Scale-Up of Rifapentine and Isoniazid for Tuberculosis Prevention Among Household Contacts in 2 Urban Centers: An Effectiveness Assessment.

BACKGROUND: Scaling up a shorter preventive regimen such as weekly isoniazid and rifapentine (3HP) for 3 months is a priority for tuberculosis (TB) preventive treatment (TPT). However, there are limited data on 3HP acceptability and completion from high-burden-TB countries. METHODS: We scaled up 3HP from 2018 to 2021 in 2 cities in Pakistan. Eligible participants were household contacts of persons diagnosed with TB disease. Participants were prescribed 3HP after ruling out TB disease. Treatment was self-administered. We analyzed the proportion who completed 3HP. RESULTS: In Karachi, we verbally screened 22 054 household contacts of all ages. Of these, 83% were clinically evaluated and 3% were diagnosed with TB. Of household contacts without TB disease, 59% initiated the 3HP regimen, of which 69% completed treatment. In Peshawar, we verbally screened 6389 household contacts of all ages. We evaluated 95% of household contacts, of whom 2% were diagnosed with TB disease. Among those without TB disease, 65% initiated 3HP, of which 93% completed. Factors associated with higher 3HP completion included residence in Peshawar (risk ratio [RR], 1.35 [95% confidence interval {CI}: 1.32-1.37]), index patient being a male (RR, 1.03 [95% CI: 1.01-1.05]), and index patient with extrapulmonary TB compared to bacteriologically positive pulmonary TB (RR, 1.10 [95% CI: 1.06-1.14]). The age of the index patient was inversely associated with completion. CONCLUSIONS: We observed a high level of acceptance and completion of 3HP in programs implemented in 2 cities in Pakistan, with differences observed across the cities. These findings suggest that 3HP can be effectively scaled up in urban settings to improve the reach and impact of TPT.

Safety and Effectiveness Outcomes From a 14-Country Cohort of Patients With Multi-Drug Resistant Tuberculosis Treated Concomitantly With Bedaquiline, Delamanid, and Other Second-Line Drugs.

BACKGROUND: Concomitant use of bedaquiline (Bdq) and delamanid (Dlm) for multi-drug/rifampicin resistant tuberculosis (MDR/RR-TB) has raised concerns about a potentially poor risk-benefit ratio. Yet this combination is an important alternative for patients infected with strains of TB with complex drug resistance profiles or who cannot tolerate other therapies. We assessed safety and treatment outcomes of MDR/RR-TB patients receiving concomitant Bdq and Dlm, along with other second-line anti-TB drugs. METHODS: We conducted a multi-centric, prospective observational cohort study across 14 countries among patients receiving concomitant Bdq-Dlm treatment. Patients were recruited between April 2015 and September 2018 and were followed until the end of treatment. All serious adverse events and adverse events of special interest (AESI), leading to a treatment change, or judged significant by a clinician, were systematically monitored and documented. RESULTS: Overall, 472 patients received Bdq and Dlm concomitantly. A large majority also received linezolid (89.6%) and clofazimine (84.5%). Nearly all (90.3%) had extensive disease; most (74.2%) had resistance to fluoroquinolones. The most common AESI were peripheral neuropathy (134, 28.4%) and electrolyte depletion (94, 19.9%). Acute kidney injury and myelosuppression were seen in 40 (8.5%) and 24 (5.1%) of patients, respectively. QT prolongation occurred in 7 patients (1.5%). Overall, 78.0% (358/458) had successful treatment outcomes, 8.9% died, and 7.2% experienced treatment failure. CONCLUSIONS: Concomitant use of Bdq and Dlm, along with linezolid and clofazimine, is safe and effective for MDR/RR-TB patients with extensive disease. Using these drugs concomitantly is a good therapeutic option for patients with resistance to many anti-TB drugs.

Risk Factors for Adverse Events in Household Contacts Prescribed Preventive Treatment for Drug-resistant Tuberculosis Exposure.

