Interventions to improve adherence to treatment for paediatric tuberculosis in low- and middle-income countries: a systematic review and meta-analysis

Weaver, Meaghann S; Lönnroth, Knut; Howard, Scott C; Roter, Debra L; Lam, Catherine G

doi:10.2471/BLT.14.147231

Abstract

Objective

To assess the design, delivery and outcomes of interventions to improve adherence to treatment for paediatric tuberculosis in low- and middle-income countries and develop a contextual framework for such interventions.

Methods

We searched PubMed and Cochrane databases for reports published between 1 January 2003 and 1 December 2013 on interventions to improve adherence to treatment for tuberculosis that included patients younger than 20 years who lived in a low- or middle-income country. For potentially relevant articles that lacked paediatric outcomes, we contacted the authors of the studies. We assessed heterogeneity and risk of bias. To evaluate treatment success - i.e. the combination of treatment completion and cure - we performed random-effects meta-analysis. We identified areas of need for improved intervention practices.

Findings

We included 15 studies in 11 countries for the qualitative analysis and of these studies, 11 qualified for the meta-analysis - representing 1279 children. Of the interventions described in the 15 studies, two focused on education, one on psychosocial support, seven on care delivery, four on health systems and one on financial provisions. The children in intervention arms had higher rates of treatment success, compared with those in control groups (odds ratio: 3.02; 95% confidence interval: 2.19-4.15). Using the results of our analyses, we developed a framework around factors that promoted or threatened treatment completion.

Conclusion

Various interventions to improve adherence to treatment for paediatric tuberculosis appear both feasible and effective in low- and middle-income countries.

Résumé

Objectif

Évaluer la conception, la mise en œuvre et les résultats des interventions visant à améliorer l'observance thérapeutique dans le traitement de la tuberculose chez l'enfant dans les pays à revenu faible et intermédiaire et élaborer un cadre contextuel pour ce type d'interventions.

Méthodes

Nous avons fait des recherches dans les bases de données PubMed et Cochrane pour trouver des rapports publiés entre le 1er janvier 2003 et le 1er décembre 2013 sur des interventions visant à améliorer l'observance thérapeutique dans le traitement de la tuberculose chez des patients de moins de vingt ans vivant dans des pays à revenu faible ou intermédiaire. Pour les articles potentiellement pertinents qui omettaient de citer spécifiquement les résultats chez l'enfant, nous avons contacté les auteurs. Nous avons évalué l'hétérogénéité et le risque de biais. Pour évaluer la réussite d'un traitement (c'est-à-dire: combinaison de l'achèvement du traitement et de la guérison), nous avons effectué une méta-analyse à effets aléatoires. Nous avons également identifié les points à améliorer en vue d'optimiser les programmes d'intervention.

Résultats

Pour notre analyse qualitative, nous avons intégré quinze études, menées dans onze pays. Sur ces études, onze ont pu être retenues pour la méta-analyse (représentant 1.279 enfants). Concernant les interventions décrites dans les quinze études, deux ciblaient l'éducation, une le soutien psychosocial, sept la délivrance des soins, quatre les systèmes de santé et une le soutien financier. Des taux de succès du traitement plus élevés ont été constatés chez les enfants qui ont bénéficié des interventions, comparativement aux enfants des groupes témoins (rapport des cotes: 3,02; intervalle de confiance de 95%: 2,19-4,15). À partir des résultats de nos analyses, nous avons conçu un cadre autour des facteurs ayant favorisé ou entravé l'achèvement du traitement.

Conclusion

Plusieurs interventions visant à améliorer l'observance thérapeutique dans le traitement de la tuberculose chez l'enfant semblent être à la fois réalisables et efficaces dans les pays à revenu faible et intermédiaire.

Resumen

Objetivo

Evaluar el diseño, la prestación y los resultados de las intervenciones para mejorar el cumplimiento del tratamiento de la tuberculosis pediátrica en países de ingresos bajos y medios y desarrollar un marco contextual para tales intervenciones.

Métodos

Se realizaron búsquedas en las bases de datos PubMed y Cochrane para encontrar informes sobre las intervenciones para mejorar el cumplimiento del tratamiento de la tuberculosis publicados entre el 1 de enero de 2003 y el 1 de diciembre de 2013 que incluyeran pacientes menores de 20 años que vivieran en países de ingresos bajos o medios. Se contactó con los autores de los estudios con artículos relevantes que carecían de resultados pediátricos. Se evaluó la heterogeneidad y el riesgo de sesgo. Se llevaron a cabo metanálisis de efectos aleatorios para evaluar el éxito del tratamiento, es decir, la combinación de finalización del tratamiento y cura. Se identificaron áreas que necesitaban una mejora de las prácticas de intervención.

Resultados

Se incluyeron 15 estudios en 11 países para el análisis cualitativo y, de esos estudios, 11 cumplieron los requisitos para el metanálisis: una representación de 1279 niños. De las intervenciones descritas en los 15 estudios, dos se centraban en la educación, uno en el apoyo psicosocial, siete en la prestación de asistencia, cuatro en los sistemas de salud y uno en las dotaciones financieras. Los niños en el brazo de intervención tenían una tasa mayor de éxito del tratamiento en comparación con aquellos en grupos de control (razón de posibilidades: 3,02; intervalo de confianza del 95%: 2.19-4.15). Utilizando los resultados en los análisis, se desarrolló un marco alrededor de los factores que promovían o amenazaban la finalización del tratamiento.

Conclusión

Varias intervenciones para mejorar el cumplimiento del tratamiento de la tuberculosis pediátrica parecen tanto viables como efectivas en países de ingresos bajos y medios.

ملخص

الغرض

تقييم التصميم والتقديم والنتائج المترتبة على عمليات التدخل بغرض رفع مستوى الالتزام بالعلاج المقدم لحالات السلّ لدى الأطفال في البلدان محدودة ومتوسطة الدخل ووضع إطار سياقي لعمليات التدخل من هذا النوع.

الطريقة لقد أجرينا بحثًا في قواعد بيانات PubMed وCochrane لإيجاد التقارير المنشورة في الفترة ما بين أول يناير/كانون الثاني من عام 2003 وأول ديسمبر/كانون الأول من عام 2013 حول عمليات التدخل الساعية إلى تحسين مستوى الالتزام بالعلاج المقدم لمرض السلّ والتي تضمنت مرضى تقل أعمارهم عن 20 عامًا ممن كانوا يعيشون في بلدان محدودة أو منخفضة الدخل. ولكي يتم إيجاد المقالات التي يحتمل أن تكون ذات صلة لكن ينقصها المحصلات المرتبطة بالمرضى من الأطفال، فقد تولينا الاتصال بمؤلفي الدراسات. كما قمنا بتقييم عنصر عدم التجانس (Heterogeneity) وخطر الانحياز. ومن أجل الوقوف على مستوى نجاح العلاج - أي التوليفة ما بين إكمال العلاج وتحقيق الشفاء - فقد أجرينا تحليلاً تجميعيًا (Meta-analysis) للآثار العشوائية. وقمنا بالتالي بتحديد جوانب الاحتياج لتطوير إجراءات التدخل.

النتائج لقد ضمّنا 15 دراسة في 11 بلدًا حرصًا على التحليل النوعي لهذه النتائج، ومن بين هذه الدرسات فقد تأهلت 11 دراسة للتحليل التجميعي مثلت 1279 طفلاً. ومن بين التدخلات الموصوفة في الدراسات البالغ عددها 15 دراسة، ركزت اثنتان على التوعية، فيما انصب تركيز دراسة واحدة على الدعم النفسي والاجتماعي، واتجهت سبع دراسات إلى التركيز على تقديم الرعاية، فيما ركزت أربع دراسات على النظم الصحية، وانفردت دراسة واحدة بالتركيز على الاعتمادات المالية. وحقق الأطفال المسجلين في الفريق الخاضع لتجربة التدخل العلاجي نسبًا أعلى من نجاح العلاج مقارنةً بالأطفال المسجلين في المجموعات المرجعية (بنسبة احتمال بلغت 3.02؛ وبنسبة أرجحية مقدارها 95%: 2.19-4.15). وبالاعتماد على النتائج المستخلصة من تحليلاتنا، فقد وضعنا إطارًا سياقيًا يقوم على العوامل التي شجعت على اكتمال العلاج أو هددت اكتماله.

الاستنتاج يتبين أن التدخلات المختلفة الساعية إلى تحسين مستوى الالتزام بالعلاج الخاص بمرض السلّ لدى الأطفال في البلدان محدودة ومتوسطة الدخل كانت فعالة وذات جدوى.

摘要

目的

针对在中低收入国家提高儿科结核病的治疗依从性，评估干预措施的设计、完成和效果，并为该种干预措施制定一个关联性框架。

方法

我们在 PubMed 和 Cochrane 数据库中搜索了于 2003 年 1 月 1 日至 2013 年 12 月 1 日之间发表的报告，这些报告与提高结核病治疗依从性的干预措施有关，其中包括居住在中低收入国家且年龄不满 20 岁的患者。相关文章可能缺少关于儿科的结果，为此，我们联系了研究的作者。我们对异质性和偏倚风险进行了评估。为了评估治疗成功率--即，完治率与治愈率相结合--我们采用随机效应开展了元分析。我们确认了有必要对干预实践作出改善的领域。

结果

我们将 11 个国家的 15 项研究纳入定向分析，其中 11 项符合元分析的条件--其代表 1279 名儿童。关于 15 项研究中描述的干预措施，其中两项侧重于教育，一项侧重于社会心理支持，七项侧重于医疗保健服务，四项侧重于卫生体系，另外一项侧重于财政拨款。与对照组的儿童相比，经干预措施庇佑的儿童具有更高的治疗成功率（比值比： 3.02；95% 置信区间： 2.19-4.15）。通过我们分析得出的结果，我们围绕促进或威胁完治率的因素制定了框架。

结论

在中低收入国家为提高儿科结核病的治疗依从性而采取的多种干预措施显得可行、有效。

Резюме

Цель.

Оценить структуру, реализацию и результаты медицинских вмешательств, способствующих соблюдению режима лечения детского туберкулеза в странах с низким и средним уровнем доходов населения, и разработать контекстуальную схему таких вмешательств.

Методы.

Был проведен поиск отчетов по медицинским вмешательствам, способствующим соблюдению режима лечения детского туберкулеза, опубликованным с 1 января 2003 г. по 1 декабря 2013 г. Поиск проводился в базах данных PubMed и Кокрановской библиотеки. Нас интересовали пациенты моложе 20 лет, проживающие в странах с низким или средним уровнем доходов. Если в потенциально релевантной статье было недостаточно данных по результатам лечения пациентов детского возраста, мы обращались за сведениями к авторам исследований. Была выполнена оценка гетерогенности данных и риска системной ошибки. Для оценки успешности лечения, т. е. завершения курса лечения и выздоровления пациента, был проведен метаанализ случайных воздействий. Были выявлены области, в которых практики медицинских вмешательств нуждаются в улучшении.

Результаты.

В количественный анализ было включено 15 исследований, выполненных в 11 странах. Из них 11 исследований было отобрано для метаанализа. В этих исследованиях было представлено 1279 детей. Среди описанных в них вмешательств две программы делали акцент на обучении, одна - на психологической поддержке, семь - на эффективности ухода, четыре касались систем здравоохранения и одна - предоставления финансирования. В тех группах, где проводилось вмешательство, дети имели более высокий показатель успешного лечения по сравнению с детьми из контрольных групп (отношение шансов: 3,02; 95% доверительный интервал: 2,19-4,15). Используя результаты наших анализов, мы разработали модель на базе факторов, которые способствуют или препятствуют завершению лечения.

Вывод.

Различного рода вмешательства, способствующие соблюдению режима лечения туберкулеза у детей, оказались осуществимой и эффективной стратегией для стран с низким и средним уровнем доходов населения.

Introduction

Paediatric tuberculosis can be controlled or cured if timely and appropriate treatment is completed.¹1. Guidance for national tuberculosis programmes on the management of tuberculosis in children. 2nd ed. Geneva: World Health Organization; 2014. ²2. Adherence to long-term therapies: evidence for action.; Geneva: World Health Organization 2003. More than 75% of affected patients live in low- and middle-income countries in Asia and Africa and have substantial tuberculosis -related morbidity and mortality.² Up to 20% of children with tuberculosis in low- and middle-income countries fail to complete treatment.³3. Pefura Yone EW, Kengne AP, Kuaban C. Incidence, time and determinants of tuberculosis treatment default in Yaounde, Cameroon: a retrospective hospital register-based cohort study. BMJ Open. 2011;1(2):e000289. http://dx.doi.org/10.1136/bmjopen-2011-000289 PMID:22116091
http://dx.doi.org/10.1136/bmjopen-2011-0...

Interrupted tuberculosis treatment poses a public health challenge because it permits the development of drug-resistant disease and allows patients to remain infectious for a relatively long time. Poor adherence results in disease progression, morbidity and death. The most extreme form of incomplete treatment is known as treatment abandonment or treatment default. For tuberculosis, such abandonment is generally represented by a break in treatment of at least two consecutive months.¹1. Guidance for national tuberculosis programmes on the management of tuberculosis in children. 2nd ed. Geneva: World Health Organization; 2014.

The barriers to treatment completion in low- and middle-income countries include medical expenses, the indirect costs of transportation and time away from work, the stigmas associated with the illness and/or the treatment, communication breakdowns between providers and patients, limited health literacy, the presence of too few health workers and problems in drug procurement.²2. Adherence to long-term therapies: evidence for action.; Geneva: World Health Organization 2003. We conducted a systematic review and meta-analysis of interventions designed to reduce such barriers to treatment completion among children with tuberculosis in low- and middle-income countries. Our main aim was to appraise the design, delivery and impact of such interventions in such a vulnerable population.

