3. Electronic Theses and Dissertations (ETDs) - All submissions
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Item Interactions between sexually transmitted infections and human immunodeficiency virus in Southern Africa(2007-02-26T12:31:40Z) Htun, YeEpidemiological information on sexually transmitted infections (STIs) is necessary to assess the magnitude of the burden of infections, to identify vulnerable population groups, to mobilise resources for intervention activities and to monitor the impact of these activities. In addition, specific STI surveillance systems, such as studies on the relative prevalence of aetiological agents of STI syndromes and their antimicrobial susceptibility patterns, are aimed at improving patient care. The studies included in this thesis were designed and implemented to improve our understanding of the epidemiology of STIs and HIV infection in southern Africa. In all the study populations, we observed that high level STI epidemics preceded the explosive spread of HIV infection among high-risk individuals. The studies reported here also demonstrate the importance of triangulating data collected from different recommended STI surveillance components, using a tiered surveillance approach. The studies reported here also explored the bidirectional interactions of HIV and STIs. We observed that different STIs have shown different magnitudes of interaction with HIV infection. We found particularly strong interactions between genital herpes and HIV. At the individual level, HIV-seropositive patients with genital herpes were more frequently found to have atypical clinical presentations, delays in spontaneous healing, longer duration of HSV shedding and increased association with HIV shedding from ulcer and genital exudates. Mixed infections involving chancroid and genital herpes were found to be common, particularly in HIV-seropositive patients. The effectiveness of syndromic treatment targeting only bacterial causes of genital ulceration was significantly reduced due to persistent ulcerations as a result of co-infection with genital herpes. The successful treatment of herpes in men and women was found to be associated with a decline or cessation in HIV shedding into ulcer exudates or genital fluid. The studies have also shown that HIV plasma viral load is the main determinant for HIV shedding in both men and women presenting with STIs. As was the case with HSV infection, there was a strong association between HIV and HPV infection in both men and women. A higher prevalence of HPV infection was found among HIV-seropositive patients in our study population and this may reflect the higher frequency of recurrences and/or longer duration of infection (i.e. persistency). The studies also found that the biological false positive reactions in syphilis serology (i.e. RPR) are not a common occurrence in our HIV-seropositive study population. On the other hand, syphilis serology could be falsely negative in patients with PCR-confirmed primary syphilis who are co-infected with HIV and other aetiological agents causing GUD. In conclusion, the findings of our studies have supported the bidirectional nature of interactions between conventional STIs and HIV infection in southern Africa.Item Early diagnosis of human immunodeficiency virus infection status in vertically exposed infants in a low resource setting.(2007-02-14T11:18:48Z) Sherman, Gayle GillianSub-Saharan Africa is the eye of the HIV epidemic. This study was conducted when treatment for the majority of HIV-infected patients in low resource settings was considered unattainable and the risks of diagnosing HIV often outweighed the benefits. Coupled with the complexities of HIV diagnosis in infancy, children typically were only diagnosed once already ill or not at all. Key strategies to address the paediatric epidemic focused on preventing mother to child transmission and reducing mortality and morbidity of infected children predominantly with co-trimoxazole prophylaxis. Both strategies required early diagnosis of HIV infection in infancy for monitoring prevention programs and identifying infected children respectively. The diagnostic algorithm for resource limited settings recommended the use of inexpensive, technically simpler HIV antibody detection assays that are unsuitable for use in HIV-exposed children under 12-months of age. Paradoxically this algorithm provided a barrier to HIV diagnosis in children because of high loss to follow-up rates and death in the first year of life. The objective of this study was to establish an accurate, affordable diagnostic algorithm for early diagnosis of HIV infection that could be rapidly implemented in South Africa and benefit other resource limited settings. The HIV infection status of 300 vertically exposed infants was determined according to first world criteria in a prospective, cohort study at Coronation Hospital, Johannesburg over 21 months. This status was used to assess the accuracy of clinical examinations and HIV assays in diagnosing HIV at 6-weeks, 3-, 7- and 12-months of age. The average cost of determining an infant’s HIV infection status was measured. A single HIV DNA PCR test at 6-weeks of age proved highly accurate in determining HIV status at a marginally increased cost to government and was incorporated by the South African Department of Health into national policy. The ultrasensitive p24 antigen assay and HIV antibody detection assays on serum and oral fluid were identified as valuable candidates where PCR testing is unavailable. Dried blood spot samples from heelpricks are critical for policy to be translated into practice since skills to perform venesection in 6-week old babies are limited. The next challenge lies in operationalising these findings at a clinical and laboratory level to the benefit of the 300 000 South African children annually exposed to HIV at birth. The urgency of early diagnosis has been increased by the availability of highly effective antiretroviral therapy.