Thesis (M.Sc. Med.) (Epidemiology and Biostatistics))--University of the Witwatersrand, Faculty of Health Sciences, 2014. / Introduction Ano-genital warts affect at least 30 million people worldwide. Ano-genital warts are caused by low risk Human Papilloma virus infections in 90% of cases. In African populations the ano-genital warts have not been adequately investigated thus our main goal was to highlight the factors associated with the occurrence of ano-genital warts among HIV infected individuals. Studies in both men and women have shown that the likelihood of getting anogenital warts is significantly increased when one is infected with HIV hence the need to investigate in this population. More over data suggests that HPV infection occur more frequently among HIV infected individuals because of the HIV associated CD4+ T-cell immune-suppression. Methods We conducted an analytical cross sectional study of routinely collected secondary medical data from Ward 21 ART clinic at the Hillbrow community centre in Hillbrow Johannesburg central. Our study participants were all HIV infected patients 16 years and older who attended the ART clinic between 01 January 2009 and 31 December 2011 and were recorded in the therapy edge database. Our outcome was clinically diagnosed ano-genital warts. We analysed data using the Chi squared test or Fischers exact test to make comparisons in bivariate analysis. Logistic regression was used to assess factors associated with ano-genital warts. Factors assessed were other STIs namely syphilis, herpes simplex virus type 2 and scabies as well as age, gender, first CD4 and employment status and ART status of a patient. The Models were assessed using the linktest and the Hosmer Lemeshow goodness of fit test. Results Ano-genital warts (AGWs) prevalence was 4% (251 out of 6634) among females and 3% (118 out 4116) among males. Prevalence of AGWs in both females and males decreased with increasing age. In females the prevalence was between 1% and 8% and in males it was between 1% and 4%. The odds of having ano-genital warts among females if one was above 25 years ranged from 1.6 to 18.3, showing an upward trend. Among females a CD4 count of less than 200 cells/ml3 was also associated with ano-genital warts occurrence, OR 1.32(1.02 - 1.72). Among males the odds of having ano-genital warts if one was not on ART were 1.53 (1.01 – 2.31) times when compared to those who were on ART. Discussion and Conclusion Prevalence of genital warts was highest among the younger age groups in both males and females and it decreased with increasing age consistent with literature. Age was strongly associated with ano-genital warts and the association became stronger with increasing age among females while no association was found among males. In line with findings from other studies we found low CD4 count of ≤ 200 cells/m3 to be associated with ano-genital warts in HIV positive females; however it was a weak association. Among males a weak association between ART status and ano-genital warts was established and none in females. This is consistent with the fact that in the post ART era there has been no substantial decline in HPV infections.

