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Background and Objectives In the absence of bacteriologic confirmation to diagnose tuberculosis (TB) in children, it is suggested that treatment should be initiated when sufficient clinical evidence of disease is available. However, it is unclear what clinical evidence is sufficient to make this decision. To identify children who would benefit from rapid initiation of TB treatment, we developed two clinical prediction tools. Methods We conducted a secondary analysis of a prospective intensified TB patient-finding intervention conducted in Pakistan in 2014-2016.TB disease was determined through either bacteriologic confirmation or a clinical diagnosis. We derived two tools; one uses Classification and Regression Tree (CART) analysis to develop decision trees while the second uses multivariable logistic regression to calculate a risk score. Results Of the 5,162 and 5,074 children included in the CART and prediction-score, respectively, 1,417 (27.5%) and 1,365 (26.9%) were eligible for TB treatment. CART identified abnormal chest radiographs and family history of TB as the most important predictors (area under the receiver operating characteristic curve [AUC]: 0.949). The final prediction-score model included age group (0-4, 5-9, 10-14), weight Conclusions Use of clinical evidence was sufficient to accurately identify children who would benefit from treatment initiation. Our tools performed well compared to existing algorithms, though needs to be externally validated prior to operationalization.

Nearly 40% of people affected by TB in Pakistan are not diagnosed each year. Guidelines recommend screening household contacts however, not all index patients or contacts are eligible. Therefore, many contacts who may have TB disease, remain unscreened.We conducted a prospective cohort study under programmatic conditions in Karachi, Pakistan from January 2018 - December 2019, to screen all household contacts of all TB index patients. We disaggregated these according to guidelines into eligible (those with bacteriologically confirmed pulmonary TB or children Out of 39,168 household contacts from 6,362 index patients, 21,035 completed clinical assessments for TB disease, and 416 were diagnosed with all forms TB. Household contacts of clinically diagnosed pulmonary TB patients were 26% more likely to be diagnosed with TB compared to the household contacts of bacteriologically confirmed pulmonary TB (adjusted Odds Ratio 1.26 [1.01 – 1.59] p-value:0.03). The yield of TB disease among child contacts (3.4%) was significantly higher than the yield among adult contacts (0.5%) (p-value:Broadening TB contact screening guidelines to include clinically diagnosed and extrapulmonary index patients ≥5 years could double the number of patients detected at a similar level of effort.

Purpose Tuberculosis (TB) is geographically heterogeneous, and geographic targeting can improve the impact of TB interventions. However, standard TB notification data may not sufficiently capture this heterogeneity. Better understanding of patient reporting patterns (discrepancies between residence and place of presentation) may improve our ability to use notifications to appropriately target interventions. Methods Using demographic data and TB reports from Dhaka North City Corporation and Dhaka South City Corporation, we identified wards of high TB incidence and developed a TB transmission model. We calibrated the model to patient-level data from selected wards under four different reporting pattern assumptions and estimated the relative impact of targeted versus untargeted active case finding. Results The impact of geographically targeted interventions varied substantially depending on reporting pattern assumptions. The relative reduction in TB incidence, comparing targeted with untargeted active case finding in Dhaka North City Corporation, was 1.20, assuming weak correlation between reporting and residence, versus 2.45, assuming perfect correlation. Similar patterns were observed in Dhaka South City Corporation (1.03 vs. 2.08). Conclusions Movement of individuals seeking TB diagnoses may substantially affect ward-level TB transmission. Better understanding of patient reporting patterns can improve estimates of the impact of targeted interventions in reducing TB incidence. Incorporating high-quality patient-level data is critical to optimizing TB interventions.

Fluoroquinolone-based preventive therapy reduced risk for tuberculosis disease by 65%., In Karachi, Pakistan, a South Asian megacity with a high prevalence of tuberculosis (TB) and low HIV prevalence, we assessed the effectiveness of fluoroquinolone-based preventive therapy for drug-resistant (DR) TB exposure. During February 2016–March 2017, high-risk household contacts of DR TB patients began a 6-month course of preventive therapy with a fluoroquinolone-based, 2-drug regimen. We assessed effectiveness in this cohort by comparing the rate and risk for TB disease over 2 years to the rates and risks reported in the literature. Of 172 participants, TB occurred in 2 persons over 336 person-years of observation. TB disease incidence rate observed in the cohort was 6.0/1,000 person-years. The incidence rate ratio ranged from 0.29 (95% CI 0.04–1.3) to 0.50 (95% CI 0.06–2.8), with a pooled estimate of 0.35 (95% CI 0.14–0.87). Overall, fluoroquinolone-based preventive therapy for DR TB exposure reduced risk for TB disease by 65%.

