scholarly journals Molecular characterization and drug resistance patterns of Mycobacterium tuberculosis complex in extrapulmonary tuberculosis patients in Addis Ababa, Ethiopia

PLoS ONE ◽  
2020 ◽  
Vol 15 (12) ◽  
pp. e0243493
Author(s):  
Getu Diriba ◽  
Abebaw Kebede ◽  
Habteyes Hailu Tola ◽  
Bazezew Yenew ◽  
Shewki Moga ◽  
...  

Background Molecular characterization of Mycobacterium tuberculosis (MTB) is important to understand the pathogenesis, diagnosis, treatment, and prevention of tuberculosis (TB). However, there is limited information on molecular characteristics and drug-resistant patterns of MTB in patients with extra-pulmonary tuberculosis (EPTB) in Ethiopia. Thus, this study aimed to determine the molecular characteristics and drug resistance patterns of MTB in patients with EPTB in Addis Ababa, Ethiopia. Methods This study was conducted on frozen stored isolates of EPTB survey conducted in Addis Ababa, Ethiopia. A drug susceptibility test was performed using BACTEC-MGIT 960. Species and strain identification were performed using the Geno-Type MTBC and spoligotyping technique, respectively. Data were entered into the MIRU-VNTRplus database to assess the spoligotype patterns of MTB. Analysis was performed using SPSS version 23, and participants’ characteristics were presented by numbers and proportions. Results Of 151 MTB isolates, 29 (19.2%) were resistant to at least one drug. The highest proportion of isolates was resistant to Isoniazid (14.6%) and Pyrazinamide (14.6%). Nine percent of isolates had multidrug-resistant TB (MDR-TB), and 21.4% of them had pre-extensively drug-resistant TB (pre-XDR-TB). Among the 151 MTB isolates characterized by spoligotyping, 142 (94.6%) had known patterns, while 9 (6.0%) isolates were not matched with the MIRU-VNTRplus spoligotype database. Of the isolates which had known patterns, 2% was M.bovis while 98% M. tuberculosis. Forty-one different spoligotype patterns were identified. The most frequently identified SpolDB4 (SIT) wereSIT149 (21.2%), SIT53 (14.6%) and SIT26 (9.6%). The predominant genotypes identified were T (53.6%), Central Asia Strain (19.2%) and Haarlem (9.9%). Conclusion The present study showed a high proportion of MDR-TB and pre-XDR-TB among EPTB patients. The strains were mostly grouped into SIT149, SIT53, and SIT26. The T family lineage was the most prevalent genotype. MDR-TB and pre-XDR-TB prevention is required to combat these strains in EPTB. A large scale study is required to describe the molecular characteristics and drug resistance patterns of MTB isolates in EPTB patients.

2021 ◽  
Vol 49 (1) ◽  
pp. 030006052098493
Author(s):  
Jie Zhang ◽  
Yixuan Ren ◽  
Liping Pan ◽  
Junli Yi ◽  
Tong Guan ◽  
...  

Objective This study analyzed drug resistance and mutations profiles in Mycobacterium tuberculosis isolates in a surveillance site in Huairou District, Beijing, China. Methods The proportion method was used to assess drug resistance profiles for four first-line and seven second-line anti-tuberculosis (TB) drugs. Molecular line probe assays were used for the rapid detection of resistance to rifampicin (RIF) and isoniazid (INH). Results Among 235 strains of M. tuberculosis, 79 (33.6%) isolates were resistant to one or more drugs. The isolates included 18 monoresistant (7.7%), 19 polyresistant (8.1%), 28 RIF-resistant (11.9%), 24 multidrug-resistant (MDR) (10.2%), 7 pre-extensively drug-resistant (XDR, 3.0%), and 2 XDR strains (0.9%). A higher rate of MDR-TB was detected among previously treated patients than among patients with newly diagnosed TB (34.5% vs. 6.8%). The majority (62.5%) of RIF-resistant isolates exhibited a mutation at S531L in the DNA-dependent RNA polymerase gene. Meanwhile, 62.9% of INH-resistant isolates carried a mutation at S315T1 in the katG gene. Conclusion Our results confirmed the high rate of drug-resistant TB, especially MDR-TB, in Huairou District, Beijing, China. Therefore, detailed drug testing is crucial in the evaluation of MDR-TB treatment.


