Extensively Drug-Resistant Tuberculosis, Pakistan

Hasan, Rumina; Jabeen, Kauser; Ali, Asho; Rafiq, Yasraba; Laiq, Rabia; Malik, Babar; Tanveer, Mahnaz; Groenheit, Ramona; Ghebremichael, Solomon; Hoffner, Sven; Hasan, Zahra

doi:10.3201/eid1609.100280

Cited by 41 publications

(41 citation statements)

References 12 publications

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“…tuberculosis strains were obtained from the strain bank at Aga Khan University Clinical Microbiology laboratory, Pakistan. Fifty XDR M. tuberculosis isolates which had previously been spoligotyped were selected randomly for the study (27). These strains were from the period of 2004 to 2009 and included 26 CAS isolates, 4 Beijing and 4 T family strains, 2 East African Indian (EAI) and 2 U family strains, 1 Pak3 and 1 X family strain, and 10 Unique strains.…”

Section: Mycobacterium Tuberculosis Isolatesmentioning

confidence: 99%

“…However, Beijing strains were found to be associated with MDR (49). CAS strains were found to be the most prevalent (42.1%) among XDR M. tuberculosis isolates, followed by Beijing (8.8%) and T (7%) family strains (27).…”

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confidence: 99%

“…Global occurrence of XDR-TB among all MDR-TB cases is reportedly 6.6%, while in Asia, including Bangladesh and Indonesia, it has been reported as 1.5% (43). Recent data from Pakistan report that the number of XDR-TB cases has increased from 11 (or 1.5%) of 728 MDR isolates in 2006 to 53 (or 4.5%) of 1,181 MDR isolates in 2009 (27). Therefore, there is an urgent need for rapid and reliable tools for diagnosis of MDR-and XDR-TB to aid appropriate treatment and management of drug-resistant TB, particularly in this high-burden setting.…”

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confidence: 99%

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Characterization of Mutations Conferring Extensive Drug Resistance to Mycobacterium tuberculosis Isolates in Pakistan

Ali

Hasan

Jabeen

et al. 2011

Antimicrob Agents Chemother

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The increasing incidence of extensively drug-resistant (XDR) Mycobacterium tuberculosis in high-tuberculosis-burden countries further highlights the need for improved rapid diagnostic assays. An increasing incidence of XDR M. tuberculosis strains in Pakistan has been reported, but drug resistance-associated mutations in these strains have not been evaluated previously. We sequenced the "hot-spot" regions of rpoB, katG, inhA, ahpC, gyrA, gyrB, and rrs genes in 50 XDR M. tuberculosis strains. It was observed that 2% of rifampin, 6% of isoniazid, 24% of fluoroquinolone, and 32% of aminoglycoside/capreomycin resistance in XDR M. tuberculosis strains would be undetected if only these common hot-spot regions were tested. The frequencies of resistanceconferring mutations were found to be comparable among all XDR M. tuberculosis strain families present, including the Central Asian Strain, Beijing, and East African Indian genogroups and the Unique isolates. Additional genetic loci need to be tested for detection of mutations conferring fluoroquinolone, aminoglycoside, and capreomycin resistance in order to improve molecular diagnosis of regional XDR M. tuberculosis strains.

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Section: Mycobacterium Tuberculosis Isolatesmentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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Characterization of Mutations Conferring Extensive Drug Resistance to Mycobacterium tuberculosis Isolates in Pakistan

Ali

Hasan

Jabeen

et al. 2011

Antimicrob Agents Chemother

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“…Extensively drug-resistant (XDR) strains, i.e., resistant to INH, RIF, fluoroquinolones, and one of three injectable second-line drugs (amikacin, kanamycin, or capreomycin), have been observed in South Africa, Russia, Eastern Europe, and East Asia (2)(3)(4). Multidrug resistance has been associated with strains belonging to nearly every Mycobacterium tuberculosis lineage (or strain family), including Beijing (5-8), Latin American-Mediterranean (LAM) (9), and Central Asian (CAS) (10,11). In all cases investigated so far, multidrug resistance in M. tuberculosis appears to result from stepwise acquisition of mutations in individual resistance genes.…”

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Multidrug-Resistant Tuberculosis in Panama Is Driven by Clonal Expansion of a Multidrug-Resistant Mycobacterium tuberculosis Strain Related to the KZN Extensively Drug-Resistant M. tuberculosis Strain from South Africa

et al. 2013

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dMultidrug-resistant tuberculosis (MDR-TB) is a significant health problem in Panama. The extent to which such cases are the result of primary or acquired resistance and the strain families involved are unknown. We performed whole-genome sequencing of a collection of 66 clinical MDR isolates, along with 31 drug-susceptible isolates, that were isolated in Panama between 2001 and 2010; 78% of the MDR isolates belong to the Latin American-Mediterranean (LAM) family. Drug resistance mutations correlated well with drug susceptibility profiles. To determine the relationships among these strains and to better understand the acquisition of resistance mutations, a phylogenetic tree was constructed based on a genome-wide single-nucleotide polymorphism analysis. The phylogenetic tree shows that the isolates are highly clustered, with a single strain (LAM9-c1) accounting for nearly one-half of the MDR isolates (29/66 isolates). The LAM9-c1 strain was most prevalent among male patients of working age and was associated with high mortality rates. Members of this cluster all share identical mutations conferring resistance to isoniazid (KatG S315T mutation), rifampin (RpoB S531L mutation), and streptomycin (rrs C517T mutation). This evidence of primary resistance supports a model in which MDR-TB in Panama is driven by clonal expansion and ongoing transmission of several strains in the LAM family, including the highly successful MDR strain LAM9-c1. The phylogenetic analysis also shows that the LAM9-c1 strain is closely related to the KwaZulu-Natal (KZN) extensively drug-resistant TB strain identified in KwaZulu-Natal, South Africa. The LAM9-c1 and KZN strains likely arose from a recent common ancestor that was transmitted between Panama and South Africa and had the capacity to tolerate an accumulation of multiple resistance mutations.

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“…[51][52][53] A recent multicountry study found that in neighbouring India, 10.1% of first-line Isoniazid and Rifampicin samples tested were substandard. 54 While a number of factors are likely to contribute to the reported increase in number of XDR-TB cases from Pakistan 55 poor quality of TB drugs and inappropriate prescription have a significant role in driving resistance. For example, both Pakistan and India have reported increasing quinolone resistance.…”

Section: Policy Efforts To Respondmentioning

confidence: 99%

Exploring the evidence base for national and regional policy interventions to combat resistance

et al. 2016

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Extensively Drug-Resistant Tuberculosis, Pakistan

Cited by 41 publications

References 12 publications

Characterization of Mutations Conferring Extensive Drug Resistance to Mycobacterium tuberculosis Isolates in Pakistan

Characterization of Mutations Conferring Extensive Drug Resistance to Mycobacterium tuberculosis Isolates in Pakistan

Multidrug-Resistant Tuberculosis in Panama Is Driven by Clonal Expansion of a Multidrug-Resistant Mycobacterium tuberculosis Strain Related to the KZN Extensively Drug-Resistant M. tuberculosis Strain from South Africa

Exploring the evidence base for national and regional policy interventions to combat resistance

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