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., In a tuberculosis-preventive treatment program in Karachi, Pakistan, the cost per completed course was lower for 12-dose isoniazid and rifapentine than for 6 months of daily isoniazid.

Clinical presentation for extrapulmonary tuberculosis (EPTB) in children can be variable and nonspecific, leading to delayed diagnosis, disease and death. We describe the age-specific clinical presentation and identify risk factors for EPTB among children in Pakistan.In 2015-2016 in 4 facilities in Sindh, Pakistan, children were diagnosed with TB either through bacteriologic confirmation or clinical-radiologic criteria. EPTB comprised any form of TB disease that did not involve the lungs. Among children with TB disease, we report demographics, clinical characteristics and symptoms, family medical history and diagnostic test results for children with and without EPTB. We conduct age-specific regression analyses to identify factors associated with an EPTB diagnosis among children age 0-4, 5-9 and 10-14 years.A total of 1163 children were diagnosed with TB disease, of which 157 (13.5%) had EPTB. Of those, 46 (29.3%) were 0-4, 53 (33.8%) were 5-9 and 58 (36.9%) were 10-14 years old. Of children with EPTB, the most frequently reported sites were lymph node (113, 72.4%) and abdominal (31, 19.9%). Weight loss was associated with an increased risk of EPTB in the 0-4-year-old (adjusted odds ratio: 2.80, 95% confidence interval: 1.05-7.47) and 10-14-year-old (adjusted odds ratio: 2.79, 95% confidence interval: 1.28-6.07) groups, and the presence of cough was associated with a decreased risk of EPTB.This study provides new knowledge about age-specific clinical presentation and risk factors of EPTB in children in Pakistan. Our results can help to optimize clinical algorithms designed to achieve a timely diagnosis in children with EPTB along with improved treatment outcomes.

We developed a novel method to align two data sources (TB notifications and the Demographic Health Survey, DHS) captured at different geographic scales. We used this method to identify sociodemographic indicators – specifically population density – that were ecologically correlated with elevated TB notification rates across wards (~100 000 people) in Dhaka, Bangladesh. We found population density was the variable most closely correlated with ward-level TB notification rates (Spearman's rank correlation 0.45). Our approach can be useful, as publicly available data (e.g. DHS data) could help identify factors that are ecologically associated with disease burden when more granular data (e.g. ward-level TB notifications) are not available. Use of this approach might help in designing spatially targeted interventions for TB and other diseases in settings of weak existing data on disease burden at the subdistrict level.

