According to the 2005 Ethiopian Demographic Health Survey, HIV prevalence in Gambella region where Fugnido refugee camp is located is 6%, which is the highest prevalence data recorded in the country. Similarly, the United Nations High Commissioner for Refugees (UNHCR) Health Information System (HIS) demonstrates that Fugnido has the highest HIV prevalence compared to other refugee camps in Ethiopia and furthermore shows variation in prevalence among the two main ethnic groups in the camp, namely Agnuak and Nuer (about 8.5% and 2.3% respectively). The study seeks to investigate why a significant difference exists in the number of people with known HIV positive status among the Agnuak community compared to the Nuer community in the Fugnido refugee camp in Ethiopia. It does this by investigating factors that are presumed to explain HIV high risk-behaviour and vulnerability. This was a cross-sectional study of Agnuak and Nuer tribes living at the Fugnido refugee camp. The sampled population involved men and women refugees from the ages of 15 to 49 years. The study used a mixed method approach or methodological triangulation. Cluster sampling technique was used for the quantitative data collection. The sample size was 831 refugees (439 Agnuak and 390 Nuer). Seven (7) Focus Group Discussions (FGDs) and 3 Key Informant (KI) interviews was used for the qualitative data collection. Findings show that the Agnuak were almost 4 times (OR=3.8, 95% CI [1.9-7.4] p < 0.05) more likely to practice risky behaviour compared to 0.3 times (OR=0.3, 95% CI [0.1- 0.9] p < 0.05) likelihood among the Nuer refugees. Factors associated with differences in risky behaviour for both Agnuak and Nuer included, inter alia, primary education as the highest level of education attained, 50% among the Agnuak (OR=0.5, 95% CI [0.3-0.8] p < 0.05), compared to Nuer community’s 30% (OR=0.3, 95% CI [0.2-0.6] p < 0.05). Access to HIV and voluntary counselling and testing (VCT) services was lower for the Agnuak (OR=1.8, 95% CI [1.1-2.9] p < 0.05) compared to the Nuer (OR=2.9, 95% CI [1.6-5.1] p < 0.05). Unlike the Nuer refugees, the Agnuak refugees who had experienced forced sex (OR=7.3, 95% CI [2.9-18.8] p < 0.05) and had a positive attitude (lack of or reduced stigma) towards HIV (OR=2.1, 95% CI [1.3-3.7] p < 0.05) were more positively associated with risky 6 behaviour (than the Nuer). The Nuer had no factor associated with risky behaviour that was different from that of the Agnuak. The study revealed more Agnuak refugees than Nuer refugees had been engaged in risky sexual behaviour by having multiple sex partners and being involved in transactional sex. The Nuer was more closed and reserved to having sexual relations outside of their group than the Agnuak were which contributed to their relatively lower HIV prevalence. Furthermore, there was very low condom use among the Nuer community compared to the Agnuak community, which was based on differential attitudes between the two communities concerning trust of partner and monogamous relations. The study findings recommend that humanitarian workers and community partners need to collaborate to develop congruent HIV interventions that go beyond traditional strategies of distributing condoms and focus on correct and consistent use of condoms in the camp. Humanitarian and community workers’ understanding the socioeconomic context of the communities and the influence of cultural and other factors, including behaviour with intervention strategies,could also curb the epidemic. / Sociology / M.A. (Sociology)

Thesis (MBA)--Stellenbosch University, 2004. / ENGLISH ABSTRACT: HIV/AIDS is one of the biggest challenges faced by many countries in this century. The rate of infection is rapidly increasing and more and more people are getting ill and dying from AIDS. Of all the people living with AIDS in the world, seven out of ten live in Sub-Saharan Africa. Namibia is one of the top five most HIV/AIDS affected countries in the world. There is therefore no question about the urgent need to accelerate actions to reduce prevalence, expand care and support and extend access to treatment. AIDS is eroding decades of progress made in extending life expectancy; thus hundreds of adults are dying young or in early middle age. The national strategic plan (2004) on HIV/AIDS indicated that the average life expectancy in Namibia is now 42 years, when it could have been 60 without AIDS. A 2003 study on the impact of HIV/AIDS on Windhoek indicated that the antenatal HIV/AIDS prevalence rate in Windhoek for 2002 was 27%, while the national prevalence rate was estimated at 22.3%. The prevalence rate for Windhoek is expected to reach its peak at 38% during 2005. Even though HIV/AIDS will have a diminishing effect on population growth, Windhoek's population is expected to continue growing, particular as a result of inward migration, but at a slower pace. Similarly, HIV/AIDS will have an abating effect on GDP growth as the virus will mainly affect the economic active and available labour force of the population and result in increased labour costs and skilled labour shortages. The impact on the informal sector is potentially more damaging than on the formal economic sector, as the majority of micro- enterprises and