BACKGROUND: Completion of tuberculosis (TB) preventive treatment is important to optimize efficacy; treatment-related adverse events (AEs) sometimes result in discontinuation. This study describes the occurrence of AEs and their risk factors during a 6-month, 2-drug, fluoroquinolone-based preventive treatment for household contacts of patients with drug-resistant TB in Karachi, Pakistan. METHODS: The primary outcome was development of any clinical AE during preventive treatment. Adverse events were categorized using the AE grading tables of the National Institutes of Health. Time-to-event analysis with Kaplan-Meier curves and Cox proportional hazards models accounting for recurrence were used to analyze associated risk factors. RESULTS: Of the 172 household contacts on preventive treatment, 36 (21%) developed 64 AEs during 813 months of treatment. The incidence of AEs over 6 months of treatment was 7.9 per 100 person-months; 16 per 100 person-months with a fluoroquinolone and ethionamide, and 4.4 per 100 person-months with a fluoroquinolone and ethambutol. There were 53 (83%) grade 1 and 11 grade 2 AEs, with no grade 3 or 4 AEs. In multivariable analysis, the risk of AEs was higher in contacts prescribed ethionamide as compared to ethambutol adjusting for age, sex, and body mass index (adjusted hazard ratio, 2.1 [95% confidence interval {CI}, 1.2-3.6]). Overall, there was no notable difference in treatment completion among the contacts who experienced an AE and those who did not (crude odds ratio, 1.1 [95% CI, .52-2.5]). CONCLUSIONS: A fluoroquinolone-based preventive treatment regimen for drug-resistant TB exposure is well tolerated. Regimens with ethionamide are more likely to result in AEs.

A shorter post-exposure prophylaxis regimen for rabies, Pakistan.

OBJECTIVE: To assess the cost and effectiveness of the two-site, 1-week, intradermal rabies post-exposure prophylaxis regimen recommended by the World Health Organization (WHO) in 2018. METHODS: We compared the number of rabies vaccine and rabies immunoglobulin ampoules consumed at The Indus Hospital in Karachi, Pakistan and their cost before and after implementing WHO's 2018 recommendations. In 2017, patients with suspected rabies-infected bites were treated using the two-site, 4-week, Thai Red Cross regimen, which involved administering four rabies vaccine doses intradermally over 4 weeks and infiltrating immunoglobulin into serious wounds, with the remainder injected into a distant muscle. In 2018, patients received three vaccine doses intradermally over 1 week, with a calculated amount of immunoglobulin infiltrated into wounds only. Remaining immunoglobulin was saved for other patients. The survival of patients bitten by apparently rabid dogs was used as a surrogate for effectiveness. FINDINGS: Despite treating 8.5% more patients in 2018 (5370 patients) than 2017 (4948 patients), 140 fewer ampoules of rabies vaccine and 436 fewer ampoules of rabies immunoglobulin were used, at a cost saving of 4202 United States dollars. Of 56 patients bitten by apparently rabid dogs, 50 were alive at 6-month follow-up. The remaining six patients could not be contacted but did not present to any hospital with rabies. CONCLUSION: The new regimen was more economical than the two-site, 4-week regimen and was equally effective. This regimen is recommended for preventing rabies in countries where the disease is endemic and rabies vaccine and immunoglobulin are in short supply.

Tuberculosis Preventive Therapy for Individuals Exposed to Drug-resistant Tuberculosis: Feasibility and Safety of a Community-based Delivery of Fluoroquinolone-containing Preventive Regimen.

BACKGROUND: Observational studies have demonstrated the effectiveness of a fluoroquinolone-based regimen to treat individuals presumed to be infected with drug-resistant tuberculosis (DR-TB). We sought to assess the feasibility of this approach in an urban setting in South Asia. METHODS: From February 2016 until March 2017, all household contacts of DR-TB patients enrolled at the Indus Hospital were screened for TB symptoms at home. Children aged 0-17 years, symptomatic adults, and those with an immunocompromising condition (human immunodeficiency virus, diabetes, or malnutrition) were evaluated for TB disease. Contacts diagnosed with TB disease were started on treatment. Contacts without TB disease aged <5 years, contacts aged between 5 and 17 years with either a positive tuberculin skin test or an immunocompromising condition, or contacts aged ≥18 years with an immunocompromising condition were offered 6 months of treatment with a fluoroquinolone. RESULTS: One hundred households with 800 contacts were enrolled: 353 (44.1%) individuals aged ≤17 years with a median age of 19 years (interquartile range, 10-32); 423 (52.9%) were males. In total, 737 (92.1%) individuals were screened, of which 8 were already on treatment for TB (1.1%); another 3 (0.4%) contacts were diagnosed with TB disease and started on treatment. Of 215 eligible for infection treatment, 172 (80.0%) contacts initiated and 121 (70.3%) completed treatment. No TB disease or significant adverse events were observed during 12 months of follow-up. CONCLUSIONS: Fluoroquinolone-based treatment for contacts with presumed DR-TB infection is feasible and well tolerated in a high TB burden setting.

