MSc(Med)Population Based Field Epidemiology, Faculty of Health Sciences, University of the Witwatersrand, 2009 / Introduction: In Africa, elderly adult mortality, just like many issues affecting the old has not been adequately addressed by research. This study explored the relationship between socioeconomic status (SES) and elderly adult mortality in an economically deprived region of rural Ghana. Methods: Data from the Navrongo DSS was used for the analysis. SES was determined from the asset data using principal component analysis. A total of 15030 adults aged over 60 years were included in the study, out of which 1315 died. We investigated the above relationship using Cox proportional hazards regression methods while controlling for other variables. Results: Socioeconomic status (SES) was found not to be a determinant of elderly mortality. Compared to the lowest SES quintile, the adjusted hazards ratios were, 0.94 (95%CI: 0.79–1.12) for second quintile, 0.91 (95%CI: 0.76–1.08) for third quintile, 0.89 (95%CI: 0.75–1.07) for fourth quintile and 1.02 (95%CI: 0.86–1.21) for the highest income quintile. However, living without a spouse [HR=1.98, 95%CI: 1.74–2.25], being male [HR=1.80, 95%CI: 1.59–2.04] and age [HR=1.05, 95%CI: 1.04– 1.05] were significant factors for elderly adult mortality. Conclusion: These results indicate that companionship, social and family ties in the health of the elderly adults are of more importance than the socioeconomic status of the household. Efforts should therefore be made to support the elderly, such as stipend for the elderly adults, especially those living alone; lowering the provision of free medical care in public hospitals to cover people over the age of 60 and not just 70 year olds and above as is currently done; encourage family care for the elderly relatives through provision of an elderly caretaker allowance among others.

MSc (Med) , Epidemiology and Biostatistics, Faculty of Health Sciences, University of the Witwatersrand, 2009

Globally, child mortality is a great concern, especially in resource-limited settings. The Millennium Development Goal (MDG) 4 was set with an aim to reduce under-5 child mortality by two-thirds between 1990 and 2015. This study examines mortality trends in infants, 1-4 and above 5-year-old children in rural KwaZulu-Natal, South Africa, the causes of death as well as the association of maternal HIV status and Antiretroviral Treatment (ART) usage to child mortality. We use a longitudinal birth cohort study design of children born between 1st January 2004 and 31st December 2010, in the Africa Centre Demographic Surveillance Area (DSA) in rural KwaZulu-Natal, South Africa. Children had to have been resident in the DSA at the time of birth. A total of 12,413 children born in the study period were eligible for this study. The main outcome measure was mortality either in infancy, the 1-4 year period or at 5 and above years of age, while assessing its association with maternal HIV and Antiretroviral Treatment uptake (ART) status on a time-varying basis. A total of 619 children died during the study period and mortality was observed to be highest in the infant group with 67% of the children dying in infancy. Fifteen percent of mothers were HIV positive at the time of birth of the child, about 59% were HIV negative while the HIV status of the rest was unknown. There was a three-fold increase in mortality observed for both infants and 1-4 year olds, who had mothers who were HIV infected compared to children whose mothers were HIV negative (p<0.05). Children whose mothers were on Antiretroviral Treatment (ART) however had a reduced mortality compared to those whose mothers were not on treatment. Infants and 1-4year olds whose mothers HIV status was not reported had a two-fold increase in mortality. Low maternal education, single motherhood, multiple births and parity of four or more children were also associated with increased child mortality. We concluded that although mortality varied by the age of the child, children born to mothers who were HIV positive had higher mortality rates than children born to HIV negative mothers but being on Anti Retroviral Treatment (ART) reduced children mortality. Interventions targeting HIV positive pregnant women and mothers should be carried out in the study area, with specific emphasis on reducing child mortality associated with maternal HIV status.