To map which tuberculosis care models are best suited for children and adolescents.We conducted a scoping review to assess the impact of decentralized, integrated and family-centred care on child and adolescent tuberculosis-related outcomes, describe approaches for these care models and identify key knowledge gaps. We searched seven literature databases on 5 February 2021 (updated 16 February 2022), searched the references of 18 published reviews and requested data from ongoing studies. We included studies from countries with a high tuberculosis burden that used a care model of interest and reported tuberculosis diagnostic, treatment or prevention outcomes for an age group 20 years old.We identified 28 studies with a comparator group for the impact assessment and added 19 non-comparative studies to a qualitative analysis of care delivery approaches. Approaches included strengthening capacity in primary-level facilities, providing services in communities, screening for tuberculosis in other health services, co-locating tuberculosis and human immunodeficiency virus treatment, offering a choice of treatment location and providing social or economic support. Strengthening both decentralized diagnostic services and community linkages led to one-to-sevenfold increases in case detection across nine studies and improved prevention outcomes. We identified only five comparative studies on integrated or family-centred care, but 11 non-comparative studies reported successful treatment outcomes for at least 71% of children and adolescents.Strengthening decentralized services in facilities and communities can improve tuberculosis outcomes for children and adolescents. Further research is needed to identify optimal integrated and family-centred care approaches.Caractériser les modèles de prise en charge de la tuberculose les mieux adaptés aux enfants et adolescents.Nous avons mené une analyse exploratoire afin d'évaluer l'impact d'une prise en charge décentralisée, intégrée et articulée autour du noyau familial sur les résultats observés chez les enfants et adolescents traités pour une tuberculose, mais aussi de décrire les approches employées pour ces modèles de soins et d'identifier les principales lacunes dans les connaissances à ce sujet. Nous avons effectué des recherches dans sept bases de données dédiées à la littérature le 5 février 2021 (mise à jour le 16 février 2022), examiné les références de 18 revues publiées et demandé des informations issues d'études en cours. Nous avons inclus des études provenant de pays fortement touchés par la tuberculose, qui utilisaient un modèle de prise en charge digne d'intérêt et faisaient mention de résultats de diagnostic, de traitement ou de prévention pour une catégorie d'âge 20 ans.Nous avons identifié 28 études avec un groupe de comparaison pour mesurer l'impact, et nous avons ajouté 19 études non comparatives à une analyse qualitative des approches de prestation de soins. Parmi ces approches figuraient le renforcement des capacités dans les établissements de niveau primaire, la fourniture de services au sein des communautés, le dépistage de la tuberculose dans d'autres services de santé, le regroupement des traitements contre la tuberculose et le virus de l'immunodéficience humaine, la possibilité pour le patient de choisir son lieu de traitement et enfin, la mise à disposition d'une aide sociale ou économique. Développer à la fois les services de diagnostic décentralisés et les réseaux communautaires a permis de multiplier par sept le dépistage des cas dans neuf études, et d'optimiser les résultats de prévention. Nous n'avons trouvé que cinq études comparatives consacrées aux soins intégrés ou articulés autour du noyau familial. En revanche, 11 études non comparatives ont indiqué que le traitement avait été couronné de succès chez au moins 71% des enfants et adolescents.Renforcer les services décentralisés dans les établissements et communautés peut contribuer à améliorer l'état des enfants et adolescents souffrant de tuberculose. D'autres recherches sont nécessaires pour dégager les meilleures approches intégrées et articulées autour du noyau familial.Establecer qué modelos de atención a la tuberculosis son los más adecuados para los niños y adolescentes.Se realizó una revisión exploratoria para evaluar los impactos de la atención descentralizada, integrada y orientada a la familia en los desenlaces relacionados con la tuberculosis en niños y adolescentes, describir los enfoques de estos modelos de atención e identificar las principales deficiencias de conocimiento. Se realizaron búsquedas en siete bases de datos bibliográficas el 5 de febrero de 2021 (actualizadas el 16 de febrero de 2022), se buscaron las referencias de 18 revisiones publicadas y se solicitaron datos de estudios en curso. Se incluyeron estudios de países con una alta carga de tuberculosis que emplearan un modelo de atención de interés e informaran sobre los resultados de diagnóstico, tratamiento o prevención de la tuberculosis en un grupo de edad20 años.Se identificaron 28 estudios con un grupo comparativo para la evaluación del impacto y se añadieron 19 estudios no comparativos a un análisis cualitativo de los enfoques de prestación de atención. Los enfoques incluyeron el