informal businesses are build around one individual. As the breadwinner dies, household income and expenditures levels deteriorate and increase poverty levels, because households within the city are very dependent on family structures to support their income levels. Informal settlements are also more volatile to HIV transmission and the majority of HIV infected individuals are likely to be found within these areas as the populations is poorer, crowded, has fewer social services facilities and is more likely migratory compared to those in affluent formal settlements. Considering that the incubation period of HIV/AIDS from infection to death takes about ten years, the real impact of current HIV infections in Windhoek will only be experienced during 2010. Health services will have to attend to a greater demand for curative services as well as to social care and support programs. Social welfare programmes will need to find ways of caring for a large population of HIV/AIDS orphans. Municipalities can playa critically important role in addressing HIV/AIDS at a local level as they are at the interface of community and government. They are ideally placed to playa coordinating and facilitating role that is needed to make sure that partnerships are built to bring prevention and care programmes to every community affected by AIDS. Therefore, in order to succeed in confronting HIV/AIDS, it is important to work closely with all levels of government as well as working with local partners in civil society that are fighting HIV/AIDS at the community level. By taking action against HIV/AIDS, municipalities are securing the future of their towns and communities. / AFRIKAANSE OPSOMMING: MIV/VIGS is een van die grootste uitdagings wat baie lande hierdie eeu in die gesig staar. Die koers van infeksie is vinnig aan die toeneem en al hoe meer mense word siek en sterf as gevolg van VIGS. Van al die mense wat met VIGS lewe in die wêreld, bly sewe uit tien in sub-Sahara Afrika. Namibië is een van die vyf mees MIV/VIGS geaffekteerde lande in die wêreld. Derhalwe is daar geen twyfel rakende die noodsaaklikheid om daadwerklike aksies te bewerkstellig om die voorkoms te verminder, sorg en ondersteuning te verhoog en toegang na behandeling uit te brei. VIGS vernietig dekades van groei behaal in die verlenging van lewensverwagting; dus sterf honderde volwassenes vroeg of gedurende hul middeljare. Die nasionale strategiese plan (2004) rakende MIV/VIGS toon dat die gemiddelde lewensverwagting in Namibië huidiglik 42 jaar is instede van 60 sonder VIGS. 'n Studie onderneem gedurende 2003, rakende die effek van MIV/VIGS in Windhoek, dui aan dat die voorgeboorte MIV/VIGS voorkoms koers 27% vir 2002 was, terwyl die nasionale voorkoms koers slegs 22.3% was. Daar word verwag dat die voorkoms koers vir Windhoek sy maksimum van 38% sal bereik gedurende 2005. Alhoewel MIV/VIGS 'n negatiewe effek op bevolkingsgroei groei gaan het, sal Windhoek se inwoners getalle steeds groei, alhoewel teen 'n stadiger koers, as gevolg van inwaartse migrasie. Terselfdertyd, gaan MIV/VIGS 'n verminderde effek het op die groei van die Bruto Binnelandse Produk (BBP), omdat die virus hoofsaaklik die ekonomiese aktiewe en beskikbare arbeidsmag van die bevolking affekteer wat as gevolg hiervan 'n verhoging in arbeidskoste en tekort aan geskoolde arbeid het. Die effek op die informele sektore is potensieel meer skadelik as op die formele ekonomiese faktore, aangesien die meeste klein en informele besighede rondom een persoon gebou is. lndien die broodwinner sterf, versleg die vlakke van huishoudelike inkomste en uitgawes wat lei tot verhoogde armoede, omdat huishoudings in die stad baie afhanklik is op familie strukture om hulle inkomste te ondersteun. Informele vestigings is meer kwesbaar in die oordrag van MIV en die meerderheid van die MIV geïnfekteerde individue word gewoonlik in hierdie areas aangetref omdat die bevolking armer is, meer persone huisves, minder welsyn dienste fasiliteite het en meer swerwend is in vergelyking met die meer welgestelde formele vestigings. As in ag geneem word dat die ontkiemings periode van MIV/VIGS vanaf infeksie tot en met sterfte omtrent tien jaar neem, sal die werklike effek van die huidige VIGS besmettings in Windhoek slegs ervaar word gedurende 2010. Gesondheidsdienste sal moet aandag skenk aan 'n groter aanvraag vir geneeslike dienste sowel as sosiale sorg en ondersteunings programme. Gemeenskaplike welsyn programme sal maniere moet vind om vir 'n groot populasie van MIV/VIGS weeskinders te sorg. Munisipaliteite kan 'n belangrike rol speel in die aanspreek van die MIV/VIGS epidemie op 'n plaaslike vlak omdat hulle die skakel is tussen die gemeenskap en die regering. Hulle is ideaal geplaas om 'n koordineerende en fasiliterende rol te speel wat nodig is om seker te maak dat vennootskappe gebou word om voorkomings en versorgings programme te lewer aan elke gemeenskap wat deur MIV/VIGS geraak word. Dus, om sukses te behaal in die bekamping van MIV/VIGS , is dit belangrik om nou saam te werk met alle vlakke van die regering sowel as met plaaslike vennote in die gemeenskap wat MIV/VIGS bekamp op gemeenskapsvlak. Deur aksie te neem teen MIV/VIGS , kan munisipaliteite die toekoms van hulle dorpe en gemeenskappe verseker.