Frequency, clinical characteristics, risks, and outcomes of Paradoxical upgrading reactions during anti-tuberculosis treatment in tuberculous lymphadenitis.

OBJECTIVES: To investigate the clinical characteristics, risks and outcomes of Paradoxical upgrading reactions (PUR) during anti-tuberculosis treatment (ATT) in superficial tuberculous lymphadenitis (TBLA). METHODS: In this nested case-control study, all patients diagnosed with TBLA based on combinations of histopathology, acid-fast bacilli (AFB) microscopy, AFB culture, and GeneXpert, between February 2013 and April 2016, were enrolled. Standard ATT was given. Demographics, clinical characteristics, occurrence of PUR and outcome were recorded. RESULTS: TBLA was diagnosed and treated in 189 patients. PUR developed in 33 (17%), of which 77% developed new inflamed glands, 20.6% had increased size and inflammation of pre-existing glands and 5.9% had superficial chest wall abscesses requiring aspiration. All responded to regular NSAIDs except one, where a steroid course was effective. No change in dose or duration of ATT was required. Presence of anorexia (OR; 95%CI: 2.6; 1.003-6.74), bilateral extensive lymphadenopathy (OR; 95%CI: 2.9; 1.1-7.5) and lymph node specimen positive for AFB (OR; 95%CI: 3.2; 1.04-10.1) were significantly associated with PUR. CONCLUSION: PUR is common in TBLA. It responded to NSAIDS and does not need any modification in ATT.

Raised levels of IFN-gamma and IL-13 are associated with pre-diabetes amongst newly diagnosed patients with Tuberculosis.

OBJECTIVE: To investigate pre-diabetes and diabetes in newly-diagnosed tuberculosis patients and to assess the association of serum cytokine levels with diabetes status. METHODS: The cross-sectional study was conducted at Indus Hospital and The Aga Khan University Hospital, Karachi from May to November 2015, and included patients of either gender aged 18 years or more with a confirmed diagnosis of tuberculosis who were either newly diagnosed or had received up to 1 month of anti-tuberculosis therapy were included. Patients were enrolled from among those presenting to the clinics at Indus Hospital, Karachi, and the Department of Medicine, Aga Khan University Hospital (AKUH), Karachi. The patients were tested for glycosylated haemoglobin and random blood glucose. Diabetes was defined as HbA1c >6.5%; pre-diabetes as HbA1c=5.7-6.4%; and normoglycaemic as HbA1c <5.7%. Serum cytokines were investigated using the Bio-plex 27, Bio-Rad assay. SPSS version 19.0 was used for data analysis.. RESULTS: Of the 211 subjects, 110(52%) were females and 101(48%) were males. The overall median age of the sample was 26 years, and 100(47.3%) subjects were underweight. Of the total, 24(11.4%) had diabetes and 45(21.3%) had pre-diabetes. Of the diabetics, only 7(29%) knew their status prior to screening. Interferon-gamma and interleukin-13 were significantly different among tuberculosis patients with diabetes, pre-diabetes and normoglycaemia (p<0.05). Glycosylated haemoglobin levels showed a significant correlation with interferon-gamma levels. CONCLUSIONS: Raised interleukin-13 and interferon-gamma levels in newly-diagnosed tuberculosis patients with pre-diabetes.

Leprosy manifesting with type 2 leprae reaction in a patient presenting with chronic fever: A case report.

Leprosy is a chronic granulomatous disease involving the skin and nerves, leading to a debilitating condition. Leprosy has been controlled in most parts of the world; therefore physicians are not very well versed in the recognition, management and assessment of this disease. The protean manifestations of leprosy often lead to delays in diagnosis and increase the morbidity. We present a case of a 33-year-old male with fever, lymphadenopathy, nodular skin lesions, uveitis and arthritis. Lymphnode, bonemarrow and skin biopsy revealed 3+ AFB smear with negative AFB cultures, leading to the diagnosis of leprosy. The course of illness was complicated by flare of Erythema Nodosum Leprosum (ENL).

Unusual case of non-resolving necrotizing pneumonia: A last resort measure for cure.

