Multidrug-resistant and heteroresistant Mycobacterium tuberculosis and associated gene mutations in Ethiopia

Mekonnen, Daniel; Admassu, Aschalew; Mulu, Wondemagegn; Amor, Arancha; Benito, Agustín; Gelaye, Woynshet; Biadglegne, Fantahun; Abera, Bayeh

doi:10.1016/j.ijid.2015.06.013

Cited by 32 publications

(50 citation statements)

References 25 publications

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“…Likewise, reports from WHO [24], Ethiopia [7] and Northeast China [25] supports this finding. The reason for this might be due to social and health seeking behavior difference and higher exposure of males to outer environment, smoking and alcoholism [24].…”

Section: Discussionsupporting

confidence: 70%

“…However, it was higher than studies observed in Ethiopia [8, 9, 31, 32], Kenya [33], Nigeria [34], Uganda [35] and South of Iraq [36]. In contrast, the proportion of rifampicin-resistant M. tuberculosis was lower than reports in other parts of Ethiopia [7, 36] and Chile [37]. The variation could be due to difference in risk for HIV acquisition, exposure to anti-TB drugs and national TB control program.…”

Section: Discussionmentioning

confidence: 65%

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Rifampicin-resistance pattern of Mycobacterium tuberculosis and associated factors among presumptive tuberculosis patients referred to Debre Markos Referral Hospital, Ethiopia: a cross-sectional study

et al. 2017

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BackgroundPrevailing data on rifampicin-resistant M. tuberculosis is essential for early management of MDR-TB. Therefore, this study was conducted to determine the prevalence of rifampicin-resistant Mycobacterium tuberculosis and associated factors among presumptive TB cases in Debre Markos Referral Hospital, Ethiopia.MethodsA cross-sectional study was conducted from September 2014 to March 2015. Detection of M. tuberculosis and resistance to rifampicin was performed using Gene Xpert MTB/RIF assay. Data was collected using structured questionnaire by face to face interview. Logistic regression analysis was computed to determine the associated factors of rifampicin-resistant M. tuberculosis.ResultsA total of 505 presumptive TB patients included in the study. The prevalence of M. tuberculosis confirmed cases was 117 (23.2%) (95% CI 19.7–27%). It was higher among males (27.9%) than females (17.9%) (AOR: 2.17; CI 1.35–3.49). Of the 117 M. tuberculosis confirmed cases, 12 (10.3%) (95% CI 6.0–17.1%) were resistant to rifampicin. Rifampicin-resistant M. tuberculosis was noticed in 7 previously treated TB patients (17.1%) and 5 treatment naive patients (6.7%) (AOR: 4.16; CI 1.04–16.63). The prevalence of rifampicin-resistant M. tuberculosis was 6 (9.8%) and 6 (11.3%) in pulmonary and extra-pulmonary infections, respectively. Of the 30, MTB/HIV co-infection, 3 (10%) were rifampicin-resistant M. tuberculosis.ConclusionRifampicin-resistant M. tuberculosis is prevalent in both pulmonary and extra-pulmonary tuberculosis patients. Previous treatment with anti-TB drugs was significantly associated with rifampicin resistance. Therefore, the use of Gene Xpert should be scaled up across the country for rapid detection and management of drug resistant M. tuberculosis.

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Section: Discussionsupporting

confidence: 70%

Section: Discussionmentioning

confidence: 65%

Rifampicin-resistance pattern of Mycobacterium tuberculosis and associated factors among presumptive tuberculosis patients referred to Debre Markos Referral Hospital, Ethiopia: a cross-sectional study

et al. 2017

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“…Before 20 years ago, reports showed that the prevalence of MDR-TB was almost nil or 1 % in different parts of Ethiopia [ 7 – 9 ]. Though, nowadays high proportion of MDR-TB were notified within the country [ 10 , 11 ]. It is well understood that bacterial and environmental factors play a great role in the spread of MDR-TB.…”

Section: Discussionmentioning

confidence: 99%

Multidrug resistant tuberculosis: prevalence and risk factors in districts of metema and west armachiho, Northwest Ethiopia

