Enteropathogen antibody dynamics and force of infection among children in low-resource settings
Abstract
Little is known about enteropathogen seroepidemiology among children in low-resource settings. We measured serological IgG responses to eight enteropathogens (Giardia intestinalis, Cryptosporidium parvum, Entamoeba histolytica, Salmonella enterica, enterotoxigenic Escherichia coli, Vibrio cholerae, Campylobacter jejuni, norovirus) in cohorts from Haiti, Kenya, and Tanzania. We studied antibody dynamics and force of infection across pathogens and cohorts. Enteropathogens shared common seroepidemiologic features that enabled between-pathogen comparisons of transmission. Overall, exposure was intense: for most pathogens the window of primary infection was <3 years old; for highest transmission pathogens primary infection occurred within the first year. Longitudinal profiles demonstrated significant IgG boosting and waning above seropositivity cutoffs, underscoring the value of longitudinal designs to estimate force of infection. Seroprevalence and force of infection were rank-preserving across pathogens, illustrating the measures provide similar information about transmission heterogeneity. Our findings suggest antibody response can be used to measure population-level transmission of diverse enteropathogens in serologic surveillance.
Data availability
Analyses were conducted in R version 3.5.3. Data and computational notebooks used to complete the analyses are available through GitHub and the Open Science Framework (osf.io/r4av7).
Article and author information
Author details
Funding
National Institutes of Health (K01-AI119180)
- Benjamin F Arnold
Bill and Melinda Gates Foundation (OPP1022543)
- Patrick J Lammie
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Mark Jit, London School of Hygiene & Tropical Medicine, and Public Health England, United Kingdom
Ethics
Human subjects: In Haiti, the human subjects protocol was reviewed and approved by the Ethical Committee of St. Croix Hospital (Leogane, Haiti) and the institutional review board at the US Centers for Disease Control and Prevention (CDC). After listening to an overview of the study, individuals were asked for verbal consent to participate. Verbal consent was deemed appropriate by both review boards because of low literacy rates in the study population. With each longitudinal visit, the study team re-consented participants before specimen collection. Mothers provided consent for children under 7, and children 7 years and older provided additional verbal assent. In Kenya, the human subjects protocol was reviewed and approved by institutional review boards at the Kenya Medical Research Institute (KEMRI) and at the US CDC. Primary caretakers provided written informed consent for their infant child's participation in the trial and blood specimen collection and testing. The original trial was registered at clinicaltrials.org (NCT01695304). In Tanzania, the human subjects protocol was reviewed and approved by the Institute for Medical Research Ethical Review Committee in Dar es Salaam, Tanzania and the institutional review board at the US CDC. Parents of enrolled children provided consent, and children 7 years and older also provided verbal assent before specimen collection.
Version history
- Received: January 29, 2019
- Accepted: August 15, 2019
- Accepted Manuscript published: August 19, 2019 (version 1)
- Version of Record published: September 16, 2019 (version 2)
Copyright
This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
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Further reading
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- Epidemiology and Global Health
Background:
The aim of our study was to test the hypothesis that the community contact tracing strategy of testing contacts in households immediately instead of at the end of quarantine had an impact on the transmission of SARS-CoV-2 in schools in Reggio Emilia Province.
Methods:
We analysed surveillance data on notification of COVID-19 cases in schools between 1 September 2020 and 4 April 2021. We have applied a mediation analysis that allows for interaction between the intervention (before/after period) and the mediator.
Results:
Median tracing delay decreased from 7 to 3.1 days and the percentage of the known infection source increased from 34–54.8% (incident rate ratio-IRR 1.61 1.40–1.86). Implementation of prompt contact tracing was associated with a 10% decrease in the number of secondary cases (excess relative risk –0.1 95% CI –0.35–0.15). Knowing the source of infection of the index case led to a decrease in secondary transmission (IRR 0.75 95% CI 0.63–0.91) while the decrease in tracing delay was associated with decreased risk of secondary cases (1/IRR 0.97 95% CI 0.94–1.01 per one day of delay). The direct effect of the intervention accounted for the 29% decrease in the number of secondary cases (excess relative risk –0.29 95%–0.61 to 0.03).
Conclusions:
Prompt contact testing in the community reduces the time of contact tracing and increases the ability to identify the source of infection in school outbreaks. Although there are strong reasons for thinking it is a causal link, observed differences can be also due to differences in the force of infection and to other control measures put in place.
Funding:
This project was carried out with the technical and financial support of the Italian Ministry of Health – CCM 2020 and Ricerca Corrente Annual Program 2023.
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- Epidemiology and Global Health
In biomedical science, it is a reality that many published results do not withstand deeper investigation, and there is growing concern over a replicability crisis in science. Recently, Ellipse of Insignificance (EOI) analysis was introduced as a tool to allow researchers to gauge the robustness of reported results in dichotomous outcome design trials, giving precise deterministic values for the degree of miscoding between events and non-events tolerable simultaneously in both control and experimental arms (Grimes, 2022). While this is useful for situations where potential miscoding might transpire, it does not account for situations where apparently significant findings might result from accidental or deliberate data redaction in either the control or experimental arms of an experiment, or from missing data or systematic redaction. To address these scenarios, we introduce Region of Attainable Redaction (ROAR), a tool that extends EOI analysis to account for situations of potential data redaction. This produces a bounded cubic curve rather than an ellipse, and we outline how this can be used to identify potential redaction through an approach analogous to EOI. Applications are illustrated, and source code, including a web-based implementation that performs EOI and ROAR analysis in tandem for dichotomous outcome trials is provided.