To our knowledge, this is an unusual case of a community-acquired pneumonia (CAP) with sepsis secondary to Streptococcus pneumoniae that required lung resection for a non-resolving consolidation. A 74 year old previously healthy woman, presented with acute fever, chills and pleuritic chest pain in Emergency Department (ED). A diagnosis of CAP was established with a Pneumonia Severity Index CURB-65 score of 5/5. In the ER, she was promptly and appropriately managed with antibiotics and aggressive supportive therapy. She remained on ten days of intravenous antibiotics. However, 48 hours post antibiotic course, she returned to ER with fever and signs of sepsis. Despite timely and appropriate management, the consolidated lobe remained the focus of sepsis for over four weeks. The patient recovered after the offending lobe was resected. Histopathology of the lung tissue revealed acute and chronic inflammation. However, no malignancy, bacterial infection or broncho-pleural fistula was found. Eighteen months post-surgery, the patient remains well.

How to avoid infections in Ramadan, especially urinary tract infections.

Prolonged and poor control of diabetes has detrimental effects on the immune system by reducing both B and T cell function, causing neutrophilic dysfunction and less production of inflammatory cytokines. This makes people with diabetes vulnerable to various bacterial, viral and fungal infections in all body organs. The commonest cause of chronic renal disease is uncontrolled diabetes, placing patients, particularly women, at high risk for recurrent and complicated urinary tract infections. Diabetic patients who opt to fast during Ramadan must be clearly counseled about keeping themselves hydrated between non-fasting hours and maintaining good glycaemic control through diet and antidiabetic drugs.

Sputum culture reversion in longer treatments with bedaquiline, delamanid, and repurposed drugs for drug-resistant tuberculosis.

Sputum culture reversion after conversion is an indicator of tuberculosis (TB) treatment failure. We analyze data from the endTB multi-country prospective observational cohort (NCT03259269) to estimate the frequency (primary endpoint) among individuals receiving a longer (18-to-20 month) regimen for multidrug- or rifampicin-resistant (MDR/RR) TB who experienced culture conversion. We also conduct Cox proportional hazard regression analyses to identify factors associated with reversion, including comorbidities, previous treatment, cavitary disease at conversion, low body mass index (BMI) at conversion, time to conversion, and number of likely-effective drugs. Of 1,286 patients, 54 (4.2%) experienced reversion, a median of 173 days (97-306) after conversion. Cavitary disease, BMI < 18.5, hepatitis C, prior treatment with second-line drugs, and longer time to initial culture conversion were positively associated with reversion. Reversion was uncommon. Those with cavitary disease, low BMI, hepatitis C, prior treatment with second-line drugs, and in whom culture conversion is delayed may benefit from close monitoring following conversion.

Expression of M. tuberculosis-induced suppressor of cytokine signaling (SOCS) 1, SOCS3, FoxP3 and secretion of IL-6 associates with differing clinical severity of tuberculosis.

BACKGROUND: Appropriate immune activation of T cells and macrophages is central for the control of Mycobacterium tuberculosis infections. IFN-γ stimulated responses are lowered in tuberculosis (TB), while expression of Suppressor of Cytokine Signaling (SOCS) molecules - 1 and 3 and CD4+CD25+FoxP3+T regulatory cells is increased. Here we investigated the association of these molecules in regard to clinical severity of TB. METHODS: Peripheral blood mononuclear cells (PBMCs) were isolated from patients with pulmonary TB (PTB, n = 33), extra-pulmonary TB (ETB, n = 33) and healthy endemic controls (EC, n = 15). Cases were classified as moderately advanced or far advanced PTB, and less severe or severe disseminated ETB. M. tuberculosis -stimulated IFN-γ, SOCS1, SOCS3 and FoxP3 gene expression and secretion of Th1 and Th2 cytokines was measured. Statistical analysis was performed using Mann-Whitney U, Wilcoxon Rank and Kruskal Wallis non-parametric tests. RESULTS: In un-stimulated PBMCs, IL-6 (p = 0.018) and IL-10 (p = 0.013) secretion levels were increased in PTB while IL-10 was also increased in ETB (p = 0.003), all in comparison with EC. M. tuberculosis-stimulated IL-6 (p = 0.003) was lowered in ETB as compared with EC. SOCS1 mRNA expression in M. tuberculosis stimulated PBMCs levels in moderately advanced PTB (p = 0.022), far advanced (p = 0.014) PTB, and severe ETB (p = 0.009) were raised as compared with EC. On the other hand, SOCS1 mRNA titers were reduced in less severe ETB, in comparison with severe ETB (p = 0.027) and far advanced PTB (p = 0.016). SOCS3 mRNA accumulation was reduced in far advanced PTB (p = 0.007) and FoxP3 mRNA expression was increased in less severe ETB as compared with EC (p = 0.017). CONCLUSIONS: The lowered SOCS1 mRNA levels in patients with less severe extra-pulmonary TB as compared to those with more severe ETB and PTB may lead to elevated IFN-γ pathway gene expression in the latter group. As localized ETB has shown to be associated with more effective Th1 immunity and adaptive responses, this suggests a role for SOCS1 in determining disease outcome in extra-pulmonary TB.

