Evidence of 'amplifier effect' in pulmonary multidrug-resistant tuberculosis: report of three cases

Introduction: A cluster of three related cases of tuberculosis (TB) with primary multidrug resistance was investigated at the Centre Hospitalier Universitaire of Kigali (CHUK) in Rwanda. The patients were HIV-1/2 seronegative. Patients 1 and 2 were hospitalized in the same room of CHUK for one month. Patient 3 was a younger sibling of patient 2. Methods: Drug susceptibility of two consecutive Mycobacterium tuberculosis isolates from each patient was tested by the BACTEC 460 radiometric method. DNA fingerprinting was performed using spoligotyping and mycobacterial interspersed repetitive units of variable numbers of tandem repeats (MIRU-VNTR) analysis. All patients initially received the World Health Organization category I regimen. Results: The isolates collected during the first TB episode were resistant to isoniazid, rifampin and ethambutol. After subsequent retreatment regimens with rifampin, isoniazid, streptomycin, pyrazinamide (8 months) and rifampin, isoniazid, streptomycin, pyrazinamide, ciprofloxacin (21 months), patients 1 and 2 developed additional resistance to streptomycin and quinolones. Patient 3 received only the category I regimen and consecutive isolates retained the initial drug susceptibility pattern. All isolates were genetically indistinguishable by spoligotyping and MIRU-VNTR, indicating the same origin. Conclusions: These observations highlight the risk of nosocomial transmission of multidrug-resistant (MDR) TB and the possible selection of secondary resistance to second-line drugs if a single new drug is added at the time of retreatment of MDR TB patients. © 2007 International Society for Infectious Diseases.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Evaluation of the resazurin microtiter assay for rapid detection of ofloxacin resistance in M. tuberculosis

SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Molecular investigation of recurrent tuberculosis in patients from Rwanda

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Diagnostic performance of smear microscopy and incremental yield of Xpert in detection of pulmonary tuberculosis in Rwanda

Background: Tuberculosis control program of Rwanda is currently phasing in light emitting diode-fluorescent microscopy (LED-FM) as an alternative to Ziehl-Neelsen (ZN) smear microscopy. This, alongside the newly introduced Xpert (Cepheid, Sunnyvale, CA, USA) is expected to improve diagnosis of tuberculosis and detection of rifampicin resistance in patients at health facilities. We assessed the accuracy of smear microscopy and the incremental sensitivity of Xpert at tuberculosis laboratories in Rwanda. Methods: This was a cross-sectional study involving four laboratories performing ZN and four laboratories performing LED-FM microscopy. The laboratories include four intermediate (ILs) and four peripheral (PLs) laboratories. After smear microscopy, the left-over of samples, of a single early-morning sputum from 648 participants, were tested using Xpert and mycobacterial culture as a reference standard. Sensitivity of each test was compared and the incremental sensitivity of Xpert after a negative smear was assessed. Results: A total of 96 presumptive pulmonary tuberculosis participants were culture positive for M. tuberculosis. The overall sensitivity in PL of ZN was 55.1 % (40.2-69.3 %), LED-FM was 37 % (19.4-57.6 %) and Xpert was 77.6 % (66.6-86.4 %) whereas in ILs the same value for ZN was 58.3 % (27.7-84.8 %), LED-FM was 62.5 % (24.5-91.5 %) and Xpert was 90 (68.3-98.8 %). The sensitivity for all tests was significantly higher among HIV-negative individuals (all test p <0.05). The overall incremental sensitivity of Xpert over smear microscopy was 32.3 %; p < 0.0001. The incremental sensitivity of Xpert was statistically significant for both smear methods at PL (32.9 %; p = 0.001) but not at the ILs (30 %; p = 0.125) for both smear methods. Conclusions: Our study findings of the early implementation of the LED-FM did not reveal significant increment in sensitivity compared to the method being phased out (ZN). This study showed a significant incremental sensitivity for Xpert from both smear methods at peripheral centers where majority of TB patients are diagnosed. Overall our findings support the recommendation for Xpert as an initial diagnostic test in adults and children presumed to have TB. © 2016 The Author(s)

Results of a national survey on drug resistance among pulmonary tuberculosis patients in Rwanda

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Geographic differences in the contribution of ubiA mutations to high-level ethambutol resistance in mycobacterium tuberculosis

Ethambutol (EMB) resistance can evolve through a multistep process, and mutations in the ubiA (Rv3806c) gene appear to be responsible for high-level EMB resistance in Mycobacterium tuberculosis. We evaluated the prevalence of ubiA and embB (Rv3795) mutations in EMB-resistant strains originating from Africa and South Korea. No differences in embB mutation frequencies were observed between strains from both origins. However, ubiA mutations were present in 45.5% ± 6.5% of the African EMB-resistant isolates but in only 9.5% ± 1.5% of the South Korean EMB-resistant isolates. The ubiA mutations associated with EMB resistance were localized to regions encoding the transmembrane domains of the protein, whereas the embB mutations were localized to regions encoding the extramembrane domains. Larger studies are needed to investigate the causes of increased ubiA mutations as a pathway to high-level EMB resistance in African countries, such as extended EMB usage during tuberculosis treatment