3. Electronic Theses and Dissertations (ETDs) - All submissions
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Item Comparison of multiple methods of diagnosis of mycobacterial infection from bone marrow samples of HIV positive patients(2011-02-18) Chosmata, Benford IvanBackground: Mycobacterium tuberculosis (MTB) infection remains a serious public health challenge in sub-Saharan Africa. Rapid and early diagnosis is critical in the successful control of this eminently treatable infection. This study compared the diagnostic usefulness of culture, bone marrow trephine biopsy granulomata, bone marrow trephine biopsy Ziehl-Neelsen (ZN) stain and bone marrow mycobacterial polymerase chain reaction (PCR) in establishing the diagnosis of mycobacterial infection in HIV infected patients. Materials and methods: The trephine biopsies of HIV positive patients done for the investigation of suspected tuberculosis were reviewed for granulomata and stained with ZN stain. The corresponding bone marrow aspirates were subjected to DNA real-time PCR analyses using LightCyler TB Kit® (Roche Diagnostic). Culture results were used as diagnostic gold standard. Results: Of the 60 patients studied, 24 were culture negative. Of the 34 culture positive, 62% were Mycobacterium tuberculosis and 38% were Mycobacterium avium intracellulare. Using the culture method as a gold standard, the sensitivities and specificities were 97% and 23% for bone marrow trephine biopsy granulomata, 65% and 58% for bone marrow trephine biopsy ZN staining and 50% and 73% for bone marrow aspirate PCR analysis respectively. Ninety-seven percent of all trephine biopsies with positive ZN stain had granulomata. Conclusion: The presence of granulomata in bone marrow trephine biopsies of HIV infected patients appear to have a high diagnostic yield whilst mycobacterial PCR has the lowest yield but highest specificity. These results should be confirmed in a prospective case controlled study because the sample size in this study was small, and the study was a retrospective one.Item Neonatal hyperbilirubinemia bilirubin encephalopathy: investigations into the diagnosis, epidemiology, pathogenesis, management and treatment of the jaundiced newborn(2009-05-22T11:24:13Z) Maisels, Michael JeffreyJaundice is probably the most common newborn infant problem dealt with on a daily basis by the family practitioner and paediatrician. Jaundice occurs when the liver cannot clear a sufficient amount of bilirubin from the plasma. When the problem is excessive bilirubin formation or limited uptake or conjugation, unconjugated (i.e., indirect reacting) bilirubin appears in the blood and indirect hyperbilirubinemia is the predominant form of jaundice found in the newborn infant. In the vast majority of newborns, hyperbilirubinemia is transient and benign but, in rare cases, the serum bilirubin rises to a level that is toxic to the central nervous system. Understanding the pathogenesis and epidemiology of neonatal hyperbilirubinemia; recognizing, the problems involved in appropriate surveillance and monitoring of the jaundiced infant and the factors contributing to bilirubin encephalopathy; and implementing treatment of the jaundiced neonate in a timely fashion, are issues that have engaged clinicians and researchers for some 6 decades. This work will summarize my contributions to the field of neonatal hyperbilirubinemia and it includes papers published between 1971 and 2007. The description of this work will not follow its chronological sequence, but will be divided into the categories of diagnosis, epidemiology, pathogenesis, management, treatment, and bilirubin encephalopathy.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.Item Factors associated with drug shortages in PHC facilities in the Mopani district of the Limpopo province(2006-11-10T11:58:10Z) Matse, Patrick MuziMost leading causes of death and disability in developing countries can be prevented, treated, or at least alleviated with cost effective essential drugs. However, hundreds of millions of people do not have regular access to essential drugs despite the fact that essential drugs can prevent many deaths. The aim of this study was to determine factors associated with essential drugs shortages in Primary Health Care (PHC) facilities (i.e. clinics and community health centres) in Mopani District in the Limpopo Province. Forty-five facilities were selected by means of stratified (by sub-district) random sampling. Forty-five professional nurses, who were in charge of the facility on the day of the interviews, were interviewed. A structured questionnaire was used for the data collection. Six pharmacists, from the six hospitals that supply drugs to the PHC facilities, were interviewed using a structured questionnaire. A one-on-one informal interview was held with 2 Hospital Superintendents and the Acting Provincial Chief Pharmaceutical Director. The study was both a retrospective and prospective observational study based on review of historical data, interviews with key players and direct observation of current practice. The tools used to collect and analyse the data were based on those developed by the World Health Organisation (WHO) and the Health Systems Trust (HST) with some adjustments and adaptation. The District STI Quality of Care (DISCA) Tool was used in the other thirty-six facilities, at which the structured questionnaire was not administered, to test prescribing indicators in relation to diagnosis, the correctness of and dosage of drugs dispensed and also drugs availability.