Thesis (MCur)--Stellenbosch University, 2011. / ENGLISH ABSTRACT: Understanding the incidence and prevalence of HIV/AIDS is important in addressing the ongoing epidemic. Understanding which factors influence the rate of transmission of the virus is critical in attempting to contain and ultimately eradicate the disease. Determining which factors influence a person’s decision to disclose his/her positive status to others, particularly the sexual partner, is essential in understanding this complex process and thereby improving disclosure rates. The aim of the study was to investigate which factors influence the disclosure of someone’s HIV positive status. The objectives were to determine whether aspects such as socio-demographic factors, stigma and discrimination, religion, culture, fear of abandonment and rejection as well as knowledge of the disease influences disclosure rates. These objectives were met through an in-depth descriptive correlational research design with a quantitative approach. The target population (N = 1200/100%) consisted of all the HIV infected clients who attended a Community Health Clinic (CHC) for HIV management in the Cape Metropolitan area. The convenience sampling method was used to select the sample of participants (n = 150/12.5%) who met the criteria and voluntarily agreed to participate in the study. A self-administered questionnaire was used consisting of mainly closed-ended questions, with a limited number of open-ended questions. Ethics approval for the study was obtained from the Health Research Ethics Committee at the Faculty of Health Sciences, Stellenbosch University. Permission was obtained from the City of Cape Town: City Health, to conduct the research. Informed consent was obtained from each participant. Reliability and validity were supported by a pilot study which was conducted on (n=15/10%) of participants at this CHC to assure the feasibility of the study. The data was analysed with the support of a statistician and was presented with histograms and frequency tables. Statistical associations were determined between the various variables. The qualitative data obtained from the open-ended questions were grouped in trends and analysed thematically and then these trends were quantified. The results show that there are numerous factors which influenced HIV status disclosure. The fear of stigmatisation was identified as a factor which influences HIV disclosure to others, especially among the male participants. The results revealed that this was the major reason for delayed or non-disclosure, as well as the fear of rejection and blame. The results showed that awareness of the sexual partner’s HIV status remained relatively low (n = 64/43%), with awareness of the partner’s status highest among married participants. The recommendations were to assure that HIV positive individuals have access to support groups and are given an opportunity to attend multiple counselling sessions. Community based initiatives are needed to reduce stigmatisation of individuals with HIV and to improve access to social support systems. It was concluded that disclosure is a multifaceted process and one particular factor does not necessarily influence disclosure of a HIV positive status but most often a combination of factors. / AFRIKAANSE OPSOMMING: Dit is belangrik om die verspreiding en voorkoms van MIV/VIGS te verstaan om die gesprek rondom die voortdurende epidemie aan te roer. Kennis van watter faktore die snelheid beïnvloed waarteen die virus oorgedra word, is krities in ’n poging om dit onder beheer te hou en uiteindelik uit te wis. Om te bepaal watter faktore ’n mens se besluit beïnvloed om jou positiewe status van MIV aan andere bekend te maak, veral aan ’n seksuele maat, is dit belangrik om die kompleksiteit van die proses te begryp en sodoende die pas van bekendmaking te verbeter. Die doel van die studie is om te bepaal watter faktore beïnvloed die bekendmaking van ’n MIV positiewe status. Die doelwitte is om vas te stel of aspekte soos sosio-demografiese faktore, stigma en diskriminasie, godsdiens, kultuur, vrees vir verlating en verwerping en kennis van die siekte, die insidensie van bekendmaking beïnvloed. ’n Beskrywende korrelatiewe navorsingsontwerp met ’n kwantitatiewe benadering is toegepas. Die teikengroep (N=1200/100%) het bestaan uit al die MIV geïnfekteerde persone wat ’n Gemeenskapgesondheidskliniek vir die bestuur van MIV in die Kaapse Metropolitaanse area besoek het. Die gerieflikheidssteekproef metode is gebruik om die steekproef van deelnemers (n=150/12.5%) te kies wat vrywillig ingestem het om aan die kriteria vir die studie te voldoen. ’n Self-geadministreerde vraelys was gebruik wat hoofsaaklik uit geslote vrae met ’n beperkte aantal ope vrae bestaan. Etiese goedkeuring vir die studie is verkry van die Gesondheidsnavorsing se Etiese Komitee by die Fakulteit van Gesondheidswetenskappe, Universiteit van Stellenbosch. Toestemming is verkry van die stad Kaapstad: Stad Gesondheid, om die navorsing uit te voer. Ingeligte toestemming is van die deelnemers verkry. Betroubaarheid en geldigheid is ondersteun deur ’n loodsstudie wat op (n=15/10%) van die deelnemers beoefen is by die Gemeenskapsgesondheidkliniek om die uitvoerbaarheid van die studie te verseker.Die data is geanaliseer met die ondersteuning van ’n statistikus en is deur histogramme en frekwensie-tabelle voorgestel. Statistiese assosiasies is vasgestel tussen die verskeie veranderlikes. Die kwalitatiewe data is geneem vanuit ope vrae wat gegroepeer is in neigings en tematies geanaliseer is en die neigings is hierna gekwantifiseer. Die uitslae bewys dat daar heelwat faktore is wat die bekendmaking van MIV statusstatus beïnvloed. Die vrees vir stigmatisering is geïdentifiseer as ’n faktor met betrekking tot die bekendmaking van MIV aan andere, veral onder die manlike deelnemers. Die uitslae bewys dat dit die hoofrede vir terughoudendheid of nie-bekendmaking van die siekte is, asook die vrees vir ververwerping en blaam. Die resultate bewys dat die bewustheid van die seksuele maat se MIV statusstatus relatief laag bly (n=64/43%) met bewustheid van die maat se status die hoogste onder getroude deelnemers. Die aanbevelings is om te verseker dat MIV positiewe individue toegang het tot ondersteuningsgroepe en dat hulle geleentheid gegee word om veelvuldige voorligtingsessies by te woon. Gemeenskapgebaseerde inisiatiewe is nodig om stigmatisering van individue met MIV te verminder en vir die verbetering van toegang tot maatskaplike ondersteuningsisteme. Ter samevatting kan die gevolgtrekking gemaak word, dat; die bekend making van MIV positiewe status word nie noodwendig beïnvloed deur ʼn spesifieke faktor of meervlakkige besluitnemings proses nie, maar eerder deur ʼn kombinasie van faktore.

