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Sandringham, South Africa

Barnard M.,Point of Reference | Barnard M.,Stellenbosch University | Barnard M.,University of Cape Town | Warren R.,Stellenbosch University | And 10 more authors.
American Journal of Respiratory and Critical Care Medicine | Year: 2012

Rationale: Conventional culture-based drug susceptibility testing (DST) for the second-line antituberculosis drugs is slow, leading to diagnostic delay with associated exacerbation of transmission, amplification of resistance, and increased mortality. Objectives: To assess the diagnostic performance of the GenoType MTBDRsl line probe assay (LPA) for the rapid detection of mutations conferring resistance to ofloxacin (OFX), amikacin (AMK), and ethambutol and to determine the impact of implementation on the turnaround time in a high-throughput diagnostic laboratory. Methods: Six hundred and fifty-seven direct patient acid-fast bacilli smear-positive specimens resistant to isoniazid, rifampin, or both according to the GenoType MTBDRplus assay were consecutively tested, using the GenoType MTBDRsl LPA. The diagnostic performance was assessed relative to the "gold standard" culture-based method, and the laboratory turnaround times for bothmethods were determined. Measurements and Main Results: A total of 516 of 657 patient specimens had valid results for both tests. The sensitivity for detecting OFX, AMK, and extensive drug resistance, using the GenoType MTBDRsl LPA, was 90.7% (95% confidence interval [CI], 80.1-96.0%), 100% (95% CI, 91.8-100%), and 92.3% (95% CI, 75.9-97.9%), respectively, and the specificity for detection was 98.1% (95% CI, 96.3-99.0%), 99.4% (95% CI, 98.2-99.8%), and 99.6% (95% CI, 98.5-99.9%), respectively. Implementation of this test significantly reduced the turnaround time by 93.3% (P < 0.001), calculated from the date that the specimen was received at the laboratory to reporting second-line results. In addition, a significant increase in diagnostic yield of 20.1% and 19.3% (P < 0.001) for OFX and AMK resistance, respectively, was obtained for isolates that were either contaminated or had lost viability. Conclusions: The GenoType MTBDRsl LPA is a rapid and reliable DST that can be easily incorporated into the diagnostic algorithm. This assay significantly improved diagnostic yield (P < 0.001) while simultaneously decreasing diagnostic delay for reporting second-line DST. The rapid dissemination of second-line DST results will guide initiation of appropriate treatment, thereby reducing transmission and improving treatment outcome. Copyright © 2012 by the American Thoracic Society. Source

Mfinanga S.G.,National Institute for Medical Research | Kirenga B.J.,Makerere University | Chanda D.M.,University of Lusaka | Mutayoba B.,National Institute for Medical Research | And 25 more authors.
The Lancet Infectious Diseases | Year: 2014