A research report submitted to the Faculty of Health Sciences, University of the Witwatersrand, in partial fulfillment for the degree Masters of Medicine in Paediatrics (MMed) Johannesburg 2014 / Introduction Mycobacterium tuberculosis meningitis (TBM) is a severe manifestation of extra-pulmonary tuberculosis (EPTB) in children, particularly under 5 years of age. Children are vulnerable to EPTB as they are immunologically immature and unable to contain Mycobacterium tuberculosis (MTB) infection in the lung. Common neurological sequelae of TBM include focal motor deficits, vision loss and hydrocephalus. Early stage diagnosis and timeous anti-tuberculosis treatment decreases the case fatality rate of TBM. Objective To characterise the burden, clinical presentation, laboratory markers and short-term outcome of TBM in HIV-infected and HIV-uninfected children. Methods The electronic databases of admission of children at Chris Hani Baragwanath Academic Hospital (CHBAH), between January 2006 and December 2011 with a diagnosis of TBM were reviewed. Individual patient records were retrospectively reviewed for clinical and laboratory data. In addition, admissions from the neurosurgery wards were also reviewed. In patients whose medical records were unavailable, laboratory data was used. Results The overall incidence of TBM in 2006 was 6.96 per 100 000 (95% Confidence Interval [95%CI]: 4.46-10.36), peaked at 9.87 per 100 000 (95% CI: 6.91-13.67) in 2009 and subsequently declined to 3.18 per 100 000 by 2011 (95% CI: 1.64-5.56). There was a 38.6% (95% CI: 10.0-58.0; p=0.011) reduction in the overall incidence of TBM when comparing the period 2006-2009 with the period 2010-2011. This decline was particularly evident in HIV-infected children (49.6% reduction; 95%CI: 1.05-74.35; p=0.042). There were no differences in the clinical symptoms of TBM or tuberculosis between HIV-infected and -uninfected children. Previous history of TB was significantly higher in HIV-infected children compared to HIV-uninfected children (OR 4.63; 1.40-15.22; p=0.011). Tuberculin skin test positive-reactivity (OR 0.09; 0.02-0.43; p=0.002) and sputum culture positivity (OR 0.29; 0.10-0.86; p=0.025) were less common in HIV-infected compared to -uninfected children. Cerebrospinal fluid cytology and biochemistry results were similar between HIV-infected compared to -uninfected children. Morbidity (22.7% in HIV-infected vs. 33.0% in -uninfected) and mortality (6.4% in HIV-infected vs. 6.9% in -uninfected) were similar between HIV-infected and -uninfected children. Conclusion The incidence of TBM has decreased over the study period 2006 to 2011.This decrease was temporally associated with an increase in the uptake of antiretroviral treatment in HIV-infected individuals.

A research report submitted to the Faculty of Health Sciences, School of Public Health, University of the Witwatersrand, Johannesburg In partial fulfillment for the requirement for the degree Master of Public Health 25 August 2014 / BACKGROUND Tuberculosis is the leading opportunistic infection among HIV-infected adults, including pregnant women, globally. Accurate screening tools are needed to identify those requiring further laboratory testing and to initiate isoniazid preventive therapy in a timely manner. This study determined the accuracy of symptom-based screening and in particular the performance of the WHO recommended TB symptom screening algorithm in HIV-infected pregnant women. METHODS A cross-sectional study was conducted among consenting HIV-infected pregnant women attending routine antenatal clinics in Matlosana, South Africa recruited >1 week after first HIV diagnosis between June 2010 and February 2011. Sputum was collected from all women followed by a systematic TB symptom screen. The performances of each symptom (cough, fever, weight loss and night sweats) alone and in combination were assessed with TB confirmed by sputa using microscopy and liquid culture (MGIT), as reference or gold standard. The sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio and negative likelihood ratio were calculated for each of the four symptoms (cough, fever, weight loss and night sweats) and their combination. Logistic regression was carried out to find associations between patient characteristics and TB. RESULTS Overall, Mycobacteria Growth Indicator Tube (MGIT) confirmed prevalence of TB was 2.4% (35/1456) in this sample group. Only 11/38 (29%) women with confirmed TB reported any symptoms. Cough, fever, weight-loss and night sweats, individually and in combination had sensitivities ranging from 2.7-27% and specificities ranging from 84-97%. The positive predictive and negative predictive values for any symptoms of cough, fever, night sweats, or weight loss were 4.2% and 98%, respectively. TB was associated with decreasing CD4 count, close TB contact, cough, and night sweats. DISCUSSION The remarkable number of asymptomatic TB in HIV-infected patients, including in the cohort included in this study highlights the limitation of symptom-based screening. The low sensitivity of the symptom screen would incorrectly stratify patients who are being considered for Isoniazid Preventive Therapy (IPT). However, one could argue that the high negative predictive value of the symptom screen would justify its use in resource-limited settings as the initial step in identifying patients who should receive IPT. Although household TB and the father of the baby having TB were found not to have statistically significant associations with active TB, they are of public health importance as they play a role in the spread of the infection. CONCLUSION The WHO 4-symptom screen had low sensitive among HIV-infected pregnant women but negative predictive value was high. Few women with TB disease reported symptoms on direct questioning; the high rate of subclinical/ asymptomatic TB is concerning. There is an urgent need for more sensitive screening tools for TB in HIV-infected pregnant women