Thesis (MBA)--Stellenbosch University, 2003. / Some digitised pages may appear illegible due to the condition of the original hard copy / ENGLISH ABSTRACT: After sexual transmission of HIV, mother-to-child (MTCT) transmission is the most common cause of HIV infection in South Africa. The Western Cape government, through the Premier, has committed itself to providing access for all HIV positive women in the province attending antenatal clinics to MTCT prevention programmes by the end of 2003. The MTCT prevention programme is aimed at intervening transmission during pregnancy, during the birth of the baby and post delivery during breast-feeding of the newborn baby. The HIV virus attacks and destroys the cells of the immune system by being incorporated into the reproductive cycle of the cell. Antiretroviral drugs in the fight against HIV target two aspects of this replication cycle of the virus and as such do not halt the infection but slow it down by preventing the replication of the virus. MTCT internationally has been reduced dramatically by the use of antiretroviral drugs (AZT) antenatally, during birth and post-natally for mother and baby. However this regimen was found to be not suitable for resource-poor countries due to the complexity in administration, compliance and costs. Poor countries have developed alternative MTCT prevention programmes based on shorter course regimens and on alternative antiretroviral drugs. MTCT prevention In South Africa initially did not have the support of the national government. However, the -Western Cape Administration had developed a regional programme phasing in MTCT prevention at all state clinics within the province. The cost drivers associated with the MTCT prevention programme include costs associated with the HIV tests, costs for pre- and post-test counselling, costs for the antiretroviral drugs and costs for substitute feeding to replace breast-feeding to prevent viral transmission during breast-feeding. Depending on the option exercised, costs can be calculated per HIV positive baby averted. As regards substitute feeding, which is a substantial cost driver and a major disadvantage to the newborn baby as regards protection from common childhood diseases such as diarrhea, research from Tanzania showed that ARV therapy during childbirth could suppress HIV transmission through breast-feeding during the first few weeks after childbirth, thus enabling an optimal combination of breast-feeding in the first few crucial weeks of the newborn's life for the protective benefits of breast-milk and formula feeding thereafter to ensure protection for the infant from HIV transmission through breastfeeding. The data were subjected to a sensitivity or a "what-if' analysis usmg an Excel spreadsheet. Costs per HIV averted were calculated for each assumed parameter in the model that was developed. As regards prevalence, the MTCT prevention programme is most cost effective at the lower levels of the seroprevalence of HIV in the population served. If the seroprevalence is above the "cross-over" or "optimal" point for the regimen an alternative regimen should be assessed. As regards levels of identification and number accepting intervention the principle of an economy of scale applies and therefore, a level of 100 percent in both cases should be targeted. This will be dependent on wide scale advertisements and support for the programme with active efforts to destigmatise the infection. Innovative programmes such as the mothers-to-mothers-to-be (M2M2B) programme must be encouraged. / AFRIKAANSE OPSOMMING: Na seksuele oordraging van HIV is moeder tot kind (MTK) oordraging die algemeenste rede van HIV infeksie in Suid Afrika. Die Wes-Kaapse regering, deur die Premier, het hulself verbind om toegang vir alle HIV positiewe vroue in die provinsie, wat voorgeboorte klinieke bywoon, tot MTK voorkomingsprogramme voor die einde van 2003 moontlik te maak. Die MTK voorkomingsprogram is gerig op die tussenkoms van transmissie gedurende swangerskap, gedurende die geboorte en die nasorg tydens die borsvoeding periode van die pasgebore baba. Die HIV virus val die selle van die immuun sisteem aan en' vernietig dit. Die virus word geïnkorporeer tot die reproduksie siklus van die sel. Antiretrovirale wat teen die virus gerig is, is gerig teen twee aspekte van die replikasie siklus van die virus en sodoende sal die medikasie die infeksie nie staak nie, maar eerder vertraag as gevolg van die voorkoming van die replikasie. Moeder-tot-kind infeksie is internasionaal drasties verminder deur die gebruik van antiretrovirale (AZT) gedurende die tydperk voor geboorte, gedurende die geboorte en gedurende nasorg van die moeder en baba. Hierdie regimen is egter nie altyd moontlik in arm lande nie vanweë die kompleksiteit van die administratiewe toepassing en kostes. Arm lande het alternatiewe MTK voorkomingsprogramme ontwikkel, gebaseer op korter kursusse en alternatiewe antiretrovirale. Die voorkoming van MTK infeksie in Suid-Afrika het eers nie die ondersteuning