Rotavirus vaccine and diarrhoeal morbidity in South Africa
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Date
2016-11-04
Authors
Groome, Michelle Jennifer
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Abstract
Background
Vaccination against rotavirus, the leading cause of diarrhoea in children under 5 years of age,
has the potential to reduce diarrhoeal morbidity and mortality. Lower vaccine efficacy and
immunogenicity were observed in clinical studies of oral rotavirus vaccines in low- and middleincome
countries in Africa compared to high-income countries. The impact of routine vaccine
use in African countries, where almost half of the global rotavirus deaths occur, is yet to be
established. In addition, factors affecting immune responses to the rotavirus vaccine warrant
further investigation.
Objectives
To assess the effectiveness and public health impact of introduction of the monovalent oral
rotavirus vaccine into the national immunisation programme in South Africa, a setting with a
high prevalence of human immunodeficiency virus infection; and to determine the effect of
maternal rotavirus-specific antibodies and abstention from breastfeeding at the time of rotavirus
vaccination on immune responses to the rotavirus vaccine.
Methods
A case-control study was used to estimate vaccine effectiveness in children under 2 years of age,
with comparison of rotavirus vaccination status among rotavirus-positive diarrhoeal cases to
rotavirus-negative and respiratory controls, respectively. The impact of routine rotavirus
vaccination on all-cause diarrhoeal hospitalisations was assessed by comparing the incidence
before and after vaccine introduction among HIV-infected and HIV-uninfected children under 5
years of age. HIV-uninfected mother-infant pairs were randomised to either abstention from
breastfeeding or unrestricted breastfeeding at the time of rotavirus vaccination to assess the
effect of breast milk on the immune response to the vaccine; in addition maternal rotavirus
serum antibodies were measured.
Results
Two doses of rotavirus vaccine provided protection of 57% (95% CI 40–68) against
hospitalisation for acute rotavirus diarrhoea. Protection extended through the first 2 years of life
and the vaccine protected against different rotavirus strains. Routine vaccine introduction was
temporally associated with a 34% to 57% decrease in the overall incidence of all-cause
diarrhoeal hospitalisations in children under 5 years of age during 2010–2014 compared to prevaccination
years (p<0.001).The greatest reductions were observed in children under 12 months
of age. Reductions were maintained for 5 years post-vaccine introduction. Abstention from
breastfeeding for 60 minutes before and after each rotavirus vaccine dose showed no significant
improvement in infant immune responses to the vaccine. However, mothers of infants who
seroconverted after the first vaccine dose had significantly lower anti-rotavirus immunoglobulin
G titres at baseline than those whose infants did not seroconvert.
Conclusion
Rotavirus vaccination was an effective intervention against severe diarrhoea in South African
children, preventing hospitalisations due to rotavirus while also reducing diarrhoeal
hospitalisations for diarrhoea of any cause. These studies add to the growing body of evidence
showing that rotavirus vaccines are reducing diarrhoeal disease in low- and middle-income
countries and should form part of comprehensive diarrhoeal disease control and prevention. A
change in breastfeeding practice at the time of rotavirus vaccination did not improve immune
responses to the vaccine, yet maternal antibodies may play an important role. Continued research
is needed to optimise the protection afforded by currently licenced vaccines and to develop novel
rotavirus vaccines.
Description
A thesis submitted to the Faculty of Health Sciences, University of the Witwatersrand,
Johannesburg, in fulfilment of the requirements for the degree of Doctor of Philosophy.
Johannesburg, 2016