Methods

Search and selection

Using a registered protocol (PROSPERO: CRD42013005800), we searched the PubMed and Cochrane databases for relevant publications that had been published between 1 January 2003 and 1 December 2013. Grey literature was hand-searched. Until 1 May 2014, we attempted to contact the authors of relevant articles and other researchers with experience of tuberculosis in low- and middle-income countries. The search strategy (Box 1; available at: http://www.who.int/bulletin/volumes/93/10/14-147231) was piloted by two researchers and reviewed by two medical librarians.

Box 1. Search strategy to identify studies on interventions to improve adherence to treatment for paediatric tuberculosis in low- and middle-income countries online

("low income economies" OR "lower middle income economies" OR "middle income economies" OR "developing countries"[MeSH Terms] OR ("developing"[All Fields] AND "countries"[All Fields]) OR "developing countries"[All Fields]) OR ("developing countries"[MeSH Terms] OR ("developing"[All Fields] AND "countries"[All Fields]) OR "developing countries"[All Fields] OR ("developing"[All Fields] AND "country"[All Fields]) OR "developing country"[All Fields]) OR ("developing countries"[MeSH Terms] OR ("developing"[All Fields] AND "countries"[All Fields]) OR "developing countries"[All Fields] OR ("underdeveloped"[All Fields] AND "countries"[All Fields]) OR "underdeveloped countries"[All Fields]) OR ("developing countries"[MeSH Terms] OR ("developing"[All Fields] AND "countries"[All Fields]) OR "developing countries"[All Fields] OR ("underdeveloped"[All Fields] AND "country"[All Fields]) OR "underdeveloped country"[All Fields]) OR (emergent[All Fields] AND countries[All Fields]) OR (emergent[All Fields] AND country[All Fields]) OR ("developing countries"[MeSH Terms] OR ("developing"[All Fields] AND "countries"[All Fields]) OR "developing countries"[All Fields] OR ("developing"[All Fields] AND "nation"[All Fields]) OR "developing nation"[All Fields]) OR (underdeveloped[All Fields] AND "nation"[All Fields])) OR (emergent[All Fields] AND "nation"[All Fields]) OR (("poverty"[MeSH Terms] OR "poverty"[All Fields] OR ("low"[All Fields] AND "income"[All Fields]) OR "low income"[All Fields]) AND countries[All Fields]) OR (("poverty"[MeSH Terms] OR "poverty"[All Fields] OR ("low"[All Fields] AND "income"[All Fields]) OR "low income"[All Fields]) AND country[All Fields]) OR angola OR Fij OR palau OR albania OR gabon OR panama OR algeria OR grenada OR peru OR american samoa OR hungary OR romania OR argentina OR iran OR serbia OR azerbaijan OR iraq OR seychelles OR belarus OR jamaica OR south africa OR belize OR jordan OR st. lucia OR bosnia and herzegovina OR kazakhstan OR st. vincent and the grenadines OR botswana OR lebanon OR suriname OR brazil OR libya OR thailand OR bulgaria OR macedonia, fyr OR tonga OR china OR malaysia OR tunisia OR colombia OR maldives OR turkey OR costa rica OR marshall islands OR turkmenistan OR cuba OR mauritius OR tuvalu OR dominica OR mexico OR venezuela, rb OR dominican republic OR montenegro OR ecuador OR namibia OR armenia OR india OR samoa OR bhutan OR kiribati OR sao tome and principe OR bolivia OR kosovo OR senegal OR cameroon OR Lao OR solomon islands OR cape verde OR lesotho OR sri lanka OR congo OR mauritania OR sudan OR cote d'ivoire OR ivory coast OR micronesia OR swaziland OR djibouti OR moldova OR syria OR egypt OR mongolia OR timor OR el salvador OR morocco OR ukraine OR georgia OR nicaragua OR uzbekistan OR ghana OR nigeria OR vanuatu OR guatemala OR pakistan OR vietnam OR guyana OR papua new guinea OR west bank OR gaza OR honduras OR paraguay OR yemen OR indonesia OR philippines OR zambia OR afghanistan OR gambia OR myanmar OR bangladesh OR guinea OR nepal OR benin OR niger OR burkina faso OR haiti OR rwanda OR burundi OR kenya OR sierra leone OR cambodia OR korea OR somalia OR central african republic OR kyrgyz OR sudan OR chad OR liberia OR tajikistan OR comoros OR madagascar OR tanzania OR congo OR malawi OR togo OR eritrea OR mali OR uganda OR ethiopia OR mozambique OR zimbabwe)) AND tuberculosis[MeSH Major Topic] AND ("Health Education"[Mesh] OR "Counseling"[Mesh] OR "Directive Counseling"[Mesh] OR "Health Promotion"[Mesh] OR "Reminder Systems"[Mesh] OR "Directly Observed Therapy"[Mesh] OR "Social Support"[Mesh] OR "Contracts"[Mesh] OR "Decision Support Techniques"[Mesh] OR intervention OR treatment OR outcome) AND (study OR trial) AND ("Treatment Refusal"[Mesh] OR "Patient Participation"[Mesh] OR "Patient Dropouts"[Mesh] OR "Patient Compliance"[Mesh] OR "Motivation"[Mesh] OR "Cooperative Behavior"[Mesh]) OR "Refusal to Treat"[Mesh]) OR "Medication Adherence"[Mesh] OR medication adherence OR nonadherence OR non-adherence OR compliance OR noncompliance OR abandonment of treatment OR abandonment of therapy OR treatment abandonment OR therapy abandonment OR treatment default OR lost to follow-up OR loss to follow up OR default* OR against medical advice OR abscond* OR refusal OR stop* treatment OR (interrupt* AND treatment) OR (treatment AND discontinu*) OR (treatment AND continu*) OR failure to complete treatment OR incomplete treatment OR treatment maintenance OR no show OR retention of care OR run away OR attrition)) AND ("last 10 years"[PDat] AND Humans[Mesh] AND (infant[MeSH] OR child[MeSH] OR adolescent[MeSH] OR "young adult"[MeSH]) NOT "case reports"[Publication Type]) NOT "review"[Publication Type]

To be included in our analyses, a study had to have participants with active tuberculosis who were younger than 20 years and lived in a country that, according to the World Bank, was low-income or middle-income in December 2013. Studies with adult participants were included only if the cohort outcomes for participants younger than 20 years were available. We were only interested in studies on interventions targeted at the improvement of treatment initiation or completion, the improvement of adherence to medications or appointments, the prevention of treatment refusal or adherence surrogates such as self-efficacy or enablement.

Included studies required a control or comparison population. Retrospective or contemporaneous comparisons from the same region were accepted if the between-population similarities and differences were clearly stated. No language, follow-up or study quality restrictions were imposed.

Data extraction

By using standardized forms, two investigators independently screened abstracts and extracted data. Discrepancies between the two investigators were resolved through discussion (16 records) or by the seeking of clarification from an author of an article of potential interest (three records).

We detected 62 studies that met all of our eligibility criteria apart from the provision of explicit outcomes for paediatric patients. Although we attempted to determine such outcomes by contacting the authors of the corresponding study reports, we successfully obtained outcomes for just 10 additional studies. The other 52 reports provided no current contact information for any author (14 studies), had authors who did not reply to our queries (20 studies) or had authors who stated that the data we wanted were not available (18 studies).

From each eligible report, we extracted information on methods, interventions, outcomes, participants, settings and co-infection with human immunodeficiency virus (HIV). Treatment outcomes were extracted according to the World Health Organization's (WHO's) classifications, with treatment success defined as completion or cure¹1. Guidance for national tuberculosis programmes on the management of tuberculosis in children. 2nd ed. Geneva: World Health Organization; 2014. - as given in the reports.

Risk of bias in the randomized trials was assessed using the Cochrane Assessment tool⁴4. Higgins JPT, Green S, editors. Cochrane handbook for systematic reviews of interventions version 5.1.0 [updated March 2011]. Oxford: The Cochrane Collaboration; 2011. Available from: Available from: www.cochrane-handbook.org [cited 2015 May 13].
www.cochrane-handbook.org... and reported according to CONSORT standards.⁵5. Enhancing the quality and transparency of health research [Internet]. Oxford: Equator Network; 2013. Available from: Available from: http://www.equator-network.org/ [cited 2014 Apr 25].
http://www.equator-network.org/... Quality of the non-randomized trials was assessed using the Effective Public Health Practice Project Quality Assessment tool⁶6. Armijo-Olivo S, Stiles CR, Hagen NA, Biondo PD, Cummings GG. Assessment of study quality for systematic reviews: a comparison of the Cochrane Collaboration Risk of Bias Tool and the Effective Public Health Practice Project Quality Assessment Tool: methodological research. J Eval Clin Pract. 2012 Feb;18(1):12-8. http://dx.doi.org/10.1111/j.1365-2753.2010.01516.x PMID:20698919
http://dx.doi.org/10.1111/j.1365-2753.20... and reported according to TREND standards.⁵5. Enhancing the quality and transparency of health research [Internet]. Oxford: Equator Network; 2013. Available from: Available from: http://www.equator-network.org/ [cited 2014 Apr 25].
http://www.equator-network.org/... ⁷7. Petticrew M, Anderson L, Elder R, Grimshaw J, Hopkins D, Hahn R, et al. Complex interventions and their implications for systematic reviews: a pragmatic approach. J Clin Epidemiol. 2013 Nov;66(11):1209-14. http://dx.doi.org/10.1016/j.jclinepi.2013.06.004 PMID:23953085
http://dx.doi.org/10.1016/j.jclinepi.201... Funding source was recorded as a possible bias source. Studies that integrated qualitative data were assessed using the relevant tools of the Critical Appraisal Skills programme.⁸8. Critical appraisal skills programme [Internet]. Oxford: CASP UK; 2014. Available from: Available from: http://www.casp-uk.net/ [cited 2014 Apr 22].
http://www.casp-uk.net/... Reporting of the systematic review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement.⁹9. Moher D, Liberati A, Tetzlaff J, Altman DG; PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009 Jul 21;6(7):e1000097. http://dx.doi.org/10.1371/journal.pmed.1000097 PMID:19621072
http://dx.doi.org/10.1371/journal.pmed.1...

Interventions to improve treatment adherence among paediatric patients of tuberculosis were summarized through independent iterative re-reading and organization of the identified themes - with discussion to achieve consensus - in alignment with WHO's adherence dimensions for long-term therapies.²2. Adherence to long-term therapies: evidence for action.; Geneva: World Health Organization 2003. For the initial data extraction, interventions were divided into five categories: education, psychosocial, care delivery, health systems and social protection or financial (Table 1). We attempted to determine those factors that promoted or threatened treatment completion. These factors might be related to: (i) the patient - e.g. literacy, (ii) the condition, including the presence of comorbidities, (iii) the therapy, including cultural lay beliefs, (iv) the health system, including accessibility, and (v) socioeconomic status, including family income.

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Table 1
Categorization of interventions aimed at improving tuberculosis treatment adherence

Statistical analysis

We did a meta-analysis of the treatment success rates recorded among paediatric patients. We used the Mantel-Haenszel model and the DerSimonian and Laird random-effects method to calculate odds ratios (ORs) and their 95% confidence intervals (CIs) from the unadjusted raw data, with the assumption that intervention effects on treatment success in one setting might differ from those in other settings. We did sensitivity analyses that included only randomized or quasi-randomized studies or excluded studies with comparison population estimates derived from another setting (available from the corresponding author). Heterogeneity across studies was assessed using the I2 statistic. We summarized the main meta-analysis results as a forest plot but used funnel plots to assess publication bias. Analyses were conducted using Review Manager version 5.2 (Cochrane Collaboration, Copenhagen, Denmark).

