No description available.

No description available.

M.P.H., Faculty of Health Sciences, University of the Witwatersrand, 2011 / Background: In Gauteng Province, South Africa, Sizwe Tropical Hospital (STH) is the designated centre for the specialized management of MDR-TB. But during the period covered by this study (2001-2002), all cases of TB (MDR-TB and NMDR-TB) were treated at STH. This was not according to the prescript of the National guidelines. This study describes the socio-demographic, treatment profile and treatment outcomes of MDR-TB patients seen and treated at STH during 2001 and 2002. Method: This was a cross sectional study involving retrospective review of records at STH. 281 systematically-sampled MDR-TB patient records were included in this study. Descriptive statistics were used to summarize the socio-demographic and treatment history characteristics and these were further analyzed to evaluate their relationship with MDR-TB treatment outcomes using Chi squared test of association. Means were compared using simple t-test. Results: The patients were majority black, unemployed, and living in townships and informal settlements. Sputum tests alone or combined with x-ray were most commonly used to diagnose MDR-TB (98%) at referring facilities; and the majority of patients arrived at STH with a referral note (98%). The median duration of stay at STH was 56 weeks (IQR 21-89). The majority of patients had a successful treatment outcome (75%); and amongst those with unsuccessful outcomes, a significant number had died (17%). Factors associated with poor iv outcomes in terms of death, default, treatment failure and transfer out were age groups (1-9 and 30-39), race, employment status, place of residence, housing structure, referral systems (referral note and feedback procedures) and HIV status. Discussion: The patients in this study had socio-demographic characteristics that facilitate TB transmission. There is a commendable referral system but various methods used to confirm MDR-TB and unjustified long duration of treatment prior to referral. Although in general the majority of patients have successful treatment outcomes, the policy guidelines of the management of MDR-TB are not implemented fully, and several factors associated to poor outcome are related to the health service and referral system. Recommendation: Effective adherence to the policy guidelines by health care providers and patients is recommended to improve treatment outcomes.

Background In 2006, South Africa documented its first outbreak of extensively drug-resistant (XDR-TB) in Tugela Ferry, Kwa-Zulu Natal. Delayed diagnosis of XDR-TB increases mortality, emphasizing the need or rapid diagnostics. The MTBDRsl assay rapidly identifies resistance to fluoroquinolones (FLQ) and aminoglycosides/capreomycin (AG/CP). Hospitalization provides the ideal opportunity for nosocomial infections of TB, including M/XDR-TB, with its associated morbidity and mortality. Occupational exposures amongst healthcare workers are also of concern. Rapid knowledge of second-line resistance patterns of these in-patients would allow for quick stratification and administration of individualized anti-chemotherapy treatment by clinicians, thereby reducing morbidity and mortality within this population. Methods ` A prospective cohort study was performed from admission sputum specimens collected from patients admitted to Sizwe Tropical Disease Hospital (Sizwe Hospital), the only M/XDR-TB referral hospital in Gauteng, South Africa. MTBDRplus (version 1) and MTBDRsl line probe assays (LPAs) were performed on all sputa, irrespective of smear positivity and subsequently on Mycobacteria Growth Indicator Tube (MGIT) isolates. The results from the LPAs were compared to the gold standard MGIT 960 culture and direct susceptibility testing (DST) results. Results From April 2011 to January 2012, 150 participants were recruited. Seventy-five (50.0%) were female, 91 (60.7%) were HIV-positive and 9 (6.00%) had an unknown HIV status. Of the MGIT cultures performed 71 (47.3%) were positive for Mycobacterium tuberculosis (MTB), 31 (20.7%) negative, 40 (26.7%) were contaminated and 8 (5.63%) were inadvertently discarded by the routinen laboratory. The proportion of smear-negative specimens in HIV- positive patients was not statistically significantly different to the smear-negatives in HIV-negative patients (57.1% vs. 46.0%; p=0.139). On phenotypic drug susceptibility testing, 47 (66.2%) were resistant to only isoniazid and rifampicin (MDR-TB), 10 (14.0%) were MDR-TB with added resistance to ofloxacin (pre-XDR-TB FLQ), 4 (5.63%) were MDR-TB with added resistance to kanamycin (pre-XDR-TB AG/CP), 4 (5.63%) were MDR-TB with added resistance to both ofloxacin and kanamycin (XDR-TB), 3 (4.23%) were mono-isoniazid resistant, 2 (2.82%) mono-rifampicin resistant, and 1 (1.41%) was TB-drug sensitive. No TB drug-sensitive sputum specimens were collected and used as a control group for the MTBDRplus (version 1) assay, thus only sensitivity indices and positive predictive values (PPVs) could be interpreted.All specimens collected were used as an inherent control group for the performance of the MTBDRsl assay, thus sensitivity and specificity indices together with the PPVs and NPVs, were calculated. From all sputum samples collected, including both smear-positives and smear-negative specimens, the sensitivity of the MTBDRplus (version 1) for RIF and INH was 98.1% for both drugs. Overall sensitivity for the MTBDRsl assay to detect ofloxacin (OFX) and kanamycin (KAN) resistance was 90.9% and 42.9%, respectively. The specificity was 100.0% and 95.7%, respectively. From smear-positive specimens, the sensitivity for OFX and KAN was 100.0% and 50.0%, respectively. The specificity was 100.0% and 96.8%, respectively. From smear-negative specimens the sensitivity was 50.0% and 33.3%, respectively. The specificity was 100.0% and 92.9%, respectively. From MGIT culture isolates, sensitivity for RIF and INH was 98.2% and 94.5% respectively. The sensitivity for OFX and KAN were 100.0% and 42.9%, respectively, whereas the specificity was 95.6% and 100.0%, respectively. Conclusion The performances of both LPAs correlate with other local and international publications. On direct, smear-positive sputa both LPAs perform well. From these, the MTBDRsl assay is a good rule-out test for detection of resistance to FLQ and AG/CP. For FLQ, it’s a good rule-in test: this indicates that the MTBDRsl assay can be used as a rapid screen for the onset of XDR-TB. As predicted, MTBDRsl does not perform well on smear-negative specimens, whereas the MTBDRplus (version 1) does. On cultures, both LPAs perform well.