fortalecimiento de la capacidad en los centros de nivel primario, la prestación de servicios en las comunidades, la detección de la tuberculosis en otros servicios sanitarios, la ubicación conjunta del tratamiento de la tuberculosis y del virus de la inmunodeficiencia humana, la posibilidad de que el paciente elija el lugar de tratamiento y la prestación de apoyo social o económico. El refuerzo de los servicios de diagnóstico descentralizados y de los vínculos con la comunidad permitió multiplicar de una a siete veces la detección de casos en nueve estudios y mejorar los resultados de la prevención. Solo se identificaron cinco estudios comparativos sobre la atención integrada u orientada a la familia, pero 11 estudios no comparativos informaron de resultados de tratamiento exitosos en al menos el 71% de los niños y adolescentes.El refuerzo de los servicios descentralizados en los centros y las comunidades puede mejorar los desenlaces de la tuberculosis en niños y adolescentes. Es preciso seguir investigando para determinar los enfoques óptimos de atención integrada y orientada a la familia.تحديد أفضل نماذج رعاية السل بالنسبة للأطفال والمراهقين.قمنا بإجراء مراجعة عن كثب لتقييم تأثير الرعاية اللامركزية المتكاملة التي تركز على الأسرة، على النتائج المتعلقة بالسل بالنسبة للأطفال والمراهقين، ووصف الاساليب الخاصة بنماذج الرعاية هذه، وتحديد الفجوات المعرفية الرئيسية. قمنا بالبحث في سبع قواعد بيانات للمنشورات في 5 فبراير/شباط 2021 (تم تحديثها في 16 فبراير/شباط 2022)، والبحث في مراجع لعدد 18 مراجعة منشورة وطلبنا البيانات من الدراسات الجارية. وكذلك قمنا بتضمين دراسات من الدول ذات العبء المرتفع من السل، والتي استخدمت نموذجًا مهمًا للرعاية، وأبلغت عن نتائج تشخيص السل أو علاجه أو الوقاية منه للفئة العمرية الأقل من 20 سنة.قمنا بتحديد 28 دراسة مع مجموعة مقارنة لتقييم التأثير، وأضفنا 19 دراسة غير مقارنة إلى التحليل النوعي لأساليب تقديم الرعاية. تضمنت الأساليب تعزيز القدرات في مرافق المستوى الأولي، وتقديم الخدمات في المجتمعات، والكشف عن مرض السل مع الخدمات الصحية الأخرى، والاشتراك في اكتشاف علاج السل وفيروس نقص المناعة البشرية، وعرض اختيار المريض لمكان العلاج، وتقديم الدعم الاجتماعي أو الاقتصادي. أدى تعزيز كل من خدمات التشخيص اللامركزية والروابط المجتمعية إلى زيادات من واحد إلى سبعة أضعاف في اكتشاف الحالات عبر تسع دراسات، كما أدى لتحسين نتائج الوقاية. قمنا بتحديد خمس دراسات مقارنة فقط حول الرعاية المتكاملة أو التي تركز على الأسرة، لكن 11 دراسة غير مقارنة أفصحت عن نتائج علاجية ناجحة على الأقل لـ %71 من الأطفال والمراهقين.يمكن أن يؤدي تعزيز الخدمات اللامركزية في المرافق والمجتمعات إلى تحسين نتائج مرض السل بالنسبة للأطفال والمراهقين. هناك حاجة لمزيد من الأبحاث لتحديد أساليب الرعاية المثلى المتكاملة والتي تركز على الأسرة.探讨哪种结核病护理模式最适合儿童和青少年。.我们开展了一项范围评审,评估分散式、综合和以家庭为中心的护理对儿童和青少年结核病相关护理效果的影响,介绍适用于此类护理模式的方法并确定关键的知识差距。我们于 2021 年 2 月 5 日从七个文献数据库中搜索了 18 份已出版评审的参考资料(于 2022 年 2 月 16 日进行了更新),并提取了目前正在开展的研究中的数据。我们纳入了存在较高结核病负担国家的研究,采用我们感兴趣的护理模式开展研究,并报告了 20 岁以下人群的结核病诊断、治疗或预防效果。.我们确定了 28 项采用对照组开展的影响评估研究和 19 项未采用对照组开展的研究,对护理方法进行了定性分析。方法包括加强初级护理机构的护理能力、面向社区提供服务、通过其他卫生服务开展结核病筛查、在同一地点协同开展结核病和艾滋病治疗、让患者选择治疗地点以及提供社会或经济支持。九项研究表明,通过加强分散式诊断服务与社区之间的联系,病例检测率提升了一至七倍,并且预防效果也显著提高。我们仅确定了五项综合或以家庭为中心护理方面的对比研究,但是 11 项非对比研究显示儿童和青少年的成功治疗结果至少提高 71%。.加强护理机构和社区内的分散式服务,可提高儿童和青少年的结核病护理效果。需开展进一步研究以确定最佳的综合和以家庭为中心的护理方法。.Определить, какие модели лечения туберкулеза лучше всего подходят для детей и подростков.Для оценки влияния децентрализованного, интегрированного и ориентированного на семью ухода на результаты лечения туберкулеза у детей и подростков, описания подходов к этим моделям ухода и выявления основных пробелов в знаниях была подготовлена концептуальная проработка. 5 февраля 2021 года был проведен поиск в семи базах данных литературы (обновлено 16 февраля 2022 года), просмотрены ссылки на 18 опубликованных обзоров и запрошены данные текущих исследований. Были включены исследования из стран с высоким уровнем заболеваемости туберкулезом, в которых использовалась интересующая модель ухода и сообщалось о результатах диагностики, лечения или профилактики туберкулеза в возрастной группе младше 20 лет.Для оценки воздействия было выделено 28 исследований с группой сравнения и добавлено 19 несравнительных исследований для качественного анализа подходов к оказанию медицинской помощи. В качестве подходов использовались: укрепление потенциала учреждений первичного звена, предоставление услуг в общинах, скрининг на наличие туберкулеза в других медицинских учреждениях, совместное лечение туберкулеза и вируса иммунодефицита человека, предоставление пациенту возможности выбора места лечения и оказание социальной или экономической поддержки. Развитие децентрализованных диагностических служб и укрепление связей с местными общинами привели к увеличению выявления случаев заболевания от одного до семи раз в девяти исследованиях и улучшению результатов профилактики. Было выявлено только пять сравнительных исследований по интегрированному или ориентированному на семью уходу, однако в 11 несравнительных исследованиях сообщалось об успешных результатах лечения не менее 71% детей и подростков.Развитие децентрализованных услуг в учреждениях и общинах может способствовать улучшению результатов лечения туберкулеза у детей и подростков. Для определения оптимальных подходов к интегрированному и ориентированному на семью уходу необходимо проведение дальнейших исследований.