Background: WHO guidelines recommend early initiation of antiretroviral therapy (ART) irrespective of CD4 cell count for all patients with tuberculosis who also have HIV, but evidence supporting this approach is poor quality. We assessed the effect of timing of ART initiation on tuberculosis treatment outcomes for HIV-positive patients with CD4 counts of 220 cells per μL or more. Methods: We did this randomised, placebo-controlled trial between Jan 1, 2008, and April 31, 2013 at 26 treatment centres in South Africa, Tanzania, Uganda, and Zambia. We enrolled HIV-positive patients with culture-confirmed tuberculosis who had tolerated 2 weeks of tuberculosis short course chemotherapy. Participants were randomly allocated (1:1) to early ART (starting after 2 weeks of tuberculosis treatment) or delayed ART (placebo, then starting ART at the end of 6 months of tuberculosis treatment). Randomisation was computer generated, with permuted blocks of size eight, and stratified by CD4 count (220-349 cells per μL vs ≥350 cells per μL). Patients and investigators were masked to treatment allocation until completion of 6-months' tuberculosis treatment, after which the study was open label. The primary endpoint was a composite of failure of tuberculosis treatment, tuberculosis recurrence, and death within 12 months of starting tuberculosis treatment in the modified intention-to-treat population. Secondary endpoints included mortality. The study is registered with controlled-trials.com (ISRCTN77861053). Findings: We screened 13-588 patients and enrolled 1675: 834 assigned early ART, 841 delayed ART. The primary endpoint was reached by 65 (8·5%) of 767 patients in the early ART group versus 71 (9·2%) of 771 in the delayed ART group (relative risk [RR] 0·91, 95% CI 0·64-1·30; p=0·9). Of patients with a CD4 cell count of 220-349 cells per μL, 26 (7·9%) of 331 patients versus 33 (9·6%) of 342 reached the primary endpoint (RR 0·80, 95% CI 0·46-1·39; p=0·6). For those with 350 cells per μL or more, 39 (8·9%) of 436 versus 38 (8·9%) of 429 reached the primary endpoint (RR 1·01, 95% CI 0·63-1·62; p=0·4). Mortality did not differ significantly between treatment groups (RR 1·4, 95% CI 0·8-2·3; p=0·23). Grade 3 and 4 adverse events occurred in 149 (18%) of 834 patients assigned early ART versus 174 (21%) of 841 assigned delayed ART (p=0·37). 87 (10%) of 834 versus 84 (10%) of 841 had immune reconstitution inflammatory syndrome (p=0·56). Interpretation: ART can be delayed until after completion of 6 months of tuberculosis treatment for HIV-positive patients with tuberculosis who have CD4 cell counts greater than 220 cells per μL. WHO guidelines should be updated accordingly. Funding: USAID, Zambia Ministry of Health, Tanzania Commission for Science and Technology, WHO-TDR. © 2014 Elsevier Ltd. Source

Barnard M.,Point of Reference | Barnard M.,Stellenbosch University | Gey Van Pittius N.C.,Stellenbosch University | Van Helden P.D.,Stellenbosch University | And 3 more authors.
Journal of Clinical Microbiology | Year: 2012

Molecular diagnostics for Mycobacterium tuberculosis have recently been endorsed by the World Health Organization. The Xpert MTB/RIF assay was endorsed for use on patient material, regardless of smear gradation, while the GenoType MTBDRplus (version 1) has been limited for use on smear-positive patient material. In this study, we evaluated the diagnostic performance of the Xpert MTB/RIF and GenoType MTBDRplus (version 2) assays on smear-positive and smear-negative patient specimens submitted to a high-throughput diagnostic laboratory. A total of 282 consecutive specimens were subjected to the two new molecular assays, and their performance characteristics were assessed relative to the routine diagnostic standard. Both assays showed similar diagnostic performance characteristics. The sensitivities of the GenoType MTBDRplus (v2.0) and Xpert MTB/RIF assays for the detection of culture-positive M. tuberculosis were 73.1% and 71.2%, respectively, while the specificities of both assays were 100%. Both assays were able to diagnose the presence of M. tuberculosis in 57 to 58% of smear-negative cases, suggesting that the performance characteristics were dependent on bacillary load. The detection of M. tuberculosis in culture-negative specimens confirmed that molecular assays should not be used for treatment monitoring. The sensitivity and specificity for rifampin resistance detection were 100% in both assays; however, the GenoType MTBDRplus (v2.0) assay provided additional information on isoniazid susceptibility. The GenoType MTBDRplus (v2.0) assay will complement the Xpert MTB/RIF screening assay by validating rifampin susceptibility and providing information on isoniazid susceptibility. In addition, the GenoType MTBDRplus (v2.0) assay will provide pharmacogenetic information that may be critical in guiding appropriate treatment. Copyright © 2012, American Society for Microbiology. All Rights Reserved. Source

Wijekoon S.,University of Colombo | Prasath T.,University of Colombo | Corea E.M.,University of Colombo | Elwitigala J.P.,National TB Reference Laboratory
BMC Research Notes | Year: 2014