Background: There is widespread concern about the rise of drug-resistant TB because treatment outcomes of affected patients remain poor and treatment options are limited. After more than a forty-year gap without any breakthrough discovery, several new (bedaquiline and delamanid) and repurposed drugs (linezolid) are increasingly becoming available for use. However, data regarding the efficacy and safety of these drugs in drug-resistant TB patients, with or without HIV infection, from a real-life programmatic setting are lacking. This thesis aims to address that knowledge gap and provide information for management of drug-resistant TB in countries with high disease burden. Methods: A total of 326 drug resistant TB patients were prospectively followed up between January 2008 and April 2018. The efficacy and safety of two new drugs (bedaquiline and delamanid) and one repurposed drug (linezolid) was determined in these patients in three studies. In the first study, 24 months treatment outcomes and adverse event profiles were compared between extensively drug resistant (XDR) TB patients who received programmatic treatment regimens with the backbone of second line injectables and fluoroquinolones (nonbedaquiline-based) and those who received a bedaquiline- and/ or linezolid-based treatment regimen. The second study determined the frequency of system-specific adverse events associated with linezolid. The third study interrogated the safety and effectiveness of a strengthened treatment regimen containing a combination of delamanid and bedaquiline in patients with poor prognostic features compared to bedaquiline-based regimen. Results: In the first study, patients who received a bedaquiline-based treatment regimen had a significantly greater favourable outcome rate (66.2% vs 13.2%; p<0.001) ), more than a fourfold reduction in treatment failure rate (5.9% vs 26%; p<0.001 ) and less than a half of mortality rate compared to patients who received a non-bedaquiline-based regimen. The bedaquiline survival and favourable outcome effect remained significant in HIV-infected patients (p<0.001). The second study showed that linezolid interruption was common in patients receiving a bedaquiline-based treatment regimen, and that system-specific toxicity occurred within predictable time frames. It also showed that anaemia (77.3% versus 7.3%; p<0.001), peripheral neuropathy (63.6% versus 14.6%; p=0.003), and optic neuritis (18.2% versus 9.8%; p=0.34) occurred more frequently in linezolid interrupters than in non-interrupters. The third study showed that the use of delamanid-bedaquiline combination regimen was safe and efficacious in drug resistant TB patients with poor prognosis when compared with outcomes in the less sick patients who received a bedaquiline-based regimen. It also showed no significant difference in culture conversion rate at 6 months (92.5% versus 81.8%; p=0.26) or favourable treatment outcome rate (63.4% versus 67.5%; p=0.66) between the two groups. Although patients who received the combination regimen had more frequent occurrence of QTcF prolongation greater than 60 ms from baseline (p=0.001) and more episodes of QTcF greater than 450 ms during treatment (p=0.001), none of them were symptomatic or had delamanid or bedaquiline withdrawn from their regimen. Conclusion: These data demonstrated that new and repurposed drugs remarkably improved treatment outcomes in patients with drug-resistant TB. Although linezolid, which is an important component of the bedaquiline-based treatment regimen, is often associated with system-specific adverse events, these occurred at predictable time frames thereby guiding physicians to make informed management decisions. Lastly, drug resistant TB patients with poor prognosis may benefit from a regimen containing delamanid and bedaquiline which seems relatively safe from an adverse event perspective. These data, despite some limitations, make a case for a widespread and accelerated roll-out of new and repurposed drugs for the treatment of drug resistant TB.

No description available.

