H3Africa Initiative aims to facilitate a contemporary research approach to the study of genomics and environmental determinants of common diseases with the goal of improving the health of African populations. To accomplish this, the H3Africa Initiative assists in the development of the necessary expertise among African scientists to establish networks of African investigators. One of the main initiatives of the H3Africa consortium are working groups which have the objective to foster scientific exchange within the consortium and with US-based partner institutions.

The nasopharynx (NP) is the reservoir for many key bacterial pathogens responsible for lower respiratory tract infection (LRTI) in children, is the portal of entry for respiratory viruses and also harbors potentially pathogenic fungi. The composition of the microbiota, including microbial diversity, density and the interaction between microbial components is likely to influence whether colonization proceeds to disease and the severity of such disease. Data from our groups and others have demonstrated patterns of dysbiosis that may be associated with the development of respiratory tract infections in children, however this has not been studied comprehensively, and accounting for all components of the microbiota. There is also evidence that the bacterial microbiota may modulate the severity of viral LRTI. Recurrent LRTI is common in African children, and may be associated with persistent dysbiosis of the respiratory microbiota. Antimicrobial resistance may be an important determinant of persistent dysbiosis after antimicrobial therapy.

The study will focus on bacterial, viral and fungal components of the NP microbiota before, at the time of, and after LRTI in African children. The aims are to determine if

1. The composition of the NP microbiota in the period before LRTI and at the time of LRTI is different from that in children who did not develop LRTI
2. The composition of the NP microbiota before LRTI and at the time of LRTI is different between children who developed severe LRTI compared with children who developed non-severe LRTI
3. The composition of the NP microbiota after LRTI is different between children who developed recurrent LRTI and those who did not develop recurrent LRTI
4. The composition of the NP microbiota after LRTI is associated with the presence of antimicrobial resistant bacteria in the NP.

An improved understanding of the association of the NP microbiota with LRTI may lead to the development of new tools for diagnosis or risk prediction. This could include tools to predict which children are at high risk of LRTI, identify children at risk of progression to severe LRTI and children at risk of recurrent LRTI. In addition, understanding the possible role of the NP in the pathogenesis of LRTI or recurrent LRTI may lead to the identification of novel strategies to prevent LRTI, progression to severe LRTI or recurrent LRTI. These could include targeted probiotic therapy, novel vaccines or vaccine strategies and new therapeutics to treat LRTI.

Under the direction of Christopher DuPont, JCVI will sequence samples for metagenomic studies and provide assembly centric shotgun sequencing analysis. Coordination and training content events will be done with support from Stephanie Mounaud.

Funding

This project was funded through National Institute of Health (NIH), National Institute of Allergy and Infectious Diseases (NIAID) grant number 1U54HG009824-01.

Publications