High isoniazid resistance rates in rifampicin susceptible mycobacterium tuberculosis pulmonary isolates from Pakistan

Background: Rapid new diagnostic methods (including Xpert MTB/RIF assay) use rifampicin resistance as a surrogate marker for multidrug resistant tuberculosis. Patients infected with rifampicin susceptible strains are prescribed first line anti-tuberculosis therapy. The roll out of such methods raises a concern that strains with resistance to other first line anti-tuberculosis drugs including isoniazid will be missed and inappropriate treatment given. To evaluate implications of using such methods review of resistance data from high burden settings such as ours is essential. Objective: To determine resistance to first line anti-tuberculosis drugs amongst rifampicin susceptible pulmonary Mycobacterium tuberculosis (MTB) isolates from Pakistan. Material and Methods: Data of pulmonary Mycobacterium tuberculosis strains isolated in Aga Khan University Hospital (AKUH) laboratory (2009-2011) was retrospectively analyzed. Antimicrobial susceptibility profile of rifampicin susceptible isolates was evaluated for resistance to isoniazid, pyrazinamide, ethambutol, and streptomycin. Results: Pulmonary specimens submitted to AKUH from 2009 to 2011 yielded 7738 strains of Mycobacterium tuberculosis. These included 54% (n 4183) rifampicin susceptible and 46% (n: 3555) rifampicin resistant strains. Analysis of rifampicin susceptible strains showed resistance to at least one of the first line drugs in 27% (n:1133) of isolates. Overall isoniazid resistance was 15.5% (n: 649), with an isoniazid mono-resistance rate of 4% (n: 174). Combined resistance to isoniazid, pyrazinamide, and ethambutol was noted in 1% (n: 40), while resistance to isoniazid, pyrazinamide, ethambutol, and streptomycin was observed in 1.7% (n: 70) of strains. Conculsion: Our data suggests that techniques (including Xpert MTB/RIF assay) relying on rifampicin susceptibility as an indicator for initiating first line therapy will not detect patients infected with MTB strains resistant to other first line drugs (including isoniazid). The roll out of these techniques must therefore be accompanied by strict monitoring ensuring early resistance detection to increase chances of improved patient outcomes

Multidrug resistant Mycobacterium tuberculosis amongst Category I & II failures and Category II relapse patients from Pakistan

AbstractObjectiveTo determine the prevalence of multidrug-resistant tuberculosis (MDR-TB) among previously treated TB patients in Khyber Pakhtunkhwa (KP) Province, Pakistan.Design and settingsA cross-sectional study was conducted (January–September 2009) in 10 districts of KP. All Category (CAT) I and CAT II failures, and CAT II relapse cases were recruited within 1week following declaration of treatment outcome or re-registration of CAT II. Clinical information and sputum was collected from each patient.ResultsTotal 139 patients were enrolled. Mycobacterium tuberculosis bacilli (MTB) was isolated in 113 (81.3%) samples; Mycobacterium other than tuberculosis (MOTT) was isolated in 7 (5%) samples. MDR-TB was noted in 66 (58.4%) patients and extensive drug resistant (XDR-TB) in 2 (1.8%) patients. Amongst MDR patients, 20 (62.5%) were CAT I failure, 19 (76%) CAT II failure and 27 (48.2%) CAT II relapse cases. Resistance to Isoniazid was most common in 84 (74%) cases, followed by Pyrazinamide in 73 (64.6%) cases, Rifampicin in 67 (59%) cases, Streptomycin in 60 (53%) cases, Ethambutol in 58 (51%) cases, and Ofloxacin in 18 (22.2%) cases.ConclusionHigh rate of drug resistance, including MDR observed among failures and relapse cases. This study emphasizes the need to review TB care delivery, particularly in failure cases in difficult regions such as KP that have seen considerable population displacement and conflict in recent years

Extensively Drug-Resistant Tuberculosis, Pakistan

Frequency of extensively drug-resistant tuberculosis in Pakistan increased from 1.5% in 2006 to 4.5% in 2009 (p<0.01). To understand the epidemiology, we genotyped selected strains by using spoligotyping, mycobacterial interspersed repetitive units–variable number of tandem repeats, and IS6110 restriction fragment length polymorphism analysis

Resistance to first line anti-tuberculosis agents^* amongst rifampicin susceptible <i>Mycobacterium tuberculosis</i> isolates.

*<p>Isoniazid (H); Pyrazinamide (Z); Ethambutol (E); Streptomycin (S).</p>#<p>Any resistance, either singly or in combination with other 1^st line drugs.</p>‡<p>%, Susceptible or resistant isolates expressed as a percentage of total rifampicin susceptible strains isolated during stated time period.</p

Province wise distribution of isoniazid mono-resistance amongst rifampicin susceptible isolates: 2009–2011.

