The value of histological examination in the diagnosis of tuberculous lymphadenitis in the era of rapid molecular diagnosis.

Extrapulmonary tuberculosis often poses a diagnostic challenge. This study aimed to assess the value of histological examination in diagnosing tuberculous lymphadenitis (LNTB) when performed simultaneously with rapid molecular assay (Xpert MTB/RIF) testing. People presumed to have LNTB were prospectively enrolled in a tertiary care hospital. Excision biopsy was performed and tested by histology, Xpert, and culture. Of 390 lymph nodes, 11 (2.8%) were positive by AFB microscopy, 124 (31.8%) by Xpert, 137 (35.1%) by culture, and histopathology was consistent with TB in 208 (53.3%). Altogether, LNTB was diagnosed in 228 and bacteriologically confirmed TB in 178 cases. Against culture, histopathology versus Xpert had higher sensitivity (93 vs. 62%) but lower specificity (68 vs. 83%). In patients with short clinical history, a significantly higher number of Xpert-positive specimens were culture-positive. Among patients with histology suggestive of TB, no difference was seen in response to treatment between bacteriology positive and negative, but a significant slow response was noted in bacteriology confirmed TB with nonspecific histology. In a country like Pakistan, with high TB and low HIV prevalence, diagnosis is possible for more than 95% of LNTB when Xpert and histopathology examination is used in combination, compared to less than 60% by Xpert alone.

Predictors of slow clinical response and extended treatment in patients with extra-pulmonary tuberculosis in Pakistan, A hospital-based prospective study.

The optimal duration of treatment in different forms of extrapulmonary tuberculosis (EPTB) is not clearly defined. This study aimed to identify predictors of slow clinical response and extended anti-TB treatment in EPTB patients. Socio-demographic, clinical, and microbiological characteristics of EPTB patients registered for anti-TB treatment at a tertiary care hospital, were analysed for identification of predictors of extended treatment. A total of 251 patients (137 lymphadenitis, and 114 pleuritis) were included in the analysis. Treatment was extended to more than 6 months in 58/251 (23%) patients. In the multivariate regression analysis, culture-positive EPTB (p = 0.007) [OR (95% CI) = 3.81 (1.43, 10.11)], history of diabetes (p = 0.014) [OR (95% CI) = 25.18 (1.94, 325.83)], smokeless tobacco use (p = 0.002) [OR (95% CI) = 17.69 (2.80, 111.72)], and slow regression of local signs and symptoms after 2 months of treatment (p < 0.001) [OR (95% CI) = 17.09 [(5.79, 50.39)] were seen to be significantly associated with treatment extension. Identification of predictors of extended treatment can help clinical decisions regarding optimal duration of treatment. Further studies are needed to identify subgroups of EPTB patients who can benefit from a shorter or longer treatment regimen.

Cost of Delivering 12-Dose Isoniazid and Rifapentine Versus 6 Months of Isoniazid for Tuberculosis Infection in a High-Burden Setting.

BACKGROUND: Successful delivery and completion of tuberculosis preventive treatment are necessary for tuberculosis elimination. Shorter preventive treatment regimens currently have higher medication costs, but patients spend less time in care and are more likely to complete treatment. It is unknown how economic costs of successful delivery differ between longer and shorter regimens in high-tuberculosis-burden settings. METHODS: We developed survey instruments to collect costs from program and patient sources, considering costs incurred from when household contacts first entered the health system. We compared the cost per completed course of preventive treatment with either 6 months of daily isoniazid (6H) or 3 months of weekly isoniazid and rifapentine (3HP), delivered by the Indus Health Network tuberculosis program in Karachi, Pakistan, between October 2016 and February 2018. RESULTS: During this period, 459 individuals initiated 6H and 643 initiated 3HP; 39% and 61% completed treatment, respectively. Considering costs to both the program and care recipients, the cost per completed course was 394 US dollars (USD) for 6H and 333 USD for 3HP. Using a new 2020 price for rifapentine reduced the cost per completed course of 3HP to 290 USD. Under varying assumptions about drug prices and costs incurred by care recipients, the cost per completed course was lower for 3HP in all scenarios, and the largest cost drivers were the salaries of clinical staff. CONCLUSIONS: In a high-burden setting, the cost of successful delivery of 3HP was lower than that of 6H, driven by higher completion.

Prevalence of tuberculosis, HIV/AIDS, and hepatitis; in a prison of Balochistan: a cross-sectional survey.