A Research Report Submitted to the School of Public Health, University of the Witwatersrand, Johannesburg, in Partial Fulfilment of the Requirements for the Degree of Master of Science in Medicine in the Field of Epidemiology and Biostatistics: March 25, 2013 / Background: More than 33 million people are estimated to be living with HIV worldwide. Sub-Saharan Africa bears a disproportionate share of the global HIV burden. An estimated 15 million people living with HIV in low and middle income countries were in need of (HAART) in December 2009. HAART services require advanced laboratory technologies to monitor disease progression and therapeutic response, which are scarce in developing countries. Several simple and widely available markers have been proposed for use in low income countries including total lymphocyte count (TLC), haemoglobin and body mass index. Methodology: This study is a secondary data analysis of prospectively collected cohort data from HIV positive adults. The study measured the effect of exposure variables of haemoglobin (Hb) and body mass index (BMI). All cause mortality was the outcome of interest. Crude estimates of mortality were made with Kaplan-Meier mortality curves. Cox proportional hazards models were used to estimate adjusted hazard ratios. Exposure status was considered at initiation period. Outcomes were measured from two weeks post initiation of treatment to a maximum of two years of follow-up period. A composite score was developed to estimate the overall risk of mortality. Results: A total of 11,884 patients who satisfied the inclusion criteria were included in the analysis. A total of 1,305 deaths were observed during the follow-up period, representing 10.2% of the cohort at baseline. Most of the deaths were observed during the first four months of follow-up period. Patients with moderated to severe anaemia experienced 2.6 (HR = 2.6, 95% CI 1.8 - 3.6) times greater hazard of mortality adjusted for possible confounders. Patients with very iv low BMI experienced twice (HR=2.0, 95% CI 1.6, -2.5) greater hazard of mortality adjusted for a list of predictors. Race, age at initiation, employment status, smoking, alcohol consumption, baseline TB and baseline WHO stage did not show significant effect in the multivariate cox regression model. A composite score was developed to estimate the overall risk of mortality in patients based on measurements of baseline BMI and haemoglobin. Cox regression model adjusted for CD4 cell count shows high risk patients experienced 4.7 (HR = 4.7, 95% CI 2.9 – 7.6) times greater hazard of mortality compared to patients in the low risk group. Patients in the medium risk group experienced 3.4 (HR = 2.6, 95% CI 2.6 – 4.4) times greater hazard of mortality as opposed to patients in the low risk group. Conclusion: Haemoglobin and body mass index provide excellent prognostic information independent of CD4 cell count in HIV positive patients newly initiated on HAART. They can be used to reliably predict mortality. Combining measurements of haemoglobin and BMI through composite scoring improves their predictive ability. They can have good clinical application in rural and remote facilities to screen patients for clinical and diagnostic services.

A research report submitted to the Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, in partial fulfillment of the requirements for the degree of Master of Science in Epidemiology (Epidemiology and Biostatistics). 2016 / Background Reducing severe acute respiratory illness (SARI)-associated mortality in African children remains a public health priority and an immense challenge. The pneumococcal conjugate vaccine (PCV) was introduced into the South African routine immunization programme in 2009. The objectives of this study were: I. To describe the demographic characteristics, clinical presentation, respiratory pathogens of children aged <5 years hospitalized with SARI in an urban (Chris Hani-Baragwanath Hospital, Soweto) and a rural (Matikwana and Mapuleng Hospitals, Mpumalanga) setting in South Africa from 2009-2013 and II. To compare the factors associated with mortality among children aged <5 years hospitalized with SARI in these two sites separately. Methods Hospitalized children with SARI were enrolled into an active, prospective sentinel surveillance program. Clinical and epidemiologic data were collected until discharge. Nasopharyngeal aspirates were tested for influenza (A and B) and eight other respiratory viruses. In-hospital case-fatality proportion (CFP) and risk factors for mortality were determined for each hospital site separately using unconditional logistic regression. Results The in-hospital CFP was significantly higher in the rural (6.9%, 103/1486) than the urban (1.3%, 51/3811) site (p<0.001). This was observed among both HIV-infected (urban: 6.6%, 17/257) vs. (rural: 12.9%, 30/233) (p=0.019) and HIV-uninfected children (urban: 0.6%, 13/2236) vs. (rural: 4.2% 36/857) (p<0.001). In the urban site the only factor that is independently associated with death on multivariate analysis was HIV infection (odds ratio (OR) 12.1, 95% confidence interval (CI) 5.8-25.2). In the rural site HIV infection (OR 3.5, 95% CI 1.7-6.9), age <1 year (OR 3.5, 95% CI 2.0-6.1) vs. 1-4 years, any respiratory virus detected (OR 0.4, 95% CI 0.2-0.6), pneumococcal infection(OR 4.5, 95% CI 1.8-10.8) and malnutrition (OR 12.8, 95%CI 1.2-134.6) were independently associated with mortality. Conclusion SARI mortality was higher in the rural setting. Even in the era of PCV availability pneumococcus is still associated with mortality in rural areas. Efforts to prevent and treat HIV infections in children and reduce malnutrition may reduce SARI deaths. / MT2017