ABSTRACT Introduction South Africa is estimated to have the largest number of HIV infected adults in Southern Africa with a higher HIV prevalence in females compared to males. While significant reductions in morbidity and mortality due to HIV and AIDS have been realized for over a decade internationally, HIV treatment involving highly active antiretroviral therapy (HAART) is still a relatively new phenomenon in this country and gender differences in HIV outcomes between males and females in South Africa have not been previously well described. This study aimed to determine and describe gender differences in clinical and immunological outcomes in a population of HIV infected South African adults initiated on HAART. Materials and Methods This retrospective data analysis reviewed 6,617 HIV-infected adultsABSTRACT Introduction South Africa is estimated to have the largest number of HIV infected adults in Southern Africa with a higher HIV prevalence in females compared to males. While significant reductions in morbidity and mortality due to HIV and AIDS have been realized for over a decade internationally, HIV treatment involving highly active antiretroviral therapy (HAART) is still a relatively new phenomenon in this country and gender differences in HIV outcomes between males and females in South Africa have not been previously well described. This study aimed to determine and describe gender differences in clinical and immunological outcomes in a population of HIV infected South African adults initiated on HAART. Materials and Methods This retrospective data analysis reviewed 6,617 HIV-infected adults initiated on HAART at the Themba Lethu Clinic, an urban public-sector antiretroviral rollout facility in Johannesburg, South Africa between 1st April 2004 and 31st March 2007. Clinical data from these antiretroviral naïve patients was analysed for gender differences in mortality, rates of loss to follow up, CD4 cell count response, virologic suppression and weight gain. Cox regression models and logistic regression models were used to estimate hazard ratios (HR) and odds ratios (OR), respectively, for associations between gender and outcomes. Models were adjusted for age and baseline CD4 count. Results At baseline, 4,388 (66.3%) women were significantly younger (p<0.0001) and less likely to be employed than the 2,229 (33.7%) men (p<0.001). Furthermore, women had significantly higher baseline CD4 counts (p<0.0001) and higher body mass index (BMI) (p<0.0001). Males experienced significantly reduced survival compared to females (p=0.0053) by Kaplan-Meier analysis. In adjusted multivariate analysis, men were 22% more likely to die or become lost to follow up than women [HR = 1.22 (95% CI 1.06 - 1.39]. The period with the highest risk of mortality or loss to follow up was within six months of starting HAART. Female gender was associated with better CD4 count response. In multivariate analysis adjusted for age and baseline CD4 count, women were 35% more likely to achieve a 100 cell increase in CD4 count at four months after initiation of HAART [OR =1.35 (95% CI = 1.19 -1.54)] and 45% more likely to increase their CD4 counts by 100 cells/mm3 after ten months on HAART [OR =1.42 (95% CI = 1.20 -1.68)] when compared to men. Women were also more likely to achieve virologic suppression at ten months post HAART initiation [OR =1.54 (95% CI =1.21-1.97)] and were more likely to have gained weight after four months on treatment than males [OR = 1.26 (95% CI = 1.07–1.49)] after adjusting for age, baseline CD4 count and baseline BMI. Conclusions Women had significant advantages over men in terms of short-term clinical and immunological outcomes. Earlier access treatment for men should be facilitated and adherence should be promoted once on treatment. Further research is required to determine if these gender differences persist during long-term HAART.

