Phenotypic and genotypic characteristics of drug resistance in Mycobacterium tuberculosis isolates from pediatric population of Chennai, India

Therese, K Lily; Gayathri, R; Balasubramanian, Sundaram; Natrajan, S; Hn, Madhavan

doi:10.4103/0255-0857.103761

Cited by 13 publications

(12 citation statements)

References 8 publications

(9 reference statements)

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“…Therefore, while culture is not the standard of care in India, we optimized TB detection by utilizing an automated liquid culture media system (MGIT). However, compared with other recently published studies (10.7–16%) [8, 24], the recovery of M. tuberculosis was lower (3%) and could be attributed to the high rates of extra-pulmonary TB (46%). While several clinical algorithms and scores for pediatric TB exist, none are sufficiently sensitive or specific.…”

Section: Discussioncontrasting

confidence: 74%

Pediatric Tuberculosis in Young Children in India: A Prospective Study

Jain

Ordoñez

Kinikar

et al. 2013

BioMed Research International

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Background. India has one of the highest tuberculosis (TB) burdens globally. However, few studies have focused on TB in young children, a vulnerable population, where lack of early diagnosis results in poor outcomes. Methods. Young children (≤5 years) with suspected TB were prospectively enrolled at a tertiary hospital in Pune, India. Detailed clinical evaluation, HIV testing, mycobacterial cultures, and drug susceptibility testing were performed. Results. 223 children with suspected TB were enrolled. The median age was 31 months, 46% were female, 86% had received BCG, 57% were malnourished, and 10% were HIV positive. 12% had TB disease (definite or probable), 35% did not have TB, while TB could not be ruled out in 53%. Extrapulmonary disease was noted in 46%, which was predominantly meningeal. Tuberculin skin test (TST) was positive in 20% of children with TB. Four of 7 (57%) children with culture-confirmed TB harbored drug-resistant (DR) strains of whom 2 (50%) were multi-DR (MDR). In adjusted analyses, HIV infection, positive TST, and exposure to household smoke were found to be significantly associated with children with TB (P ≤ 0.04). Mortality (at 1 year) was 3 of 26 (12%) and 1 of 79 (1%), respectively, in children with TB and those without TB (P < 0.05). Conclusions. Diagnosis of TB is challenging in young children, with high rates of extra-pulmonary and meningeal disease. While the data on DR-TB are limited by the small sample size, they are however concerning, and additional studies are needed to more accurately define the prevalence of DR strains in this vulnerable population.

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Section: Discussioncontrasting

confidence: 74%

Pediatric Tuberculosis in Young Children in India: A Prospective Study

Jain

Ordoñez

Kinikar

et al. 2013

BioMed Research International

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“…treated PTB patients281674.95.60.60.042.053.253.25.965.334.72.5LJTB research center44Joseph M R et al, 2007 [39]Eranakulam2003Newly diagnosed PTB patients30527.92.61.017.42.02.0Not specifiedDesignated microscopycenters45James P et al, 2011 [82]Vellore2003–2007Prev. treated PTB patients17772.95.72.858.258.2Not specifiedTertiary hospital46Rajasekaran S et al, 2009 [32]Chennai2004–2007Combined PTB patients292756.433.91.6Tertiary hospital47Nagaraja C et al, 2012 [83]Bangalore2005–2010Combined PTB patients30972.5LJTertiary hospital48Therese K L et al (a), 2012 [84]Chennai2007–2009Combined PTB patients955.611.122.222.2BACT-ECTertiary hospital49Duraisamy K et al, 2014 [85]Kerala2009–2010Prev. treated PTB patients120714.814.8LJRecords from state RNTCP50Bhat S et al, 2010 [86]…”

Section: Resultsmentioning

confidence: 99%

Prevalence of drug-resistant pulmonary tuberculosis in India: systematic review and meta-analysis

