3. Electronic Theses and Dissertations (ETDs) - All submissions
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Item Molecular biological characterisation of the novel Rifampicin inactivation mechanism in Nocardioform bacteria(1996) Andersen, Susan JeanRifampicin is one of the major antibiotics used in the treatment of Mycobacterium tuberculosis. This organism causes tuberculosis. Other related nocardioform bacteria which include the Rhodococci are opportunistic pathogens in AIDS patients. These organisms cause tuberculosis-like disease and are currently treated with rifampicin and other drugs. The presence of a low level rifampicin resistance mechanism was identified in seven rhodococcal strains and five other related and unrelated bacteria. Abbreviated Abstract. Open document to view full version]Item Characteristics of infants exposed to maternal tuberculosis and chemoprophylaxis using three months of isoniazid and rifampicin(2016) Mathivha, Khakhu TshilidziBackground: Though features of infants with congenital tubercuiosis (TB) are known including being low-birth-weight (LBw), features of in-utero TB-exposed infants including non-infected are not well reported. Infants bom to TB-infected women are at risk of contracting TB post-delivery, therefore chemoprophylaxis is recommended, and this includes use of isoniazid and rifampicin combination, but littie is known about its effectiveness. Objective: To determine features of in-utero TB-exposed infants and proportion with TB after chemoprophylaxis with isoniazid and rifampicin. Methods: Retrospective review of records of TB-infected women and their infants, from ZA07-20rc. Clinical features of mothers and infants at time of delivery; and follow-up of infants after completion of isoniazid and rifampicin are described. Results: Eighty-eight infants bom to 86 women with a diagnosis of TB were studied. TB diagnosis was made peripartum in24.4Yoof women, 23.3%had exka-pulmonary TB. Among those diagnosed antepa$um 46.2o/owere on treatment for >2 months. Human immunodeficiency virus (HIV) was positive in 97.7Yo;wi& CD4 count <200 cells/mm3 in 74'6yo' Eight mothers (9.3%) died before discharge. There were 56 {63.6%)LBW and 45 (51'2W preterun infants. Culture for acid-fast-bacilli was positive in 4 (4.5%)infants. At 3- months follow-up, 17 (20.2%)defaulted, and among 67 who returned, 7 OAoA)did not return for Mantoux test reading, 1160 (1.7%)had positive Manroux. Conclusion: Majority of TB-exposed infants are born to mothers with TB/ HIV co-infection. A high proportion of TB-exposed infants are born preterm and LBW. The high attrition rate made it difficult to assess effectiveness of chemoprophylaxis with isoniazid and rifampicinItem The evaluation of the Xpert MTB/RIF in the diagnosis of mycobacterium tuberculosis complex and detection of rifampicin resistance in extrapulmonary (pleural and ascitic) fluid samples received for routine immunophenotypic analysis in a high-burden tuberculosis setting(2015) Kilfoil, Kim MichelleIntroduction: The Gene Xpert MTB/Rif assay (Xpert) is a nucleic acid amplification technique that has been studied in the diagnosis of both pulmonary and, to a lesser extent, extrapulmonary tuberculosis (TB). This study was performed in the National Health Laboratory Services (NHLS) laboratory at Charlotte Maxeke Hospital which services a population with a high prevalence of Mycobacterium Tuberculosis Complex (MTBC) infection. The study aimed to develop a protocol for the processing of pleural and ascitic fluid samples to be run on Xpert for MTBC diagnosis, to evaluate the sensitivity and specificity of the Xpert assay as compared to the gold standard MTBC culture assays and to assess the utility of the Xpert assay as part of the diagnostic algorithm for fluid samples received in high prevalence MTBC laboratories. Materials and methods: A total of 392 pleural and ascitic fluid specimens were received for routine immunophenotypic analysis between August 2012 and February 2013 at the NHLS flow cytometry laboratory in Charlotte Maxeke hospital. Of these specimens, 229 had sufficient residual volume (>0.5ml) after routine immunophenotypic analysis to be tested on Xpert. Specimens were processed as per the manufacturer’s guidelines for pulmonary specimens and results were compared to the gold standard culture for Mycobacterium tuberculosis. Results: Xpert positivity was detected in 8.7% (20/229) of the total specimens. Only 43% (99/229) of these specimens were submitted for concurrent MTBC liquid culture (Mycobacterium Growth Indicator tube, MGIT) testing based on the laboratory information system history. Positivity on Xpert was shown in 9% (9/99) of specimens compared to 17% (17/99) on MGIT. One false positive was detected on Xpert. More than half of the specimens, 57% (130/229) were not referred for concurrent MTBC culture. The Xpert detected MTBC in 8.5% (11/130) of these specimens, with 1 Rifampicin resistant case identified. Xpert sensitivity and specificity in this study were 50% (CI:26-75%) and 99% (CI:91-100%) respectively Conclusion: The sensitivity and specificity of Xpert in this study was comparable to that found in other studies performed on fluid samples. Importantly, this study demonstrates that in a high burden HIV/TB setting like South Africa, more than 50% of fluid specimens referred for immunophenotypic analysis to exclude lymphoma are not referred for concurrent MTBC culture testing. Incorporation of Xpert into the laboratory diagnostic algorithm (LDA) in the immunophenotypic laboratory would, therefore, have a number of benefits, improving overall patient work-up and care. Implementation and policy uptake, however, would require a full costing analysis as Xpert testing would be performed in addition to, and not instead of, routine testing.