A dissertation submitted to the Faculty of Medicine, University of the Witwatersrand, in partial fulfilment of the requirements for the degree Master of Medicine (Virology) / This study was undertaken to determine the role of human parvovlrus B19 (B19) in chronic anaemia of HIV infected TB patients. Patlents were selected from an existing databank of 307 patients included in a MRC HIV/TB study. Twenty-nine patients, 15 colnfected with HIV /TB and 14 Infected with TB only, were identified for further evaluation. These patient's era were subjected to serological and DNA detection studies using IgG and IgM ELISA methods and a nested polymerase chain reaction (PCR) assay. The selection of the nested PCR was based on comparative evaluation of a new rapid 99 cycle PCR method recommended for hepatitis B DNA detection and the nested PCR method established for B19. The nested assay was shown to be the more sensitive system in the context of B19 DNA detection. Serological evaluation of these 29 patients suggested that a greater proportion of HIV/TB patients with chronic anaemia had evidence of recent or past exposure to B19 than those not experiencing anaemia. The nested PCR demonstrated the presence of circulating B19 DNA in 2 coinfected individuals with haematological pictures compatible with persistent B19 infection. B19 DNA was also demonstrated in a TB only patient without anaemia; further haematological and serological evidence in this patient suggested recent exposure to B19. The serological and DNA amplification assay results of these 29 patients would suggest a possible role - either causal or co-factorial - for persistent B19 infection in the establishment of chronic anaemia in HIV/TB patients. / Andrew Chakane 2019

Introduction: Cystic lymphoid hyperplasia (CLH) is a common yet under recognised entity affecting the parotid gland in HIV infected patients. This is the largest global clinicopathological study of CLH to date consisting of 167 cases (85M, 82F). Aim: To define the clinical parameters, histology and immunopathological features of CLH with a view to elucidating the aetio-pathogenesis. Material and Methods: This retrospective study on archival cases of CLH included patient’s age, race, gender, nature of CLH, HIV status, CD4 counts and viral loads where available. Of the 167 confirmed cases of CLH, 109 cases were histologically reviewed and 25 cases were immunohistochemically analysed with CD3, CD20, CD4, CD8 and p24 using standard procedures. Ethics clearance (M080927 and M080850) was obtained. Results: CLH mainly affects the parotid gland with a male predominance. Submandibular gland (p = 0.27) and bilateral parotid involvement favours females (2:1). CLH affects females at a younger mean age in both the parotid and submandibular glands (36.5, 31 years) respectively compared to males (40.9, 42.4 years) (p = 0.0032). Intra-lymph nodal origin is favoured with 76.1% of cases occurring within entrapped salivary gland remnants. P24 staining reveals ~90% specificity in HIV associated CLH. Immunostaining showed a CD8:CD4 of ~1:1 except in selected cases where CD4 was decreased in the interfollicular areas. Conclusion: CLH is the preferred term to describe bilateral parotid enlargement in HIV infected patients. This study strongly supports origin of CLH following ductal ectasia of entrapped salivary gland inclusions within atypical lymphoid hyperplasia arising within lymph nodes in the context of an HIV setting. CLH should be classified as an orofacial lesion strongly associated with HIV and AIDS.

A research report submitted to the Faculty of Health Sciences, University of the Witwatersrand, Johannesburg in partial fulfilment of the requirements for the degree of Master of Science Physiotherapy. Johannesburg, 2014 / HIV is a global epidemic with the majority of people infected living in Sub-Saharan Africa. The era of Highly-Active Antiretroviral Therapy has resulted in HIV infected children living longer lives and more commonly reaching school going age. These children are expected to participate at the same level as their peers despite the numerous effects that HIV and HAART have on the body. The aim of this cross sectional comparative study was to compare the exercise endurance of a group of HIV infected children to that of their uninfected peers. Sixty children aged between seven and ten years were enrolled in the study; 30 HIV infected children and 30 children not infected with HIV. Children were assessed using the six minute walk test (6MWT) according to American Thoracic Society guidelines. The two groups were well matched in terms of socio-economic status, gender and age. Statistically significant differences were found when comparing anthropometric measurements of height and weight with HIV infected participants being shorter and weighing less than their non-infected peers. The distance walked in the 6MWT was significantly reduced in the HIV infected participants with these children walking 57.86 metres less than the non-infected participants. It was also found that HIV infected children had significantly lower heart rates at all stages of testing. Correlations were found between the distance walked in the 6MWT and average and maximum heart rates. This study confirms that the exercise endurance of a group of HIV infected children is significantly reduced when compared to their age matched non-infected peers. It indicates the need for further investigation into the exercise endurance in HIV-infected children in a larger more representative sample of the population. Further investigation into the possible benefits of the prescription of exercise programmes in children needs to be done.