van die nasionale regering geniet nie. Die Wes-Kaapse Adminstrasie het onafhanklik van die nasionale regering, streeksprogramme ontwikkel vir die infasering van MTK voorkoming in alle klinieke in die Provinsie. Die kostedrywers wat met MTK voorkomingsprogramme geassosieer word, sluit in die koste van HIV toetse, koste van voor-en-na toets berading, koste van die antiretrovirale en alternatiewe voeding om virale transmissie te voorkom gedurende die tydperk van borsvoeding. Afhangende van die opsies wat gebruik is, kan die koste van elke baba wat nie HIV opdoen nie, bereken word. Sover dit alternatiewe voeding aangaan, wat 'n belangrike kostedrywer is en 'n nadeel vir elke baba is sover dit teen beskerming van algemene kindersiekte soos diarrhea gaan het navorsing in Tanzanië bewys dat ARV terapie gedurende geboorte ook HIV transmissie deur borsvoeding gedurende die eerste paar weke na geboorte onderdruk wat 'n optimale kombinasie van borsvoeding in die eerste paar kritiese weke van die nuutgebore baba se lewe vir die beskermende voordele van moedersmelk en formulêre voeding daarna te versterk met beskerming van die baba teen HIV transmissie deur borsvoeding. Deur die gebruik van 'n Excel werkblad en 'n "wat as" metode van analiese koste van HIV opdoen in bereken word vir elke aanvaarding. Sover dit voorkoms betref is die MTK voorkomingsprogramme die mees effektief hoe laer die "seroprevalence" van HIV in die populasie gedien word. As die "seroprevalence" hoër as die optimale punt is, moet 'n ander metode bereken word. Sover dit die mate van identifisering en hoeveelheid die tussenkoms aanvaar in 'n mate van 100 persent moet in beide gevalle die mikpunt wees. Dit sal afhang van grootskaalse advertensies en ondersteuning van die programme met bedrywige pogings om die' infeksie te destigmatiseer. Nuwe programme soos die moeder tot nuwe moeder (M2M2B) program moet aangemoedig word.

Thesis (PhD)--Stellenbosch University, 2004. / ENGLISH ABSTRACT: A simple and rapid scatter-based flow cytometric assay was developed to detect apoptosis in CD4+ and CD8+ T cells from a mixed population of cells. The assay was suitable for children. Apoptotic PBMCs were confirmed by morphologic assessment in clinical samples ex vivo and after overnight culture. The scatter-based assay was validated in a number of ways. Firstly, PBMCs were irradiated with 500 rads and cultured overnight to induce apoptosis. Thereafter, PBMCs were labeled with a CD4 MAb. CD4+ cells were sorted into apoptotic and viable populations by scatter characteristics (diminished forward and increased side scatter). Morphology was assessed by fluorescence microscopy. The majority of cells with apoptotic scatter characteristics had apoptotic morphology (chromatin condensation) (80.6%). Ninety-two percent of cells from the viable region had normal morphology. CD4+ T cell apoptosis measured by scatter was then correlated with the TdT assay for DNA fragmentation. Lastly, CD4+ T cell apoptosis by scatter and annexin V uptake were also shown to correlate. In the latter experiments, PBMC morphology and cell death by trypan blue uptake were studied simultaneously and confirmed the two flow cytometric assays. Apoptosis of CD4+ and CD8+ T cells has been shown in PBMCs from HIV infected adults analyzed after overnight culture. Since cell death may be an artifact of in vitro culture, and because there is little information on apoptosis in paediatric HIV disease, I undertook a cross-sectional analysis in PBMCs analyzed immediately ex vivo from HIV infected children and adults. Patients were studied in Denver, CO, USA. PBMCs from 21 children, 4 adolescents and 9 adults and seronegative age-matched controls were stained for CD4 and CD8 surface markers. Apoptotic cells were detected in a newly characterized flow cytometric assay by diminished forward and increased side scatter. For the scatter assay, PBMCs had been labeled initially by an indirect method involving an intermediary incubation in the presence of biotinylated MAbs at 37°C for 30 minutes prior to incubating with streptavidin-FITC at 4°C for 20 minutes. Thereafter, the intermediary incubation step was removed and PBMCs were incubated with PE-conjugated CD4+ and CD8+ MAbs. Both CD4+ and CD8+ T cell apoptosis appeared enhanced in the indirect method. The significant differences were abolished after subtraction of data from simultaneously studied time-matched controls. CD4+ and CD8+ T cell apoptosis were significantly higher in HIV-infected study subjects than in simultaneously studied seronegative controls. PBMCs were assayed immediately ex vivo and after overnight culture after stimulation by an anti-TCR MAb as well as spontaneously. There was a direct correlation between CD4+ and CD8+ T cell apoptosis and CD4+ T cell depletion. A significant correlation was also shown between apoptosis immediately ex vivo and after overnight culture. I then studied apoptosis in a South African population comprising 18 symptomatic children and 4 seroreverters. CD4+ and CD8+ T cell