2005 ◽  
Vol 49 (9) ◽  
pp. 3794-3802 ◽  
Author(s):  
Manzour Hernando Hazbón ◽  
Miriam Bobadilla del Valle ◽  
Marta Inírida Guerrero ◽  
Mandira Varma-Basil ◽  
Ingrid Filliol ◽  
...  

ABSTRACT Mutations at position 306 of embB (embB306) have been proposed as a marker for ethambutol resistance in Mycobacterium tuberculosis; however, recent reports of embB306 mutations in ethambutol-susceptible isolates caused us to question the biological role of this mutation. We tested 1,020 clinical M. tuberculosis isolates with different drug susceptibility patterns and of different geographical origins for associations between embB306 mutations, drug resistance patterns, and major genetic group. One hundred isolates (10%) contained a mutation in embB306; however, only 55 of these mutants were ethambutol resistant. Mutations in embB306 could not be uniquely associated with any particular type of drug resistance and were found in all three major genetic groups. A striking association was observed between these mutations and resistance to any drug (P < 0.001), and the association between embB306 mutations and resistance to increasing numbers of drugs was highly significant (P < 0.001 for trend). We examined the association between embB306 mutations and IS6110 clustering (as a proxy for transmission) among all drug-resistant isolates. Mutations in embB306 were significantly associated with clustering by univariate analysis (odds ratio, 2.44; P = 0.004). In a multivariate model that also included mutations in katG315, katG463, gyrA95, and kasA269, only mutations in embB306 (odds ratio, 2.14; P = 0.008) and katG315 (odds ratio, 1.99; P = 0.015) were found to be independently associated with clustering. In conclusion, embB306 mutations do not cause classical ethambutol resistance but may predispose M. tuberculosis isolates to the development of resistance to increasing numbers of antibiotics and may increase the ability of drug-resistant isolates to be transmitted between subjects.


Author(s):  
Rubeena Hakkak ◽  
Saqib Rishi ◽  
Javid Ahmed Bhat

India is the highest TB burden country in the world having an estimated incidence of 26.9 lakh cases in 2019. With a population of 1.32 billion, India has the highest burden of drug resistant TB (DR-TB) in the world. North zone of India is the second highest MDR-TB prevalent zone after the West zone of India. MDR TB treatment involves prolonged treatment with injectable second-line drugs, associated with more adverse effects, suboptimal treatment outcomes and higher risks of mortality compared to patients with drug-sensitive TB and those with lesser resistant forms of TB. Materials methods: This retrospective study was conducted in the department of Microbiology Government Medical College Anantnag, data was analyzed from March 2017 to February 2018. Non-sterile specimens were processed by Modified Petroff Method. Sterile specimens were concentrated by centrifugation and smear and cultures was inoculated from the sediment. CBNAAT assay was performed by Gene Xpert (Cepheid) 4 system according to the manufacturers’ recommendations. Results: Of the total 1497 clinically suspected tuberculosis specimens collected, 1370 (91.5%) were pulmonary and 127 (8.5%) were presumptive extra pulmonary tuberculosis received from different anatomical sites. Maximum clustering of cases was seen in 10-20 years age group. Out of the total 1497 samples 200 were CBNAAT confirmed Mycobacterium Tuberculosis positive samples. In which 155 were pulmonary and 45 were extra pulmonary. The average percentage positivity rate (i.e. percentage of MTB positive samples out of total samples tested) was 13.3% (200/1497).  Rifampicin resistance (RR-TB) was seen in 5.5% (11/200) samples. Out of the samples detected positive (200): 155 were pulmonary samples and out of these 155 pulmonary samples 8 were found to be RR MTB 5.1% (8/155).  Also out of the 200 positive samples 45 were extra pulmonary and out of these 45 extra pulmonary samples 3 were found to be RR MTB 6.6% (3/45). Conclusion: In this study we found that in our region 5.5%  cases of TB were RR-TB, 3.2% were new cases and 13% RR-TB was seen in  previously treated cases of MTB. The screening of drug resistance has to be expanded to offer universal DST including expanded DST .The second and most important activity is to strengthen drug resistance surveillance under the various national programs with inclusion of laboratories in the private sector as well. The state level regional studies also give us the opportunity to plan and execute intervention prioritization, based on the drug resistance trends observed.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Lin Liu ◽  
Xiujuan Zhao ◽  
Xingyong Wu ◽  
Sijing Li ◽  
Biao Liu ◽  
...  