The effect of anti-retroviral therapy (ART) rollout can be measured in a number of ways including treatment coverage, behaviour change and the emergence of resistance. However, changes in population mortality are undoubtedly the most important measurable effect. Objectives: To describe trends in child and adult all-cause mortality versus HIV/AIDS related mortality before and after ART rollout; and to identify significant clusters of child and adult all-cause mortality versus HIV/AIDS related mortality in space-time, during pre and post ART rollout eras at Agincourt and Dikgale health and demographic surveillance systems (HDSSs) in South Africa. Design: Mortality data were extracted from both the Agincourt and Dikgale HDSSs for the period 1996–2010. Mortality rates by age group, year and village were calculated assuming a Poisson distribution and using precise person-years as the denominator. The Kulldorff spatial scan statistic was used to test for clusters of age group all-cause and HIV-related mortality both in space and time. Clusters were mapped using Quantum geographic information systems (GIS) software. Results: Both HIV-related and all-cause mortality decreased gradually over the years after the introduction of ART in 2007 for the two HDSS sites. Several statistically significant clusters of higher all-cause and HIV-related mortality were identified both in space and time. In the Agincourt HDSS, specific areas were consistently identified as high risk areas; namely, the east/south-east corner and upper central to west regions, pre ART. In the Dikgale HDSS, no significant clusters were identified using the spatial only analysis but one significant cluster, located towards the north of the Dikgale HDSS site, was identified using the space-time scanning, post ART. In Agincourt, no significant clusters of mortality were detected after the introduction of ART whereas in Dikgale, a significant cluster for all-cause mortality in the under-five age group was detected for the years after the introduction of ART. Conclusion: This work revealed the existence of spatio-temporal clusters of both child and adult mortality at the Agincourt and Dikgale HDSSs and that the introduction of ART had a substantial influence in reducing both HIV-related and all-cause mortality in rural South Africa. There is need though to take into account socio-demographic characteristics so as to determine fundamental risk factors influencing these spatio-temporal HIV-related and all-cause mortality patterns.

Ph.D., Faculty of Science, University of the Witwatersrand, 2011 / 1 Investigating the life history strategy of an African savanna tree, Sclerocarya birrea subsp. caffra (marula) Chantal Vinisia Helm Abstract Lack of understanding of the life history attributes and responses of savanna woody plants to disturbances, as well as the observation of unstable population structures in a keystone, savanna tree, Sclerocarya birrea subsp. caffra (marula), prompted this study. This study employed a combination of empirical, experimental and model formulation techniques, aimed at achieving its ultimate purpose of understanding the life history strategy of marula in the face of disturbance. Four main population structures were identified for marula in the low altitude savannas of South Africa: 1) adult dominated, 2) juvenile dominated, 3) with a “missing size class” and 4) stable (negative J-shaped). Spatial variability in structure indicated different drivers affecting different populations. High annual mortality rates of up to 4.6% in adult trees, no recruitment out of the fire trap and little regeneration were observed in the Kruger National Park (KNP) between 2001 and 2010, and consequently even greater instability in the structure of these populations already observed earlier in the decade. Growth rates of saplings between 2 and 8 m in height and 2 and 30 cm in stem diameter in the field were monitored between 2007 and 2010. Annual growth rates of up to 11 mm in diameter and up to 22 cm in height were observed. Annual relative growth rates ranged between 1.9 and 4.8% across sites. Growth rates were positively linked with rainfall and plant size. Growth rates, biomass allocation patterns, as well as storage and defence allocation in 3 to 28 month old marula seedlings were assessed under glasshouse conditions. Relative growth rates were highest directly after germination (20%), but did not exceed 5% thereafter. Allocation to roots (already 65% of the overall biomass at 3 months of age and >80% when