Results

We initially identified 413 articles of potential interest. Of these, 164 qualified for full-text review and we included 15 articles in our qualitative synthesis (Fig. 1).¹⁰10. Satti H, McLaughlin MM, Omotayo DB, Keshavjee S, Becerra MC, Mukherjee JS, et al. Outcomes of comprehensive care for children empirically treated for multidrug-resistant tuberculosis in a setting of high HIV prevalence. PLoS ONE. 2012;7(5):e37114. http://dx.doi.org/10.1371/journal.pone.0037114 PMID:22629356
http://dx.doi.org/10.1371/journal.pone.0... ²⁴24. Lönnroth K, Aung T, Maung W, Kluge H, Uplekar M. Social franchising of TB care through private GPs in Myanmar: an assessment of treatment results, access, equity and financial protection. Health Policy Plan. 2007 May;22(3):156-66. http://dx.doi.org/10.1093/heapol/czm007 PMID:17434870
http://dx.doi.org/10.1093/heapol/czm007... The articles were on 15 separate studies (Table 2). Three of the studies were published in Portuguese¹¹11. Heck MA, da Costa JS, Nunes MF. Prevalência de abandono do tratamento da tuberculose e fatores associados no município de Sapucaia do Sul (RS), Brasil, 2000-2008. Rev Bras Epidemiol. 2011 Sep;14(3):478-85. http://dx.doi.org/10.1590/S1415-790X2011000300012 PMID:22069015 Portuguese.
http://dx.doi.org/10.1590/S1415-790X2011... ¹³13. Cantalice Filho JP. Efeito do incentivo alimentício sobre o desfecho do tratamento de pacientes com tuberculose em uma unidade primária de saúde no município de Duque de Caxias, Rio de Janeiro. J Bras Pneumol. 2009 Oct;35(10):992-7. http://dx.doi.org/10.1590/S1806-37132009001000008 PMID:19918632 Portuguese.
http://dx.doi.org/10.1590/S1806-37132009... ¹⁴14. Marques AM, da Cunha RV. A medicação assistida e os índices de cura de tuberculose e de abandono de tratamento na população indígena Guaraní-Kaiwá no Município de Dourados, Mato Grosso do Sul, Brasil. Cad Saude Publica. 2003 Sep-Oct;19(5):1405-11. http://dx.doi.org/10.1590/S0102-311X2003000500019 PMID:14666222 Portuguese.
http://dx.doi.org/10.1590/S0102-311X2003... and the remainder in English. Five studies were based in the upper-middle-income countries of Brazil¹¹11. Heck MA, da Costa JS, Nunes MF. Prevalência de abandono do tratamento da tuberculose e fatores associados no município de Sapucaia do Sul (RS), Brasil, 2000-2008. Rev Bras Epidemiol. 2011 Sep;14(3):478-85. http://dx.doi.org/10.1590/S1415-790X2011000300012 PMID:22069015 Portuguese.
http://dx.doi.org/10.1590/S1415-790X2011... ¹³13. Cantalice Filho JP. Efeito do incentivo alimentício sobre o desfecho do tratamento de pacientes com tuberculose em uma unidade primária de saúde no município de Duque de Caxias, Rio de Janeiro. J Bras Pneumol. 2009 Oct;35(10):992-7. http://dx.doi.org/10.1590/S1806-37132009001000008 PMID:19918632 Portuguese.
http://dx.doi.org/10.1590/S1806-37132009... ¹⁴14. Marques AM, da Cunha RV. A medicação assistida e os índices de cura de tuberculose e de abandono de tratamento na população indígena Guaraní-Kaiwá no Município de Dourados, Mato Grosso do Sul, Brasil. Cad Saude Publica. 2003 Sep-Oct;19(5):1405-11. http://dx.doi.org/10.1590/S0102-311X2003000500019 PMID:14666222 Portuguese.
http://dx.doi.org/10.1590/S0102-311X2003... and Thailand,¹⁵15. Anuwatnonthakate A, Limsomboon P, Nateniyom S, Wattanaamornkiat W, Komsakorn S, Moolphate S, et al. Directly observed therapy and improved tuberculosis treatment outcomes in Thailand.. PLoS ONE 2008;3(8):e3089. http://dx.doi.org/10.1371/journal.pone.0003089 PMID:18769479
http://dx.doi.org/10.1371/journal.pone.0... ¹⁶16. Khortwong P, Kaewkungwal J. Thai health education program for improving TB migrant's compliance. J Med Assoc Thai. 2013 Mar;96(3):365-73. PMID:23539943 three in the lower-middle-income countries of India,¹²12. Mathew A, Binks C, Kuruvilla J, Davies PD. A comparison of two methods of undertaking directly observed therapy in a rural Indian setting. Int J Tuberc Lung Dis. 2005 Jan;9(1):69-74. PMID:15675553 Lesotho¹⁰10. Satti H, McLaughlin MM, Omotayo DB, Keshavjee S, Becerra MC, Mukherjee JS, et al. Outcomes of comprehensive care for children empirically treated for multidrug-resistant tuberculosis in a setting of high HIV prevalence. PLoS ONE. 2012;7(5):e37114. http://dx.doi.org/10.1371/journal.pone.0037114 PMID:22629356
http://dx.doi.org/10.1371/journal.pone.0... and Pakistan,¹⁷17. Badar D, Ohkado A, Naeem M, Khurshid-ul-Zaman S, Tsukamoto M. Strengthening tuberculosis patient referral mechanisms among health facilities in Punjab, Pakistan.. Int J Tuberc Lung Dis 2011 Oct;15(10):1362-6. http://dx.doi.org/10.5588/ijtld.10.0620 PMID:22283896
http://dx.doi.org/10.5588/ijtld.10.0620... and seven in the low-income countries of Bangladesh,²³23. Lee S, Khan OF, Seo JH, Kim DY, Park KH, Jung SI, et al. Impact of physician's education on adherence to tuberculosis treatment for patients of low socioeconomic status in Bangladesh. Chonnam Med J. 2013 Apr;49(1):27-30. http://dx.doi.org/10.4068/cmj.2013.49.1.27 PMID:23678474
http://dx.doi.org/10.4068/cmj.2013.49.1.... Ethiopia,¹⁸18. Datiko DG, Lindtjørn B. Health extension workers improve tuberculosis case detection and treatment success in southern Ethiopia: a community randomized trial.. PLoS ONE 2009;4(5):e5443. http://dx.doi.org/10.1371/journal.pone.0005443 PMID:19424460
http://dx.doi.org/10.1371/journal.pone.0... ¹⁹19. Demissie M, Getahun H, Lindtjørn B. Community tuberculosis care through "TB clubs" in rural North Ethiopia. Soc Sci Med. 2003 May;56(10):2009-18. http://dx.doi.org/10.1016/S0277-9536(02)00182-X PMID:12697193
http://dx.doi.org/10.1016/S0277-9536(02)... Kenya,²²22. Ong'ang'o JR, Mwachari C, Kipruto H, Karanja S. The effects on tuberculosis treatment adherence from utilising community health workers: a comparison of selected rural and urban settings in Kenya.. PLoS ONE 2014;9(2):e88937. http://dx.doi.org/10.1371/journal.pone.0088937 PMID:24558452
http://dx.doi.org/10.1371/journal.pone.0... Myanmar,²⁴24. Lönnroth K, Aung T, Maung W, Kluge H, Uplekar M. Social franchising of TB care through private GPs in Myanmar: an assessment of treatment results, access, equity and financial protection. Health Policy Plan. 2007 May;22(3):156-66. http://dx.doi.org/10.1093/heapol/czm007 PMID:17434870
http://dx.doi.org/10.1093/heapol/czm007... South Sudan²¹21. Keus K, Houston S, Melaku Y, Burling S. Field research in humanitarian medical programmes. Treatment of a cohort of tuberculosis patients using the Manyatta regimen in a conflict zone in South Sudan. Trans R Soc Trop Med Hyg. 2003 Nov-Dec;97(6):614-8. http://dx.doi.org/10.1016/S0035-9203(03)80048-2 PMID:16134258
http://dx.doi.org/10.1016/S0035-9203(03)... and the United Republic of Tanzania.²⁰20. van den Boogaard J, Lyimo R, Irongo CF, Boeree MJ, Schaalma H, Aarnoutse RE, et al. Community vs. facility-based directly observed treatment for tuberculosis in Tanzania's Kilimanjaro Region.. Int J Tuberc Lung Dis 2009 Dec;13(12):1524-9. PMID:19919771 Four settings were urban outpatient,¹¹11. Heck MA, da Costa JS, Nunes MF. Prevalência de abandono do tratamento da tuberculose e fatores associados no município de Sapucaia do Sul (RS), Brasil, 2000-2008. Rev Bras Epidemiol. 2011 Sep;14(3):478-85. http://dx.doi.org/10.1590/S1415-790X2011000300012 PMID:22069015 Portuguese.
http://dx.doi.org/10.1590/S1415-790X2011... ¹³13. Cantalice Filho JP. Efeito do incentivo alimentício sobre o desfecho do tratamento de pacientes com tuberculose em uma unidade primária de saúde no município de Duque de Caxias, Rio de Janeiro. J Bras Pneumol. 2009 Oct;35(10):992-7. http://dx.doi.org/10.1590/S1806-37132009001000008 PMID:19918632 Portuguese.
http://dx.doi.org/10.1590/S1806-37132009... ¹⁶16. Khortwong P, Kaewkungwal J. Thai health education program for improving TB migrant's compliance. J Med Assoc Thai. 2013 Mar;96(3):365-73. PMID:23539943 ¹⁷17. Badar D, Ohkado A, Naeem M, Khurshid-ul-Zaman S, Tsukamoto M. Strengthening tuberculosis patient referral mechanisms among health facilities in Punjab, Pakistan.. Int J Tuberc Lung Dis 2011 Oct;15(10):1362-6. http://dx.doi.org/10.5588/ijtld.10.0620 PMID:22283896
http://dx.doi.org/10.5588/ijtld.10.0620... three rural outpatient,¹²12. Mathew A, Binks C, Kuruvilla J, Davies PD. A comparison of two methods of undertaking directly observed therapy in a rural Indian setting. Int J Tuberc Lung Dis. 2005 Jan;9(1):69-74. PMID:15675553 ¹⁸18. Datiko DG, Lindtjørn B. Health extension workers improve tuberculosis case detection and treatment success in southern Ethiopia: a community randomized trial.. PLoS ONE 2009;4(5):e5443. http://dx.doi.org/10.1371/journal.pone.0005443 PMID:19424460
http://dx.doi.org/10.1371/journal.pone.0... ¹⁹19. Demissie M, Getahun H, Lindtjørn B. Community tuberculosis care through "TB clubs" in rural North Ethiopia. Soc Sci Med. 2003 May;56(10):2009-18. http://dx.doi.org/10.1016/S0277-9536(02)00182-X PMID:12697193
http://dx.doi.org/10.1016/S0277-9536(02)... two suburban outpatient,²³23. Lee S, Khan OF, Seo JH, Kim DY, Park KH, Jung SI, et al. Impact of physician's education on adherence to tuberculosis treatment for patients of low socioeconomic status in Bangladesh. Chonnam Med J. 2013 Apr;49(1):27-30. http://dx.doi.org/10.4068/cmj.2013.49.1.27 PMID:23678474
http://dx.doi.org/10.4068/cmj.2013.49.1.... ²⁴24. Lönnroth K, Aung T, Maung W, Kluge H, Uplekar M. Social franchising of TB care through private GPs in Myanmar: an assessment of treatment results, access, equity and financial protection. Health Policy Plan. 2007 May;22(3):156-66. http://dx.doi.org/10.1093/heapol/czm007 PMID:17434870
http://dx.doi.org/10.1093/heapol/czm007... one rural camp.²¹21. Keus K, Houston S, Melaku Y, Burling S. Field research in humanitarian medical programmes. Treatment of a cohort of tuberculosis patients using the Manyatta regimen in a conflict zone in South Sudan. Trans R Soc Trop Med Hyg. 2003 Nov-Dec;97(6):614-8. http://dx.doi.org/10.1016/S0035-9203(03)80048-2 PMID:16134258
http://dx.doi.org/10.1016/S0035-9203(03)... The remaining studies were done in variable settings.¹⁰10. Satti H, McLaughlin MM, Omotayo DB, Keshavjee S, Becerra MC, Mukherjee JS, et al. Outcomes of comprehensive care for children empirically treated for multidrug-resistant tuberculosis in a setting of high HIV prevalence. PLoS ONE. 2012;7(5):e37114. http://dx.doi.org/10.1371/journal.pone.0037114 PMID:22629356
http://dx.doi.org/10.1371/journal.pone.0... ¹⁴14. Marques AM, da Cunha RV. A medicação assistida e os índices de cura de tuberculose e de abandono de tratamento na população indígena Guaraní-Kaiwá no Município de Dourados, Mato Grosso do Sul, Brasil. Cad Saude Publica. 2003 Sep-Oct;19(5):1405-11. http://dx.doi.org/10.1590/S0102-311X2003000500019 PMID:14666222 Portuguese.
http://dx.doi.org/10.1590/S0102-311X2003... ¹⁵15. Anuwatnonthakate A, Limsomboon P, Nateniyom S, Wattanaamornkiat W, Komsakorn S, Moolphate S, et al. Directly observed therapy and improved tuberculosis treatment outcomes in Thailand.. PLoS ONE 2008;3(8):e3089. http://dx.doi.org/10.1371/journal.pone.0003089 PMID:18769479
http://dx.doi.org/10.1371/journal.pone.0... ²⁰20. van den Boogaard J, Lyimo R, Irongo CF, Boeree MJ, Schaalma H, Aarnoutse RE, et al. Community vs. facility-based directly observed treatment for tuberculosis in Tanzania's Kilimanjaro Region.. Int J Tuberc Lung Dis 2009 Dec;13(12):1524-9. PMID:19919771 ²²22. Ong'ang'o JR, Mwachari C, Kipruto H, Karanja S. The effects on tuberculosis treatment adherence from utilising community health workers: a comparison of selected rural and urban settings in Kenya.. PLoS ONE 2014;9(2):e88937. http://dx.doi.org/10.1371/journal.pone.0088937 PMID:24558452
http://dx.doi.org/10.1371/journal.pone.0...

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Fig. 1
Flowchart for the selection of studies on interventions to improve adherence to treatment for paediatric tuberculosis in low- and middle-income countries

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Table 2
Studies on interventions to improve treatment adherence for paediatric tuberculosis in low- and middle-income countries, 1996-2011

