R01AI162867

Enteric pathogen infections are a leading cause of the global disease burden, with the largest burden among children in low-resource settings. Stool-based PCR methods have dramatically improved our ability to measure enteric infections, but the challenge of collecting stool and the need for near-continuous monitoring to detect many globally important pathogens has thwarted broader use in large-scale surveillance.

Large-scale, population-based surveys now regularly collect blood to monitor transmission and burden of diseases such as HIV, malaria, and dengue. Broader testing of blood collected in such surveys with multiplex assays represents a new opportunity to measure enteric pathogen transmission and burden. Antibody-based measures could complement stool-based PCR testing because antibody responses remain elevated for many months after infection, thus providing more information in studies with infrequent measurements.

Our team has developed multiplex bead assays that measure immunoglobulin G (IgG) response to diverse enteric pathogens. In preliminary studies, we have shown that IgG levels can be used to measure heterogeneity in enteric pathogen transmission between populations. We have also shown that the results generalize to pathogens that span taxa.

In this application, we propose to complete a series of studies that address key next steps to advance the seroepidemiology of enteric pathogens in low-resource settings. We will conduct a longitudinal birth cohort in Ecuador that pairs high resolution, multiplex stool-based PCR infection with longitudinal, multiplex IgG and IgA measurements. Our 17-year research history at the site has documented substantial variation in enteric pathogen infection across a rural-urban gradient, making it an ideal setting for the research.

The cohort will enroll 600 children from three sites across a rural-urban gradient and measure them frequently from birth to 24 months. On the Luminex platform, we will pair multiplex PCR assessment for 15 enteric pathogens with IgG and IgA assessment in a multiplex bead assay that includes antigens to 7 enteric pathogens: Campylobacter jejuni, enterotoxigenic Escherichia coli, Salmonella enterica, Giardia duodenalis, Cryptosporidium parvum, Entamoeba histolytica, and norovirus.

In Aim 1, we will use molecular and antibody-based measures to study force of infection of the enteric pathogens across a rural-urban gradient. This will represent the first broad-based comparison of seroepidemiologic measures against patent infection for enterics.

In Aim 2, we will estimate enteric pathogen force of infection by applying current-status models to population-based, cross-sectional serology surveys in the region, and will benchmark the cross-sectional estimates against those obtained in the concurrent longitudinal study.

In Aim 3, we will study IgG and IgA kinetics following infection for each of the 7 pathogens and develop models to accurately predict recent infections and incidence from antibody levels measured in cross-sectional serology surveys.

Completion of these aims will result in generalizable seroepidemiologic methods that have the potential to transform measurement of enteric pathogen transmission and burden in low-resource settings.

San Francisco Regents Of The University Of California

TO ASSIST PUBLIC AND PRIVATE NONPROFIT INSTITUTIONS AND INDIVIDUALS TO ESTABLISH, EXPAND AND IMPROVE BIOMEDICAL RESEARCH AND RESEARCH TRAINING IN INFECTIOUS DISEASES AND RELATED AREAS, TO CONDUCT DEVELOPMENTAL RESEARCH, TO PRODUCE AND TEST RESEARCH MATERIALS. TO ASSIST PUBLIC, PRIVATE AND COMMERCIAL INSTITUTIONS TO CONDUCT DEVELOPMENTAL RESEARCH, TO PRODUCE AND TEST RESEARCH MATERIALS, TO PROVIDE RESEARCH SERVICES AS REQUIRED BY THE AGENCY FOR PROGRAMS IN INFECTIOUS DISEASES, AND CONTROLLING DISEASE CAUSED BY INFECTIOUS OR PARASITIC AGENTS, ALLERGIC AND IMMUNOLOGIC DISEASES AND RELATED AREAS. PROJECTS RANGE FROM STUDIES OF MICROBIAL PHYSIOLOGY AND ANTIGENIC STRUCTURE TO COLLABORATIVE TRIALS OF EXPERIMENTAL DRUGS AND VACCINES, MECHANISMS OF RESISTANCE TO ANTIBIOTICS AS WELL AS RESEARCH DEALING WITH EPIDEMIOLOGICAL OBSERVATIONS IN HOSPITALIZED PATIENTS OR COMMUNITY POPULATIONS AND PROGRESS IN ALLERGIC AND IMMUNOLOGIC DISEASES. BECAUSE OF THIS DUAL FOCUS, THE PROGRAM ENCOMPASSES BOTH BASIC RESEARCH AND CLINICAL RESEARCH. SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM EXPANDS AND IMPROVES PRIVATE SECTOR PARTICIPATION IN BIOMEDICAL RESEARCH. THE SBIR PROGRAM INTENDS TO INCREASE AND FACILITATE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, TO INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. THE SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM STIMULATES AND FOSTERS SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH AND DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO FOSTER TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. RESEARCH CAREER DEVELOPMENT AWARDS SUPPORT THE DEVELOPMENT OF SCIENTISTS DURING THE FORMATIVE STAGES OF THEIR CAREERS. INDIVIDUAL NATIONAL RESEARCH SERVICE AWARDS (NRSAS) ARE MADE DIRECTLY TO APPROVE APPLICANTS FOR RESEARCH TRAINING IN SPECIFIED BIOMEDICAL SHORTAGE AREAS. IN ADDITION, INSTITUTIONAL NATIONAL RESEARCH SERVICE AWARDS ARE MADE TO ENABLE INSTITUTIONS TO SELECT AND MAKE AWARDS TO INDIVIDUALS TO RECEIVE TRAINING UNDER THE AEGIS OF THEIR INSTITUTIONAL PROGRAM.

93.855 - Allergy and Infectious Diseases Research

National Institute of Allergy and Infectious Diseases (NIAID) [HHS - NIH]

San Francisco, California 941432510 United States

Single Zip Code

NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed) (PA-20-185)

Amendment Since initial award the total obligations have increased 376% from $781,015 to $3,719,600.