0.69; 95% CI, .48-1.00), vs IPTp-DP. Counterintuitively, respiratory NMFI incidence was positively correlated with birthweight in multigravidae. In total 75% of respiratory NMFIs were treated with antibiotics. Although overall antibiotic prescriptions were similar between arms, for each antibiotic prescribed, "birthweight for gestational age" Z scores increased by 0.038 points (95% CI, .001-.074).Monthly IPTp-SP was associated with reduced respiratory NMFI incidence, revealing a potential nonmalarial mechanism of SP and supporting current World Health Organization recommendations for IPTp-SP, even in areas with high-grade SP resistance. While maternal respiratory NMFIs are known risk factors of lower birthweight, most women in our study were presumptively treated with antibiotics, masking the potential benefit of SP on birthweight mediated through preventing respiratory NMFIs.

  View details for DOI 10.1093/ofid/ofae143

  View details for PubMedID 38585183

  View details for PubMedCentralID PMC10995957

• Observations of Respiratory Syncytial Virus (RSV) Nucleic Acids in Wastewater Solids Across the United States in the 2022-2023 Season: Relationships with RSV Infection Positivity and Hospitalization Rates ACS ES&T WATER Zulli, A., Varkila, M. J., Parsonnet, J., Wolfe, M. K., Boehm, A. B. 2024

  View details for DOI 10.1021/acsestwater.3c00725

  View details for Web of Science ID 001178631400001

• Comparison of US emergency departments by HIV priority jurisdiction designation: A case for geographically targeted screening in teaching hospitals. PloS one Bennett, C. L., Detsky, A. S., Clay, C. E., Espinola, J. A., Parsonnet, J., Camargo, C. A. 2023; 18 (10): e0292869

  Abstract

  The Ending the HIV Epidemic (EHE) Initiative targets a subset of United States (US) priority jurisdictions hardest hit by HIV. It remains unclear which emergency departments (EDs) are the most appropriate targets for EHE-related efforts. To explore this, we used the 2001-2019 National Emergency Department Inventories (NEDI)-USA as a framework to characterize all US EDs, focusing on those in priority jurisdictions and those affiliated with a teaching hospital. We then incorporate multivariable regression to explore the association between ED characteristics and location in an HIV priority jurisdiction. Further, to provide context on the communities these EDs serve, demographic and socioeconomic information and sexually transmitted infection case rate data were included. This reflected 2019 US Census Bureau data on age, race, ethnicity, and proportion uninsured and living in poverty along with 2001-2019 Centers for Disease Control and Prevention case rate data on chlamydia, gonorrhea, and syphilis. We found that EDs in priority jurisdictions (compared to EDs not in priority jurisdictions) more often served populations emphasized in HIV-related efforts (i.e., Black or African American or Hispanic or Latino populations), communities with higher proportions uninsured and living in poverty, and counties with higher rates of chlamydia, gonorrhea, and syphilis. Further, of the groups studied, EDs with teaching hospital affiliations had the highest visit volumes and had steady visit volume growth. In regression, ED annual visit volume was associated with an increased odds of an ED being located in a priority jurisdiction. Our results suggest that geographically targeted screening for HIV in a subset of US priority jurisdiction EDs with a teaching hospital affiliation could be an efficient means to reach vulnerable populations and reduce the burden of undiagnosed HIV in the US.

  View details for DOI 10.1371/journal.pone.0292869

  View details for PubMedID 37851641

• Recruitment into antibody prevalence studies: a randomized trial of postcards vs. letters as invitations. BMC medical research methodology Ley, C., Duan, H., Parsonnet, J. 2023; 23 (1): 170

  Abstract

  In a potential epidemic of an emerging infection, representative population-based serologic studies are required to determine the extent of immunity to the infectious agent, either from natural infection or vaccination. Recruitment strategies need to optimize response rates.Within a seroepidemiologic study to determine the true burden of SARS-CoV2 infection in two Bay Area counties, we evaluated whether letter (L) or postcard (P) invitations with reminders were more effective at recruiting participant households. Using geographic, probability-based sampling, 9,999 representative addresses, split between Santa Clara and Solano counties, were randomized to receive an initial invitation (L or P); a randomized reminder mailing sent two weeks later to all non-respondents created four mailing type groups (L/L, L/P, P/L, P/P). Interested households provided contact information via survey to perform blood spot collection at home for testing and then receive SARS-CoV2 serology results. Comparison of demographics among respondents and non-respondents used census tract data.Receiving any reminder mailing increased household response rates from 4.2% to between 8-13% depending on mailing combination. Response rates from two letters were 71% higher than from two postcards (13.2% vs. 7.7%, OR = 1.83 [95% CI: 1.5-2.2]). Respondents were older, more educated and more likely white than non-respondents. Compared to Solano county, Santa Clara county had different demographics and increased household response rates (L/L: 15.7% vs 10.7%; P/P: 9.2% vs. 6.1%; p < 0.0001); the effect of mailing types, however, was the same (L/L vs. P/P: Santa Clara: OR = 1.83 [95% CI: 1.4-2.3]; Solano: OR = 1.84 [95% CI:1.4-2.5]).Letters, as both invitations and reminders, are a more effective recruitment tool than postcards and should be considered when seeking a representative population-based sample for serological testing.

  View details for DOI 10.1186/s12874-023-01992-8

  View details for PubMedID 37481522

  View details for PubMedCentralID PMC10363298

• A modified Michaelis-Menten equation estimates growth from birth to 3 years in healthy babies in the US. Research square Walters, W., Ley, C., Hastie, T., Ley, R., Parsonnet, J. 2023

  Abstract

  Standard pediatric growth curves cannot be used to impute missing height or weight measurements in individual children. The Michaelis-Menten equation, used for characterizing substrate-enzyme saturation curves, has been shown to model growth in many organisms including nonhuman vertebrates. We investigated this equation could be used to interpolate missing growth data in children in the first three years of life.We developed a modified Michaelis-Menten equation and compared expected to actual growth, first in a local birth cohort (N=97) then in a large, outpatient, pediatric sample (N=14,695).The modified Michaelis-Menten equation showed excellent fit for both infant weight (median RMSE: boys: 0.22kg [IQR:0.19; 90%<0.43]; girls: 0.20kg [IQR:0.17; 90%<0.39]) and height (median RMSE: boys: 0.93cm [IQR:0.53; 90%<1.0]; girls: 0.91cm [IQR:0.50;90%<1.0]). Growth data were modeled accurately with as few as four values from routine well-baby visits in year 1 and seven values in years 1-3; birth weight or length was essential for best fit.A modified Michaelis-Menten equation accurately describes growth in healthy babies aged 0-36 months, allowing interpolation of missing weight and height values in individual longitudinal measurement series. The growth pattern in healthy babies in resource-rich environments mirrors an enzymatic saturation curve.

  View details for DOI 10.21203/rs.3.rs-2375831/v1

  View details for PubMedID 36711501

  View details for PubMedCentralID PMC9882604

• Evaluation of acebilustat, a selective inhibitor of leukotriene B4 biosynthesis, for treatment of outpatients with mild-moderate COVID-19 disease: A randomized, double-blind, placebo- controlled Phase 2 trial. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America Levitt, J. E., Hedlin, H., Duong, S., Lu, D., Lee, J., Bunning, B., Elkarra, N., Pinsky, B. A., Heffernan, E., Springman, E., Moss, R. B., Bonilla, H. F., Parsonnet, J., Zamanian, R. T., Langguth, J. J., Bollyky, J., Khosla, C., Nicolls, M. R., Desai, M., Rogers, A. J. 2023

  Abstract

  The vast majority of COVID-19 disease occurs in outpatients where treatment is limited to anti-virals for high-risk subgroups. Acebilustat, a leukotriene B4 (LTB4) inhibitor, has potential to reduce inflammation and symptom duration.In a single-center trial spanning Delta and Omicron variants, outpatients were randomized to 100 mg of oral acebilustat or placebo for 28 days. Patients reported daily symptoms via electronic query through Day 28 with phone follow-up on Day 120 and collected nasal swabs on Days 1-10. The primary outcome was sustained symptom resolution to Day 28. Secondary 28-day outcomes included time to first symptom resolution, area under the curve (AUC) of longitudinal daily symptom scores; duration of viral shedding through Day 10; and symptoms on Day 120.Sixty participants were randomized to each study arm. At enrollment, median duration and number of symptoms were 4 (IQR 3-5) days and 9 (IQR 7-11) symptoms. Most patients (90%) were vaccinated with 73% having neutralizing antibodies. A minority (44%) of participants (35% in the acebilustat arm and 53% in placebo) had sustained symptom resolution at Day 28 (HR 0.6, 95% CI 0.34-1.04, p = 0.07 favoring placebo). There was no difference in mean AUC of symptom scores over 28 days (difference in mean of AUC 9.4, 95% CI -42.1-60.9, p=0.72). Acebilustat did not impact viral shedding or symptoms at Day 120.Sustained symptoms through Day 28 were common in this low-risk population. Despite this, LTB4 antagonism with acebilustat did not shorten symptom duration in outpatients with COVID-19.

  View details for DOI 10.1093/cid/ciad187

  View details for PubMedID 36996150

• Feasibility and Acceptability of SARS-CoV-2 Screening among Patients Receiving Hemodialysis: A Pilot Study. Clinical journal of the American Society of Nephrology : CJASN Anand, S., Montez-Rath, M., Varkila, M., Yu, X., Block, M., Brillhart, S., Leppink, A., Hunsader, P., Owens, D. K., Chertow, G. M., Parsonnet, J., Block, G. 2023

  View details for DOI 10.2215/CJN.0000000000000137

  View details for PubMedID 36976655

• Use of wastewater metrics to track COVID-19 in the U.S.: a national time-series analysis over the first three quarters of 2022. medRxiv : the preprint server for health sciences Varkila, M., Montez-Rath, M., Salomon, J., Yu, X., Block, G., Owens, D. K., Chertow, G. M., Parsonnet, J., Anand, S. 2023

  Abstract

  Widespread use of at-home COVID-19 tests hampers determination of community COVID-19 incidence. Using nationwide data available through the US National Wastewater Surveillance System, we examined the performance of two wastewater metrics in predicting high case and hospitalizations rates both before and after widespread use of at-home tests.We performed area under the receiver operating characteristic (ROC) curve analysis (AUC) for two wastewater metrics-viral concentration relative to the peak of January 2022 ("wastewater percentile") and 15-day percent change in SARS-CoV-2 ("percent change"). Dichotomized reported cases (≥ 200 or <200 cases per 100,000) and new hospitalizations (≥ 10 or <10 per 100,000) were our dependent variables, stratified by calendar quarter. Using logistic regression, we assessed the performance of combining wastewater metrics.Among 268 counties across 22 states, wastewater percentile detected high reported case and hospitalizations rates in the first quarter of 2022 (AUC 0.95 and 0.86 respectively) whereas the percent change did not (AUC 0.54 and 0.49 respectively). A wastewater percentile of 51% maximized sensitivity (0.93) and specificity (0.82) for detecting high case rates. A model inclusive of both metrics performed no better than using wastewater percentile alone. The predictive capability of wastewater percentile declined over time (AUC 0.84 and 0.72 for cases for second and third quarters of 2022).Nationwide, county wastewater levels above 51% relative to the historic peak predicted high COVID rates and hospitalization in the first quarter of 2022, but performed less well in subsequent quarters. Decline over time in predictive performance of this metric likely reflects underreporting of cases, reduced testing, and possibly lower virulence of infection due to vaccines and treatments.

  View details for DOI 10.1101/2023.02.06.23285542

  View details for PubMedID 36798337

  View details for PubMedCentralID PMC9934789

• Characteristics of California Emergency Departments in Centers for Disease Control and Prevention-Designated HIV Priority Counties. The Journal of emergency medicine Bennett, C. L., Clay, C. E., Siddiqi, K. A., Olatosi, B. A., Parsonnet, J., Camargo, J. C. 2023

  Abstract

  Refocused national HIV testing initiatives include a geographic focus.Using a geographic focus, we sought to identify which emergency departments (EDs) might be the most efficient targets for future HIV testing efforts, using California as an example.Retrospective analysis of California EDs, emergency physicians, and patients served, along with county-level estimates of HIV prevalence and proportion of the population living in poverty. Emphasis was placed on characterizing EDs affiliated with teaching hospitals and those located in Centers for Disease Control (CDC) and Prevention HIV priority counties.Of the 320 EDs studied, 178 were in priority counties, 29 were affiliated with teaching hospitals, and 24 had both characteristics. Of the 12,869,889 ED visits included, 61.8% occurred in priority counties, 14.7% in EDs affiliated with teaching hospitals, and 12.0% in EDs with both characteristics. The subset of EDs in priority counties with teaching hospital affiliations (compared with priority and nonpriority county ED groups without a teaching hospital affiliation) had higher overall median visit volumes and higher proportions of visits by at-risk and CDC-targeted populations (e.g., individuals who were homeless, those who identified as Black or African American race, and those who identified as Hispanic or Latino ethnicity, all p < 0.01).EDs in priority counties affiliated with teaching hospitals are major sources of health care in California. These EDs more often serve populations disproportionately impacted by HIV. These departments are efficient targets to direct testing efforts. Increasing testing in these EDs could reduce the burden of undiagnosed HIV in California.

  View details for DOI 10.1016/j.jemermed.2022.10.020

  View details for PubMedID 36650074

• Gestational diabetes is driven by microbiota-induced inflammation months before diagnosis. Gut Pinto, Y., Frishman, S., Turjeman, S., Eshel, A., Nuriel-Ohayon, M., Shrossel, O., Ziv, O., Walters, W., Parsonnet, J., Ley, C., Johnson, E. L., Kumar, K., Schweitzer, R., Khatib, S., Magzal, F., Muller, E., Tamir, S., Tenenbaum-Gavish, K., Rautava, S., Salminen, S., Isolauri, E., Yariv, O., Peled, Y., Poran, E., Pardo, J., Chen, R., Hod, M., Borenstein, E., Ley, R. E., Schwartz, B., Louzoun, Y., Hadar, E., Koren, O. 2023

  Abstract

  OBJECTIVE: Gestational diabetes mellitus (GDM) is a condition in which women without diabetes are diagnosed with glucose intolerance during pregnancy, typically in the second or third trimester. Early diagnosis, along with a better understanding of its pathophysiology during the first trimester of pregnancy, may be effective in reducing incidence and associated short-term and long-term morbidities.DESIGN: We comprehensively profiled the gut microbiome, metabolome, inflammatory cytokines, nutrition and clinical records of 394women during the first trimester of pregnancy, before GDM diagnosis. We then built a model that can predict GDM onset weeks before it is typically diagnosed. Further, we demonstrated the role of the microbiome in disease using faecal microbiota transplant (FMT) of first trimester samples from pregnant women across three unique cohorts.RESULTS: We found elevated levels of proinflammatory cytokines in women who later developed GDM, decreased faecal short-chain fatty acids and altered microbiome. We next confirmed that differences in GDM-associated microbial composition during the first trimester drove inflammation and insulin resistance more than 10 weeks prior to GDM diagnosis using FMT experiments. Following these observations, we used a machine learning approach to predict GDM based on first trimester clinical, microbial and inflammatory markers with high accuracy.CONCLUSION: GDM onset can be identified in the first trimester of pregnancy, earlier than currently accepted. Furthermore, the gut microbiome appears to play a role in inflammation-induced GDM pathogenesis, with interleukin-6 as a potential contributor to pathogenesis. Potential GDM markers, including microbiota, can serve as targets for early diagnostics and therapeutic intervention leading to prevention.

  View details for DOI 10.1136/gutjnl-2022-328406

  View details for PubMedID 36627187

• Microbiota-mediated reactivation of triclosan oxidative metabolites in colon tissues. Journal of hazardous materials Zhang, H., Sanidad, K. Z., Zhang, J., Wang, G., Zhang, R., Hu, C., Lin, Y., Haggerty, T. D., Parsonnet, J., Zheng, Y., Zhang, G., Cai, Z. 2022; 445: 130509

  Abstract

  Triclosan (TCS) is a widespread antimicrobial agent that is associated with many adverse health outcomes. Its gut toxicity has been attributed to the molecular modifications mediated by commensal microbes, but microbial transformations of TCS derivatives in the gut lumen are still largely unknown. Aromatic hydroxylation is the predominant oxidative metabolism of TCS that linked to its toxicological effects in host tissues. Here, we aimed to reveal the biological fates of hydroxyl-TCS (OH-TCS) in the colon, where intestinal microbes mainly reside. Unlike the profiles generated via host metabolism, OH-TCS species remain unconjugated in human stools from a cohort study. Through tracking molecular compositions in mouse intestinal tract, elevated abundance of free-form OH-TCS while reduced abundance of conjugated forms was observed in the colon digesta and mucosa. Using antibiotic-treated and germ-free mice, as well as in vitro approaches, we demonstrate that gut microbiota-encoded enzymes efficiently convert glucuronide/sulfate-conjugated OH-TCS, which are generated from host metabolism, back to their bioactive free-forms in colon tissues. Thus, host-gut microbiota metabolic interactions of TCS derivatives were proposed. These results shed light on the crucial roles of microbial metabolism in TCS toxicity, and highlight the importance of incorporating gut microbial transformations in health risk assessment of environmental chemicals.

  View details for DOI 10.1016/j.jhazmat.2022.130509

  View details for PubMedID 36463744

• Early immune markers of clinical, virological, and immunological outcomes in patients with COVID-19: a multi-omics study. eLife Hu, Z., van der Ploeg, K., Chakraborty, S., Arunachalam, P. S., Mori, D. A., Jacobson, K. B., Bonilla, H., Parsonnet, J., Andrews, J. R., Holubar, M., Subramanian, A., Khosla, C., Maldonado, Y., Hedlin, H., de la Parte, L., Press, K., Ty, M., Tan, G. S., Blish, C., Takahashi, S., Rodriguez-Barraquer, I., Greenhouse, B., Butte, A. J., Singh, U., Pulendran, B., Wang, T. T., Jagannathan, P. 2022; 11

  Abstract

  The great majority of severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) infections are mild and uncomplicated, but some individuals with initially mild COVID-19 progressively develop more severe symptoms. Furthermore, there is substantial heterogeneity in SARS-CoV-2-specific memory immune responses following infection. There remains a critical need to identify host immune biomarkers predictive of clinical and immunological outcomes in SARS-CoV-2-infected patients.Leveraging longitudinal samples and data from a clinical trial (N=108) in SARS-CoV-2-infected outpatients, we used host proteomics and transcriptomics to characterize the trajectory of the immune response in COVID-19 patients. We characterized the association between early immune markers and subsequent disease progression, control of viral shedding, and SARS-CoV-2-specific T cell and antibody responses measured up to 7 months after enrollment. We further compared associations between early immune markers and subsequent T cell and antibody responses following natural infection with those following mRNA vaccination. We developed machine-learning models to predict patient outcomes and validated the predictive model using data from 54 individuals enrolled in an independent clinical trial.We identify early immune signatures, including plasma RIG-I levels, early IFN signaling, and related cytokines (CXCL10, MCP1, MCP-2, and MCP-3) associated with subsequent disease progression, control of viral shedding, and the SARS-CoV-2-specific T cell and antibody response measured up to 7 months after enrollment. We found that several biomarkers for immunological outcomes are shared between individuals receiving BNT162b2 (Pfizer-BioNTech) vaccine and COVID-19 patients. Finally, we demonstrate that machine-learning models using 2-7 plasma protein markers measured early within the course of infection are able to accurately predict disease progression, T cell memory, and the antibody response post-infection in a second, independent dataset.Early immune signatures following infection can accurately predict clinical and immunological outcomes in outpatients with COVID-19 using validated machine-learning models.Support for the study was provided from National Institute of Health/National Institute of Allergy and Infectious Diseases (NIH/NIAID) (U01 AI150741-01S1 and T32-AI052073), the Stanford's Innovative Medicines Accelerator, National Institutes of Health/National Institute on Drug Abuse (NIH/NIDA) DP1DA046089, and anonymous donors to Stanford University. Peginterferon lambda provided by Eiger BioPharmaceuticals.

  View details for DOI 10.7554/eLife.77943

  View details for PubMedID 36239699

• SARS-CoV-2 Infection during the Omicron Surge among Patients Receiving Dialysis: The Role of Circulating Receptor-Binding Domain Antibodies and Vaccine Doses. Journal of the American Society of Nephrology : JASN Montez-Rath, M. E., Garcia, P., Han, J., Cadden, L., Hunsader, P., Morgan, C., Kerschmann, R., Beyer, P., Dittrich, M., Block, G. A., Parsonnet, J., Chertow, G. M., Anand, S. 2022

  Abstract

  It is unclear whether circulating antibody levels conferred protection against SARS-CoV-2 infection among patients receiving dialysis during the Omicron-dominant period.We followed monthly semiquantitative SARS-CoV-2 RBD IgG index values in a randomly selected nationwide cohort of patients receiving dialysis and ascertained SARS-CoV-2 infection during the Omicron-dominant period of December 25, 2021 to January 31, 2022 using electronic health records. We estimated the relative risk for documented SARS-CoV-2 infection by vaccination status and by circulating RBD IgG using a log-binomial model accounting for age, sex, and prior COVID-19.Among 3576 patients receiving dialysis, 901 (25%) received a third mRNA vaccine dose as of December 24, 2021. Early antibody responses to third doses were robust (median peak index IgG value at assay limit of 150). During the Omicron-dominant period, SARS-CoV-2 infection was documented in 340 (7%) patients. Risk for infection was higher among patients without vaccination and with one to two doses (RR, 2.1; 95% CI, 1.6 to 2.8, and RR, 1.3; 95% CI, 1.0 to 1.8 versus three doses, respectively). Irrespective of the number of vaccine doses, risk for infection was higher among patients with circulating RBD IgG <23 (506 BAU/ml) (RR range, 2.1 to 3.2, 95% CI, 1.3 to 3.4 and 95% CI, 2.2 to 4.5, respectively) compared with RBD IgG ≥23.Among patients receiving dialysis, a third mRNA vaccine dose enhanced protection against SARS-CoV-2 infection during the Omicron-dominant period, but a low circulating RBD antibody response was associated with risk for infection independent of the number of vaccine doses. Measuring circulating antibody levels in this high-risk group could inform optimal timing of vaccination and other measures to reduce risk of SARS-CoV-2 infection.

  View details for DOI 10.1681/ASN.2022040504

  View details for PubMedID 35973733

• Validity of at-home rapid antigen lateral flow assay and artificial intelligence read to detect SARS-CoV-2. Diagnostic microbiology and infectious disease Richardson, S., Kohn, M. A., Bollyky, J., Parsonnet, J. 2022; 104 (3): 115763

  Abstract

  BACKGROUND: The gold standard for COVID-19 diagnosis-reverse-transcriptase polymerase chain reaction (RT-PCR)- is expensive and often slow to yield results whereas lateral flow tests can lack sensitivity.METHODS: We tested a rapid, lateral flow antigen (LFA) assay with artificial intelligence read (LFAIR) in subjects from COVID-19 treatment trials (N=37; daily tests for 5 days) and from a population-based study (N=88; single test). LFAIR was compared to RT-PCR from same-day samples.RESULTS: Using each participant's first sample, LFAIR showed 86.2% sensitivity (95% CI 73.6%-98.8) and 94.3% specificity (88.8%-99.7%) compared to RT-PCR. Adjusting for days since symptom onset and repeat testing, sensitivity was 97.8% (89.9%-99.5%) on the first symptomatic day and decreased with each additional day. Sensitivity improved with artificial intelligence (AI) read (86.2%) compared to the human eye (71.4%).CONCLUSION: LFAIR showed improved accuracy compared to LFA alone. particularly early in infection.

  View details for DOI 10.1016/j.diagmicrobio.2022.115763

  View details for PubMedID 36070629

• CalScope: Monitoring Severe Acute Respiratory Syndrome Coronavirus 2 Seroprevalence From Vaccination and Prior Infection in Adults and Children in California May 2021-July 2021. Open forum infectious diseases Mehrotra, M. L., Lim, E., Lamba, K., Kamali, A., Lai, K. W., Meza, E., Szeto, I., Robinson, P., Tsai, C., Gebhart, D., Fonseca, N., Martin, A. B., Ley, C., Scherf, S., Watt, J., Seftel, D., Parsonnet, J., Jain, S. 2022; 9 (7): ofac246

  Abstract

  Background: Understanding the distribution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies from vaccination and/or prior infection is critical to the public health response to the pandemic. CalScope is a population-based serosurvey in 7 counties in California.Methods: We invited 200000 randomly sampled households to enroll up to 1 adult and 1 child between April 20, 2021 and June 16, 2021. We tested all specimens for antibodies against SARS-CoV-2 nucleocapsid and spike proteins, and each participant completed an online survey. We classified participants into categories: seronegative, antibodies from infection only, antibodies from infection and vaccination, and antibodies from vaccination only.Results: A total of 11161 households enrolled (5.6%), with 7483 adults and 1375 children completing antibody testing. As of June 2021, 33% (95% confidence interval [CI], 28%-37%) of adults and 57% (95% CI, 48%-66%) of children were seronegative; 18% (95% CI, 14%-22%) of adults and 26% (95% CI, 19%-32%) of children had antibodies from infection alone; 9% (95% CI, 6%-11%) of adults and 5% (95% CI, 1%-8%) of children had antibodies from infection and vaccination; and 41% (95% CI, 37%-45%) of adults and 13% (95% CI, 7%-18%) of children had antibodies from vaccination alone.Conclusions: As of June 2021, one third of adults and most children in California were seronegative. Serostatus varied regionally and by demographic group.

  View details for DOI 10.1093/ofid/ofac246

  View details for PubMedID 35855959

• TNF-alpha+ CD4+ Tcells dominate the SARS-CoV-2 specific T cell response in COVID-19 outpatients and are associated with durable antibodies. Cell reports. Medicine van der Ploeg, K., Kirosingh, A. S., Mori, D. A., Chakraborty, S., Hu, Z., Sievers, B. L., Jacobson, K. B., Bonilla, H., Parsonnet, J., Andrews, J. R., Press, K. D., Ty, M. C., Ruiz-Betancourt, D. R., de la Parte, L., Tan, G. S., Blish, C. A., Takahashi, S., Rodriguez-Barraquer, I., Greenhouse, B., Singh, U., Wang, T. T., Jagannathan, P. 2022: 100640

  Abstract

  Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific CD4+ Tcells are likely important in immunity against coronavirus 2019 (COVID-19), but our understanding of CD4+ longitudinal dynamics following infection and of specific features that correlate with the maintenance of neutralizing antibodies remains limited. Here, we characterize SARS-CoV-2-specific CD4+ Tcells in a longitudinal cohort of 109 COVID-19 outpatients enrolled during acute infection. The quality of the SARS-CoV-2-specific CD4+ response shifts from cells producing interferon gamma (IFNgamma) to tumor necrosis factor alpha (TNF-alpha) from 5days to 4months post-enrollment, with IFNgamma-IL-21-TNF-alpha+ CD4+ Tcells the predominant population detected at later time points. Greater percentages of IFNgamma-IL-21-TNF-alpha+ CD4+ Tcells on day 28 correlate with SARS-CoV-2-neutralizing antibodies measured 7months post-infection (⍴= 0.4, p= 0.01). mRNA vaccination following SARS-CoV-2 infection boosts both IFNgamma- and TNF-alpha-producing, spike-protein-specific CD4+ Tcells. These data suggest that SARS-CoV-2-specific, TNF-alpha-producing CD4+ Tcells may play an important role in antibody maintenance following COVID-19.

  View details for DOI 10.1016/j.xcrm.2022.100640

  View details for PubMedID 35588734

• Favipiravir for treatment of outpatients with asymptomatic or uncomplicated COVID-19: a double-blind randomized, placebo-controlled, phase 2 trial. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America Holubar, M., Subramanian, A., Purington, N., Hedlin, H., Bunning, B., Walter, K. S., Bonilla, H., Boumis, A., Chen, M., Clinton, K., Dewhurst, L., Epstein, C., Jagannathan, P., Kaszynski, R. H., Panu, L., Parsonnet, J., Ponder, E. L., Quintero, O., Sefton, E., Singh, U., Soberanis, L., Truong, H., Andrews, J. R., Desai, M., Khosla, C., Maldonado, Y. 2022

  Abstract

  Favipiravir is an oral, RNA-dependent RNA polymerase inhibitor with in vitro activity against SARS-CoV2. Despite limited data, favipiravir is administered to patients with COVID-19 in several countries.We conducted a phase 2 double-blind randomized controlled outpatient trial of favipiravir in asymptomatic or mildly symptomatic adults with a positive SARS-CoV2 RT-PCR within 72 hours of enrollment. Participants were randomized 1: 1 to receive placebo or favipiravir (1800mg BID Day 1, 800 mg BID Days 2-10). The primary outcome was SARS-CoV-2 shedding cessation in a modified intention-to-treat (mITT) cohort of participants with positive enrollment RT-PCRs. Using SARS-CoV-2 amplicon-based sequencing, we assessed favipiravir's impact on mutagenesis.From July 8, 2020 - March 23, 2021, we randomized 149 participants with 116 included in the mITT cohort. The participants' mean age was 43 years (SD 12.5) and 57 (49%) were women. We found no difference in time to shedding cessation by treatment arm overall (HR 0.76 favoring placebo, 95% confidence interval [CI] 0.48-1.20) or in sub-group analyses (age, sex, high-risk comorbidities, seropositivity or symptom duration at enrollment). We observed no difference in time to symptom resolution (initial: HR 0.84, 95% CI 0.54-1.29; sustained: HR 0.87, 95% CI 0.52-1.45). We detected no difference in accumulation of transition mutations in the viral genome during treatment.Our data do not support favipiravir use at commonly used doses in outpatients with uncomplicated COVID-19. Further research is needed to ascertain if higher doses of favipiravir are effective and safe for patients with COVID-19.

  View details for DOI 10.1093/cid/ciac312

  View details for PubMedID 35446944

• Gastrointestinal symptoms and fecal shedding of SARS-CoV-2 RNA suggest prolonged gastrointestinal infection. Med (New York, N.Y.) Natarajan, A., Zlitni, S., Brooks, E. F., Vance, S. E., Dahlen, A., Hedlin, H., Park, R. M., Han, A., Schmidtke, D. T., Verma, R., Jacobson, K. B., Parsonnet, J., Bonilla, H. F., Singh, U., Pinsky, B. A., Andrews, J. R., Jagannathan, P., Bhatt, A. S. 2022

  Abstract

  COVID-19 manifests with respiratory, systemic, and gastrointestinal (GI) symptoms.1,2 SARS-CoV-2 RNA is detected in respiratory and fecal samples, and recent reports demonstrate viral replication in both the lung and intestinal tissue.3-5 Although much is known about early fecal RNA shedding, little is known about the long term shedding, especially in those with mild COVID-19. Furthermore, most reports of fecal RNA shedding do not correlate these findings with GI symptoms.6.We analyze the dynamics of fecal RNA shedding up to 10 months after COVID-19 diagnosis in 113 individuals with mild to moderate disease. We also correlate shedding with disease symptoms.Fecal SARS-CoV-2 RNA is detected in 49.2% [95% Confidence interval = 38.2%-60.3%] of participants within the first week after diagnosis. Whereas there was no ongoing oropharyngeal SARS-CoV-2 RNA shedding in subjects at and after 4 months, 12.7% [8.5%-18.4%] of participants continued to shed SARS-CoV-2 RNA in the feces at 4 months after diagnosis and 3.8% [2.0%-7.3%] shed at 7 months. Finally, we find that GI symptoms (abdominal pain, nausea, vomiting) are associated with fecal shedding of SARS-CoV-2 RNA.The extended presence of viral RNA in feces, but not respiratory samples, along with the association of fecal viral RNA shedding with GI symptoms suggest that SARS-CoV-2 infects the GI tract, and that this infection can be prolonged in a subset of individuals with COVID-19.

  View details for DOI 10.1016/j.medj.2022.04.001

  View details for PubMedID 35434682

  View details for PubMedCentralID PMC9005383

• SARS-CoV-2 Booster Vaccine Response among Patients Receiving Dialysis. Clinical journal of the American Society of Nephrology : CJASN Garcia, P., Han, J., Montez-Rath, M., Sun, S., Shang, T., Parsonnet, J., Chertow, G., Anand, S., Schiller, B., Abra, G. 2022

  Abstract

  N/A.