apoptosis were significantly higher in symptomatic HIV-1-infected children than in seroreverters and seronegative controls. CD4+ T cell apoptosis correlated with depletion of CD4+ T cell percentage in symptomatic HIV-1-infected children. I also noted elevated CD4+ T cell apoptosis in patients recovering from intercurrent disease in comparison to those who were either acutely ill or relatively asymptomatic outpatient attendees. Lastly, I compared CD4+ and CD8+ T cell apoptosis in cohorts from Denver, CO and Tygerberg Children’s Hospital, South Africa. I selected only patients with moderate or severe HIV infection from both centers. South African patients were significantly younger, more malnourished, had higher gamma globulin levels and were less likely to receive ART. CD8+ T cell apoptosis was higher in North American patients suggesting a possible impairment in CD8+ activity in the South African study subjects. / AFRIKAANSE OPSOMMING: ‘n Eenvoudige en vinnige vloei sitometriese toets is ontwikkel om apoptose aan te toon vanuit ‘n gemengde populasie selle. Dit moes geskik wees vir kinders van wie net klein volumes bloed getrek kan word. Die teenwoordigheid van apoptotiese perifere bloed mononuklere selle (PBMS) was vasgestel deur morfologiese beoordeling in kliniese monsters ex vivo en na oornag kultuur. Die ondersoek is gebasseer op die verstrooings patroon van bestraalde PBMS wat apoptose induseer. PBMS is gemerk met a CD4 MAb. CD4+ selle is gesorteer in apoptotiese en lewensvatbare populasies deur verstrooings karakteristieke. Morfologie is beoordeel deur fluoreserende mikroskopie. Die meerderheid van selle met apoptotiese verstrooings karakteristieke (verminderde voorwaartse en verhoogde sywaartse verstrooings patroon) het apoptotiese karakteristieke gehad (80.6%). Twee-en-negentig persent van selle van die lewensvatbare area het normale morfologie gehad. Verstrooings patroon is ook gekorreleer met die TdT meting vir DNA fragmentasie in kliniese monsters van MIV-geinfekteerde kinders. Daarna is Annexin V gekorreleer met verstrooings patroon, apoptotiese morfologie en trypan blou opname in selle wat blootgestel is na verskillende konsentrasies van beauvericin. Apoptose van CD4+ en CD8+ T-selle is bewys in PBMS van MIV-geinfekteerde volwassenes na oornag kultuur. Omdat sel dood ‘n artefak van in vitro kultuur kan wees, en omdat daar min inligting is oor apoptose in paediatriese MIV siekte, het ek onderneem om ‘n deursnee analiese te doen in PBMS wat onmiddelik ex vivo geanaliseer is vanaf MlV-geinfekteerde kinders en volwassenes. Die pasiente is bestudeer in Denver, Colorado, VS A. PBMS van 22 kinders, 4 adolessente en 9 volwassenes en seronegatiewe ouderdoms-gepasde kontroles is gekleur vir CD4+ en CD8+ oppervlaksmerkers. Apoptotiese selle is vloeisitometries aangedui deur verandering in verstrooings patroon. Vir die doeleindes van die verstrooings assay is die PBMS aanvanklik deur ‘n indirekte metode gemerk, wat ‘n intermediere inkubasie in die teenwoordigheid van biogetinileerde MAbs by 37°C vir 30 minute voor dit geinkubeer is met streptavidin- FITC by 4°C vir 20 minute behels. Daarna is die intermediere inkubasie stap verwyder en PBMC is geinkubeer met PE - gekonjugeerde CD4+ and CD8+ MAbs. Beide die CD4+ en CD8+ T-sel apoptose het verhoog voorgekom met die indirekte metode. Die betekenisvolle verskille het verdwyn na data van gelyktydige tyd - gepaarde kontroles afgetrek is. CD4+ en CD8+ T-sel apoptose was betekenisvol hoër in MIV-geinfekteerde studie gevalle as in gelyktydig bestudeerde seronegatiewe kontroles. PBMS assays is gedoen onmiddelik ex vivo en na oornag inkubasie na stimulasie deur ‘n anti-TCR MAb, sowel as spontaan. Daar was ‘n direkte korrelasie tussen CD4+ en CD8+ T sel apoptosis en CD4+ T sel vermindering. ‘n Beduidende korrelasie is ook getoon tussen apoptose onmiddelik ex vivo en na oornag kultuur. Daaropvolgend het ek apoptose in ‘n Suid Afrikaanse populasie van 18 simptomatiese kinders en 4 serologies terukerende gevalle bestudeer. CD4+ en CD8+ T sel apoptose was aansienlik hoër in siptomatiese MIV - 1-geinfekteerde kinders as in die serologies terukerende gevalle en seronegatiewe kontroles. CD4+ T sel apoptose het gekorrelleer met vermindering van CD4+ T sel persentasie. Ek het ook opgemerk dat daar ‘n tendens bestaan het tot verhoogde CD4+ T sel apoptose in pasiente wat besig was om te herstel van bykomende siektes. Ek het CD4+ en CD8+ T sel apoptose in kohorte van Denver, Colorado en Tygerberg, Suid Afrika vergelyk. Suid Afrikaanse pasiente was jonger en meer wangevoed as hul Noord Amerikaanse ewekniee. Suid Afrikaanse kinders het ook meer gevorderde siekte gehad. Wanneer pasiente gepas is vir die graad van ernstigheid van siekte en slegs die minder ernstige (B) en ernstige siekte (C) vergelyk is, was CD8+ T sel apoptose beduidend hoër in Noord Amerikaanse pasiente. Hierdie waarneming ondersteun die hipotese dat CD 8+ T sel aktiwiteit moontlik onderdruk mag wees in simptomatiese Suid Afrikaanse MIV-1-geinfekteerde kinders.

