Journal Article

Enteropathogen antibody dynamics and force of infection among children in low-resource settings

Vinjé, Jan, Lammie, Patrick J, Cooley, Gretchen M, Costantini, Veronica, Goodhew, E Brook, Arnold, Benjamin F, Martin, Diana L, Priest, Jeffrey W, Morris, Jamae F, Omore, Richard, Juma, Jane, Ochieng, John B, Mkocha, Harran

2019

Overview

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. Diarrhea, which is caused by bacteria such as Salmonella or by viruses like norovirus, is the fourth leading cause of death among children worldwide, with children in low-resource settings being at highest risk. The pathogens that cause diarrhea spread when stool from infected people comes into contact with new hosts, for example, through inadequate sanitation or by drinking contaminated water. Currently, the best way to track these infections is to collect stool samples from people and test them for the presence of the pathogens. Unfortunately, this is costly and difficult to do on a large scale outside of clinical settings, making it hard to track the spread of diarrhea-causing pathogens. The body produces antibodies – small proteins that can detect specific pathogens – in response to an infection. These antibodies help ward off future infections by the same pathogen, so if they are present in the blood, this indicates a current or previous infection. Scientists already collect blood samples to track malaria, HIV and vaccine-preventable diseases in low-resource settings. These samples could be tested more broadly to measure the levels of antibodies against diarrhea-causing pathogens. Now, Arnold et al. have used blood samples collected from children in Haiti, Kenya, and Tanzania to measure antibody responses to 8 diarrhea-causing pathogens. The results showed that many children in these settings had been infected with all 8 pathogens before age three, and that all of the pathogens shared similar age-dependent patterns of antibody response. This finding enabled Arnold et al. to combine antibody measurements with statistical models to estimate each pathogen’s force of infection, that is, the rate at which susceptible individuals in the population become infected. This is a key step for epidemiologists to understand which pathogens cause the most infections in a population. The experiments show that testing blood samples for antibodies could provide scientists with a new tool to track the transmission of diarrhea-causing pathogens in low-resource settings. This information could help public health officials design and test efforts to prevent diarrhea, for example, by improving water treatment or developing vaccines.

• Publisher: eLife Sciences Publications Ltd,eLife Sciences Publications, Ltd
• Subject: Age Factors / Antibodies, Bacterial - blood / Antibodies, Protozoan - blood / Antibodies, Viral - blood / Antibody response / Bacterial Infections - epidemiology / Caliciviridae Infections - epidemiology / Campylobacter / Campylobacter jejuni / Child / Children / Children & youth / Cryptosporidium parvum / Developing Countries / Disease control / Disease prevention / Disease Transmission, Infectious / Drinking water / Enrollments / Entamoeba histolytica / Epidemiological Monitoring / Epidemiology and Global Health / Estimates / Giardia intestinalis / Haiti - epidemiology / Health surveillance / Humans / Immunoglobulin G / Immunoglobulin G - blood / Infections / Intestinal Diseases, Parasitic - epidemiology / Kenya - epidemiology / Longitudinal Studies / Norovirus / Pathogens / Population / Public health / Salmonella / Salmonella enterica / Seroepidemiologic Studies / Seroepidemiology / Tanzania - epidemiology / Tropical diseases