A Thesis Submitted to the School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, in fulfilment of the requirements for the degree of Doctor of Philosophy Johannesburg, South Africa 2016. / Introduction Human immunodeficiency virus (HIV) has been associated with invasive enteric infections in HIV-infected patients, since it was first described in the 1980s. In South Africa, HIV remains an important health challenge, despite the introduction of antiretroviral therapy (ART) in 2003. In association with this, is an ongoing problem of invasive enteric infections, including those due to Shigella and Salmonella, including Salmonella enterica serovar Typhi (Salmonella Typhi). There are few South African data available as to the incidence of invasive disease due to these pathogens and how these data may contrast with the presentation and outcome in HIV-uninfected patients. The associated risk factors for mortality due to invasive enteric pathogens and whether there has been a response with ART as an intervention also needs further elucidation. Aims This work was undertaken to better describe the burden of invasive enteric infections (Shigella, nontyphoidal Salmonella and Salmonella Typhi) in association with HIV, define risk factors for mortality and establish whether the introduction of ART has impacted on disease burdens due to these pathogens. Methods Laboratory-based surveillance for enteric pathogens was initiated in 2003. Basic demographic details (age and gender) were collected on all patients where possible. In 25 hospital sites in all nine provinces, additional clinical information was collected by trained surveillance officers, including HIV status, data reflecting severity of illness, other immune suppressive conditions, antimicrobial and antiretroviral usage and outcome (survival versus death). Laboratories were requested to transport all isolates to the Centre for Enteric Diseases (CED) at the National Institute for Communicable Diseases of the National Health Laboratory Service (NHLS) in Johannesburg for further characterisation, including serotyping, antimicrobial susceptibility testing and molecular typing where relevant (whether isolates could respectively be classified as Salmonella Typhimurium ST313 and Salmonella Typhi H58). Additional cases were sought through audits of the Central Data Warehouse (CDW) of the NHLS. Annual incidence rates were calculated according to published estimates of population by age group by the Actuarial Society of South Africa for the Department of Statistics of the South African government. Analyses were specifically directed at invasive shigellosis, Salmonella meningitis, typhoid fever in South Africa and nontyphoidal salmonellosis in Gauteng Province, South Africa. Data were recorded in an Access database and analysed using chisquared test to establish differences between HIV-infected and uninfected individuals and univariate and multivariate analysis to compare risk factors for mortality. Data in the number of patients accessing ART were derived through audits of the CDW, by using the numbers of patients on whom viral loads were done annually as a proxy. Results Between 2003 and 2013, a total of 10111 invasive enteric isolates were received by CED. For patients for whom sex was recorded, 3283/6244 (52.6%) of patients presenting with invasive enteric infections were male; invasive disease was predominantly observed in children less than five years of age (1605/6131; 26.2%) and those who were aged between 25 and 54 years (3186/6131; 52.0%), with the exception of typhoid fever where the major burden was in patients aged 5 to 14 years (302/855; 35.3%). KH Keddy 81-11384 PhD iv More HIV-infected adult women were observed with invasive shigellosis (P=0.002) and with typhoid fever compared with adult men (P=0.009). Adults aged ≥ 15 years were more likely to die than children aged < 15 years (invasive shigellosis, odds ratio [OR]=3.2, 95% confidence interval [CI]=1.6 – 6.6, P=0.001; Salmonella meningitis, OR=3.7, 95% CI=1.7 – 8.1, P=0.001; typhoid fever, OR=3.7, 95% CI=1.1 – 14.9, P=0.03; invasive nontyphoidal salmonellosis, OR=2.0, 95% CI=1.6 – 2.5, P<0.001). HIV-infected patients had a significantly higher risk of mortality compared with HIVuninfected patients (invasive shigellosis, OR=4.1, 95% CI=1.5 – 11.8, P=0.008; Salmonella meningitis OR=5.3, 95% CI=1.4-20.0, P=0.013; typhoid fever, OR=11.3, 95% CI=3.0 – 42.4, P<0.001; invasive nontyphoidal salmonellosis OR=2.5, 95% CI=1.7 – 3.5, P<0.001). In all patients, severity of illness was the most significant factor contributing to mortality (invasive shigellosis, OR=22.9, 95% CI=2.7 – 194.2, P=0.004; Salmonella meningitis OR=21.6, 95% CI=3.5 – 133.3, P=0.01; typhoid fever, OR=10.8, 95% CI=2.9 – 39.5, P<0.001; invasive nontyphoidal salmonellosis OR=5.4, 95% CI=3.6 – 8.1, P<0.001). Between 2003 and 2013, ART was significantly associated with decreasing incidence rates of invasive nontyphoidal salmonellosis in adults aged 25 - 49 years (R=-0.92; P<0.001), but not in children (R=-0.50; P=0.14). Conclusion Decreasing incidence rates of invasive nontyphoidal salmonellosis and shigellosis suggest that ART is having an impact on opportunistic enteric disease in HIV. Further work is necessary however, to fully understand the associations between age, sex and invasive enteric pathogens. Specifically, this work would include typhoid fever, Shigella transmission from child to adult carer, development of invasive enteric infections in HIV-exposed children and whether the decreasing incidence rates can be sustained. Moving forward, an understanding of invasive enteric infections in the HIV-uninfected patient may assist in targeting severity of illness as a risk factor for mortality. / MT2017