The payment system for health services was not described in nine studies¹¹11. Heck MA, da Costa JS, Nunes MF. Prevalência de abandono do tratamento da tuberculose e fatores associados no município de Sapucaia do Sul (RS), Brasil, 2000-2008. Rev Bras Epidemiol. 2011 Sep;14(3):478-85. http://dx.doi.org/10.1590/S1415-790X2011000300012 PMID:22069015 Portuguese.
http://dx.doi.org/10.1590/S1415-790X2011... ¹²12. Mathew A, Binks C, Kuruvilla J, Davies PD. A comparison of two methods of undertaking directly observed therapy in a rural Indian setting. Int J Tuberc Lung Dis. 2005 Jan;9(1):69-74. PMID:15675553 ¹⁴14. Marques AM, da Cunha RV. A medicação assistida e os índices de cura de tuberculose e de abandono de tratamento na população indígena Guaraní-Kaiwá no Município de Dourados, Mato Grosso do Sul, Brasil. Cad Saude Publica. 2003 Sep-Oct;19(5):1405-11. http://dx.doi.org/10.1590/S0102-311X2003000500019 PMID:14666222 Portuguese.
http://dx.doi.org/10.1590/S0102-311X2003... ²⁰20. van den Boogaard J, Lyimo R, Irongo CF, Boeree MJ, Schaalma H, Aarnoutse RE, et al. Community vs. facility-based directly observed treatment for tuberculosis in Tanzania's Kilimanjaro Region.. Int J Tuberc Lung Dis 2009 Dec;13(12):1524-9. PMID:19919771 but the reports on four studies described capped fees²⁴24. Lönnroth K, Aung T, Maung W, Kluge H, Uplekar M. Social franchising of TB care through private GPs in Myanmar: an assessment of treatment results, access, equity and financial protection. Health Policy Plan. 2007 May;22(3):156-66. http://dx.doi.org/10.1093/heapol/czm007 PMID:17434870
http://dx.doi.org/10.1093/heapol/czm007... or clinic fee coverage.¹⁶16. Khortwong P, Kaewkungwal J. Thai health education program for improving TB migrant's compliance. J Med Assoc Thai. 2013 Mar;96(3):365-73. PMID:23539943 ²³23. Lee S, Khan OF, Seo JH, Kim DY, Park KH, Jung SI, et al. Impact of physician's education on adherence to tuberculosis treatment for patients of low socioeconomic status in Bangladesh. Chonnam Med J. 2013 Apr;49(1):27-30. http://dx.doi.org/10.4068/cmj.2013.49.1.27 PMID:23678474
http://dx.doi.org/10.4068/cmj.2013.49.1.... ²⁴24. Lönnroth K, Aung T, Maung W, Kluge H, Uplekar M. Social franchising of TB care through private GPs in Myanmar: an assessment of treatment results, access, equity and financial protection. Health Policy Plan. 2007 May;22(3):156-66. http://dx.doi.org/10.1093/heapol/czm007 PMID:17434870
http://dx.doi.org/10.1093/heapol/czm007... In seven studies, drug expenses were covered for one intervention group only,¹²12. Mathew A, Binks C, Kuruvilla J, Davies PD. A comparison of two methods of undertaking directly observed therapy in a rural Indian setting. Int J Tuberc Lung Dis. 2005 Jan;9(1):69-74. PMID:15675553 for both the intervention and comparison groups, as part of a national scheme,¹⁶16. Khortwong P, Kaewkungwal J. Thai health education program for improving TB migrant's compliance. J Med Assoc Thai. 2013 Mar;96(3):365-73. PMID:23539943 ²²22. Ong'ang'o JR, Mwachari C, Kipruto H, Karanja S. The effects on tuberculosis treatment adherence from utilising community health workers: a comparison of selected rural and urban settings in Kenya.. PLoS ONE 2014;9(2):e88937. http://dx.doi.org/10.1371/journal.pone.0088937 PMID:24558452
http://dx.doi.org/10.1371/journal.pone.0... ²⁴24. Lönnroth K, Aung T, Maung W, Kluge H, Uplekar M. Social franchising of TB care through private GPs in Myanmar: an assessment of treatment results, access, equity and financial protection. Health Policy Plan. 2007 May;22(3):156-66. http://dx.doi.org/10.1093/heapol/czm007 PMID:17434870
http://dx.doi.org/10.1093/heapol/czm007... or for at least the intervention group - with unclear indication if the drug expenses of the comparison group were also covered.¹⁰10. Satti H, McLaughlin MM, Omotayo DB, Keshavjee S, Becerra MC, Mukherjee JS, et al. Outcomes of comprehensive care for children empirically treated for multidrug-resistant tuberculosis in a setting of high HIV prevalence. PLoS ONE. 2012;7(5):e37114. http://dx.doi.org/10.1371/journal.pone.0037114 PMID:22629356
http://dx.doi.org/10.1371/journal.pone.0... ²¹21. Keus K, Houston S, Melaku Y, Burling S. Field research in humanitarian medical programmes. Treatment of a cohort of tuberculosis patients using the Manyatta regimen in a conflict zone in South Sudan. Trans R Soc Trop Med Hyg. 2003 Nov-Dec;97(6):614-8. http://dx.doi.org/10.1016/S0035-9203(03)80048-2 PMID:16134258
http://dx.doi.org/10.1016/S0035-9203(03)...

The included studies were conducted between 1996 and 2011 and reported - including the unpublished data supplied by authors - between 2003 and 2014. The median duration of the investigated interventions was 24 months (range: 9-96). The number of participants younger than 20 years - which had to be clarified through author contact for six studies and excluded population-based comparison samples - varied from four to 308 (mean: 106; median: 61) and totalled 1587 across all 15 studies. Such paediatric patients represented between 3% and 100% of the patients investigated (mean: 22%; median: 11%). The prevalence of HIV co-infection, which was only reported for six studies, ranged from less than 5% to 74%.¹⁰10. Satti H, McLaughlin MM, Omotayo DB, Keshavjee S, Becerra MC, Mukherjee JS, et al. Outcomes of comprehensive care for children empirically treated for multidrug-resistant tuberculosis in a setting of high HIV prevalence. PLoS ONE. 2012;7(5):e37114. http://dx.doi.org/10.1371/journal.pone.0037114 PMID:22629356
http://dx.doi.org/10.1371/journal.pone.0... ¹¹11. Heck MA, da Costa JS, Nunes MF. Prevalência de abandono do tratamento da tuberculose e fatores associados no município de Sapucaia do Sul (RS), Brasil, 2000-2008. Rev Bras Epidemiol. 2011 Sep;14(3):478-85. http://dx.doi.org/10.1590/S1415-790X2011000300012 PMID:22069015 Portuguese.
http://dx.doi.org/10.1590/S1415-790X2011... ¹³13. Cantalice Filho JP. Efeito do incentivo alimentício sobre o desfecho do tratamento de pacientes com tuberculose em uma unidade primária de saúde no município de Duque de Caxias, Rio de Janeiro. J Bras Pneumol. 2009 Oct;35(10):992-7. http://dx.doi.org/10.1590/S1806-37132009001000008 PMID:19918632 Portuguese.
http://dx.doi.org/10.1590/S1806-37132009... ¹⁵15. Anuwatnonthakate A, Limsomboon P, Nateniyom S, Wattanaamornkiat W, Komsakorn S, Moolphate S, et al. Directly observed therapy and improved tuberculosis treatment outcomes in Thailand.. PLoS ONE 2008;3(8):e3089. http://dx.doi.org/10.1371/journal.pone.0003089 PMID:18769479
http://dx.doi.org/10.1371/journal.pone.0... ²⁰20. van den Boogaard J, Lyimo R, Irongo CF, Boeree MJ, Schaalma H, Aarnoutse RE, et al. Community vs. facility-based directly observed treatment for tuberculosis in Tanzania's Kilimanjaro Region.. Int J Tuberc Lung Dis 2009 Dec;13(12):1524-9. PMID:19919771 ²¹21. Keus K, Houston S, Melaku Y, Burling S. Field research in humanitarian medical programmes. Treatment of a cohort of tuberculosis patients using the Manyatta regimen in a conflict zone in South Sudan. Trans R Soc Trop Med Hyg. 2003 Nov-Dec;97(6):614-8. http://dx.doi.org/10.1016/S0035-9203(03)80048-2 PMID:16134258
http://dx.doi.org/10.1016/S0035-9203(03)...

Interventions

The timing of interventions either included referral¹⁰10. Satti H, McLaughlin MM, Omotayo DB, Keshavjee S, Becerra MC, Mukherjee JS, et al. Outcomes of comprehensive care for children empirically treated for multidrug-resistant tuberculosis in a setting of high HIV prevalence. PLoS ONE. 2012;7(5):e37114. http://dx.doi.org/10.1371/journal.pone.0037114 PMID:22629356
http://dx.doi.org/10.1371/journal.pone.0... or induction¹⁵15. Anuwatnonthakate A, Limsomboon P, Nateniyom S, Wattanaamornkiat W, Komsakorn S, Moolphate S, et al. Directly observed therapy and improved tuberculosis treatment outcomes in Thailand.. PLoS ONE 2008;3(8):e3089. http://dx.doi.org/10.1371/journal.pone.0003089 PMID:18769479
http://dx.doi.org/10.1371/journal.pone.0... or ran just from treatment initiation to treatment completion.¹¹11. Heck MA, da Costa JS, Nunes MF. Prevalência de abandono do tratamento da tuberculose e fatores associados no município de Sapucaia do Sul (RS), Brasil, 2000-2008. Rev Bras Epidemiol. 2011 Sep;14(3):478-85. http://dx.doi.org/10.1590/S1415-790X2011000300012 PMID:22069015 Portuguese.
http://dx.doi.org/10.1590/S1415-790X2011... ¹⁴14. Marques AM, da Cunha RV. A medicação assistida e os índices de cura de tuberculose e de abandono de tratamento na população indígena Guaraní-Kaiwá no Município de Dourados, Mato Grosso do Sul, Brasil. Cad Saude Publica. 2003 Sep-Oct;19(5):1405-11. http://dx.doi.org/10.1590/S0102-311X2003000500019 PMID:14666222 Portuguese.
http://dx.doi.org/10.1590/S0102-311X2003... ¹⁶16. Khortwong P, Kaewkungwal J. Thai health education program for improving TB migrant's compliance. J Med Assoc Thai. 2013 Mar;96(3):365-73. PMID:23539943 ²⁴24. Lönnroth K, Aung T, Maung W, Kluge H, Uplekar M. Social franchising of TB care through private GPs in Myanmar: an assessment of treatment results, access, equity and financial protection. Health Policy Plan. 2007 May;22(3):156-66. http://dx.doi.org/10.1093/heapol/czm007 PMID:17434870
http://dx.doi.org/10.1093/heapol/czm007... Health behaviour models informing intervention design were mentioned in two studies - the precede-proceed model was used to help engage patients in one study¹⁶16. Khortwong P, Kaewkungwal J. Thai health education program for improving TB migrant's compliance. J Med Assoc Thai. 2013 Mar;96(3):365-73. PMID:23539943 while social franchising was used to help engage providers in another study.²⁴24. Lönnroth K, Aung T, Maung W, Kluge H, Uplekar M. Social franchising of TB care through private GPs in Myanmar: an assessment of treatment results, access, equity and financial protection. Health Policy Plan. 2007 May;22(3):156-66. http://dx.doi.org/10.1093/heapol/czm007 PMID:17434870
http://dx.doi.org/10.1093/heapol/czm007...

