Doctoral Degrees (Epidemiology and Biostatistics)
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Browsing Doctoral Degrees (Epidemiology and Biostatistics) by browse.metadata.advisor "Wiysonge, Charles S."
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- ItemBurden of congenital rubella syndrome and potential impact of rubella vaccine introduction in South Africa(Stellenbosch : Stellenbosch University, 2021-12) Motaze, Nkengafac Villyen; Wiysonge, Charles S.; Suchard, Melinda S.; Metcalf, C. Jessica E.; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Global Health. Epidemiology and Biostatistics.ENGLISH SUMMARY : Background: Introduction of rubella vaccines into public vaccination schedules of all countries is necessary if global rubella elimination is to be achieved. Rubella is targeted for elimination in five World Health Organization (WHO) regions and several international organizations, under the stewardship of the WHO, are working towards this goal. Although there is no rubella elimination or control target for the WHO Africa region, there has been accelerated introduction of rubella vaccination on the continent. South African government is planning to introduce rubella vaccination in its Expanded Programme on Immunization (EPI) schedule and several epidemiological studies have been conducted to aid preparation of this public health intervention. In the absence of vaccination, rubella is mainly a mild endemic childhood viral illness that is asymptomatic in up to 50% of cases. The most severe consequences of rubella occur when infection occurs during pregnancy. These include miscarriages, stillbirths, intra-uterine growth restriction and congenital rubella syndrome. Rubella vaccines are therefore intended to prevent rubella and associated complications. In South Africa, rubella vaccines are not part of the EPI schedule and there is limited information on the epidemiology of rubella and its complications. In addition, the South African government has to cover the cost of introducing rubella vaccination. Therefore, the aim of this research project was to characterize the epidemiology of rubella and congenital rubella syndrome in South Africa, to assess the potential impact of introducing rubella vaccination in the EPI schedule. Methods: Four different studies were carried out as part of this PhD project: a cross-sectional descriptive study, a sero-survey, a mathematical modelling study and a systematic review. Results: The findings of a newly established CRS surveillance system to provide data on disease trends in the absence of rubella vaccination are presented in the first research component. We provided baseline data on laboratory-confirmed CRS that will enable planning and monitoring of RCV implementation in the South African EPI program. Ninety-eight percent of mothers of infants with CRS were young women 14 to 30 years old, indicating a potential immunity gap in this age group for consideration during introduction of RCV. In the second research component, we present results of testing on residual samples collected from public health facilities to identify immunity gaps in various age groups and genders. The bulk of individuals susceptible to rubella are children under sixteen years old and about 20% of individuals 16 to 49 years old are susceptible to rubella. In multivariable logistic regression, age and province of residence were found to be associated with rubella susceptibility.Webuilt on a previously published mathematical model adapted to the South African context in the third research component and provide insights into optimal scenarios for RCV introduction into the South African public immunization schedule. We simulated a number of scenarios that combined infant vaccination with vaccination of older individuals. Routine vaccination at 12 months of age coupled with vaccination of nine-year-old children was associated with the lowest RCV cost per CRS case averted for a similar percentage CRS reduction. Interestingly, at 80% RCV coverage, all vaccine introduction scenarios could achieve rubella and CRS elimination in South Africa.In the final research component, we systematically reviewed mathematical modelling studies to identify the most effective approach for countries introducing RCV into their public immunization schedules. There were variations in the manner in which individual studies reported outcomes. However, we found that better outcomes are obtained when rubella vaccination is introduced into public vaccination schedules at coverage figures of 80%, as recommended by WHO, or higher. Conclusion: The results from these different studies support the implementation of a strategy involving infant vaccination in combination with vaccination of older individuals. Further research projects are required to provide more detail on the burden of CRS and the economic impact of RCV introduction into the EPI schedule.