HIV is a prominent infection in society and its health implications are seen in the paediatric wards daily. Despite its multi-system effect on the body, it particularly results in many respiratory infections. Effective understanding of the disease profile and management of patients with HIV relies on correct statistics and proper use of resources. Since the introduction of anti-retrovirals in 2004 in South Africa, the impact of HIV/AIDS on respiratory disease needs to be re-evaluated. The purpose of the study is to understand the disease profile of children with HIV/AIDS with regard to the presence of respiratory conditions with which they present, the need for chest physiotherapy and their health status. Of the 125 patients recruited in this study 55% were boys, average age was 20.55 months (SD= 23.64), average length of hospital stay of 2 ½ weeks (mean=18.76, SD=19.19), 80% discharged and 9.6% died. The most common respiratory conditions presented included bacterial pneumonia (66.4%), tuberculosis (48%) and pneumocystis jirovecii pneumonia (23.2%). The least common condition was lymphoid interstitial pneumonitis (4.8%). Two thirds of the children (68.8%) presented with a high burden of disease. Physiotherapy treatment was indicated for 96% of the patients mainly due to excess secretions and poor air entry. About forty percent (40.8%) of children were taking anti-retrovirals with an average length of use of 9.81 months (SD=11.61). Three out of four (75%) mothers were not involved in a PMTCT program. The analysis of immune status revealed a mean CD4 percentage 17.33% (SD=10.96), CD4 absolute 631.36 cell/mm3 (SD=610.36) and viral load 2.6 million copies /ml (SD=9.08 million copies/ml). A higher burden of disease was related to the use of anti-retrovirals, a lower immunity, female patients, longer length of hospital stay and incidences of mortality occuring at later periods of hospital stay. Results of this study highlight the characteristics of respiratory disease burden among children with HIV in a South African setting in a post HAART era.

