Genetic diversity and drug susceptibility profiles of Mycobacterium tuberculosis obtained from Saint Peter’s TB specialized Hospital, Ethiopia

Damena, Delesa; Tolosa, Samuel; HaileMariam, Milkessa; Zewude, Aboma; Worku, Adane; Mekonnen, Biruk; Mohammed, Temesgen; Admasu, Addisu; Chimusa, Emile R.; Mihret, Adane; Abebe, Tamrat; Ameni, Gobena

doi:10.1371/journal.pone.0218545

Cited by 23 publications

(61 citation statements)

References 30 publications

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“…Among the lineages identified, lineage 4 (Euro-American lineage) was the predominant lineage comprising 79.3% of the isolates. In agreement with our finding, the Euro-American lineage was found to be the most prevalent and widespread lineage in Ethiopia [8,11,27]. This lineage is reported to be prevalent in the central highlands of Ethiopia [25,28].…”

Section: Discussionsupporting

confidence: 91%

Spoligotyping and drug sensitivity of Mycobacterium tuberculosis isolated from pulmonary tuberculosis patients in the Arsi Zone of southeastern Ethiopia

Haile

Tafess

Zewude

et al. 2020

New Microbes and New Infections

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Tuberculosis (TB) is one of the leading causes of morbidity and mortality in different zones of Ethiopia. This study was undertaken to identify the strains of Mycobacterium tuberculosis and evaluate their drug sensitivity profiles in the Arsi Zone. A total of 111 isolates of M. tuberculosis from individuals with pulmonary TB were included and speciation and strain identification were performed using Region of difference 9 and spoligotyping, respectively. The drug sensitivity patterns were assessed using Bactec MGIT 960 SIRE and GenoType MTBDRplus line probe assays. Of 111 isolates, 83% were interpretable and 56 different spoligotype patterns were identified. From these, 22 patterns were shared types while the remaining 34 were orphans. The predominant shared types were spoligotype international type (SIT) 149 and SIT53, comprising 12 and 11 isolates, respectively. Euro-American lineage was the dominant lineage followed by East-African-Indian. Phenotypically, 17.2% of tested isolates were resistant to any first-line drugs and 3.1% were multidrug-resistant. Higher (6.2%) mono-resistance was observed to streptomycin, and no resistance was observed to rifampicin or ethambutol. Genotypically, five (5.4%) isolates were resistant to isoniazid and mutated at codon S315T1 of katG. In contrast, only 1.1% of the isolates were resistant to rifampicin and were mutated at codon S531L of rpoB gene. In this study, a high proportion of orphan strains were isolated, which could suggest the presence of new strains and a high percentage of mono-resistance, warranting the need to strengthen control efforts.

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Section: Discussionsupporting

confidence: 91%

Spoligotyping and drug sensitivity of Mycobacterium tuberculosis isolated from pulmonary tuberculosis patients in the Arsi Zone of southeastern Ethiopia

Haile

Tafess

Zewude

et al. 2020

New Microbes and New Infections

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“…The 15.9% (11/69) drug resistant detection rate using BACTEC MGIT 960 in this study was at greater proportion than similar studies [31,32]. On the contrary, less proportion of drug resistances were reported in this study than other research reports by using the same detection system [20,33] which might be due to different study areas and sample size.…”

Section: Socio-demographic Characteristics Genotypic and Phenotypic contrasting

confidence: 71%

Phenotypic and genotypic drug sensitivity profiles of Mycobacterium tuberculosis infection and associated factors in northeastern Ethiopia

Gashaw

Erko

Mekonnen

et al. 2020

Preprint

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Background Tuberculosis is a devastating and a deadly disease despite the novel advances in its diagnostic tools and drug therapy. Drug resistant Mycobacterium contributes a great share to tuberculosis mortality. Status of drug resistance and patients’ awareness toward the disease is unknown in northeastern Ethiopia. Thus, the aim of this study was to determine the phenotypic and genotypic drug sensitivity patterns and associated factors in Oromia Special Zone and Dessie Town, northeastern Ethiopia. Methods In a cross-sectional study, 384 smear positive tuberculosis cases were recruited and Löwenstein-Jensen culture was done. The performance of GenoTypic MTBDRplus assay using the conventional BACTEC MGIT 960 as a "gold standard" was determined. Drug resistant strains were identified using spoligotyping. Pearson Chi-square test was used to determine the association of drug sensitivity test and tuberculosis type, lineages, dominant strains and clustering of the isolates. For the assessment of patients’ awareness towards the disease questionnaires were used. Results A fair agreement was found between MTBDRplus assay and the conventional MGIT test in detecting the Mycobacterium tuberculosis with sensitivity, specificity, positive and negative predictive value of 94.2%, 30.2%, 68.4% and 76.5%, respectively. The MTBDRplus assay detected 16.8% (16/95) of the isolates as drug resistant and MGIT detected a comparable number 15.9% (11/69) as resistant. Cohen's kappa value showed almost a perfect agreement between the two testing methods in detecting rifampicin (sensitivity 100% and specificity 98.3%) and multi-drug resistance (sensitivity 83.3% and specificity 100%). Spoligotyping identified 76.5% (13/17) of the drug resistant isolates as Euro-American and family 33 as the predominant family. Significant association was observed between drug resistant isolates and the dominant strains (χ2: 34.861; p = 0.040). Majority of the patients heard about tuberculosis as compared to drug resistant Mycobacterium. Conclusion Higher magnitude of drug resistance was found in the study area. The GenoTypic MDRTBplus assay had an acceptable drug sensitivity testing performance. Patients’ awareness towards the disease specifically to the resistant Mycobacterium was low.