Many studies involved several categories and subcategories of interventions (Table 3). Some used interventions combining cognitive and behavioural components, as exemplified by education for patients,¹⁰10. Satti H, McLaughlin MM, Omotayo DB, Keshavjee S, Becerra MC, Mukherjee JS, et al. Outcomes of comprehensive care for children empirically treated for multidrug-resistant tuberculosis in a setting of high HIV prevalence. PLoS ONE. 2012;7(5):e37114. http://dx.doi.org/10.1371/journal.pone.0037114 PMID:22629356
http://dx.doi.org/10.1371/journal.pone.0... ¹²12. Mathew A, Binks C, Kuruvilla J, Davies PD. A comparison of two methods of undertaking directly observed therapy in a rural Indian setting. Int J Tuberc Lung Dis. 2005 Jan;9(1):69-74. PMID:15675553 ¹⁶16. Khortwong P, Kaewkungwal J. Thai health education program for improving TB migrant's compliance. J Med Assoc Thai. 2013 Mar;96(3):365-73. PMID:23539943 ¹⁸18. Datiko DG, Lindtjørn B. Health extension workers improve tuberculosis case detection and treatment success in southern Ethiopia: a community randomized trial.. PLoS ONE 2009;4(5):e5443. http://dx.doi.org/10.1371/journal.pone.0005443 PMID:19424460
http://dx.doi.org/10.1371/journal.pone.0... ¹⁹19. Demissie M, Getahun H, Lindtjørn B. Community tuberculosis care through "TB clubs" in rural North Ethiopia. Soc Sci Med. 2003 May;56(10):2009-18. http://dx.doi.org/10.1016/S0277-9536(02)00182-X PMID:12697193
http://dx.doi.org/10.1016/S0277-9536(02)... ²¹21. Keus K, Houston S, Melaku Y, Burling S. Field research in humanitarian medical programmes. Treatment of a cohort of tuberculosis patients using the Manyatta regimen in a conflict zone in South Sudan. Trans R Soc Trop Med Hyg. 2003 Nov-Dec;97(6):614-8. http://dx.doi.org/10.1016/S0035-9203(03)80048-2 PMID:16134258
http://dx.doi.org/10.1016/S0035-9203(03)... ²⁴24. Lönnroth K, Aung T, Maung W, Kluge H, Uplekar M. Social franchising of TB care through private GPs in Myanmar: an assessment of treatment results, access, equity and financial protection. Health Policy Plan. 2007 May;22(3):156-66. http://dx.doi.org/10.1093/heapol/czm007 PMID:17434870
http://dx.doi.org/10.1093/heapol/czm007... family members,¹⁰10. Satti H, McLaughlin MM, Omotayo DB, Keshavjee S, Becerra MC, Mukherjee JS, et al. Outcomes of comprehensive care for children empirically treated for multidrug-resistant tuberculosis in a setting of high HIV prevalence. PLoS ONE. 2012;7(5):e37114. http://dx.doi.org/10.1371/journal.pone.0037114 PMID:22629356
http://dx.doi.org/10.1371/journal.pone.0... ¹²12. Mathew A, Binks C, Kuruvilla J, Davies PD. A comparison of two methods of undertaking directly observed therapy in a rural Indian setting. Int J Tuberc Lung Dis. 2005 Jan;9(1):69-74. PMID:15675553 ²⁰20. van den Boogaard J, Lyimo R, Irongo CF, Boeree MJ, Schaalma H, Aarnoutse RE, et al. Community vs. facility-based directly observed treatment for tuberculosis in Tanzania's Kilimanjaro Region.. Int J Tuberc Lung Dis 2009 Dec;13(12):1524-9. PMID:19919771 ²¹21. Keus K, Houston S, Melaku Y, Burling S. Field research in humanitarian medical programmes. Treatment of a cohort of tuberculosis patients using the Manyatta regimen in a conflict zone in South Sudan. Trans R Soc Trop Med Hyg. 2003 Nov-Dec;97(6):614-8. http://dx.doi.org/10.1016/S0035-9203(03)80048-2 PMID:16134258
http://dx.doi.org/10.1016/S0035-9203(03)... or community leaders.¹²12. Mathew A, Binks C, Kuruvilla J, Davies PD. A comparison of two methods of undertaking directly observed therapy in a rural Indian setting. Int J Tuberc Lung Dis. 2005 Jan;9(1):69-74. PMID:15675553 ¹⁸18. Datiko DG, Lindtjørn B. Health extension workers improve tuberculosis case detection and treatment success in southern Ethiopia: a community randomized trial.. PLoS ONE 2009;4(5):e5443. http://dx.doi.org/10.1371/journal.pone.0005443 PMID:19424460
http://dx.doi.org/10.1371/journal.pone.0... ¹⁹19. Demissie M, Getahun H, Lindtjørn B. Community tuberculosis care through "TB clubs" in rural North Ethiopia. Soc Sci Med. 2003 May;56(10):2009-18. http://dx.doi.org/10.1016/S0277-9536(02)00182-X PMID:12697193
http://dx.doi.org/10.1016/S0277-9536(02)... ²¹21. Keus K, Houston S, Melaku Y, Burling S. Field research in humanitarian medical programmes. Treatment of a cohort of tuberculosis patients using the Manyatta regimen in a conflict zone in South Sudan. Trans R Soc Trop Med Hyg. 2003 Nov-Dec;97(6):614-8. http://dx.doi.org/10.1016/S0035-9203(03)80048-2 PMID:16134258
http://dx.doi.org/10.1016/S0035-9203(03)... ²⁴24. Lönnroth K, Aung T, Maung W, Kluge H, Uplekar M. Social franchising of TB care through private GPs in Myanmar: an assessment of treatment results, access, equity and financial protection. Health Policy Plan. 2007 May;22(3):156-66. http://dx.doi.org/10.1093/heapol/czm007 PMID:17434870
http://dx.doi.org/10.1093/heapol/czm007... Educational curricula addressed the administration¹¹11. Heck MA, da Costa JS, Nunes MF. Prevalência de abandono do tratamento da tuberculose e fatores associados no município de Sapucaia do Sul (RS), Brasil, 2000-2008. Rev Bras Epidemiol. 2011 Sep;14(3):478-85. http://dx.doi.org/10.1590/S1415-790X2011000300012 PMID:22069015 Portuguese.
http://dx.doi.org/10.1590/S1415-790X2011... ¹⁶16. Khortwong P, Kaewkungwal J. Thai health education program for improving TB migrant's compliance. J Med Assoc Thai. 2013 Mar;96(3):365-73. PMID:23539943 ¹⁸18. Datiko DG, Lindtjørn B. Health extension workers improve tuberculosis case detection and treatment success in southern Ethiopia: a community randomized trial.. PLoS ONE 2009;4(5):e5443. http://dx.doi.org/10.1371/journal.pone.0005443 PMID:19424460
http://dx.doi.org/10.1371/journal.pone.0... ²⁰20. van den Boogaard J, Lyimo R, Irongo CF, Boeree MJ, Schaalma H, Aarnoutse RE, et al. Community vs. facility-based directly observed treatment for tuberculosis in Tanzania's Kilimanjaro Region.. Int J Tuberc Lung Dis 2009 Dec;13(12):1524-9. PMID:19919771 ²²22. Ong'ang'o JR, Mwachari C, Kipruto H, Karanja S. The effects on tuberculosis treatment adherence from utilising community health workers: a comparison of selected rural and urban settings in Kenya.. PLoS ONE 2014;9(2):e88937. http://dx.doi.org/10.1371/journal.pone.0088937 PMID:24558452
http://dx.doi.org/10.1371/journal.pone.0... ²³23. Lee S, Khan OF, Seo JH, Kim DY, Park KH, Jung SI, et al. Impact of physician's education on adherence to tuberculosis treatment for patients of low socioeconomic status in Bangladesh. Chonnam Med J. 2013 Apr;49(1):27-30. http://dx.doi.org/10.4068/cmj.2013.49.1.27 PMID:23678474
http://dx.doi.org/10.4068/cmj.2013.49.1.... and adverse effects of medication,¹⁶16. Khortwong P, Kaewkungwal J. Thai health education program for improving TB migrant's compliance. J Med Assoc Thai. 2013 Mar;96(3):365-73. PMID:23539943 ¹⁹19. Demissie M, Getahun H, Lindtjørn B. Community tuberculosis care through "TB clubs" in rural North Ethiopia. Soc Sci Med. 2003 May;56(10):2009-18. http://dx.doi.org/10.1016/S0277-9536(02)00182-X PMID:12697193
http://dx.doi.org/10.1016/S0277-9536(02)... ²³23. Lee S, Khan OF, Seo JH, Kim DY, Park KH, Jung SI, et al. Impact of physician's education on adherence to tuberculosis treatment for patients of low socioeconomic status in Bangladesh. Chonnam Med J. 2013 Apr;49(1):27-30. http://dx.doi.org/10.4068/cmj.2013.49.1.27 PMID:23678474
http://dx.doi.org/10.4068/cmj.2013.49.1.... ²⁴24. Lönnroth K, Aung T, Maung W, Kluge H, Uplekar M. Social franchising of TB care through private GPs in Myanmar: an assessment of treatment results, access, equity and financial protection. Health Policy Plan. 2007 May;22(3):156-66. http://dx.doi.org/10.1093/heapol/czm007 PMID:17434870
http://dx.doi.org/10.1093/heapol/czm007... the personal or public health consequences of early treatment discontinuation¹⁶16. Khortwong P, Kaewkungwal J. Thai health education program for improving TB migrant's compliance. J Med Assoc Thai. 2013 Mar;96(3):365-73. PMID:23539943 ¹⁹19. Demissie M, Getahun H, Lindtjørn B. Community tuberculosis care through "TB clubs" in rural North Ethiopia. Soc Sci Med. 2003 May;56(10):2009-18. http://dx.doi.org/10.1016/S0277-9536(02)00182-X PMID:12697193
http://dx.doi.org/10.1016/S0277-9536(02)... ²¹21. Keus K, Houston S, Melaku Y, Burling S. Field research in humanitarian medical programmes. Treatment of a cohort of tuberculosis patients using the Manyatta regimen in a conflict zone in South Sudan. Trans R Soc Trop Med Hyg. 2003 Nov-Dec;97(6):614-8. http://dx.doi.org/10.1016/S0035-9203(03)80048-2 PMID:16134258
http://dx.doi.org/10.1016/S0035-9203(03)... ²³23. Lee S, Khan OF, Seo JH, Kim DY, Park KH, Jung SI, et al. Impact of physician's education on adherence to tuberculosis treatment for patients of low socioeconomic status in Bangladesh. Chonnam Med J. 2013 Apr;49(1):27-30. http://dx.doi.org/10.4068/cmj.2013.49.1.27 PMID:23678474
http://dx.doi.org/10.4068/cmj.2013.49.1.... and overall health or hygiene.¹⁶16. Khortwong P, Kaewkungwal J. Thai health education program for improving TB migrant's compliance. J Med Assoc Thai. 2013 Mar;96(3):365-73. PMID:23539943 ¹⁸18. Datiko DG, Lindtjørn B. Health extension workers improve tuberculosis case detection and treatment success in southern Ethiopia: a community randomized trial.. PLoS ONE 2009;4(5):e5443. http://dx.doi.org/10.1371/journal.pone.0005443 PMID:19424460
http://dx.doi.org/10.1371/journal.pone.0... ¹⁹19. Demissie M, Getahun H, Lindtjørn B. Community tuberculosis care through "TB clubs" in rural North Ethiopia. Soc Sci Med. 2003 May;56(10):2009-18. http://dx.doi.org/10.1016/S0277-9536(02)00182-X PMID:12697193
http://dx.doi.org/10.1016/S0277-9536(02)... ²¹21. Keus K, Houston S, Melaku Y, Burling S. Field research in humanitarian medical programmes. Treatment of a cohort of tuberculosis patients using the Manyatta regimen in a conflict zone in South Sudan. Trans R Soc Trop Med Hyg. 2003 Nov-Dec;97(6):614-8. http://dx.doi.org/10.1016/S0035-9203(03)80048-2 PMID:16134258
http://dx.doi.org/10.1016/S0035-9203(03)...

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Table 3
Interventions to improve adherence to treatment for paediatric tuberculosis in low- and middle-income countries, 1996-2011

Eleven studies incorporated affective and behavioural components, through psychosocial support with therapeutic alliances (i.e. relationship-building between providers and patients),¹⁰10. Satti H, McLaughlin MM, Omotayo DB, Keshavjee S, Becerra MC, Mukherjee JS, et al. Outcomes of comprehensive care for children empirically treated for multidrug-resistant tuberculosis in a setting of high HIV prevalence. PLoS ONE. 2012;7(5):e37114. http://dx.doi.org/10.1371/journal.pone.0037114 PMID:22629356
http://dx.doi.org/10.1371/journal.pone.0... ¹⁶16. Khortwong P, Kaewkungwal J. Thai health education program for improving TB migrant's compliance. J Med Assoc Thai. 2013 Mar;96(3):365-73. PMID:23539943 ¹⁸18. Datiko DG, Lindtjørn B. Health extension workers improve tuberculosis case detection and treatment success in southern Ethiopia: a community randomized trial.. PLoS ONE 2009;4(5):e5443. http://dx.doi.org/10.1371/journal.pone.0005443 PMID:19424460
http://dx.doi.org/10.1371/journal.pone.0... ¹⁹19. Demissie M, Getahun H, Lindtjørn B. Community tuberculosis care through "TB clubs" in rural North Ethiopia. Soc Sci Med. 2003 May;56(10):2009-18. http://dx.doi.org/10.1016/S0277-9536(02)00182-X PMID:12697193
http://dx.doi.org/10.1016/S0277-9536(02)... ²¹21. Keus K, Houston S, Melaku Y, Burling S. Field research in humanitarian medical programmes. Treatment of a cohort of tuberculosis patients using the Manyatta regimen in a conflict zone in South Sudan. Trans R Soc Trop Med Hyg. 2003 Nov-Dec;97(6):614-8. http://dx.doi.org/10.1016/S0035-9203(03)80048-2 PMID:16134258
http://dx.doi.org/10.1016/S0035-9203(03)... ²³23. Lee S, Khan OF, Seo JH, Kim DY, Park KH, Jung SI, et al. Impact of physician's education on adherence to tuberculosis treatment for patients of low socioeconomic status in Bangladesh. Chonnam Med J. 2013 Apr;49(1):27-30. http://dx.doi.org/10.4068/cmj.2013.49.1.27 PMID:23678474
http://dx.doi.org/10.4068/cmj.2013.49.1.... patient empowerment to select a treatment supporter or location,¹²12. Mathew A, Binks C, Kuruvilla J, Davies PD. A comparison of two methods of undertaking directly observed therapy in a rural Indian setting. Int J Tuberc Lung Dis. 2005 Jan;9(1):69-74. PMID:15675553 ¹⁵15. Anuwatnonthakate A, Limsomboon P, Nateniyom S, Wattanaamornkiat W, Komsakorn S, Moolphate S, et al. Directly observed therapy and improved tuberculosis treatment outcomes in Thailand.. PLoS ONE 2008;3(8):e3089. http://dx.doi.org/10.1371/journal.pone.0003089 PMID:18769479
http://dx.doi.org/10.1371/journal.pone.0... ¹⁶16. Khortwong P, Kaewkungwal J. Thai health education program for improving TB migrant's compliance. J Med Assoc Thai. 2013 Mar;96(3):365-73. PMID:23539943 ¹⁸18. Datiko DG, Lindtjørn B. Health extension workers improve tuberculosis case detection and treatment success in southern Ethiopia: a community randomized trial.. PLoS ONE 2009;4(5):e5443. http://dx.doi.org/10.1371/journal.pone.0005443 PMID:19424460
http://dx.doi.org/10.1371/journal.pone.0... ²⁰20. van den Boogaard J, Lyimo R, Irongo CF, Boeree MJ, Schaalma H, Aarnoutse RE, et al. Community vs. facility-based directly observed treatment for tuberculosis in Tanzania's Kilimanjaro Region.. Int J Tuberc Lung Dis 2009 Dec;13(12):1524-9. PMID:19919771 ²²22. Ong'ang'o JR, Mwachari C, Kipruto H, Karanja S. The effects on tuberculosis treatment adherence from utilising community health workers: a comparison of selected rural and urban settings in Kenya.. PLoS ONE 2014;9(2):e88937. http://dx.doi.org/10.1371/journal.pone.0088937 PMID:24558452
http://dx.doi.org/10.1371/journal.pone.0... counselling,¹⁰10. Satti H, McLaughlin MM, Omotayo DB, Keshavjee S, Becerra MC, Mukherjee JS, et al. Outcomes of comprehensive care for children empirically treated for multidrug-resistant tuberculosis in a setting of high HIV prevalence. PLoS ONE. 2012;7(5):e37114. http://dx.doi.org/10.1371/journal.pone.0037114 PMID:22629356
http://dx.doi.org/10.1371/journal.pone.0... ¹⁶16. Khortwong P, Kaewkungwal J. Thai health education program for improving TB migrant's compliance. J Med Assoc Thai. 2013 Mar;96(3):365-73. PMID:23539943 ²¹21. Keus K, Houston S, Melaku Y, Burling S. Field research in humanitarian medical programmes. Treatment of a cohort of tuberculosis patients using the Manyatta regimen in a conflict zone in South Sudan. Trans R Soc Trop Med Hyg. 2003 Nov-Dec;97(6):614-8. http://dx.doi.org/10.1016/S0035-9203(03)80048-2 PMID:16134258
http://dx.doi.org/10.1016/S0035-9203(03)... ²²22. Ong'ang'o JR, Mwachari C, Kipruto H, Karanja S. The effects on tuberculosis treatment adherence from utilising community health workers: a comparison of selected rural and urban settings in Kenya.. PLoS ONE 2014;9(2):e88937. http://dx.doi.org/10.1371/journal.pone.0088937 PMID:24558452
http://dx.doi.org/10.1371/journal.pone.0... problem-solving,¹⁶16. Khortwong P, Kaewkungwal J. Thai health education program for improving TB migrant's compliance. J Med Assoc Thai. 2013 Mar;96(3):365-73. PMID:23539943 decreasing stigma¹⁴14. Marques AM, da Cunha RV. A medicação assistida e os índices de cura de tuberculose e de abandono de tratamento na população indígena Guaraní-Kaiwá no Município de Dourados, Mato Grosso do Sul, Brasil. Cad Saude Publica. 2003 Sep-Oct;19(5):1405-11. http://dx.doi.org/10.1590/S0102-311X2003000500019 PMID:14666222 Portuguese.
http://dx.doi.org/10.1590/S0102-311X2003... ¹⁹19. Demissie M, Getahun H, Lindtjørn B. Community tuberculosis care through "TB clubs" in rural North Ethiopia. Soc Sci Med. 2003 May;56(10):2009-18. http://dx.doi.org/10.1016/S0277-9536(02)00182-X PMID:12697193
http://dx.doi.org/10.1016/S0277-9536(02)... ²¹21. Keus K, Houston S, Melaku Y, Burling S. Field research in humanitarian medical programmes. Treatment of a cohort of tuberculosis patients using the Manyatta regimen in a conflict zone in South Sudan. Trans R Soc Trop Med Hyg. 2003 Nov-Dec;97(6):614-8. http://dx.doi.org/10.1016/S0035-9203(03)80048-2 PMID:16134258
http://dx.doi.org/10.1016/S0035-9203(03)... and peer support.¹⁴14. Marques AM, da Cunha RV. A medicação assistida e os índices de cura de tuberculose e de abandono de tratamento na população indígena Guaraní-Kaiwá no Município de Dourados, Mato Grosso do Sul, Brasil. Cad Saude Publica. 2003 Sep-Oct;19(5):1405-11. http://dx.doi.org/10.1590/S0102-311X2003000500019 PMID:14666222 Portuguese.
http://dx.doi.org/10.1590/S0102-311X2003... ¹⁶16. Khortwong P, Kaewkungwal J. Thai health education program for improving TB migrant's compliance. J Med Assoc Thai. 2013 Mar;96(3):365-73. PMID:23539943 ¹⁹19. Demissie M, Getahun H, Lindtjørn B. Community tuberculosis care through "TB clubs" in rural North Ethiopia. Soc Sci Med. 2003 May;56(10):2009-18. http://dx.doi.org/10.1016/S0277-9536(02)00182-X PMID:12697193
http://dx.doi.org/10.1016/S0277-9536(02)... ²¹21. Keus K, Houston S, Melaku Y, Burling S. Field research in humanitarian medical programmes. Treatment of a cohort of tuberculosis patients using the Manyatta regimen in a conflict zone in South Sudan. Trans R Soc Trop Med Hyg. 2003 Nov-Dec;97(6):614-8. http://dx.doi.org/10.1016/S0035-9203(03)80048-2 PMID:16134258
http://dx.doi.org/10.1016/S0035-9203(03)... ²²22. Ong'ang'o JR, Mwachari C, Kipruto H, Karanja S. The effects on tuberculosis treatment adherence from utilising community health workers: a comparison of selected rural and urban settings in Kenya.. PLoS ONE 2014;9(2):e88937. http://dx.doi.org/10.1371/journal.pone.0088937 PMID:24558452
http://dx.doi.org/10.1371/journal.pone.0...