Thesis (M. Med.(Family Medicine))--University of Limpopo (Medunsa Campus), 2010. / A study on Factors associated with non-disclosure of HIV positive status to sexual partners by adult patients attending the VCT clinic at Nhlangano health centre, Swaziland. Aim: To describe the factors associated with non-disclosure of known HIV sero-positive status to sexual partners by adult patients attending the VCT clinic at Nhlangano health center, Swaziland. Design:- Cross-sectional study using questionnaire administered by a trained research assistant. Setting:- Nhlangano health center VCT clinic, Nhlangano town in the Shiselweni region, Southern Swaziland. Study population:- All adult patients above the age of 18 years who had undergone HIV testing, who knew their positive HIV status and had follow up visits at the VCT clinic of Nhlangano health centre, from November 2005 (when the centre started rendering VCT service) till the beginning of the data collection, in September, 2008. Results:-The vast majority (89.1%) disclosed their positive HIV status to their sexual partners and 94.6% believed that letting their sexual partner/s know about their HIV status was very important. In terms of knowing the HIV status of their partners, 55.4% knew the HIV status of all of their sexual partners and 44.6% knew only the status of the regular partner/s. With regard to condom use, 96.7% believed that using condoms helps them to prevent transmission of HIV and 91.3% expected that letting their partners know about their HIV status would help them use condom IV more frequently. Only 53.3% said they would insist on condom use even if their partner is not willing to use. Conclusion:-  The rate of positive HIV status disclosure to sexual partner found in this study compared to many studies done in other settings is considerably high. This is encouraging especially considering the existing very high prevalence of HIV infection in the country. Despite this though, knowing partner's HIV status was relatively lower. Therefore, people are more likely to share their HIV status with a partner than insist that the partner does the same.  Even though the study was done only amongst patients attending VCT, it is important to note that the majority of the patients had positive attitudes about HIV status disclosure to a partner, and believed in the importance of letting their sexual partner/s know about their HIV status. Patients understood the unethical nature of engaging into sexual intercourse without disclosing their positive HIV status to their partner. It is possible to conclude that factors which contributed to these positive results should be implemented at a larger scale, namely creating awareness, health education, good counseling and follow up of treatment.  Awareness of the importance of condom use in preventing HIV transmission (including the fact that disclosure of HIV status to a partner enhances its better use) was impressively high amongst almost all participants. But it is worrisome that only half of the participants said they would insist on condom use irrespective of their partners’ willingness to use it or not. V  The variables that were found to be independently associated with disclosure to a partner comparing those who disclosed with those who did not were gender, age, marital status, education, number of sexual partners, and stage of the HIV condition.

Thesis submitted for the degree: Doctor of Philosophy, School of Public Health, Faculty of Health Sciences, University of Witwatersrand, Johannesburg June 2017. / The epidemics of tuberculosis (TB) and Human Immunodeficiency Virus (HIV) in sub-Saharan Africa are closely related and particularly persistent, proving a considerable burden for healthcare provision, and complicating utilization of care. Concern has been expressed about patients’ experience at healthcare facilities as this may impact on drug adherence, treatment success and willingness to return for regular monitoring and drug pick-up. This is particularly relevant for HIV programmes, with HIV now a chronic disease, with daily treatment necessary for life; TB treatment is limited in duration, to six months although can be as long as two years in case of multiple drug resistant TB. Utilization of healthcare services is an important determinant of health outcomes generally, with public health relevance, particularly for HIV and TB services in areas of high prevalence. The main aim of universal health coverage is to make healthcare accessible without barriers based on affordability, availability or acceptability of services. Various factors have been shown to hinder or enable patient utilization of healthcare services, such as organization of services, costs of transport to and from clinics, time loss at clinics receiving care, staff attitudes, waiting times and cleanliness of facilities. Objectives This study aimed to determine and quantify factors associated with healthcare utilization in patients utilizing HIV care (including those not yet initiated on antiretroviral treatment (ART) - pre-ART) or TB treatments in a rural sub-district of Hlabisa in KwaZulu-Natal and to understand healthcare providers’ perspectives regarding patient care and provision of quality care. The study used data from patient exit interviews, and additionally findings from interviews with healthcare providers in the local HIV treatment and care programme, structured around the responses from the patient-exit interviews. The study had three specific objectives: 1) to establish and quantify factors associated with healthcare utilization, with utilization decomposed to availability, affordability and acceptability of healthcare services, for patients in HIV or TB treatment and care; 2) to quantify ability-to-pay for healthcare and identify associated factors for patients in pre-ART care, or on ART or TB treatment; 3) to understand the healthcare providers’ perspectives regarding patient care and provision of quality HIV care. Methods In 2009 patient-exit interviews were conducted in six primary healthcare (phc) clinics in rural South Africa with 300 patients receiving ART and 300 patients receiving TB treatment; patients were randomly selected using a two-stage cluster random sampling approach with primary sampling units (phc) selected with probability-proportional-to-size. In 2010 an additional 200 HIV-infected patients in pre-ART care from the same clinics were interviewed. Patient-exit interviews were conducted in a private room outside the facility and all data were analysed using STATA 11. In 2012, a qualitative study was carried out with healthcare providers in eight (of 17) randomly selected phc clinics; 25 ART healthcare providers were engaged in discussion structured around patient-exit interviews feedback to assess possible challenges/facilitators ART healthcare providers face when providing care. Discussions took place in the consultation rooms when no clinical sessions were ongoing and these were recorded and transcribed; and data were managed using Nvivo 10. Thematic content analysis was conducted using both inductive and deductive approaches and clinic or healthcare provider identifiers were removed and replaced with pseudonyms. Summary statistics describe patient characteristics by patient group and key availability, acceptability and affordability factors associated with utilization of healthcare services; separate univariate and multivariable regression models were run to assess associations between patient characteristics and these key availability, acceptability and affordability factors. Patient socio-demographic characteristics (sex, age, education, employment and marital status) were controlled for and adjusted for clustering at facility-level. Factor analysis was performed to investigate underlying patient satisfaction factors. Results Socio-demographic characteristics of the patients More women than men were seen in the primary care clinic, especially among pre-ART patients (79%), followed by 62% HIV and 53% utilized TB care, with an age-sex profile comparable to previous studies in the area. Pre-ART patients were significantly younger than ART and TB patients, with a median age of 32 years for pre-ART patients, 39 years for ART patients and 37 years for TB patients. Unemployment at household level was high, up to 86% of ART patients’ head of households were unemployed and only 9% of TB patients were employed. / MT2017

