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.

Triage of Persons With Tuberculosis Symptoms Using Artificial Intelligence-Based Chest Radiograph Interpretation: A Cost-Effectiveness Analysis.

BACKGROUND: In settings without access to rapid expert radiographic interpretation, artificial intelligence (AI)-based chest radiograph (CXR) analysis can triage persons presenting with possible tuberculosis (TB) symptoms, to identify those who require additional microbiological testing. However, there is limited evidence of the cost-effectiveness of this technology as a triage tool. METHODS: A decision analysis model was developed to evaluate the cost-effectiveness of triage strategies with AI-based CXR analysis for patients presenting with symptoms suggestive of pulmonary TB in Karachi, Pakistan. These strategies were compared to the current standard of care using microbiological testing with smear microscopy or GeneXpert, without prior triage. Positive triage CXRs were considered to improve referral success for microbiologic testing, from 91% to 100% for eligible persons. Software diagnostic accuracy was based on a prospective field study in Karachi. Other inputs were obtained from the Pakistan TB Program. The analysis was conducted from the healthcare provider perspective, and costs were expressed in 2020 US dollars. RESULTS: Compared to upfront smear microscopy for all persons with presumptive TB, triage strategies with AI-based CXR analysis were projected to lower costs by 19%, from $23233 per 1000 persons, and avert 3%-4% disability-adjusted life-years (DALYs), from 372 DALYs. Compared to upfront GeneXpert, AI-based triage strategies lowered projected costs by 37%, from $34346 and averted 4% additional DALYs, from 369 DALYs. Reinforced follow-up for persons with positive triage CXRs but negative microbiologic tests was particularly cost-effective. CONCLUSIONS: In lower-resource settings, the addition of AI-based CXR triage before microbiologic testing for persons with possible TB symptoms can reduce costs, avert additional DALYs, and improve TB detection.

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.

Correction to: The cost-effectiveness of incentive-based active case finding for tuberculosis (TB) control in the private sector Karachi, Pakistan.

In the original publication of this article [1], an author's name needs to be revised from Jacob Creswel to Jacob Creswell.

The cost-effectiveness of incentive-based active case finding for tuberculosis (TB) control in the private sector Karachi, Pakistan.

BACKGROUND: In Asia, over 50% of patients with symptoms of tuberculosis (TB) access health care from private providers. These patients are usually not notified to the National TB Control Programs, which contributes to low notification rates in many countries. METHODS: From January 1, 2011 to December 31, 2012, Karachi's Indus Hospital - a private sector partner to the National TB Programme - engaged 80 private family clinics in its catchment area in active case finding using health worker incentives to increase notification of TB disease. The costs incurred were estimated from the perspective of patients, health facility and the program providing TB services. A Markov decision tree model was developed to calculate the cost-effectiveness of the active case finding as compared to case detection through the routine passive TB centers. Pakistan has a large private health sector, which can be mobilized for TB screening using an incentivized active case finding strategy. Currently, TB screening is largely performed in specialist public TB centers through passive case finding. Active and passive case finding strategies are assumed to operate independently from each other. RESULTS: The incentive-based active case finding program costed USD 223 per patient treated. In contrast, the center based non-incentive arm was 23.4% cheaper, costing USD 171 per patient treated. Cost-effectiveness analysis showed that the incentive-based active case finding program was more effective and less expensive per DALY averted when compared to the baseline passive case finding as it averts an additional 0.01966 DALYs and saved 15.74 US$ per patient treated. CONCLUSION: Both screening strategies appear to be cost-effective in an urban Pakistan context. Incentive driven active case findings of TB in the private sector costs less and averts more DALYs per health seeker than passive case finding, when both alternatives are compared to a common baseline situation of no screening.

Operationalization of bi-directional screening for tuberculosis and diabetes in private sector healthcare clinics in Karachi, Pakistan.

BACKGROUND: Many countries are facing overlapping epidemics of tuberculosis (TB) and diabetes mellitus (DM). Diabetes increases the overall risk of developing Tuberculosis (TB) and contributes to adverse treatment outcomes. Active screening for both diseases can reduce TB transmission and prevent the development of complications of DM. We investigated bi-directional TB-DM screening in Karachi, Pakistan, a country that ranks fifth among high TB burden countries, and has the seventh highest country burden for DM. METHODS: Between February to November 2014, community-based screeners identified presumptive TB and DM through verbal screening at private health clinics. Individuals with presumptive TB were referred for a chest X-ray and Xpert MTB/RIF. Presumptive DM cases had random blood glucose (RBS) tested. All individuals with bacteriologically positive TB were referred for diabetes testing (RBS). All pre-diabetics and diabetics were referred for a chest X-ray and Xpert MTB/RIF test. The primary outcomes of this study were uptake of TB and DM testing. RESULTS: A total of 450,385 individuals were screened, of whom 18,109 had presumptive DM and 90,137 had presumptive TB. 14,550 of these individuals were presumptive for both DM and TB. The uptake of DM testing among those with presumptive diabetes was 26.1% while the uptake of TB testing among presumptive TB cases was 5.9%. Despite efforts to promote bi-directional screening of TB and DM, the uptake of TB testing among pre-diabetes and diabetes cases was only 4.7%, while the uptake of DM testing among MTB positive cases was 21.8%. CONCLUSION: While a high yield for TB was identified among pre-diabetics and diabetics along with a high yield of DM among individuals diagnosed with TB, there was a low uptake of TB testing amongst presumptive TB patients who were recorded as pre-diabetic or diabetic. Bi-directional screening for TB and DM which includes the integration of TB diagnostics, DM screening and TB-DM treatment within existing health care programs will need to address the operational challenges identified before implementing this as a strategy in public health programs.

