Abstract
BackgroundNewly diagnosed patients without anti-tuberculosis (TB) treatment histories have not often undergone drug susceptibility testing (DST), but have received the standard treatment regimen without information about their DST profiles in many countries with inadequate resources.MethodsWe collected 346 clinical isolates from previously untreated patients with smear-positive active TB in Hanoi, the capital of Vietnam. Of these, 339 were tested for susceptibility to four first-line anti-TB drugs, including isoniazid (INH), rifampicin (RMP), streptomycin (SM), and ethambutol (EMB), using the proportion method. A pyrazinamidase (PZase) test was used to assess pyrazinamide (PZA) resistance. Results of the culture-based drug susceptibility tests were confirmed by those from reverse hybridization-based line probe assays (LiPAs) that detected mutations associated with RMP, INH, PZA, and fluoroquinolone (FQ) resistance. To investigate a diversity of these strains, IS6110-probed restriction fragment length polymorphisms (RFLPs) were analyzed. Nucleotide sequences for furA-katG and fabG1-inhA operons, transcription units responsible for INH resistance, were also determined.ResultsOf the isolates tested, 127 (37.5%) were resistant to at least one of the four drugs, which included 93 (27.4%) isolates that were resistant to INH. RFLP analysis identified four clusters defined by similarity of the band patterns, which accounted for 46.1% of the tested isolates. Among the clustered isolates, 37.7% were resistant to INH, most of which (85.4%) carried a g944c mutation, which causes an S315T amino acid substitution, in the katG gene.ConclusionsOur results suggest that drug-resistant strains, particularly those with INH resistance characterized by a single mutation, S315T, are spreading in Hanoi, Vietnam. When RMP resistance is combined with this setting, patients are not easily cured by conventional short-term treatment. We will need to carefully monitor these trends and search for the origins and transmission routes of these strains.
Highlights
Diagnosed patients without anti-tuberculosis (TB) treatment histories have not often undergone drug susceptibility testing (DST), but have received the standard treatment regimen without information about their DST profiles in many countries with inadequate resources
A single standard anti-tuberculosis (TB) treatment without information regarding drug susceptibility is prone to failure or relapse, as initial drug resistance increases the chance of acquiring additional drug resistance [1]
Clinical isolates from acid-fast bacilli (AFB)-positive sputum Clinical isolates were consecutively collected from previously untreated patients with AFB-positive active TB in Hanoi city between August 2007 and August 2008
Summary
Diagnosed patients without anti-tuberculosis (TB) treatment histories have not often undergone drug susceptibility testing (DST), but have received the standard treatment regimen without information about their DST profiles in many countries with inadequate resources. The drug susceptibility profiles of clinically isolated Mycobacterium tuberculosis (MTB) strains, those from previously untreated patients, have not been included in clinical practice in many countries with inadequate resources. Molecular fingerprinting of MTB strains has been used extensively and is crucial for elucidating the transmission routes of drug-resistant TB [2,3]. Vietnam is a Southeast Asian country stretching over 1,800 km from north to south. It is one of 22 high-burden countries worldwide, and its TB prevalence remains high (323 per 100,000 in 2011) [4]. Vietnam reported an incidence of 2.7% multi-drug resistant-TB among new cases in a 2006 survey (95% confidence interval: 2.0–3.6) [5]
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