M.Sc. (Nursing), Faculty of Health Sciences, University of the Witwatersrand, 2011

M.P.H., Faculty of Health Sciences, University of the Witwatersrand, 2011 / Introduction Botswana still has the second highest HIV prevalence in the world with little indication of any significant decline. In Botswana, women are disproportionately affected: young women account for more than half (58 %) of the adults living with HIV thus indicating a significant gender disparity in HIV infection. University educated, urban young women aged 19-39 have been identified as group at particularly high risk of HIV infection. Aim This study aimed to assess knowledge and attitudes regarding HIV and AIDS and how such knowledge and attitudes have implications for participation in risky sexual behavior among female University of Botswana students in their first and fourth years of study. Methodology This study was conducted at the University of Botswana (UB) in Gaborone. Data was collected using a selfadministered questionnaire on Knowledge of HIV/AIDS and participation in Risky Sexual Behavior among female students in first and fourth year of studies at University of Botswana. Results The knowledge regarding the “window period” and infectivity during the window period was significantly lower for first year students compared to fourth years. Attitudes towards people with HIV were positive in both groups, while affirmative attitudes towards premarital sex are increasing as the students progress academically. The analyses highlight that the percentage of women who reported having been sexually active the proceeding year was significantly higher among fourth year students (82.6%) than their first year counterparts (56.9 %), (p<0.01), with the number of partners significantly higher among women in their fourth year. Significantly, 3% of first year female students stated that their partners did not want to use a condom while 7 percent of the participants themselves said that that was the case. Amongst fourth year UB female students responding, 4% said that their partners did not want to use a condom, yet 14% participant said that they themselves did not want to use one. Overall, the prevalence of self-reported STI’s was significantly higher among fourth year students when compared with first year students 19 of 155 [12.26% ]vs. 4 of 144 [2.78 %] p<0.01 . Conclusion This study explored the knowledge of HIV/AIDS and participation in risky sexual behavior amongst female students in their first and fourth years at the University of Botswana. The study supported the findings that higher levels of formal education are associated with better knowledge of how to protect oneself from HIV/AIDS transmission. Although many HIV/AIDS prevention campaigns might have contributed to educated women being knowledgeable about how to protect themselves from HIV/AIDS transmission and the importance from abstaining from risky sexual behavior, a small but significant proportion of women still do not use condoms consistently