Community-based assessment of surgical symptoms in a low-income urban population.

BACKGROUND: The global burden of surgical disease has not been well quantified, but is potentially immense. Given the enormity of the problem and the relative paucity of data, definition and monitoring of surgical burden of disease is an essential step in confronting the problem. This study aimed to estimate the prevalence of non-acute surgical disease symptoms in a low-income population. METHODS: The survey was conducted as part of the Indus Hospital Community Cohort in Karachi, Pakistan. A systematic random sampling design was used to enroll 667 households from March to August 2011. An unvalidated questionnaire intending to measure prevalence of surgical symptoms was administered to 780 participants. RESULTS: 761 participants completed the screening questionnaire, with 346 (45%) reporting one or more symptoms requiring surgical assessment (excluding those screened positive for symptoms of osteoarthritis), of which only 8.4% followed up on scheduled appointments at the referral hospital. A total of 126 past surgical procedures were recorded in 120 participants. CONCLUSION: There is a high prevalence of symptoms suggestive of surgical diseases in our urban catchment population with relatively convenient access to health facilities including a tertiary care hospital providing free of cost care. The perceived severity of symptoms, and a complex interaction of other factors, may play an important role in understanding health seeking behavior in our population. Developing a context-specific validated tool to correctly identify surgical symptoms disease in the community with appropriate referral for early management is essential to identify and therefore reduce the burden of surgical diseases within the community. This must happen hand in hand with further studies to understand the barriers to seeking timely health care.

Equitable access to comprehensive surgical care: the potential of indigenous private philanthropy in low-income settings.

INTRODUCTION: Equitable access to surgical care is necessary for improving global health. We report on the performance, financial sustainability, and policy impact of a free-of-cost multispecialty surgical delivery program in Karachi, Pakistan built upon local private philanthropy. MATERIALS AND METHODS: We evaluated trends in surgical service delivery, expenditures, and philanthropic donations from Indus Hospital's first 5 years of operation (2007-2012), projected these over the hospital's current expansion phase, compared these to publicly accessible records of other philanthropic hospitals providing surgical care, and documented the government's evolving policies toward this model. RESULTS: Between 2007 and 2012, Indus Hospital treated 40,012 in-patients free of cost, 33,606 (84 %) of them for surgical procedures. Surgical procedures increased fivefold to 9,478 during 2011-2012 from 1,838 during 2007-2008. Bed occupancy increased to 91 % from 65 % over the same period. External surgical missions accounted for less than 0.5 % of patients served. Ninety-eight percent (98 %) of all philanthropic donations--totaling USD 26.6 million over 2007-2012--were locally generated. Zakat (obligatory annual religious alms in the Islamic faith) constituted 34 % of all donations, followed by unrestricted funds (24 %) and donations-in-kind (24 %), buildings (12 %), grants (5 %), and return on investments (1 %). Overall, donations received between 2007 and 2012 increased sevenfold, with Zakat increasing 12-fold. During 2013-2014, the Government of Pakistan provided land lease and annual operational grants totaling USD 9 million. CONCLUSIONS: Local philanthropy can sustain and grow the provision of free, high-quality surgical care in low-income settings, and encourage the development of hybrid government-philanthropic models of surgical care.

The burden of non-communicable disease in transition communities in an Asian megacity: baseline findings from a cohort study in Karachi, Pakistan.

BACKGROUND: The demographic transition in South Asia coupled with unplanned urbanization and lifestyle changes are increasing the burden of non-communicable disease (NCD) where infectious diseases are still highly prevalent. The true magnitude and impact of this double burden of disease, although predicted to be immense, is largely unknown due to the absence of recent, population-based longitudinal data. The present study was designed as a unique 'Framingham-like' Pakistan cohort with the objective of measuring the prevalence and risk factors for hypertension, obesity, diabetes, coronary artery disease and hepatitis B and C infection in a multi-ethnic, middle to low income population of Karachi, Pakistan. METHODS: We selected two administrative areas from a private charitable hospital's catchment population for enrolment of a random selection of cohort households in Karachi, Pakistan. A baseline survey measured the prevalence and risk factors for hypertension, obesity, diabetes, coronary artery disease and hepatitis B and C infection. RESULTS: Six hundred and sixty-seven households were enrolled between March 2010 and August 2011. A majority of households lived in permanent structures (85%) with access to basic utilities (77%) and sanitation facilities (98%) but limited access to clean drinking water (68%). Households had high ownership of communication technologies in the form of cable television (69%) and mobile phones (83%). Risk factors for NCD, such as tobacco use (45%), overweight (20%), abdominal obesity (53%), hypertension (18%), diabetes (8%) and pre-diabetes (40%) were high. At the same time, infectious diseases such as hepatitis B (24%) and hepatitis C (8%) were prevalent in this population. CONCLUSION: Our findings highlight the need to monitor risk factors and disease trends through longitudinal research in high-burden transition communities in the context of rapid urbanization and changing lifestyles. They also demonstrate the urgency of public health intervention programs tailored for these transition communities.