by Yiu-kuen Kam. / Bibliography: leaves 108-118 / Thesis (M.Phil.) -- Chinese University of Hong Kong, 1983

In the context of decreasing mortality and increasing prevalence, prevention of HIV-transmission represents a public health priority. In the United States, the majority of infections are sexually-acquired, with men who have sex with men and minorities disproportionately affected. Although a number of promising biomedical prevention approaches have emerged over the past decade, a further 20 years could be needed before a suitable product becomes widely available. Evidence from vaccine and microbicide trials has shown that success in one population may not be replicated in another. To understand surprising or unexpected results, investigators need chronologically concordant evidence of both study product adherence and viral exposure. Since exposure to HIV cannot yet be independently verified, in seeking to measure this variable, investigators target the sexual behaviors through which it takes place deriving data for these surrogate measures from study participants' voluntary self-reports. Likely sources of reporting bias and efforts to minimize this phenomenon in the context of HIV-prevention research are critically reviewed in Chapter 1. Research describing the role of cognitive and affective functioning in the preparation of responses to potentially threatening questions is examined. Studies investigating techniques such as the use of colloquial language to facilitate comprehension, or variation in the length of the reference period to enhance recall are explored. Research comparing the effect of mode of administration on the amount of proscribed behavior reported - widely believed to correlate with validity - is reviewed. Contextual factors facilitating versus inhibiting disclosure of sensitive information are examined. Finally, risk-behavior measurement approaches used in selected HIV-prevention trials are inspected. Thereafter, the dissertation focuses on the properties of risk-assessment items, formulated specifically to elicit Global recall over six months, or Event-Specific (episodic) memory for selected recent episodes of limited duration, to capture sexual behaviors or temporally related activities. The capacity of the different questionnaire item formats to elicit responses with sufficient construct validity to serve as proxies for HIV-exposure is examined. Data for these studies are drawn from a large randomized controlled trial of a behavioral intervention to prevent HIV-transmission among men who have sex with men. Using a subset of 1295 cases and controls, models with good discriminant validity for HIV are derived separately for the Global and Event-Specific items. Thereafter, selected items from the two formats are combined to produce a single model with excellent discriminant validity, suggesting that these items can adequately represent true HIV-exposure. Next, a preliminary investigation of the contribution of psychosocial items to the predictive model based on exposure measures is undertaken. Specifically, interaction with exposure measures and the increase in discriminant validity obtained using data derived from constructs of partner type/relationship status, substance use, depressive symptoms and perceived self-efficacy is examined first in stratified analysis and then in logistic regression analysis using the case-control data. Effect-modification is observed for perceived relationship status and non-injection drug use. Evaluation of psychosocial items continues in a cohort study with prospective analysis of follow-up data from all trial participants who returned for at least one follow-up visit. Informed by the case-control study, a series of items representing psychosocial constructs known for their association with HIV-infection are tested for main effects and effect-modification. Evidence of the interaction observed in stratified analyses and confirmed in ordinary logistic regression persists in separate, topic-specific GEE analyses with assorted exposure measures, but abates in repeated measures analyses drawing on all available psychosocial items. Lastly, a single lagged variable indicating primary relationship status of the most recent partner (with respect to the preceding study visit) provides a significant addition to the model. Significant main effects for all except depressive symptoms and perceived self-efficacy and the increase in discriminant validity obtained for the multivariable model versus the `exposure-only' model are sufficient to warrant continued use of these risk-assessment items. Despite good predictive validity demonstrated for the sexual risk-behavior and psychosocial items, some inconsistent reporting between the Global and Event-specific formats is evident. Likely sources of this reporting bias are considered in light of the literature, and strengths and limitations of the overall study are discussed in the closing chapter.

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