Abstract Background The emergence of antimicrobial resistance against Mycobacterium tuberculosis (M. tuberculosis) has become the major concern in global tuberculosis control due to its limited therapy options and high mortality. However, the clinical and molecular characteristics of drug-resistant strains vary in different geographical areas. Hainan Island located in southern China, is a high drug-resistant tuberculosis burden area. This study aimed to determine the dynamic changes of drug-resistance patterns and drug-related gene mutation types of M. tuberculosis in Hainan from 2014 to 2019. Results A total of 1484 culture-confirmed M. tuberculosis were included in this study. It was found that the proportions of drug resistance to isoniazid and rifampin were 31.3 and 31.1% respectively. Overall the proportion of multidrug resistant M. tuberculosis was 24.9%. Multivariate logistic regression analysis showed that age and the treatment history were independent influencing factors of drug resistant tuberculosis. The proportions of drug-resistant tuberculosis in retreatment patients were considerably higher than those in new patients. The most common mutation types of isoniazid were Ser315 → Thr (66.3%), and the most common mutation types of rifampin were Ser531 → Leu (41.5%). Conclusions Our data suggests that the prevalence of drug resistant TB remains high in Hainan, and the risks for developing drug resistance with diversified mutation types increased significantly in retreatment patients. These results contribute to the knowledge of the prevalence of drug resistance in Hainan Province and expand the molecular characteristics of drug resistance in China simultaneously.


Author(s):  
F Arif ◽  
T Tahir ◽  
S Suhail ◽  
R Anees ◽  
I Nadeem ◽  
...  

Mycobacterium tuberculosis shows drug resistance patterns (drug-resistance tuberculosis DR-TB) for strains that are induced with high mortality rates. Because this acid-fast bacterium resists extensively against drugs and masks their effects to control the disease. However, these chromosomal mutations and genetic factors lead towards recent anti-TB drug discoveries. Anti-TB regimens are dearth to control this pandemic problem due to the high prevalence of this disease. These situations are remarkably given new ray to discover newer drugs that target such bacilli strains genetic factors and mutations. Also, it provides molecular updates to the resistance mechanism of mutations and genetic factors as a basic target then screened-out recent new anti-TB agents to limit the MDR-TB.


2021 ◽  
Vol 2 (4) ◽  
pp. 232-243
Author(s):  
DK Mumena ◽  
G Kwenda ◽  
CW Ngugi ◽  
AK Nyerere