  View details for DOI 10.2215/CJN.00890122

  View details for PubMedID 35383042

• SARS-CoV-2 infection during the Omicron surge among patients receiving dialysis: the role of circulating receptor-binding domain antibodies and vaccine doses. medRxiv : the preprint server for health sciences Montez-Rath, M. E., Garcia, P., Han, J., Cadden, L., Hunsader, P., Morgan, C., Kerschmann, R., Beyer, P., Dittrich, M., Block, G. A., Anand, S., Parsonnet, J., Chertow, G. M. 2022

  Abstract

  Background: It is unclear whether a third dose of mRNA platform vaccines, or antibody response to prior infection or vaccination confer protection from the Omicron variant among patients receiving dialysis.Methods: Monthly since February 2021, we tested plasma from 4,697 patients receiving dialysis for antibodies to the receptor-binding domain (RBD) of SARS-CoV-2. We assessed semiquantitative median IgG index values over time among patients vaccinated with at least one dose of the two mRNA vaccines. We ascertained documented COVID-19 diagnoses after December 25, 2021 and up to January 31, 2022. We estimated the relative risk for documented SARS-CoV-2 infection by vaccination status using a log-binomial model accounting for age, sex, and prior clinical COVID-19. Among patients with RBD IgG index value available during December 1-December 24, 2021, we also evaluated the association between the circulating RBD IgG titer and risk for Omicron variant SARS-CoV-2 infection.Results: Of the 4,697 patients we followed with monthly RBD assays, 3576 are included in the main analysis cohort; among these, 852 (24%) were unvaccinated. Antibody response to third doses was robust (median peak index IgG value at assay limit of 150, equivalent to 3270 binding antibody units/mL). Between December 25-January 31, 2022, SARS-CoV-2 infection was documented 340 patients (7%), 115 (36%) of whom were hospitalized. The final doses of vaccines were given a median of 272 (25 th , 75 th percentile, 245-303) days and 58 (25 th , 75 th percentile, 51-95) days prior to infection for the 1-2 dose and 3 dose vaccine groups respectively. Relative risks for infection were higher among patients without vaccination (RR 2.1 [95%CI 1.6, 2.8]), and patients with 1-2 doses (RR 1.3 [95%CI 1.0, 1.8]), compared with patients with three doses of the mRNA vaccines. Relative risks for infection were higher among patients with RBD index values < 23 (506 BAU/mL), compared with RBD index value a 23 (RR 2.4 [95%CI 1.9, 3.0]). The higher risk for infection among patients with RBD index values < 23 was present among patients who received three doses (RR 2.1 [95%CI 1.3, 3.4]).Conclusions: Among patients receiving hemodialysis, patients unvaccinated, without a third mRNA vaccine dose, or those lacking robust circulating antibody response are at higher risk for Omicron variant infection. Low circulating antibodies could identify the subgroup needing intensified surveillance, prophylaxis or treatment in this patient population.

  View details for DOI 10.1101/2022.03.15.22272426

  View details for PubMedID 35313586

• Early immune responses have long-term associations with clinical, virologic, and immunologic outcomes in patients with COVID-19. Research square Hu, Z., van der Ploeg, K., Chakraborty, S., Arunachalam, P., Mori, D., Jacobson, K., Bonilla, H., Parsonnet, J., Andrews, J., Hedlin, H., de la Parte, L., Dantzler, K., Ty, M., Tan, G., Blish, C., Takahashi, S., Rodriguez-Barraquer, I., Greenhouse, B., Butte, A., Singh, U., Pulendran, B., Wang, T., Jagannathan, P. 2022

  Abstract

  The great majority of SARS-CoV-2 infections are mild and uncomplicated, but some individuals with initially mild COVID-19 progressively develop more severe symptoms. Furthermore, there is substantial heterogeneity in SARS-CoV-2-specific memory immune responses following infection. There remains a critical need to identify host immune biomarkers predictive of clinical and immunologic outcomes in SARS-CoV-2-infected patients. Leveraging longitudinal samples and data from a clinical trial in SARS-CoV-2 infected outpatients, we used host proteomics and transcriptomics to characterize the trajectory of the immune response in COVID-19 patients within the first 2 weeks of symptom onset. We identify early immune signatures, including plasma RIG-I levels, early interferon signaling, and related cytokines (CXCL10, MCP1, MCP-2 and MCP-3) associated with subsequent disease progression, control of viral shedding, and the SARS-CoV-2 specific T cell and antibody response measured up to 7 months after enrollment. We found that several biomarkers for immunological outcomes are shared between individuals receiving BNT162b2 (Pfizera"BioNTech) vaccine and COVID-19 patients. Finally, we demonstrate that machine learning models using 7-10 plasma protein markers measured early within the course of infection are able to accurately predict disease progression, T cell memory, and the antibody response post-infection in a second, independent dataset.

  View details for DOI 10.21203/rs.3.rs-847082/v1

  View details for PubMedID 35132407

• Microbial enzymes induce colitis by reactivating triclosan in the mouse gastrointestinal tract. Nature communications Zhang, J., Walker, M. E., Sanidad, K. Z., Zhang, H., Liang, Y., Zhao, E., Chacon-Vargas, K., Yeliseyev, V., Parsonnet, J., Haggerty, T. D., Wang, G., Simpson, J. B., Jariwala, P. B., Beaty, V. V., Yang, J., Yang, H., Panigrahy, A., Minter, L. M., Kim, D., Gibbons, J. G., Liu, L., Li, Z., Xiao, H., Borlandelli, V., Overkleeft, H. S., Cloer, E. W., Major, M. B., Goldfarb, D., Cai, Z., Redinbo, M. R., Zhang, G. 1800; 13 (1): 136

  Abstract

  Emerging research supports that triclosan (TCS), an antimicrobial agent found in thousands of consumer products, exacerbates colitis and colitis-associated colorectal tumorigenesis in animal models. While the intestinal toxicities of TCS require the presence of gut microbiota, the molecular mechanisms involved have not been defined. Here we show that intestinal commensal microbes mediate metabolic activation of TCS in the colon and drive its gut toxicology. Using a range of in vitro, ex vivo, and in vivo approaches, we identify specific microbial beta-glucuronidase (GUS) enzymes involved and pinpoint molecular motifs required to metabolically activate TCS in the gut. Finally, we show that targeted inhibition of bacterial GUS enzymes abolishes the colitis-promoting effects of TCS, supporting an essential role of specific microbial proteins in TCS toxicity. Together, our results define a mechanism by which intestinal microbes contribute to the metabolic activation and gut toxicity of TCS, and highlight the importance of considering the contributions of the gut microbiota in evaluating the toxic potential of environmental chemicals.

  View details for DOI 10.1038/s41467-021-27762-y

  View details for PubMedID 35013263

• Long Term Accuracy of SARS-CoV-2 Interferon-γ Release Assay and its Application in Household Investigation. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America Murugesan, K., Jagannathan, P., Altamirano, J., Maldonado, Y. A., Bonilla, H. F., Jacobson, K. B., Parsonnet, J., Andrews, J. R., Shi, R. Z., Boyd, S., Pinsky, B. A., Singh, U., Banaei, N. 2022

  Abstract

  An immunodiagnostic assay that sensitively detects a cell-mediated immune response to SARS-CoV-2 is needed for epidemiological investigation and for clinical assessment of T cell-mediated immune response to vaccines, particularly in the context of emerging variants that might escape antibody responses.The performance of a whole blood interferon-gamma (IFN-γ) release assay (IGRA) for the detection of SARS-CoV-2 antigen-specific T cells was evaluated in COVID-19 convalescents tested serially up to 10 months post-infection and in healthy blood donors. SARS-CoV-2 IGRA was applied in contacts of households with index cases. Freshly collected blood in the lithium heparin tube was left unstimulated, stimulated with a SARS-CoV-2 peptide pool, and stimulated with mitogen.The overall sensitivity and specificity of IGRA were 84.5% (153/181; 95% confidence interval [CI] 79.0-89.0) and 86.6% (123/142; 95% CI;80.0-91.2), respectively. The sensitivity declined from 100% (16/16; 95% CI 80.6-100) at 0.5-month post-infection to 79.5% (31/39; 95% CI 64.4-89.2) at 10 months post-infection (P<0.01). The IFN-γ response remained relatively robust at 10 months post-infection (3.8 vs. 1.3 IU/mL, respectively). In 14 households, IGRA showed a positivity rate of 100% (12/12) and 65.2% (15/23), and IgG of 50.0% (6/12) and 43.5% (10/23) in index cases and contacts, respectively, exhibiting a difference of +50% (95% CI +25.4-+74.6) and +21.7% (95% CI, +9.23-+42.3), respectively. Either IGRA or IgG was positive in 100% (12/12) of index cases and 73.9% (17/23) of contacts.The SARS-CoV-2 IGRA is a useful clinical diagnostic tool for assessing cell-mediated immune response to SARS-CoV-2.

  View details for DOI 10.1093/cid/ciac045

  View details for PubMedID 35079772

• COVID19 Vaccine Type and Humoral Immune Response in Patients Receiving Dialysis. Journal of the American Society of Nephrology : JASN Garcia, P., Anand, S., Han, J., Montez-Rath, M., Sun, S., Shang, T., Parsonnet, J., Chertow, G., Schiller, B., Abra, G. 2021

  View details for DOI 10.1681/ASN.2021070936

  View details for PubMedID 34645698

• The COVID-19 Outpatient Pragmatic Platform Study (COPPS): Study design of a multi-center pragmatic platform trial. Contemporary clinical trials Bunning, B., Hedlin, H., Purington, N., Sundaram, V., Kapphahn, K., Weng, Y., Cunanan, K., Maldonado, Y., Singh, U., Khosla, C., O'Hara, R., Nicolls, M., Springman, E., Parsonnet, J., Rogers, A., Levitt, J., Desai, M. 2021: 106509

  Abstract

  More than 3000 clinical trials related to COVID-19 have been registered through clinicaltrials.gov. With so many trials, there is a risk that many will be inconclusive due to being underpowered or due to an inability to recruit patients. At academic medical centers, multiple trials are competing for the same resources; the success of one may come at the expense of another. The COVID-19 Outpatient Pragmatic Protocol Study (COPPS) is a flexible phase 2, multi-site, randomized, blinded trial based at Stanford University designed to overcome these issues by simultaneously evaluating multiple COVID-19 treatments in the outpatient setting in one common platform with shared controls. This approach reduces the overall number of patients required for statistical power, while improving the likelihood that any enrolled patient receives active treatment. The platform study has two main domains designed to evaluate COVID-19 treatments by assessing their ability to reduce viral shedding (Viral Domain), measured with self-collected nasal swabs, or improve clinical outcomes (Clinical Domain), measured through self-reported symptomology data. Data are collected on both domains for all participants enrolled. Participants are followed over a 28-day period. COPPS has the advantage of pragmatism created around its workflow that is also appealing to potential participants because of a lower probability of inactive treatment. At the conclusion of this clinical trial we expect to have identified potentially effective therapeutic strategy/ies for treating COVID-19 in the outpatient setting, which will have a transformative impact on medicine and public health.

  View details for DOI 10.1016/j.cct.2021.106509

  View details for PubMedID 34274494

• Antibody Response to COVID-19 Vaccination in Patients Receiving Dialysis. Journal of the American Society of Nephrology : JASN Anand, S., Montez-Rath, M., Han, J., Garcia, P., Cadden, L., Hunsader, P., Kerschmann, R., Beyer, P., Dittrich, M., Block, G., Boyd, S., Parsonnet, J., Chertow, G. 2021

  View details for DOI 10.1681/ASN.2021050611

  View details for PubMedID 34117129

• Metabolic fate of environmental chemical triclocarban in colon tissues: roles of gut microbiota involved. The Science of the total environment Wang, G., Zhang, H., Zhang, J., Sanidad, K. Z., Yeliseyev, V., Parsonnet, J., Haggerty, T. D., Yang, H., Ai, L., Xie, M., Cai, Z., Zhang, G. 2021; 787: 147677

  Abstract

  Metabolic transformations play critical roles in the bioavailability and toxicities of environmental pollutants and toxicants. However, most previous research has focused on the metabolic reactions in host tissues, the gut microbiota-mediated biotransformation of environmental compounds is understudied. Using triclocarban (TCC) as a model environmental compound, here we study the metabolic fate of TCC in gut tissues and determine the roles of gut microbiota involved. We find that compared with other tissues, the colon tissue has a unique metabolic profile of TCC, with high abundance of the parent compound TCC and its free-form metabolites. Using a variety of approaches including antibiotic-mediated suppression of gut bacteria in vivo, germ-free mice, and in vitro culture of fecal bacteria, we found that the unique metabolic profile of TCC in the colon is mediated by the actions of gut microbiota. Overall, our findings support that gut microbiota plays important roles in colonic metabolism of TCC, highlighting the importance to consider the contributions of gut microbiota in toxicology evaluation of environmental compounds.

  View details for DOI 10.1016/j.scitotenv.2021.147677

  View details for PubMedID 34004538

• SARS-COV-2 VACCINE ACCEPTABILITY IN PATIENTS ON DIALYSIS: A NATIONWIDE SURVEY Garcia, P., Montez-Rath, M., Moore, H., Flotte, J., Fults, C., Block, M., Han, J., Dittrich, M., Parsonnet, J., Chertow, G., Block, G., Anand, S. W B SAUNDERS CO-ELSEVIER INC. 2021: 831

  View details for Web of Science ID 000642322000031

• SARS-CoV-2 Vaccine Acceptability in Patients on Hemodialysis: A Nationwide Survey. Journal of the American Society of Nephrology : JASN Garcia, P., Montez-Rath, M. E., Moore, H., Flotte, J., Fults, C., Block, M. S., Han, J., Dittrich, M., Parsonnet, J., Chertow, G. M., Block, G. A., Anand, S. 2021

  Abstract

  BACKGROUND: Patients on dialysis are at increased risk for COVID-19-related complications. However, a substantial fraction of patients on dialysis belong to groups more likely to be hesitant about vaccination.METHODS: With the goal of identifying strategies to increase COVID-19 vaccine uptake among patients on hemodialysis, we conducted a nationwide vaccine acceptability survey, partnering with a dialysis network to distribute an anonymized English and Spanish language online survey in 150 randomly selected facilities in the United States. We used logistic regression to evaluate characteristics of vaccine-hesitant persons.RESULTS: A total of 1515 (14% of eligible) patients responded; 20% of all responders, 29% of patients aged 18-44 years, and 29% of Black responders reported being hesitant to seek the COVID-19 vaccine, even if the vaccine was considered safe for the general population. Odds of vaccine hesitancy were higher among patients aged 18-44 years versus those 45-64 years (odds ratio [OR], 1.5; 95% confidence interval [95% CI], 1.0 to 2.3), Black patients versus non-Hispanic White patients (OR, 1.9; 95% CI, 1.3 to 2.7), Native Americans or Pacific Islanders versus non-Hispanic White patients (OR, 2.0; 95% CI, 1.1 to 3.7), and women versus men (OR, 1.6; 95% CI, 1.2 to 2.0). About half (53%) of patients who were vaccine hesitant expressed concerns about side effects. Responders' main information sources about COVID-19 vaccines were television news and dialysis staff (68% and 38%, respectively).CONCLUSIONS: A substantial proportion of patients receiving in-center hemodialysis in the United States are hesitant about seeking COVID-19 vaccination. Facilitating uptake requires outreach to younger patients, women, and Black, Native American, or Pacific Islander patients, and addressing concerns about side effects.

  View details for DOI 10.1681/ASN.2021010104

  View details for PubMedID 33927004

• Temperature Measurement at Well-Child Visits in the United States. The Journal of pediatrics Dang, R. n., Schroeder, A. R., Patel, A. I., Parsonnet, J. n., Wang, M. n. 2021

  Abstract

  To determine the frequency and predictors of temperature measurement at well-child visits in the US and report rates of interventions associated with visits at which temperature is measured and fever is detected.In this cross-sectional study, we analyzed 22,518 sampled well-child visits from the National Ambulatory Medical Care Survey (NAMCS) between 2003 and 2015. We estimated the frequency of temperature measurement and performed multivariable regression to identify patient, provider/clinic and seasonal factors associated with the practice. We described rates of interventions (complete blood count, x-ray, urinalysis, antibiotic prescription, and emergency department/hospital referral) by measurement and fever (temperature ≥100.4˚F, ≥38.0˚C) status.Temperature was measured in 48.5% (95% CI 45.6-51.4) of well-child visits. Measurement was more common during visits by non-pediatric providers (adjusted odds ratio [aOR] 2.0, 95% CI 1.6-2.5; ref: pediatricians), in Hispanic (aOR 1.9, 95% CI 1.6-2.3) and Black (aOR 1.5, 95% CI 1.2-1.9; ref: non-Hispanic White) patients, and in patients with government (aOR 2.0, 95% CI 1.7-2.4; ref: private) insurance. Interventions were more commonly pursued when temperature was measured (aOR 1.3, 95% CI 1.1-1.6) and fever was detected (aOR 3.8, 95% CI 1.5-9.4).Temperature was measured in nearly half of all well-child visits. Interventions were more common when temperature was measured and fever was detected. The value of routine temperature measurement during well-child visits warrants further evaluation.

  View details for DOI 10.1016/j.jpeds.2021.01.045

  View details for PubMedID 33508277

• Antibody Response to COVID-19 vaccination in Patients Receiving Dialysis. medRxiv : the preprint server for health sciences Anand, S., Montez-Rath, M. E., Han, J., Garcia, P., Cadden, L., Hunsader, P., Kerschmann, R., Beyer, P., Dittrich, M., Block, G. A., Boyd, S. D., Parsonnet, J., Chertow, G. M. 2021

  Abstract

  Patients receiving dialysis may mount impaired responses to COVID19 vaccination.We report antibody response to vaccination from 1140 patients without, and 493 patients with pre-vaccination SARS-CoV-2 RBD antibody. We used commercially available assays (Siemens) to test remainder plasma monthly in association with vaccination date and type, and assess prevalence of absent total receptor binding antibody, and absent or attenuated (index value < 10) semiquantitative receptor binding domain IgG index values. We used Poisson regression to evaluate risk factors for absent or attenuated response to vaccination.Among patients who were seronegative versus seropositive before vaccination, 62% and 56% were ≥65 years old, 20% and 24% were Hispanic, and 22% and 23% were Black. Median IgG index values rose steadily over time, and were higher among the seropositive than in the seronegative patients after completing vaccination (150 [25 th , 75 th percentile 23.2, 150.0] versus 41.6 [11.3, 150.0]). Among 610 patients who completed vaccination (assessed ≥14 days later, median 29 days later), the prevalence of absent total RBD response, and absent and attenuated semiquantitative IgG response was 4.4% (95% CI 3.1, 6.4%), 3.4% (2.4, 5.2%), and 14.3% (11.7, 17.3%) respectively. Risk factors for absent or attenuated response included longer vintage of end-stage kidney disease, and lower pre-vaccination serum albumin.More than one in five patients receiving dialysis had evidence of an attenuated immune response to COVID19 vaccination.Patients receiving dialysis face high likelihood of severe COVID19; at the same time, vaccination may be less efficacious, as prior data indicate impaired immune responses to influenza and Hepatitis B vaccination. We found that 22% of patients receiving dialysis had suboptimal responses to vaccination, irrespective of whether or not they had evidence of prior SARS-CoV-2 infection. Poorer health status and longer duration of end-stage kidney disease increased likelihood of suboptimal response. Ongoing vigilance for COVID19 in dialysis facilities and studies of modified vaccination dosing schedules will be critical to protecting patients receiving dialysis.

  View details for DOI 10.1101/2021.05.06.21256768

  View details for PubMedID 34013281

  View details for PubMedCentralID PMC8132255

• SARS-CoV-2 subgenomic RNA kinetics in longitudinal clinical samples Open Forum Infectious Diseases Verma, R., Kim, E., Martinez, G., Jagannathan, ., Rustagi, A., Parsonnet, J., Bonilla, H., Khosla, C., Holubar, M., Subramanian, A., Singh, ., Maldonado, Y., Blish, C., Andrews, J. 2021

  View details for DOI 10.1093/ofid/ofab310

• Inflammatory but not respiratory symptoms are associated with ongoing upper airway viral shedding in outpatients with uncomplicated COVID-19. Diagnostic microbiology and infectious disease Jacobson, K. B., Purington, N., Parsonnet, J., Andrews, J., Balasubramanian, V., Bonilla, H., Edwards, K., Desai, M., Singh, U., Hedlin, H., Jagannathan, P. 2021; 102 (3): 115612

  Abstract

  Although the vast majority of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infections are uncomplicated, our understanding of predictors of symptom resolution and viral shedding cessation remains limited. We characterized symptom trajectories and oropharyngeal viral shedding among 120 outpatients with uncomplicated Coronavirus Disease of 2019 (COVID-19) enrolled in a clinical trial of Peginterferon Lambda, which demonstrated no clinical or virologic benefit compared with placebo. In the combined trial cohort, objective fever was uncommon, inflammatory symptoms (myalgias, fatigue) peaked at 4 to 5 days postsymptom onset, and cough peaked at 9 days. The median time to symptom resolution from earliest symptom onset was 17 days (95% confidence interval 14-18). SARS-CoV-2 IgG seropositivity at enrollment was associated with hastened resolution of viral shedding (hazard ratio 1.80, 95% confidence interval 1.05-3.1, P = 0.03), but not with symptom resolution. Inflammatory symptoms were associated with a significantly greater odds of oropharyngeal SARS-CoV-2 RNA detection; respiratory symptoms were not. These findings have important implications for COVID-19 screening approaches and trial design.

  View details for DOI 10.1016/j.diagmicrobio.2021.115612

  View details for PubMedID 34974350

• Laboratory correlates of SARS-CoV-2 seropositivity in a nationwide sample of patients on dialysis in the U.S. PloS one Anand, S., Montez-Rath, M. E., Han, J., Garcia, P., Bozeman, J., Kerschmann, R., Beyer, P., Parsonnet, J., Chertow, G. M. 2021; 16 (4): e0249466

  Abstract

  Patients on dialysis are at high risk for death due to COVID-19, yet a significant proportion do survive as evidenced by presence of SARS-CoV-2 antibodies in 8% of patients in the U.S. in July 2020. It is unclear whether patients with seropositivity represent the subgroup with robust health status, who would be more likely to mount a durable antibody response. Using data from a July 2020 sample of 28,503 patients receiving dialysis, we evaluated the cross-sectional association of SARS-CoV-2 seropositivity with laboratory surrogates of patient health. In separate logistic regression models, we assessed the association of SARS-CoV-2 seropositivity with seven laboratory-based covariates (albumin, creatinine, hemoglobin, sodium, potassium, phosphate, and parathyroid hormone), across the entire range of the laboratory and in comparison to a referent value. Models accounted for age, sex, region, race and ethnicity, and county-level COVID-19 deaths per 100,000. Odds of seropositivity for albumin 3 and 3.5 g/dL were 2.1 (95% CI 1.9-2.3) and 1.3 (1.2-1.4) respectively, compared with 4 g/dL. Odds of seropositivity for serum creatinine 5 and 8 mg/dL were 1.8 (1.6-2.0) and 1.3 (1.2-1.4) respectively, compared with 12.5 mg/dL. Lower values of hemoglobin, sodium, potassium, phosphate, and parathyroid hormone were associated with higher odds of seropositivity. Laboratory values associated with poorer health status and higher risk for mortality were also associated with higher likelihood of SARS-CoV-2 antibodies in patients receiving dialysis.

  View details for DOI 10.1371/journal.pone.0249466

  View details for PubMedID 33857168

• SARS-CoV-2 Seroprevalence in Healthcare Personnel in Northern California Early in the COVID-19 Pandemic. Infection control and hospital epidemiology Rosser, J. I., Roltgen, K., Dymock, M., Shepard, J., Martin, A., Hogan, C. A., Blomkalns, A., Mathew, R., Parsonnet, J., Pinsky, B. A., Maldonado, Y. A., Boyd, S. D., Chang, S., Holubar, M., Stanford Healthcare COVID-19 Workforce Response Group 2020: 1–27

  Abstract

  OBJECTIVE: We aimed to assess the magnitude of unidentified SARS-CoV-2 infections in our healthcare personnel (HCP) early in the COVID-19 pandemic and evaluate risk factors for infection in order to identify areas for infection control practice improvement in a northern California academic medical center.METHODS: We reviewed the anti-SARS-CoV-2 receptor binding domain (RBD) IgG serologic test results and self-reported risk factors for seropositivity among 10,449 asymptomatic HCP who underwent voluntary serology testing between April 20 and May 20, 2020.RESULTS: In total, 136 employees (1.3%) tested positive for SARS-CoV-2 IgG. This included 41 (30.1%) individuals who had previously tested positive for SARS-CoV-2 by nasopharyngeal reverse transcription polymerase chain reaction (RT-PCR) between March 13 and April 16, 2020. In multivariable analysis, employees of Hispanic ethnicity (OR = 2.01; 95% CI = 1.22-3.46) and those working in environmental services/food services/patient transport (OR = 4.81; 95% CI = 2.08-10.30) were at increased risk for seropositivity compared to other groups. Employees reporting a household contact with COVID-19 were also at higher risk for seropositivity (OR = 3.25; 95% CI = 1.47-6.44), but those with a work exposure were not (OR = 1.27; 95% CI = 0.58-2.47). Importantly, one-third of seropositive individuals reported no prior symptoms, no suspected exposures, and no prior positive RT-PCR test.CONCLUSION: In this study, SARS-CoV-2 seropositivity among HCP early in the northern California epidemic appeared to be quite low and was more likely attributable to community rather than occupational exposure.

  View details for DOI 10.1017/ice.2020.1358

  View details for PubMedID 33292895

• Metagenomic sequencing of stool samples in Bangladeshi infants: virome association with poliovirus shedding after oral poliovirus vaccination. Scientific reports Tan, S. K., Granados, A. C., Bouquet, J., Hoy-Schulz, Y. E., Green, L., Federman, S., Stryke, D., Haggerty, T. D., Ley, C., Yeh, M., Jannat, K., Maldonado, Y. A., Andino, R., Parsonnet, J., Chiu, C. Y. 2020; 10 (1): 15392

  Abstract

  The potential role of enteric viral infections and the developing infant virome in affecting immune responses to the oral poliovirus vaccine (OPV) is unknown. Here we performed viral metagenomic sequencing on 3 serially collected stool samples from 30 Bangladeshi infants following OPV vaccination and compared findings to stool samples from 16 age-matched infants in the United States (US). In 14 Bangladeshi infants, available post-vaccination serum samples were tested for polio-neutralizing antibodies. The abundance (p=0.006) and richness (p=0.013) of the eukaryotic virome increased with age and were higher than seen in age-matched US infants (p<0.001). In contrast, phage diversity metrics remained stable and were similar to those in US infants. Non-poliovirus eukaryotic virus abundance (3.68 log10 vs. 2.25 log10, p=0.002), particularly from potential viral pathogens (2.78log10 vs. 0.83log10, p=0.002), and richness (p=0.016) were inversely associated with poliovirus shedding. Following vaccination, 28.6% of 14 infants tested developed neutralizing antibodies to all three Sabin types and also exhibited higher rates of poliovirus shedding (p=0.020). No vaccine-derived poliovirus variants were detected. These results reveal an inverse association between eukaryotic virome abundance and poliovirus shedding. Overall gut virome ecology and concurrent viral infections may impact oral vaccine responsiveness in Bangladeshi infants.

  View details for DOI 10.1038/s41598-020-71791-4

  View details for PubMedID 32958861

• A Summary of the 2020 Gastric Cancer Summit at Stanford University. Gastroenterology Huang, R. J., Koh, H., Hwang, J. H., Summit Leaders, Abnet, C. C., Alarid-Escudero, F., Amieva, M. R., Bruce, M. G., Camargo, M. C., Chan, A. T., Choi, I. J., Corvalan, A., Davis, J. L., Deapen, D., Epplein, M., Greenwald, D. A., Hamashima, C., Hur, C., Inadomi, J. M., Ji, H. P., Jung, H., Lee, E., Lin, B., Palaniappan, L. P., Parsonnet, J., Peek, R. M., Piazuelo, M. B., Rabkin, C. S., Shah, S. C., Smith, A., So, S., Stoffel, E. M., Umar, A., Wilson, K. T., Woo, Y., Yeoh, K. G. 2020

  View details for DOI 10.1053/j.gastro.2020.05.100

  View details for PubMedID 32707045

• The risk of tuberculosis in children after close exposure: a systematic review and individual-participant meta-analysis LANCET Martinez, L., Cords, O., Horsburgh, C., Andrews, J. R., Pediat TB Contact Studies 2020; 395 (10228): 973–84

  View details for Web of Science ID 000521744600028

• Gut microbiota plasticity is correlated with sustained weight loss on a low-carb or low-fat dietary intervention Scientific Reports Grembi, J. A., Nguyen, L. H., Haggerty, T. D., Gardner, C. D., Holmes, S. P., Parsonnet, J. 2020; 10

  View details for DOI 10.1038/s41598-020-58000-y

• Frequent occurrence of triclosan hydroxylation in mammals: A combined theoretical and experimental investigation. Journal of hazardous materials Zhang, H. n., Sanidad, K. Z., Zhu, L. n., Parsonnet, J. n., Haggerty, T. D., Zhang, G. n., Cai, Z. n. 2020; 407: 124803

  Abstract

  Triclosan (TCS) is a widespread antimicrobial agent with many adverse health risks. Its hepatoxicity invariably points to the activation of constitutive androstane receptor (CAR), which regulates cytochrome P450 (CYP) genes that are critical for oxidative metabolism. Here, we provide the theoretical and experimental evidences showing that metabolic activation of TCS frequently occurs through aromatic hydroxylation in mammals. CYP-mediated oxidation was predicted to take place at each aromatic C‒H bond. Molecular docking and in vitro approaches reveal oxidative reaction could be efficiently catalyzed by CAR-regulated CYP2B6 enzyme. Parallel reaction monitoring (PRM) high-resolution mass spectrometry was utilized to identify and profile TCS oxidative metabolites in paired mouse liver, bile, feces, plasma and urine. We found multiple hydroxylated isomers including the products generated via the NIH shift of chlorine, as well as their subsequent conjugates. These metabolites showed isomer-specific retention in mice. Glucuronide conjugates are more readily excreted than the sulfates. Moreover, for the first time, isomeric hydroxylated metabolites were detected in the urine and stool of human subjects used TCS-contained household and personal care products. Collectively, these findings suggest that hydroxylation is an important, yet often underestimated element that worth considering to fully evaluate the biological fates and health risks of TCS.

  View details for DOI 10.1016/j.jhazmat.2020.124803

  View details for PubMedID 33338815

• Symptomatic SARS-CoV-2 infections display specific IgG Fc structures. medRxiv : the preprint server for health sciences Chakraborty, S. n., Edwards, K. n., Buzzanco, A. S., Memoli, M. J., Sherwood, R. n., Mallajosyula, V. n., Xie, M. M., Gonzalez, J. n., Buffone, C. n., Kathale, N. n., Providenza, S. n., Jagannathan, P. n., Andrews, J. R., Blish, C. A., Krammer, F. n., Dugan, H. n., Wilson, P. C., Pham, T. D., Boyd, S. D., Zhang, S. n., Taubenberger, J. K., Morales, T. n., Schapiro, J. M., Parsonnet, J. n., Wang, T. T. 2020

  Abstract

  The ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has caused a public health crisis that is exacerbated by our poor understanding of correlates of immunity. SARS-CoV-2 infection can cause Coronavirus Disease 2019 (COVID-19), with a spectrum of symptoms ranging from asymptomatic carriage to life threatening pneumonia and cytokine dysregulation [1-3]. Although antibodies have been shown in a variety of in vitro assays to promote coronavirus infections through mechanisms requiring interactions between IgG antibodies and Fc gamma receptors (FcγRs), the relevance of these observations to coronavirus infections in humans is not known [4-7]. In light of ongoing clinical trials examining convalescent serum therapy for COVID-19 patients and expedited SARS-CoV-2 vaccine testing in humans, it is essential to clarify the role of antibodies in the pathogenesis of COVID-19. Here we show that adults with PCR-diagnosed COVID-19 produce IgG antibodies with a specific Fc domain repertoire that is characterized by reduced fucosylation, a modification that enhances interactions with the activating FcγR, FcγRIIIa. Fc fucosylation was reduced when compared with SARS-CoV-2-seropositive children and relative to adults with symptomatic influenza virus infections. These results demonstrate an antibody correlate of symptomatic SARS-CoV-2 infections in adults and have implications for novel therapeutic strategies targeting FcγRIIIa pathways.

  View details for DOI 10.1101/2020.05.15.20103341

  View details for PubMedID 32511463

  View details for PubMedCentralID PMC7252581

• Interferon-gamma release assay for accurate detection of SARS-CoV-2 T cell response. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America Murugesan, K. n., Jagannathan, P. n., Pham, T. D., Pandey, S. n., Bonilla, H. F., Jacobson, K. n., Parsonnet, J. n., Andrews, J. R., Weiskopf, D. n., Sette, A. n., Pinsky, B. A., Singh, U. n., Banaei, N. n. 2020

  Abstract

  We investigated feasibility and accuracy of an interferon-gamma release assay (IGRA) for detection of T cell responses to SARS-CoV-2. Whole blood IGRA accurately distinguished between convalescents and uninfected healthy blood donors with a predominantly CD4+ T cell response. SARS-CoV-2 IGRA may serve as a useful diagnostic tool in managing the COVID-19 pandemic.

  View details for DOI 10.1093/cid/ciaa1537

  View details for PubMedID 33035306

• Combating gastric cancer in Alaska Native people: An expert and community symposium: Alaska Native Gastric Cancer Symposium. Gastroenterology Nolen, L. D., Vindigni, S. M., Parsonnet, J., Symposium Leaders, Bruce, M. G., Martinson, H. A., Thomas, T. K., Sacco, F., Nash, S., Olnes, M. J., Miernyk, K., Bruden, D., Ramaswamy, M., McMahon, B., Goodman, K. J., Bass, A. J., Hur, C., Inoue, M., Camargo, M. C., Cho, S., Parnell, K., Allen, E., Woods, T., Melkonian, S. 2019

  Abstract

  Alaska Native (AN) people experience higher incidence of, and mortality from, gastric cancer compared to other U.S. populations1, 2. Compared to the general U.S. population, gastric cancer in AN people occurs at a younger age, is diagnosed at later stages, is more evenly distributed between the sexes, and is more frequently signet-ring or diffuse histology3. It is known that the prevalence of Helicobacter pylori (Hp) infection, a risk factor for gastric cancer, is high in AN people4; however, high antimicrobial resistance combined with high reinfection rates in Alaska make treatment at the population level complex5. In addition, health issues in AN people are uniquely challenging due to the extremely remote locations of many residents. A multiagency workgroup hosted a symposium in Anchorage that brought internationally-recognized experts and local leaders together to evaluate issues around gastric cancer in the AN population. The overall goal of this symposium was to identify the best strategies to combat gastric cancer in the AN population through prevention and early diagnosis.