Care delivery interventions included health provider training,¹⁰10. Satti H, McLaughlin MM, Omotayo DB, Keshavjee S, Becerra MC, Mukherjee JS, et al. Outcomes of comprehensive care for children empirically treated for multidrug-resistant tuberculosis in a setting of high HIV prevalence. PLoS ONE. 2012;7(5):e37114. http://dx.doi.org/10.1371/journal.pone.0037114 PMID:22629356
http://dx.doi.org/10.1371/journal.pone.0... ¹⁶16. Khortwong P, Kaewkungwal J. Thai health education program for improving TB migrant's compliance. J Med Assoc Thai. 2013 Mar;96(3):365-73. PMID:23539943 ¹⁹19. Demissie M, Getahun H, Lindtjørn B. Community tuberculosis care through "TB clubs" in rural North Ethiopia. Soc Sci Med. 2003 May;56(10):2009-18. http://dx.doi.org/10.1016/S0277-9536(02)00182-X PMID:12697193
http://dx.doi.org/10.1016/S0277-9536(02)... ²¹21. Keus K, Houston S, Melaku Y, Burling S. Field research in humanitarian medical programmes. Treatment of a cohort of tuberculosis patients using the Manyatta regimen in a conflict zone in South Sudan. Trans R Soc Trop Med Hyg. 2003 Nov-Dec;97(6):614-8. http://dx.doi.org/10.1016/S0035-9203(03)80048-2 PMID:16134258
http://dx.doi.org/10.1016/S0035-9203(03)... ²²22. Ong'ang'o JR, Mwachari C, Kipruto H, Karanja S. The effects on tuberculosis treatment adherence from utilising community health workers: a comparison of selected rural and urban settings in Kenya.. PLoS ONE 2014;9(2):e88937. http://dx.doi.org/10.1371/journal.pone.0088937 PMID:24558452
http://dx.doi.org/10.1371/journal.pone.0... ²⁴24. Lönnroth K, Aung T, Maung W, Kluge H, Uplekar M. Social franchising of TB care through private GPs in Myanmar: an assessment of treatment results, access, equity and financial protection. Health Policy Plan. 2007 May;22(3):156-66. http://dx.doi.org/10.1093/heapol/czm007 PMID:17434870
http://dx.doi.org/10.1093/heapol/czm007... convenient appointment scheduling,¹⁰10. Satti H, McLaughlin MM, Omotayo DB, Keshavjee S, Becerra MC, Mukherjee JS, et al. Outcomes of comprehensive care for children empirically treated for multidrug-resistant tuberculosis in a setting of high HIV prevalence. PLoS ONE. 2012;7(5):e37114. http://dx.doi.org/10.1371/journal.pone.0037114 PMID:22629356
http://dx.doi.org/10.1371/journal.pone.0... ¹²12. Mathew A, Binks C, Kuruvilla J, Davies PD. A comparison of two methods of undertaking directly observed therapy in a rural Indian setting. Int J Tuberc Lung Dis. 2005 Jan;9(1):69-74. PMID:15675553 ¹⁹19. Demissie M, Getahun H, Lindtjørn B. Community tuberculosis care through "TB clubs" in rural North Ethiopia. Soc Sci Med. 2003 May;56(10):2009-18. http://dx.doi.org/10.1016/S0277-9536(02)00182-X PMID:12697193
http://dx.doi.org/10.1016/S0277-9536(02)... ²³23. Lee S, Khan OF, Seo JH, Kim DY, Park KH, Jung SI, et al. Impact of physician's education on adherence to tuberculosis treatment for patients of low socioeconomic status in Bangladesh. Chonnam Med J. 2013 Apr;49(1):27-30. http://dx.doi.org/10.4068/cmj.2013.49.1.27 PMID:23678474
http://dx.doi.org/10.4068/cmj.2013.49.1.... migration-sensitive therapy duration²¹21. Keus K, Houston S, Melaku Y, Burling S. Field research in humanitarian medical programmes. Treatment of a cohort of tuberculosis patients using the Manyatta regimen in a conflict zone in South Sudan. Trans R Soc Trop Med Hyg. 2003 Nov-Dec;97(6):614-8. http://dx.doi.org/10.1016/S0035-9203(03)80048-2 PMID:16134258
http://dx.doi.org/10.1016/S0035-9203(03)... and easier dosing schedules.¹⁰10. Satti H, McLaughlin MM, Omotayo DB, Keshavjee S, Becerra MC, Mukherjee JS, et al. Outcomes of comprehensive care for children empirically treated for multidrug-resistant tuberculosis in a setting of high HIV prevalence. PLoS ONE. 2012;7(5):e37114. http://dx.doi.org/10.1371/journal.pone.0037114 PMID:22629356
http://dx.doi.org/10.1371/journal.pone.0... ¹²12. Mathew A, Binks C, Kuruvilla J, Davies PD. A comparison of two methods of undertaking directly observed therapy in a rural Indian setting. Int J Tuberc Lung Dis. 2005 Jan;9(1):69-74. PMID:15675553 ¹⁸18. Datiko DG, Lindtjørn B. Health extension workers improve tuberculosis case detection and treatment success in southern Ethiopia: a community randomized trial.. PLoS ONE 2009;4(5):e5443. http://dx.doi.org/10.1371/journal.pone.0005443 PMID:19424460
http://dx.doi.org/10.1371/journal.pone.0... ²⁴24. Lönnroth K, Aung T, Maung W, Kluge H, Uplekar M. Social franchising of TB care through private GPs in Myanmar: an assessment of treatment results, access, equity and financial protection. Health Policy Plan. 2007 May;22(3):156-66. http://dx.doi.org/10.1093/heapol/czm007 PMID:17434870
http://dx.doi.org/10.1093/heapol/czm007... Health system interventions included the directly observed treatment, short-course strategy,¹⁰10. Satti H, McLaughlin MM, Omotayo DB, Keshavjee S, Becerra MC, Mukherjee JS, et al. Outcomes of comprehensive care for children empirically treated for multidrug-resistant tuberculosis in a setting of high HIV prevalence. PLoS ONE. 2012;7(5):e37114. http://dx.doi.org/10.1371/journal.pone.0037114 PMID:22629356
http://dx.doi.org/10.1371/journal.pone.0... ¹²12. Mathew A, Binks C, Kuruvilla J, Davies PD. A comparison of two methods of undertaking directly observed therapy in a rural Indian setting. Int J Tuberc Lung Dis. 2005 Jan;9(1):69-74. PMID:15675553 ¹⁵15. Anuwatnonthakate A, Limsomboon P, Nateniyom S, Wattanaamornkiat W, Komsakorn S, Moolphate S, et al. Directly observed therapy and improved tuberculosis treatment outcomes in Thailand.. PLoS ONE 2008;3(8):e3089. http://dx.doi.org/10.1371/journal.pone.0003089 PMID:18769479
http://dx.doi.org/10.1371/journal.pone.0... ¹⁶16. Khortwong P, Kaewkungwal J. Thai health education program for improving TB migrant's compliance. J Med Assoc Thai. 2013 Mar;96(3):365-73. PMID:23539943 ¹⁸18. Datiko DG, Lindtjørn B. Health extension workers improve tuberculosis case detection and treatment success in southern Ethiopia: a community randomized trial.. PLoS ONE 2009;4(5):e5443. http://dx.doi.org/10.1371/journal.pone.0005443 PMID:19424460
http://dx.doi.org/10.1371/journal.pone.0... ²²22. Ong'ang'o JR, Mwachari C, Kipruto H, Karanja S. The effects on tuberculosis treatment adherence from utilising community health workers: a comparison of selected rural and urban settings in Kenya.. PLoS ONE 2014;9(2):e88937. http://dx.doi.org/10.1371/journal.pone.0088937 PMID:24558452
http://dx.doi.org/10.1371/journal.pone.0... referral support,¹⁷17. Badar D, Ohkado A, Naeem M, Khurshid-ul-Zaman S, Tsukamoto M. Strengthening tuberculosis patient referral mechanisms among health facilities in Punjab, Pakistan.. Int J Tuberc Lung Dis 2011 Oct;15(10):1362-6. http://dx.doi.org/10.5588/ijtld.10.0620 PMID:22283896
http://dx.doi.org/10.5588/ijtld.10.0620... ¹⁹19. Demissie M, Getahun H, Lindtjørn B. Community tuberculosis care through "TB clubs" in rural North Ethiopia. Soc Sci Med. 2003 May;56(10):2009-18. http://dx.doi.org/10.1016/S0277-9536(02)00182-X PMID:12697193
http://dx.doi.org/10.1016/S0277-9536(02)... patient tracers¹⁰10. Satti H, McLaughlin MM, Omotayo DB, Keshavjee S, Becerra MC, Mukherjee JS, et al. Outcomes of comprehensive care for children empirically treated for multidrug-resistant tuberculosis in a setting of high HIV prevalence. PLoS ONE. 2012;7(5):e37114. http://dx.doi.org/10.1371/journal.pone.0037114 PMID:22629356
http://dx.doi.org/10.1371/journal.pone.0... ¹²12. Mathew A, Binks C, Kuruvilla J, Davies PD. A comparison of two methods of undertaking directly observed therapy in a rural Indian setting. Int J Tuberc Lung Dis. 2005 Jan;9(1):69-74. PMID:15675553 ¹⁶16. Khortwong P, Kaewkungwal J. Thai health education program for improving TB migrant's compliance. J Med Assoc Thai. 2013 Mar;96(3):365-73. PMID:23539943 ¹⁹19. Demissie M, Getahun H, Lindtjørn B. Community tuberculosis care through "TB clubs" in rural North Ethiopia. Soc Sci Med. 2003 May;56(10):2009-18. http://dx.doi.org/10.1016/S0277-9536(02)00182-X PMID:12697193
http://dx.doi.org/10.1016/S0277-9536(02)... ²¹21. Keus K, Houston S, Melaku Y, Burling S. Field research in humanitarian medical programmes. Treatment of a cohort of tuberculosis patients using the Manyatta regimen in a conflict zone in South Sudan. Trans R Soc Trop Med Hyg. 2003 Nov-Dec;97(6):614-8. http://dx.doi.org/10.1016/S0035-9203(03)80048-2 PMID:16134258
http://dx.doi.org/10.1016/S0035-9203(03)... ²²22. Ong'ang'o JR, Mwachari C, Kipruto H, Karanja S. The effects on tuberculosis treatment adherence from utilising community health workers: a comparison of selected rural and urban settings in Kenya.. PLoS ONE 2014;9(2):e88937. http://dx.doi.org/10.1371/journal.pone.0088937 PMID:24558452
http://dx.doi.org/10.1371/journal.pone.0... ²⁴24. Lönnroth K, Aung T, Maung W, Kluge H, Uplekar M. Social franchising of TB care through private GPs in Myanmar: an assessment of treatment results, access, equity and financial protection. Health Policy Plan. 2007 May;22(3):156-66. http://dx.doi.org/10.1093/heapol/czm007 PMID:17434870
http://dx.doi.org/10.1093/heapol/czm007... - including tracing within 24 hours¹²12. Mathew A, Binks C, Kuruvilla J, Davies PD. A comparison of two methods of undertaking directly observed therapy in a rural Indian setting. Int J Tuberc Lung Dis. 2005 Jan;9(1):69-74. PMID:15675553 ²¹21. Keus K, Houston S, Melaku Y, Burling S. Field research in humanitarian medical programmes. Treatment of a cohort of tuberculosis patients using the Manyatta regimen in a conflict zone in South Sudan. Trans R Soc Trop Med Hyg. 2003 Nov-Dec;97(6):614-8. http://dx.doi.org/10.1016/S0035-9203(03)80048-2 PMID:16134258
http://dx.doi.org/10.1016/S0035-9203(03)... - and home visiting.¹⁶16. Khortwong P, Kaewkungwal J. Thai health education program for improving TB migrant's compliance. J Med Assoc Thai. 2013 Mar;96(3):365-73. PMID:23539943 ²²22. Ong'ang'o JR, Mwachari C, Kipruto H, Karanja S. The effects on tuberculosis treatment adherence from utilising community health workers: a comparison of selected rural and urban settings in Kenya.. PLoS ONE 2014;9(2):e88937. http://dx.doi.org/10.1371/journal.pone.0088937 PMID:24558452
http://dx.doi.org/10.1371/journal.pone.0...