<p>R(s), rifampicin susceptible strains.</p><p>H(r), Isoniazid mono-resistant strains amongst rifampicin susceptible strains of the respective province.</p>*<p>%, Isoniazid mono-resistance amongst rifampicin susceptible strains of the respective province.</p><p>KPK, Khyber Pakhtunkhwa.</p

Prevalence of ST26 among untreated smear-positive tuberculosis patients from Karachi indicating ongoing transmission

Tuberculosis (TB) control is a major healthcare priority for Pakistan. We have studied Mycobacterium tuberculosis strains from the sputa of 100 treatment-naive, smear-positive pulmonary TB cases from Karachi, Pakistan, to identify strains most responsible for active transmission in this population. DNA extracted from M. tuberculosis isolates were subjected to spacer oligotyping (spoligotyping). Sixty-six (66%) clinical isolates were grouped into 9 different clusters. The largest cluster comprised the Central Asian Strain (CAS) 1 or ST26 (n = 40). The remaining isolates (34%) had unique spoligotypes. We conclude that ST26 being the most prevalent strain in smear-positive cases contributes greatly towards ongoing transmission in Karachi. Our data further suggest that ST26 may have a selection advantage not afforded by other genotypes. This conclusion is further supported by DESTUS analysis (Detecting Emerging Strains of Tuberculosis Using Spoligotypes) identifying ST26 as the only emerging spoligotype. Reasons for the spread of ST26 require further study

Prevalence of multi-drug resistant tuberculosis in Karachi, Pakistan: identification of at risk groups

Multidrug-resistant tuberculosis (MDR-TB) is a possible threat to global tuberculosis control. Despite a disease prevalence of 263/100 000 population Pakistan lacks information on prevalence of drug resistant TB. Our objective was to estimate prevalence of MDR and associated risk factors in Patients with pulmonary tuberculosis in Karachi. Six hundred and forty consenting adult Patients were enrolled from field clinics from July 2006 to August 2008 through passive case finding. Prevalence of MDR-TB with 95% confidence interval (CI) was calculated with Epi-Info. Logistic Regression analyses were performed for risk factors associated with MDR. Overall MDR rate was 5.0%, 95% Cl: 3.3-6.6% (untreated 2.3%, treated 17.9%). Mean age was 32.5 (+/- 15.6) years and there were 292 (45.6%) females and 348 (54.4%) males. Factors independently associated with MDR were: female gender (OR 3.12, 95% CI: 1.40-6.91), and prior history of incomplete treatment (OR 10.1, 95% CI: 4.71-21.64). Ethnic groups at higher risk for MDR included Sindhis (OR 4.5, 95% CI: 1.42-14.71) and Pashtoons (OR 3.6, 95% CI: 1.12-11.62). This study reports an overall MDR rate of 5.0% in our study population. It further highlights the need for MDR prevention through re-focusing Directly Observed Treatment, Short-course DOTS delivery with emphasis on women and certain high risk sub groups. (C) 2010 Royal Society of Tropical Medicine and Hygiene

Fluoroquinolone Resistance among Mycobacterium tuberculosis Strains from Karachi, Pakistan: Data from Community-Based Field Clinics ▿

A fluoroquinolone (FQ) resistance rate of 5.9% is reported in 205 Mycobacterium tuberculosis isolates from patients presenting to field clinics in Karachi, Pakistan (2006 to 2009). FQ resistance among multidrug-resistant (MDR) strains was 11.1% (5/45), and it was 4.9% (5/103) in M. tuberculosis strains susceptible to all first-line agents. Spoligotyping of resistant strains did not show dominance of one strain type. Our data reflect considerable FQ-resistant M. tuberculosis isolates and the need to consider inclusion of FQ within first-line sensitivity testing in such settings

Characterizing Mycobacterium tuberculosis isolates from Karachi, Pakistan: drug resistance and genotypes

Objectives: To study the prevalence, risk factors, and genotypes of drug-resistant Mycobacterium tuberculosis in Karachi. Methods: Pulmonary tuberculosis (TB) Patients were recruited in a cross-sectional study (2006-2009). Drug susceptibility testing was performed for culture-positive cases (n = 1004). Factors associated with drug resistance were evaluated using logistic regression analysis. Strains were typed using spoligotyping and mycobacterial interspersed repetitive units-variable number tandem repeat (MIRU-VNTR). The associations of genotype and drug resistance were explored using the Chi-square test. Results: Resistance rates - new and previously treated - were as follows: multidrug-resistant (MDR)-TB, 2.4% and 13.9%, respectively, rifampin (RIF) monoresistance, 0.1% and 0.6%, respectively, any isoniazid (INH) resistance, 8.9% and 28.5%, respectively, and INH monoresistance, 3.0% and 6.3%, respectively. Prior TB treatment was a risk factor for MDR-TB (adjusted odds ratio (AOR) 6.8, 95% confidence interval (CI) 3.5-13.1) and INH monoresistance (AOR 2.4, 95% CI 1.1-5.2). Additional risk factors included low socioeconomic status for INH monoresistance (AOR 3.3, 95% CI 1.7-6.5), and belonging to Balouchi (AOR 9.2, 95% CI 2.5-33.4), Sindhi (AOR 4.1, 95% CI 1.2-13.5), or Pakhtun (AOR 3.4, 95% CI 1.0-11.2) ethnicity for MDR-TB. Although Central Asian strain (55.6%) was the most prevalent genotype, MDR-TB was significantly associated with Haarlem (H) genogroup (crude OR 9.2, 95% CI 3.6-23.8). Conclusion: An MDR-TB rate of 2.4% is reported in new Patients. Low RIF monoresistance supports the use of RIF as a marker for MDR-TB in this population. The need to strengthen TB care in the identified at-risk groups is emphasized. Based on INH resistance rates, a review of national treatment/prevention regimens relying on INH is suggested