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Objective: To assess the patterns of drug resistance (DR) among patients previously treated for pulmonary tuberculosis (TB). Study Design: Cross-sectional study. Place and Duration of Study: Department of Medicine, Pak-Emirates Military Hospital, Rawalpindi Pakistan, from Jul 2020 to Mar 2021. Methodology: Patients with previously treated pulmonary TB were included, based on their clinical history and characteristic chest X-ray findings. Patients were evaluated through an examination of sputum and/or bronchoalveolar washings for acid-fast bacilli (AFB), Mycobacterium TB-GeneXpert/RIF (Rifampicin) assay, and mycobacterial culture with drug susceptibility testing (DST). Patients with resistance to any anti-TB drug were classified as cases of DR-TB, and a pattern of drug resistance was documented. Results: One hundred twenty patients were identified as having been previously treated for TB. DST demonstrated DR-TB among 38(31.7%) cases, while isoniazid (INH) resistance was the most commonly reported problem in 29(24.2%) cases. Up to 26(21.6%) relapsing cases were resistant to Rifampicin (RFM). Moreover, 15(12.5%) instances of resistance against second-line anti-TB drugs (fluoroquinolones and aminoglycosides) were documented. Multidrug-resistant TB (MDR-TB) was the most prevalent resistance pattern in 20(16.7%) cases, followed by mono-drug-resistant TB in 7(5.8%) and extensively resistant TB (XDR-TB) in 2(1.6%) cases. No definitive resistance pattern was evident among 9(7.5%) cases. Conclusion: MDR-TB constitutes a major barrier in the line of TB eradication in Pakistan. Strict compliance with anti-TB protocols, along with a universal application of DST, can minimize the overall prevalence of relapsing cases of TB. [ABSTRACT FROM AUTHOR]

BACKGROUND: Sputum smear microscopy is the most useful tool used for the screening of presumptive tuberculosis cases. Conventionally Ziehl-Neelsen (ZN) based staining is used to microscopically screen sputum from the presumptive Tuberculosis Cases. However, Fluorescent microscopy (FM) is now gradually replacing the conventional ZN microscopy because of its higher efficiency and efficacy in detecting Mycobacterium tuberculosis. In patients, who do not produce sufficiently high number of bacilli, and are known as Smear-negative, efficacy of both types of microscopy remains questionable as no Mycobacteria are detected in the sputum of these patients and they are falsely labelled as smear-negative. OBJECTIVE: This retrospective study was conducted on the patient samples received from different parts of Sindh to study the proportions of false-negative tuberculosis using fluorescent microscopy. MATERIALS AND METHODS: A retrospective cross-sectional study was conducted from June 2014 to June 2016 at the Tuberculosis Laboratories of Dow University of Health Sciences. Data analyzed for 1439 samples received during 24-month period, which had subsequently been confirmed by culture. All laboratory work was performed as per guidelines of the National Program. Statistical analysis was performed on MedCalc® and Open Epi®. RESULTS: During 24-month period, among the 1439 cases, 832(57.81%) were from males and 499 (34.67%) were smear negative. Culture showed that 72 (14.42%) were false-negative among all-negatives. Overall sensitivity observed was 92.21% [95%CI 90.29%-93.85%] and specificity 82.91% [95%CI 79.38%-86.06%]. The proportion of false negativity among all negatives in females (16.11%) was significantly higher (p=0.002) as compared to males (13.47%). Conclusions: Even with the introduction of Fluorescent Microscopy, smear microscopy cannot be solely relied upon for the diagnosis of tuberculosis, as considerable number of patients producing insufficient number of bacilli to be detected by microscopy. [ABSTRACT FROM AUTHOR]

