The occurrence and frequency of genomic mutations that mediate Isoniazid and Rifampicin resistance in Mycobacterium tuberculosis isolates from untreated pulmonary Tuberculosis cases in urban Blantyre, Malawi

Kumwenda, Geoffrey Peterkins; Chipungu, Geoffrey; Sloan, Derek J.; Kaimila, Yankho; Chiumya, Kondwani; Pangani, Harry

doi:10.4314/mmj.v30i1.1

Cited by 7 publications

(9 citation statements)

References 43 publications

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“… 12 , 27 Moreover, the study reported from Malawi indicated that the S315T1 mutation and the mutation in the inhA gene that occurred in C15T are associated with INH resistance. 37 However, a study in India showed a higher proportion of C15T mutations. 27 Similarly, a study reported from Sudan found a C15T mutation that resulted in INH resistance.…”

Section: Discussionmentioning

confidence: 98%

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Utility of line probe assay in detecting drug resistance and the associated mutations in patients with extrapulmonary tuberculosis in Addis Ababa, Ethiopia

et al. 2022

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Introduction: Molecular tests allow rapid detection of Mycobacterium tuberculosis and drug resistance in a few days. Identifying the mutations in genes associated with drug resistance may contribute to the development of appropriate interventions to improve tuberculosis control. So far, there is little information in Ethiopia about the diagnostic performance of line probe assay (LPA) and the M. tuberculosis common gene mutations associated with drug resistance in extrapulmonary tuberculosis. Thus, this study aimed to assess the frequency of drug resistance-associated mutations in patients with extrapulmonary tuberculosis (EPTB) and to compare the agreement and determine the utility of the genotypic in the detection of drug resistance in Addis Ababa, Ethiopia. Methods: A cross-sectional study was conducted on stored M. tuberculosis isolates. The genotypic and phenotypic drug susceptibility tests were performed using LPA and BACTEC-MGIT-960, respectively. The common mutations were noted, and the agreement and the utility of the LPA were determined using the BACTEC-MGIT-960 as a gold standard. Results: Of the 151 isolates, the sensitivity and specificity of MTBDR plus in detecting isoniazid resistance were 90.9% and 100%, respectively. While for rifampicin, it was 100% and 99.3% for sensitivity and specificity, respectively. The katG S315Tl was the most common mutation observed in 85.7% of the isoniazid-resistant isolates. In the case of rifampicin, the most common mutation (61.9%) was observed at position rpoB S531L. Mutations in the gyrA promoter region were strongly associated with Levofloxacin and Moxifloxacin resistance. Conclusion: Line probe assay has high test performance in detecting resistance to anti-TB drugs in EPTB isolates. The MTBDR plus test was slightly less sensitive for the detection of isoniazid resistance as compared to the detection of rifampicin. The most prevalent mutations associated with isoniazid and rifampicin resistance were observed at katG S315Tl and rpoB S531L respectively. Besides, all the fluoroquinolone-resistant cases were associated with gyrA gene. Finally, a validation study with DNA sequencing is recommended.

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Section: Discussionmentioning

confidence: 98%

“… 27 , 35 , 36 However, our finding was similar to the previous study reported from Ethiopia and Sudan in S531L and H526Y mutations. 37 , 38 …”

Section: Discussionmentioning

confidence: 99%

Utility of line probe assay in detecting drug resistance and the associated mutations in patients with extrapulmonary tuberculosis in Addis Ababa, Ethiopia

et al. 2022

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“…The first step in easing the burden of DR-TB is to comprehend the geographical distribution of the disease and identify regions with the greatest prevalence of notified cases [29]. Drug resistance in Mtb is singularly mediated by chromosomal mutations [31]. Our study detected mutations in rpoB, katG and inhA from the four municipalities.…”

Section: Discussionmentioning

confidence: 93%

“…Strategic measures in combating the spread of DR-TB include active surveillance, screening for DR-TB, early isolation, and management of confirmed cases [31]. The first step in easing the burden of DR-TB is to comprehend the geographical distribution of the disease and identify regions with the greatest prevalence of notified cases [29].…”

Section: Discussionmentioning

confidence: 99%

Spatial Distribution and Clustering of Drug-Resistant <em>Mycobacterium Tuberculosis</em> Infections in Rural Eastern Cape Province of South Africa

