Center for Research on the Respiratory Microbiota of African Children (ReMAC): Abstract
The microbiota (community of microorganisms) of the upper airways plays a key role in the development of
lower respiratory tract infection (LRTI) in children. Most of the important bacterial LRTI pathogens also colonize
the nasopharynx (NP), which often serves as the source of infection for LRTI in a child as well as the reservoir
for transmission to other children. We have assembled an interdisciplinary collaboration between investigators
at three leading African research institutions, in South Africa, The Gambia and Malawi, and a leading genomic
center in the USA to address key questions on the determinants, composition and biological significance of the
microbiota of the upper airways in African children. We will leverage several large existing cohorts and sample
repositories to conduct three complementary but not co-dependent research projects, each done at multiple
African sites. The first project will focus on comprehensive description of the NP microbiota (bacterial, fungal
and viral components) in healthy African children over the first year of life, using longitudinal, frequently
sampled cohorts. We will also study the role of the NP microbiota in resistance to colonization with the
respiratory pathogen, Streptococcus pneumoniae, including modulation of vaccine-induced protection. The
second project will investigate the role of the NP microbiota, including consideration of antimicrobial resistance,
in the incidence, severity, and recurrence of LRTI in African children. The third project will examine the
association between seasonality, inhaled environmental exposures (or pollutants), the household dust
microbiota, and the microbiota of the NP and oropharynx in children from South Africa and The Gambia. We
will use amplicon sequencing to define the bacterial and fungal components of the microbiota, targeted nucleic
acid amplification testing for the viral component, and shotgun metagenomic sequencing to complement,
validate and extend our findings. We will apply statistical modeling tools, including those derived from ecology,
to understand the evolution of, interactions within, and determinants of, the microbiota.
We will develop a Center for Research into the Respiratory Microbiota of African Children (ReMAC) which will
build capacity for respiratory microbiota research in Africa, by establishing a sustainable, collaborative network
of African and US investigators, with focus on specialized training, postgraduate study, technology transfer and
career development. Successful completion of the proposed work will enhance our understanding of the
ecology of the nasopharynx and of the pathogenesis of LRTI, promote the development of diagnostic or
prognostic tools for children with LRTI, provide insight into whether therapeutic manipulation of the microbiota
may be desirable and identify modifiable risk factors which negatively influence the composition of the
microbiota.
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