  View details for DOI 10.1053/j.gastro.2019.11.299

  View details for PubMedID 31836529

• Increased T Cell Differentiation and Cytolytic Function in Bangladeshi Compared to American Children FRONTIERS IN IMMUNOLOGY Wager, L. E., Bolen, C. R., Sigel, N., Angel, C., Guan, L., Kirkpatrick, B. D., Haque, R., Tibshirani, R. J., Parsonnet, J., Petri, W. A., Davis, M. M. 2019; 10

  View details for DOI 10.3389/fimmu.2019.02239

  View details for Web of Science ID 000487188500001

• Circulating inflammation-related markers and advanced gastric premalignant lesions JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY Song, M., Rabkin, C. S., Torres, J., Kemp, T. J., Zabaleta, J., Pinto, L. A., Hildesheim, A., Sanchez-Figueroa, L., Guarner, J., Herrera-Goepfert, R., Parsonnet, J., Camargo, M. 2019; 34 (5): 852–56

  View details for DOI 10.1111/jgh.14518

  View details for Web of Science ID 000466565500011

• Recall accuracy of weekly automated surveys of health care utilization and infectious disease symptoms among infants over the first year of life. PloS one Ley, C., Willis, L., de la Luz Sanchez, M., Parsonnet, J. 2019; 14 (12): e0226623

  Abstract

  Automated surveys, by interactive voice response (IVR) or email, are increasingly used for clinical research. Although convenient and inexpensive, they have uncertain validity. We sought to assess the accuracy of longitudinally-collected automated survey responses compared to medical records. Using data collected from a well-characterized, prospective birth cohort over the first year of life, we examined concordance between guardians' reports of their infants' health care visits ascertained by weekly automated survey (IVR or email) and those identified by medical chart review. Among 180 survey-visit pairs, concordance was 51%, with no change as number of visits per baby increased. Accuracy of recall was higher by email compared to IVR (61 vs. 43%; adjusted OR = 2.5 95% CI: 1.3-4.8), did not vary by health care encounter type (hospitalization: 50%, ER: 64%, urgent care: 44%, primary care: 52%; p = 0.75), but was higher for fever (77%, adjusted OR = 5.1 95%CI: 1.5-17.7) and respiratory illness (58%, adjusted OR = 2.9 95%CI: 1.5-5.8) than for other diagnoses. For the 75 mothers in these encounters, 69% recalled at least one visit; among 41 mothers with two or more visits, 85% recalled at least one visit. Predictors of accurate reporting by mothers after adjusting for illness in the baby included increased age and increased years of education (age per year, beta = 0.05, p = 0.03; education per year, beta = 0.08, p = 0.04). Additional strategies beyond use of automated surveys are needed to ascertain accurate health care utilization in longitudinal cohort studies, particularly in healthy populations with little motivation for accurate reporting.

  View details for DOI 10.1371/journal.pone.0226623

  View details for PubMedID 31846482

• Vitamin D status and risk of incident tuberculosis disease: A nested case-control study, systematic review, and individual-participant data meta-analysis. PLoS medicine Aibana, O. n., Huang, C. C., Aboud, S. n., Arnedo-Pena, A. n., Becerra, M. C., Bellido-Blasco, J. B., Bhosale, R. n., Calderon, R. n., Chiang, S. n., Contreras, C. n., Davaasambuu, G. n., Fawzi, W. W., Franke, M. F., Galea, J. T., Garcia-Ferrer, D. n., Gil-Fortuño, M. n., Gomila-Sard, B. n., Gupta, A. n., Gupte, N. n., Hussain, R. n., Iborra-Millet, J. n., Iqbal, N. T., Juan-Cerdán, J. V., Kinikar, A. n., Lecca, L. n., Mave, V. n., Meseguer-Ferrer, N. n., Montepiedra, G. n., Mugusi, F. M., Owolabi, O. A., Parsonnet, J. n., Roach-Poblete, F. n., Romeu-García, M. A., Spector, S. A., Sudfeld, C. R., Tenforde, M. W., Togun, T. O., Yataco, R. n., Zhang, Z. n., Murray, M. B. 2019; 16 (9): e1002907

  Abstract

  Few studies have evaluated the association between preexisting vitamin D deficiency and incident tuberculosis (TB). We assessed the impact of baseline vitamins D levels on TB disease risk.We assessed the association between baseline vitamin D and incident TB in a prospective cohort of 6,751 HIV-negative household contacts of TB patients enrolled between September 1, 2009, and August 29, 2012, in Lima, Peru. We screened for TB disease at 2, 6, and 12 months after enrollment. We defined cases as household contacts who developed TB disease at least 15 days after enrollment of the index patient. For each case, we randomly selected four controls from among contacts who did not develop TB disease, matching on gender and year of age. We also conducted a one-stage individual-participant data (IPD) meta-analysis searching PubMed and Embase to identify prospective studies of vitamin D and TB disease until June 8, 2019. We included studies that assessed vitamin D before TB diagnosis. In the primary analysis, we defined vitamin D deficiency as 25-(OH)D < 50 nmol/L, insufficiency as 50-75 nmol/L, and sufficiency as >75nmol/L. We estimated the association between baseline vitamin D status and incident TB using conditional logistic regression in the Lima cohort and generalized linear mixed models in the meta-analysis. We further defined severe vitamin D deficiency as 25-(OH)D < 25 nmol/L and performed stratified analyses by HIV status in the IPD meta-analysis. In the Lima cohort, we analyzed 180 cases and 709 matched controls. The adjusted odds ratio (aOR) for TB risk among participants with baseline vitamin D deficiency compared to sufficient vitamin D was 1.63 (95% CI 0.75-3.52; p = 0.22). We included seven published studies in the meta-analysis and analyzed 3,544 participants. In the pooled analysis, the aOR was 1.48 (95% CI 1.04-2.10; p = 0.03). The aOR for severe vitamin D deficiency was 2.05 (95% CI 0.87-4.87; p trend for decreasing 25-(OH)D levels from sufficient vitamin D to severe deficiency = 0.02). Among 1,576 HIV-positive patients, vitamin D deficiency conferred a 2-fold (aOR 2.18, 95% CI 1.22-3.90; p = 0.01) increased risk of TB, and the aOR for severe vitamin D deficiency compared to sufficient vitamin D was 4.28 (95% CI 0.85-21.45; p = 0.08). Our Lima cohort study is limited by the short duration of follow-up, and the IPD meta-analysis is limited by the number of possible confounding covariates available across all studies.Our findings suggest vitamin D predicts TB disease risk in a dose-dependent manner and that the risk of TB disease is highest among HIV-positive individuals with severe vitamin D deficiency. Randomized control trials are needed to evaluate the possible role of vitamin D supplementation on reducing TB disease risk.

  View details for DOI 10.1371/journal.pmed.1002907

  View details for PubMedID 31509529

• Circulating Inflammation-related Markers and Advanced Gastric Premalignant Lesions. Journal of gastroenterology and hepatology Song, M., Rabkin, C. S., Torres, J., Kemp, T. J., Zabaleta, J., Pinto, L. A., Hildesheim, A., Sanchez-Figueroa, L., Guarner, J., Herrera-Goepfert, R., Parsonnet, J., Camargo, M. C. 2018

  Abstract

  BACKGROUND AND AIM: Chronic Helicobacter pylori infection causes gastric mucosal inflammation as an important antecedent of gastric cancer. We aimed to evaluate associations of blood markers of inflammation with gastric intestinal metaplasia and dysplasia in H. pylori-infected individuals.METHODS: We compared pre-treatment serum levels of immune- and inflammation-related markers between 99 individuals with intestinal metaplasia or dysplasia, and 75 control individuals with non-atrophic gastritis within an H. pylori eradication trial in Mexico. Serum levels of 28 markers measured with Luminex bead-based assays were categorized in tertiles as low (T1), middle (T2) and high (T3). Logistic regression models were used to calculate age- and sex- adjusted odds ratios (OR) and 95% confidence intervals (CI). All statistical tests were two-sided and significance values were adjusted for multiple comparisons using false discovery rate (FDR) methods.RESULTS: Five markers were nominally associated (p-trends <0.05) with the presence of advanced premalignant gastric lesions. Adjusted ORs (95% CI) of T2 and T3 vs. T1 were 4.09 (1.65-10.17) and 3.08 (1.23-7.68) for CCL3/MIP1a, 3.21 (1.33-7.75) and 2.69 (1.10-6.57) for CCL20/MIP3a levels, 1.79 (0.77-4.18) and 2.39 (1.02-5.60) for IL1beta, 1.34 (0.56-3.19) and 3.02 (1.29-7.12) for IL4, and 1.07 (0.44-2.59) and 3.07 (1.32-7.14) for IL5, respectively. Two (IL4 and IL5) of the five markers had FDR adjusted p-trend <0.2.CONCLUSIONS: Our results suggest certain Th2 and other cytokines may have a role in promoting carcinogenesis in the setting of H. pylori infection. Additional research is needed to replicate these findings, extend to pre-diagnostic samples and elucidate the underlying mechanisms.

  View details for PubMedID 30357905

• Evidence of inflated exclusive breastfeeding estimates from a clinical trial in Bangladesh INTERNATIONAL BREASTFEEDING JOURNAL Roberts, T. J., Hoy-Schulz, Y. E., Jannat, K., Parsonnet, J. 2018; 13: 39

  Abstract

  Suboptimal breastfeeding is a major cause of infant morbidity and mortality across the world. Inconsistent data has hampered quantification of this practice, however, limiting breastfeeding promotion efforts. As part of a clinical trial in Dhaka, Bangladesh, data was collected on breastfeeding patterns among 125 infants. Infants were ages 4 to 12 weeks (mean = 8.05, SD = 2.13) at the time of enrollment, and breastfeeding data were collected at 24 study visits during a twelve-week period. Breastfeeding status was assessed using the WHO-recommended "current status" (24-h recall) method. These data were used to calculate two measures: a longitudinal estimate of exclusive breastfeeding since birth and a simulated cross-sectional prevalence to approximate common data collection methods. Infants were then ranked based on their breastfeeding status at all study visits and grouped into quartiles and compared using hospitalization data recorded for all infants as part of the original study. These data showed large differences in estimates of exclusive breastfeeding behaviors when assessed longitudinally (8.8% exclusive breastfeeding) vs. calculating a cross-sectional prevalence (56.2% exclusive breastfeeding). Additionally, when infants were grouped by quartile of breastfeeding behavior and matched with hospitalization records, it was found that infants in the lowest quartile of breastfeeding behaviors were significantly more likely to be hospitalized than infants in the highest quartile. These results provide further evidence that current breastfeeding epidemiology studies may overestimate rates of exclusive breastfeeding. They also provide further evidence to support the significant infant health benefits from breastfeeding promotion.ClinicalTrials.gov NCT01899378. Registered July 10, 2013.

  View details for PubMedID 30159001

• Triclosan and triclocarban exposure, infectious disease symptoms and antibiotic prescription in infants-A community-based randomized intervention. PloS one Ley, C., Sundaram, V., Sanchez, M. d., Desai, M., Parsonnet, J. 2018; 13 (6): e0199298

  Abstract

  BACKGROUND: Triclosan and triclocarban (TCs) are broad-spectrum antimicrobials that, until recently, were found in a wide variety of household and personal wash products. Popular with consumers, TCs have not been shown to protect against infectious diseases.OBJECTIVES: To determine whether use of TC-containing wash products reduces incidence of infection in children less than one year of age.METHODS: Starting in 2011, we nested a randomized intervention of wash products with and without TCs within a multiethnic birth cohort. Maternal reports of infectious disease symptoms and antibiotic use were collected weekly by automated survey; household visits occurred every four months. Antibiotic prescriptions were identified by medical chart review. Urinary triclosan levels were measured in a participant subset. Differences by intervention group in reported infectious disease (primary outcome) and antibiotic use (secondary outcome) were assessed using mixed effects logistic regression and Fisher's Exact tests, respectively.RESULTS: Infectious illness occurred in 6% of weeks, with upper respiratory illness the predominant syndrome. Among 60 (45%) TC-exposed and 73 (55%) non-TC-exposed babies, infectious disease reports did not differ in frequency between groups (likelihood ratio test: p = 0.88). Medical visits with antibiotic prescriptions were less common in the TC group than in the non-TC group (7.8% vs. 16.6%, respectively; p = 0.02).CONCLUSIONS: Although randomization to TC-containing wash products was not associated with decreased infectious disease reports by mothers, TCs were associated with decreased antibiotic prescriptions, suggesting a benefit against bacterial infection. The recent removal of TCs from consumer wash products makes further elucidation of benefits and risks impracticable.

  View details for DOI 10.1371/journal.pone.0199298

  View details for PubMedID 29953463

• Triclosan and triclocarban exposure and thyroid function during pregnancy-A randomized intervention REPRODUCTIVE TOXICOLOGY Ley, C., Pischel, L., Parsonnet, J. 2017; 74: 143–49

  Abstract

  Triclosan and triclocarban (TCs) are broad-spectrum microbicides found in household and personal wash products. We sought to determine whether TC exposure from wash products or urinary triclosan level modified thyroid function during pregnancy or anthropometric measurements at birth. A randomized intervention of wash products with or without TCs, including toothpaste, enrolled pregnant women from 20 weeks' gestation. Urinary triclosan, TSH, T4 and T3 were assessed at enrollment, 36weeks' gestation and/or post-delivery; anthropometric measures at birth were ascertained from medical records. 78 and 76 mothers were assigned to the TC-containing and no-TC-containing product arms, respectively. No differences were observed in any thyroid function measure at any time point or in any anthropometric measurement at birth between either exposure arms or lowest and highest urinary triclosan quartile groups. TCs from wash products, primarily liquid and bar soaps, did not affect thyroid function measures during pregnancy or babies' anthropometric measures at delivery.

  View details for DOI 10.1016/j.reprotox.2017.09.005

  View details for Web of Science ID 000418315100016

  View details for PubMedID 28939492

  View details for PubMedCentralID PMC5718922

• A survey of probiotic use practices among patients at a tertiary medical centre. Beneficial microbes Draper, K., Ley, C., Parsonnet, J. 2017; 8 (3): 345-351

  Abstract

  Probiotic use has skyrocketed in recent years. Little is known, however, about patient knowledge and practices regarding probiotic use, especially in the context of antibiotic use. An invitation to complete a short, anonymous, electronic survey was sent by email to 965 patients at a tertiary medical centre in California who had agreed to be contacted for participation in research studies. Questions were asked about both probiotic and antibiotic use in the prior three months. Of 333 survey respondents, 55% had recently used probiotics, including food products and/or supplements (90 and 60% of probiotic users, respectively). Women were more likely than men to have used probiotics (odds ratio (OR): 1.99; 95% confidence interval (CI): 1.2-3.4). Health care providers (HCP) had prescribed antibiotics to 79 (24%) respondents in the preceding three months. Among antibiotic users, 33% had initiated or changed probiotics at the time of antibiotic use, usually without a recommendation from their prescribing HCP (72%). Only 12% of those who took probiotics with antibiotics had received a specific recommendation from their HCP. Most patients chose to take probiotic mixtures (56%), with few selecting evidence-based strains, such as Lactobacillus rhamnosus GG (11%). Regular probiotic use among patients is common. Typically, these probiotics are not recommended by a HCP, even in conjunction with antibiotic prescriptions. While a growing body of evidence supports specific probiotic strains for the prevention of antibiotic-associated diarrhoea, patients are often not receiving a specific recommendation from their HCP and appear to be taking strains without guidance from supporting evidence.

  View details for DOI 10.3920/BM2016.0148

  View details for PubMedID 28403649

• Reply to "Triclocarban and Health: the Jury Is Still Out". mSphere Pischel, L., Poole, A. C., Ley, C., Suh, G., Goodrich, J. K., Haggerty, T. D., Ley, R. E., Parsonnet, J. 2016; 1 (6)

  View details for DOI 10.1128/mSphere.00255-16

  View details for PubMedID 27841373

  View details for PubMedCentralID PMC5093150

• Effect of long-term antibiotic use on weight in adolescents with acne. journal of antimicrobial chemotherapy Contopoulos-Ioannidis, D. G., Ley, C., Wang, W., Ma, T., Olson, C., Shi, X., Luft, H. S., Hastie, T., Parsonnet, J. 2016; 71 (4): 1098-1105

  Abstract

  Antibiotics increase weight in farm animals and may cause weight gain in humans. We used electronic health records from a large primary care organization to determine the effect of antibiotics on weight and BMI in healthy adolescents with acne.We performed a retrospective cohort study of adolescents with acne prescribed ≥4 weeks of oral antibiotics with weight measurements within 18 months pre-antibiotics and 12 months post-antibiotics. We compared within-individual changes in weight-for-age Z-scores (WAZs) and BMI-for-age Z-scores (BMIZs). We used: (i) paired t-tests to analyse changes between the last pre-antibiotics versus the first post-antibiotic measurements; (ii) piecewise-constant-mixed models to capture changes between mean measurements pre- versus post-antibiotics; (iii) piecewise-linear-mixed models to capture changes in trajectory slopes pre- versus post-antibiotics; and (iv) χ(2) tests to compare proportions of adolescents with ≥0.2 Z-scores WAZ or BMIZ increase or decrease.Our cohort included 1012 adolescents with WAZs; 542 also had BMIZs. WAZs decreased post-antibiotics in all analyses [change between last WAZ pre-antibiotics versus first WAZ post-antibiotics = -0.041 Z-scores (P < 0.001); change between mean WAZ pre- versus post-antibiotics = -0.050 Z-scores (P < 0.001); change in WAZ trajectory slopes pre- versus post-antibiotics = -0.025 Z-scores/6 months (P = 0.002)]. More adolescents had a WAZ decrease post-antibiotics ≥0.2 Z-scores than an increase (26% versus 18%; P < 0.001). Trends were similar, though not statistically significant, for BMIZ changes.Contrary to original expectations, long-term antibiotic use in healthy adolescents with acne was not associated with weight gain. This finding, which was consistent across all analyses, does not support a weight-promoting effect of antibiotics in adolescents.

  View details for DOI 10.1093/jac/dkv455

  View details for PubMedID 26782773

  View details for PubMedCentralID PMC4790625

• Safety and acceptability of Lactobacillus reuteri DSM 17938 and Bifidobacterium longum subspecies infantis 35624 in Bangladeshi infants: a phase I randomized clinical trial. BMC complementary and alternative medicine Hoy-Schulz, Y. E., Jannat, K., Roberts, T., Zaidi, S. H., Unicomb, L., Luby, S., Parsonnet, J. 2016; 16 (1): 44-?

  Abstract

  Probiotics have rarely been studied in young healthy infants from low-income countries. This phase I study investigated the safety and acceptability of two probiotics in Bangladesh.Healthy infants aged four to twelve weeks from urban slums in Bangladesh were randomized to one of three different intervention dosing arms (daily, weekly, biweekly - once every two weeks) of Lactobacillus reuteri DSM 17938 and Bifidobacterium longum subspecies infantis 35624 over one month or to a fourth arm that received no probiotics. All subjects were followed for two additional months. Reported gastrointestinal and respiratory symptoms as well as breastfeeding rates, hospitalizations, differential withdrawals, and caretakers' perception of probiotic use were compared among arms.In total, 160 infants were randomized (40 to each arm) with 137 (Daily n = 35, Weekly n = 35, Biweekly n = 35, Control n = 32) followed up for a median of twelve weeks; 113 completed the study. Illness and breastfeeding rates were similar across all arms. Ten hospitalizations unrelated to probiotic use occurred. Forty eight percent of the caretakers of infants in intervention arms believed that probiotics improved their baby's health.These two commonly used probiotics appeared safe and well-accepted by Bangladeshi families.ClinicalTrials.gov NCT01899378 . Registered July 10, 2013.

  View details for DOI 10.1186/s12906-016-1016-1

  View details for PubMedID 26832746

  View details for PubMedCentralID PMC4736167

• Stanford's Outcomes Research in Kids (STORK): a prospective study of healthy pregnant women and their babies in Northern California. BMJ open Ley, C., Sanchez, M. d., Mathur, A., Yang, S., Sundaram, V., Parsonnet, J. 2016; 6 (4)

  Abstract

  Stanford's Outcomes Research in Kids (STORK) is an ongoing prospective cohort of healthy pregnant women and their babies established to determine the effect of infectious diseases on weight, linear growth and immune system development during childhood. Additionally, a nested randomised intervention of household and personal cleaning products tests the effects of the microbicides triclosan and triclocarban on these outcomes and incidence of infection.Healthy pregnant women were identified and enrolled primarily at public clinics; their babies, enrolled shortly after birth, are followed to age 36 months. Automated weekly surveys assess daily health status, infectious disease symptoms, healthcare provider visits and antibiotic use, in the mother during pregnancy and the baby once born. At 4-monthly household visits, information and samples are collected from the mother (urine, stool, saliva, skin swab), the baby (blood by heel/toe stick, urine, stool, saliva, skin swab) and the household (environmental swabs). Annual blood samples are obtained by venipuncture (mother and baby). Medical charts are abstracted for allergy and infectious illness in the mother during pregnancy and the baby.From 7/2011 to 2/2015, 158 mothers were enrolled at approximately 20 weeks gestation; 127 babies were enrolled. Two-thirds of mothers are Hispanic, one-third are non-US born and one-third speak primarily Spanish; mean years of education is 13 (SD 6.2) years. Households have on average 4.5 residents. Most households (97%) were randomised to participate in the intervention. Completion of weekly surveys (86%) and follow-up (75% after 14 months) is excellent in this young, mobile population; collection of samples is ongoing with thousands of specimens stored.Enrolled babies will be followed until age 36 months (last anticipated visit: 07/2018) with medical chart review completed soon thereafter. All epidemiological information and samples will be available for collaborative hypothesis testing.NCT01442701; Pre-results.

  View details for DOI 10.1136/bmjopen-2015-010810

  View details for PubMedID 27075843

  View details for PubMedCentralID PMC4838723

• In vitro immunomodulation for enhancing T cell-based diagnosis of Mycobacterium tuberculosis infection DIAGNOSTIC MICROBIOLOGY AND INFECTIOUS DISEASE Slater, M., Minh-Chi Tran, M. C., Platt, L., Luu, L. T., Phan, H. T., Pham, P. T., Do, T. B., Nguyen, H. T., Gaur, R. L., Parsonnet, J., Cattamanchi, A., Luo, R., Nahid, P., Banaei, N. 2015; 83 (1): 41-45

  Abstract

  Interferon-gamma release assays have limited sensitivity for detecting latent tuberculosis infection. In this study, we determine if the addition of immunomodulators to the QuantiFERON-TB Gold In-Tube (QFT-GIT) increased test sensitivity without compromising specificity. We prospectively compared QFT-GIT results with and without incubation with 2 immunomodulators (lipopolysaccharide [LPS] and polyinosine-polycytidylic acid [PolyIC]) in 2 cohorts-113 culture-confirmed tuberculosis (TB) subjects in Hanoi, Vietnam, and 226 documented QFT-GIT-negative, low TB risk health care workers undergoing annual TB screening at a US academic institution. Sensitivity of the tests in TB subjects was 84.1% with the standard QFT-GIT and 85.8% and 74.3% after incubation with LPS and PolyIC, respectively. Specificity in low TB risk health care workers was 100% with the standard QFT-GIT by design and 86.7% with LPS and 63.3% with PolyIC. In conclusion, use of the 2 immunomodulators did not improve sensitivity of the QFT-GIT in TB patients and reduced specificity in low-risk health care workers.

  View details for DOI 10.1016/j.diagmicrobio.2015.05.007

  View details for Web of Science ID 000359754000010

  View details for PubMedID 26081239

• Prevention of gastric cancer. JAMA Herrero, R., Parsonnet, J., Greenberg, E. R. 2014; 312 (12): 1197-8

  View details for DOI 10.1001/jama.2014.10498

  View details for PubMedID 25247512

• Maternal prepregnancy body mass index and risk of spontaneous preterm birth. Paediatric and perinatal epidemiology Shaw, G. M., Wise, P. H., Mayo, J., Carmichael, S. L., Ley, C., Lyell, D. J., Shachar, B. Z., Melsop, K., Phibbs, C. S., Stevenson, D. K., Parsonnet, J., Gould, J. B. 2014; 28 (4): 302-311

  Abstract

  Findings from studies examining risk of preterm birth associated with elevated prepregnancy body mass index (BMI) have been inconsistent.Within a large population-based cohort, we explored associations between prepregnancy BMI and spontaneous preterm birth across a spectrum of BMI, gestational age, and racial/ethnic categories. We analysed data for 989 687 singleton births in California, 2007-09. Preterm birth was grouped as 20-23, 24-27, 28-31, or 32-36 weeks gestation (compared with 37-41 weeks). BMI was categorised as <18.5 (underweight); 18.5-24.9 (normal); 25.0-29.9 (overweight); 30.0-34.9 (obese I); 35.0-39.9 (obese II); and ≥40.0 (obese III). We assessed associations between BMI and spontaneous preterm birth of varying severity among non-Hispanic White, Hispanic, and non-Hispanic Black women.Analyses of mothers without hypertension and diabetes, adjusted for age, education, height, and prenatal care initiation, showed obesity categories I-III to be associated with increased risk of spontaneous preterm birth at 20-23 and 24-27 weeks among those of parity 1 in each race/ethnic group. Relative risks for obese III and preterm birth at 20-23 weeks were 6.29 [95% confidence interval (CI) 3.06, 12.9], 4.34 [95% CI 2.30, 8.16], and 4.45 [95% CI 2.53, 7.82] for non-Hispanic Whites, non-Hispanic Blacks, and Hispanics, respectively. A similar, but lower risk, pattern was observed for women of parity ≥2 and preterm birth at 20-23 weeks. Underweight was associated with modest risks for preterm birth at ≥24 weeks among women in each racial/ethnic group regardless of parity.The association between women's prepregnancy BMI and risk of spontaneous preterm birth is complex and is influenced by race/ethnicity, gestational age, and parity.

  View details for DOI 10.1111/ppe.12125

  View details for PubMedID 24810721

• Comparison of two methods - regression predictive model and intake shift model - for adjusting self-reported dietary recall of total energy intake of populations. Frontiers in public health Lankester, J., Perry, S., Parsonnet, J. 2014; 2: 249-?

  Abstract

  Daily dietary intake data derived from self-reported dietary recall surveys are widely considered inaccurate. In this study, methods were developed for adjusting these dietary recalls to more plausible values. In a simulation model of two National Health and Nutrition Examination Surveys (NHANES), NHANES I and NHANES 2007-2008, a predicted one-third of raw data fell outside a range of physiologically plausible bounds for dietary intake (designated a 33% failure rate baseline). To explore the nature and magnitude of this bias, primary data obtained from an observational study were used to derive models that predicted more plausible dietary intake. Two models were then applied for correcting dietary recall bias in the NHANES datasets: (a) a linear regression to model percent under-reporting as a function of subject characteristics and (b) a shift of dietary intake reports to align with experimental data on energy expenditure. After adjustment, the failure rates improved to <2% with the regression model and 4-9% with the intake shift model - both substantial improvements over the raw data. Both methods gave more reliable estimates of plausible dietary intake based on dietary recall and have the potential for more far-reaching application in correction of self-reported exposures.

  View details for DOI 10.3389/fpubh.2014.00249

  View details for PubMedID 25506048

  View details for PubMedCentralID PMC4245891

• Challenges with QuantiFERON-TB Gold Assay for Large-Scale, Routine Screening of U.S. Healthcare Workers AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE Slater, M. L., Welland, G., Pai, M., Parsonnet, J., Banaei, N. 2013; 188 (8): 1005-1010

  Abstract

  North American occupational health programs that switched from the tuberculin skin test (TST) to IFN-γ release assays for latent tuberculosis screening are reporting challenges with interpretation of serial testing results in healthcare workers (HCWs). However, limited data exist on the reproducibility of serial IFN-γ release assay results in low-risk HCWs.To evaluate the short-term reproducibility of QuantiFERON-TB Gold In-Tube (QFT) in a large cohort of HCWs and to define a QFT cutoff yielding a conversion rate equivalent to historical TST rates.We retrospectively evaluated the QFT results from HCWs with two or more QFT tests performed between June 2008 and July 2010 at an academic institution. Outcome measures were proportions of reproducibility, quantitative results, and conversion rates with alternate QFT cutoffs.A total of 9,153 HCWs with two or more QFT tests were included in the analysis. Of 8,227 individuals with a negative result, 4.4% (n = 361) converted their QFT result over 2 years. A total of 261 (72.3%) of the HCWs with conversions underwent repeat short-term testing after the first positive result with 64.8% reverting (n = 169). An IFN-γ cutoff of 5.3 IU/ml or higher (manufacturer's cutoff is ≥0.35 IU/ml) yielded a conversion rate of 0.4%, equal to our institution's historical TST conversion rate.The manufacturer's definition of QFT conversion results in an inflated conversion rate that is incompatible with our low-risk setting. A significantly higher QFT cutoff value is needed to match the historical TST conversion rate. Nonreproducible conversions in most converters suggested false-positive results.

  View details for DOI 10.1164/rccm.201305-0831OC

  View details for Web of Science ID 000325789700021

  View details for PubMedID 23978270

• The immune response to tuberculosis infection in the setting of Helicobacter pylori and helminth infections. Epidemiology and infection Perry, S., Chang, A. H., Sanchez, L., Yang, S., Haggerty, T. D., Parsonnet, J. 2013; 141 (6): 1232-1243

  Abstract

  We screened 176 healthy, adult (aged 18-55 years) US refugees from tuberculosis (TB)-endemic countries to evaluate whether cytokine responses to latent TB infection (LTBI) are modified in the setting of concurrent H. pylori and helminth infection. As measured by the Quantiferon-TB GOLD interferon-γ release assay, a total 38 (22%) subjects had LTBI, of which 28 (74%) also were H. pylori seropositive and/or helminth infected. Relative to ten subjects with LTBI only, 16 subjects with concurrent H. pylori infection had significantly elevated levels of IFN-γ, and nine subjects with both H. pylori and helminth infection had significantly elevated levels of IFN-γ, IL-2, IL-13, and IL-5. H. pylori is associated with enhanced IFN-γ responses to TB, even in the setting of concurrent helminth infection. Efficacy of TB vaccines may vary with the co-existence of these three infections in the developing world.

  View details for DOI 10.1017/S0950268812001823

  View details for PubMedID 22954328

  View details for PubMedCentralID PMC3785541

• Urinary Triclosan is Associated with Elevated Body Mass Index in NHANES. PloS one Lankester, J., Patel, C., Cullen, M. R., Ley, C., Parsonnet, J. 2013; 8 (11)

  Abstract

  Triclosan-a ubiquitous chemical in toothpastes, soaps, and household cleaning supplies-has the potential to alter both gut microbiota and endocrine function and thereby affect body weight.We investigated the relationship between triclosan and body mass index (BMI) using National Health and Nutrition Examination Surveys (NHANES) from 2003-2008. BMI and spot urinary triclosan levels were obtained from adults. Using two different exposure measures-either presence vs. absence or quartiles of triclosan-we assessed the association between triclosan and BMI. We also screened all NHANES serum and urine biomarkers to identify correlated factors that might confound observed associations.Compared with undetectable triclosan, a detectable level was associated with a 0.9-point increase in BMI (p<0.001). In analysis by quartile, compared to the lowest quartile, the 2nd, 3rd and 4th quartiles of urinary triclosan were associated with BMI increases of 1.5 (p<0.001), 1.0 (p = 0.002), and 0.3 (p = 0.33) respectively. The one strong correlate of triclosan identified in NHANES was its metabolite, 2,4-dichlorophenol (ρ = 0.4); its association with BMI, however, was weaker than that of triclosan. No other likely confounder was identified.Triclosan exposure is associated with increased BMI. Stronger effect at moderate than high levels suggests a complex mechanism of action.

  View details for DOI 10.1371/journal.pone.0080057

  View details for PubMedID 24278238

  View details for PubMedCentralID PMC3836985

• Decreasing Intestinal Parasites in Recent Northern California Refugees AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE Chang, A. H., Perry, S., Du, J. N., Agunbiade, A., Polesky, A., Parsonnet, J. 2013; 88 (1): 191-197

  Abstract

  Beginning in 2005, the Centers for Disease Control and Prevention (CDC) expanded the overseas presumptive treatment of intestinal parasites with albendazole to include refugees from the Middle East. We surveyed the prevalence of helminths and protozoa in recent Middle Eastern refugees (2008-2010) in comparison with refugees from other geographical regions and from a previous survey (2001-2004) in Santa Clara County, California. Based on stool microscopy, helminth infections decreased, particularly in Middle Eastern refugees (0.1% versus 2.3% 2001-2004, P = 0.01). Among all refugees, Giardia intestinalis was the most common protozoan found. Protozoa infections also decreased somewhat in Middle Eastern refugees (7.2%, 2008-2010 versus 12.9%, 2001-2004, P = 0.08). Serology for Strongyloides stercoralis and Schistosoma spp. identified more infected individuals than stool exams. Helminth infections are increasingly rare in refugees to Northern California. Routine screening stool microscopy may be unnecessary in all refugees.