BACKGROUND: Human Immunodeficiency Virus (HIV), Hepatitis, and Tuberculosis (TB) are three primary communicable infections have the likely potential to cause severe morbidity in prison settings. The prison has the most favorable environment for the transmission of infections. We conducted this survey to determine the prevalence and feasibility of rapid diagnostic tests in an active screening of these infectious diseases in prison. METHODS: This cross-sectional survey conducted in central Jail Gaddani, one of the largest prisons in the Balochistan province of Pakistan. All prisoners, jail staffs, and staff's family members participated. Informed consent obtained from each participant before the screening. Van equipped with digital X-ray linked with Computer-Aided Detection for TB (CAD4TB) software used for testing. Sputum samples tested on Xpert for MTB/RIF assay and blood specimens collected for HIV and hepatitis serology. Diagnosed TB patients enrolled for treatment at Basic Management Unit (BMU), reactive on hepatitis Rapid Diagnostic Tools (RDTs) were referred for further testing and management, while HIV reactive referred to Anti Retro Viral (ARV) center for Anti Retro Viral Treatment (ART). RESULTS: A total of 567 participants offered screening, 63% (356) prisoners, 23% (129) staff's family members, and 14% (82) jail staffs. Among tested 10.3% (58/562) were hepatitis seropositive (Hepatitis-C 41 [7.29%] Hepatitis-B, 16 [2.84%] Hepatitis B&C both, 01 [0.17%]). In reactive participants, 49 were prisoners, 08 were jail staffs, and 01 was the staff's family member. HIV seropositive was 4% (24/566), and all were prisoners. Almost 99% (565/567) screened by digital X-ray, 172 (30%) were with abnormal CAD4TB suggestion (score > 50), out of them sputum of 26% (148) tested on Xpert, and 2% (03) found Mycobacterium tuberculosis Positive (MTB+). A total of five TB patients were detected; out of two were diagnosed clinically. Co-morbidities observed in 15 patients, (01 TB/HIV co-infected, 12 HIV/HCV, 01 HIV/HBV, and 01 HBV/HCV). CONCLUSION: The high frequency of infectious diseases in prison is alarming. For limiting the transmission of infections among prison and community, immediate steps are needed to be taken for improvement of prisons condition by application of recommended screening protocols at the time of the first entry of prisoners in prisons.

Diabetes Prevalence Survey of Pakistan (DPS-PAK): prevalence of type 2 diabetes mellitus and prediabetes using HbA1c: a population-based survey from Pakistan.

OBJECTIVES: We conducted a Pakistan-wide community-based survey on the prevalence of type 2 diabetes using glycated haemoglobin (HbA1c) as the screening test. The aim was to estimate diabetes prevalence across different demographic groups as well as all regions of Pakistan. DESIGN, SETTINGS AND PARTICIPANTS: Multistaged stratified cluster sampling was used for the representative selection of people aged ≥20 years, residing in 378 sampled clusters of 16 randomly selected districts, in this cross-sectional study. Eligible participants had blood drawn for HbA1c analyses at field clinics near to their homes. The oral glucose tolerance test (OGTT) was conducted on a subsample of the participants. Overall and stratified prevalence of type 2 diabetes and its association with risk factors were estimated using logistic regression models. MAIN OUTCOME MEASURES: Prevalence of prediabetes and type 2 diabetes. RESULTS: Of 18 856 eligible participants the prevalence of prediabetes was 10.91% (95% CI 10.46 to 11.36, n=2057) and type 2 diabetes was 16.98% (95% CI 16.44 to 17.51, n=3201). Overall, the mean HbA1c level was 5.62% (SD 1.96), and among newly diagnosed was 8.56% (SD 2.08). The prevalence was highest in age 51-60 years (26.03%, p<0.001), no formal education (17.66%, p<0.001), class III obese (35.09%, p<0.001), family history (31.29%, p<0.001) and female (17.80%, p=0.009). On multivariate analysis, there was a significant association between type 2 diabetes and older age, increase in body mass index and central obesity, positive family history, and having hypertension and an inverse relation with education as a categorical variable. On a subsample (n=1027), summary statistics for diagnosis of diabetes on HbA1c showed a sensitivity of 84.7%, specificity of 87.2% and area under the receiver operating characteristic curve 0.86, compared with OGTT. CONCLUSIONS: The prevalence of type 2 diabetes and prediabetes is much higher than previously thought in Pakistan. Comprehensive strategies need to be developed to incorporate screening, prevention and treatment of type 2 diabetes at a community level.

TB patients learning about second hand smoke (TBLASS): a pilot individual randomised controlled trial.

BACKGROUND: Living with a smoker is a key determinant of exposure to Second Hand Smoke (SHS) and its exposure mainly occurs at home. Exposure to SHS from tobacco in the household predisposes to the development of tuberculosis (TB) and outcome of the disease gets worse. We aim to develop and evaluate a behavioural intervention 'Smoke Free Homes' (SFH) for TB patients that encourages them to negotiate a smoke free environment within their homes. METHODS AND DESIGN: The pilot individual randomised controlled trial of SFH will inform the design of a future definitive trial. We will first develop SFH intervention using taxonomy of behaviour change techniques aimed at encouraging families of non-smoking TB patients to implement smoking restrictions at home following a logic model of the intervention. This will be followed by conducting a pilot randomised controlled trial of intervention within the context of routine TB control programme. The eligible non-smoking TB patients will be randomised and allocated to one of the two trial arms consisting of "individual based care" and "individual based care" plus "supplementary support". We aim to recruit 150 newly registered pulmonary TB patients from two selected TB centres with 75 cases in each arm. The Primary outcome measure will be SFH of non-smoker TB patient by validating through 'Urine Cotinine' test. We will also determine qualitatively the barriers and key drivers to the creation of smoke free homes followed by developing a definitive trial. DISCUSSION: The male to female distribution of TB cases in Pakistan is almost equal whereas, tobacco use among males is much high as compared to females in Pakistan. This reflects a strong possibility that women health can be affected by men behaviour. Appropriate storage, restricted access and disposal arrangements for participant's personal details will be implemented. All ethical issues will be addressed. There will be no extra burden, financial or otherwise, on the participants. They will not receive any financial incentive to participate in the study. TRIAL REGISTRATION NUMBER: ISRCTN83630841.