Thesis (PhD)--University of Stellenbosch, 2003. / ENGLISH ABSTRACT: The risk of human immunodeficiency virus type-1 (HIV-1) infection and rate of progression towards development of the acquired immunodeficiency syndrome (AIDS) is determined by a combination of viral characteristics, immune function and host genetic variation. Although mutations of the chemokine and chemokine co-receptor genes and allelic variation of the major histocompatibility complex (MHC) have been studied extensively, variation in these host genetic factors does not explain the differences in HIV/AIDS susceptibility in all cases. This study represents the first analysis of new candidate genes implicated in iron metabolism and immune function in relation to HIV-1 disease in the African context. Both case-control association studies and genotype-phenotype correlations were performed to determine the potential functional significance of genetic variants that may be involved, either directly or indirectly, in susceptibility to HIV-1 disease in the South African population. Genotyping was performed to identify potentially important polymorphisms in the solute carrier family 11 member 1 (SLC11A 1), haemochromatosis (HFE) and protein-tyrosine phosphatase receptor-type C (PTPRC/CD45) genes in HIV-seropositive versus HIVseronegative individuals. This was followed by HLA-B27 genotyping in HIV-1 infected individuals with known disease status to determine the potential impact of combined genotypes for different mutations identified in the same study cohort. Preferential association with any of the mutations screened for in the CCR5, SLC 11A1, HFE or CD45 genes were not detected in HLA-B27 positive individuals identified. These findings were in accordance with the independent protective role of HLA-B27 in relation to disease progression in HIV-1 infected individuals. Although differences in allelic distribution were not significant between the study groups, an apparently African-specific mutation 32A~G, identified in an exonic splicing silencer element (ESS-1) of the CD45 gene, appeared to predominate in HIV-1 infected subjects with WHO Class I disease status and slow progression to AIDS. This mutation was present in 35.7% (5/14) of HIV-seropositive individuals with WHO Class I disease status, whilst absent in 22 HIV-seropositive patients with rapid disease progression. This finding may be related to differences in proportions of both CD4+ and CD8+ subsets observed following flow cytometry (FACs) analys.s in two HIV-seropositive individuals with mutation 32A~G, compared with an HIV-seropositive individual without this mutation. Analysis of the iron-related SLC11A1 and HFE genes did not reveal significant associations with modified risk of HIV-1 infection or progression to AIDS in our predominantly African study population. However, the effect of the virus on iron metabolism was demonstrated for the first time at the DNA level. Haemoglobin levels were significantly reduced in both HIV-seropositive (P=O.004) and HIV-seronegative (P=O.02) Black Africans with mutation IVS3-48c~g in the HFE gene, compared with mutationnegative individuals in both groups. Since this effect was more pronounced in HIV-infected individuals compared with controls, presence of the HFE mutation seems to result in an even stronger effect on haemoglobin levels, which may be related to the acute phase response following virus infection. This effect possibly results from genetic variation in a nearby gene involved in innate immunity, most likely in the HLA region on chromosome 6. It therefore seems possible that genetic variation in any of the host molecules involved in response to infection could contribute to clinical outcome. The significance of the multitude of host genetic factors investigated in this study, or previously implicated in susceptibility to HIV-1 infection and disease progression, revealed a complex interrelationship between the host and HIV-1. In some instances the disease process following HIV-1 infection depends on combined effects of different mutations occurring in the same individual, while independent effects of specific genes in conjunction with environmental influences may explain diverse clinical outcomes in others. / AFRIKAANSE OPSOMMING: Die risiko vir menslike immuniteitsgebrek virus tipe-1 (MIV-1) infeksie en die progressietempo vir ontwikkeling van die verworwe immuniteits gebrek sindroom (VIGS) word hoofsaaklik deur fn kombinasie van virale eienskappe, immuunfunksie en gasheer genetiese variasie bepaal. Alhoewel mutasies van die chemokien en chemokien koreseptor gene en alleliese variasie van die major weefsel-verenigbaarheidskompleks (MWVK) reeds omvattend bestudeer is, verklaar variasie van hierdie gasheer genetiese faktore nie noodwendig verskille in vatbaarheid vir MIVNIGS in alle gevalle nie. Hierdie studie verteenwoordig die eerste analise van nuwe kandidaatgene, geïmpliseer in yster metabolisme