et al. 2017

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BackgroundDrug-resistant pulmonary tuberculosis (DR-TB) is a significant public health issue that considerably deters the ongoing TB control efforts in India. The purpose of this review was to investigate the prevalence of DR-TB and understand the regional variation in resistance pattern across India from 1995 to 2015, based on a large body of published epidemiological studies.MethodsA systematic review of published studies reporting prevalence of DR-TB from biomedical databases (PubMed and IndMed) was conducted. Meta-analysis was performed using random effects model and the pooled prevalence estimate (95% confidence interval [CI]) of DR-TB, multidrug resistant (MDR-) TB, pre-extensively drug-resistant (pre-XDR) TB and XDR-TB were calculated across two study periods (decade 1: 1995 to 2005; decade 2: 2006 to 2015), countrywide and in different regions. Heterogeneity in this meta-analysis was assessed using I2 statistic.ResultsA total of 75 of 635 screened studies that fulfilled the inclusion criteria were selected. Over 40% of 45,076 isolates suspected for resistance to any first-line anti-TB drugs tested positive. Comparative analysis revealed a worsening trend in DR-TB between the two study decades (decade 1: 37.7% [95% CI = 29.0; 46.4], n = 25 vs decade 2: 46.1% [95% CI = 39.0; 53.2], n = 36). The pooled estimate of MDR-TB resistance was higher in previously treated patients (decade 1: 29.8% [95% CI = 20.7; 39.0], n = 13; decade 2: 35.8% [95% CI = 29.2; 42.4], n = 24) as compared with the newly diagnosed cases (decade 1: 4.1% [95% CI = 2.7; 5.6], n = 13; decade 2: 5.6% [95% CI = 3.8; 7.4], n = 17). Overall, studies from Western states of India reported highest prevalence of DR-TB (57.8% [95% CI = 37.4; 78.2], n = 6) and MDR-TB (39.9% [95% CI = 21.7; 58.0], n = 6) during decade 2. Prevalence of pre-XDR TB was 7.9% (95% CI = 4.4; 11.4, n = 5) with resistance to fluoroquinolone (66.3% [95% CI = 58.2; 74.4], n = 5) being the highest. The prevalence of XDR-TB was 1.9% (95% CI = 1.2; 2.6, n = 14) over the 20-year period.ConclusionThe alarming increase in the trend of anti-TB drug resistance in India warrants the need for a structured nationwide surveillance to assist the National TB Control Program in strengthening treatment strategies for improved outcomes.

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“…For instance, some authors may have only chosen isolates from patients in whom treatment failed or may have chosen isolates based on a specific resistance profile, such as MDR-or XDR-TB. Several studies did not indicate the isolate selection process, which makes the assessment of selection bias impossible (8,25,51,65,67,71,75,83,84). More focused studies are needed in order to determine whether specific cohorts, such as PZA monoresistant strains, have a unique mechanism of PZA resistance.…”

Section: Discussionmentioning

confidence: 99%

“…1 illustrates the breakdown of the number of articles excluded because of the specified criteria. Of the 61 studies, the earliest study was from 1996, while 20 (33%) were published in the last 3 years (8,25,30,31,35,41,43,47,60,70,73,75,77,(81)(82)(83)(84)(85). In total, there were 6,089 isolates, 2,760 phenotypically PZA r and 3,329 phenotypically PZA s , in the 61 articles that had at least the pncA coding region sequenced.…”

Section: Description Of Included Studies a Search Through Pubmed (Mementioning

confidence: 99%

Systematic Review of Mutations in Pyrazinamidase Associated with Pyrazinamide Resistance in Mycobacterium tuberculosis Clinical Isolates

Ramirez-Busby

Valafar

2015

Antimicrob Agents Chemother

105

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Pyrazinamide (PZA) is an important first-line drug in the treatment of tuberculosis (TB) and of significant interest to the HIV-infected community due to the prevalence of TB-HIV coinfection in some regions of the world. The mechanism of resistance to PZA is unlike that of any other anti-TB drug. The gene pncA, encoding pyrazinamidase (PZase), is associated with resistance to PZA. However, because single mutations in PZase have a low prevalence, the individual sensitivities are low. Hundreds of distinct mutations in the enzyme have been associated with resistance, while some only appear in susceptible isolates. This makes interpretation of molecular testing difficult and often leads to the simplification that any PZase mutation causes resistance. This systematic review reports a comprehensive global list of mutations observed in PZase and its promoter region in clinical strains, their phenotypic association, their global frequencies and diversity, the method of phenotypic determination, their MIC values when given, and the method of MIC determination and assesses the strength of the association between mutations and phenotypic resistance to PZA. In this systematic review, we report global statistics for 641 mutations in 171 (of 187) codons from 2,760 resistant strains and 96 mutations from 3,329 susceptible strains reported in 61 studies. For diagnostics, individual mutations (or any subset) were not sufficiently sensitive. Assuming similar error profiles of the 5 phenotyping platforms included in this study, the entire enzyme and its promoter provide a combined estimated sensitivity of 83%. This review highlights the need for identification of an alternative mechanism(s) of resistance, at least for the unexplained 17% of cases.

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Phenotypic and genotypic characteristics of drug resistance in Mycobacterium tuberculosis isolates from pediatric population of Chennai, India

Cited by 13 publications

References 8 publications

Pediatric Tuberculosis in Young Children in India: A Prospective Study

Pediatric Tuberculosis in Young Children in India: A Prospective Study

Prevalence of drug-resistant pulmonary tuberculosis in India: systematic review and meta-analysis

Systematic Review of Mutations in Pyrazinamidase Associated with Pyrazinamide Resistance in Mycobacterium tuberculosis Clinical Isolates

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