  View details for DOI 10.4269/ajtmh.2012.12-0349

  View details for Web of Science ID 000313757500031

  View details for PubMedID 23149583

  View details for PubMedCentralID PMC3541735

• Discovery of a Novel Polyomavirus in Acute Diarrheal Samples from Children PLOS ONE Yu, G., Greninger, A. L., Isa, P., Phan, T. G., Angel Martinez, M., Sanchez, M. d., Francisco Contreras, J., Ignacio Santos-Preciado, J., Parsonnet, J., Miller, S., DeRisi, J. L., Delwart, E., Arias, C. F., Chiu, C. Y. 2012; 7 (11)

  View details for DOI 10.1371/journal.pone.0049449

  View details for Web of Science ID 000311151900142

• Infectious Diseases in Children and Body Mass Index in Young Adults EMERGING INFECTIOUS DISEASES Suh, G., Ley, C., Parsonnet, J. 2012; 18 (9): 1490-1492

  Abstract

  In a cohort of 1,863 Filipinos, diarrhea, fever, and unsanitary conditions in infancy were associated with a decreased body mass index in adulthood; upper respiratory tract infection was associated with an increased body mass index. These finding support the hypothesis that infections early in life play a role in body habitus in adulthood.

  View details for DOI 10.3201/eid1809.111821

  View details for Web of Science ID 000307989700017

  View details for PubMedID 22932124

  View details for PubMedCentralID PMC3437733

• Investigation of False-Positive Results Given by the QuantiFERON-TB Gold In-Tube Assay JOURNAL OF CLINICAL MICROBIOLOGY Slater, M., Parsonnet, J., Banaei, N. 2012; 50 (9): 3105-3107

  Abstract

  We investigated a sudden increase in the rate of positive QuantiFERON-TB Gold In-Tube results from 10% to 31% at a U.S. academic institution. Direct comparison of the TB antigen tubes with tubes from a different lot number identified that a potential problem with the TB antigen vials in a certain tube lot was the likely cause of the elevated positive rate. The underlying defect remains unknown. This finding warrants refinement of quality control programs by the manufacturer and users.

  View details for DOI 10.1128/JCM.00730-12

  View details for Web of Science ID 000307941900046

  View details for PubMedID 22785197

  View details for PubMedCentralID PMC3421800

• Gastric Cancer Incidence among Hispanics in California: Patterns by Time, Nativity, and Neighborhood Characteristics CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION Chang, E. T., Gomez, S. L., Fish, K., Schupp, C. W., Parsonnet, J., DeRouen, M. C., Keegan, T. H., Clarke, C. A., Glaser, S. L. 2012; 21 (5): 709-719

  Abstract

  Better understanding about gastric cancer incidence patterns among Hispanics by birthplace, socioeconomic status (SES), and acculturation can improve preventive strategies and disease models.Incidence rates, rate ratios, and estimated annual percent change (EAPC) in rates of anatomic and histologic subtype-specific gastric cancer were calculated by age, sex, and nativity among Hispanics using California Cancer Registry data from 1988 through 2004. Incidence rates in 1998 to 2002 were compared by neighborhood SES and Hispanic enclave status according to 2000 US Census data.Incidence rates of diffuse gastric cancer increased from 1988 through 2004 among foreign-born Hispanic men (EAPC: 3.5%, 95% CI: 1.5%-5.5%) and U.S.-born Hispanic women (EAPC: 3.0%, 95% CI: 0.7%-5.3%). During the same time period, incidence rates of intestinal gastric cancer declined significantly and both cardia and noncardia gastric cancer were steady or declined among foreign-born and U.S.-born Hispanic men and women. Noncardia and both intestinal and diffuse gastric cancer were more common in foreign-born than U.S.-born Hispanic men and women, and in those from lower SES, higher enclave neighborhoods. By contrast, among younger and middle-aged Hispanic men, cardia tumors were more common in the U.S.-born than the foreign-born, and in higher SES, lower enclave neighborhoods.Varying gastric cancer risk factors among Hispanic subgroups and increasing rates of diffuse gastric cancer in foreign-born Hispanic men and U.S.-born Hispanic women merit further investigation to identify separate disease etiologies.Age, sex, birthplace, SES, and acculturation modify gastric cancer incidence in Hispanics and should be considered when examining disease risk and prevention.

  View details for DOI 10.1158/1055-9965.EPI-11-1208

  View details for Web of Science ID 000303908200004

  View details for PubMedID 22374991

• Discovery of a novel polyomavirus in acute diarrheal samples from children. PloS one Yu, G., Greninger, A. L., Isa, P., Phan, T. G., Martínez, M. A., de la Luz Sanchez, M., Contreras, J. F., Santos-Preciado, J. I., Parsonnet, J., Miller, S., DeRisi, J. L., Delwart, E., Arias, C. F., Chiu, C. Y. 2012; 7 (11)

  Abstract

  Polyomaviruses are small circular DNA viruses associated with chronic infections and tumors in both human and animal hosts. Using an unbiased deep sequencing approach, we identified a novel, highly divergent polyomavirus, provisionally named MX polyomavirus (MXPyV), in stool samples from children. The ∼5.0 kB viral genome exhibits little overall homology (<46% amino acid identity) to known polyomaviruses, and, due to phylogenetic variation among its individual proteins, cannot be placed in any existing taxonomic group. PCR-based screening detected MXPyV in 28 of 834 (3.4%) fecal samples collected from California, Mexico, and Chile, and 1 of 136 (0.74%) of respiratory samples from Mexico, but not in blood or urine samples from immunocompromised patients. By quantitative PCR, the measured titers of MXPyV in human stool at 10% (weight/volume) were as high as 15,075 copies. No association was found between the presence of MXPyV and diarrhea, although girls were more likely to shed MXPyV in the stool than boys (p=0.012). In one child, viral shedding was observed in two stools obtained 91 days apart, raising the possibility of chronic infection by MXPyV. A multiple sequence alignment revealed that MXPyV is a closely related variant of the recently reported MWPyV and HPyV10 polyomaviruses. Further studies will be important to determine the association, if any, of MXPyV with disease in humans.

  View details for DOI 10.1371/journal.pone.0049449

  View details for PubMedID 23166671

• Local epidemic history as a predictor of tuberculosis incidence in Saskatchewan Aboriginal communities INTERNATIONAL JOURNAL OF TUBERCULOSIS AND LUNG DISEASE Pepperell, C., Chang, A. H., Wobeser, W., Parsonnet, J., Hoeppner, V. H. 2011; 15 (7): 899-905

  Abstract

  Average tuberculosis (TB) incidence rates are high in Canadian Aboriginal communities, but there is significant variability within this group.To determine whether local history of post-contact TB epidemics is predictive of contemporary epidemiology among Aboriginal communities in Saskatchewan, Canada.TB incidence, age-specific morbidity patterns and rates of clustering of TB genotypes from 1986 to 2004 were compared between two groups of communities: Group 1, in which post-contact epidemics of TB were established around 1870, and Group 2, in which they were delayed until after 1920. Concomitant effects of socio-economic and geographic variables were explored with multivariate models.Group 2 communities were characterized by higher annual incidence of TB (median 431 per 100,000 population vs. 38/100,000). In multivariate models that included socio-economic and geographic variables, historical grouping remained a significant independent predictor of community incidence of TB. Clustering of TB genotypes was associated with Group 2 (OR 8.7, 95%CI 3.3-22.7) and age 10-34 years (OR 2.5, 95%CI 1.1-5.7).TB transmission dynamics can vary significantly as a function of a population's historical experience with TB. Populations at different stages along the epidemic trajectory may be amenable to different types of interventions.

  View details for DOI 10.5588/ijtld.10.0556

  View details for Web of Science ID 000292234000008

  View details for PubMedID 21682962

  View details for PubMedCentralID PMC3292043

• The impact of mucosal infections on acquisition and progression of tuberculosis MUCOSAL IMMUNOLOGY Perry, S., Hussain, R., Parsonnet, J. 2011; 4 (3): 246-251

  Abstract

  More than one-third of the world's population, or over 2 billion people, are infected with Mycobacterium tuberculosis, the causative pathogen of tuberculosis in humans. Why only 10% of those infected develop active disease while the remainder harbor latent infection remains one of the greatest scientific and public health mysteries. Bacterial persistence is characterized by a dynamic state of immunological tolerance between pathogen and host. The critical role of CD4(+) T cells in defense against intracellular pathogens became evident during epidemiological studies of HIV-1 infection, which showed a clear inverse relationship between CD4(+) T-cell count in peripheral blood and increased risk of infection with M. tuberculosis, pneumocystis and Toxoplasma gondii. There is also growing evidence of a common mucosal immune system, whereby immune cells activated at one mucosal site may disseminate to remote effector sites. In this commentary, we review emerging evidence from human studies that the outcome of M. tuberculosis infection is influenced by concurrent mucosal infections, using Helicobacter pylori and geohelminths as examples. Understanding how the complexity of microbial exposures influences host immunity may have important implications for vaccine development and therapeutic interventions.

  View details for DOI 10.1038/mi.2011.11

  View details for Web of Science ID 000289616800001

  View details for PubMedID 21412228

• Clinical Application and Limitations of Interferon-gamma Release Assays for the Diagnosis of Latent Tuberculosis Infection CLINICAL INFECTIOUS DISEASES Herrera, V., Perry, S., Parsonnet, J., Banaei, N. 2011; 52 (8): 1031-1037

  Abstract

  Interferon-release assays (IGRAs) represent advances in tuberculosis immunology and evolutionary biology. IGRAs were designed to replace tuberculin skin test (TST) for the diagnosis of latent tuberculosis infection because of their logistical advantages and enhanced specificity over TST. Although IGRAs and TST have been useful in epidemiologic studies, they lack the sensitivity and reproducibility normally expected from diagnostic tests in clinical practice. In this review, we present an overview of the current recommendations and knowledge in the field and discuss practical approaches in areas of uncertainty related to discordant IGRA results.

  View details for DOI 10.1093/cid/cir068

  View details for Web of Science ID 000289300100014

  View details for PubMedID 21460320

• Effect of Helicobacter pylori Infection on Symptoms of Gastroenteritis Due to Enteropathogenic Escherichia coli in Adults DIGESTIVE DISEASES AND SCIENCES Chang, A. H., Haggerty, T. D., de Martel, C., Leung, C. W., Parsonnet, J. 2011; 56 (2): 457-464

  Abstract

  Helicobacter pylori can cause hypochlorhydria in some hosts and predispose to diarrheal infections.We tested the hypothesis that chronic H. pylori infection increases the risk of diarrheal illness due to an acid-sensitive organism: enteropathogenic Escherichia coli (EPEC).After testing healthy adult volunteers for H. pylori, 19 infected and 26 uninfected subjects had gastric pH probes placed and were given 5-10 × 10(9) EPEC organisms; six had previously received a proton pump inhibitor. We measured diarrhea and created a composite gastroenteritis severity score based on symptoms in the 48 h following exposure. Outcomes were compared using logistic regression and analysis of covariance.More H. pylori-infected (36.8%) than H. pylori-uninfected subjects (7.7%) were hypochlorhydric (P = 0.02). Six (31.6%) H. pylori-infected and five H. pylori-uninfected subjects (19.2%) developed diarrhea (P = 0.34). Hypochlorhydria was a strong risk factor for diarrhea [odds ratio (OR) 6.25, confidence interval (CI): 1.29-30.35]. After adjusting for hypochlorhydria and EPEC dose, H. pylori was not associated with diarrhea (OR 0.89, CI: 0.17-4.58). Among those with symptoms, H. pylori-infected subjects had lower gastroenteritis severity score than did H. pylori-uninfected subjects (2.6, CI: 1.9-3.4 versus 1.5, CI: 1.1-1.9, P = 0.01), particularly if they were also hypochlorhydric (3.8, CI: 2.3-5.3 versus 1.9, CI: 1.3-2.5, P = 0.02).In adults, H. pylori infection was associated with hypochlorhydria but had no detectable effect on occurrence of diarrhea. Among symptomatic subjects, H. pylori infection decreased severity of gastroenteritis.

  View details for DOI 10.1007/s10620-010-1309-z

  View details for Web of Science ID 000286664900025

  View details for PubMedID 20635147

  View details for PubMedCentralID PMC4005911

• Role of Bacteria in Oncogenesis CLINICAL MICROBIOLOGY REVIEWS Chang, A. H., Parsonnet, J. 2010; 23 (4): 837-?

  Abstract

  Although scientific knowledge in viral oncology has exploded in the 20th century, the role of bacteria as mediators of oncogenesis has been less well elucidated. Understanding bacterial carcinogenesis has become increasingly important as a possible means of cancer prevention. This review summarizes clinical, epidemiological, and experimental evidence as well as possible mechanisms of bacterial induction of or protection from malignancy.

  View details for DOI 10.1128/CMR.00012-10

  View details for Web of Science ID 000282635900006

  View details for PubMedID 20930075

  View details for PubMedCentralID PMC2952975

• Immediate Incubation Reduces Indeterminate Results for QuantiFERON-TB Gold In-Tube Assay JOURNAL OF CLINICAL MICROBIOLOGY Herrera, V., Yeh, E., Murphy, K., Parsonnet, J., Banaei, N. 2010; 48 (8): 2672-2676

  Abstract

  In vitro gamma interferon release assays (IGRAs) are increasingly used as an alternative to the traditional tuberculin skin test for the diagnosis of latent Mycobacterium tuberculosis infection. Evaluation of the QuantiFERON-TB Gold in-tube assay (QFT-IT) prior to large-scale implementation at the Stanford Hospital and Clinics for a health care worker screening program revealed a critical preanalytical factor affecting the results. We found that incubation delay significantly increased the frequency of indeterminate results. In this study, QFT-IT was performed with samples from healthy volunteers, and replicate tubes were incubated at 37 degrees C either immediately or after a delay at room temperature for 6 and 12 h. No indeterminate results (0/41) were seen when the assay was performed with immediate incubation. Incubation delays of 6 and 12 h yielded indeterminate results at rates of 10% (2/20) (P = 0.10) and 17.1% (7/41) (P = 0.01), respectively. The increased rate of indeterminate results was due to a decrease in the mean values for the mitogen-nil tubes when incubation was delayed for 6 h (P = 0.004) and 12 h (P < 0.001). The rates of concordance of positive or negative results obtained following immediate incubation and following 6- and 12-h delays were 77.8% (14/18) and 79.4% (27/34), respectively. Subsequent implementation of the immediate incubation procedure in our screening program for 14,830 health care workers yielded an indeterminate result rate of 0.36% over a period of 12 months, a significant improvement over the reported rates of 5 to 40% for QFT-IT. We conclude that immediate incubation of QFT-IT tubes is an effective way to minimize indeterminate results. The effect of incubation delay on the accuracy of QFT-IT remains to be determined.

  View details for DOI 10.1128/JCM.00482-10

  View details for PubMedID 20519472

• Cultivation and Serological Characterization of a Human Theiler's-Like Cardiovirus Associated with Diarrheal Disease JOURNAL OF VIROLOGY Chiu, C. Y., Greninger, A. L., Chen, E. C., Haggerty, T. D., Parsonnet, J., Delwart, E., DeRisi, J. L., Ganem, D. 2010; 84 (9): 4407-4414

  Abstract

  Cardioviruses (e.g., Theiler's murine encephalomyelitis virus [TMEV]) are members of the Picornaviridae family that cause myocarditis and encephalitis in rodents. Recently, several studies have identified human cardioviruses, including Saffold virus (SAFV) and a related virus named human TMEV-like cardiovirus (HTCV). At least eight cardiovirus genotypes are now recognized, with SAFV and most strains of HTCV belonging to genotypes 1 and 2, respectively; genotype 2 strains are the most common in the population. Although a genotype 3 cardiovirus has recently been cultured (SAFV-3), the genotype 1 and 2 cardioviruses have been difficult to propagate in vitro, hindering efforts to understand their seroprevalence and pathogenicity. Here we present the isolation and characterization of a genotype 2 human cardiovirus (HTCV-UC6). Notably, successful cultivation of HTCV-UC6 from stool required the addition of cytokine-blocking antibodies to interrupt downstream antiviral pathways. Unlike SAFV-3, HTCV-UC6 exhibited slow replication kinetics and demonstrated only a moderate cytopathic effect. Serologic assays revealed that 91% of U.S. adults carry antibodies to the genotype 2 cardioviruses, of which 80% generate neutralizing antibodies, in agreement with previous data showing that cardiovirus infection is widespread in humans. We also demonstrate an acute cardiovirus seroconversion event in a child with diarrhea and vomiting, thus reporting for the first time evidence linking cardiovirus infection to diarrheal disease in humans.

  View details for DOI 10.1128/JVI.02536-09

  View details for Web of Science ID 000276358000027

  View details for PubMedID 20164225

  View details for PubMedCentralID PMC2863762

• Vitamin D Deficiency and Tuberculosis Progression EMERGING INFECTIOUS DISEASES Talat, N., Perry, S., Parsonnet, J., Dawood, G., Hussain, R. 2010; 16 (5): 853-855

  Abstract

  To assess the association between vitamin D deficiency and tuberculosis disease progression, we studied vitamin D levels in a cohort of tuberculosis patients and their contacts (N = 129) in Pakistan. Most (79%) persons showed deficiency. Low vitamin D levels were associated with a 5-fold increased risk for progression to tuberculosis.

  View details for DOI 10.3201/eid1605.091693

  View details for Web of Science ID 000277209900020

  View details for PubMedID 20409383

• Encouraging Scholarship: Medical School Programs to Promote Student Inquiry Beyond the Traditional Medical Curriculum ACADEMIC MEDICINE Green, E. P., Borkan, J. M., Pross, S. H., Adler, S. R., Nothnagle, M., Parsonnet, J., Gruppuso, P. A. 2010; 85 (3): 409-418

  Abstract

  Many medical curricula now include programs that provide students with opportunities for scholarship beyond that provided by their traditional, core curricula. These scholarly concentration (SC) programs vary greatly in focus and structure, but they share the goal of producing physicians with improved analytic, creative, and critical-thinking skills. In this article, the authors explore models of both required and elective SC programs. They gathered information through a review of medical school Web sites and direct contact with representatives of individual programs. Additionally, they discuss in-depth the SC programs of the Warren Alpert Medical School of Brown University; the University of South Florida College of Medicine; the University of California, San Francisco; and Stanford University School of Medicine. The authors describe each program's focus, participation, duration, centralization, capstone requirement, faculty involvement, and areas of concentration. Established to address a variety of challenges in the U.S. medical education system, these four programs provide an array of possible models for schools that are considering the establishment of an SC program. Although data on the impact of SC programs are lacking, the authors believe that this type of program has the potential to significantly impact the education of medical students through scholarly, in-depth inquiry and longitudinal faculty mentorship.

  View details for DOI 10.1097/ACM.0b013e3181cd3e00

  View details for Web of Science ID 000276132100014

  View details for PubMedID 20182113

• Engaging Students in Dedicated Research and Scholarship During Medical School: The Long-Term Experiences at Duke and Stanford ACADEMIC MEDICINE Laskowitz, D. T., Drucker, R. P., Parsonnet, J., Cross, P. C., Gesundheit, N. 2010; 85 (3): 419-428

  Abstract

  For more than 40 years, the faculties of Duke University School of Medicine (SOM) and Stanford University SOM have encouraged or required students to engage in scholarship as a way to broaden their education and attract them to careers in academic medicine. A dedicated period of research was first integrated into the Duke curriculum in 1959 to provide an opportunity for students to develop into physician leaders through a rigorous scholarly experience in biomedically related research. Originally designed to foster experience in laboratory-based basic research, the third-year program has evolved in response to the changing landscape of medicine and shifting needs and career interests of the medical student population. Stanford University SOM also has a long-standing commitment to biomedical research and currently requires each student to complete an in-depth, mentored "scholarly concentration." In contrast to Duke, where most of the scholarly research experiences take place in an immersive third year, the Stanford program encourages a longitudinal, multiyear exposure over all four (or five) years of medical school. Although the enduring effects of embedding a rigorous research program are not yet fully known, preliminary data suggest that these experiences instill an appreciation for research, impart research rigor and methodologies, and may motivate students to pursue careers in academic medicine. The authors discuss the histories, evolution, logistics, and ongoing challenges of the research programs at Duke University SOM and Stanford University SOM.

  View details for DOI 10.1097/ACM.0b013e3181ccc77a

  View details for Web of Science ID 000276132100015

  View details for PubMedID 20182114

• Required vs. Elective Research and In-Depth Scholarship Programs in the Medical Student Curriculum ACADEMIC MEDICINE Parsonnet, J., Gruppuso, P. A., Kanter, S. L., Boninger, M. 2010; 85 (3): 405-408

  Abstract

  The ability to understand and integrate new knowledge into clinical practice is a necessary quality of good physicians. Student participation in in-depth scholarship could enhance this skill in physicians while also creating a larger cadre of physician-scientists prepared to advance the field of medicine. However, because no definitive data exist demonstrating that in-depth scholarship in medical school leads to improved patient care or to productive academic careers, whether such scholarship should be required as part of the medical school curriculum is unclear. In this article, the authors present both sides of this debate. Theoretical benefits to students of a required scholarly program include closer mentorship by individual faculty, enhanced capabilities in critical interpretation of research findings, and increased confidence to investigate conundrums encountered in clinical care. Society may also benefit by having physicians available to create and apply new knowledge related to biomedicine. These theoretical benefits must be balanced, however, by pragmatic considerations of required scholarly projects including their impact on medical school applications, their effect on the medical curriculum, their costs, the availability of mentors, and their effects on the school's educational culture.

  View details for DOI 10.1097/ACM.0b013e3181cccdc4

  View details for Web of Science ID 000276132100013

  View details for PubMedID 20182112

• Infection with Helicobacter pylori Is Associated with Protection against Tuberculosis PLOS ONE Perry, S., de Jong, B. C., Solnick, J. V., Sanchez, M. d., Yang, S., Lin, P. L., Hansen, L. M., Talat, N., Hill, P. C., Hussain, R., Adegbola, R. A., Flynn, J., Canfield, D., Parsonnet, J. 2010; 5 (1)

  Abstract

  Helicobacter pylori, a lifelong and typically asymptomatic infection of the stomach, profoundly alters gastric immune responses, and may benefit the host in protection against other pathogens. We explored the hypothesis that H. pylori contributes to the control of infection with Mycobacterium tuberculosis.We first examined M. tuberculosis-specific IFN-gamma and H. pylori antibody responses in 339 healthy Northern Californians undergoing routine tuberculin skin testing. Of 97 subjects (29%) meeting criteria for latent tuberculosis (TB) infection (LTBI), 45 (46%) were H. pylori seropositive. Subjects with LTBI who were H. pylori-seropositive had 1.5-fold higher TB antigen-induced IFN-gamma responses (p = 0.04, ANOVA), and a more Th-1 like cytokine profile in peripheral blood mononuclear cells, compared to those who were H. pylori seronegative. To explore an association between H. pylori infection and clinical outcome of TB exposure, we evaluated H. pylori seroprevalence in baseline samples from two high risk TB case-contact cohorts, and from cynomolgus macaques experimentally challenged with M. tuberculosis. Compared to 513 household contacts who did not progress to active disease during a median 24 months follow-up, 120 prevalent TB cases were significantly less likely to be H. pylori infected (AOR: 0.55, 95% CI 0.0.36-0.83, p = 0.005), though seroprevalence was not significantly different from non-progressors in 37 incident TB cases (AOR: 1.35 [95% CI 0.63-2.9] p = 0.44). Cynomolgus macaques with natural H. pylori infection were significantly less likely to progress to TB 6 to 8 months after M. tuberculosis challenge (RR: 0.31 [95% CI 0.12-0.80], p = 0.04).H. pylori infection may induce bystander effects that modify the risk of active TB in humans and non-human primates. That immunity to TB may be enhanced by exposure to other microbial agents may have important implications for vaccine development and disease control.

  View details for DOI 10.1371/journal.pone.0008804

  View details for Web of Science ID 000273779000030

  View details for PubMedID 20098711

  View details for PubMedCentralID PMC2808360

• Helicobacter pylori and gastric adenocarcinoma CLINICAL MICROBIOLOGY AND INFECTION Herrera, V., Parsonnet, J. 2009; 15 (11): 971-976

  Abstract

  Gastric cancer is the second most common cause of cancer death worldwide. A large body of evidence supports a causal role of Helicobacter pylori in the majority of gastric malignancies. Great strides have been made in understanding the pathogenesis of this relationship, but much remains to be learned. Moreover, because of the high prevalence of infection, the lack of definitive trials, and the challenges of H. pylori treatment, there remains no consensus on the role of routine screening and treatment of this infection to prevent cancer. This article reviews the current knowledge on H. pylori and gastric cancer and presents some of the clinical and public health challenges associated with this pathogen.

  View details for DOI 10.1111/j.1469-0691.2009.03031.x

  View details for Web of Science ID 000271055600003

  View details for PubMedID 19874380

• The complete genome of klassevirus - a novel picornavirus in pediatric stool VIROLOGY JOURNAL Greninger, A. L., Runckel, C., Chiu, C. Y., Haggerty, T., Parsonnet, J., Ganem, D., DeRisi, J. L. 2009; 6

  Abstract

  Diarrhea kills 2 million children worldwide each year, yet an etiological agent is not found in approximately 30-50% of cases. Picornaviral genera such as enterovirus, kobuvirus, cosavirus, parechovirus, hepatovirus, teschovirus, and cardiovirus have all been found in human and animal diarrhea. Modern technologies, especially deep sequencing, allow rapid, high-throughput screening of clinical samples such as stool for new infectious agents associated with human disease.A pool of 141 pediatric gastroenteritis samples that were previously found to be negative for known diarrheal viruses was subjected to pyrosequencing. From a total of 937,935 sequence reads, a collection of 849 reads distantly related to Aichi virus were assembled and found to comprise 75% of a novel picornavirus genome. The complete genome was subsequently cloned and found to share 52.3% nucleotide pairwise identity and 38.9% amino acid identity to Aichi virus. The low level of sequence identity suggests a novel picornavirus genus which we have designated klassevirus. Blinded screening of 751 stool specimens from both symptomatic and asymptomatic individuals revealed a second positive case of klassevirus infection, which was subsequently found to be from the index case's 11-month old twin.We report the discovery of human klassevirus 1, a member of a novel picornavirus genus, in stool from two infants from Northern California. Further characterization and epidemiological studies will be required to establish whether klasseviruses are significant causes of human infection.

  View details for DOI 10.1186/1743-422X-6-82

  View details for Web of Science ID 000268409500001

  View details for PubMedID 19538752

• Helicobacter species in cancers of the gallbladder and extrahepatic biliary tract BRITISH JOURNAL OF CANCER de Martel, C., Plummer, M., Parsonnet, J., van Doorn, L., Franceschi, S. 2009; 100 (1): 194-199

  Abstract

  Helicobacter species have been found in human bile and biliary tract (BT) tissue and are suspected to cause BT diseases, including gallbladder and extrahepatic cancers, collectively referred to in this work as BT cancers. We conducted a literature review of the epidemiological evidence linking the presence of Helicobacter species in bile or BT biopsies to BT cancers and benign diseases. Reports showed great variability with respect to study methods. Nine studies of BT cancers were identified, all with 30 or fewer BT cancers; eight included cancer-free control subjects and used polymerase chain reaction (PCR) as a means of Helicobacter species detection. In four of these studies, Helicobacter species were detected in patients with BT cancer significantly more frequently than in controls, at least when controls without BT diseases were used. In two studies, no Helicobacter species were detected in either cases or controls. Helicobacter species were also often detected in benign BT diseases such as gallstone disease or chronic cholecystitis. As our current knowledge relies on a few small studies that showed substantial differences, larger studies and more standardised protocols for detecting DNA and antibodies against Helicobacter species are needed to investigate a potential association with BT cancer.

  View details for DOI 10.1038/sj.bjc.6604780

  View details for Web of Science ID 000262267700032

  View details for PubMedID 19034278

• Helicobacter pylori and gastroesophageal reflux disease: A case-control study HELICOBACTER Corley, D. A., Kubo, A., Levin, T. R., Block, G., Habel, L., Rumore, G., Quesenberry, C., Buffler, P., Parsonnet, J. 2008; 13 (5): 352-360

  Abstract

  Gastric colonization with Helicobacter pylori is a proposed protective factor against gastroesophageal reflux disease (GERD), but little population-based data exist and other data conflict.We conducted a case-control study within the membership of a large integrated health-care system that compared GERD-free subjects with two groups: subjects with a physician-assigned GERD diagnosis and randomly selected members with self-described weekly GERD symptoms. Subjects completed interviews, GERD questionnaires, and antibody testing for H. pylori and its cagA protein.Serologic data were available for 301 physician-assigned GERD patients, 81 general membership subjects with GERD symptoms, and 175 general membership subjects without GERD symptoms. Physician-assigned GERD patients were less likely to have H. pylori antibodies than GERD-free member controls (odds ratio (OR) = 0.27, 95% confidence interval (CI) 0.15-0.47); there was also an inverse association between H. pylori and GERD symptom severity (OR = 0.18, 95% CI 0.08-0.41; severe or very severe symptoms) and GERD frequency (OR = 0.18, 95% CI 0.09-0.38; for symptoms at least weekly). The association was stronger among persons with erosive GERD and was similar between H. pylori-positive subjects with and without cagA. There was no association among persons who were cagA positive, but H. pylori negative. Similar findings were found in analyses of the general membership with self-described GERD symptoms.H. pylori antibody status was inversely associated with a GERD diagnosis and GERD symptoms compared with a general membership population.

  View details for Web of Science ID 000258404600005

  View details for PubMedID 19250510

• Identification of cardioviruses related to Theiler's murine encephalomyelitis virus in human infections PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Chiu, C. Y., Greninger, A. L., Kanada, K., Kwok, T., Fischer, K. F., Runckel, C., Louie, J. K., Glaser, C. A., Yagi, S., Schnurr, D. P., Haggerty, T. D., Parsonnet, J., Ganem, D., DeRisi, J. L. 2008; 105 (37): 14124-14129

  Abstract

  Cardioviruses comprise a genus of picornaviruses that cause severe illnesses in rodents, but little is known about the prevalence, diversity, or spectrum of disease of such agents among humans. A single cardiovirus isolate, Saffold virus, was cultured in 1981 in stool from an infant with fever. Here, we describe the identification of a group of human cardioviruses that have been cloned directly from patient specimens, the first of which was detected using a pan-viral microarray in respiratory secretions from a child with influenza-like illness. Phylogenetic analysis of the nearly complete viral genome (7961 bp) revealed that this virus belongs to the Theiler's murine encephalomyelitis virus (TMEV) subgroup of cardioviruses and is most closely related to Saffold virus. Subsequent screening by RT-PCR of 719 additional respiratory specimens [637 (89%) from patients with acute respiratory illness] and 400 cerebrospinal fluid specimens from patients with neurological disease (aseptic meningitis, encephalitis, and multiple sclerosis) revealed no evidence of cardiovirus infection. However, screening of 751 stool specimens from 498 individuals in a gastroenteritis cohort resulted in the detection of 6 additional cardioviruses (1.2%). Although all 8 human cardioviruses (including Saffold virus) clustered together by phylogenetic analysis, significant sequence diversity was observed in the VP1 gene (66.9%-100% pairwise amino acid identities). These findings suggest that there exists a diverse group of novel human Theiler's murine encephalomyelitis virus-like cardioviruses that hitherto have gone largely undetected, are found primarily in the gastrointestinal tract, can be shed asymptomatically, and have potential links to enteric and extraintestinal disease.

  View details for DOI 10.1073/pnas.0805968105

  View details for Web of Science ID 000259438500079

  View details for PubMedID 18768820

  View details for PubMedCentralID PMC2528868

• Estimating disease prevalence using census data EPIDEMIOLOGY AND INFECTION Choy, M., Switzer, P., de Martel, C., Parsonnet, J. 2008; 136 (9): 1253-1260

  Abstract

  We describe a method of working on publicly available data to estimate disease prevalence in small geographic areas using Helicobacter pylori as a model infection. Using data from the Third National Health and Nutrition Examination Survey, risk parameters for H. pylori infection were obtained by logistic regression and validated by predicting 737.5 infections in an independent cohort with 736 observed infections. The prevalence of H. pylori infection in the San Francisco Bay Area was estimated with the probabilities obtained from a predictive logistic model, using risk parameters with individual-level 1990 U.S. Census data as input. Predicted H. pylori prevalence was also compared to gastric cancer incidence obtained from the Northern California Cancer Center and showed a positive correlation with gastric cancer incidence (P<0.001, R2=0.87), and no statistically significant association with other malignancies. By exclusively using publicly available data, these methods may be applied to selected conditions with strong demographic predictors.