Social protection or financial support interventions included weekly food rations,¹⁰10. Satti H, McLaughlin MM, Omotayo DB, Keshavjee S, Becerra MC, Mukherjee JS, et al. Outcomes of comprehensive care for children empirically treated for multidrug-resistant tuberculosis in a setting of high HIV prevalence. PLoS ONE. 2012;7(5):e37114. http://dx.doi.org/10.1371/journal.pone.0037114 PMID:22629356
http://dx.doi.org/10.1371/journal.pone.0... ²¹21. Keus K, Houston S, Melaku Y, Burling S. Field research in humanitarian medical programmes. Treatment of a cohort of tuberculosis patients using the Manyatta regimen in a conflict zone in South Sudan. Trans R Soc Trop Med Hyg. 2003 Nov-Dec;97(6):614-8. http://dx.doi.org/10.1016/S0035-9203(03)80048-2 PMID:16134258
http://dx.doi.org/10.1016/S0035-9203(03)... monthly food baskets,¹³13. Cantalice Filho JP. Efeito do incentivo alimentício sobre o desfecho do tratamento de pacientes com tuberculose em uma unidade primária de saúde no município de Duque de Caxias, Rio de Janeiro. J Bras Pneumol. 2009 Oct;35(10):992-7. http://dx.doi.org/10.1590/S1806-37132009001000008 PMID:19918632 Portuguese.
http://dx.doi.org/10.1590/S1806-37132009... housing,²¹21. Keus K, Houston S, Melaku Y, Burling S. Field research in humanitarian medical programmes. Treatment of a cohort of tuberculosis patients using the Manyatta regimen in a conflict zone in South Sudan. Trans R Soc Trop Med Hyg. 2003 Nov-Dec;97(6):614-8. http://dx.doi.org/10.1016/S0035-9203(03)80048-2 PMID:16134258
http://dx.doi.org/10.1016/S0035-9203(03)... medication coverage,¹²12. Mathew A, Binks C, Kuruvilla J, Davies PD. A comparison of two methods of undertaking directly observed therapy in a rural Indian setting. Int J Tuberc Lung Dis. 2005 Jan;9(1):69-74. PMID:15675553 ²¹21. Keus K, Houston S, Melaku Y, Burling S. Field research in humanitarian medical programmes. Treatment of a cohort of tuberculosis patients using the Manyatta regimen in a conflict zone in South Sudan. Trans R Soc Trop Med Hyg. 2003 Nov-Dec;97(6):614-8. http://dx.doi.org/10.1016/S0035-9203(03)80048-2 PMID:16134258
http://dx.doi.org/10.1016/S0035-9203(03)... recognition of the importance of employment¹⁴14. Marques AM, da Cunha RV. A medicação assistida e os índices de cura de tuberculose e de abandono de tratamento na população indígena Guaraní-Kaiwá no Município de Dourados, Mato Grosso do Sul, Brasil. Cad Saude Publica. 2003 Sep-Oct;19(5):1405-11. http://dx.doi.org/10.1590/S0102-311X2003000500019 PMID:14666222 Portuguese.
http://dx.doi.org/10.1590/S0102-311X2003... ¹⁶16. Khortwong P, Kaewkungwal J. Thai health education program for improving TB migrant's compliance. J Med Assoc Thai. 2013 Mar;96(3):365-73. PMID:23539943 or school,¹⁰10. Satti H, McLaughlin MM, Omotayo DB, Keshavjee S, Becerra MC, Mukherjee JS, et al. Outcomes of comprehensive care for children empirically treated for multidrug-resistant tuberculosis in a setting of high HIV prevalence. PLoS ONE. 2012;7(5):e37114. http://dx.doi.org/10.1371/journal.pone.0037114 PMID:22629356
http://dx.doi.org/10.1371/journal.pone.0... essential supplies for daily life,¹⁶16. Khortwong P, Kaewkungwal J. Thai health education program for improving TB migrant's compliance. J Med Assoc Thai. 2013 Mar;96(3):365-73. PMID:23539943 transport reimbursement¹⁰10. Satti H, McLaughlin MM, Omotayo DB, Keshavjee S, Becerra MC, Mukherjee JS, et al. Outcomes of comprehensive care for children empirically treated for multidrug-resistant tuberculosis in a setting of high HIV prevalence. PLoS ONE. 2012;7(5):e37114. http://dx.doi.org/10.1371/journal.pone.0037114 PMID:22629356
http://dx.doi.org/10.1371/journal.pone.0... and income-generation support.¹⁰10. Satti H, McLaughlin MM, Omotayo DB, Keshavjee S, Becerra MC, Mukherjee JS, et al. Outcomes of comprehensive care for children empirically treated for multidrug-resistant tuberculosis in a setting of high HIV prevalence. PLoS ONE. 2012;7(5):e37114. http://dx.doi.org/10.1371/journal.pone.0037114 PMID:22629356
http://dx.doi.org/10.1371/journal.pone.0... One study required a deposit that was refundable upon treatment completion.¹²12. Mathew A, Binks C, Kuruvilla J, Davies PD. A comparison of two methods of undertaking directly observed therapy in a rural Indian setting. Int J Tuberc Lung Dis. 2005 Jan;9(1):69-74. PMID:15675553

Treatment adherence

Adherence-related measures included those extracted from self-reports,¹⁶16. Khortwong P, Kaewkungwal J. Thai health education program for improving TB migrant's compliance. J Med Assoc Thai. 2013 Mar;96(3):365-73. PMID:23539943 ²⁴24. Lönnroth K, Aung T, Maung W, Kluge H, Uplekar M. Social franchising of TB care through private GPs in Myanmar: an assessment of treatment results, access, equity and financial protection. Health Policy Plan. 2007 May;22(3):156-66. http://dx.doi.org/10.1093/heapol/czm007 PMID:17434870
http://dx.doi.org/10.1093/heapol/czm007... pharmacy refill data,²³23. Lee S, Khan OF, Seo JH, Kim DY, Park KH, Jung SI, et al. Impact of physician's education on adherence to tuberculosis treatment for patients of low socioeconomic status in Bangladesh. Chonnam Med J. 2013 Apr;49(1):27-30. http://dx.doi.org/10.4068/cmj.2013.49.1.27 PMID:23678474
http://dx.doi.org/10.4068/cmj.2013.49.1.... medication records maintained by treatment supporters,¹²12. Mathew A, Binks C, Kuruvilla J, Davies PD. A comparison of two methods of undertaking directly observed therapy in a rural Indian setting. Int J Tuberc Lung Dis. 2005 Jan;9(1):69-74. PMID:15675553 ¹⁹19. Demissie M, Getahun H, Lindtjørn B. Community tuberculosis care through "TB clubs" in rural North Ethiopia. Soc Sci Med. 2003 May;56(10):2009-18. http://dx.doi.org/10.1016/S0277-9536(02)00182-X PMID:12697193
http://dx.doi.org/10.1016/S0277-9536(02)... clinic attendance records,²³23. Lee S, Khan OF, Seo JH, Kim DY, Park KH, Jung SI, et al. Impact of physician's education on adherence to tuberculosis treatment for patients of low socioeconomic status in Bangladesh. Chonnam Med J. 2013 Apr;49(1):27-30. http://dx.doi.org/10.4068/cmj.2013.49.1.27 PMID:23678474
http://dx.doi.org/10.4068/cmj.2013.49.1.... confirmation of referrals¹⁷17. Badar D, Ohkado A, Naeem M, Khurshid-ul-Zaman S, Tsukamoto M. Strengthening tuberculosis patient referral mechanisms among health facilities in Punjab, Pakistan.. Int J Tuberc Lung Dis 2011 Oct;15(10):1362-6. http://dx.doi.org/10.5588/ijtld.10.0620 PMID:22283896
http://dx.doi.org/10.5588/ijtld.10.0620... and medical records.¹⁰10. Satti H, McLaughlin MM, Omotayo DB, Keshavjee S, Becerra MC, Mukherjee JS, et al. Outcomes of comprehensive care for children empirically treated for multidrug-resistant tuberculosis in a setting of high HIV prevalence. PLoS ONE. 2012;7(5):e37114. http://dx.doi.org/10.1371/journal.pone.0037114 PMID:22629356
http://dx.doi.org/10.1371/journal.pone.0... ¹¹11. Heck MA, da Costa JS, Nunes MF. Prevalência de abandono do tratamento da tuberculose e fatores associados no município de Sapucaia do Sul (RS), Brasil, 2000-2008. Rev Bras Epidemiol. 2011 Sep;14(3):478-85. http://dx.doi.org/10.1590/S1415-790X2011000300012 PMID:22069015 Portuguese.
http://dx.doi.org/10.1590/S1415-790X2011... ¹³13. Cantalice Filho JP. Efeito do incentivo alimentício sobre o desfecho do tratamento de pacientes com tuberculose em uma unidade primária de saúde no município de Duque de Caxias, Rio de Janeiro. J Bras Pneumol. 2009 Oct;35(10):992-7. http://dx.doi.org/10.1590/S1806-37132009001000008 PMID:19918632 Portuguese.
http://dx.doi.org/10.1590/S1806-37132009... ¹⁵15. Anuwatnonthakate A, Limsomboon P, Nateniyom S, Wattanaamornkiat W, Komsakorn S, Moolphate S, et al. Directly observed therapy and improved tuberculosis treatment outcomes in Thailand.. PLoS ONE 2008;3(8):e3089. http://dx.doi.org/10.1371/journal.pone.0003089 PMID:18769479
http://dx.doi.org/10.1371/journal.pone.0... ¹⁸18. Datiko DG, Lindtjørn B. Health extension workers improve tuberculosis case detection and treatment success in southern Ethiopia: a community randomized trial.. PLoS ONE 2009;4(5):e5443. http://dx.doi.org/10.1371/journal.pone.0005443 PMID:19424460
http://dx.doi.org/10.1371/journal.pone.0... ²⁰20. van den Boogaard J, Lyimo R, Irongo CF, Boeree MJ, Schaalma H, Aarnoutse RE, et al. Community vs. facility-based directly observed treatment for tuberculosis in Tanzania's Kilimanjaro Region.. Int J Tuberc Lung Dis 2009 Dec;13(12):1524-9. PMID:19919771 ²²22. Ong'ang'o JR, Mwachari C, Kipruto H, Karanja S. The effects on tuberculosis treatment adherence from utilising community health workers: a comparison of selected rural and urban settings in Kenya.. PLoS ONE 2014;9(2):e88937. http://dx.doi.org/10.1371/journal.pone.0088937 PMID:24558452
http://dx.doi.org/10.1371/journal.pone.0... ²⁴24. Lönnroth K, Aung T, Maung W, Kluge H, Uplekar M. Social franchising of TB care through private GPs in Myanmar: an assessment of treatment results, access, equity and financial protection. Health Policy Plan. 2007 May;22(3):156-66. http://dx.doi.org/10.1093/heapol/czm007 PMID:17434870
http://dx.doi.org/10.1093/heapol/czm007...