older) was high regardless of soil type or provenance. Provenance affected height gain, and plants germinating from seeds collected at higher rainfall sites had faster height growth rates than those from seeds collected at lower 2 rainfall sites. Allocation to storage in the form of root starch peaked at 35%, while allocation to defence in the form of phenolics in the leaves peaked at 18%, being relatively higher than other species. No trade-off between growth and defence allocation was observed. However, in the second growing season, growth at the start coincided with a 50% decrease in starch reserves in the roots. Reproductive maturity was found to occur after 46 years and escape from the fire trap after 12 years in a disturbance free environment. Marula trees appear to be able to live for up to 300 years of age. High temporal variability in fruit production was observed, marginally linked to rainfall. Only 2% of seeds persisted for more than one year, and hence marula relied mostly on the current season’s fruit crop for input of new germinants. Fruit production was highly synchronous across trees at a site. Very high levels of seed predation were observed. Marula seeds can remain dormant for at least 10 years when stored in the laboratory. Germination takes place after 3 mm of rainfall every four days for two weeks and is enhanced by acid digestion and high temperatures. Germination percentages are relatively low (<50% of the endocarps). Marula seedlings appear highly adapted to fire, with high allocation to below-ground biomass and starch storage, as well as very thick bark from very small stem diameters, including a well developed resprouting response from very young. Marula stems were able to resist fire from 3.4 cm in stem diameter, and were completely resistant above 7 cm. Stem diameter growth was prioritised above stem height growth, indicating that in marula, diameter gain is more important than height gain in escaping the fire trap. Topkilled marula saplings are able to regain their prefire height within one season. However, rainfall patterns may have an overriding effect on these growth patterns. Adult trees appear to be made vulnerable to fire through bark stripping, toppling and pollarding and the subsequent invasion of the soft wood by borers. On nutrient-poor granite soils, marula has a resistant strategy to herbivory, however on nutrient-rich basalt soils, marula overcompensates for herbivory even at very low levels. This may explain why marulas are more vulnerable on basalt soils in the KNP, having 3 already been extirpated from the northern arid basaltic plains. Marula seedlings are extremely drought resistant through fast root penetration rates and high root: shoot ratios. A simple demographic model was developed which predicted that marula populations are unlikely to survive given the current elephant impact in the KNP and if the fire interval is less than once every seven years. Even though marula is highly resilient to damage from herbivory or fire alone, the combination of frequent fire and heavy utilisation is proving fatal for marula populations in the KNP and elsewhere. In terms of other savanna tree species, marula is an outlier in its life history strategy, being extremely well adapted to the effects of fire with very thick bark, extensive resprouting ability and fast growth rates, combined with very high allocation to root mass, and levels of storage and chemical defence, as well as having very drought tolerant seedlings. Its main weakness as an adult, appears to be its soft wood, which is susceptible to wood borer attack. The perplexing lack of recruitment at some sites in spite of the extraordinary ability of marula seedlings to resprout from an early age, withstand extensive drought, have fast root penetration rates, extremely high root reserve storage and resistance to fire at small stem diameters, combined with high levels of fruit production and low water requirements for germination, is probably due to a combination of the lack of a dense persistent seed bank, high inter-annual variability in fruit production, low germination percentages, high seed and /or seedling predation rates and possibly dispersal of seeds away from suitable habitats. Overall, the unstable population structures observed in the low altitude savannas of South Africa, specifically in the KNP, do not bode well for the future persistence of marula as a dominant canopy tree species. Keywords: elephant, fire, growth, mortality, recruitment, regeneration