Engaging the private sector to increase tuberculosis case detection: an impact evaluation study.

BACKGROUND: In many countries with a high burden of tuberculosis, most patients receive treatment in the private sector. We evaluated a multifaceted case-detection strategy in Karachi, Pakistan, targeting the private sector. METHODS: A year-long communications campaign advised people with 2 weeks or more of productive cough to seek care at one of 54 private family medical clinics or a private hospital that was also a national tuberculosis programme (NTP) reporting centre. Community laypeople participated as screeners, using an interactive algorithm on mobile phones to assess patients and visitors in family-clinic waiting areas and the hospital's outpatient department. Screeners received cash incentives for case detection. Patients with suspected tuberculosis also came directly to the hospital's tuberculosis clinic (self-referrals) or were referred there (referrals). The primary outcome was the change (from 2010 to 2011) in tuberculosis notifications to the NTP in the intervention area compared with that in an adjacent control area. FINDINGS: Screeners assessed 388,196 individuals at family clinics and 81,700 at Indus Hospital's outpatient department from January-December, 2011. A total of 2416 tuberculosis cases were detected and notified via the NTP reporting centre at Indus Hospital: 603 through family clinics, 273 through the outpatient department, 1020 from self-referrals, and 520 from referrals. In the intervention area overall, tuberculosis case notification to the NTP increased two times (from 1569 to 3140 cases) from 2010 to 2011--a 2·21 times increase (95% CI 1·93-2·53) relative to the change in number of case notifications in the control area. From 2010 to 2011, pulmonary tuberculosis notifications at Indus Hospital increased by 3·77 times for adults and 7·32 times for children. INTERPRETATION: Novel approaches to tuberculosis case-finding involving the private sector and using laypeople, mobile phone software and incentives, and communication campaigns can substantially increase case notification in dense urban settings. FUNDING: TB REACH, Stop TB Partnership.

Economic analysis of childhood pneumonia in Northern Pakistan.

OBJECTIVES: This study estimates household costs for treatment of pneumonia, severe pneumonia and very severe febrile disease. Combined with reported costs from the health care provider perspective, an estimate of the overall financial burden of these diseases has been developed for the Northern Areas of Pakistan. METHODS: Data on the duration and economic implications of the illnesses for households were collected from caretakers of children under 3 years of age enrolled in a surveillance study who sought care at a health facility. Trained study physicians and health workers identified children with pneumonia, severe pneumonia and very severe febrile disease--as defined by protocols for the Integrated Management of Childhood Illness (IMCI). RESULTS: From January to December 2002, 141 health facility visits for pneumonia (n = 41, 29%), severe pneumonia (n = 65, 46%) and very severe febrile disease (n = 35, 25%) were recorded for 112 children who sought care at various levels of health facilities in the Northern Areas of Pakistan. The total societal average cost per episode was US$22.62 for pneumonia, US$142.90 for severe pneumonia and US$62.48 for very severe febrile disease. For household expenditures, medicines constituted the highest proportion (40.54%) of costs incurred during a visit to the health facility, followed by meals (23.68%), hospitalization (13.23%) and transportation (12.19%). CONCLUSION: Pneumonia is one of the leading killers of children in Pakistan with a correspondingly high economic burden to society. The results of this study suggest that there is a strong economic justification for expanding the availability of existing interventions to fight pneumonia, and for introducing measures such as vaccines to prevent pneumonia episodes.

Sexually transmitted infections treatment and care available to high risk populations in Pakistan.

Limited literature exists on the quality and availability of treatment and care of sexually transmitted infections (STIs) in Pakistan. This article aims to document existing services for the care and treatment of STIs available in Pakistan's public and private sectors to high risk groups (HRG), particularly the transgendered population. We conducted a cross-sectional survey to document STI services in Lahore, Karachi, Rawalpindi, Peshawar, and Quetta. Seventy-three interviews were administered with health service providers at the 3 largest public sector hospitals in each city, as well as with general physicians and traditional healers in the private sector. Twenty-five nongovernmental organizations (NGO) providing STI services were also interviewed. Fewer than 45% of private and public sector general practitioners had been trained in STI treatment after the completion of their medical curriculum, and none of the traditional healers had received any formal training or information on STIs. The World Health Organization (WHO) syndromic management guidelines were followed for STI management by 29% of public and private sector doctors and 5% of traditional healers. STI drugs were available at no cost at 44% of NGOs and at some public sector hospitals. Our findings show that although providers do treat HRGs for STIs, there are significant limitations in their ability to provide these services. These deterrents include, but are not limited to, a lack of STI training of service providers, privacy and adherence to recommended WHO syndromic management guidelines, and costly diagnostic and consultation fees.