- ItemTranscutaneous bilirubin screening for hyperbilirubinemia in African newborns(Stellenbosch : Stellenbosch University, 2019-04) Okwundu, Charles I.; Wiysonge, Charles S.; Smith, Johan; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Global Health. Epidemiology and Biostatistics.ENGLISH SUMMARY : Background: In many parts of the world, including African countries, apparently healthy newborns are usually discharged home early. Serum bilirubin levels usually peaks on postnatal days 3 to 5, by when many newborns have already been discharged home. Severe neonatal hyperbilirubinemia constitutes an important cause of neonatal mortality and morbidity in Africa. There is a need for ways of identifying newborns at risk of severe jaundice before hospital discharge especially in developing countries with poor health systems and inadequate follow-up procedures after discharge from hospital. Objectives: The objective of this combination of studies is to provide evidence for the use of transcutaneous bilirubin (TcB) screening in a population of indigenous African newborns. Methods: We summarized the available evidence on the accuracy and effectiveness of TcB screening in two Cochrane systematic reviews. In the first systematic review, we summarized the evidence on the effectiveness of TcB screening in newborns. The second review summarized the evidence on the accuracy of TcB measurement compared to total serum bilirubin (TsB) measurement. We also conducted research on the effects of TcB screening and on the accuracy of the TcB measurement in a population of South African newborns. Results: For our first systematic review, we did not identify any randomized controlled trial that assessed the effect of TcB screening on readmission for jaundice or on the incidence of severe hyperbilirubinemia in newborns. Findings from included observational studies from North America suggest that universal pre-discharge TcB screening in newborns reduces readmission for hyperbilirubinemia and also reduces the incidence of severe hyperbilirubinemia. We conducted a randomized controlled trial of TcB screening in an indigenous population of African newborns from South Africa. Findings from our trial confirmed that TcB screening reliably identified newborns at risk of severe hyperbilirubinemia and led to a 75% reduction in the readmission rate for hyperbilirubinemia and up to 73% decrease in the incidence of severe hyperbilirubinemia. However, the effect of TcB screening on kernicterus and bilirubin induced neurology dysfunction is not known. Findings from our second systematic review of accuracy of TcB measurement compared to TsB measurement in the laboratory, suggest a significant correlation coefficient of up to 0.98 between these two measurements. However, there are mixed findings from the included studies on the effect of various factors including: gestational age, race, postnatal age, TsB concentration, on the correlation. Also, there are limited studies in indigenous African newborns. Our cross-sectional study on the accuracy of the TcB measurement in a population of South African newborns showed a good correlation between TcB measurement and TsB measured in the laboratory. Conclusion: The TcB tool can be used to reliably estimate TsB in African newborns and can help identify newborns who need phototherapy before hospital discharge. We recommend that every newborn should be assessed for hyperbilirubinemia using objective means of measuring or estimating serum bilirubin measurement such as the TcB or TsB before discharge from hospital. This could go a long way in reducing hyperbilirubinemia related readmissions and incidence of severe hyperbilirubinemia. Pre-discharge TcB screening in newborns can therefore be used to identify newborns in need of phototherapy or those who are at risk of readmission for hyperbilirubinemia after discharge.
- ItemUnderstanding the relationship between vaccination, vaccine-preventable diseases, and HIV infection among sub-Saharan African children(Stellenbosch : Stellenbosch University, 2019-04) Adetokunboh, Olatunji Oluseyi; Wiysonge, Charles S.; Uthman, Olalekan A.; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Global Health. Epidemiology and Biostatistics.ENGLISH SUMMARY : Numerous care and treatment guidelines pinpoint vaccination as a crucial preventive strategy for HIV-infected patients, but data regarding these vaccines among children living with HIV are still very scanty. There are knowledge gaps concerning the understanding of the mediators of vaccine protection, adverse effects and fundamental aspects of the epidemiology of various vaccine-preventable diseases. Likewise, there is also limited information on the determinants of vaccine non-uptake within the HIV-infected population, and on the association between maternal HIV status and the vaccination status of her HIV-exposed child. Further synthesis of all available evidence is required to provide reliable and easily accessible information for decision-makers and healthcare workers. We completed evidence synthesis of existing studies and secondary analyses of existing data sets using different research methods such as systematic review, meta-analysis, meta-regression and multivariable logistic regression models. We found that the burden of vaccine-preventable diseases is still high among HIV-infected and HIV-exposed children in sub-Saharan Africa. Several routine vaccines show possibilities for direct and indirect protection against various vaccine-preventable diseases among HIV-infected and HIV-exposed children. However, HIV-infected children are less likely to be protected against vaccine-preventable diseases when compared to non-exposed children. There is no significant difference in the uptake of the full series of three doses of diphtheria-tetanus-pertussis containing vaccines (DTP3) among infants of HIV-infected mothers and those of uninfected mothers in sub-Saharan Africa. Vaccination coverage for both HIV-exposed children and non-exposed children is still sub-optimal. Furthermore, individual and contextual factors such as maternal age, educational level, unemployment, and adult literacy level contributed significantly to non-uptake of DTP3 among the children of HIV-infected women across sub-Saharan Africa. The symptoms of acute respiratory infections show no statistical difference in the overall estimates between the children of HIV-infected mothers who were vaccinated with DTP3 and the ones who were not vaccinated. The data for episodes of diarrhoea were pooled together with resultant nil significant difference in the overall estimates between the children of HIV-infected mothers who were vaccinated with DTP3 and those not vaccinated. Many African countries also recorded high rates of respiratory infections and diarrhoeal diseases among both HIV-exposed and unexposed children. Residency in communities with high unemployment was an independent predictor of acute respiratory infections among immunised and HIV-exposed children while those born to women aged 15-24 or 25-34 years old were significantly more likely to develop diarrhoeal diseases. There is a need to address sub-optimal uptake of vaccines among HIV-exposed and non-exposed children. Epidemiological studies on vaccine-preventable diseases and the development of more efficacious vaccines are required for vaccine-preventable diseases studies with respect to HIV-infected and HIV-exposed uninfected children. The findings of this research would be useful in advocating for a more equitable share of healthcare resources especially for preventive services such as vaccination of both HIV-exposed and non-exposed children with subsequent reduction in the burden of vaccine-preventable diseases.
