New Serological Measures of Infectious Disease Transmission Intensity

Investigator: Benjamin F. Arnold, PhD
Sponsor: NIH National Institute of Allergy and Infectious Disease

Location(s): Kenya; Tanzania; Haiti


Antibodies measured in blood provide a sensitive measure of infection for many infectious diseases. Statistical methods that enable us to measure disease transmission intensity at the population level from blood antibody levels are an important tool for public health efforts because they help identify populations in greatest need of intervention and help measure the effectiveness of interventions designed to reduce transmission. No statistical tools like this exist for enteric pathogens (those that cause diarrhea) and neglected tropical diseases, which together cause an immense health burden among the world's poorest people, and so we propose to develop new methods to measure population-level transmission intensity of these diseases based on antibodies measured in blood from children in Kenya, Tanzania, and Haiti.

 Recent advances in multiplex antigen assays have led to the development of low-cost and sensitive methods to measure enteric pathogens and neglected tropical diseases (NTDs). There have not been commensurate advances in the statistical methods used to derive measures of transmission intensity from antibody response. Translating antibody response into metrics of transmission intensity is a key step from a public health perspective because it enables us to target intervention programs to the populations most in need and then measure the effectiveness of those programs. Aims and Methods: The overarching goal of this research is to develop a methodologic framework to translate antibody response measured in cross-sectional surveys into measures of transmission intensity for enteric pathogens (7 included in the study, e.g., Cryptosporidium parvum, enterotoxigenic E. coli) and neglected tropical diseases (principal focus: lymphatic filariasis). We approach this goal from two novel perspectives. In Aim 1, we draw on the "peak shift" phenomenon for infectious diseases, and hypothesize that changes in transmission will be detectable in the age-specific antibody response curve. At lower transmission, antibody levels should decline across all ages due to fewer and less frequent active infections, leading to an overall shift in the age-specific response curve. We will evaluate the approach by comparing antibody response curves for young children with different exposures (improved vs. unimproved drinking water for enteric pathogens; pre- versus post- mass drug administration for lymphatic filariasis) in large, well characterized cohorts in Kenya, Tanzania, and Haiti. In Aim 2, we will develop semi-parametric methods to estimate the force of infection (seroconversion rate) from seroprevalence data for pathogens where seroreversion is possible, using lymphatic filariasis as an example. Our new approach marks a significant advance over previous work in this area by making few modeling assumptions and by allowing for the flexible control of confounding between comparison groups. We will evaluate the approach in Haiti by measuring the effect of mass drug administration on the force of infection for lymphatic filariasis For all of the methods, we will create user-friendly, open source software to accelerate translation to applied research.