Background: Drug-Resistant Tuberculosis (DR-TB) is one of the major public health issues globally. Zambia is highly burdened by TB and multi-drug resistant TB. In this study, sputum samples obtained from the new and previously treated cases of TB were examined for drug-resistant Mycobacterium tuberculosis (MTB). Methods: Sputum specimens were processed using the N-acetyl-L-cysteine-sodium hydroxide method, stained and examined using fluorescent technique and microscopy respectively. Mycobacterial DNA was extracted using the Genolyse kit, then subjected to multiplex polymerase chain reaction amplification and reverse hybridization. Drug-resistance and mutations in MTB genes were detected using the Genotype MTBDRplus VER 2.0 and MTBDRsl VER 2.0 assays. Results: A total of 329 MTB-positive sputum specimens, 102 from the new TB cases and 227 from previously treated TB cases, were analysed for drug-resistance. Among the new TB cases, 3.9% had Rifampicin (RIF) mono-resistance, 12.8% Isoniazid (INH) mono-resistance, and 17.7% had Multi-Drug Resistance (MDR). For the previously treated TB cases, 10.1% had RIF mono-resistance, 6.6% INH mono-resistance, 33.0% MDR, 1.8% poly-drug resistance, and 0.8% had pre-Extensively Drug-Resistance (pre-XDR). Mutations identified were rpoB (Ser531Leu, His526Asp, Asp516Val, His526Tyr, and Glu510His), katG (Ser315Thr 1 and Ser315Thr 2), InhA (Cys15Thr), gyrA (Ala90Val and Asp94Gly), and eis (Cys14Thr), each with a varying frequency. Conclusion: DR-TB is prevalent, especially MDR-TB, which is currently the most worrisome form of DR-TB and an emerging threat hampering efforts in the control of TB in Zambia. The early detection and effective treatment of TB cases are key in the control of DR-TB.


1970 ◽  
Vol 7 (1) ◽  
pp. 33-41
Author(s):  
S Subba ◽  
S Singh ◽  
AR Khagi ◽  
R Tuladhar ◽  
B Lekhak ◽  
...  

Background: The emergence and spread of DR and MDR-TB threat global TB control. The susceptibility patterns of M. tuberculosis isolates against anti-tuberculosis drugs informs an important aspect of TB controls and surveillance and analysis of local rates of TB drug resistance helps in the detection and monitoring of the extent of DR and MDR strains, indicating the quality of TB control in the country. Methods: A cross sectional study was conducted to find out antibiotic susceptibility pattern of Mycobacterium tuberculosis in pulmonary tuberculosis patients at national tuberculosis center. All the samples were stained by auramine fluorochrome method; processed by NaOH Ogawa Method; primary cultured; subcultured in 2% Ogawa media; cultured in drug LJ media and finally results observed and interpreted. Here Drug susceptibility test was done on M. tuberculosis isolate from each patient by Proportion method as standard protocol. Results: Ethambutol (66.10%) was found to be the most effective anti-TB drug according to the susceptibility test followed by RMP (60.33%), SM (59.66%) and INH (41.69%) against M. tuberculosis. Among 45 isolated untreated patients, primary drug resistance was observed in 20%, to two drugs in 17.77%, to three drugs in 11.11%, to four drugs in 6.66% and primary Multi-drug resistant in 22.22%. Among 250 isolated from previous treated patients, acquired resistance to one drug was found in 23.60%, to two drugs in 12.40%, to three drugs in 16.40%, to four drugs in 18.80% an acquired Multi-drug resistant in 37.20%. Among 250 treated 68.40% (n=171) were relapse,18% ( n=45) were chronic, 7.6% (n=19) were follow-up, 3.2% (n=8) were defaulter, and 2.8% (n=7) were treatment failure. MDR-TB was found the highest in chronic cases (64.44%) followed by follow-up case (47.36%), treatment failure cases (42.85%), relapse cases (27.48%) and default cases (12.5%). A statistical analysis reveals significant relationship between prior history of treatment and the development of drug resistance. However, no significant relationship between age and sex with the emergence of drug resistance isolates. Conclusion: MDR-TB was found the highest in chronic cases (64.44%) followed by follow-up case (47.36%), treatment failure cases (42.85%), relapse cases (27.48%) and Default cases (12.5%). Key words: multi drug, relapse, resistant, sensitivity, tuberculosis   DOI: 10.3126/jnhrc.v7i1.2277 Journal of Nepal Health Research Council Vol. 7, No. 1, 2009 April 33-41


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