David Aronoff of the University of Michigan in the U.S., with an interdisciplinary team of experts in microbiology, immunology, reproductive biology, and vaccine development, will examine how infections of the female reproductive tract interact with and evade the immune system, resulting in infections of the uterus that cause preterm birth and stillbirth. This work will research potential targets for prevention of invasive infections of the female genital tract, including plans to investigate strains of group B Streptococcus (GBS) from low-income countries for vaccine and drug development. Funding partners: Global Alliance to Prevent Prematurity and Stillbirth (GAPPS) and Bill & Melinda Gates Foundation.

Richard Guerrant of the University of Virginia in the U.S. and co-­investigators will develop and validate non-­invasive metabolic biomarkers of gut health to identify children at risk of environmental enteropathy and developmental impairment, in order to assess interventions. They will use ongoing MAL­-ED (malnutrition and enteric diseases) and NIH­-supported clinical studies in malnourished and control children, and their own studies in novel murine models, along with a nuclear magnetic resonance approach to perform metabolic profiling of urine, plasma and feces samples. Their goal is to improve the growth, nutrition and development of children at high risk of environmental enteropathy that can lead to morbidity and mortality.

Iruka Okeke of the University of Ibadan, College of Medicine in Nigeria and Kat Holt of Monash University in Australia will set-up a remote laboratory that uses nanopore sequencing as a low-cost, portable method to monitor the spread of antimicrobial resistance in rural areas of Africa and combine it with genome editing tools for more rapid diagnosis and improved treatment. Antimicrobial resistance (AMR) occurs when pathogens are able to survive treatments that previously would have killed them. Infection persists in these patients and spreads to others in the community, increasing both the risk of serious complications and the economic costs. To combat AMR, it needs to be tracked locally and quickly enough to inform treatment. However, traditional tracking methods are slow, and difficult to use in rural settings because of limited resources. Nanopore sequencing technology is a highly portable method of sequencing DNA that is suitable for resource-poor settings. They will setup a prototype minimal bacterial genomics lab at a provincial hospital laboratory in Africa, and use nanopore sequencing to catalog pathogens collected from patients and monitor AMR. They will also combine the sequencing with a genome editing tool - CRISPR-Cas - to enrich for known resistant pathogens and enable much faster diagnosis directly from blood or stool samples. Once optimized in the initial location, the remote lab can be recreated in other areas of Africa.

Scientists have long known that only relatively old mosquitoes can transmit the agents that cause certain diseases, including dengue fever and malaria. Dr. O'Neill and his multinational team are working on a plan to shorten the lifespan of mosquitoes that transmit the dengue virus, which infects up to 100 million people each year. They are introducing into populations of Aedes mosquitoes, strains of a naturally occurring bacterial symbiont, Wolbachia, that kill infected insects before they are old enough to transmit disease. Wolbachia are inherited though the eggs of the mosquitoes and so are passed on from generation to generation. O'Neill (Grand Challenges in Global Health: 2005-2015 retrospective)