Background Existing screening methods for TB involve trade-offs among sensitivity, specificity and cost. Recent advances mean that dual-energy X-ray is more sensitive and only slightly more costly than conventional chest X-ray and could be a high-performing alternative for TB screening, particularly if associated computer-aided diagnostic (CAD) software were developed. Methods Existing data on sensitivity,specificity and cost were used for six screening methods (sputum testing, conventional chest X-ray with and without CAD software, dual-energy X-ray with and without CAD software, and nucleic acid amplification testing (NAAT), used in various sequences. Cost and effectiveness of 20 different screening pathwayswere examined using data for Pakistan. Monte-carlo based sensitivity analysis focused on parameters for dual-energy X-ray. Results Sputum followed by NAAT is the best pathway when government budgets are low, and NAAT alone is the best when budgets are unlimited. With intermediate budgets, pathways including dual-energy X-ray dominate those including conventional X-rays, particularly if CAD software is developed for dual-energy X-ray. Conclusions Dual-energy X-ray can be a valuable addition to the screening options for TB. Our study provides different TB screening options for policy makers and TB program managers, which could be used as a guide for planning and implementation of TB screening programs.

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.

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., We evaluated the cost-effectiveness of artificial intelligence–based chest radiograph analysis for tuberculosis detection, based on a trial in Pakistan. Compared to upfront sputum testing, use of this technology to triage people with symptoms reduced costs and averted disability-adjusted life-years.

Objective To apply a cascade-of-care framework to evaluate the effectiveness—by age of the child—of an intensified tuberculosis patient-finding intervention. Design From a prospective screening program at four hospitals in Pakistan (2014–2016) we constructed a care cascade comprising six steps: screened, positive screen, evaluated, diagnosed, started treatment, and successful outcome. We evaluated the cascade by each year of age from 0 to 14 and report the age-specific mean proportion and standard deviation. Results On average across all ages, only 12.5% (standard deviation: 2.0%) of children with a positive screen were not evaluated. Among children who had a complete evaluation, the highest percentages of children diagnosed with tuberculosis were observed in children 0–4 (mean: 31.9%; standard deviation: 4.8%), followed by lower percentages in children 5–9 (mean: 22.4%; standard deviation: 2.2%), and 10–14 (mean: 26.0%; standard deviation:5.4%). Nearly all children diagnosed with tuberculosis initiated treatment, and an average of 93.3% (standard deviation: 3.3%) across all ages had successful treatment outcomes. Conclusions This intervention was highly effective across ages 0–14 years. Our study illustrates the utility of applying operational analyses of age-stratified cascades to identify age-specific gaps in pediatric tuberculosis care that can guide future, novel interventions to close these gaps.