Comparative effectiveness of adding delamanid to a multidrug-resistant tuberculosis regimen comprised of three drugs likely to be effective.

Clarity about the role of delamanid in longer regimens for multidrug-resistant TB is needed after discordant Phase IIb and Phase III randomized controlled trial results. The Phase IIb trial found that the addition of delamanid to a background regimen hastened culture conversion; the results of the Phase III trial were equivocal. We evaluated the effect of adding delamanid for 24 weeks to three-drug MDR/RR-TB regimens on two- and six-month culture conversion in the endTB observational study. We used pooled logistic regression to estimate the observational analogue of the intention-to-treat effect (aITT) adjusting for baseline confounders and to estimate the observational analogue of the per-protocol effect (aPP) using inverse probability of censoring weighting to control for time-varying confounding. At treatment initiation, 362 patients received three likely effective drugs (delamanid-free) or three likely effective drugs plus delamanid (delamanid-containing). Over 80% of patients received two to three Group A drugs (bedaquiline, linezolid, moxifloxacin/levofloxacin) in their regimen. We found no evidence the addition of delamanid to a three-drug regimen increased two-month (aITT relative risk: 0.90 (95% CI: 0.73-1.11), aPP relative risk: 0.89 (95% CI: 0.66-1.21)) or six-month culture conversion (aITT relative risk: 0.94 (95% CI: 0.84, 1.02), aPP relative risk: 0.93 (95% CI: 0.83, 1.04)). In regimens containing combinations of three likely effective, highly active anti-TB drugs the addition of delamanid had no discernible effect on culture conversion at two or six months. As the standard of care for MDR/RR-TB treatment becomes more potent, it may become increasingly difficult to detect the benefit of adding a single agent to standard of care MDR/RR-TB regimens. Novel approaches like those implemented may help account for background regimens and establish effectiveness of new chemical entities.

WHO Point Prevalence Survey to Describe the Use of Antimicrobials at a Tertiary Care Center in Pakistan: A Situation Analysis for Establishing an Antimicrobial Stewardship Program.

Antimicrobial stewardship is a systematic approach for promoting and monitoring responsible antimicrobial use globally. We conducted a prospective point prevalence survey of antimicrobial utilization among hospitalized adult patients during September 2021. The survey instrument was adapted from the WHO methodology for point prevalence surveys, and it was conducted at The Indus Hospital and Health Network, Karachi. Among the 300 admitted patients, 55% were males and the mean age was 44 (±18) years. At least 67% of the patients received one antimicrobial agent and the most common indication was surgical prophylaxis (40%). The most frequently used were antibacterial agents (97%) among all antimicrobials. Amoxicillin/Clavulanic acid and Ceftriaxone were the most frequently used antibacterial agents, i.e., 14% each. At least 56% of the antibacterial agents were amenable to antimicrobial stewardship when reviewed by infectious disease (ID) experts. Reasons for stewardship were: antibacterial not indicated (n = 39, 17.0%), unjustified prolonged duration of antibacterial (n = 32, 13.9%), extended surgical prophylaxis (n = 60, 26.2%), non-compliance to surgical prophylaxis guidelines (n = 30, 13.1%), and antibacterial not needed on discharge (n = 27, 11.7%). Median days of therapy (DOT) per agent was 3 days (IQR 2-4), while median DOT per patient was 2 days (IQR 1-4). These data have described the pattern of antimicrobial utilization in our institute. We found a higher prevalence of antimicrobial use overall as compared to the global figures, but similar to other low- and middle-income countries. Two important areas identified were the use of antimicrobials on discharge and extended surgical prophylaxis. As a result of these data, our institutional guidelines were updated, and surgical teams were educated. A post-intervention survey will help us to further determine the impact. We strongly recommend PPS at all major tertiary care hospitals in Pakistan for estimating antimicrobial utilization and identifying areas for stewardship interventions.

Drug-Resistant Tuberculosis Treatment Outcomes among Children and Adolescents in Karachi, Pakistan.

