Enteric and Diarrheal Disease

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Alexander Aiken of the London School of Hygiene and Tropical Medicine in the United Kingdom will use the Matched Parallel Cohort (MPC) method in a multi-site study to measure the impact of antibiotic-resistant infections on mortality in low-income countries in sub-Saharan Africa. More complete data on antimicrobial resistance for this population is greatly needed, even though preliminary data suggests that mortality rates are likely higher than for high-income countries.

Matthew DeLisa of Cornell University in the U.S. will create a cell-free synthetic biology platform for low-income settings that produces thermostable polysaccharide-based conjugate vaccines against diarrheal pathogens upon the addition of water to a single tube. Half-a-million children under age five die each year from diarrhea and dysentery, the majority in low- and middle-income countries. Two major causes of bacterial diarrhea are enterotoxigenic E. coli (ETEC) and Shigella strains.

Pamela Schnupf of Paris Descartes University in France will develop an oral vaccine to prevent infectious diarrhea in children by engineering a non-pathogenic bacteria to express pathogen molecules that can be safely delivered in bacterial spores. Diarrheal disease caused largely by Shigella and enterotoxigenic Escherichia coli is a major cause of morbidity and mortality in children under five years of age in low-resource settings.

An innovative global model for prevention of diarrheal deaths with ORS and zinc that uses faith networks in Nigeria to identify and train a cadre of ""ORS moms"to serve as vehicles for behaviour change messaging and community-based suppliers.

Chelsea Marie of the University of Virginia in the U.S. will perform a genetic screen using CRISPR-Cas9 gene knockout technology to identify the human genes required for infection by the parasite Cryptosporidium, which causes severe childhood diarrhea in developing countries, in order to develop new treatments. They will create pooled libraries of knockout human cells where all the genes in the genome are disrupted to enable high-throughput screens, and infect them with Cryptosporidium hominis, which is the strain causing major health problems in many regions including Brazil and India.

Alexander Aiken of the London School of Hygiene and Tropical Medicine in the United Kingdom will use the Matched Parallel Cohort (MPC) method in a multi-site study to measure the impact of antibiotic-resistant infections on mortality in low-income countries in sub-Saharan Africa. More complete data on antimicrobial resistance for this population is greatly needed, even though preliminary data suggests that mortality rates are likely higher than for high-income countries.

Ngalla Jillani of the Institute of Primate Research in Kenya will build an infectious infant baboon model of cryptosporidiosis that mimics the disease in human infants under two years old to help identify new treatments. Childhood Cryptosporidium infections are common in developing countries and cause substantial morbidity and mortality. Current models in small animals fail to fully recapitulate the course of infection and disease symptoms in humans, making them less valuable for studying the disease and identifying effective treatments.

Alejandro Castellanos-Gonzalez of the University of Texas Medical Branch in the U.S. will use their gene silencing approach involving premade complexes of protein and small RNA to identify drug targets in the Cryptosporidium parasite, which causes severe diarrhea in young children in developing countries. Their gene silencing method involves synthesizing the so-called argonaute protein that is able to cut a single gene and attaching it to a single-strand antisense RNA that is designed to target a specific gene. This method can be easily scaled up for high-throughput drug target screens.

Boris Striepen of the University of Georgia in the U.S. will develop a new, more natural mouse model for cryptosporidiosis, which is a leading cause of severe diarrhea in children, to help identify effective treatments. Unlike previous mouse models of this disease, these mice do not need to be immune deficient as they can be infected by a natural strain of the Cryptosporidium parasite, which they previous isolated from house mice. They will genetically modify this strain so it will fluoresce and can thus be easily located in the mice and within individual cells.