  View details for DOI 10.1017/S0950268807009752

  View details for Web of Science ID 000259332400014

  View details for PubMedID 18047747

• Helicobacter pylori infection and the risk of Barrett's oesophagus: a community-based study GUT Corley, D. A., Kubo, A., Levin, T. R., Block, G., Habel, L., Zhao, W., Leighton, P., Rumore, G., Quesenberry, C., Buffler, P., Parsonnet, J. 2008; 57 (6): 727-733

  Abstract

  Gastric colonisation with the Helicobacter pylori bacterium is a proposed protective factor against oesophageal adenocarcinoma, but its point of action is unknown. Its associations with Barrett's oesophagus, a metaplastic change that is a probable early event in the carcinogenesis of oesophageal adenocarcinoma, were evaluatedA case-control study was carried out in the Kaiser Permanente Northern California population, a large health services delivery organisation. Persons with a new Barrett's oesophagus diagnosis (cases) were matched to subjects with gastro-oesophageal reflux disease (GORD) without Barrett's oesophagus and to population controls. Subjects completed direct in-person interviews and antibody testing for H pylori and its CagA (cytotoxin-associated gene product A) protein.Serological data were available on 318 Barrett's oesophagus cases, 312 GORD patients and 299 population controls. Patients with Barrett's oesophagus were substantially less likely to have antibodies for H pylori (OR = 0.42, 95% CI 0.26 to 0.70) than population controls; this inverse association was stronger among those with lower body mass indexes (BMIs < 25, OR = 0.03, 95% CI 0.00 to 0.20) and those with CagA+ strains (OR = 0.08, 95% CI 0.02 to 0.35). The associations were diminished after adjustment for GORD symptoms. The H pylori status was not an independent risk factor for Barrett's oesophagus compared with the GORD controls.Helicobacter pylori infection and CagA+ status were inversely associated with a new diagnosis of Barrett's oesophagus. The findings are consistent with the hypothesis that H pylori colonisation protects against Barrett's oesophagus and that the association may be at least partially mediated through GORD.

  View details for DOI 10.1136/gut.2007.132068

  View details for Web of Science ID 000255802900005

  View details for PubMedID 17895354

• Helicobacter pylori infection and development of pancreatic cancer CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION de Martel, C., Llosa, A. E., Friedmana, G. D., Vogelman, J. H., Orentreich, N., Stolzenberg-Solomon, R. Z., Parsonnet, J. 2008; 17 (5): 1188-1194

  Abstract

  Infection with Helicobacter pylori is an established risk factor for gastric cancer. Results from two studies suggest that it may also be a risk factor for pancreatic cancer.We conducted a nested case control study among 128,992 adult subscribers to the Kaiser Permanente Medical Care Program who had been enrolled in a multiphasic health checkup from 1964 to 1969. Serum collected during the checkup was maintained frozen, and subjects were followed for cancer. Cases consisted of 104 randomly selected subjects among 507 who developed pancreatic cancer in the cohort. Controls consisted of 262 pancreatic cancer-free subjects from a pool of 730 controls previously tested for studies conducted on this cohort. Controls were individually matched to cases on age, gender, race, site, and date of multiphasic health checkup. Control sera were compared with cases for antibodies to H. pylori and the CagA protein. The effects of smoking, alcohol consumption, obesity, and years of education were also investigated.Neither H. pylori [odds ratio (OR), 0.85; 95% confidence interval (95% CI), 0.49-1.48] nor its CagA protein (OR, 0.96; 95% CI, 0.48-1.92) was associated with subsequent development of pancreatic cancer. Smoking (OR, 2.09; 95% CI, 1.17-3.74) and greater number of years of education (OR, 2.13; 95% CI, 1.23-3.69) were risk factors for pancreatic cancer, whereas alcohol consumption and obesity were not.Our results suggest that H. pylori infection is not associated with development of pancreatic cancer.

  View details for DOI 10.1158/1055-9965.EPI-08-0185

  View details for Web of Science ID 000256012800024

  View details for PubMedID 18483341

• Reproducibility of QuantiFERON-TB gold in-tube assay CLINICAL AND VACCINE IMMUNOLOGY Perry, S., Sanchez, L., Yang, S., Agarwal, Z., Hurst, P., Parsonnet, J. 2008; 15 (3): 425-432

  Abstract

  Studies are needed to characterize the reproducibility of QuantiFERON-TB Gold (QFT-G) for targeted U.S. screening populations. Members of northern California households were tested with the QFT-G in-tube assay (QFT-G-IT) at two home visits 3 months apart. Reproducibility and agreement with the tuberculin skin test (TST) were assessed. Monte Carlo simulation was used to evaluate the role of test-related error. Of 63 individuals (49 adults and 14 children) completing QFT-G-IT at both time points, 79% were foreign-born (98% from Latin America) and 68% reported Mycobacterium bovis BCG vaccination. At the baseline visit, 23 (37%) were TST positive and 15 (24%) were QFT-G-IT positive (kappa = 0.48 [+/- 0.11]). At 3 months, 3/48 (6.3%; 95% confidence interval [95CI], 2 to 17) of those initially QFT-G-IT negative converted, and 5/15 (33%; 95CI, 15 to 58) of those initially QFT-G-IT positive reverted. Among the 8 individuals with inconsistent QFT-G-IT results, the maximum gamma interferon response at either visit was 0.68 IU/ml versus means of 4.99 (+/- 3.74) and 6.95 (+/- 5.6) for 10 persistent positives at the first and second visits, respectively. Expected false-reversion and -conversion rates were 32% (90CI, 25 to 39%) and 6.95% (90CI, 4.6 to 9.8%) when the sensitivity and specificity were assumed to average 70% and 98%, respectively. Transient responses to QFT-G-IT are common, and low positive results need to be interpreted with caution. Further studies are needed to characterize the predictive value of the test for U.S. foreign-born and other targeted screening populations.

  View details for DOI 10.1128/CVI.00398-07

  View details for Web of Science ID 000258666700005

  View details for PubMedID 18199741

  View details for PubMedCentralID PMC2268272

• Cerebral myiasis associated with angiosarcoma of the scalp: case report. Neurosurgery Cheshier, S. H., Bababeygy, S. R., Higgins, D., Parsonnet, J., Huhn, S. L. 2007; 61 (1): E167-?

  Abstract

  Primary human cerebral myiasis is an exceedingly rare condition and is almost never encountered by physicians in developed countries. The case report summarizes a case of extensive cerebral myiasis in a periurban community in the United States.After a minor motor vehicle accident, police brought a 75-year-old man to the emergency room because he was observed to have a large cranial lesion. Examination revealed a 15 x 17 cm frontal bone defect with eroded frontal dura, exposed cortex, and massive cortical maggot infestation.The patient was empirically treated with intravenous antibiotics for meningitis. Maggots (Phaenicia sericata, or the green bottle fly) were removed by suction, attrition, and gentle contact exposure to a mild bleach solution. Biopsy of the scalp and cranium revealed angiosarcoma, for which operative treatment was refused. The patient was transferred to a skilled nursing facility for palliative care where he died 3 months later.This is the first published case of cerebral myiasis in the United States. Although human cerebral myiasis is rare, conditions do exist in this country that permit myiasis.

  View details for PubMedID 17621006

• Serum ghrelin levels and risk of subsequent adenocarcinoma of the esophagus AMERICAN JOURNAL OF GASTROENTEROLOGY de Martel, C., Haggerty, T. D., Corley, D. A., Vogelman, J. H., Orentreich, N., Parsonnet, J. 2007; 102 (6): 1166-1172

  Abstract

  Several large studies have shown a negative association between Helicobacter pylori (H. pylori) infection and esophageal adenocarcinoma. Diminution of gastric ghrelin secretion by H. pylori could protect against esophageal malignancy by decreasing appetite, food intake, and acid production, thereby decreasing weight and gastroesophageal reflux.We evaluated the association of ghrelin with esophageal adenocarcinoma using a population from a previous nested case-control study. Among 128,992 enrolled in a multiphasic health checkup (MHC) between 1964 and 1969, 52 patients developed esophageal adenocarcinoma by the year 2000. Three random controls from the MHC cohort were matched to each case by age, sex, race, and the date and site of their MHC. Serum samples collected at the MHC had been previously tested for IgG antibodies against H. pylori and the CagA protein. Serum ghrelin concentrations were determined by a commercial EIA on 52% of the initial subjects (31 cases and 79 controls).A concentration of ghrelin greater than 3,200 pg/mL at MHC (fourth quartile) was associated with a lower risk of esophageal cancer (H. pylori and body mass index [BMI] adjusted OR=0.18 [CI 0.04-0.78]). This inverse association was seen only in overweight subjects (BMI>or=25, P value for interaction=0.09). The effects of H. pylori and ghrelin were independent.Contrary to the original hypothesis, high rather than low serum ghrelin was associated with protection against esophageal adenocarcinoma but only among overweight subjects.

  View details for DOI 10.1111/j.1572-0241.2007.01116.x

  View details for Web of Science ID 000246702100006

  View details for PubMedID 17378911

• Helicobacter pylori infection and gender: A meta-analysis of population-based prevalence surveys DIGESTIVE DISEASES AND SCIENCES de Martel, C., Parsonnet, J. 2006; 51 (12): 2292-2301

  Abstract

  Although most of Helicobacter pylori-related diseases are associated with male gender, the role of gender as a risk factor for H. pylori infection is still debated. To assess the true association between H. pylori and gender, we conducted a meta-analysis of large, population-based studies where the measure of association had been adjusted at least for age and socioeconomic status, and obtained primary data from authors when information on gender associations were not presented. In 18 adult populations, the test of heterogeneity was not significant and male gender was significantly associated with H. pylori infection (summary odds ratio [OR] 1.16 [95% confidence interval (CI) 1.11, 1.22]). In 10 pediatric populations, the test of heterogeneity was of borderline significance, and the summary OR computed using a random effect model was close to 1 (summary OR 1.03 [95% CI 0.91, 1.17]). This study confirms the male predominance of H. pylori infection in adults as a global and homogeneous phenomenon; such predominance is not apparent in children. Differential antibiotic exposure or differential protective immunity between genders may explain the different results observed between children and adult studies.

  View details for DOI 10.1007/s10620-006-9210-5

  View details for Web of Science ID 000243188600028

  View details for PubMedID 17089189

• Gastroenteritis and transmission of Helicobacter pylori infection in households Digestive Disease Week Meeting/106th Annual Meeting of the American-Gastroenterological-Association Perry, S., Sanchez, M. d., Yang, S., Haggerty, T. D., Hurst, P., Perez-Perez, G., Parsonnet, J. CENTERS DISEASE CONTROL. 2006: 1701–8

  Abstract

  The mode of transmission of Helicobacter pylori infection is poorly characterized. In northern California, 2,752 household members were tested for H. pylori infection in serum or stool at a baseline visit and 3 months later. Among 1,752 person considered uninfected at baseline, 30 new infections (7 definite, 7 probable, and 16 possible) occurred, for an annual incidence of 7% overall and 21% in children <2 years of age. Exposure to an infected household member with gastroenteritis was associated with a 4.8-fold (95% confidence interval [CI] 1.4-17.1) increased risk for definite or probable new infection, with vomiting a greater risk factor (adjusted odds ratio [AOR] 6.3, CI 1.6-24.5) than diarrhea only (AOR 3.0, p = 0.65). Of probable or definite new infections, 75% were attributable to exposure to an infected person with gastroenteritis. Exposure to an H. pylori-infected person with gastroenteritis, particularly vomiting, markedly increased risk for new infection.

  View details for Web of Science ID 000241573900011

  View details for PubMedID 17283620

• Acquisition of Helicobacter pylori infection in rhesus macaques is most consistent with oral-oral transmission JOURNAL OF CLINICAL MICROBIOLOGY Solnick, J. V., Fong, J., Hansen, L. M., Chang, K., Canfield, D. R., Parsonnet, J. 2006; 44 (10): 3799-3803

  Abstract

  Socially housed rhesus monkeys rapidly acquired Helicobacter pylori infection, although the organism was rarely cultivated from saliva, feces, or the environment. Since the concentrations of H. pylori in vomit were compatible with what is known about the infectious dose, our results are most consistent with an oral-oral means of transmission.

  View details for DOI 10.1128/JCM.01482-06

  View details for Web of Science ID 000241138800053

  View details for PubMedID 17021115

  View details for PubMedCentralID PMC1594807

• Concordance of Helicobacter pylori infection among children in extended-family homes 132nd Annual Meeting of the American-Public-Health-Association Garg, P. K., Perry, S., Sanchez, L., Parsonnet, J. CAMBRIDGE UNIV PRESS. 2006: 450–59

  Abstract

  Helicobacter pylori is transmitted within households and high concordance is observed among siblings. To better understand the contributions of close interpersonal contact and family relatedness to transmission, we compared concordance of H. pylori infection among 241 sibling and non-sibling children aged 2-18 years in 68, predominantly low-income, Hispanic households with at least two nuclear families. Prevalence of H. pylori infection was 24%. Compared to children with no infected siblings or non-siblings and adjusting for age, odds of H. pylori infection were 1.2 (95% CI 0.52-2.9), 3.2 (95% CI 1.14-9.1), and 9.4 (95% CI 3.1-28.5) for children residing with at least one infected non-sibling, one infected sibling, and with at least one infected sibling and non-sibling, respectively. The study further implicates intersibling transmission as a pathway for H. pylori infection in childhood. In addition, living with a non-sibling in extended-family homes may contribute to infection risk but only in households with prevalent H. pylori infection within all family groups.

  View details for DOI 10.1017/S0950268805005352

  View details for Web of Science ID 000237786200002

  View details for PubMedID 16283949

• Investigation of mediastinitis due to coagulase-negative staphylococci after cardiothoracic surgery INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY Van Kerkhove, M. D., Parsonnet, J., Weingart, M., Tompkins, L. S. 2006; 27 (3): 305-307

  Abstract

  Six cases of coagulase-negative staphylococcal mediastinitis were identified in the latter half of 1999. A new preoperative cleansing solution was suspected by hospital staff to be a factor in the outbreak. We evaluated this possible risk factor along with other known and suspected surgical site infection risk factors in this case-control study.

  View details for Web of Science ID 000249035800015

  View details for PubMedID 16532421

• Associations of serologic markers of infection and inflammation with vascular disease events and mortality in American dialysis patients. Clinical and experimental nephrology Lentine, K. L., Parsonnet, J., Taylor, I., Wrone, E. M., Lafayette, R. A. 2006; 10 (1): 55-62

  Abstract

  Inflammatory markers predict cardiovascular risk and mortality in endstage renal disease. The relationship of chronic infections to inflammation and vascular disease events has not been reported among American dialysis patients.We performed a cross-sectional and prospective study of a multiracial cohort of 97 chronic hemodialysis patients in California. Anti-Chlamydia pneumoniae IgA and IgG antibodies (Cp-IgA and Cp-IgG), anti-Helicobacter pylori antibodies (Hp-IgG), and highly sensitive C-reactive protein (hsCRP) levels were measured at enrollment. We ascertained the prevalence of atherosclerotic vascular (coronary artery, cerebrovascular, and peripheral vascular) disease (AVD) events, and observed participants for at least 1 year for incident events and mortality. We defined statistical significance as P < 0.01.Elevated hsCRP levels (77%) and seropositivity to C. pneumoniae were common (Cp-IgA, 49%; Cp-IgG, 64%), whereas the seroprevalence of Hp-IgG was relatively low (25%). The hsCRP levels did not vary with infection status. In bivariate analysis, Cp-IgA and Cp-IgG were each associated with approximately fourfold higher odds of prevalent AVD (P < 0.01). Although anti-chlamydial antibodies maintained nearly significant associations with AVD after covariate adjustment (P < 0.05), antibodies did not predict outcomes over the period of observation. However, hsCRP was a nearly significant independent predictor of prevalent AVD (P = 0.02) and of mortality during follow-up (P = 0.01). We did not detect an association of Hp-IgG with any study outcome.Our findings generalize a possible link between C. pneumoniae and prevalent atherosclerosis in American hemodialysis patients and confirm the importance of hsCRP as a prognostic indicator. Our work does not support H. pylori as an important mediator of cardiovascular risk in dialysis patients.

  View details for PubMedID 16544178

• Changes of gene expression in gastric preneoplasia following Helicobacter pylori eradication therapy CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION Tsai, C. J., Herrera-Goepfert, R., Tibshirani, R. J., Yang, S. F., Mohar, A., Guarner, J., Parsonnet, J. 2006; 15 (2): 272-280

  Abstract

  Helicobacter pylori causes gastric preneoplasia and neoplasia. Eradicating H. pylori can result in partial regression of preneoplastic lesions; however, the molecular underpinning of this change is unknown. To identify molecular changes in the gastric mucosa following H. pylori eradication, we used cDNA microarrays (with each array containing approximately 30,300 genes) to analyze 54 gastric biopsies from a randomized, placebo-controlled trial of H. pylori therapy. The 54 biopsies were obtained from 27 subjects (13 from the treatment and 14 from the placebo group) with chronic gastritis, atrophy, and/or intestinal metaplasia. Each subject contributed one biopsy before and another biopsy 1 year after the intervention. Significant analysis of microarrays (SAM) was used to compare the gene expression profiles of pre-intervention and post-intervention biopsies. In the treatment group, SAM identified 30 genes whose expression changed significantly from baseline to 1 year after treatment (0 up-regulated and 30 down-regulated). In the placebo group, the expression of 55 genes differed significantly over the 1-year period (32 up-regulated and 23 down-regulated). Five genes involved in cell-cell adhesion and lining (TACSTD1 and MUC13), cell cycle differentiation (S100A10), and lipid metabolism and transport (FABP1 and MTP) were down-regulated over time in the treatment group but up-regulated in the placebo group. Immunohistochemistry for one of these differentially expressed genes (FABP1) confirmed the changes in gene expression observed by microarray. In conclusion, H. pylori eradication may stop or reverse ongoing molecular processes in the stomach. Further studies are needed to evaluate the use of these genes as markers for gastric cancer risk.

  View details for DOI 10.1158/1055-9965.EPI-05-0362

  View details for Web of Science ID 000235587200012

  View details for PubMedID 16492915

• Validation of the blood quininium resin test for assessing gastric hypochlorhydria DIGESTIVE DISEASES AND SCIENCES de Martel, C., Ratanasopa, S., Passaro, D., Parsonnet, J. 2006; 51 (1): 84-88

  Abstract

  Although gastric hypochlorhydria is a risk factor for gastroenteritis and for gastric cancer, no reliable, inexpensive, noninvasive test exists for screening or epidemiologic studies. We aimed to evaluate the sensitivity and specificity of the blood quininium resin test (bQRT) for hypochlorhydria, against pH monitoring. Twelve fasting adult volunteers-seven with and five without H. pylori infection-ingested 80 mg/kg of quininium resin twice, once with and once without acid suppression. Gastric pH was monitored for 75 minutes; serum samples were obtained at times 0 and 75 minutes. The bQRT levels were compared to gastric pH, controlling for omeprazole use and H. pylori infection. Subjects with a median recorded pH > or =3.5 were considered hypochlorhydric. Using a bQRT level of 10 as a cutoff for hypochlorhydria, the sensitivity and specificity of the bQRT were 100% and 37.5%, respectively. The bQRT predicted omeprazole use more accurately than pH monitoring. In conclusions, The bQRT has a high sensitivity for hypochlorhydria, making it potentially useful in populations with a high prevalence of hypochlorhydria. In its current formulation, the bQRT's low specificity makes it less useful in low-risk population.

  View details for DOI 10.1007/s10620-006-3089-z

  View details for Web of Science ID 000234602300018

  View details for PubMedID 16416217

• Clinician-discoverers - Marshall, Warren, and H-Pylori NEW ENGLAND JOURNAL OF MEDICINE Parsonnet, J. 2005; 353 (23): 2421-2423

  View details for Web of Science ID 000233754400001

  View details for PubMedID 16339090

• Commentary: H. pylori infection in early life and the problem of imperfect tests INTERNATIONAL JOURNAL OF EPIDEMIOLOGY Perry, S., Parsonnet, J. 2005; 34 (6): 1356-1358

  View details for DOI 10.1093/ije/dyi243

  View details for Web of Science ID 000233845900035

  View details for PubMedID 16303814

• Cell proliferation and inflammation on biopsy samples with multifocal atrophic gastritis before and 1 year after Helicobacter pylori eradication ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE Guarner, J., Bartlett, J., Seitz, R., Whistler, T., Herrera-Goepfert, R., Mohar, A., Sanchez, L., Halperin, D., Parsonnet, J. 2005; 129 (11): 1451-1456

  Abstract

  Results of clinical trials that have assessed whether gastric cancer is preventable with Helicobacter pylori eradication therapy remain inconclusive. These trials have used atrophy, intestinal metaplasia, and dysplasia as histopathologic end points that reflect possible preneoplastic lesions. Trial results would be more compelling if cell proliferation and inflammatory markers improved simultaneously with histopathologic lesions.To study the presence of cell proliferation markers and type of inflammatory cells in biopsy specimens with gastritis, atrophy, and intestinal metaplasia before and 1 year after H pylori therapy and to determine if immunohistochemistry can be used to study these.We evaluated 12 subjects with gastritis and 16 with gastritis and multiple foci of atrophy and intestinal metaplasia by using immunohistochemical assays for tumor suppressor protein p53, proliferation marker Ki-67, cell cycle regulator cyclin D1, T and B lymphocytes, macrophages, and TUNEL (terminal deoxynucleotide transferase deoxyuridine triphosphate nick end labeling) assay for apoptosis. The biopsy specimens were selected from a randomized clinical trial that studied improvement of histopathologic gastric lesions after H pylori eradication.Groups of surface epithelial cells that expressed p53 and Ki-67 were observed more often in subjects with atrophy and intestinal metaplasia compared with those with gastritis alone. T lymphocytes in the lamina propria were frequently observed 1 year after treatment in subjects with atrophy and intestinal metaplasia.Immunohistochemical assays for cell proliferation and inflammatory cell markers showed different distribution patterns in these gastric biopsy specimens. The presence of T lymphocytes and groups of cells that expressed proliferation markers in subjects with multiple foci of atrophy and intestinal metaplasia needs further study.

  View details for Web of Science ID 000233093400015

  View details for PubMedID 16253026

• QuantiFERON (R)-TB predicts tuberculin skin test boosting in US foreign-born INTERNATIONAL JOURNAL OF TUBERCULOSIS AND LUNG DISEASE Nguyen, M., Perry, S., Parsonnet, J. 2005; 9 (9): 985-991

  Abstract

  Santa Clara County, Northern California.To characterize agreement of tuberculin skin test (TST) and QuantiFERON-TB (QFT) with repeated testing.Fifty-two subjects participating in an ongoing prospective study of infectious disease transmission were tested by TST and QFT at two home visits 3 months apart. Boosting was defined as reclassification of TST from negative to positive. Agreement and reproducibility of TST and QFT were assessed using kappa and McNemar statistics.Of 48 individuals completing all tests, 75% were foreign-born (92% Latin America) and 58% were BCG-vaccinated. Initial TST and QFT were positive in 13 (27%) and 21 (44%), respectively, with an overall agreement of 67% (K = 0.29). Ten (29%) of 35 initial TST-negative reactions boosted, nine of whom were BCG-vaccinated subjects. Boosting occurred in eight (67%) of 12 subjects who were initially QFT-positive/TST-negative. Compared to the second TST, initial QFT had a relative post-test probability of 76% (95% CI 0.58-0.95); boosting accounted for 8/16 (50%) of initial testing discordances.Positive QFT in the setting of negative TST frequently anticipates a TST boost. This finding helps explain discordance between the two tests and may provide an alternative to serial TST testing.

  View details for Web of Science ID 000231607600008

  View details for PubMedID 16158890

• Helicobacter pylori infection in different generations of Hispanics in the San Francisco Bay Area AMERICAN JOURNAL OF EPIDEMIOLOGY Tsai, C. J., Perry, S., Sanchez, L., Parsonnet, J. 2005; 162 (4): 351-357

  Abstract

  To quantify the contributions of household and environmental factors to Helicobacter pylori infection, the authors examined H. pylori infection among several generations of Hispanics in the San Francisco Bay Area. Between 2000 and 2004, household members were tested for H. pylori and interviewed about demographic factors and household pedigree. An immigrant was defined as someone born in Latin America with at least one Latin America-born parent; a first-generation US-born Hispanic was defined as someone born in the United States with at least one Latin America-born parent; and a second-generation US-born Hispanic was defined as someone born in the United States with at least one US-born parent. Prevalences of H. pylori in immigrants and first- and second-generation US-born Hispanics were 31.4% (102/325), 9.1% (98/1,076), and 3.1% (2/64), respectively. Compared with second-generation US-born Hispanics, the age-adjusted odds ratios for H. pylori were 9.70 (95% confidence interval (CI): 1.57, 60.00) for immigrants and 4.32 (95% CI: 0.69, 26.96) for first-generation US-born Hispanics (p(trend) < 0.001). These odds ratios decreased to 6.19 (95% CI: 1.13, 33.77) and 3.24 (95% CI: 0.59, 17.82), respectively, after adjustment for parental infection (odds ratio (OR) = 2.94, 95% CI: 1.59, 4.38), low education (OR = 1.76, 95% CI: 1.20, 2.68), and crowding (OR = 1.23, 95% CI: 0.84, 1.79). Both the household and birth-country environments probably contributed to declining H. pylori prevalence among successive generations of Hispanics.

  View details for DOI 10.1093/aje/kwi207

  View details for Web of Science ID 000231150600008

  View details for PubMedID 16014772

• Risk of intestinal helminth and protozoan infection in a refugee population AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE Garg, P. K., Perry, S., Dorn, M., Hardcastle, L., Parsonnet, J. 2005; 73 (2): 386-391

  Abstract

  With continuing emigration from endemic countries, screening for parasitic infections remains a priority in U.S. communities serving refugee and immigrant populations. We report the prevalence of helminths and protozoa as well as demographic risk factors associated with these infections among 533 refugees seen at the Santa Clara County, California, Refugee Clinic between October 2001 and January 2004. Stool parasites were identified from 14% of refugees, including 9% found to have one or more protozoa and 6% found to have at least one helminth. Most common protozoan infections were Giardia lamblia (6%) and Dientamoeba fragilis (3%), and for helminths, hookworm (2%). Protozoa were more frequent in refugees < 18 years of age (OR: 2.2 [1.2-4.2]), whereas helminths were more common in refugees from South Central Asia (OR: 8.0 [2.3-27.7]) and Africa (OR: 5.9 [1.6-21.6]) when compared with refugees from Eastern Europe and the Middle East. Among helminths, Ascaris lumbricoides and hookworm were concentrated among South Central Asians (6 of 7 and 10 of 11 cases, respectively), whereas Strongyloides stercoralis was predominantly found in Africans (5 of 7 cases). Although predeparture empirical treatment programs in Saharan Africa may have helped to reduce prevalence among arriving refugees from this region, parasitic infection is still common among refugees to the United States with helminth infections found in more specific populations. As refugees represent only a fraction of recent immigrants from endemic countries, current studies in nonrefugee groups are also needed.

  View details for Web of Science ID 000231272700032

  View details for PubMedID 16103610

• Use of insecticide-treated nets (ITNs) following a malaria education intervention in Piron, Mali: a control trial with systematic allocation of households MALARIA JOURNAL Rhee, M., Sissoko, M., Perry, S., McFarland, W., Parsonnet, J., Doumbo, O. 2005; 4

  Abstract

  Insecticide-treated nets (ITNs) reduce malaria morbidity and mortality, but use is limited. A barrier to ITN use may be lack of knowledge regarding malaria transmission and prevention. This study is a controlled trial comparing ITN use and malaria knowledge levels between households in Piron, Mali, undertaken in 2003.Households received net impregnation services either with or without antecedent education. The main outcome measure was ITN use, defined as impregnation of at least one of the household's existing bednets with insecticide during the study. Knowledge about malaria and prevention practices was assessed pre- and post- educational intervention. Results were analysed by household and by individual.Forty-nine percent (34/70) of households who received the educational component impregnated their nets in comparison to 35% (22/62) of households who did not (OR = 1.6 CI = 0.8-3.3, P = 0.19). In individual analysis, ITN use was significantly greater in participants who had received the educational intervention (48%) vs. individuals who did not (33%, OR = 1.9, P = 0.012). Knowledge levels about malaria significantly increased for each individual pre- versus post- educational intervention (average change score = 2.13, standard deviation = 1.97, t = -17.78, P < 0.001), although there was no difference found between educational (change score = 2.14) and control groups (change score = 2.12).It is possible to educate individuals about malaria and to implement net impregnation services with limited resources. Greater accessibility to net-impregnation services is necessary but not sufficient to increase ITN use.

  View details for DOI 10.1186/1475-2875-4-35

  View details for Web of Science ID 000231880100001

  View details for PubMedID 16042793

  View details for PubMedCentralID PMC1208942

• Household transmission of gastroenteritis EMERGING INFECTIOUS DISEASES Perry, S., Sanchez, M. D., Hurst, P. K., Parsonnet, J. 2005; 11 (7): 1093-1096

  Abstract

  Transmission of infectious gastroenteritis was studied in 936 predominately Hispanic households in northern California. Among 3,916 contacts of 1,099 primary case-patients, the secondary attack rate was 8.8% (95% confidence interval 7.9-9.7); children had a 2- to 8-fold greater risk than adults. Bed-sharing among children in crowded homes is a potentially modifiable risk.

  View details for Web of Science ID 000230106600018

  View details for PubMedID 16022787

• Significance of transiently positive enzyme-linked immunosorbent assay results in detection of Helicobacter pylori in stool samples from children JOURNAL OF CLINICAL MICROBIOLOGY Haggerty, T. D., Perry, S., Sanchez, L., Perez-Perez, G., Parsonnet, J. 2005; 43 (5): 2220-2223

  Abstract

  In young children, the significance of stool samples transiently positive for Helicobacter pylori antigen is unknown. As part of a larger prospective study on enteric infections, stool samples were obtained from 323 children at two time points 3 months apart and tested for H. pylori antigen using a commercially available enzyme-linked immunosorbent assay (ELISA) test. Seminested PCR for a Helicobacter-specific 16S rRNA gene was performed on all 26 pairs reverting from positive to negative (transient positives), all 4 persistent antigen-positive pairs, and 10 randomly selected persistent antigen-negative pairs. Helicobacter species were amplified from the first stool samples of 15/26 (58%) of the transient positives and 1 (25%) of 4 persistent positives. No Helicobacter species were amplified from the 10 persistent negatives. Among the 15 amplicons from transient-positive stool, H. pylori was sequenced and identified from 12 (80%; 95% confidence interval, 52% to 96%) and other Helicobacter spp. were identified from three (Helicobacter canis, Helicobacter winghamensis, and MIT 99-5504). Four of the 15 remained positive by PCR for the second (antigen-negative) stool sample, including all 3 initially identified as non-H. pylori. Helicobacter bilis was amplified from the second sample of a persistent positive. Two of eight transient positives from whom serum was available had accompanying transient elevations in anti-H. pylori antibodies. Transiently positive stool ELISAs for H. pylori are common and represent H. pylori in the majority of cases where sequences can be obtained. A not-insignificant percentage of antigen-positive stools, however, may represent other Helicobacter species.

  View details for DOI 10.1128/JCM.43.5.2220-2220.2005

  View details for Web of Science ID 000229090100027

  View details for PubMedID 15872245

  View details for PubMedCentralID PMC1153794

• Helicobacter pylori infection and the risk of development of esophageal adenocarcinoma Bay Area Clinical Research Symposium de Martel, C., Llosa, A. E., Farr, S. M., Friedman, G. D., Vogelman, J. H., Orentreich, N., Corley, D. A., Parsonnet, J. OXFORD UNIV PRESS INC. 2005: 761–67

  Abstract

  An increase in the incidence of esophageal adenocarcinoma has coincided with a decrease in the prevalence of Helicobacter pylori infection. Whether these 2 phenomena are associated is unknown.We conducted a nested case-control study of 128,992 members of an integrated health care system who had participated in a multiphasic health checkup (MHC) during 1964-1969. During follow-up, 52 patients developed esophageal adenocarcinoma. Three randomly chosen control subjects from the MHC cohort were matched to each case subject, on the basis of age at the MHC, sex, race, and the date and site of the MHC. Data on cigarette smoking, alcohol consumption, body mass index (BMI), and education level were obtained at the MHC. Serum samples collected at the MHC were tested for IgG antibodies to H. pylori and to the H. pylori CagA protein.Subjects with H. pylori infections were less likely than uninfected subjects to develop esophageal adenocarcinoma (odds ratio [OR], 0.37 [95% confidence interval (CI), 0.16-0.88]). This significant association was restricted to case subjects and control subjects <50 years old at the MHC (OR, 0.20 [95% CI, 0.06-0.68]). In patients with H. pylori infections, the OR for those who tested positive for IgG antibodies to the CagA protein was similar to that for those who tested negative for it. BMI >/=25 and cigarette smoking were strong independent risk factors for development of esophageal adenocarcinoma.The absence of H. pylori infection, independent of cigarette smoking and BMI, is associated with a markedly increased risk of development of esophageal adenocarcinoma.

  View details for Web of Science ID 000226862400018

  View details for PubMedID 15688293

• Helicobacter pylori and risk of gastroenteritis Digestive Disease Week Meeting/104th Annual Meeting of the American-Gastroenterological-Association Perry, S., Sanchez, L., Yang, S. F., Haggerty, T. D., Hurst, P., Parsonnet, J. OXFORD UNIV PRESS INC. 2004: 303–10

  Abstract

  Helicobacter pylori infection is thought to modify susceptibility to gastroenteritis.Members of northern California households with an index case of gastroenteritis were interviewed regarding recent episodes and tested for H. pylori. Conditional logistic regression was used to evaluate the risk of secondary gastroenteritis within households matched for members with secondary gastroenteritis (cases) and those without symptoms (control subjects). Case and control subjects were also tested for hepatitis A virus (HAV).Of 801 households, 205 (26%) had at least 1 member with secondary gastroenteritis, of which 116 (56%) also included at least 1 member without symptoms (158 case and 285 control subjects). Compared with uninfected members and adjusting for age, those with antibodies to only 1 infection were at a decreased risk of secondary gastroenteritis (odds ratio [OR] for H. pylori infection, 0.25 [95% confidence interval [CI], 0.08-0.82]; OR for HAV, 0.45 [95% CI, 0.23-0.87]). Having antibodies to both H. pylori and HAV did not add to this negative effect (adjusted OR, 0.39 [95% CI, 0.18-0.84]).H. pylori did not increase the risk of gastroenteritis in these households. A strong negative association between H. pylori infection and gastroenteritis is likely explained by prior exposure and immunity to other enteric pathogens.

