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.

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.

Correction: Malik et al. Integrated Tuberculosis and COVID-19 Activities in Karachi and Tuberculosis Case Notifications. Trop. Med. Infect. Dis. 2022, 7, 12.

The authors wish to revise the second citation of reference [26] to [27] in the original article main text [...].

Integrated Tuberculosis and COVID-19 Activities in Karachi and Tuberculosis Case Notifications.

As the COVID-19 pandemic surged, lockdowns led to the cancellation of essential health services. As part of our Zero TB activities in Karachi, we adapted our approach to integrate activities for TB and COVID-19 to decrease the impact on diagnosis and linkage to care for TB treatment. We implemented the following: (1) integrated COVID-19 screening and testing within existing TB program activities, along with the use of an artificial intelligence (AI) software reader on digital chest X-rays; (2) home delivery of medication; (3) use of telehealth and mental health counseling; (4) provision of PPE; (5) burnout monitoring of health workers; and (6) patient safety and disinfectant protocol. We used programmatic data for six districts of Karachi from January 2018 to March 2021 to explore the time trends in case notifications, the impact of the COVID-19 pandemic, and service adaptations in the city. The case notifications in all six districts in Karachi were over 80% of the trend-adjusted expected notifications with three districts having over 90% of the expected case notifications. Overall, Karachi reached 90% of the expected case notifications during the COVID-19 pandemic. The collaborative efforts by the provincial TB program and private sector partners facilitated this reduced loss in case notifications.

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.

Safety and feasibility of 1 month of daily rifapentine plus isoniazid to prevent tuberculosis in children and adolescents: a prospective cohort study.

BACKGROUND: Shorter regimens for tuberculosis prevention can improve completion rates and protection against developing active tuberculosis disease after tuberculosis exposure. We aimed to assess the safety and feasibility of 1 month of daily isoniazid and rifapentine (1HP) in children and adolescents in a low-resource setting in south Asia with low prevalence of HIV. METHODS: This prospective cohort study was done in eight tuberculosis facilities in Karachi, Pakistan. Eligible participants were aged 2-19 years and were household contacts of patients with drug-susceptible tuberculosis infection. After clinical, radiological, and laboratory evaluation to rule out tuberculosis disease, participants were prescribed 1HP as a preventive regimen. Isoniazid was administered as 100 mg or 300 mg oral tablets and rifapentine was administered as 150 mg oral tablets. Dosing was according to participant bodyweight. The primary endpoints were the cumulative probability of a household contact completing all stages of the preventive care cascade, assessed in all eligible participants, and the proportion of household contacts completing 1HP, assessed among all those who initiated the regimen. Safety was assessed in all household contacts who initiated the 1HP regimen. FINDINGS: Between Dec 21, 2019, and March 20, 2020, 1395 household contacts of 253 patients with tuberculosis were identified, including 678 household contacts who were eligible to participate. 628 (93%) completed evaluation, of whom ten (2%) had active tuberculosis disease. Of the 618 individuals eligible for tuberculosis prevention, 408 (66%) initiated 1HP, 385 (94%) of whom completed the regimen. The median duration of 1HP was 31 days (IQR 30-32) in those who completed the regimen. The cumulative probability of completing all steps of the tuberculosis prevention cascade was 58%. A girl aged 11 years developed tuberculosis disease within 6 months of completing 1HP. A boy aged 14 years developed a burning sensation during 1HP therapy and discontinued the regimen. No other adverse events were observed. INTERPRETATION: 1HP can be safely and feasibly implemented as tuberculosis prevention in children and adolescents in programmatic settings. FUNDING: The Global Fund to Fight AIDS, Tuberculosis and Malaria.

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.

Extrapulmonary tuberculosis in Pakistan- A nation-wide multicenter retrospective study.