- ItemUsing quality improvement approach to address missed opportunities for vaccination in Kano Metropolis, Nigeria(Stellenbosch : Stellenbosch University, 2019-12) Adamu, Abdu Abdullahi; Wiysonge, Charles S.; Uthman, Olalekan A.; Gadanya, Muktar A.; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Family and Emergency Medicine. Family Medicine and Primary Care.ENGLISH SUMMARY : Background Strategies to reduce missed opportunities for vaccination (MOV) can potentially increase immunization coverage in health facilities and invariably improve immunization coverage at the district and national level. Yet, there is a dearth of synthesized literature on MOV in Africa, despite being the region with the lowest immunization coverage globally. Furthermore, the use of quality improvement (QI) in health facilities to rapidly address health system problems is growing, but evidence of its use in the immunization sub-system to reduce MOV is scarce. Moreover, it is unclear how the QI approach can be applied in a low resource, low immunization coverage setting like Kano, Nigeria. Therefore in this project, empirical evidence on the burden and dynamics of MOV in Africa was generated as well as the extent to which practitioners in healthcare facilities have used QI to address it. This was followed by the implementation and evaluation of a QI programme to reduce MOV in Nassarawa Local Government Area, Kano State, Nigeria. Methodology A combination of methods including systematic review, scoping review, multilevel modelling, qualitative inquiry, time series, and mixed methods were used. Result The first component of the first phase, a systematic review, revealed that MOV is common among children aged 0 – 23 months who made contact with health facilities in Africa, with a pooled prevalence of 27.26%. However, only 20 MOV assessments from 14 African countries were found. The reasons for MOV were multifactorial and complex because they were interrelated and interdependent. The second component of the first phase, a scoping review, revealed that evidence on the use of QI to reduce MOV and improve immunization coverage in health facilities exists. However, the QI interventions that were found were all implemented in the United States. Plan-do-study-act (PDSA) cycles were the most commonly used models. In these QI programmes, practitioners used multiple change ideas simultaneously. The change ideas were client-related, health worker-related, and cross-cutting health system-related change ideas. The second phase was the pre-implementation period of a QI programme in Kano, Nigeria. The first component of the second phase, a cross sectional study, revealed an MOV prevalence of 36.15% among children aged 0 – 23 months who visited PHC facilities in Nassarawa Local Government Area (LGA) of Kano, Nigeria. MOV was more likely to occur among children who were accompanying a caregiver to the health facility and failure to offer vaccination on the day of clinic visit. In the second component of this phase, a qualitative study based on the lived experiences of caregivers, showed that non-screening of immunization history, refusal to offer vaccination, husband’s refusal and fear of side effects were responsible for MOV. In the third phase, locally relevant change ideas were implemented in five PHC facilities in Nassarawa LGA to address the identified factors. In the first component of the third phase, frontline health workers in these facilities systematically selected and implemented change ideas in two plan-do-study-act (PDSA) cycles that were four weeks apart. Using p-charts, reduction in proportion of MOV per day was seen in two facilities at the sixth week following implementation of the PDSA cycles. Then, an evaluation of the implementation context revealed that several facilitators and barriers influenced the implementation of the QI programme. Conclusion This study confirmed that MOV is a common immunization problem in Kano, like other settings in Africa. A bottom-up QI approach to address MOV, that is led by health workers in facilities, is feasible in this setting. However, rapid assessment of implementation context should be built into the QI process.