  View details for Web of Science ID 000222254800013

  View details for PubMedID 15216465

• Antimicrobial resistance incidence and risk factors among Helicobacter pylori-infected persons, United States EMERGING INFECTIOUS DISEASES Duck, W. M., SOBEL, J., Pruckler, J. M., Song, O. S., Swerdlow, D., Friedman, C., Sulka, A., Swaminathan, B., Taylor, T., Hoekstra, M., Griffin, P., Smoot, D., Peek, R., Metz, D. C., Bloom, P. B., Goldschmid, S., Parsonnet, J., Triadafilopoulos, G., Perez-Perez, G. I., Vakil, N., Ernst, P., Czinn, S., Dunne, D., Gold, B. D. 2004; 10 (6): 1088-1094

  Abstract

  Helicobacter pylori is the primary cause of peptic ulcer disease and an etiologic agent in the development of gastric cancer. H. pylori infection is curable with regimens of multiple antimicrobial agents, and antimicrobial resistance is a leading cause of treatment failure. The Helicobacter pylori Antimicrobial Resistance Monitoring Program (HARP) is a prospective, multicenter U.S. network that tracks national incidence rates of H. pylori antimicrobial resistance. Of 347 clinical H. pylori isolates collected from December 1998 through 2002, 101 (29.1%) were resistant to one antimicrobial agent, and 17 (5%) were resistant to two or more antimicrobial agents. Eighty-seven (25.1%) isolates were resistant to metronidazole, 45 (12.9%) to clarithromycin, and 3 (0.9%) to amoxicillin. On multivariate analysis, black race was the only significant risk factor (p < 0.01, hazard ratio 2.04) for infection with a resistant H. pylori strain. Formulating pretreatment screening strategies or providing alternative therapeutic regimens for high-risk populations may be important for future clinical practice.

  View details for Web of Science ID 000221749300018

  View details for PubMedID 15207062

  View details for PubMedCentralID PMC3323181

• Bacterial infection and MALT lymphoma NEW ENGLAND JOURNAL OF MEDICINE Parsonnet, J., Isaacson, P. G. 2004; 350 (3): 213-215

  View details for Web of Science ID 000188078400002

  View details for PubMedID 14724298

• Helicobacter pylori infection and gastric cancer - For want of more outcomes JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Parsonnet, J., Forman, D. 2004; 291 (2): 244-245

  View details for Web of Science ID 000188040900034

  View details for PubMedID 14722152

• Helicobacter pylori eradication and gastric preneoplastic conditions: A randomized, double-blind, placebo-controlled trial CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION Ley, C., Mohar, A., Guarner, J., Herrera-Goepfert, R., Figueroa, L. S., Halperin, D., Johnstone, I., Parsonnet, J. 2004; 13 (1): 4-10

  Abstract

  Helicobacter pylori causes gastric adenocarcinoma; whether treatment of H. pylori infection prevents this cancer remains unknown. In a randomized, double-blind, placebo-controlled trial of H. pylori eradication, we determined whether treatment for H. pylori decreases gastric cancer risk, using preneoplastic conditions as surrogate markers. A total of 248 healthy volunteers (age >40 years) randomly received H. pylori treatment (omeprazole, amoxicillin, clarythromycin; n = 122) or matched placebo (n = 126) for 1 week. Endoscopy was performed at baseline and at 6 weeks and 1 year. Seven biopsies from each endoscopy were reviewed by two pathologists using the revised Sydney classification. Outcome measures were both a consensus "worst biopsy" diagnosis and a weighted index score that incorporated degrees of severity of preneoplasia from all biopsies. We compared change in these outcomes over time between the two treatment groups. H. pylori cure rates for compliant subjects in the treatment arm were 79.2% and 75.7% at 6 weeks and 1 year, respectively. No statistically significant change in the worst biopsy diagnosis was observed from 6 weeks to 1 year between placebo and treated subjects (for improvement/worsening, placebo, 19.4%/10.5%; treatment, 22.5%/8.3%; P = 0.74). Change in index score was favorably greater in treatment compared with placebo subjects (intention-to-treat analysis, P = 0.03); this finding was particularly evident in the antrum. H. pylori eradication gave more favorable gastric histopathologies over 1 year than no treatment. Such incomplete regression suggests but does not prove that eradication of H. pylori decreases cancer risk.

  View details for Web of Science ID 000188438300004

  View details for PubMedID 14744726

• Natural acquisition of Helicobacter pylori infection in newborn rhesus Macaques JOURNAL OF CLINICAL MICROBIOLOGY Solnick, J. V., Chang, K., Canfield, D. R., Parsonnet, J. 2003; 41 (12): 5511-5516

  Abstract

  Helicobacter pylori infection is usually acquired in childhood, but precise estimates of the age of acquisition are difficult to obtain in young children. Since serial endoscopic biopsies are not feasible in human infants, we examined acquisition of H. pylori infection that is known to occur in socially housed nonhuman primates. By 12 weeks of age, 8 of 20 newborns (40%) were culture positive for H. pylori, and prevalence reached 90% by 1 year of age. Newborns from infected dams were more commonly infected than those from uninfected dams, particularly during the peripartum period, suggesting that close contact during this time may facilitate transmission. Transient infection was uncommon and occurred only after the first positive culture. These results suggest that in a high-prevalence environment, persistent H. pylori infection may be acquired at an earlier age than was previously thought. Since clean, potable water was readily available, contamination of water supply is not essential for widespread infection at an early age in areas where hygiene is otherwise poor. Furthermore, breastfeeding seems to offer little protection, since newborn macaques breastfeed during the first year of life and typically are fully weaned only when another newborn arrives the following spring.

  View details for DOI 10.1128/JCM.41.12.5511-5516.2003

  View details for Web of Science ID 000187228800022

  View details for PubMedID 14662932

  View details for PubMedCentralID PMC309038

• Changes in gene expression in intermediate endpoints of gastric cancer: A randomized, placebo-controlled trial of Helicobacter pylori eradication therapy. 2nd Annual Conference on Frontiers in Cancer Prevention Research Tsai, C. J., Yang, S. F., Tibshirani, R. J., Guarner, J., Mohar, A., Herrera-Goepfert, R., Parsonnet, J. AMER ASSOC CANCER RESEARCH. 2003: 1280S–1280S

  View details for Web of Science ID 000187153300018

• What is the Helicobacter pylori global reinfection rate? Canadian journal of gastroenterology = Journal canadien de gastroenterologie Parsonnet, J. 2003; 17: 46B-48B

  Abstract

  Reinfection with any organism is related to the force of infection in the population and on both innate and acquired immunity to infection. Little is yet known about primary immune protection against Helicobacter pylori. Some data suggest that children can be recurrently infected, spontaneously eliminating the organism only to be infected again and again until the organism takes hold. This pattern of recurrent infection is not observed in patients who receive eradication therapy for chronic infection. After eradication of infection, the rate of reinfection is probably slightly lower than the primary infection rate in that age group, suggesting some level of acquired immunity. In developed countries, reinfection of adults in unusual, and recurrence usually represents failure of primary eradication rather than new infection. Some cases of reinfection do occur, however. Given that acquired immunity probably varies little from population to population, reinfections will most likely occur in areas where the force of infection is high, ie, where both the prevalence of infection and the opportunities for transmission are high.

  View details for PubMedID 12845351

• C-reactive protein, Helicobacter pylori, Chlamydia pneumoniae, cytomegalovirus and risk for myocardial infarction ANNALS OF EPIDEMIOLOGY Witherell, H. L., Smith, K. L., Friedman, G. D., Ley, C., Thom, D. H., Orentreich, N., Vogelman, J. H., Parsonnet, J. 2003; 13 (3): 170-177

  Abstract

  C-reactive protein (CRP), Chlamydia pneumonia, Helicobacter pylori, and cytomegalovirus (CMV) have each been associated with atherosclerosis. We assessed how infection and CRP related to risk for subsequent myocardial infarction (MI).Using a nested case-control design, we assessed how these factors independently and jointly affected risk for myocardial infarction (MI). Cases of first MI (N = 121) were identified from among participants in a multiphasic health check-up cohort. Controls without MI (N = 204) were matched to cases by gender, age, race, and date of serum collection. Sera collected at enrollment were tested for antibodies to infection and for CRP.In multivariate analysis (mean follow-up of 5.1 years), CRP was associated with MI only in subjects older than 51 years (p = 0.004). Although H. pylori infection increased risk for MI, this association was modest (OR = 1.90, 95% CI = 0.97-3.71) and was not evident in non-smokers or when adjusted for education. No association between C. pneumoniae or cytomegalovirus and MI was observed, nor was the association between CRP and MI explained by these infections.Elevated CRP is a risk factor for subsequent MI in older individuals. The relationship between Hp and MI may be due to confounding or co-linearity with socioeconomic status.

  View details for Web of Science ID 000181526000004

  View details for PubMedID 12604160

• Variability in antibiotic prescribing patterns and outcomes in patients with clinically suspected ventilator-associated pneumonia CHEST Fowler, R. A., Flavin, K. E., Barr, J., Weinacker, A. B., Parsonnet, J., Gould, M. K. 2003; 123 (3): 835-844

  Abstract

  To describe the variation in clinical practice strategies for the treatment of suspected ventilator-associated pneumonia (VAP) in a population of critically ill patients, and to determine whether initial empiric treatment with certain antibiotics, monotherapy vs combination antibiotic therapy, or appropriate vs inappropriate antibiotic therapy is associated with survival, length of hospital stay, or days free of antibiotics.Prospective, observational cohort study.Medical-surgical ICUs of two university-affiliated tertiary medical centers.Between May 1, 1998, and August 1, 2000, we screened 7,030 ICU patients and identified 156 patients with clinically suspected VAP. Patients were followed up until death or discharge from the hospital.The mean age was 62 years, mean APACHE (acute physiology and chronic health evaluation) II score was 14, and mortality was 34%. Combination antibiotic therapy was used in 53% of patients. Piperacillin-tazobactam, fluoroquinolones, vancomycin, cephalosporins, and aminoglycosides were the most commonly employed antibiotics. Initial empiric antibiotics were deemed appropriate in 92% of patients. The predominant organisms isolated from respiratory secretions included Pseudomonas aeruginosa and Staphylococcus aureus. Patients had lower in-hospital mortality rates if their initial treatment regimen included an antipseudomonal penicillin plus beta-lactamase inhibitor (hazard ratio [HR], 0.41; 95% confidence interval [CI], 0.21 to 0.80; p = 0.009). There was also a strong trend toward reduced mortality rates in patients treated with aminoglycosides (HR, 0.43; 95% CI, 0.16 to 1.11; p = 0.08). Specific antibiotic therapy was not associated with length of hospital stay or days free of antibiotics. Outcomes were similar for patients treated with monotherapy vs combination therapy, and for patients who received initial appropriate vs inappropriate therapy.Patients with clinically suspected VAP who receive initial empiric therapy with antipseudomonal penicillins plus beta-lactamase inhibitors, and possibly aminoglycosides, have lower in-hospital mortality rates when compared with those who are not treated with these antibiotics. These agents should be considered for the initial empiric therapy of VAP.

  View details for Web of Science ID 000181536500035

  View details for PubMedID 12628886

• Helicobacter pylori in cathartic stools of subjects with and without cimetidine-induced hypochlorhydria JOURNAL OF MEDICAL MICROBIOLOGY Haggerty, T., Shmuely, H., Parsonnet, J. 2003; 52 (2): 189-191

  Abstract

  We previously identified viable Helicobacter pylori in stools from asymptomatic hosts. We now report whether a decrease in gastric acidity enhances faecal shedding. Sixteen asymptomatic H. pylori-positive patients underwent two separate days of phosphosoda-induced diarrhoea, both with normal gastric acidity and under hypochlorhydric conditions induced with the H2-blocker cimetidine. Stool samples were collected for culture to determine the presence of viable H. pylori. Five of the 16 patients gave positive cultures with at least one stool from both normal pH and cimetidine-induced hypochlorhydria. Four were negative for all samples with both. Six gave positive stools only after cimetidine treatments, while one gave positive samples with normal pH but not with cimetidine (two-tailed P value, 0.13; McNemar test). These numbers show a trend suggesting that cimetidine-induced hypochlorhydria increases shedding of viable H. pylori.

  View details for DOI 10.1099/jmm.0.04917-0

  View details for Web of Science ID 000181168900014

  View details for PubMedID 12543927

• No association between Helicobacter pylori and Mycobacterium tuberculosis infections among gastrointestinal clinic attendees in Lima, Peru EPIDEMIOLOGY AND INFECTION Torres, M. A., Passaro, D. J., Watanabe, J., Parsonnet, J., Small, P., Miyagui, J., Rodriquez, C., Astete, M., Gilman, R. H. 2003; 130 (1): 87-91

  Abstract

  Helicobacter pylori (HP) infection can cause hypochlorhydria, a positive risk factor for Mycobacterium tuberculosis (MTB) infection. This study examined the association between HP and MTB infections among persons attending the Policlinico Peruano Japonés Gastrointestinal Clinic in Lima, Peru. From 23 June 2000 to 18 August 2000, consenting 18-55 year olds who attended the clinic for gastric biopsy gave blood for HP serologic testing, underwent tuberculin skin testing (TST) and completed a social and medical history. Of 128 participating patients, 78 (61%) were TST positive for MTB, and 107 (84%) were infected with HP by serology. Of the patients who were HP positive, 67 (63%) developed positive TST reactions compared to 11 (52%) of 21 HP-seronegative subjects (OR 1.29; 95% CI 0.54-3.11; P = 0.6). There was no association after adjusting for covariates of H. pylori infection (OR 0.78; 95% CI 0.23-2.71; P = 0.7). However, study power was limited by high prevalence of the two infections.

  View details for DOI 10.1017/S0950268802007653

  View details for Web of Science ID 000182506900010

  View details for PubMedID 12613749

  View details for PubMedCentralID PMC2869942

• Diagnostic yield of gastric biopsy specimens when screening for preneoplastic lesions HUMAN PATHOLOGY Guarner, J., Herrera-Goepfert, R., Mohar, A., Smith, C., Schofield, A., Halperin, D., Sanchez, L., Parsonnet, J. 2003; 34 (1): 28-31

  Abstract

  The Sydney system recommends sites and numbers of stomach biopsies (mapping) for evaluation of Helicobacter pylori-associated lesions. The diagnostic yield of the recommended mapping technique in populations at high risk for gastric preneoplastic lesions has not been established. We evaluated pathology data from 733 endoscopies performed as part of an intervention study that assessed the effects of H. pylori treatment on preneoplastic conditions. Two pathologists assessed whether the mapping sequence of the 7 biopsy specimens obtained during each endoscopy was correctly followed and graded the specimens using the Sydney classification for gastritis. If the mapping sequence was followed, then we evaluated whether the amount of information obtained from 3 biopsy samples approximated that obtained from 5 and 7 biopsy samples. The mapping sequence was followed in only 239 (33%) endoscopies, indicating that experienced endoscopists can inadvertently misidentify sites in the stomach when obtaining specimens. When data from 7 specimens were used, H. pylori was found in 205 endoscopies, atrophy in 152, metaplasia in 135, and dysplasia in 22. When data from 3 specimens were used, the sensitivity was 99% for presence of H. pylori, 82% for atrophy and metaplasia, and 81% for dysplasia. When data from 5 specimens were used, the sensitivity was 100% for H. pylori, 96% for atrophy, and 95% for metaplasia and dysplasia. Although site-specific biopsy mapping is difficult in practice, the recommendations of the Sydney system as to the location and number of gastric biopsy specimens can adequately identify significant gastric histopathology.

  View details for DOI 10.1053/hupa.2003.3

  View details for Web of Science ID 000180732200005

  View details for PubMedID 12605363

• Growth slowing after acute Helicobacter pylori infection is age-dependent JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION Passaro, D. J., TAYLOR, D. N., Gilman, R. H., Cabrera, L., Parsonnet, J. 2002; 35 (4): 522-526

  Abstract

  Most infections occur during childhood, but the health effects of childhood infection are poorly understood. We investigated whether growth decreases in the 2 months after acute seroconversion.We performed a nested case-control study among children 6 months to 12 years of age in a community on the outskirts of Lima, Peru. Health interviews were completed daily. Anthropometric measurements were taken monthly. Sera were collected every 4 months and tested for immunoglobulin G. Two-month height and weight gains of seroconverters were compared with gains of sex, age, and size-matched seronegative controls.In the 2 months after infection, 26 seroconverters gained a median of 24% less weight than 26 matched controls (interquartile range, 63% less to 21% more). In multivariate analysis, infection attenuated weight gain only among children aged 2 years or older. This decrease was not explained by increased diarrhea.seroconversion is associated with a slowing of weight gain in children aged 2 years or older. Reasons for this finding merit additional study.

  View details for Web of Science ID 000178665500012

  View details for PubMedID 12394378

• Eradication rate of Helicobacter pylori in a Mexican population at high risk for gastric cancer and use of serology to assess cure AMERICAN JOURNAL OF GASTROENTEROLOGY Mohar, A., Ley, C., Guarner, J., Herrera-Goepfert, R., Figueroa, L. S., Halperin, D., Parsonnet, J. 2002; 97 (10): 2530-2535

  Abstract

  Helicobacter pylori causes gastric adenocarcinoma. We assessed the success of H. pylori eradication therapy in a medically underserved population in Chiapas, Mexico, that is at high risk for gastric cancer risk.Healthy volunteers with both antibodies to CagA and gastrin levels > or = 25 ng/ml were randomly assigned to receive either a combination of omeprazole, amoxicillin, and clarithromycin or matched placebo for 1 wk. Endoscopy with seven biopsies was performed at baseline, at 6 wk, and 1 yr after treatment. Treatment success was defined as loss of H. pylori by histological analysis. Cure was assessed using change in serology based on the standardized absorbance of a H. pylori ELISA.H. pylori eradication rates were high (intent-to-treat analysis: 76.3% [95% CI = 68.7-84.0%] after 6 wk and 76.1% [95% CI = 67.7-84.6%] after 1 yr; per protocol analysis: 77.8% [95% CI = 70.1-85.4%] after 6 wk and 75.2% [95% CI = 66.5-84.0%] after 1 yr). Nine subjects on active treatment and one subject on placebo who were without H. pylori at 6 wk were infected at 1 yr (recurrence rates 10.7% and 33.3%, respectively, p = 0.31). Median changes in standardized absorbance at 1 yr were 47% and 1% for successfully and unsuccessfully treated patients, respectively. A 10% decline in standardized absorbance after 1 yr had 84% sensitivity and 100% specificity for H. pylori eradication.Even with a short course of treatment against H. pylori, a high rate of eradication rate can be achieved in populations at high risk for stomach cancer. Serum antibodies are useful in assessing efficacy of therapy.

  View details for Web of Science ID 000178504800009

  View details for PubMedID 12385434

• [High frequency of precancerous lesions of gastric cancer associated with Helicobacter pylori and response to treatment, in Chiapas, Mexico]. Gaceta médica de México Mohar, A., Ley, C., Guarner, J., Herrera-Goepfert, R., Sánchez, L., Halperin, D., Parsonnet, J. 2002; 138 (5): 405-410

  Abstract

  Stomach cancer is the second cause of death in Mexico in patients with malignant tumors. This disease represents a public health problem. A strong association has been described between chronic infection with Helicobacter pylori and gastric cancer. This malignancy is preceded by a series of preneoplastic conditions, including chronic atrophic gastritis (CAG), intestinal metaplasia (IM), and dysplasia. The objective of this study was to establish the prevalence of preneoplastic conditions associated with infection of Helicobacter pylori in the state of Chiapas and its eradication with antibiotics. Persons infected with Helicobacter pylori and with CAG were identified by serology against CagA protein and serologic levels of gastrin. An endoscopy with biopsy was performed at the beginning of the study, and at 6 weeks and 1 year thereafter. A total of 281 people were enrolled and randomly assigned to treatment or placebo group. CAG was found in 59%, IM in 51%, and dysplasia in 13%. In intent-to-treat and per-protocol analysis, Helicobacter pylori was eliminated in 70 and 76%, respectively. These results indicate high frequency of preneoplastic conditions associated with Helicobacter pylori and an excellent eradication rate. They also offer a possible alternative for preventing gastric cancer.

  View details for PubMedID 12412571

• Helicobacter pylori: Consensus and controversy CLINICAL INFECTIOUS DISEASES Passaro, D. J., Chosy, E. J., Parsonnet, J. 2002; 35 (3): 298-304

  Abstract

  Helicobacter pylori is uniquely adapted to colonize the human stomach. Infection leads to a range of subclinical and clinical outcomes that depend on properties of the infecting strain, the host, and the environment. Eradication therapy is indicated for infected persons who develop peptic ulcer disease or gastric lymphoma or who are beginning long-term treatment with nonsteroidal anti-inflammatory drugs. However, treatment may worsen gastroesophageal reflux disease and increase the risk of esophageal cancer. H. pylori infections can be diagnosed noninvasively and can be eradicated with approximately 85% success by a variety of multidrug, 7-14-day regimens. Unfortunately, antibiotic resistance is affecting treatment effectiveness in the United States and abroad. A more complete understanding of the variation in H. pylori pathogenesis should lead to clearer recommendations about treatment for infected persons who have neither peptic ulcer disease nor gastric lymphoma.

  View details for Web of Science ID 000176841300013

  View details for PubMedID 12115096

• A modification of the quininium resin test for assessing gastric acidity ALIMENTARY PHARMACOLOGY & THERAPEUTICS Passaro, D. J., Hurwitz, A., Triadafilopoulos, G., Parsonnet, J. 2002; 16 (5): 875-880

  Abstract

  Gastric acid is an important defence against enteric infection. Studies investigating the relationship between hypochlorhydria and enteric infections or gastric malignancy have been limited by difficulties in the non-invasive measurement of gastric acidity.To develop a blood test for hypochlorhydria based on the quininium resin test.Quininium resin dissociates to liberate free quinine at pH

  View details for Web of Science ID 000175411100003

  View details for PubMedID 11966494

• CagA status of Helicobacter pylori infection and p53 gene mutations in gastric adenocarcinoma CARCINOGENESIS Shibata, A., Parsonnet, J., Longacre, T. A., Garcia, M. I., Puligandla, B., Davis, R. E., Vogelman, J. H., Orentreich, N., Habel, L. A. 2002; 23 (3): 419-424

  Abstract

  Infection with Helicobacter pylori (H. pylori) increases stomach cancer risk. Helicobacter pylori strains with the cag pathogenicity island (PAI) induce more severe inflammation in the gastric epithelium and are more strongly associated with stomach cancer risk than strains lacking the PAI. We examined whether the prevalence of somatic p53 mutation in gastric adenocarcinoma differed between subjects with and without infection with CagA(+) (a marker for the PAI) H. pylori strains. DNA from 105 microdissected tumor specimens was analyzed for mutation in exons 5-8 of the p53 gene by polymerase chain reaction-based single-strand conformation polymorphism followed by direct DNA sequencing. Enzyme-linked immunosorbent assays for IgG antibodies against H. pylori and CagA were performed on sera collected 2-31 years prior to cancer diagnosis. Tumors from CagA(+) subjects were significantly more likely to have p53 mutations than tumors from CagA(-) subjects (including H. pylori- and H. pylori(+)/CagA(-)): odds ratio = 3.72; 95% confidence interval, 1.06-13.07 after adjustment for histologic type and anatomic subsite of tumor and age at diagnosis and sex of subjects. Mutations were predominantly insertions and deletions (43%) as well as transition mutations at CpG dinucleotides (33%). The data suggest that CagA(+) H. pylori infection, when compared with CagA(-) infection or the absence of H. pylori infection, is associated with a higher prevalence of p53 mutation in gastric adenocarcinoma.

  View details for Web of Science ID 000174710400006

  View details for PubMedID 11895856

• Validation of Spanish Language Dyspepsia Questionnaire DIGESTIVE DISEASES AND SCIENCES Goldman, J., Conrad, D. F., Ley, C., Halperin, D., Sanchez, M. D., Villacorta, R., Parsonnet, J. 2002; 47 (3): 624-640

  Abstract

  No dyspepsia-specific questionnaire currently exists in Spanish. The Spanish Language Dyspepsia Questionnaire (SLDQ) was developed based on Rome dyspepsia criteria, other questionnaires, and common symptoms. Self-reported normal and dyspeptic volunteers (N = 63) in Chiapas, Mexico, participated in a validation study. We assessed intra- and interrater reliability by test-retest studies and established validity by both correlation to the Short Form-36 (SF-36) and comparison of scores between normals and dyspeptics. The total SLDQ score showed a wide distribution (range 0-78, mean 23.7 +/- 21.9). Internal reliability of the SLDQ was high (Cronbach's a = 0.93). Intra- and interrater reliability were excellent (scores from the first and second interviews not statistically different; P = 0.94; intraclass correlation coefficient = 0.96). SLDQ scales correlated appropriately with the SF-36. The SLDQ distinguished self-classified normals from dyspeptics (P < 0.001). The SLDQ fills the unmet need for a valid, reproducible, and multidimensional Spanish-language instrument to measure dyspepsia. Additionally, we have made suggestions for the development of symptom-quantifying questionnaires.

  View details for Web of Science ID 000174401000024

  View details for PubMedID 11913412

• Quantifying the population impact of a prophylactic Helicobacter pylori vaccine VACCINE Rupnow, M. F., Shachter, R. D., Owens, D. K., Parsonnet, J. 2001; 20 (5-6): 879-885

  Abstract

  Helicobacter pylori vaccines, which have been suggested as promising interventions to control infection, are under development. We sought to quantify the potential population impact of a prophylactic H. pylori vaccine.We developed a mathematical model that compartmentalized the population according to age, infection status and clinical state. A proportion of individuals was assumed to acquire infection and develop gastritis, duodenal ulcer (DU), chronic atrophic gastritis and gastric cancer (GC). We first simulated the model without vaccine intervention, to obtain estimates of H. pylori prevalence, and GC and DU incidences based on intrinsic dynamics. We then incorporated a prophylactic vaccine (80% efficacy, lifetime protection, 80% coverage) targeting all infants. We tested vaccination programs over unlimited as well as limited time spans. Analyses were performed for the US, Japan and a prototypical developing country.In the US, our model predicted a decrease in H. pylori prevalence from 12.0% in 2010 to 4.2% in 2100 without intervention. With 10 years of vaccination beginning in 2010, prevalence would decrease to 0.7% by year 2100. In the same period, incidence of H. pylori-attributable GC would decrease from 4.5 to 0.4 per 100,000 with vaccine (compared to 1.3 per 100,000 without vaccine). Incidence of H. pylori-attributable DU would decrease from 33.3 to 2.5 per 100,000 with vaccine (compared to 12.2 per 100,000 without vaccine). In Japan, incidence of H. pylori-attributable GC would decrease from 17.6 to 1.0 per 100,000 after 10 years of vaccination (compared to 3.0 per 100,000 without vaccine). In a prototypical developing country, after 10 years of vaccination, H. pylori-attributable GC would decrease from 31.8 to 22.5 per 100,000 by 2090, returning to the original level by mid-2100s. Under continuous vaccination, it would decrease to 5.8 per 100,000 by 2100.In the US and Japan, a 10-year vaccination program would confer almost the same reduction in H. pylori and associated diseases as a vaccination effort that extends beyond 10 years. In developing countries, a continuous vaccination effort would be required to eliminate the pathogen and its associated diseases.

  View details for PubMedID 11738753

• Determination of the infectious dose of Helicobacter pylori during primary and secondary infection in rhesus monkeys (Macaca mulatta) INFECTION AND IMMUNITY Solnick, J. V., Hansen, L. M., Canfield, D. R., Parsonnet, J. 2001; 69 (11): 6887-6892

  Abstract

  We sought to determine the infectious dose of Helicobacter pylori during primary and secondary infection in the rhesus monkey and to determine whether preinoculation acid suppression is necessary to produce colonization. Mixed inoculation with three human-derived strains showed that H. pylori J166 is particularly adapted to colonization of rhesus monkeys, since it outcompeted two other strains. The minimum infectious dose of H. pylori J166 was 10(4) bacteria in specific-pathogen (H. pylori)-free monkeys. Rechallenge of these monkeys after antibiotic therapy was characterized by a 10- to 100-fold decrease in bacterial load compared to primary infection, but with little change in the infectious dose. Acid suppression prior to inoculation was not necessary for colonization to occur. These results provide a basis for future animal experiments using more ecologically relevant conditions of inoculation and suggest that reduction in bacterial load rather than complete protection may be a more realistic goal for H. pylori vaccination.

  View details for Web of Science ID 000171739200041

  View details for PubMedID 11598063

• Acute Helicobacter pylori infection is followed by an increase in diarrheal disease among Peruvian children. Pediatrics Passaro, D. J., TAYLOR, D. N., MEZA, R., Cabrera, L., Gilman, R. H., Parsonnet, J. 2001; 108 (5): E87-?

  Abstract

  Cohort and case-crossover studies were conducted to evaluate whether new Helicobacter pylori infections are followed by increased diarrhea.Participants were 6-month-old to 12-year-old shantytown residents living near Lima, Peru. Baseline data were collected from community households. Health interviews were completed daily, and sera, drawn every 4 months, were tested for H pylori immunoglobulin G. Diarrhea rates among newly H pylori-infected (seroconverting) children were compared with rates among persistently uninfected and infected children using cohort and case-crossover analyses.Sera were obtained from 345 children from January 1, 1995, through September 1, 1997. H pylori incidence was 12% per year (36 H pylori infections in 109 866 seronegative days). In adjusted cohort analyses, seroconverters had more diarrhea days (rate ratio: 2.0; 95% confidence interval: 1.6-2.4), episodes, and sick days in the year after infection than did uninfected children; and more diarrhea days and sick days than did persistently infected children. This effect was strongest in the first 2 months. Case-crossover analyses supported these findings.Preventing H pylori infection may help reduce pediatric diarrheal disease.

  View details for PubMedID 11694671

• Acute Helicobacter pylori infection is followed by an increase in diarrheal disease among Peruvian children 36th Annual Meeting of the Infectious-Diseases-Society-of-America Passaro, D. J., TAYLOR, D. N., MEZA, R., Cabrera, L., Gilman, R. H., Parsonnet, J. AMER ACAD PEDIATRICS. 2001: U61–U68

  View details for Web of Science ID 000171925200010

• Maternal infection with Helicobacter pylori as a risk factor for infection in children of different ages Tamburini, B. A., Tsai, C. J., Garcia, M. I., Sanchez, L., Villacorta, R., Nguyen, Q., Ley, C., Parsonnet, J. OXFORD UNIV PRESS INC. 2001: 1140–40

  View details for Web of Science ID 000171226900327

• Helicobacter pylori and risk for gastric adenocarcinoma. Seminars in gastrointestinal disease Asghar, R. J., Parsonnet, J. 2001; 12 (3): 203-208

  Abstract

  Gastric cancer is the second most common cause of cancer death in the world. Helicobacter pylori infection is now a well-accepted cause of this malignancy; in some parts of the world, up to eighty percent of all gastric cancers are at least in part caused by H. pylori infection. H. pylori infection typically starts in childhood as an inflammatory process in the stomach. The changes in the gastric microenvironment facilitate gastric cancer over time. Among infected individuals, genotype of H. pylori, coincident environmental exposures, and genetic factors of host seem to play roles in determining who will get gastric cancer and who will not. Unfortunately, it remains unknown whether treatment of H. pylori prevents gastric cancer. Thus, screening for H. pylori to prevent cancer is not yet widely recommended. Some consensus groups, however, have recommended screening for and treating H. pylori infection in individuals with family histories of gastric malignancy. In high-risk countries, screening programs for early gastric cancer itself may improve therapeutic outcome for this highly lethal disease.

  View details for PubMedID 11478753

• Epidemiology of Helicobacter pylori infection in Northern Californian households with diarrheal diseases Rahman, M. M., Asghar, R. J., Tsai, C. J., Parsonnet, J. W B SAUNDERS CO-ELSEVIER INC. 2001: A738–A738

  View details for Web of Science ID 000168514703670

• Comparison of stool and serologic tests for Helicobacter pylori infection in infants Garcia, M. I., Haggerty, T. D., Parsonnet, J. W B SAUNDERS CO-ELSEVIER INC. 2001: A492–A492

  View details for Web of Science ID 000168514702438

• Screening markers for chronic atrophic gastritis in Chiapas, Mexico CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION Ley, C., Mohar, A., Guarner, J., Herrera-Goepfert, R., Figueroa, L. S., Halperin, D., Parsonnet, J. 2001; 10 (2): 107-112

  Abstract

  Intestinal-type gastric adenocarcinomas usually are preceded by chronic atrophic gastritis. Studies of gastric cancer prevention often rely on identification of this condition. In a clinical trial, we sought to determine the best serological screening method for chronic atrophic gastritis and compared our findings to the published literature. Test characteristics of potential screening tests (antibodies to Helicobacter pyloni or CagA, elevated gastrin, low pepsinogen, increased age) alone or in combination were examined among consecutive subjects enrolled in a study of H. pylori and preneoplastic gastric lesions in Chiapas, Mexico; 70% had chronic atrophic gastritis. English-language articles concerning screening for chronic atrophic gastritis were also reviewed. Sensitivity for chronic atrophic gastritis was highest for antibodies to H. pylori (92%) or CagA, or gastrin levels >25 ng/l (both 83%). Specificity, however, was low for these tests (18, 41, and 22%, respectively). Pepsinogen levels were highly specific but insensitive markers of chronic atrophic gastritis (for pepsinogen I <25 microg/l, sensitivity was 6% and specificity was 100%; for pepsinogen I:pepsinogen II ratio <2.5, sensitivity was 14% and specificity was 96%). Combinations of markers did not improve test characteristics. Screening test characteristics from the literature varied widely and did not consistently identify a good screening strategy. In this study, CagA antibodies alone had the best combination of test characteristics for chronic atrophic gastritis screening. However, no screening test was both highly sensitive and highly specific for chronic atrophic gastritis.