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“…An earlier study in our country indicated that the majority of INH resistance was due to katG gene mutations which involved base changes at codon 315 (S315T1 substitution) [ 7 – 10 ]. In agreement with this finding, 76.9% of INH-resistant strains from Addis Ababa have a mutation at the katG gene (S315T1 substitution) revealed high-level INH resistance.…”

Section: Discussionmentioning

confidence: 99%

“…In agreement with this finding, 76.9% of INH-resistant strains from Addis Ababa have a mutation at the katG gene (S315T1 substitution) revealed high-level INH resistance. Mutation in the inhA (C15T substitution) promoter region usually reported in INH monoresistant isolates [ 8 , 10 ]. In line with this result, in our study, 30.8% of mutations in the promoter region of the inhA gene (C15T substitution) were found in the INH monoresistant isolates.…”

Section: Discussionmentioning

confidence: 99%

“…A study conducted in Saint Peter’s TB Referral Hospital between 2015 and 2016 showed that 5.2% of MDR-TB cases were identified among newly diagnosed PTB cases. All the DR-TB cases exhibited drug resistance-conferring gene mutations [ 10 ], which indicate the magnitude of the problem in Addis Ababa, Ethiopia. Drug resistance mutations are diverse and may change over time as different clones expand or shrink, and these changes need to be monitored over time.…”

Section: Introductionmentioning

confidence: 99%

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Molecular detection of multidrug resistance pattern and associated gene mutations in M. tuberculosis isolates from newly diagnosed pulmonary tuberculosis patients in Addis Ababa, Ethiopia

et al. 2020

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Introduction Multi-drug resistance is a major challenge in the control of tuberculosis. Despite newer modalities for diagnosis and treatment, people are still suffering from this disease. Understanding the common gene mutations conferring rifampicin and isoniazid resistance is crucial for the implementation of effective molecular tools at local and national levels. Hence, this study aimed to evaluate the molecular detection of rifampicin and isoniazid-resistant gene mutations in M . tuberculosis isolates in Addis Ababa, Ethiopia. Method Health Center-based cross-sectional study was conducted between January and September 2017 in Addis Ababa, Ethiopia. The collected sputum samples were processed for mycobacterial isolation and Region of difference 9 based polymerase chain reaction for species identification. To characterize the rifampicin and isoniazid-resistant M . tuberculosis isolates, a molecular genetic assay (GenoType MTBDR plus ) was used; the assay is based on DNA-STRIP technology. Result Culture positivity was confirmed in 82.6% (190/230) of smear-positive newly diagnosed pulmonary tuberculosis cases enrolled in the study. From 190 isolates 93.2% were sensitive for both rifampicin and isoniazid, and 6.8% of the isolates were resistant to at least one of the tested anti-TB drugs. Gene mutations were observed in all studied multidrug resistance-associated gene loci ( rpoB , katG , and inhA ). Two isolates exhibited heteroresistance, a mutated, as well as wild type sequences, were detected in the respective strains. MDR-TB case was observed in 1.1% (2/190) of the cases. All the MDR-TB cases were positive for HIV and found to have a history of prior hospital admission. Conclusion In our finding a relatively high prevalence of any drug resistance was observed and the overall prevalence of multidrug-resistant tuberculosis was 1.1%.The majority of drug-resistant isolates demonstrated common mutations. Heteroresistant strains were detected, signaling the existence of an M . tuberculosis population with variable responses to anti-tuberculosis drugs or of mixed infections.

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Genetic diversity and drug susceptibility profiles of Mycobacterium tuberculosis obtained from Saint Peter’s TB specialized Hospital, Ethiopia

Cited by 23 publications

References 30 publications

Spoligotyping and drug sensitivity of Mycobacterium tuberculosis isolated from pulmonary tuberculosis patients in the Arsi Zone of southeastern Ethiopia

Spoligotyping and drug sensitivity of Mycobacterium tuberculosis isolated from pulmonary tuberculosis patients in the Arsi Zone of southeastern Ethiopia

Phenotypic and genotypic drug sensitivity profiles of Mycobacterium tuberculosis infection and associated factors in northeastern Ethiopia

Molecular detection of multidrug resistance pattern and associated gene mutations in M. tuberculosis isolates from newly diagnosed pulmonary tuberculosis patients in Addis Ababa, Ethiopia

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