BACKGROUND: Significant data gaps exist for children and adolescents with drug-resistant (DR) TB, particularly from high TB incidence settings. This report provides a descriptive analysis of programmatic outcomes among children and adolescents treated for DR-TB in Pakistan. METHODS: We extracted programmatic data from January 2014 to December 2019 from a tertiary care hospital with specialised child and adolescent DR-TB services. A physician assessed all children and adolescents (0-19 years) with presumptive DR-TB, including details of exposure to DR-TB, medical history, radiology, and laboratory results. All patients received treatment as per national DR-TB management guidelines based on WHO recommendations. RESULTS: There were 262 treatment episodes for 247 patients enrolled during the study period. The median age of the cohort was 16 years (IQR: 13-18 years) with 16 (6.1%) children being under 5 years; 237 (90.5%) patients had pulmonary TB. The majority of the patients (194 or 74.1%) experienced a favourable treatment outcome and 26 (9.9%) died while on treatment. Female patients (78.5%) were more likely to experience favourable outcomes compared to males (64.7%; chi-sqr p-value = 0.02). CONCLUSIONS: We found high rates of favourable outcomes in children and adolescents treated for DR-TB. However, there were few young children in our cohort and there was a considerable gender gap that enhanced efforts to diagnose DR-TB in young children and to elucidate and mitigate the reasons for poor outcomes amongst males.

Re-evaluating the merits of decentralization as a core strategy for effective delivery of drug-resistant tuberculosis care in Pakistan.

Decentralized, person-centred models of care delivery for drug-resistant tuberculosis (DR-TB) continue to be under-resourced in high-burden TB countries. The implementation of such models-made increasingly urgent by the COVID-19 pandemic-are key to addressing gaps in DR-TB care. We abstracted data of rifampicin-resistant (RR)/multidrug-resistant tuberculosis (MDR-TB) patients initiated on treatment at 11 facilities between 2010 and 2017 in Sindh and Balochistan provinces of Pakistan. We analysed trends in treatment outcomes relating to programme expansion to peri-urban and rural areas and estimated driving distance from patient residence to treatment facility. Among the 5586 RR/MDR-TB patients in the analysis, overall treatment success decreased from 82% to 66% between 2010 and 2017, as the programme expanded. The adjusted risk ratio for unfavourable outcomes was 1.013 (95% confidence interval 1.005-1.021) for every 20 km of driving distance. Our analysis suggests that expanding DR-TB care to centralized hubs added to increased unfavourable outcomes for people accessing care in peri-urban and rural districts. We propose that as enrolments increase, expanding DR-TB services close to or within affected communities is essential.

One Health for neglected tropical diseases.

The forthcoming World Health Organization road map for neglected tropical diseases (NTDs) 2021-2030 recognises the complexity surrounding control and elimination of these 20 diseases of poverty. It emphasises the need for a paradigm shift from disease-specific interventions to holistic cross-cutting approaches coordinating with adjacent disciplines. The One Health approach exemplifies this shift, extending beyond a conventional model of zoonotic disease control to consider the interactions of human and animal health systems within their shared environment and the wider social and economic context. This approach can also promote sustainability and resilience within these systems. To achieve the global ambition on NTD elimination and control, political will, along with contextualised innovative scientific strategies, is required.

Extrapulmonary tuberculosis: a retrospective review of 194 cases at a tertiary care hospital in Karachi, Pakistan.

OBJECTIVE: To describe the types and treatment outcomes of the extra-pulmonary tuberculosis (EPTB) cases in a tertiary care hospital in a high burden tuberculosis country. METHOD: A retrospective case series study was conducted at Liaquat National Hospital (LNH), the largest private tertiary care hospital in Karachi, Pakistan. All cases diagnosed and treated as EPTB between November 2005 and February 2007 were included. Data was retrieved from medical records on demographics, clinical, laboratory, and outcome status. RESULTS: A total of 194 patients treated for EPTB were identified. Mean age of patients was 34 +/- 16.4 years, and 75% of patients were female. Lymph nodes and spine were the most common sites involved (60%). The cure rate was 40.7%. There was no difference in cure rate of males and females (p=0.99). CONCLUSION: EPTB is an important clinical problem in Pakistan. Due to lack of guidelines for diagnosis and duration of treatment in EPTB most physicians in Pakistan treat patients based on clinical symptoms and for prolonged duration of 12, to even as long as 24 months. The National TB Program, and chest and infectious disease societies must develop standardized guidelines for the diagnosis and treatment of EPTB.