Thesis (M.Sc. (Med.))--University of the Witwatersrand, Faculty of Health Sciences, 2013. / Human immune deficiency virus (HIV) infection contributes to child mortality rates in South Africa. Investigations of newer technologies for improving early infant diagnosis of HIV in the South African setting could reduce child mortality as life saving treatment can be accessed early in life. This study investigated three technologies: a fourth generation rapid HIV test and two viral load (VL) platforms. Determine Combo (DC) is a qualitative fourth generation rapid test that is able to detect HIV antibodies and p24 antigen simultaneously. The performance of DC was evaluated in the field on samples from pregnant and postpartum women; in the laboratory, on stored samples from children and with the addition of heat denaturation. In the maternal DC study 90 (8 .8%) of 1019 women tested HIV positive of whom 59 (17.1% prevalence) were pregnant and 31 % (4.6% prevalence) were postpartum. The sensitivity and specificity of the antibody component of DC on plasma was 100%(Confidence Interval (CI): 95.9- 100%) and 99.8%(CI: 99.2-99.9%) respectively. Three postpartum patients tested false positive for HIV antibodies (n=2) and p24 antigen (n=1). No true positive p24 antigen was detected DC was performed on stored samples from 182 (90%) HIV-exposed and 20 (10%) HIV-unexposed children aged from birth to six years. The DC HIV antibody component returned false negative results in 2 HIV-infected children; one clinically symptomatic and one asymptomatic aged 7 and 23 months respectively. The sensitivity of DC HIV antibody was 100% (CI :94.3-100%) in infants aged 6 months and younger with a specificity of 100% (CI:81.6-100%) for all ages. Of the 61 HIV infected infants tested , the DC p24 antigen was reactive in only one clinically symptomatic infant resulting in a sensitivity for detection of HIV infection of 1.7% (CI 0.3-8.9%). A heat denaturation technique designed to improve p24 antigen detection was applied to HIVinfected samples but failed to enhance p24 antigen detection on DC. HIV viral load (VL) molecular assays are used to confirm an HIV-infected diagnosis and for VL monitoring. In South Africa, plasma is the gold standard sample for VL monitoring in infants even though dried blood spots (OBS) are the preferred specimen type in resource-constrained settings and for early infant diagnosis. The use of OBS specimens for HIV VL monitoring would convenience resource limited settings. The OBS matrix therefore requires validation to determine accuracy (for establishing diagnosis) and precision (for VL monitoring) compared to plasma VL. This study investigated the accuracy and precision limits of OBS VL on the Roche Cobas AmpliPrep-Cobas TaqMan HIV-1 v2.0 assay (CAP/CTM) and the Abbott RealTime HIV-1 assay (m2000) platforms on samples from HIV-infected adults and children. The CAP/CTM was investigated on OBS containing 751J1 blood and the m2000 was investigated using one (50IJI) and two (2x501J1) OBS. Compared to plasma VL, OBS VL from adults and children were higher in the lower range «310g,<1000copies/ml) and lower values in the higher range (>510g, >185,000copies/ml) on the CAP/CTM in the study of OBS VL accuracy. Additionally, OBS VL values were >log1.0 higher in 42/100 (42%) of adult and 16/49 (33%) of measurements from children, which will have clinical significance. On the m2000 platform, the differences between plasma and OBS VL were lower in the range >5 log and higher in the range 2 log copies/ml (100 copies/ml) to 4 log copies/ml (10000 copies/ml). Compared to plasma VL, OBS VL values were >log1.0 higher in 20/82 (24%) adult and 7/43 (16%) of measurements from children. Both platforms demonstrated 100% specificity in testing stored OBS from HIV-uninfected infants who were diagnosed negative on HIV DNA PCR. Acceptable limits for plasma VL precision is a coefficient of variation (CV) <35% and standard deviation (SO) :50.19 log. Where plasma VL :5510g, OBS VL demonstrated poor precision with CV>40% in 8/10 patients and total SO>0.30 log in 4/10 patients on the CAP/CTM. The m2000 total SO was >210g between adult plasma and OBS VLs under the 4 log copies/ml cut-off, irrespective of the number of DBS used. DBS VLs were unreliable when using precision limits used on plasma VLs on both platforms. In conclusion the DC test does not offer any advantage over currently available rapid tests in diagnosing new infection in women and children. The two VL platforms can be used to establish an HIV status in treatment naive patients in view of the 100% specificity. HIV-infected patients on treatment with undetectable plasma VL will always have detectable DBS VL on CAP/CTM, but equally undetectable DBS VL on the m2000. With DBS, the CAP/CTM assay generates higher VL values in the lower VL range than on plasma likely due to amplification of proviral DNA. Both platforms display poor intra- and inter- assay precision, using plasma VL based criteria and the variances would potentially affect clinical decision making. The acceptable limits for plasma VL precision cannot be applied to DBS VL on either platform.

Diss. Stockholm : Karol. inst.

Thesis (M.P.H.M.)--Mahidol University, 1999.

Thesis (M.S.)--University of Wisconsin-Madison, 1993. / Typescript. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 57-62).