en immuunfunksie in die konteks van MIV-1 siekte in Swart bevolkingsgroepe. Beide gevalle-kontrole assosiasie-studies en genotipe-fenotipe korrelasies is uitgevoer om moontlik betekenisvolle verwantskappe met genetiese variante te bepaal, wat moontlik direk of indirek betrokke mag wees in vatbaarheid vir MIV-1 siekte in die Suid Afrikaanse populasie. Genotipering van die solute draer familie 11 lid 1 (SLC11A1), hemochromatose (HFE) en protein-tirosien fosfatase reseptor-tipe C (PTFRC/CD45) gene is uitgevoer in beide MIVseropositiewe en MIV-seronegatiewe individue. Daaropvolgend is genotipering van die menslike leukosien antigeen-B27 (MLA-B27) uitgevoer in MIV-1 geïnfekteerde individue met bekende siekte-status, om die potensiële impak van gekombineerde genotipes te bepaal vir verskillende mutasies wat in dieselfde studie populasie geïdentifiseer is. Voorkeur-assosiasie is nie waargeneem vir enige van die mutasies waarvoor geanaliseer is in die CCR5, SLC11A1, HFE of CD45 gene nie. Hierdie bevinding is in ooreenstemming met die onafhanklike rol van MLA-B27 in verwantskap met siekte progressie in MIV-1 geïnfekteerde individue. Alhoewel die alleelverspreiding van In Afrika-spesifieke mutasie 32A~GI wat in In eksoniese splytingsdemper-element (ESS-1) van die CD45 geen geïdentifiseer is, nie statisties betekenisvolle verskille getoon het tussen studiegroepe nie, is die mutasie oorheersend waargeneem in MIV-1 geïnfekteerde individue met WGO Klas I siektestatus en stadige progressie na VIGS. Hierdie mutasie was teenwoordig in 35.7% (5/14) van HIV-seropositiewe individue met WGO Klas I siekte-status, terwyl dit afwesig was in 22 HIV-seropositiewe pasiënte met vinnige siekteprogressie. Hierdie bevinding mag moontlik verband hou met verskille in verhoudings van beide die CD4+ en CD8+ substelle, soos waargeneem gedurende vloei sitometriese (VAS, FACs) analise in twee HIV-seropositiewe individue met mutasie 32A---+G, in vergelyking met en HIV-seropositiewe individu sonder hierdie mutasie. Analise van die yster-verwante SLC11A 1 en HFE gene het nie betekenisvolle assosiasies opgelewer met gemodifiseerde risiko vir MIV-1 siekte of progressie na VIGS in die hoofsaaklik Swart studie-populasie nie. Die effek van die virus op ystermetabolisme is wel vir die eerste keer op DNS vlak gedemonstreer. Hemoglobien vlakke was betekenisvol verlaag in beide MIV-seropositiewe (P=O.004) en MIV-seronegatiewe (P=O.02) Swart individue met die HFE geen IVS3-48C---+G mutasie, in vergelyking met mutasie-negatiewe individue in beide groepe. Aangesien hierdie effek meer uitgesproke was in MIVgeïnfekteerde individue as in kontroles, blyk dit dat die teenwoordigheid van die HFE mutasie die hemoglobienvlakke tot engroter mate beïnvloed weens die akute fase respons wat verband hou met die virusinfeksie. Hierdie effek kan moontlik toegeskryf word aan genetiese variasie in ennaasliggende geen wat in aangebore immuniteit betrokke is, heel moontlik in die MLA gebied van chromosoom 6. Dit wil dus voorkom asof genetiese variasie in enige van die gasheer molekules betrokke by respons op infeksie kan bydra tot die kliniese uitkoms. Die belangrike rol van die veelvuldige gasheer genetiese faktore wat in hierdie studie bestudeer is, of wat voorheen geïmpliseer is in vatbaarheid vir MIV-1 infeksie en siekte progressie, het enkomplekse inter-verwantskap tussen gasheer en MIV-1 geopenbaar. In sommige gevalle is die siekte-proses na MIV-1 infeksie afhanklik van gekombineerde effekte van verskillende mutasies in dieselfde individu, terwylonafhanklike effekte van spesifieke gene tesame met omgewings-invloede uiteenlopende kliniese uitkomste in ander mag verklaar.

published_or_final_version / Dentistry / Doctoral / Doctor of Philosophy

published_or_final_version / abstract / Public Administration / Master / Master of Public Administration

This study focused on perceptions and experiences of pregnant women who opted in against those who opted out of voluntary antenatal HIV counseling and testing. The pregnant women's perceptions and experiences were assessed in order to gain insight into their views towards voluntary antenatal counseling and testing.

<p>HIV and AIDS present challenges to the well-being of individuals and to public health proportions unpresedented in modern history, and stigma has been identified as the single most contributor to the spread of the HI-virus. While the challenges presented by the AIDS pandemic are scientific and medical, it also has a psychological, legal,&nbsp / economic, social, ethical and religious impact on those infected and affected. The underlying question in this thesis is not whether the church should respond to this urgent societal challenge, but how it ought to respond. To explore this question, the thesis investigated how a New Testament text (as primary resource), particularly Luke's Gospel, could be a resource for shaping/sharpening the church's response to the pandemic.</p>