BACKGROUNDExisting models to increase TB case notifications from the private sector in Pakistan are financially unsustainable and have achieved modest success due to limited coverage.OBJECTIVETo evaluate the impact of a social enterprise model (SEM) intervention on TB case detection in Karachi, Pakistan, and to assess its financial sustainability.METHODSPurpose-built centres were established within the private sector that integrated TB screening, diagnostics and treatment and operated 12 hours per day with convenient locations to improve access. TB services were offered free of cost, and revenue generation took place through user fees from other diagnostics. Private providers with a focus on the informal sector were engaged through community workers to generate screening referrals.RESULTSOverall 171,488 people were screened and 18,683 cases were notified, including 197 individuals with drug-resistant TB. Annual TB notifications in Karachi increased from 18,105 in 2014 to a maximum of 25,840 (40% increase). The proportion of cases in Karachi notified by the centres grew to 27% in 2020. Commercial revenue reached USD288,065 and enabled operating cost recovery of 15%. Average cost per TB case notified was USD203.CONCLUSIONThe SEM intervention contributed a large proportion of notifications in Karachi and achieved modest cost recovery.

BACKGROUND: We assessed treatment uptake and completion for 6 months of isoniazid (6H) and 3 months of isoniazid plus rifapentine weekly (3HP) in a programmatic setting in Pakistan.METHODS: All household contacts were clinically evaluated to rule out TB disease. 6H was used for TB preventive treatment (TPT) from October 2016 to April 2017; from May to September 2017, 3HP was used for contacts aged ≥2 years. We compared clinical evaluation, TPT uptake and completion rates between contacts aged ≥2 years in the 6H period and in the 3HP period.RESULTS: We identified 3,442 contacts for the 6H regimen. After clinical evaluation, 744/1,036 (72%) started treatment, while 46% completed treatment. In contrast, 3,722 contacts were identified for 3HP. After clinical evaluation, 990/1,366 (72%) started treatment, while 67% completed treatment. Uptake of TPT did not differ significantly between the 6H and 3HP groups (OR 1.03, 95%CI 0.86-1.24). However, people who initiated 3HP had 2.3 times greater odds (95% CI 1.9-2.8) of completing treatment than those who initiated 6H after adjusting for age and sex.CONCLUSION: In programmatic settings in a high-burden country, household contacts of all ages were more likely to complete TPT with shorter weekly regimens, although treatment uptake rate for the two regimens was similar.

BACKGROUND: Systematic screening for TB using automated chest radiography (ACR) with computer-aided detection software (CAD4TB) has been implemented at scale in Karachi, Pakistan. Despite evidence supporting the use of ACR as a pre-screen prior to Xpert ® MTB/RIF diagnostic testing in presumptive TB patients, there has been no data published on its use in mass screening in real-world settings. METHOD: Screening was undertaken using mobile digital X-ray vehicles at hospital facilities and community camps. Chest X-rays were offered to individuals aged ≥15 years, regardless of symptoms. Those with a CAD4TB score of ≥70 were offered Xpert testing. The association between Xpert positivity and CAD4TB scores was examined using data collected between 1 January and 30 June 2018 using a custom-built data collection tool. RESULTS: Of the 127 062 individuals screened, 97.2% had a valid CAD4TB score; 11 184 (9.1%) individuals had a CAD4TB score ≥70. Prevalence of Xpert positivity rose from 0.7% in the <50 category to 23.5% in the >90 category. The strong linear association between CAD4TB score and Xpert positivity was found in both community and hospital settings. CONCLUSION: The strong association between CAD4TB scores and Xpert positivity provide evidence that an ACR-based pre-screening performs well when implemented at scale in a high-burden setting.

SETTING:Pakistan ranks fourth among the countries with a high burden of multidrug-resistant tuberculosis (MDR-TB), with only 19.2% of the 15 000 estimated incident cases being notified. Increasing treatment coverage for MDR-TB is a key priority for Pakistan's National Tuberculosis Programme. The World Health Organization recommends the use of the Xpert® MTB/RIF assay as the first-line diagnostic test for individuals with presumed TB.OBJECTIVE:To describe a multifaceted case-finding intervention targeting public and private sector health care facilities that used the Xpert assay as a frontline diagnostic test for individuals with presumptive TB, in Karachi, Pakistan, and its impact on case notifications of MDR-TB.DESIGN:Cross-sectional study.RESULTS:A total of 51 168 individuals were tested using Xpert, of whom respectively 7581 and 1534 people were diagnosed with TB in the public sector (reverse public-private mix) and private sector (social business model) arms; 574 (6.3% of all TB cases) were identified as having rifampicin (RMP) resistance. A total of 517 (90.1%) people with RMP-resistant TB (RR-TB) identified through the project were initiated on second-line treatment. The intervention resulted in 194 additional cases of RR-TB, an increase of 43% over the baseline.CONCLUSION:This project, one of the largest Xpert testing programmes conducted at city level, resulted in significantly increased detection and treatment of MDR-TB.

SETTING Urban Karachi, Pakistan. OBJECTIVE To describe the yield of a contact investigation protocol implemented among children living with drug-resistant tuberculosis (DR-TB) patients. DESIGN We implemented a contact investigation protocol in households of DR-TB patients treated at the Indus Hospital, Karachi, between January 2008 and April 2011. This included a detailed history and physical examination, tuberculin skin test, chest radiograph, smear microscopy and culture of sputum or gastric aspirate specimens, and drug susceptibility testing. Treatment supporters who visited DR-TB patients at home referred all child contacts for baseline evaluation and performed monthly assessments. We evaluated two age groups: 1) children aged <5 years, and 2) those aged 5-14 years. RESULTS Among 133 children aged <15 years in 40 households, 40.4% (51/125) were moderately to severely underweight (weight-for-age Z-score <-2). Overall, 7.5% (10/133) had TB disease. This proportion was 6.5% (2/31) in those aged <5 years and 7.8% (8/102) in those aged 5-14 years. Seven (7/10) were smear-positive, and 4/10 had culture-confirmed multidrug-resistant Mycobacterium tuberculosis CONCLUSION We detected a high prevalence of TB in children who live with DR-TB patients, regardless of the age of the child. Child contacts of DR-TB patients are a high-yield population for detecting TB cases.

Culture conversion is an interim monitoring tool for treatment of multidrug-resistant tuberculosis (MDR-TB). We evaluated the time to and predictors of culture conversion in pulmonary MDR-TB patients enrolled in the community-based MDR-TB management program at the Indus Hospital in Karachi, Pakistan. Despite strict daily directly observed therapy, monthly food incentives and patient counseling, the median time to culture conversion was 196 days (range 32-471). The cumulative probabilities of culture conversion by 2, 4, 6 and 12 months were respectively 6%, 33%, 47%, and 73%. Smoking, high smear grade at baseline and previous use of second-line drugs delayed culture conversion.

This study introduced food/medicine vouchers as an incentive to mothers of infants visiting Expanded Program on Immunization (EPI) centers in a low socio-economic area. The timely completion of diphtheria, tetanus and pertussis vaccines combined (DTP) series immunization rates between intervention and control cohorts were compared. The DTP up-to-date immunization coverage at 18 weeks of age increased two-fold (RR 2.20, 95% CI: 1.95–2.48, p<0.001) in the incentive cohort compared to the no-incentive cohort. While increasing immunization coverage is a complex structural and behavioral process, food/medicine coupon may improve routine immunization coverage in developing countries.