Background: Melioidosis is an infection caused by the facultative intracellular gram-negative bacterium; Burkholderia pseudomallei. It gives rise to protean clinical manifestations and has a varied prognosis. Although it was rare in Sri Lanka increasing numbers of cases are being reported with high morbidity and mortality. Here we report a case of melioidosis presenting with lymphadenitis which was diagnosed early and treated promptly with a good outcome. Case presentation. A 53-year-old Sinhalese woman with diabetes presented with fever and left sided painful inguinal lymphadenitis for one month. She had undergone incision and drainage of a thigh abscess three months previously and had been treated with a short course of antibiotics. There was no record that abscess material was tested microbiologically.She had neutrophil leukocytosis and elevated inflammatory markers. Initial pus culture revealed a scanty growth of "Pseudomonas sp." and Escherichia coli which were sensitive to ceftazidime and resistant to gentamicin.Due to the history of diabetes, recurrent abscess formation and the suggestive sensitivity pattern of the bacterial isolates, we actively investigated for melioidosis. The bacterial isolate was subsequently identified as B. pseudomallei by polymerase chain reaction and antibodies to melioidin antigen were found to be raised at a titre of 1:160.The patient was treated with high dose intravenous ceftazidime for four weeks followed by eradication therapy with cotrimoxazole and doxycycline. As the patient was intolerant to cotrimoxazole, the antibiotics were changed to a combination of co-amoxyclav and doxycycline and continued for 12 weeks. The patient was well after 6 months without any relapse. Conclusions: Melioidosis is an emerging infection in South Asia. It may present with recurrent abscesses. Therefore it is very important to send pus for culture whenever an abscess is drained. However, it should be noted that the reporting laboratory may be unfamiliar with this bacterium and the isolate may be misidentified as Pseudomonas or even E. coli. Melioidosis should be suspected when an isolate with the typical antibiotic sensitivity pattern of ceftazidime sensitivity and gentamicin resistance is cultured, especially in a patient with diabetes. This will expedite diagnosis and prompt treatment leading to an excellent prognosis. © 2014 Wijekoon et al.; licensee BioMed Central Ltd. Source

Lukoye D.,National Tuberculosis and Leprosy Program | Ssengooba W.,Makerere University | Musisi K.,National TB Reference Laboratory | Kasule G.W.,National TB Reference Laboratory | And 2 more authors.
BMC public health | Year: 2015

BACKGROUND: Prevalence of multidrug resistant tuberculosis (MDR-TB), defined as in vitro resistance to both rifampicin and isoniazid with or without resistance to other TB drugs, in sub-Saharan Africa (SSA) is reportedly low compared to other regions. These estimates are based on data reported to the World Health Organization (WHO) on drug resistance surveys, which may suffer from a reporting bias. We set out to evaluate the variation in prevalence of drug resistant tuberculosis (DR-TB) and its determinants across SSA countries among new and previously treated TB patients.METHODS: The aim was to perform a systematic review and meta-analysis of DR-TB prevalence and associated risk factors in SSA. PubMed, EMBASE, Cochrane and bibliographies of DR-TB studies were searched. Surveys at national or sub-national level, with reported DR-TB prevalence (or sufficient data to calculate a prevalence) to isoniazid (INH), rifampicin (RMP), ethambutol (EMB), and streptomycin (SM) conducted in SSA excluding the Republic of South Africa, published between 2003 and 2013 with no language restriction were considered. Two authors searched and reviewed the studies for eligibility and extracted the data in pre-defined forms. Forest plots of all prevalence estimates by resistance outcome were performed. Summary estimates were calculated using random effects models, when appropriate. Associations between any DR-TB and MDR-TB with potential risk factors were examined through subgroup analyses stratified by new and previously treated patients.RESULTS: A total of 726 studies were identified, of which 27 articles fulfilled the inclusion criteria. Studies reported drug susceptibility testing (DST) results for a total of 13,465 new and 1,776 previously treated TB patients. Pooled estimate of any DR-TB prevalence among the new cases was 12.6% (95% CI 10.6-15.0) while for MDR-TB this was 1.5% (95% CI 1.0-2.3). Among previously treated patients, these were 27.2% (95% CI 21.4-33.8) and 10.3% (95% CI 5.8-17.4%), respectively. DR-TB (any and MDR-TB) did not vary significantly with respect to study characteristics.CONCLUSIONS: The reported prevalence of DR-TB in SSA is low compared to WHO estimates. MDR-TB in this region does not seem to be driven by the high HIV prevalence rates. Source

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