BACKGROUND: Pakistan is fifth among high burden countries for tuberculosis. A steady increase is seen in extrapulmonary tuberculosis (EPTB), which now accounts for 20% of all notified TB cases. There is very limited information on the epidemiology of EPTB. This study was performed with the aim to describe the demographic characteristics, clinical manifestations and treatment outcomes of EPTB patients in Pakistan. METHOD: We performed descriptive analysis on routinely collected data for cohorts of TB patients registered nationwide in 2016 at health facilities selected using stratified convenient sampling. FINDINGS: Altogether 54092 TB including 15790 (29.2%) EPTB cases were registered in 2016 at 50 study sites. The median age was 24 years for EPTB and 30 years for PTB patients. The crude prevalence of EPTB in females was 30.5% (95%CI; 29.9-31.0) compared to 27.9% (95%CI; 27.3-28.4) in males. The likelihood of having EPTB (OR), was 1.1 times greater for females, 2.0 times for children, and 3.3 times for residents of provinces in the North-West. The most common forms of EPTB were pleural (29.6%), lymphatic (22.7%) and abdominal TB (21.0%). Pleural TB was the most common clinical manifestation in adults (34.2%) and abdominal TB in children (38.4%). An increase in the prevalence of pleural and osteoarticular and decline in lymphatic and abdominal TB was observed with advancing age. Diversity in demography and clinical manifestations were noted between provinces. The treatment success rate for all type EPTB was significantly high compared to bacteriology confirmed PTB with the exception of EPTB affecting CNS with a high mortality rate. CONCLUSIONS: The study provides an insight into demography, clinical manifestations and treatment outcomes of EPTB. Further studies are needed to explain significant diversities observed between provinces, specific risk factors and challenges concerning EPTB management.

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.

Childhood tuberculosis deskguide and monitoring: an intervention to improve case management in Pakistan.

BACKGROUND: Childhood tuberculosis (TB) has been a neglected area in national TB control programme (NTCP) in high burden countries. The NTP Pakistan adapted the global approaches by developing and piloting its policy guideline on childhood TB in ten districts of the country. We developed an intervention package including a deskguide and a monitoring tool and tested with the ongoing childhood TB care in a district. The objective of our study was to measure effectiveness of intervention package with deskguide and monitoring tool by comparing TB case finding and treatment outcomes among districts in 2008, and performance assessment in intervention district. METHOD: An intervention study with cohort design within a routine TB control programme comparing case findings and treatment outcomes before and after the intervention, and in districts with and without intervention. We enrolled all children below 15 years registered at all nine public sector hospitals in three districts of Pakistan. The data was collected from hospital TB records. RESULTS: In eight months during 2007 there were 164 childhood TB cases notified, and after intervention in 2008 a total of 194 cases were notified. In intervention district case finding doubled (110% increase) and correct treatment practice significantly increased in eight months. Successful outcomes were significantly higher in intervention district (37,100%) compared to control district A (18, 18%, p < 0.05) and control district B (41, 72%, p < 0.05). CONCLUSION: Childhood TB deskguide and structured monitoring was associated with improved case management and it augmented NTP policy. More development and implementation in all health services of the district are indicated.

Are children with tuberculosis in Pakistan managed according to National programme policy guidelines? A study from 3 districts in Punjab.

BACKGROUND: The adherence to policies of National TB Control Programme (NTP) to manage a case of tuberculosis (TB) is a fundamental step to have a successful programme in any country. Childhood TB services faces an unmet challenge of case management due to difficulty with diagnosis and relatively new policies. For control of childhood TB in Pakistan, NTP developed and piloted its guidelines in 2006-2007. The objective of this study was to compare the documented case management practices of pediatricians and its impact on the outcome before and after introducing NTP policy guidelines. FINDINGS: An audit of case management practices of a historical cohort study was done in children below 15 years who were put on anti-tuberculosis treatment at all nine public hospitals in three districts in province of Punjab. The study period was two years pre-intervention (2004-05) and two years post-intervention (2006-07) after implementation of new NTP policy guidelines for childhood TB. There were 920 childhood TB cases registered during four years, 189 in pre-intervention period and 731 in post-intervention period. The practices changed significantly in post-intervention period for use of tuberculin skin test (63% of pulmonary cases, 19% of extrapulmonary cases and 67% for site unknown), and for the use of chest x-ray (69% of pulmonary cases, 16% of extrapulmonary cases and 74% for site unknown). Diagnostic scores were recorded for only a minority of cases (18%). The proportion of correct drugs pre- and post-intervention remained same. There were unknown treatment outcomes in 38 out of 141 cases (27%) in pre-intervention and in 483 out of 551 cases (87%) post-intervention, all among the 692 cases without documented treatment supporter. CONCLUSIONS: The study has shown that pediatricians have started following parts of the national policy guidelines for management of childhood TB. The documented use of diagnostic tools is increased but record keeping of case management practices remained inadequate. This seems to increase case finding substantially but the treatment outcomes were poor mainly due to unknown outcomes. Development and implementation of standardized operational tools and regular monitoring system may improve the services.