Faculty of Health School of Medicine 9101327d swadee@xsinet.co.za / Little is known about the epidemiological and mortality patterns of systemic lupus erythematosus (SLE) in Africa. Aims of this study- to determine the demographics, clinical features and causes and predictors death in patients attending the Lupus clinic at the Chris Hani Baragwanath hospital in Soweto. Methods- the records of 226 patients who fulfilled American College of Rheumatism criteria for the diagnosis of SLE were reviewed. The mean (± SD) age at presentation was 34 (± 12.5) years. The female to male ratio was 18:1. The commonest clinical feature found was arthritis in 70.4% of patients. Nephritis was present in 43.8% and CNS lupus in 15.9% of patients. 55 patients in this group had died and 64 were lost to follow up. The 5-year survival was 57% uncensored and 72% if censored for loss to follow up. Infection (32.7%) was the commonest cause of death followed by renal failure (16.4%). Nephritis, CNS lupus and hypocomplementaemia were associated with mortality on univariate analysis. Lupus nephritis was the only independant predictor of mortality on multivariate analysis. Conclusion- this study confirms the poor outcome of SLE in the developing world and demonstrates that renal disease is a factor commonly implicated in mortality. The 5-year survival and pattern of mortality is similar to that reported elsewhere in the developing world

MSc (Med) (Population-Based Field Epidemiology), Faculty of Health Sciences, University of the Witwatersrand / Introduction: Studies of factors affecting infant mortality have rarely considered the role of birth order. Despite the recent gains in child mortality in Tanzania, infant mortality rate is still high (68 per 1000 live births) according to the Tanzania Demographic Health Survey (2004-5). This study investigated the risk factors associated with infant mortality in Ifakara Health and Demographic Surveillance Systems area in rural Tanzania from January 2005 to December 2007 with specific reference to birth order, and identified causes of infant death for the study period. Materials and Methods: The study was a secondary analysis of existing data from the Ifakara Health and Demographic Surveillance Systems (HDSS). Child data for 8916 live births born from 1st January 2005 to 31st December 2007 were extracted for analysis. The binary outcome variable was infant mortality. Tables and graphs were used to describe the distribution of maternal demographic and study population characteristics. Poisson regression analyses were used to establish the association between infant mortality and exposure variables. Results: We recorded 562 infant deaths. Neonatal mortality rate was 38 per 1000 person-years while infant mortality rate was 70 per 1000 person-years. Birth order of 2nd to 5th was associated significantly with 22% reduced risk of infant mortality (IRR=0.78, 95%CI: 0.64, 0.96; p=0.02) compared with first births. The infant mortality rates per 1000 person-years for first births was 84, 2nd to 5th was 66 and sixth and higher was 71 per 1000 person-years. Male infants were 17% more at risk of infant deaths as compared to their female counterparts, but not statistically significant (IRR=1.17, 95%CI: 0.99, 1.38; p=0.06). Mothers aged 20 to 34 years had 19% reduced risk of infant death (IRR=0.81, 95%CI: 0.65, 1.00; p=0.05) as compared v to mother of less than 20 years of age. Singleton births had 71% reduced risk of infant mortality (IRR=0.29, 95%CI: 0.22, 0.37; p<0.001) compared with twin births. Mothers who did not attend antenatal care had 2% reduced risk of infant deaths (IRR=0.98, 95%CI: 0.49, 1.97) but not statistically significant compared with mothers who attended antenatal care. Mothers who delivered at home were 1.05 times more at risk of infant deaths but not statistically significant (IRR=1.05, 95%CI: 0.89, 1.24; p=0.56). Mothers who had no formal education were 1.41 times more likely to have infant deaths (IRR=1.41, 95%CI: 0.72, 2.79; p=0.32) as compared to those who had education beyond primary. When adjusted for sex, maternal age and twin births, second to fifth birth order had 20% reduced risk of infant death (IRR=0.80, 95%CI: 0.61, 1.03; p=0.08), but statistically not significant as compared to first births. Malaria (30%), Birth injury/asphyxia (16%), Pneumonia (10%), Premature and/or low birth weight (8%), Anaemia (3%) and Diarrhoeal diseases (2%) were the major causes of infant deaths from 2005 to 2007. Discussion and conclusion: First births and higher birth orders were associated with higher infant mortality. Twin birth was a risk factor for infant mortality. The health systems should be strengthened in providing care for mothers and child survival. We recommend that the high-risk group, first or sixth or higher pregnancies, need special care and the existing health management system may be strengthened to create awareness among potential mothers for seeking appropriate health care from the beginning of pregnancy. Also, antenatal care follow-up can be emphasized for high-risk mothers. Efforts to control mosquitoes must be accelerated in the Ifakara sub-district.

A research report submitted to the Faculty of Health Sciences, University of the Witwatersrand, in partial fulfilment of the requirements for the degree of Master of Public Health Johannesburg, May 2015 / Worldwide, an estimated 800 women die each day from preventable causes related to pregnancy and childbirth, the majority in low-and middle-income countries (WHO, 2014:1). The Safe Motherhood Initiative (SMI) aims to achieve safe pregnancies and childbirth, but maternal mortality remains a significant problem in Botswana. Aim and Objectives: The aim of this study was to analyse the implementation process of the SMI policy in Botswana, with specific reference to the training component. The specific objectives of the study were to: describe the context of policy implementation; analyse the content of the SMI policy guidelines; describe the process of implementation of the 2005 SMI policy guidelines; describe the key policy actors, their roles and their influence on the implementation of the policy; and describe the factors influencing the implementation of the SMI policy in Botswana. Methods: The study used a contemporary health policy analysis framework. During 2008, key informants were selected purposively in the southern health region of Botswana. Following informed consent, 12 in-depth interviews were conducted with key informants to obtain their views and perceptions of the content, context, process and the actors of the SMI policy implementation process. The data were analysed using thematic content analysis. Results: The study found that there was high level government commitment, with the SMI driven by the Ministry of Health. Key successes of the SMI policy included: the integration of the Prevention of Mother-to-Child Transmission (PMTCT) of HIV component into the SMI policy, the integration of SMI into the midwifery curriculum and the development, standardisation and distribution of reference manuals or protocols. However, legislative and health system barriers, as well as unsustainable funding, insufficient consultation with and support by stakeholders, and inadequate coordination of the policy process hindered the successful implementation of the SMI policy. Conclusion: The findings draw attention to the value of stakeholder involvement in policy formulation and implementation; the importance of addressing policy implementation barriers and resource availability; and the need for effective coordination and communication.