Background: Even with newer and repurposed anti-TB drugs almost a third of patients with XDR-TB have unfavourable outcomes. In patients with localised disease and adequate pulmonary reserve, surgery is an important adjunctive treatment. However, there are no outcome data from TB endemic countries, and the prognostic significance of pre-operative PET-CT findings remains unknown. Objectives: To report outcomes for resectional surgery in our setting, and to study whether PET activity outside of the resection influences treatment outcomes. Methods: A retrospective study of all XDR-TB patients undergoing surgery at Groote Schuur Hospital (GSH) between July 2010 and December 2016 was performed. PET-CT was performed in a subgroup. Patients were followed up to determine treatment outcomes at 24-months post- surgery. Treatment success and failure, including all-cause mortality, was determined. Results: In total, 35 patients underwent surgery. The mean age was 36, 49% were male and 26% were HIV-infected. Pneumonectomy was the most common procedure (57%). Three patients (9%) were lost to follow up by 24 months. Total all-cause mortality was 34%. Treatment success was achieved in 15/35 (43%). In patients who underwent pre-operative PET-CT, there were no overall radiological features or PET parameters that were found to be prognostic for treatment failure. Conclusion: Resectional surgery for DR-TB in combination with chemotherapy resulted in cure in less than half of patients. Our data do not support the use of PET-CT to preselect patients or prognosticate about their outcome. These data inform clinical practice and underscore the need to support antibiotic stewardship strategies in TB-endemic settings.

The study aimed to explore and describe the experiences of people treated for multidrug resistant tuberculosis (MDR-TB) in Omaheke region, Namibia in order to make relevant recommendations regarding their management. A descriptive qualitative design approach was used. Data was collected using in-depth individual interviews with six participants. The interview transcripts were analysed using thematic content analysis. Three themes emerged namely (1) Stressors related to MDR-TB diagnosis and treatment which involved nature of disease and compulsory hospitalisation (2) Impact of being treated for MDR-TB which related to emotional , social , spiritual and financial impact (3) Support structures for people treated for MDR-TB which included family members, health care professionals and friends. Systemic practical patient-centred, staff-centred and community-centred recommendations are suggested as well as recommendations for future research and an appraisal of the limitations of this study. / Health Studies / M.A. (Public Health)

No description available.

MMed (Clinical Microbiology), Faculty of Health Sciences, University of the Witwatersrand, 2009 / Introduction: The clinical laboratory is required to rapidly identify Staphylococcus aureus as a cause of bacteraemia, and in particular, to detect methicillin resistance amongst bacteraemic isolates, to facilitate prompt initiation of appropriate therapy which may directly impact on patient survival, and to allow for implementation of appropriate infection control measures. Hence, the laboratory needs to choose tests to detect methicillin-resistant S. aureus (MRSA) bacteraemia which are rapid, accurate, simple, cost-effective and appropriate for the setting. Primary study objective: To determine the accuracy of four phenotypic susceptibility tests to directly detect MRSA from blood culture specimens (BC) compared with detection of the mecA gene by the polymerase chain reaction (PCR) from S. aureus cultured from the same BC. Materials and Methods: BCs were selected from patients with incident, S. aureus bacteraemic episodes at two hospitals, during January and February 2006. S. aureus was identified by standard phenotypic tests, including the presence of a deoxyribonuclease (DNAse). Direct susceptibility tests (DST) were performed (oxacillin (1μg) and cefoxitin (30μg) disk diffusion (DD), oxacillin Etest® (AB bioMérieux) and CHROMagar®-MRSA (CHROMagar® Microbiology)), and repeated on stored cultures. Detection of nuc and mecA genes by PCR confirmed S. aureus and methicillin resistance respectively. The sensitivity and specificity of the DST were calculated with reference to the mecA PCR result, to fulfil the primary study objective. Results: During the two-month study period, 9,400 BC were submitted to the clinical laboratories at the 2 hospitals; S. aureus was isolated from 156 specimens. Of these, 89 BC from 89 incident cases were included in the study, and 65 were subjected to all tests, including PCR. Of the 65 nuc-positive S. aureus isolates from 65 BC, all were positive with the direct DNAse test, and 25 (38%) were mecA positive. Compared to PCR, sensitivity and specificity for the direct oxacillin DD, cefoxitin DD, oxacillin Etest® and CHROMagar®- MRSA was 100% and 90%, 98% and 100%, 100% and 100%, and 96% and 42% respectively. Discussion: In this study, we found that, compared to PCR for the nuc and mecA genes, the combination of a direct DNAse test and oxacillin Etest®, facilitated accurate detection of MRSA bacteraemia. The direct oxacillin Etest® result did not appear to be influenced by a non-standardised inoculum, in contrast to the other direct tests, and provided an oxacillin minimum inhibitory concentration. The direct cefoxitin DD test produced more accurate results than the direct oxacillin DD test, was easier to read and distinguished MRSA from MSSA with zone diameters clustering into more clearly defined susceptibility categories. Although the chromogenic agar performed well when used to identify methicillin resistance amongst cultured S. aureus isolates, it was apparent that this test, read at 24 hours, could not be used reliably as a DST. Since the Etest® is more costly than the DD test; its use should be reserved for BC from patients in “high-risk” hospital areas, e.g. intensive care units. The direct cefoxitin DD could be used for all BC positive for GPCC, and could be used without a direct identification test because of its lower cost; it is further recommended that the direct cefoxitin DD test replace the direct oxacillin test.