et al. 2015

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BackgroundMulti drug resistant tuberculosis (MDR-TB) is an emerging challenge for TB control programs globally. According to World health organization, 2012 report Ethiopia stands 15th out of the 27 high priority countries in the world and 3rd in Africa. Updated knowledge of the magnitude of MDR-TB is so substantial to allocate resources, and to address prevention and control measures. Therefore, the aim of this study was to assess the prevalence of MDR-TB and associated risk factors in West Armachiho and Metema districts of North Gondar.MethodsA cross-sectional study was conducted in West Armachiho and Metema districts between February 01 and June 25, 2014. A total of 124 consecutive smear positive pulmonary tuberculosis patients were included in the study. Socio-demographic and possible risk factor data were collected using a semi-structured questionnaire. Drug susceptibility testing was first performed for rifampicin using GeneXpert MTB/RIF. For those rifampicin resistant strains, drug susceptibility testing was performed for both isoniazid and rifampicin to identify MDR-TB using the proportional method on LJ media. Data were analyzed using statistical Package SPSS version 20; binary logistic regression was used to assess the association. P-values < 0.05 were considered as statistically significant.ResultsOf 124 smear-positive pulmonary TB patients, 117 (94.4 %) were susceptible to Rifampicin, while 7 (5.7 %) were confirmed to be resistant to Rifampicin and Isoniazid. The overall prevalence of MDR-TB was 5.7 % (2.3 % among new cases and 13.9 % among previously treated cases). History of previous treatment (OR = 7, P = 0.025) was significantly associated risk factor for MDR-TB.ConclusionThe overall prevalence of MDR-TB was 5.7 % among cases at five health centers and a history of previous treatment was found to be a risk factor for being infected by an MDR-TB strain. Therefore, maximizing early case detection and treatment, strengthening TB infection control activities and proper implementation of DOTS are recommended to reduce the burden of MDR-TB.

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“…Detection of heteroresistance. Patients infected with a mixture of susceptible and resistant clones (heteroresistant clones) have been increasingly described in both MDR-TB and XDR-TB cases (47)(48)(49)(50). Detection of heteroresistance can be challenging for molecular assays; however, these mixtures of sequences may be detected as double peaks in T m -based detection systems (42).…”

Section: Resultsmentioning

confidence: 99%

Detection of Isoniazid-, Fluoroquinolone-, Amikacin-, and Kanamycin-Resistant Tuberculosis in an Automated, Multiplexed 10-Color Assay Suitable for Point-of-Care Use

Chakravorty

Roh

Glass³

et al. 2017

J Clin Microbiol

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Extensively drug-resistant (XDR) tuberculosis (TB) cannot be easily or quickly diagnosed. We developed a rapid, automated assay for the detection of XDR-TB plus resistance to the drug isoniazid (INH) for point-of-care use. Using a simple filter-based cartridge with an integrated sample processing function, the assay identified a wide selection of wild-type and mutant sequences associated with XDR-TB directly from sputum. Four new large-Stokes-shift fluorophores were developed. When these four Stokes-shift fluorophores were combined with six conventional fluorophores, 10-color probe detection in a single PCR tube was enabled. A new three-phase, double-nested PCR approach allowed robust melting temperature analysis with enhanced limits of detection (LODs). Finally, newly designed sloppy molecular beacons identified many different mutations using a small number of probes. The assay correctly distinguished wild-type sequences from 32 commonly occurring mutant sequences tested in gyrA, gyrB, katG, and rrs genes and the promoters of inhA and eis genes responsible for resistance to INH, the fluoroquinolone (FQ) drugs, amikacin (AMK), and kanamycin (KAN). The LOD was 300 CFU of Mycobacterium tuberculosis in 1 ml sputum. The rate of detection of heteroresistance by the assay was equivalent to that by Sanger sequencing. In a blind study of 24 clinical sputum samples, resistance mutations were detected in all targets with 100% sensitivity, with the specificity being 93.7 to 100%. Compared to the results of phenotypic susceptibility testing, the sensitivity of the assay was 75% for FQs and 100% each for INH, AMK, and KAN and the specificity was 100% for INH and FQ and 94% for AMK and KAN. Our approach could enable testing for XDR-TB in point-of-care settings, potentially identifying highly drug-resistant TB more quickly and simply than currently available methods.KEYWORDS 10-color assay, three-phase PCR, XDR-TB, point-of-care test

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Multidrug-resistant and heteroresistant Mycobacterium tuberculosis and associated gene mutations in Ethiopia

Abstract: The prevalence of multidrug-resistant M. tuberculosis was high in the study area. Ser531Leu and Ser315Thr1 substitutions were the highest gene mutations for rifampicin and isoniazid, respectively.

Cited by 32 publications

References 25 publications

Rifampicin-resistance pattern of Mycobacterium tuberculosis and associated factors among presumptive tuberculosis patients referred to Debre Markos Referral Hospital, Ethiopia: a cross-sectional study

Rifampicin-resistance pattern of Mycobacterium tuberculosis and associated factors among presumptive tuberculosis patients referred to Debre Markos Referral Hospital, Ethiopia: a cross-sectional study

Multidrug resistant tuberculosis: prevalence and risk factors in districts of metema and west armachiho, Northwest Ethiopia

Detection of Isoniazid-, Fluoroquinolone-, Amikacin-, and Kanamycin-Resistant Tuberculosis in an Automated, Multiplexed 10-Color Assay Suitable for Point-of-Care Use

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