BackgroundIn rapidly growing, high burden urban centers, identifying tuberculosis (TB) transmission hotspots and understanding potential impact of interventions can inform future control and prevention strategies.MethodsUsing data on local demography, TB reports, and patient reporting patterns in Dhaka South City Corporation (DSCC) and Dhaka North City Corporation (DNCC), Bangladesh, between 2010 and 2017, we developed maps of TB reporting rates across wards in DSCC and DNCC and identified wards with high rates of reported TB (i.e. “hotspots”) in DSCC and DNCC. We developed ward-level transmission models and estimated the potential epidemiological impact of three TB interventions: active case finding (ACF), mass preventive therapy (PT), and a combination of ACF and PT, implemented either citywide or targeted to high-incidence hotspots.ResultsThere was substantial geographic heterogeneity in the estimated TB incidence in both DSCC and DNCC: incidence in the highest-incidence wards was over ten times higher than in the lowest-incidence wards in each city corporation. ACF, PT and combined ACF plus PT delivered to 10% of the population reduced TB incidence by a projected 7-9%, 13-15%, and 19-23% over five years, respectively. Targeting TB hotspots increased the projected reduction in TB incidence achieved by each intervention 1.4- to 1.8-fold.ConclusionsThe geographical pattern of TB notifications suggests high levels of ongoing TB transmission in DSCC and DNCC, with substantial heterogeneity at the ward level. Interventions that reduce transmission are likely to be highly effective, and incorporating notification data at the local level can further improve intervention efficiency.

In a matched case-control study in Pakistan, we found that quantified tuberculosis (TB) exposure using a 10-point score is associated with prevalent TB disease in pediatric household contacts. A 1 unit increase in TB exposure score increased the odds of TB disease by 44% (conditional odds ratio: 1.44, 95% confidence interval: 1.33-1.56). Collecting well-documented exposure history can help TB diagnosis in resource-limited settings.

Background Every year, about 239 000 children die from tuberculosis (TB), despite availability of highly effective regimens. Few studies have evaluated predictors for poor treatment outcomes in children treated for TB. Methods We assessed predictors of unsuccessful TB treatment outcomes in a prospective cohort of children diagnosed by an intensified TB patient-finding intervention at four facilities in Pakistan between 2014 and 2016. A case of TB disease was determined through either bacteriologic confirmation of disease or a clinical diagnosis. To estimate characteristics predictive of experiencing an unsuccessful treatment outcome, we used a multi-level model with a modified Poisson approach, accounting for clustering at the facility level. We report estimated relative risks (RR) and 95% confidence intervals (CI). Results During the study period, 1404 children less than 15 years old were initiated on treatment for drug-susceptible TB. In total, 709 (50.5%) were 0-4, 406 (28.9%) were 5-9 years, and 289 (20.6%) were 10-14 years old; 614 (43.7%) were female; and of the 1377 children assessed for malnourishment, 1161 (84.3%) were malnourished. A total of 1322 (94.2%) children experienced a successful treatment outcome, 14 (1.0%) children transferred out to a different facility, and 68 (4.8%) children experienced an unsuccessful treatment outcome: 14 (1.0%) died, 20 (1.4%) failed treatment, and 34 (2.4%) were lost to follow-up. After adjustment for age group, sex, and malnutrition status, we identified increased risk of unsuccessful treatment outcome in children presenting with fever (RR = 2.56, 95% CI = 1.02-6.44; P = 0.05) or an abdominal examination suggestive of TB disease (RR = 2.34, 95% CI = 1.20-4.58; P = 0.01), and a decreased risk in children who initiated treatment at a rural facility (RR = 0.05, 95% CI = 0.00-0.74; P = 0.03). Conclusions More than 94% of children experienced successful treatment outcomes. We identified individual-, facility-, and clinical-factors predictive of experiencing unsuccessful treatment outcomes. Children with fevers and abdominal findings suggestive of TB disease should be tested for TB and followed closely throughout treatment to ensure necessary support for successful completion of treatment.

