3. Electronic Theses and Dissertations (ETDs) - All submissions
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Item Rotavirus vaccine and diarrhoeal morbidity in South Africa(2016-11-04) Groome, Michelle JenniferBackground 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.Item The burden of severe acute gastroenteritis and risk factors associated with poor outcome in a cohort of Sowetan children under five years of age(2011-01-26) Groome, Michelle JenniferIntroduction In developing countries, diarrhoea is a major cause of morbidity and mortality among children under five years of age. This study aimed to determine the effect of age and HIV infection status on incidence of acute gastroenteritis and to identify risk factors associated with death and prolonged hospitalisation. Methods A secondary data analysis was performed using an existing cohort of children enrolled on a pneumococcal vaccine efficacy study performed in 1998-2005 in Soweto. Results The incidence rate of acute gastroenteritis requiring hospitalisation was 10.13 (CI95% 9.68, 10.58) per 1000 person years. Incidence was highest in those under six months of age, decreased with increasing age, and was 5.42 times (CI95% 4.89, 6.01) higher in those infected with HIV compared to that in HIV-uninfected children. HIV-infected children were more likely to be malnourished, have severe dehydration and have a concomitant diagnosis of lower respiratory tract infection (LRTI). HIV-infected children were four times more likely to die in hospital (OR 3.99 CI95% 2.04, 7.81) and almost twice as likely to be hospitalized > 2 days (OR 1.81 CI95% 1.38, 2.38) compared to HIV-uninfected children. Presence of malnutrition, severe dehydration and a concomitant diagnosis of LRTI were also significant risk factors for death and prolonged hospitalisation. Conclusions Acute gastroenteritis is an important cause of hospitalisation in children under 2 years, especially among HIV-infected children. Prevention and management of severe dehydration, malnutrition, HIV infection and concomitant LRTI need to be targeted to decrease mortality and shorten the duration of hospitalisation in children admitted with acute gastroenteritis.