Occurrence of adverse events in patient receiving community-based therapy for multidrug-resistant tuberculosis in Pakistan.

INTRODUCTION: Pakistan ranks 4th among 22 multidrug resistant tuberculosis (MDR-TB) high burden countries. The increasing rate of MDR-TB in Pakistan underscores the importance of effective treatment programs of drug-resistant TB. Clinical management of MDR-TB requires prolonged multidrug regimens that often cause adverse events (AEs). MATERIALS AND METHODS: This retrospective case series study include all patients who were enrolled for MDR-TB treatment during January 2014 till April 2015 at Programmatic Management of Drug Resistant TB (PMDT) unit at tertiary care hospital, Lady Reading Hospital (LRH) Peshawar Pakistan. In this study we sought to ascertain the occurrence of treatment related adverse events and factors associated with these events. Here we also examined the frequency of and reasons for changing drug regimens. We further sought to determine whether the occurrence of adverse events negatively impacts the treatment outcome and management of adverse effects without requiring the discontinuation of MDR-TB therapy. RESULT: At the time of analysis final outcomes of all 200 enrolled patients exist. Among these 52.5% were females and (81.5%) were aged ≤ 44 years. Among study cases 155 (77.2%) experienced at least one adverse event during treatment. The most commonly reported events were psychiatric issues (70%) whereas the less common was skin rashes (7.5%). A change in drug dose due to adverse events occurred in 16.5% cases, while 13.5% cases had at least one drug discontinued temporarily. Younger age and lung cavities at baseline were positive association with occurrence of adverse events. Association was also found between adverse events and treatment outcomes (OR 0.480, 0.236-0.978, p= 0.041). CONCLUSIONS: Adverse events were prevalent among MDR-TB patients treated at PMDT-LRH Peshawar. All patients who were younger aged and cavitory lungs should be closely monitored for occurrence of adverse events.

Screening outcomes of household contacts of multidrug-resistant tuberculosis patients in Peshawar, Pakistan.

OBJECTIVE: To assess the profile of TB/multidrug-resistant TB (MDR-TB) among household contacts of MDR-TB patients. METHODS: Close contacts of MDR-TB patients were traced in the cross-sectional study. Different clinical, radiological and bacteriological were performed to rule out the evidence of TB/MDR-TB. RESULTS: Between January 2012 and December 2012, a total of 200 index MDR-TB patients were initiated on MDR-TB treatment, out of which home visit and contacts screening were conducted for 154 index cases. Of 610 contacts who could be studied, 41 (17.4%) were diagnosed with MDR-TB and 10 (4.2%) had TB. The most common symptoms observed were cough, chest pain and fever. CONCLUSIONS: The high incidence of MDR-TB among close contacts emphasize the need for effective contact screening programme of index MDR-TB cases in order to cut the chain of transmission of this disease.

Rifampicin resistance mutations in the 81 bp RRDR of rpoB gene in Mycobacterium tuberculosis clinical isolates using Xpert MTB/RIF in Khyber Pakhtunkhwa, Pakistan: a retrospective study.

BACKGROUND: Multi-drug resistant tuberculosis (MDR-TB) is a major public health problem especially in developing countries. World Health Organization (WHO) recommends use of Xpert MTB/RIF assay to simultaneously detecting Mycobacterium tuberculosis (MTB) and rifampicin (RIF) resistance. The primary objective of this study was to determine the frequency of MDR-TB in patients suspected to have drug resistance in Khyber Pakhtunkhwa. The frequency of probes for various rpoB gene mutations using Xpert MTB/RIF assay within 81 bp RRDR (Rifampicin Resistance Determining Region) was the secondary objective. METHODS: A total of 2391 specimens, received at Programmatic Management of Drug Resistant TB (PMDT) Unit, Lady Reading Hospital (LRH) Peshawar, Pakistan, between October 2011 and December 2014, were analyzed by Xpert MTB/RIF test. MTB positive with rifampicin resistance were further analyzed to first line anti-mycobacterial drug susceptibility testing (DST) using middle brook 7H10 medium. The data was analyzed using statistical software; SPSS version 18. RESULTS: Out of 2391 specimens, 1408 (59 %) were found positive for MTB and among them, 408 (29 %) showed rifampicin-resistance with four different rpoB gene mutations within 81 bp RRDR. The frequency of various probes among RIF-resistant isolates was observed as: probe E, in 314 out of 408 isolates; B, 44 out of 408; A, 5 out of 408; D, 34 out of 408; and probe C was observed among 6 out of 408 RIF-resistant isolates. The probe A&B and E&D mutation combination was found in only 1 isolate in each case, while B&D mutation combination was detected among 3 out of 408 RIF-resistant isolates. CONCLUSIONS: Hence, it is concluded from our study on a selected population, 29 % of patients had MDR-TB. Probe E related mutations (also known as codon 531and 533) were the most common rpoB genetic mutation [314 (77 %)], acknowledged by Xpert MTB/RIF assay. Least mutation was detected within the sequence 511 (1.2 %).

Characteristics and treatment outcomes of patients with multi-drug resistant tuberculosis at a tertiary care hospital in Peshawar, Pakistan.

OBJECTIVES: To determine characteristics and treatment outcomes of multidrugs resistant tuberculosis (MDR-TB) patients and risk factors for poor outcomes in MDR-TB patients in a tertiary care hospital in Peshawar, Pakistan.  METHODS: This retrospective study was conducted at the Programmatic Management of Drug Resistant TB Unit, Lady Reading Hospital Peshawar, Pakistan and included all MDR-TB patients registered between January 2012 and December 2012. A special proforma was used for data collection. Analysis was performed using SPSS version 16, after exporting data from the proforma. Differences in proportions were assessed using Pearson's Chi square test whereas for predictors of poor outcomes, multivariate logistic regression analysis with Wald Statistical criteria using backward elimination method was performed.  RESULTS: The treatment success rate was 74.3%. In univariate analysis, poor outcomes were associated in patients with age ≥44 years (odds ratio [OR]=0.250; 95% confidence interval [CI]: 0.114-0.519, p=0.001), rural residence (OR=0.417; 95% CI: 0.18-0.937, p=0.03), lung cavitation (OR=0.22; 95% CI, 0.007-0.067, p=0.001), resistance to second line drugs (SLD) (OR=3.441; 95% CI: 1.579-7.497, p=0.001), and resistance to ofloxacin (OR=2.944; 95% CI: 1.361-6.365, p=0.005); whereas multivariate logistic regression analysis, poor outcomes were associated in patients with age ≥44 years (OR=0.249, 95% CI: 0.075-0.828, p=0.023), rural residence (OR=0.143, 95% CI: 0.052-0.774, p=0.032), and cavitatory lungs (OR=0.022, 95% CI: 0.007-0.072, p=0.000).  CONCLUSION: The MDR-TB patient needs special attention for better treatment outcomes. The presence of older age, rural area residence, resistance to ofloxacin, SLD resistance, and cavitary disease are independent prognostic factors for poor outcome in patients with MDR-TB.