Measuring epidemiology and sero-correlates of protection against severe respiratory syncytial virus (RSV) associated hospitalisation in HIV exposed and unexposed South African children
No Thumbnail Available
Date
2021
Authors
Agosti, Yasmeen Mele
Journal Title
Journal ISSN
Volume Title
Publisher
Abstract
Introduction: RSV is a leading cause of respiratory related hospitalisations in children less
than five years globally. The majority of the morbidity and mortality of RSV disease occurs
in lower and middle income countries. Decades of epidemiological work have demonstrated
that the risk for RSV hospitalisation is highly concentrated in the first six months of life,
when infants’ immune systems are immature and the protective effects of maternally derived
antibody are waning. The South African paediatric population is comprised of a significant
percentage of HIV exposed uninfected (HEU) infants who reportedly have higher risk for
infectious morbidity and mortality.
Methods: This thesis utilized a prospective, inpatient paediatric surveillance program; and a
prospective birth cohort to describe RSV hospitalisations, maternally derived immunity and
explore for a sero-correlate of protection against RSV LRTI hospitalisation among HIV
unexposed and HEU infants.
Results: RSV hospitalisation incidence was 21.4 per 1000 live births among Sowetan infants.
A peak of disease occurred in the first month of life and constituted a large percentage (53%)
of all-cause LRTI hospitalisation during the RSV epidemic period. The majority of
hospitalisations (69%) occurred among infants in their first six months of life. RSV
hospitalisation incidence of HIV unexposed and exposed infants did not differ significantly
(21 vs 20 per 1000 live births, respectively). Most RSV hospitalisation cases were discharged
home, with a low cases fatality risk (0.002). The majority of RSV-associated hospitalisations
received antibiotics (69%). Infants without and with HIV exposure acquired maternally
derived neutralizing RSV antibody via transplacental transfer (HUU 0.82 vs HEU 0.67, padj
0.1222). The cord to maternal blood ratio (CMR) of RSV neutralizing antibody was 0.74. The
CMR was significantly associated with maternal hypergammaglobulinemia. Cord blood titres
demonstrated an inverse relationship between maternally derived neutralising RSV antibody
and risk of RSV hospitalisation in infants up to six months of age. While a definitive
threshold of protection was not identified, it was observed that for every unit rise in log2 titre,
there was a 43% reduction in odds for hospitalisation
Conclusion: RSV hospitalisation among Sowetan infants represents a significant burden of
disease that is highly concentrated within the first six months of life. Maternally derived
neutralising RSV antibody is present in infants at the time of birth, albeit at levels lower than
what has been described in other parts of the world. Maternally derived neutralising RSV
antibody is associated with protection against disease but a definitive correlate of protection
has not yet been identified.
Description
A thesis submitted in fulfilment of the requirements for the degree of Doctor of Philosophy to the Faculty of Health Sciences, School of Physiology, University of the Witwatersrand, Johannesburg, 2021