Rotavirus Genomics and Metagenomics of African Stool Samples
Acute severe dehydrating rotavirus diarrhoea remains a major contributor towards childhood mortality worldwide (Estes and Kapikian, 2007). Rotavirus infection causes an estimated 527,000 deaths in children less than 5 years of age each year (Parashar, et al, 2009). Approximately 85% of these cases occur in developing countries in Africa and Asia (WHO, 2008). The two new rotavirus vaccines (Rotateq and Rotarix) have been designed to protect against one or more of the globally most common rotavirus strains (G1-G4). The introduction of rotavirus vaccines in Africa is now considered as the most promising approach to contribute to Millennium Development Goal for 2015, which has as Target 4 "to reduce by two thirds the under-five mortality rate between 1990 and 2015". Although the availability of rotavirus vaccines has pioneered the prospect of substantial reductions of childhood morbidity and mortality globally due to rotavirus infection, the key issue with currently licensed vaccines is suboptimal immune response and efficacy (60% for developing vs. 85-90% in developed countries) in African children.
This project will explore in-depth genomic diversity of rotavirus strains circulating in African human and animal populations in order to uncover unusual rotavirus strains and animal-human reassortants, with a view of generating data to support strain selection for design of next generation rotavirus vaccines and diagnostics relevant for Africa. Additionally, the project will take advantage of the same stool specimens to study the effects of infection on the microbiome/metagenomics of the gut of African children. Archival diarrheal stool specimens from children under the age of five years and collected from 1998 to 2010 and previously characterized for rotavirus infection will form the basis of this study. The samples are currently accessible from the WHO Rotavirus Regional Reference Laboratory. Dr. Jeffrey Mphahlele will select and prepare 300 specimens for shipment to Dr. Wentworth and Dr. Nelson at the JCVI for analysis.
1.Estes MK, Kapikian AZ. Rotaviruses and their replication. In Fields Virology. Edited by Knipe, D.M. & Howley, P.M. 5th edition; 2007. Philadelphia: Lipincott -Williams and Wilkins.
2. Parashar UD, Burton A, Lanata C, Boschi-Pinto C, Shibuya K, Steele D, Birmingham M, Glass RI. Global mortality associated with rotavirus disease among children in 2004. J Infect Dis 2009; 200: S9-S15.
3. World Heath Organisation (WHO). Weekly epidemiological record. Wkly Epidemiol Records, No. 32, 2008; 82, 285296.
This project has been funded in whole or part with federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services under contract numbers N01-AI30071 and/or HHSN272200900007C.