  View details for Web of Science ID 000166922600005

  View details for PubMedID 11219766

• Gastric atrophy and extent of intestinal metaplasia in a cohort of Helicobacter pylori-infected patients HUMAN PATHOLOGY Guarner, J., Herrera-Goepfert, R., Mohar, A., Sanchez, L., Halperin, D., Ley, C., Parsonnet, J. 2001; 32 (1): 31-35

  Abstract

  Atrophy and intestinal metaplasia (IM) are preneoplastic gastric lesions associated with Helicobacter pylori infection. Atrophy and IM are usually found together; however, the association between increasing degrees of severity of both atrophy and IM has not been evaluated completely. Two pathologists graded atrophy and IM using the visual analog scale of the Sydney classification in gastric biopsies from 368 H pylori-infected patients. Extent of IM also included determining the number of specimens affected. We then correlated the degree of atrophy with the degree and number of specimens affected with IM by calculating relative risks (RR) and 95% confidence intervals (95% CI). The mean number of biopsies examined from each patient was 6.5. Atrophy and IM were found more frequently in the antrum (85% and 75% of biopsies, respectively). One hundred thirty-eight patients had a combination of atrophy and IM, 48 had IM only, and 89 had atrophy only. Fifty-three subjects had mild atrophy and IM (RR = 1.57; 95% CI 1.2-2.1), 69 had moderate atrophy and IM (RR = 1.86; 95% CI 1.9-2.4), and 16 had marked atrophy and IM (RR = 2.47; 95% CI 1.8-3.3). The median number of biopsy specimens with IM increased from 0 in subjects with no atrophy to 3 in subjects with severe atrophy. The degree of IM correlated with the degree of atrophy; the median degree was 0.6 in subjects with no atrophy and increased to 2.32 in those with severe atrophy. Our data suggest that higher degrees of IM in an individual specimen and increasing number of specimens with IM are associated with moderate or severe degrees of atrophy.

  View details for DOI 10.1053/hupa.2001.20889

  View details for Web of Science ID 000166729700006

  View details for PubMedID 11172292

• Is anything safe to eat? Current clinical topics in infectious diseases SOBEL, J., Swerdlow, D. L., Parsonnet, J. 2001; 21: 114-134

  View details for PubMedID 11572148

• Histological classification of gastric adenocarcinoma for epidemiological research: Concordance between pathologists CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION Shibata, A., Longacre, T. A., Puligandla, B., Parsonnet, J., Habel, L. A. 2001; 10 (1): 75-78

  Abstract

  Epidemiology of gastric adenocarcinoma suggests that intestinal-type and diffuse-type cancers develop through distinct causal pathways. To examine the differences in risk factors and molecular changes between the histological types, reliable data on histological typing are essential. We evaluated the concordance between two pathologists in assessment of 95 gastric adenocarcinomas for Laurén classification and tumor grade. Two pathologists, each blinded to the other's assessment, reviewed H&E-stained slides of gastric tumor. The responses of the two pathologists for histological type were considered as concordant if they fell on one of the three categories (intestinal type, diffuse type, or other). Tumor grade was classified into three categories (well, moderately, or poorly differentiated). The pathologists agreed on the classification of histological type for 71 of 92 (77%) tumors. Kappa coefficient was 0.59 (95% confidence interval, 0.44-0.73). Concordance for tumor grade was 87%, with a kappa coefficient of 0.72 (95% confidence interval, 0.57-0.87). Both observed concordance and kappa coefficient for histological type and tumor grade were similar across three calendar periods of study. Interobserver agreement was virtually identical between tumors with biopsy specimens only and those with surgical specimens. Although the level of disagreement for histological type observed in this study is comparable with that in other studies, the resulting misclassification would lead to the reduction in observed differences in prevalence and odds ratio estimates between two histological types.

  View details for Web of Science ID 000166651600012

  View details for PubMedID 11205493

• Helicobacter pylori infection and gastric cancer GASTROENTEROLOGY Ley, C., Parsonnet, J. 2001; 120 (1): 324-324

  View details for Web of Science ID 000166390800046

  View details for PubMedID 11246513

• Variability of serologic testing for H-pylori using US and Peruvian antigens GASTROENTEROLOGY De Arruda, S. M., Passaro, D. J., Yang, S. F., Parsonnet, J. 2001; 120 (1): 325-326

  View details for DOI 10.1053/gast.2001.21387

  View details for Web of Science ID 000166390800048

  View details for PubMedID 11246514

• Confirmatory serologic testing for acute toxoplasmosis and rate of induced abortions among women reported to have positive Toxoplasma immunoglobulin M antibody titers 35th Annual Meeting of the Infectious-Diseases-Society-of-America Liesenfeld, O., Montoya, J. G., Tathineni, N. J., Davis, M., Brown, B. W., Cobb, K. L., Parsonnet, J., Remington, J. S. MOSBY-ELSEVIER. 2001: 140–45

  Abstract

  Results obtained with commercial testing kits for immunoglobulin M Toxoplasma antibodies may be inaccurate or may be inaccurately interpreted, which may influence whether a woman decides to terminate the pregnancy. This study was undertaken to determine whether confirmatory testing at a reference laboratory and communication of the results and an expert interpretation to the patient's physician would affect the rate of induced abortions among pregnant women with positive results of testing for immunoglobulin M Toxoplasma antibodies in outside laboratories.This was a retrospective cohort study of 811 consecutive pregnant women for whom the toxoplasma serologic profile was performed at a reference laboratory. Almost all the patients had been informed by their physicians that a result of a test for immunoglobulin M Toxoplasma antibodies performed in an outside laboratory was positive. Women were separated into those with a toxoplasma serologic profile result suggestive of a recently acquired infection (group 1) and those with a result suggestive of an infection acquired in the more distant past (group 2). Physician reports of induced abortions were used to determine rates of induced abortion in groups 1 and 2.Of the 811 women 321 (39.6%) were considered likely to have a recent infection (group 1) and 490 (60.4%) were considered likely to have a past infection (group 2). Physicians reported pregnancy outcomes for 433 (53.4%) of 811 women (65.1% and 45.7% in groups 1 and 2, respectively). Whereas 36 of 209 women in group 1 (17.2%) terminated the pregnancy, only 1 of 224 women in group 2 (0.4%) chose abortion (P <.001).Confirmatory serologic testing in a reference laboratory and communication of the results and their correct interpretation by an expert to the patient's physician decreased the rate of unnecessary abortions by approximately 50% among women for whom positive immunoglobulin M Toxoplasma test results had been reported by outside laboratories.

  View details for Web of Science ID 000166679700023

  View details for PubMedID 11174493

• p53 overexpression and cell proliferation index in gastric cancer by anatomic subsite. Shibata, A., Garcia, M. I., Longacre, T. A., Puligandla, B., Parsonnet, J., Vogelman, J., Orentreich, N., Habel, L. A. OXFORD UNIV PRESS INC. 2000: S77–S77

  View details for Web of Science ID 000087460400307

• A dynamic transmission model for predicting trends in Helicobacter pylori and associated diseases in the United States EMERGING INFECTIOUS DISEASES Rupnow, M. F., Shachter, R. D., Owens, D. K., Parsonnet, J. 2000; 6 (3): 228-237

  Abstract

  To assess the benefits of intervention programs against Helicobacter pylori infection, we estimated the baseline curves of its incidence and prevalence. We developed a mathematical (compartmental) model of the intrinsic dynamics of H. pylori, which represents the natural history of infection and disease progression. Our model divided the population according to age, infection status, and clinical state. Case-patients were followed from birth to death. A proportion of the population acquired H. pylori infection and became ill with gastritis, duodenal ulcer, chronic atrophic gastritis, or gastric cancer. We simulated the change in transmissibility consistent with the incidence of gastric cancer and duodenal ulcer over time, as well as current H. pylori prevalence. In the United States, transmissibility of H. pylori has decreased to values so low that, should this trend continue, the organism will disappear from the population without targeted intervention; this process, however, will take more than a century.

  View details for PubMedID 10827112

• Helicobacter pylori and epidemic Vibrio cholerae 01 infection in Peru LANCET Shahinian, M. L., Passaro, D. J., Swerdlow, D. L., Mintz, E. D., Rodriguez, M., Parsonnet, J. 2000; 355 (9201): 377-378

  Abstract

  In a cross-sectional study of the 1991 Peruvian cholera epidemic, Vibrio cholerae O1 infection was associated with Helicobacter pylori infection, particularly in young children. These data support the hypothesis that hypochlorhydria induced by H. pylori is important in the pathogenesis of diarrhoeal disease.

  View details for Web of Science ID 000085122100017

  View details for PubMedID 10665561

• When heredity is infectious GASTROENTEROLOGY Parsonnet, J. 2000; 118 (1): 222-224

  View details for Web of Science ID 000084405100030

  View details for PubMedID 10611171

• Helicobacter pylori vaccine development and use: A cost-effectiveness analysis using the institute of medicine methodology HELICOBACTER Rupnow, M. F., Owens, D. K., Shachter, R., Parsonnet, J. 1999; 4 (4): 272-280

  Abstract

  Prophylactic vaccination has been suggested as a better strategy than antibiotics to control Helicobacter pylori infection. We evaluated the cost-effectiveness (CE) of H. pylori vaccine development and use in the United States and developing countries, using a method developed by the Institute of Medicine (IOM).The IOM model includes costs of vaccine development, vaccination program, and averted medical treatments; morbidity and mortality prevented; expected efficacy and use; and proportion of disease that is vaccine-preventable. The model employs infant mortality equivalence (IME) to estimate disease burden; with IME, the societal cost of infection-related morbidity is expressed as equivalent to a specific rate of infant deaths. We tested model assumptions by univariate sensitivity analyses.In the United States, H. pylori vaccine would save 1,176 IME and would cost $58.71 million (1997 dollars) annually, yielding a CE ratio of $49,932 per IME; the health benefits would exceed all IOM-studied vaccines, even when efficacy dropped to 55%. H. pylori vaccine could be cost-saving if priced at less than $60 per course. In developing countries, H. pylori vaccine would rank unfavorably both in terms of health benefits (33,518 IME) and costs ($5,254 million). None of the changes in assumptions improved significantly the H. pylori vaccine's ranking relative to other IOM-studied vaccines.Compared to other vaccines evaluated in the IOM study, H. pylori vaccine warrants public resource allocation for accelerated development and use in the United States but not for use in developing countries.

  View details for PubMedID 10597398

• Interobserver variability in application of the revised Sydney classification for gastritis HUMAN PATHOLOGY Guarner, J., Herrera-Goepfert, R., Mohar, A., Sanchez, L., Halperin, D., Ley, C., Parsonnet, J. 1999; 30 (12): 1431-1434

  Abstract

  The Sydney classification for gastritis provides guidelines for histological grading of gastric biopsies. In an ongoing study of gastric preneoplastic lesions in Chiapas, Mexico, 7 biopsies from 150 patients (4 from the antrum and 3 from the body) were obtained during endoscopy and studied histologically. The first 74 endoscopy specimens were read independently by 2 general surgical pathologists. We assessed diagnostic concordance using kappa statistics. The 2 pathologists then jointly reviewed biopsies about which they had disagreed to reach a final diagnosis. A second group of 76 endoscopies was subsequently evaluated independently by the 2 pathologists, and concordance was again assessed. In the first group of biopsies, we found low concordance rates (Heliobacter pylori 0.59, acute inflammation 0.22, intestinal metaplasia 0.60, and atrophy 0.04). In the second group, of independently reviewed cases, there was better concordance (H pylori 0.77, acute inflammation 0.50, intestinal metaplasia 0.70, and atrophy 0.64). We presumed that use of the Sydney classification would result in minimal interpretational differences achieving ideal kappas greater than 0.80. Because pathology results are based on subjective interpretation of this classification, complete diagnostic agreement is practically impossible. Concordance by general surgical pathologists after joint review of cases was similar to that obtained by gastrointestinal pathologists.

  View details for Web of Science ID 000084564500010

  View details for PubMedID 10667420

• Prevalence and incidence of herpes simplex virus type 2 infection among male Zimbabwean factory workers 12th World AIDS Conference McFarland, W., Gwanzura, L., Bassett, M. T., Machekano, R., Latif, A. S., Ley, C., Parsonnet, J., BURKE, R. L., KATZENSTEIN, D. UNIV CHICAGO PRESS. 1999: 1459–65

  Abstract

  Stored sera from a cohort of 2397 male factory workers in Harare, Zimbabwe, were screened for herpes simplex virus type 2 (HSV-2)-specific antibodies, to estimate the prevalence and incidence of genital herpes infection and to assess the relation between HSV-2 and human immunodeficiency virus (HIV) acquisition. The prevalence of HSV-2 at enrollment was 39.8%. Correlates of HSV-2 seropositivity were HIV seropositivity, marital status, history of sexually transmitted disease (STD), older age, and higher income. The incidence of HSV-2 seroconversion during follow-up was 6.2/100 person-years. Correlates of HSV-2 seroconversion were enrollment while HIV-positive or seroconversion during follow-up, reported genital ulcer, history of STD, and number of sex partners. No evidence was found that HSV-2 infection was more likely to precede HIV or vice versa. HSV-2 and HIV seropositivity are strong markers for high-risk sexual behavior. Improved interventions targeted to populations in which the incidence of either viral infection is high are needed.

  View details for Web of Science ID 000083519500007

  View details for PubMedID 10515804

• Helicobacter pylori and gastric cancer: What are the benefits of screening only for the CagA phenotype of H. pylori? HELICOBACTER Harris, R. A., Owens, D. K., Witherell, H., Parsonnet, J. 1999; 4 (2): 69-76

  Abstract

  Strains of Helicobacter pylori that express the CagA protein are associated with a threefold increased gastric cancer risk as compared to H. pylori strains that do not express CagA. Screening and treatment only for CagA antibodies should target those individuals at highest gastric cancer risk while reducing the number of patients requiring antibiotics. We compared the costs and benefits of screening asymptomatic 50-year-old individuals for CagA, screening for all H. pylori strains, and no screening, both in the United States and abroad.We employed Markov cost-effectiveness analysis using data from randomized, case-control, and cohort studies.In the United States, CagA screening would result in 1.5 million fewer antibiotic treatments but would prevent 1,400 fewer gastric cancers than would screening for all H. pylori. The incremental cost-effectiveness of CagA screening is $23,900 per life-year gained; for H. pylori screening, it is $25,100. Screening in countries with epidemiological characteristics similar to those of Colombia, Finland, and Japan costs less than $5,000 per life-year gained, and the difference between CagA and H. pylori screening is smaller than that in the United States.Screening only for CagA-positive H. pylori is not substantially better than is screening for all H. pylori, either in the United States nor abroad. Screening is substantially more cost-effective outside the United States. Whether population screening is justified, however, is uncertain pending conclusive data regarding the reduction in gastric cancer risk from antibiotics.

  View details for PubMedID 10382118

• Helicobacter pylori virulence and genetic geography SCIENCE Covacci, A., Telford, J. L., Del Giudice, G., Parsonnet, J., Rappuoli, R. 1999; 284 (5418): 1328-1333

  Abstract

  Isolated for the first time in 1982 from human gastric biopsy, Helicobacter pylori is responsible for gastritis, peptic ulcer, and gastric cancer. A pathogenicity island acquired by horizontal transfer, coding for a type IV secretion system, is a major determinant of virulence. The infection is now treated with antibiotics, and vaccines are in preparation. The geographic distribution suggests coevolution of man and Helicobacter pylori.

  View details for Web of Science ID 000080430600045

  View details for PubMedID 10334982

• Rhesus monkey (Macaca mulatta) model of Helicobacter pylori: Noninvasive detection and derivation of specific-pathogen-free monkeys LABORATORY ANIMAL SCIENCE Solnick, J. V., Canfield, D. R., Yang, S. F., Parsonnet, J. 1999; 49 (2): 197-201

  Abstract

  Development of the rhesus monkey model of Helicobacter pylori has been hampered by problems with serodetection and by the difficulty of identifying specific-pathogen (Helicobacter)-free animals. Our purpose was to determine whether detection could be improved and to determine if pathogen-free monkeys could be derived by nursery rearing.An enzyme-linked immunoabsorbent assay (ELISA) and a [14C]urea breath test were compared to endoscopy to determine H. pylori infection status in rhesus macaques; 18 animals were hand raised in the nursery to determine whether pathogen-free animals could be selected.Helicobacter pylori infection was common in colony-raised young rhesus monkeys and was nearly universal by adulthood. Serodetection, using antigen from rhesus-derived H. pylori strains, was 95% sensitive and 94% specific. The [14C]urea breath test was 96% sensitive and 88% specific for detection of chronic Helicobacter infection in rhesus monkeys. Segregation of newborn animals within the first 24 h of life was a reliable method to obtain pathogen-free rhesus monkeys.Isolation of specific-pathogen-free animals, together with better detection methods, may improve the value of the rhesus monkey model for the study of H. pylori pathogenesis, immune response, and vaccine development.

  View details for Web of Science ID 000080082000012

  View details for PubMedID 10331550

• Predicting the next century of H-pylori prevalence and associated diseases in the United States Tsugawa, M. F., Shachter, R., Owens, D. K., Parsonnet, J. W B SAUNDERS CO-ELSEVIER INC. 1999: A339–A339

  View details for Web of Science ID 000079778401483

• Learning about H-pylori transmission dynamics from the distinct patterns of duodenal ulcer and gastric cancer Tsugawa, M. F., Shachter, R., Owens, D. K., Parsonnet, J. W B SAUNDERS CO-ELSEVIER INC. 1999: A338–A338

  View details for Web of Science ID 000079778401482

• Patterns of health seeking behavior during episodes of childhood diarrhea: a study of Tzotzil-speaking Mayans in the highlands of Chiapas, Mexico SOCIAL SCIENCE & MEDICINE Granich, R., Cantwell, M. F., Long, K., Maldonado, Y., Parsonnet, J. 1999; 48 (4): 489-495

  Abstract

  In Chiapas, Mexico, diarrheal disease causes the majority of all deaths in children under the age of five. Treatment of childhood diarrhea may be influenced by local beliefs and cultural practices. Few studies have attempted to quantitatively evaluate health seeking behavior (HSB) for diarrheal diseases in indigenous communities, while controlling for potential confounding factors such as parental education or socioeconomic status. A rapid ethnographic survey was conducted in Nabenchauc, Chiapas, to determine hypothetical HSB patterns for each of four major types of childhood diarrhea. Additionally, we examined the actual HSB for the last episode of childhood diarrheal illness within the household. One hundred households participated in the survey; 94 households with children < 5 years old reported a mean of 1.9 diarrheal episodes during the preceding month. Households reported using a mean of 1.3 types of in-home remedies. Oral rehydration therapy (ORT) was used in <2% of the 368 HSB patterns elicited for the four types of diarrhea. HSB patterns utilized an eclectic combination of traditional, allopathic, local and distant health care options. A mean of 2.5 outside-the-home health care options were reported for each diarrheal type; the local grocery store was reported in 245 (67%) of the hypothetical HSB patterns and as a first option in 199 (54%). Maternal and/or paternal education had little impact on hypothetical HSB. Households with lower SES were more likely to report using local grocery stores as a first option and were less likely to use options outside the village. The rapid ethnographic survey approach allows for assessment of changes in the approach to health care option utilization in cultures incorporating new health care paradigms. Public health interventions targeting local stores may lead to increased use of ORT, thereby potentially reducing early morbidity and mortality due to childhood diarrhea.

  View details for Web of Science ID 000077986300005

  View details for PubMedID 10075174

• Microbes and Malignancy: Infection as a Cause of Human Cancer Parsonnet J(ed) 1999: Oxford Univ. Press
• Gastrin and colorectal cancer: A prospective study GASTROENTEROLOGY Thorburn, C. M., Friedman, G. D., Dickinson, C. J., Vogelman, J. H., Orentreich, N., Parsonnet, J. 1998; 115 (2): 275-280

  Abstract

  Gastrin is a putative promoter of colorectal carcinomas. The aim of this study was to evaluate the temporal relationship between gastrinemia and development of colorectal malignancy.We conducted a nested case-control study among 128,992 subscribers to a health maintenance program who had participated in a multiphasic health checkup between 1964 and 1969. Serum had been frozen since the checkup and the cohort followed up for cancer. Of 1881 incident colorectal carcinoma cases, 250 were randomly selected; 1 control without cancer was matched to each case by age, sex, education, and date of serum collection. Stored sera were tested for Helicobacter pylori immunoglobulin G and for gastrin and glycine-extended gastrin.Verified cases included 166 colon cancers, 58 rectal cancers, and 9 with cancer in both locations. A mean of 15.3 years had elapsed between serum collection and diagnosis of cancer. Median gastrin levels were similar in cases and controls (41.7 vs. 40.7 pg/mL). However, a gastrin level above normal was associated with increased risk for colorectal malignancy (odds ratio, 3.9; 95% confidence interval, 1.5-9.8). If this association is causal, 8.6% of colorectal cancers could be attributed to high serum gastrin level.Hypergastrinemia is associated with an increased risk of colorectal carcinoma.

  View details for Web of Science ID 000075293400009

  View details for PubMedID 9679032

• Helicobacter pylori: the size of the problem Educational Training Workshop on Helicobacter pylori Parsonnet, J. B M J PUBLISHING GROUP. 1998: S6–S9

  View details for Web of Science ID 000074771300003

  View details for PubMedID 9764031

• Helicobacter pylori INFECTIOUS DISEASE CLINICS OF NORTH AMERICA Parsonnet, J. 1998; 12 (1): 185-?

  Abstract

  Helicobacter pylori infection causes peptic ulcer disease, gastric adenocarcinoma, gastric lymphoma, and probably nonulcer dyspepsia. Although the prevalence of infection is declining over time, the organism still infects approximately one half of the world's population. Only a minority will ever suffer serious consequences from their infection. This article reviews current knowledge about H. pylori and presents some of the dilemmas surrounding clinical and public health approaches to this widespread pathogen.

  View details for Web of Science ID 000072123000015

  View details for PubMedID 9494838

• Helicobacter pylori infection and urinary excretion of 8-hydroxy-2-deoxyguanosine, an oxidative DNA adduct CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION Witherell, H. L., Hiatt, R. A., Replogle, M., Parsonnet, J. 1998; 7 (2): 91-96

  Abstract

  To assess whether Helicobacter pylori-related inflammation increases oxidative DNA damage, we evaluated the association between H. pylori infection and urinary excretion of an adduct of oxidative DNA damage, 8-hydroxy-2-deoxyguanosine (8ohdG). Subjects included 555 healthy persons, ages 20-39, within the Kaiser Permanente Medical Care Program in Northern California. We tested sera for antibodies to H. pylori by ELISA; collected demographic, dietary, smoking, and alcohol data by questionnaire; and assayed 24-h urine samples for 8ohdG with a newly developed ELISA kit. Two hundred eighty-one subjects provided adequate 24-h urine samples for 8ohdG and creatinine assays and had detectable levels of 8ohdG. After adjusting for 24-h urinary creatinine (Ucr) and demographic factors, persons without H. pylori infection had significantly higher amounts of 24-h urinary 8ohdG than infected persons (geometric mean, 18.04 microg 8ohdG/Ucr g versus 14.36 microg 8ohdG/Ucr g, respectively; P = 0.008). Excretion of 8ohdG was higher in whites and Hispanics (17.44 and 18.09 microl/Ucr g) than in blacks (13.21 microg/Ucr g; P < 0.001). Gender was not significantly associated with 8ohdG excretion (16.18 microg/Ucr g for males versus 16.01 microg/Ucr g for females; P = 0.883). Of the dietary factors evaluated, vitamin C negatively correlated (P < 0.001) and carbohydrate intake positively correlated with 8ohdG excretion (P = 0.003). Infection with H. pylori was strongly associated with decreased 8ohdG excretion in the urine. This unexpected finding suggests either that DNA repair is deficient in infected subjects, that inflammation destroys the adduct, or that urinary 8ohdG is not an accurate measure of gastric damage.

  View details for Web of Science ID 000072333900001

  View details for PubMedID 9488581

• Advances in the prevention and management of traveler's diarrhea. Current clinical topics in infectious diseases Passaro, D. J., Parsonnet, J. 1998; 18: 217-236

  View details for PubMedID 9779357

• Risk for gastric lymphoma in persons with CagA(+) and CagA(-) Helicobacter pylori infection Digestive Diseases Week 97 Meeting Witherell, H. L., Hansen, S., Jellum, E., Orentreich, N., Vogelman, J. H., Parsonnet, J. OXFORD UNIV PRESS INC. 1997: 1641–44

  Abstract

  Infection with Helicobacter pylori increases the risk for gastric non-Hodgkin's lymphoma (GNHL). Strains that express CagA protein are thought to be particularly virulent. It was determined whether CagA+ H. pylori infection increased the risk for GNHL more than CagA infection. Thirty-two cases and 130 controls previously tested for H. pylori antibodies were tested for CagA antibodies by ELISA. The risk for GNHL was compared among CagA+, CagA-, and uninfected persons by use of conditional logistic regression. CagA+ subjects had 8.2 times the risk for GNHL than uninfected persons (95% confidence interval [CI], 2.5-26.7). CagA- subjects had 4.4 times the risk for GNHL than uninfected persons (95% CI, 1.2-16.5). Among infected subjects only, CagA+ infection was not associated with significantly increased risk for GNHL when compared with CagA- infection (odds ratio, 2.1; 95% CI, 0.8-5.4). This study does not support a major role for CagA in lymphomagenesis.

  View details for Web of Science ID A1997YH16000035

  View details for PubMedID 9395383

• Molecular mechanisms for inflammation-promoted pathogenesis of cancer - The Sixteenth International Symposium of the Sapporo Cancer Seminar CANCER RESEARCH Parsonnet, J. 1997; 57 (16): 3620-3624

  View details for Web of Science ID A1997XQ99500051

  View details for PubMedID 9270037

• Urinary phytoestrogen levels in young women from a multiethnic population CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION HORNROSS, P. L., Barnes, S., KIRK, M., Coward, L., Parsonnet, J., Hiatt, R. A. 1997; 6 (5): 339-345

  Abstract

  Phytoestrogens include several classes of chemical compounds (i.e., isoflavones, coumestans, and lignans) which are structurally similar to endogenous estrogens. In biological systems, they have both estrogenic and antiestrogenic effects and may reduce the risk of developing certain types of hormonally related diseases. However, little information is available on population differences in exposure to phytoestrogens. To examine racial/ethnic differences in urinary phytoestrogen levels, 50 young women (ages 20-40 years) were randomly selected from participants in a previous epidemiological study in which 24-h urine specimens and a dietary assessment were obtained. Subjects were members of the Kaiser Permanente Medical Care Program of northern California. Selection was stratified on race/ethnicity. Urinary levels of seven phytoestrogens were measured using high-performance liquid chromatography-mass spectrometry. Substantial variation in phytoestrogen levels was observed and racial/ethnic differences are described. The highest levels of coumestrol and the lignans were observed in white women and the lowest levels in Latina and African American women. Genistein levels, however, were highest in Latina women; other isoflavone levels did not differ significantly by race/ethnicity.

  View details for Web of Science ID A1997WZ60300008

  View details for PubMedID 9149894

• Seroprevalence of CagA-positive strains among Helicobacter pylori-infected, healthy young adults 1996 Digestive Diseases Week Meeting Parsonnet, J., Replogle, M., Yang, S. F., Hiatt, R. OXFORD UNIV PRESS INC. 1997: 1240–42

  Abstract

  Helicobacter pylori is categorized into two phenotypes on the basis of the presence or absence of the CagA protein. CagA protein-positive H. pylori are more closely associated with peptic ulcer disease and cancer. Whether CagA-positive strains are similarly represented among racial or ethnic groups in northern California was investigated. Sera from 152 H. pylori-infected healthy young adults were tested by ELISA for IgG against CagA. CagA antibodies were detected in 79.4% of blacks, 63.8% of Hispanics, and 50% of whites. After adjusting for demographic factors, blacks had significantly more infections with CagA-positive H. pylori than did whites (odds ratio [OR] = 5.0; 95% confidence interval [CI] = 1.6-15.3) or Hispanics (OR = 5.5, 95% CI = 1.9-16.0). Also, there was a higher prevalence of CagA in persons born in developing countries than in persons born in industrialized nations (OR = 3.5, 95% CI = 1.3-9.4). This suggests either a genetic predisposition of racial or ethnic groups to infection with particular H. pylori phenotypes or transmission of H. pylori within relatively segregated population groups.

  View details for Web of Science ID A1997WW72600033

  View details for PubMedID 9129095

• Should we treat H. pylori infection to prevent gastric cancer? Gastroenterology Parsonnet, J., Harris, R. A., HACK, H. M., Owens, D. K. 1997; 112 (3): 1044-1045

  View details for PubMedID 9041272

• Risk for gastric cancer in people with CagA positive or CagA negative Helicobacter pylori infection GUT Parsonnet, J., Friedman, G. D., Orentreich, N., VOGELMAN, H. 1997; 40 (3): 297-301

  Abstract

  It is not known why some people with Helicobacter pylori infection develop gastric cancer whereas others do not. Whether the CagA phenotype of H pylori infection affected risk for cancer independently of other posited risk factors was evaluated.242 persons who participated in a previous nested case-control study of gastric cancer. 179 (90 cases and 89 controls) were infected with H pylori as determined by enzyme linked immunosorbent assay (ELISA) in serum and 63 (13 cases and 50 controls) were uninfected.Serum samples from cases and controls, obtained a mean of 14.2 years before diagnosis of cancer in the cases, were tested by ELISA for IgG antibodies against the CagA gene product of H pylori. They had previously been tested for pepsinogen I. Using logistic regression analysis, risk for cancer was compared among infected persons with CagA antibodies, infected persons without CagA antibodies, and uninfected persons.Subjects infected with H pylori who had CagA antibodies were 5.8-fold more likely than uninfected subjects to develop gastric cancer (95% confidence interval (95% CI) = 2.6-13.0). This was true for both intestinal (odds ratio (OR) 5.1, 95% CI = 2.1-12.2) and diffuse type (OR 10.1, 95% CI = 2.2-47.4) cancers. By contrast, H pylori infected subjects without CagA antibodies were only slightly, and not significantly, at increased risk for cancer (OR 2.2, 95% CI = 0.9-5.4) and any possible association was restricted to diffuse type carcinoma (OR 9.0, 95% CI = 1.2-65.8). Pepsinogen 1 < 50 ng/ml significantly increased risk for both cancer types in H pylori infected persons and lessened the magnitude of association between CagA and cancer. Educational attainment, cigarette smoking, and ABO blood group were not associated with malignancy.When compared with uninfected subjects, persons infected with CagA positive H pylori are at considerably increased risk of gastric cancer. CagA negative H pylori are less strongly linked to malignancy and may only be associated with diffuse type disease.

  View details for Web of Science ID A1997WQ75200003

  View details for PubMedID 9135515

• Association between prior cytomegalovirus infection and the risk of restenosis after coronary atherectomy NEW ENGLAND JOURNAL OF MEDICINE Smith, K., Parsonnet, J. 1997; 336 (8): 587-587

  View details for Web of Science ID A1997WJ24000023

  View details for PubMedID 9036313

• Helicobacter pylori in the stomach - A paradox unmasked NEW ENGLAND JOURNAL OF MEDICINE Parsonnet, J. 1996; 335 (4): 278-280

  View details for Web of Science ID A1996UZ53200011

  View details for PubMedID 8657247

• Epidemiology of gastric non-Hodgkin's lymphoma patients: parallels with Helicobacter pylori. Helicobacter Thorburn, C., Rodriguez, L., Parsonnet, J. 1996; 1 (2): 75-78

  Abstract

  The incidence of gastric non-Hodgkin's lymphoma (NHL) is increasing in the United States. However, little is known about the etiology of the disease. Some studies have shown an association between gastric NHL and Helicobacter pylori. No study has specifically delineated demographic features that distinguish gastric NHL patients from nongastric NHL patients.To obtain information about the differences between gastric and nongastric NHL patients, we conducted a hospital chart review study. We examined charts of all 25 cases of primary gastric NHL, as well as charts of 75 randomly selected nongastric NHL patients as controls. All patients were seen in the Division of Oncology at Stanford University Medical Center from 1972 to 1991. Demographic information was tabulated, and differences between the cases and controls were noted. The identified risk factors were determined by both univariate and logistic regression analyses.There was no difference between gastric NHL cases and nongastric controls with respect to age, gender, race, and family history of any cancer. However, in logistical regression, persons with gastric NHL were more likely than those with other forms of NHL to be born outside the United States (odds ratio = 12.8; 95% confidence interval = 2.9-56.0) and also to have a family history of stomach cancer (odds ratio = 18.4; 95% confidence interval 2.1-160.1).Gastric NHL is more likely than NHL at other sites to occur in persons with a family history of gastric cancer or in those born in developing countries. This epidemiological pattern supports the identified role of H. pylori in the development of gastric lymphoma.