Summary 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.

Health-related quality of life (HRQoL) of pulmonary TB patients has not been assessed in Pakistan. We assessed self-reported HRQoL of pulmonary TB patients in Karachi, Pakistan utilizing the EQ-5D and EQ-VAS prior to, during, and after completion of TB treatment. We enrolled 226 pulmonary TB patients in a longitudinal cohort study. Health-utility scores were estimated by the EQ-5D five dimensions and the EQ-Visual Analogue Scale (VAS) at baseline (month 0) and each monthly follow-up visit until treatment completion at month 6. Repeated-measures ANOVA was used to investigate effect of time into treatment on EQ-5D and EQ-VAS scores. EQ-5D health utility and EQ-VAS scores increase with treatment progression. For the enrolled TB patients, the mean EQ-5D utility scores more than doubled from 0.43 to 0.88, p

SETTING Many children with tuberculosis (TB) remain undiagnosed due to the absence of services, lack of child-friendly diagnostics and underappreciation of TB as a common cause of childhood illness. OBJECTIVE To show the impact of systematic verbal screening and contact tracing with appropriate management services on TB case finding in pediatric populations. DESIGN Between October 2014 and March 2016, children were verbally screened at the pediatric out-patient departments of four public hospitals in Jamshoro District, Pakistan. Children with symptoms or risk of TB were referred for clinical evaluation and free chest X-ray and bacteriological tests. Children with TB were started on treatment and their care givers asked to bring household members to the hospital for screening. RESULTS Over 105 000 children were verbally screened and 5880 presumptive childhood TB patients were identified; 1417 children (prevalence 1.3%) were diagnosed with TB; 43% were female. The median age was 5 years; 82% had pulmonary TB. An additional 390 children with TB were diagnosed through contact tracing. These activities resulted in a three-fold increase in pediatric TB case notifications. CONCLUSION Systematic verbal screening with clinical evaluation and free diagnostics can identify children with TB who may otherwise be missed in rural health settings.

The COVID-19 pandemic has impacted health systems and health programs across the world. For tuberculosis (TB), it is predicted to set back progress by at least twelve years. Public private mix (PPM)has made a vital contribution to reach End TB targets with a ten-fold rise in TB notifications from private providers between 2012 and 2019. This is due in large part to the efforts of intermediary agencies, which aggregate demand from private providers. The COVID-19 pandemic has put these gains at risk over the past year. In this rapid assessment, representatives of 15 intermediary agencies from seven countries that are considered the highest priority for PPM in TB care (the Big Seven) share their views on the impact of COVID-19 on their programs, the private providers operating under their PPM schemes, and their private TB clients. All intermediaries reported a drop in TB testing and notifications, and the closure of some private practices. While travel restrictions and the fear of contracting COVID-19 were the main contributing factors, there were also unanticipated expenses for private providers, which were transferred to patients via increased prices. Intermediaries also had their routine activities disrupted and had to shift tasks and budgets to meet the new needs. However, the intermediaries and their partners rapidly adapted, including an increased use of digital tools, patient-centric services, and ancillary support for private providers. Despite many setbacks, the COVID-19 pandemic has underlined the importance of effective private sector engagement. The robust approach to fight COVID-19 has shown the possibilities for ending TB with a similar approach, augmented by the digital revolution around treatment and diagnostics and the push to decentralize health services.

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.

This study is a review of routine programmatically collected data to describe the 5-year trend in childhood case notification in Jamshoro district, Pakistan from January 2013 to June 2018 and review of financial data for the two active case finding projects implemented during this period. The average case notification in the district was 86 per quarter before the start of active case finding project in October 2014. The average case notification rose to 322 per quarter during the implementation period (October 2014 to March 2016) and plateaued at 245 per quarter during the post-implementation period (April 2016 to June 2018). In a specialized chest center located in the district, where active case finding was re-introduced during the post implementation period (October 2016), the average case notification was 218 per quarter in the implementation period and 172 per quarter in the post implementation period. In the rest of the district, the average case notification was 160 per quarter in the implementation period and 78 during the post implementation period. The cost per additional child with TB found ranged from USD 28 to USD 42 during the interventions. A continuous stream of resources is necessary to sustain high notifications of childhood TB.