We describe gender-based differences in a community-wide TB screening programme in Karachi, Pakistan, in which 311 732 individuals were screened in mobile camps using symptom questionnaires and van-mounted digital chest X-ray, between 1 January 2018 and 31 December 2019. Only 22.4% (69 869) of camp attendees were women. Female attendees were less likely to have sputum collected and tested (31.5% (95% CI 30.4% to 32.7%) vs 38.5% (95% CI 37.6% to 39.1%)) or to initiate TB treatment (75.9% (95% CI 68.1% to 82.6%) vs 82.8% (95% CI 78.9% to 86.2%)), when indicated. Among the participants, the age-standardised prevalence of active TB was higher among women (prevalence ratio 1.4, 95% CI 1.1 to 1.7). These findings underscore the importance of integrating gender into the design and monitoring of TB screening programmes to ensure that women and men benefit equally from this important intervention. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB) remains as one of the deadliest diseases after HIV globally with 95% of deaths confined to low-and-middle income countries. Pakistan is fifth among the 22 high-burden TB countries with the incidence rate of 230/100,000 persons, however, studies related to prevalent Mycobacterium tuberculosis strains and their spread, drug resistance pattern and evolutionary genetics are inadequate. The present study was undertaken to highlight the circulation of M. tuberculosis strains causing drug resistant TB in our community by targeting the molecular marker IS6110 and then characterization of these strains as Beijing and Non-Beijing genotypes. Sputum samples from 102 MDR TB suspects from different cities of Punjab were collected and their record was stored in a database. Sputum samples were evaluated by Ziehl Neelson staining and cultured on Lownstein Jensen medium by Modified Petroff's method. DST was performed for first-line anti-mycobacterial drugs by indirect proportion method. Mycobacterium tuberculosis isolates were investigated for the presence of IS6110 and further identification as Beijing, Non-Beijing or mixed genotype. Percentage of male and female patients was found to be 58.8 and 41.2% respectively. DST showed resistance of 93% of isolates to isoniazid and rifampicin. All of the isolates showed positive results for IS6110 amplification. Based on PCR amplification of Beijing and non-Beijing primer sets 4.9% of the patients showed infection with pure Beijing isolates, 14.7% with both Beijing and non-Beijing isolates and 80.3% with pure non-Beijing isolates. Analysis of IS6110 and Beijing sequences showed the presence of putative transposase conserved domain while non-Beijing sequences were epitomized with RAMP_I_III superfamily domain (CRISPR-associated protein family). TB in Pakistan is predominantly caused by Non-Beijing genotypes, but Beijing strains showed incessant circulation in our community as both single and mixed (co-infecting Non-Beijing and Beijing) strains. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To evaluate risk factors for multidrug-resistant tuberculosis (MDR-TB) in an urban setting of Pakistan. Design and methods: In this multicenter case–control study, patients aged 15years old or older with sputum culture and sensitivity (C/S) diagnosed with pulmonary MDR-TB were defined as cases, whereas patients aged 15years old or older with sputum C/S diagnosed and susceptible to pulmonary TB were regarded as controls. Fifty cases and 75 controls were enrolled from three tertiary-care hospitals in Karachi. Results: Multivariable logistic regression models showed that cases were more likely to have had a TB patient in the house prior to the diagnosis of MDR-TB (adjusted odds ratio [ORadj]=3.1, 95% confidence interval [CI]: 1.2, 8.3) or had a history of prior TB treatment (ORadj =4.2, 95% CI: 1.1, 15.4). Furthermore, cases compared with controls tended to be male (ORadj =3.6, 95% CI: 1.4, 9.7), 15–25years of age (ORadj =3.7, 95% CI: 1.2, 11.3), of Sindhi ethnicity (adjusted OR=9.1, 95% CI: 1.9, 43.4) or with low educational attainment (ORadj OR=5.5, 95% CI: 1.7–17.6, for no formal schooling; ORadj =3.8, 95% CI: 1.1–14.1, 1 for 1–5 school years). Conclusions: A TB patient in the house or a history of prior TB treatment was strongly associated with MDR-TB in this study. Furthermore, younger age, male gender, Sindhi ethnicity and poor educational attainment entailed a high risk for MDR-TB. Targeted educational intervention for patients and their contacts may minimize the noncompliance with prescribed TB treatment and lessen MDR-TB magnitude in settings like Karachi. [Copyright &y& Elsevier]

Objectives To investigate whether visual assessment or microscopic grading of the cellular composition of specimens is a better strategy to screen specimen quality for tuberculosis (TB) diagnosis. Methods About 2643 specimens were collected from TB suspects at the Federal TB centre in Pakistan. Specimens were classified as sputum or saliva visually and microscopically using the criteria proposed by McCarter and Robinson, Van Scoy, Geckler et al., Murray and Washington and Bartlett. The acid-fast bacilli (AFB)-positivity of specimens was also assessed. Results Despite being the least ‘technical’ and time consuming, visual assessment rejected the lowest proportion of AFB-positive specimens (0.3%). Most microscopic grading criteria, particularly those that considered the squamous epithelial cell count, rejected a large proportion of specimens (30–66%), of which a sizeable fraction contained AFB (6–12%). Conclusions Our results indicate that visual assessment by trained technicians is more effective and suitable than microscopic grading for screening specimens for TB diagnosis. TB control resources could be better allocated to optimizing visual screening than investing in more ‘strict’ microscopic grading tools. [ABSTRACT FROM AUTHOR]

Background: Pulmonary tuberculosis (TB) with detectable Mycobacterium tuberculosis in the sputum is a major source of transmission. In resource limited TB endemic settings, cure is declared through sputum smear examination for acid fast bacilli without performing culture. This may lead to erroneous treatment outcomes as viable bacteria may be missed due to the low sensitivity of direct smear method. The aim of this study was to investigate if sterilizing cure is achieved among the new pulmonary TB cases declared cured by sputum smear conversion and to evaluate the impact of addition of ethambutol in the continuation phase in achieving it.Methods: New sputum smear-positive pulmonary TB patients registered at a tertiary care hospital in Pakistan from November 2013 to March 2014 were followed under standard Directly Observed Treatment Short Course strategy for 6 months. Half of these patients received ethambutol in addition to isoniazid and rifampicin in the continuation phase. Sputum specimens were examined on microscopy at 2 months and at the end of treatment. Sputa of patients with negative direct smear examination at the end of treatment were cultured.Results: Among 5746 TB suspects, 1595 were new sputum smear positive pulmonary TB cases, and 533 were registered at our hospital. Among these, 504 converted sputum negative at 2 months and 348 converted at the end of 6 months of treatment and were declared cured. Sputa of 204/348 patients were cultured, and 12/204 (6%) were culture-positive. Culture positivity at 6 months was not associated with bacterial load, smoking, diabetes, presence of cavities, history of contact with TB patients, age, sex, socioeconomic status, or addition of ethambutol in the continuation phase.Conclusion: Viable cultivable bacilli were detected in 6% of cured patients, which would have significant impact on the control of TB. This highlights the need for an inexpensive and accurate surrogate marker for culture as it is not feasible to perform culture in routine for monitoring treatment response in the low-resource settings. The treatment outcome did not improve by addition of ethambutol emphasizing the need to find the optimal duration of treatment for individual or carefully selected groups of patients. [ABSTRACT FROM AUTHOR]