  View details for PubMedID 9398881

• Principles of screening and surveillance 10th World Congress of Gastroenterology Parsonnet, J., Axon, A. T. NATURE PUBLISHING GROUP. 1996: 847–49

  View details for Web of Science ID A1996UJ97500006

  View details for PubMedID 8633570

• Increased risk of Helicobacter pylori associated with birth in wartime and post-war Japan INTERNATIONAL JOURNAL OF EPIDEMIOLOGY Replogle, M. L., Kasumi, W., Ishikawa, K. B., Yang, S. F., Juji, T., Miki, K., Kabat, G. C., Parsonnet, J. 1996; 25 (1): 210-214

  Abstract

  Helicobacter pylori infection is now widely recognized as a cause of stomach cancer. We assessed trends in H. pylori infection in Japan, a population with high rates of gastric malignancy.Using an enzyme-linked immunosorbent assay (ELISA), we tested sera collected between 1980 and 1993 from Tokyo University Hospital patients for anti-H. pylori IgG. Patients ranged in age from 0 to 94 years. Helicobacter pylori prevalence was then assessed for age and/or birth cohort effects.Of 1207 sera, 470 (38.9%) were positive for H. pylori IgG. By univariate analysis, both older age and birth in an earlier decade were associated with an increased risk of infection. Age-specific prevalence of H. pylori by birth cohort suggested increases in infection during the decades from 1900 to 1959, and age-specific decreases since 1960. In multivariate analysis, H. pylori infection increased with age and was most prevalent among those born in the 1940s and 1950s.Relative to other birth cohorts, people born in the 1940s and 1950s have a higher prevalence of H. pylori. This increased prevalence of infection among those born in wartime Japan likely attests to the impact of compromised living conditions on acquisition of H. pylori, and may portend continued high rates of gastric cancer in forthcoming years.

  View details for Web of Science ID A1996TY24900027

  View details for PubMedID 8666492

• Bacterial infection as a cause of cancer ENVIRONMENTAL HEALTH PERSPECTIVES Parsonnet, J. 1995; 103: 263-268

  Abstract

  Bacterial infections traditionally have not been considered major causes of cancer. Recently, however, bacteria have been linked to cancer by two mechanisms: induction of chronic inflammation and production of carcinogenic bacterial metabolites. The most specific example of the inflammatory mechanism of carcinogenesis is Helicobacter pylori infection. H. pylori has been epidemiologically linked to adenocarcinoma of the distal stomach by its propensity to cause lifelong inflammation. This inflammation is in turn thought to cause cancer by inducing cell proliferation and production of mutagenic free radicals and N-nitroso compounds. H. pylori is the first bacterium to be termed a definite cause of cancer in humans by the International Agency for Research on Cancer. Mutagenic bacterial metabolites are also suspected to increase risk for cancer. This model is best exemplified in colon cancer. Bile salt metabolites increase colonic cell proliferation. Exogenous compounds such as rutin may be metabolized into mutagens by resident colonic flora. Moreover, Bacteroides species can produce fecapentaenes, potent in vitro mutagens, in relatively high concentrations. In vivo data on human carcinogenesis by bacterial metabolites, however, are inconsistent. Local bacterial infections may also predispose to nonnodal lymphomas, although the mechanisms for this are unknown. Gastric lymphomas and immunoproliferative small intestinal disease have been most strongly linked to underlying bacterial infection. Because bacterial infections can be cured with antibiotics, identification of bacterial causes of malignancy could have important implications for cancer prevention.

  View details for Web of Science ID 000202841100026

  View details for PubMedID 8741796

• BIOLOGIC SEX AS A RISK FACTOR FOR HELICOBACTER-PYLORI INFECTION IN HEALTHY-YOUNG ADULTS AMERICAN JOURNAL OF EPIDEMIOLOGY Replogle, M. L., Glaser, S. L., Hiatt, R. A., Parsonnet, J. 1995; 142 (8): 856-863

  Abstract

  Diseases associated with Helicobacter pylori infection, such as peptic ulcer disease and gastric cancer, afflict men more frequently than women. No study, however, has demonstrated any difference in sex-specific rates of H. pylori infection. In a healthy population undergoing multiphasic health evaluations in 1992-1993 as members of the Kaiser Permanente Medical Care Program of Northern California, adults aged 20-39 years were screened for antibodies to H. pylori infection using a serum enzyme-linked immunosorbent assay and were surveyed with regard to their demographic characteristics and health practices. Among 556 African-American, Hispanic, and white men and women, male sex was a significant risk factor for infection. Other risk factors included African-American race and Hispanic ethnicity, increasing age, living with children, birth in a developing country, and lower levels of income and education. Men consistently had a higher prevalence of antibodies across all strata of race/ethnicity, age, education, and income, and in multivariate analysis male sex remained significantly associated with infection (odds ratio = 2.0, 95% confidence interval 1.2-3.1). African-American race, Hispanic ethnicity, increasing age, lower levels of education, and birth in a developing country were also associated with infection in multivariate analysis. Data from previously reported seroprevalence studies support a tendency for men to have a higher risk of infection. The higher prevalence of infection among young males as observed in Northern California may account in part for the increased incidence of H. pylori-related diseases among men in later decades of life.

  View details for Web of Science ID A1995TA75600010

  View details for PubMedID 7572962

• FLAGELLAR SEROTYPES OF SALMONELLA-TYPHI IN INDONESIA - RELATIONSHIPS AMONG MOTILITY, INVASIVENESS, AND CLINICAL ILLNESS JOURNAL OF INFECTIOUS DISEASES Grossman, D. A., WITHAM, N. D., Burr, D. H., Lesmana, M., Rubin, F. A., SCHOOLNIK, G. K., Parsonnet, J. 1995; 171 (1): 212-216

  Abstract

  While the H1-d flagellar serotype of Salmonella typhi has been found worldwide, the H1-j serotype occurs only in Indonesia. A cross-sectional survey in Indonesia compared epidemiologic, clinical, and pathogenetic characteristics of these two serotypes. S. typhi isolates were collected from patients with acute typhoid fever in four Indonesian cities. Flagellar serotype was determined by polymerase chain reaction amplification of the fliC locus of the flg gene. Of 321 isolates, 51 (15.9%) were H1-j. Patients with H1-j infection were older than those with H1-d (P < .001). Among 30 patients with known clinical outcomes, H1-j infection was associated with milder clinical illness than H1-d (P = .06). In vitro, H1-j isolates were both less motile on semi-solid agar plates (P = .004) and less invasive of HEp-2 cells (P = .002) than H1-d isolates. The association of decreased severity of illness with decreased motility and invasiveness suggests that flagellar properties are a component of S. typhi's virulence.

  View details for Web of Science ID A1995PZ87300033

  View details for PubMedID 7798666

• THE INCIDENCE OF HELICOBACTER-PYLORI INFECTION Roundtable Meeting on Epidemiology of Helicobacter pylori Infection Parsonnet, J. BLACKWELL SCIENCE LTD. 1995: 45–51

  Abstract

  Acute Helicobacter pylori infection invariably passes undetected. Consequently, the incidence of infection has been determined indirectly from epidemiological studies. In adults of industrialized countries, an estimated 0.5% of the susceptible population becomes infected each year. This incidence has been decreasing over time. Thus, adults who currently harbour the organism are more likely to have been infected in childhood than adulthood. The incidence of H. pylori infection continues to be high (between 3% and 10% per year) in developing countries. Throughout the world, incidence of H. pylori infection appears to be higher in children than in adults, possibly due to lower standards of personal hygiene in younger populations.

  View details for Web of Science ID A1995RU71700007

  View details for PubMedID 8547528

• GASTRIC ADENOCARCINOMA AND HELICOBACTER-PYLORI INFECTION WESTERN JOURNAL OF MEDICINE Parsonnet, J. 1994; 161 (1): 60-60

  View details for Web of Science ID A1994NY52600010

  View details for PubMedID 7941511

• PARASITISM BY THE SLOW BACTERIUM HELICOBACTER-PYLORI LEADS TO ALTERED GASTRIC HOMEOSTASIS AND NEOPLASIA JOURNAL OF CLINICAL INVESTIGATION Blaser, M. J., Parsonnet, J. 1994; 94 (1): 4-8

  View details for Web of Science ID A1994NW49600004

  View details for PubMedID 8040281

• THE EPIDEMIOLOGY OF TUBERCULOSIS IN SAN-FRANCISCO - A POPULATION-BASED STUDY USING CONVENTIONAL AND MOLECULAR METHODS NEW ENGLAND JOURNAL OF MEDICINE Small, P. M., Hopewell, P. C., Singh, S. P., Paz, A., Parsonnet, J., Ruston, D. C., Schecter, G. F., Daley, C. L., SCHOOLNIK, G. K. 1994; 330 (24): 1703-1709

  Abstract

  The epidemiology of tuberculosis in urban populations is changing. Combining conventional epidemiologic techniques with DNA fingerprinting of Mycobacterium tuberculosis can improve the understanding of how tuberculosis is transmitted.We used restriction-fragment-length polymorphism (RFLP) analysis to study M. tuberculosis isolates from all patients reported to the tuberculosis registry in San Francisco during 1991 and 1992. These results were interpreted along with clinical, demographic, and epidemiologic data. Patients infected with the same strains were identified according to their RFLP patterns, and patients with identical patterns were grouped in clusters. Risk factors for being in a cluster were analyzed.Of 473 patients studied, 191 appeared to have active tuberculosis as a result of recent infection. Tracing of patients' contacts with the use of conventional methods identified links among only 10 percent of these patients. DNA fingerprinting, however, identified 44 clusters, 20 of which consisted of only 2 persons and the largest of which consisted of 30 persons. In patients under 60 years of age, Hispanic ethnicity (odds ratio, 3.3; P = 0.02), black race (odds ratio, 2.3; P = 0.02), birth in the United States (odds ratio, 5.8; P < 0.001), and a diagnosis of the acquired immunodeficiency syndrome (odds ratio, 1.8; P = 0.04) were independently associated with being in a cluster. Further study of patients in clusters confirmed that poorly compliant patients with infectious tuberculosis have a substantial adverse effect on the control of this disease.Despite an efficient tuberculosis-control program, nearly a third of new cases of tuberculosis in San Francisco are the result of recent infection. Few of these instances of transmission are identified by conventional contact tracing.

  View details for Web of Science ID A1994NR10900002

  View details for PubMedID 7910661

• REVERSAL OF INTESTINAL METAPLASIA AFTER TREATMENT OF HELICOBACTER-PYLORI INFECTION HACK, H. M., Fennerty, M. B., Sampliner, R., Egbert, B., Triadafilopoulos, G., Parsonnet, J. W B SAUNDERS CO-ELSEVIER INC. 1994: A87–A87

  View details for Web of Science ID A1994NH90900340

• PREVENTION OF GASTRIC-CANCER - A COST-EFFECTIVENESS ANALYSIS OF SCREENING FOR HELICOBACTER-PYLORI HACK, H. M., Harris, R. A., Owens, D. K., Parsonnet, J. SLACK INC. 1994: A226–A226

  View details for Web of Science ID A1994NF02000655

• PREVENTION OF GASTRIC-CANCER - A COST-EFFECTIVENESS ANALYSIS OF SCREENING FOR HELICOBACTER-PYLORI HACK, H. M., Harris, R., Owens, D. K., Parsonnet, J. SLACK INC. 1994: A23–A23

  View details for Web of Science ID A1994MR21400121

• H pylori and gastric cancer. Lancet Forman, D., Webb, P., Parsonnet, J. 1994; 343 (8891): 243-244

  View details for PubMedID 7904707

• AZATHIOPRINE HYPERSENSITIVITY MIMICKING SEPSIS IN A PATIENT WITH CROHNS-DISEASE CLINICAL INFECTIOUS DISEASES Wilson, B. E., Parsonnet, J. 1993; 17 (5): 940-941

  View details for Web of Science ID A1993ME52300039

  View details for PubMedID 8286654

• HELICOBACTER-PYLORI, PEPSINOGEN, AND RISK FOR GASTRIC ADENOCARCINOMA CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION Parsonnet, J., Samloff, I. M., Nelson, L. M., Orentreich, N., Vogelman, J. H., Friedman, G. D. 1993; 2 (5): 461-466

  Abstract

  The objective of this project was to determine the association of Helicobacter pylori infection and serum pepsinogen levels on subsequent risk for gastric adenocarcinoma. This nested case-control study was set in a large health maintenance organization. One hundred thirty-six cases of gastric adenocarcinoma and 136 matched controls without adenocarcinoma from a large cohort that had contributed serum in the 1960's were studied. The presence of IgG against H. pylori had previously been determined by enzyme-linked immunosorbent assay. Serum levels of pepsinogens I and II were ascertained by radioimmunoassay. In a sample of subjects, the presence of antiparietal cell antibodies was determined by immunofluorescent antibody assay (Nichols Laboratory). There were 98 cases of adenocarcinoma of the antrum, body, or fundus (distal cancers) and 30 of the cardia or gastroesophageal junction (proximal cancers). By univariate analysis, H. pylori infection [odds ratio (OR), 3.6; P < 0.001] and serum pepsinogen I < 50 ng/ml (OR = 2.9; P = 0.003) were both associated with development of distal cancer. In multivariate analysis, there was interaction between the two variables; H. pylori in the absence of low pepsinogen I was independently associated with cancer (OR, 2.4; P = 0.04) but low pepsinogen I in the absence of H. pylori infection was not associated with cancer (OR, 0.8; P > 0.5). In combination, however, H. pylori infection and a low pepsinogen I were associated with a marked increase in the risk of developing distal malignancy (OR, 10.0; P = 0.08).(ABSTRACT TRUNCATED AT 250 WORDS)

  View details for Web of Science ID A1993LX26100010

  View details for PubMedID 8220091

• CHRONIC IDIOPATHIC DIARRHEA NEW ENGLAND JOURNAL OF MEDICINE Mintz, E. D., Parsonnet, J., Osterholm, M. T. 1993; 328 (23): 1713-1714

  View details for Web of Science ID A1993LF05400020

  View details for PubMedID 8487837

• ANOTHER CASE OF POLYMYOSITIS AFTER CIGUATERA TOXIN EXPOSURE ARCHIVES OF NEUROLOGY Stommel, E. W., Jenkyn, L. R., Parsonnet, J. 1993; 50 (6): 571-571

  View details for Web of Science ID A1993LF29900004

  View details for PubMedID 8503792

• PARAQUAT POISONING IN SOUTHERN MEXICO - A REPORT OF 25 CASES ARCHIVES OF ENVIRONMENTAL HEALTH Tinoco, R., Tinoco, R., Parsonnet, J., Halperin, D. 1993; 48 (2): 78-80

  Abstract

  Paraquat is a bipyridyl herbicide used world-wide. Although accidental and deliberate ingestions of lethal doses have been reported from many countries, no case has ever been described in Mexico. The authors report on 25 cases of Paraquat poisoning in the state of Chiapas, Mexico, that occurred between 1988 and 1990. Eighty percent of the cases were men, and 64% of the cases died. Alcohol intoxication or suicidal intent were factors at the time of Paraquat ingestion in 75% of the cases. The majority of cases had learned to use Paraquat from a friend; none had been instructed by a professional. Eighty percent of cases did not know the dilution for the proper use of the herbicide, and none kept the herbicide in its original container. Attention to the law, redesign of the Paraquat packaging, and educational efforts directed at populations at risk might reduce the occurrence of poisoning in this region.

  View details for Web of Science ID A1993LA30000003

  View details for PubMedID 8476308

• HELICOBACTER-PYLORI AND GASTRIC-CANCER GASTROENTEROLOGY CLINICS OF NORTH AMERICA Parsonnet, J. 1993; 22 (1): 89-104

  Abstract

  Gastric cancer remains among the leading types of cancer worldwide. There is now convincing evidence linking H. pylori to adenocarcinomas of the gastric antrum, body, and fundus. These tumors are rapidly decreasing in incidence in the United States, whereas cardia tumors, tumors unassociated with H. pylori infection, are on the increase. Although criteria for causality have not been completely fulfilled for H. pylori and adenocarcinoma, there are plausible mechanisms by which chronic inflammation could induce carcinogenesis ("mitosis causes mutagenesis"). Because gastric cancer is unusual in the United States, screening and treatment of H. pylori in the general population are unwarranted. Chemoprevention in high-risk populations, however, could potentially be used to decrease risk for adenocarcinomas distal to the cardia.

  View details for Web of Science ID A1993KQ44400007

  View details for PubMedID 8449573

• THE ASSOCIATION OF HELICOBACTER-PYLORI WITH GASTRIC-CANCER AND PRENEOPLASTIC GASTRIC-LESIONS IN CHIAPAS, MEXICO CANCER Guarner, J., Mohar, A., Parsonnet, J., Halperin, D. 1993; 71 (2): 297-301

  Abstract

  Helicobacter pylori recently was identified as a risk factor for gastric cancer. Its association with preneoplastic conditions of the stomach, however, is undocumented.Gastric biopsy specimens from 245 symptomatic patients were examined for neoplastic and preneoplastic lesions and for gastric H. pylori infection. The sera of 183 subjects were tested by enzyme-linked immunosorbent assay (ELISA) for anti-H. pylori immunoglobulin G.Histologic H. pylori infection, usually accompanied by acute and chronic gastritis, was found in 85.7% of patients. There was a strong association between H. pylori in the tissue and atrophy (relative risk, 15.0; 95% confidence interval, 4.2-56.6), intestinal metaplasia (relative risk, 5.7; 95% confidence interval, 1.9-16.8), and dysplasia or cancer (relative risk, 4.0; 95% confidence interval, 1.1-14.8). The ELISA was 93.2% sensitive and 57.1% specific for histologic infection with a positive predictive value of 96.1%. The overall seroprevalence rate was 86.1%, with no significant difference in rates between patients with cancer precursors and those with normal stomachs.In this high-risk population, precursor lesions for adenocarcinoma were associated universally with H. pylori infection.

  View details for Web of Science ID A1993KG99800004

  View details for PubMedID 8422620

• Hemolytic uremic syndrome: clinical picture and bacterial connection. Current clinical topics in infectious diseases Parsonnet, J., Griffin, P. M. 1993; 13: 172-187

  View details for PubMedID 8397909

• SALT INTAKE AND STOMACH-CANCER - SOME CONTRARY EVIDENCE CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION Friedman, G. D., Parsonnet, J. 1992; 1 (7): 607-608

  View details for Web of Science ID A1992JY26400014

  View details for PubMedID 1302576

• SYMPTOMS AND RISK-FACTORS OF HELICOBACTER-PYLORI INFECTION IN A COHORT OF EPIDEMIOLOGISTS GASTROENTEROLOGY Parsonnet, J., Blaser, M. J., PEREZPEREZ, G. I., HARGRETTBEAN, N., Tauxe, R. V. 1992; 102 (1): 41-46

  Abstract

  To identify symptoms and risk factors associated with Helicobacter pylori infection, a cohort of 341 epidemiologists was studied. All subjects had one banked serum (collected between 1969 and 1987) and one recent serum sample (collected in 1988) evaluated for H. pylori immunoglobulin G by enzyme-linked immunosorbent assay; subjects provided information on gastrointestinal symptoms and risk factors for gastritis and peptic ulcer disease. Prevalence of infection decreased from the early 1970s to the present. Eleven subjects (3% of the total cohort) seroconverted during the interval between serum samples, giving a crude conversion rate of 0.49% per person-year (95% confidence interval, 0.3-0.9). Nonreactors on the 1988 serum sample described similar symptoms to reactors. However, subjects who seroconverted in the interval between the two serum samples were more likely than either persistent nonreactors [relative risk (RR), 4.1] or persistent reactors (RR, 3.7) to have experienced upper gastrointestinal symptoms in the interval years. Consumption of caffeinated beverages (RR, 4.6) and residence in the northeastern United States (RR, 5.3) seemed to increase risk for infection. Because pain was similarly common in H. pylori-positive and -negative patients, H. pylori cannot be summarily accepted as the cause of dyspeptic symptoms even when infection is confirmed.

  View details for Web of Science ID A1992GX35500008

  View details for PubMedID 1727779

• POLYMYOSITIS AFTER CIGUATERA TOXIN EXPOSURE ARCHIVES OF NEUROLOGY Stommel, E. W., Parsonnet, J., Jenkyn, L. R. 1991; 48 (8): 874-877

  Abstract

  Biopsy-proved polymyositis subsequently developed in two patients who were severely poisoned by ciguatera fish toxin. Ciguatera toxin may have several mechanisms of action and may represent more than one toxin. The patients' clinical courses and the unlikelihood of coincidence of contracting both diseases suggested to us a causal relationship. Although we cannot prove this relationship, we suggest a mechanism by which the toxin predisposed the muscle to inflammation.

  View details for Web of Science ID A1991GA13100024

  View details for PubMedID 1898267

• HELICOBACTER-PYLORI INFECTION IN INTESTINAL-TYPE AND DIFFUSE-TYPE GASTRIC ADENOCARCINOMAS JOURNAL OF THE NATIONAL CANCER INSTITUTE Parsonnet, J., Vandersteen, D., GOATES, J., Sibley, R. K., PRITIKIN, J., Chang, Y. 1991; 83 (9): 640-643

  Abstract

  Gastric cancer can be divided into two histologic types: intestinal and diffuse. To determine whether Helicobacter pylori, a bacterium linked with gastritis, was associated with either cancer type, we reviewed histologic sections from stomachs of patients who had undergone gastrectomy for gastric cancer. Of 37 of the sections with evidence of intestinal-type cancer, 33 (89.2%) contained H pylori in noncancerous tissue compared with 7 (31.8%) of 22 of the sections with evidence of diffuse-type cancer (odds ratio = 17.7; P less than .001). This association remained strong when controlled for age, sex, site, and number of sections reviewed. The prevalence of H pylori in intestinal-type gastric cancer far exceeded the prevalence of H pylori in diffuse disease and that described in the normal US population. This finding suggests that H pylori may be a cofactor in development of intestinal-type gastric cancer.

  View details for Web of Science ID A1991FH75900017

  View details for PubMedID 2023282

• MOLECULAR EPIDEMIOLOGIC TECHNIQUES IN ANALYSIS OF EPIDEMIC AND ENDEMIC SHIGELLA-DYSENTERIAE TYPE-1 STRAINS JOURNAL OF INFECTIOUS DISEASES STROCKBINE, N. A., Parsonnet, J., Greene, K., KIEHLBAUCH, J. A., WACHSMUTH, I. K. 1991; 163 (2): 406-409

  Abstract

  During 1988 the number of Shigella dysenteriae type 1 infections reported in the United States increased fivefold. To determine if recent isolates from Mexico were related to those that caused epidemics of dysentery worldwide, Southern hybridization analysis was done with Shiga toxin and ribosomal RNA gene probes. Western hemisphere and Eastern Hemisphere strains differed by the size of a single EcoRI fragment carrying the Shiga toxin genes. Three ribosomal DNA (rDNA) patterns were observed, which correlated with the strain's continental origin for 81 of 83 isolates tested. Together the Shiga toxin and rDNA probe results indicated that recent Mexican isolates were chromosomally similar to earlier Central American isolates and distinct from Asian and African strains. This suggests there has been no significant exchange of organisms between continents in recent decades and that the 1988 outbreak in Mexico was caused by strains present in Central America since at least 1962.

  View details for Web of Science ID A1991EU57300033

  View details for PubMedID 1671055

• MULTIFOCAL COLITIS ASSOCIATED WITH AN EPIDEMIC OF CHRONIC DIARRHEA GASTROENTEROLOGY JANDA, R. C., Conklin, J. L., Mitros, F. A., Parsonnet, J. 1991; 100 (2): 458-464

  Abstract

  An outbreak of a chronic diarrheal syndrome was detected between May and August 1987 in rural Henderson County, Illinois. Seventy-two individuals were affected. Epidemiological studies performed by the Center for Disease Control implicated the water of a local restaurant as the source of the outbreak. Five patients underwent a comprehensive evaluation. Their mean age was 51 years, and they had a mean of 12 watery stools daily (range, 6-40). Detailed microbiological evaluations failed to identify a pathological organism. Stool studies showed a mean stool weight of 392 g/24 h with a normal fat content. Results of all biochemical studies of serum were normal. Chemical analysis of stool water suggested a secretory diarrhea. Colonoscopy revealed patchy erythema, and light microscopic examination of colonic biopsy specimens revealed multifocal areas of acute inflammation in the superficial mucosa in 4 of 5 patients. Electron microscopy of the affected areas revealed no viral particles. After 2 years, all of our patients continued to experience chronic diarrhea. One patient agreed to a follow-up colonoscopy; histological abnormalities of the colonic mucosa persisted after 2 years. We speculate that an infectious process arising from a contaminated water system induced a chronic, secretory diarrhea characterized by multifocal colitis. This histological abnormality may serve as a marker of an infectious, chronic diarrhea.

  View details for Web of Science ID A1991ER72200022

  View details for PubMedID 1985042

• ASSOCIATION OF HELICOBACTER-PYLORI INFECTION WITH DYSPEPTIC SYMPTOMS IN PATIENTS UNDERGOING GASTRODUODENOSCOPY AMERICAN JOURNAL OF MEDICINE Strauss, R. M., Wang, T. C., Kelsey, P. B., COMPTON, C. C., Ferraro, M. J., PerezPerez, G., Parsonnet, J., Blaser, M. J. 1990; 89 (4): 464-469

  Abstract

  To determine the prevalence of Helicobacter pylori in patients with non-ulcer dyspepsia and ulcer disease as well as in a control population undergoing endoscopic retrograde cholangiopancreatography (ERCP) for suspected pancreatic or biliary disease.Forty-six eligible patients undergoing upper endoscopy at Massachusetts General Hospital were studied over a period of 18 months, as well as 24 patients undergoing ERCP for presumed pancreatic or biliary disease. Two biopsy specimens from the fundus and two from the antrum were taken for microbiologic and histopathologic analysis. Sera were examined by enzyme-linked immunoabsorbent assay. All specimens were processed in a blind fashion. Chi-square test with Yates' correction was used for statistical analysis.H. pylori was found in 31 of 46 (67%) study patients and in six of 24 (25%) control patients (by microbiologic or histologic techniques) (p less than 0.01). H. pylori was found in all patients with peptic ulcer disease and in 60% of patients without ulcers. No association between H. pylori and any specific gastrointestinal symptom was observed. H. pylori was identified in the fundus as often as in the antrum, although in the antrum the organism was more often associated with histologic gastritis. Compared with histology, serologic assays for IgG and IgA antibodies to H. pylori had sensitivities of 100% and 94%, and specificities of 86% and 76%, respectively. Reexamination of selected specimens without knowledge of their identity revealed that the specificity of serology exceeded 94% while the sensitivity of histologic and microbiologic studies may have been closer to 80%.H. pylori was more common in dyspeptic patients than in our control subjects undergoing ERCP. Multiple biopsy sites from fundus and antrum are required to exclude infection. Serologies of IgG and IgA were sensitive and specific for H. pylori, suggesting a possible role for non-endoscopic diagnosis of this infection. The frequent association of H. pylori with active inflammation rather than with quiescent gastritis is consistent with a pathologic role of this organism.

  View details for Web of Science ID A1990ED07400012

  View details for PubMedID 2220879

• INTERNATIONAL TRAVEL AND THE CHILD YOUNGER THAN 2 YEARS .2. RECOMMENDATIONS FOR PREVENTION OF TRAVELERS DIARRHEA AND MALARIA CHEMOPROPHYLAXIS PEDIATRIC INFECTIOUS DISEASE JOURNAL Nahlen, B. L., Parsonnet, J., PREBLUD, S. R., Tsai, T. F., Brink, E. W. 1989; 8 (11): 735-739

  View details for Web of Science ID A1989AZ59300001

  View details for PubMedID 2687786

• SHIGELLA-DYSENTERIAE TYPE-1 INFECTIONS IN UNITED-STATES TRAVELERS TO MEXICO, 1988 LANCET Parsonnet, J., Greene, K. D., Gerber, A. R., Tauxe, R. V., AGUILAR, O. J., Blake, P. A. 1989; 2 (8662): 543-545

  Abstract

  In 1988, the number of Shigella dysenteriae type 1 (Sd1) infections reported in the USA increased five-fold over the annual mean from the previous decade. 44 (94%) of 47 interviewed patients reported recent travel to Mexico; 33 (75%) of these had been tourists to the Yucatan peninsula. 27 patients who had travelled to Mexico were admitted to hospital, of whom 2 had a haemolytic uraemic syndrome; none died. The antimicrobial resistance pattern and plasmid profile of the Yucatan strain were similar to those of the 1969-72 pandemic strain. Antimicrobial resistances and plasmid profiles were different in sporadic Western hemisphere strains. This is the first outbreak of Sd1 among US tourists and it is the largest known outbreak in the Western hemisphere since the early 1970s. The dominant Sd1 strain is similar to that which caused the catastrophic 1969-72 pandemic. Surveillance and control measures have been instituted in the Yucatan peninsula.

  View details for Web of Science ID A1989AN01000011

  View details for PubMedID 2570242

• TRICHOSPORON-BEIGELII PERITONITIS SOUTHERN MEDICAL JOURNAL Parsonnet, J. 1989; 82 (8): 1062-1063

  Abstract

  A patient receiving continuous ambulatory peritoneal dialysis, and who was known to be seropositive for human immunodeficiency virus but without AIDS or ARC, had peritonitis secondary to Trichosporon beigelii. The patient had been receiving oral antibiotics and had had recurrent bouts of bacterial peritonitis. Infection was cured with removal of the peritoneal catheter and intraperitoneal and intravenous amphotericin B. The course of this episode of Trichosporon beigelii peritonitis was similar to that of peritonitis caused by other yeasts.

  View details for Web of Science ID A1989AM33000037

  View details for PubMedID 2762891

• INTERNATIONAL TRAVEL AND THE CHILD YOUNGER THAN 2 YEARS .1. RECOMMENDATIONS FOR IMMUNIZATION PEDIATRIC INFECTIOUS DISEASE JOURNAL PREBLUD, S. R., Tsai, T. F., Brink, E. W., Nahlen, B. L., Parsonnet, J. 1989; 8 (7): 416-425

  View details for Web of Science ID A1989AE93900001

  View details for PubMedID 2666941

• CHRONIC DIARRHEA ASSOCIATED WITH DRINKING UNTREATED WATER ANNALS OF INTERNAL MEDICINE Parsonnet, J., Trock, S. C., Bopp, C. A., Wood, C. J., Addiss, D. G., ALAI, F., GORELKIN, L., HARGRETTBEAN, N., Gunn, R. A., Tauxe, R. V. 1989; 110 (12): 985-991

  Abstract

  To determine the cause of an outbreak of chronic diarrhea and to define the clinical profile of the illness.A case series of patients with chronic diarrhea and case-control and cohort studies to determine the vehicle and cause of the illness.Rural Henderson County, Illinois.Seventy-two patients who had onset of chronic diarrheal illness between May and August 1987. Controls were local residents and eating companions who did not have diarrheal illness. A cohort study included 80 truck drivers from a local firm.Nonbloody diarrhea was characterized by extreme frequency (median, 12 stools/d), marked urgency, fecal incontinence, and weight loss (mean, 4.5 kg). The median incubation period was 10 days. Nine patients were hospitalized; none died. Diarrhea persisted in 87% of patients after 6 months. Antimicrobial therapy produced no clinical improvement. No bacterial, mycobacterial, viral, or parasitic agents known to be enteropathogenic were detected in stools or implicated water. Three of five small-bowel biopsies showed mild inflammatory changes. Mild inflammation was also seen in two of nine colonic biopsies. Case-control studies implicated a local restaurant (P = 0.0001, odds ratio = 19) and subsequently the untreated well water served in the restaurant (P = 0.04, odds ratio = 9.3) as the vehicle of transmission.This is the first outbreak of chronic diarrhea linked to drinking untreated water. The causative agent and pathophysiologic mechanism of the illness remain elusive.

  View details for Web of Science ID A1989AB29600007

  View details for PubMedID 2729809

• SIMPLE MICROBIOLOGIC DETECTION OF CAMPYLOBACTER-PYLORI JOURNAL OF CLINICAL MICROBIOLOGY Parsonnet, J., Welch, K., Compton, C., Strauss, R., Wang, T., Kelsey, P., Ferraro, M. J. 1988; 26 (5): 948-949

  Abstract

  A study of 84 gastric biopsies taken from 42 adult patients revealed simple techniques for Gram stain and culture for Campylobacter pylori. In an initial study of 18 biopsies, Gram stains prepared from ground, diluted tissue were all negative for curved, gram-negative rods, whereas 13 of these specimens were positive for C. pylori by culture. The Gram stains for the remaining 66 biopsies were prepared by a rinse-imprint technique. In this group, there were 30 Gram stains positive for organisms resembling C. pylori and 32 positive cultures. By Gram-staining two sites, fundus and antrum, the sensitivity of the Gram stain for identifying a positive specimen increased from 91 to 100%. Gram stain may be the preferred technique for rapid diagnosis. When cultured, C. pylori was recovered most often on modified Thayer-Martin medium incubated microaerophilically at 35 degrees C. The presence of antibiotics in modified Thayer-Martin medium limited upper respiratory flora overgrowth, which was often present on nonselective media.

  View details for Web of Science ID A1988N130600031

  View details for PubMedID 3384915