Faye¹,

Hosu²,

Vasaikar³

et al. 2022

Preprint

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Tuberculosis (TB), an infectious airborne disease caused by Mycobacterium tuberculosis (Mtb), is a serious public health threat reported as the leading cause of morbidity and mortality worldwide. South Africa is a high TB burden country with TB being the highest infectious disease killer. The study investigated the distribution and clustering of Mtb mutations and spoligotypes in rural Eastern Cape Province. The Mtb isolates included were 1,157 from DR-TB patients and analysed by LPA followed by spoligotyping of 441 isolates, of these, 36 were whole genome sequenced. Distribution of mutations and spoligotypes was done by spatial analysis and clustering analysis was done by Bayesian model-based clustering of allele frequencies at heterozygous sites, using Mclust package in R. The rpoB gene had highest number of mutations. The distribution of rpoB and katG mutations was more prevalent in four health care facilities, inhA mutations were more prevalent in three healthcare facilities and heteroresistant isolates were more prevalent in five healthcare facilities. The Mtb was genetically diverse with Beijing more prevalent and largely distributed. Spatial analysis and mapping of gene mutations and spoligotypes revealed better picture of distribution. Clustering of isolates indicates that there is transmission of mixed infection in this area.

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“…The most highly resistant forms of TB have been described in the literature in a number of different ways, aside from XDR-TB. These include: total drug-resistant TB, 27 , 28 totally drug-resistant TB, 11–14 (TDR-TB), super extensively drug-resistant TB (SXDR-TB or super XDR-TB), 12 , 29 extra extensively drug-resistant TB (XXDR-TB), 11 , 30 pan-resistant TB, 36 , 37 pan drug-resistant TB (PDR-TB), 30 – 33 , 38 , 39 untreatable TB, 34 , 35 , 40 untreatable drug-resistant TB, 36 , 37 incurable TB, 20 , 41 and incurable drug-resistant TB. 42 , 43 The term extremely drug-resistant TB has also, in some cases, been given the same abbreviation as extra extensively drug-resistant TB (XXDR-TB), 38 , 42 and, in others, the same as abbreviation as extensively drug-resistant TB (XDR-TB) 39 , 40 In order to account for this variation in terminology, all of these terms were included as search terms in our review.…”

Section: Methodsmentioning

confidence: 99%

Risk Factors for Poor Outcomes Among Patients with Extensively Drug-Resistant Tuberculosis (XDR-TB): A Scoping Review

Varshney¹,

Anaele²,

Molaei³

et al. 2021

IDR

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In recent years, there has been an upsurge in cases of drug-resistant TB, and strains of TB resistant to all forms of treatment have begun to emerge; the highest level of resistance is classified as extensively drug-resistant tuberculosis (XDR-TB). There is an urgent need to prevent poor outcomes (death/default/failed treatment) of XDR-TB, and knowing the risk factors can inform such efforts. The objective of this scoping review was to therefore identify risk factors for poor outcomes among XDR-TB patients. We searched three scientific databases, PubMed, Scopus, and ProQuest, and identified 25 articles that examined relevant risk factors. Across the included studies, the proportion of patients with poor outcomes ranged from 8.6 to 88.7%. We found that the most commonly reported risk factor for patients with XDR-TB developing poor outcomes was having a history of TB. Other risk factors were human immunodeficiency virus (HIV), a history of incarceration, low body mass, being a smoker, alcohol use, unemployment, being male, and being middle-aged. Knowledge and understanding of the risk factors associated with poor outcomes of XDR-TB can help policy makers and organizations in the process of designing and implementing effective programs.

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The occurrence and frequency of genomic mutations that mediate Isoniazid and Rifampicin resistance in Mycobacterium tuberculosis isolates from untreated pulmonary Tuberculosis cases in urban Blantyre, Malawi

Cited by 7 publications

References 43 publications

Utility of line probe assay in detecting drug resistance and the associated mutations in patients with extrapulmonary tuberculosis in Addis Ababa, Ethiopia

Utility of line probe assay in detecting drug resistance and the associated mutations in patients with extrapulmonary tuberculosis in Addis Ababa, Ethiopia

Spatial Distribution and Clustering of Drug-Resistant <em>Mycobacterium Tuberculosis</em> Infections in Rural Eastern Cape Province of South Africa

Risk Factors for Poor Outcomes Among Patients with Extensively Drug-Resistant Tuberculosis (XDR-TB): A Scoping Review

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