Terminology describing unfavourable outcomes included default,¹⁰10. Satti H, McLaughlin MM, Omotayo DB, Keshavjee S, Becerra MC, Mukherjee JS, et al. Outcomes of comprehensive care for children empirically treated for multidrug-resistant tuberculosis in a setting of high HIV prevalence. PLoS ONE. 2012;7(5):e37114. http://dx.doi.org/10.1371/journal.pone.0037114 PMID:22629356
http://dx.doi.org/10.1371/journal.pone.0... ¹²12. Mathew A, Binks C, Kuruvilla J, Davies PD. A comparison of two methods of undertaking directly observed therapy in a rural Indian setting. Int J Tuberc Lung Dis. 2005 Jan;9(1):69-74. PMID:15675553 ¹⁵15. Anuwatnonthakate A, Limsomboon P, Nateniyom S, Wattanaamornkiat W, Komsakorn S, Moolphate S, et al. Directly observed therapy and improved tuberculosis treatment outcomes in Thailand.. PLoS ONE 2008;3(8):e3089. http://dx.doi.org/10.1371/journal.pone.0003089 PMID:18769479
http://dx.doi.org/10.1371/journal.pone.0... ¹⁶16. Khortwong P, Kaewkungwal J. Thai health education program for improving TB migrant's compliance. J Med Assoc Thai. 2013 Mar;96(3):365-73. PMID:23539943 ¹⁸18. Datiko DG, Lindtjørn B. Health extension workers improve tuberculosis case detection and treatment success in southern Ethiopia: a community randomized trial.. PLoS ONE 2009;4(5):e5443. http://dx.doi.org/10.1371/journal.pone.0005443 PMID:19424460
http://dx.doi.org/10.1371/journal.pone.0... ²²22. Ong'ang'o JR, Mwachari C, Kipruto H, Karanja S. The effects on tuberculosis treatment adherence from utilising community health workers: a comparison of selected rural and urban settings in Kenya.. PLoS ONE 2014;9(2):e88937. http://dx.doi.org/10.1371/journal.pone.0088937 PMID:24558452
http://dx.doi.org/10.1371/journal.pone.0... ²⁴24. Lönnroth K, Aung T, Maung W, Kluge H, Uplekar M. Social franchising of TB care through private GPs in Myanmar: an assessment of treatment results, access, equity and financial protection. Health Policy Plan. 2007 May;22(3):156-66. http://dx.doi.org/10.1093/heapol/czm007 PMID:17434870
http://dx.doi.org/10.1093/heapol/czm007... drop-out,¹¹11. Heck MA, da Costa JS, Nunes MF. Prevalência de abandono do tratamento da tuberculose e fatores associados no município de Sapucaia do Sul (RS), Brasil, 2000-2008. Rev Bras Epidemiol. 2011 Sep;14(3):478-85. http://dx.doi.org/10.1590/S1415-790X2011000300012 PMID:22069015 Portuguese.
http://dx.doi.org/10.1590/S1415-790X2011... ¹⁴14. Marques AM, da Cunha RV. A medicação assistida e os índices de cura de tuberculose e de abandono de tratamento na população indígena Guaraní-Kaiwá no Município de Dourados, Mato Grosso do Sul, Brasil. Cad Saude Publica. 2003 Sep-Oct;19(5):1405-11. http://dx.doi.org/10.1590/S0102-311X2003000500019 PMID:14666222 Portuguese.
http://dx.doi.org/10.1590/S0102-311X2003... abandonment¹³13. Cantalice Filho JP. Efeito do incentivo alimentício sobre o desfecho do tratamento de pacientes com tuberculose em uma unidade primária de saúde no município de Duque de Caxias, Rio de Janeiro. J Bras Pneumol. 2009 Oct;35(10):992-7. http://dx.doi.org/10.1590/S1806-37132009001000008 PMID:19918632 Portuguese.
http://dx.doi.org/10.1590/S1806-37132009... ¹⁴14. Marques AM, da Cunha RV. A medicação assistida e os índices de cura de tuberculose e de abandono de tratamento na população indígena Guaraní-Kaiwá no Município de Dourados, Mato Grosso do Sul, Brasil. Cad Saude Publica. 2003 Sep-Oct;19(5):1405-11. http://dx.doi.org/10.1590/S0102-311X2003000500019 PMID:14666222 Portuguese.
http://dx.doi.org/10.1590/S0102-311X2003... and treatment interruption.¹⁹19. Demissie M, Getahun H, Lindtjørn B. Community tuberculosis care through "TB clubs" in rural North Ethiopia. Soc Sci Med. 2003 May;56(10):2009-18. http://dx.doi.org/10.1016/S0277-9536(02)00182-X PMID:12697193
http://dx.doi.org/10.1016/S0277-9536(02)... Three of 10 studies used the term default and, in defining their default criteria, were consistent with WHO definitions.¹⁰10. Satti H, McLaughlin MM, Omotayo DB, Keshavjee S, Becerra MC, Mukherjee JS, et al. Outcomes of comprehensive care for children empirically treated for multidrug-resistant tuberculosis in a setting of high HIV prevalence. PLoS ONE. 2012;7(5):e37114. http://dx.doi.org/10.1371/journal.pone.0037114 PMID:22629356
http://dx.doi.org/10.1371/journal.pone.0... ¹⁹19. Demissie M, Getahun H, Lindtjørn B. Community tuberculosis care through "TB clubs" in rural North Ethiopia. Soc Sci Med. 2003 May;56(10):2009-18. http://dx.doi.org/10.1016/S0277-9536(02)00182-X PMID:12697193
http://dx.doi.org/10.1016/S0277-9536(02)... ²⁴24. Lönnroth K, Aung T, Maung W, Kluge H, Uplekar M. Social franchising of TB care through private GPs in Myanmar: an assessment of treatment results, access, equity and financial protection. Health Policy Plan. 2007 May;22(3):156-66. http://dx.doi.org/10.1093/heapol/czm007 PMID:17434870
http://dx.doi.org/10.1093/heapol/czm007... Drop-out was defined in one study as treatment interruption for more than 30 days.¹¹11. Heck MA, da Costa JS, Nunes MF. Prevalência de abandono do tratamento da tuberculose e fatores associados no município de Sapucaia do Sul (RS), Brasil, 2000-2008. Rev Bras Epidemiol. 2011 Sep;14(3):478-85. http://dx.doi.org/10.1590/S1415-790X2011000300012 PMID:22069015 Portuguese.
http://dx.doi.org/10.1590/S1415-790X2011... Treatment abandonment was not defined in the two studies using the term.¹³13. Cantalice Filho JP. Efeito do incentivo alimentício sobre o desfecho do tratamento de pacientes com tuberculose em uma unidade primária de saúde no município de Duque de Caxias, Rio de Janeiro. J Bras Pneumol. 2009 Oct;35(10):992-7. http://dx.doi.org/10.1590/S1806-37132009001000008 PMID:19918632 Portuguese.
http://dx.doi.org/10.1590/S1806-37132009... ¹⁴14. Marques AM, da Cunha RV. A medicação assistida e os índices de cura de tuberculose e de abandono de tratamento na população indígena Guaraní-Kaiwá no Município de Dourados, Mato Grosso do Sul, Brasil. Cad Saude Publica. 2003 Sep-Oct;19(5):1405-11. http://dx.doi.org/10.1590/S0102-311X2003000500019 PMID:14666222 Portuguese.
http://dx.doi.org/10.1590/S0102-311X2003...

In addition to treatment success - i.e. completion or cure - positive outcomes were defined in the study reports as successful referral - i.e. confirmed arrival at the referral facility,¹⁷17. Badar D, Ohkado A, Naeem M, Khurshid-ul-Zaman S, Tsukamoto M. Strengthening tuberculosis patient referral mechanisms among health facilities in Punjab, Pakistan.. Int J Tuberc Lung Dis 2011 Oct;15(10):1362-6. http://dx.doi.org/10.5588/ijtld.10.0620 PMID:22283896
http://dx.doi.org/10.5588/ijtld.10.0620... continuous attendance at scheduled visits,²²22. Ong'ang'o JR, Mwachari C, Kipruto H, Karanja S. The effects on tuberculosis treatment adherence from utilising community health workers: a comparison of selected rural and urban settings in Kenya.. PLoS ONE 2014;9(2):e88937. http://dx.doi.org/10.1371/journal.pone.0088937 PMID:24558452
http://dx.doi.org/10.1371/journal.pone.0... ²³23. Lee S, Khan OF, Seo JH, Kim DY, Park KH, Jung SI, et al. Impact of physician's education on adherence to tuberculosis treatment for patients of low socioeconomic status in Bangladesh. Chonnam Med J. 2013 Apr;49(1):27-30. http://dx.doi.org/10.4068/cmj.2013.49.1.27 PMID:23678474
http://dx.doi.org/10.4068/cmj.2013.49.1.... more than 90% medication adherence²³23. Lee S, Khan OF, Seo JH, Kim DY, Park KH, Jung SI, et al. Impact of physician's education on adherence to tuberculosis treatment for patients of low socioeconomic status in Bangladesh. Chonnam Med J. 2013 Apr;49(1):27-30. http://dx.doi.org/10.4068/cmj.2013.49.1.27 PMID:23678474
http://dx.doi.org/10.4068/cmj.2013.49.1.... or self-reported beneficial health behaviours.¹⁶16. Khortwong P, Kaewkungwal J. Thai health education program for improving TB migrant's compliance. J Med Assoc Thai. 2013 Mar;96(3):365-73. PMID:23539943

Risk of bias

The benefits of the investigated interventions may be overestimated because of short follow-up and failure to assess adherence after the interventions were discontinued. Confounders, such as the extra attention given to participants during educational interventions,¹⁶16. Khortwong P, Kaewkungwal J. Thai health education program for improving TB migrant's compliance. J Med Assoc Thai. 2013 Mar;96(3):365-73. PMID:23539943 ²³23. Lee S, Khan OF, Seo JH, Kim DY, Park KH, Jung SI, et al. Impact of physician's education on adherence to tuberculosis treatment for patients of low socioeconomic status in Bangladesh. Chonnam Med J. 2013 Apr;49(1):27-30. http://dx.doi.org/10.4068/cmj.2013.49.1.27 PMID:23678474
http://dx.doi.org/10.4068/cmj.2013.49.1.... complicate our analyses. Although one study report details how controls - who did not receive the educational intervention - were supervised by health volunteers,¹⁶16. Khortwong P, Kaewkungwal J. Thai health education program for improving TB migrant's compliance. J Med Assoc Thai. 2013 Mar;96(3):365-73. PMID:23539943 it failed to give any idea of the corresponding contact time. The concurrent use of several interventions makes it hard to determine the main reason for successful outcomes. Social feedback loops - in which successful interventions foster a dynamic for more community adherence - were subjectively recognized by several research teams.¹⁶16. Khortwong P, Kaewkungwal J. Thai health education program for improving TB migrant's compliance. J Med Assoc Thai. 2013 Mar;96(3):365-73. PMID:23539943 ¹⁸18. Datiko DG, Lindtjørn B. Health extension workers improve tuberculosis case detection and treatment success in southern Ethiopia: a community randomized trial.. PLoS ONE 2009;4(5):e5443. http://dx.doi.org/10.1371/journal.pone.0005443 PMID:19424460
http://dx.doi.org/10.1371/journal.pone.0... ¹⁹19. Demissie M, Getahun H, Lindtjørn B. Community tuberculosis care through "TB clubs" in rural North Ethiopia. Soc Sci Med. 2003 May;56(10):2009-18. http://dx.doi.org/10.1016/S0277-9536(02)00182-X PMID:12697193
http://dx.doi.org/10.1016/S0277-9536(02)... ²¹21. Keus K, Houston S, Melaku Y, Burling S. Field research in humanitarian medical programmes. Treatment of a cohort of tuberculosis patients using the Manyatta regimen in a conflict zone in South Sudan. Trans R Soc Trop Med Hyg. 2003 Nov-Dec;97(6):614-8. http://dx.doi.org/10.1016/S0035-9203(03)80048-2 PMID:16134258
http://dx.doi.org/10.1016/S0035-9203(03)... ²⁴24. Lönnroth K, Aung T, Maung W, Kluge H, Uplekar M. Social franchising of TB care through private GPs in Myanmar: an assessment of treatment results, access, equity and financial protection. Health Policy Plan. 2007 May;22(3):156-66. http://dx.doi.org/10.1093/heapol/czm007 PMID:17434870
http://dx.doi.org/10.1093/heapol/czm007... Intervention complexity increased as attention expanded beyond the patient to include the provider,²³23. Lee S, Khan OF, Seo JH, Kim DY, Park KH, Jung SI, et al. Impact of physician's education on adherence to tuberculosis treatment for patients of low socioeconomic status in Bangladesh. Chonnam Med J. 2013 Apr;49(1):27-30. http://dx.doi.org/10.4068/cmj.2013.49.1.27 PMID:23678474
http://dx.doi.org/10.4068/cmj.2013.49.1.... the family,¹³13. Cantalice Filho JP. Efeito do incentivo alimentício sobre o desfecho do tratamento de pacientes com tuberculose em uma unidade primária de saúde no município de Duque de Caxias, Rio de Janeiro. J Bras Pneumol. 2009 Oct;35(10):992-7. http://dx.doi.org/10.1590/S1806-37132009001000008 PMID:19918632 Portuguese.
http://dx.doi.org/10.1590/S1806-37132009... ¹⁵15. Anuwatnonthakate A, Limsomboon P, Nateniyom S, Wattanaamornkiat W, Komsakorn S, Moolphate S, et al. Directly observed therapy and improved tuberculosis treatment outcomes in Thailand.. PLoS ONE 2008;3(8):e3089. http://dx.doi.org/10.1371/journal.pone.0003089 PMID:18769479
http://dx.doi.org/10.1371/journal.pone.0... both the provider and family¹⁰10. Satti H, McLaughlin MM, Omotayo DB, Keshavjee S, Becerra MC, Mukherjee JS, et al. Outcomes of comprehensive care for children empirically treated for multidrug-resistant tuberculosis in a setting of high HIV prevalence. PLoS ONE. 2012;7(5):e37114. http://dx.doi.org/10.1371/journal.pone.0037114 PMID:22629356
http://dx.doi.org/10.1371/journal.pone.0... ¹²12. Mathew A, Binks C, Kuruvilla J, Davies PD. A comparison of two methods of undertaking directly observed therapy in a rural Indian setting. Int J Tuberc Lung Dis. 2005 Jan;9(1):69-74. PMID:15675553 ¹⁶16. Khortwong P, Kaewkungwal J. Thai health education program for improving TB migrant's compliance. J Med Assoc Thai. 2013 Mar;96(3):365-73. PMID:23539943 ¹⁷17. Badar D, Ohkado A, Naeem M, Khurshid-ul-Zaman S, Tsukamoto M. Strengthening tuberculosis patient referral mechanisms among health facilities in Punjab, Pakistan.. Int J Tuberc Lung Dis 2011 Oct;15(10):1362-6. http://dx.doi.org/10.5588/ijtld.10.0620 PMID:22283896
http://dx.doi.org/10.5588/ijtld.10.0620... ²⁰20. van den Boogaard J, Lyimo R, Irongo CF, Boeree MJ, Schaalma H, Aarnoutse RE, et al. Community vs. facility-based directly observed treatment for tuberculosis in Tanzania's Kilimanjaro Region.. Int J Tuberc Lung Dis 2009 Dec;13(12):1524-9. PMID:19919771 or the provider, family and community.¹⁸18. Datiko DG, Lindtjørn B. Health extension workers improve tuberculosis case detection and treatment success in southern Ethiopia: a community randomized trial.. PLoS ONE 2009;4(5):e5443. http://dx.doi.org/10.1371/journal.pone.0005443 PMID:19424460
http://dx.doi.org/10.1371/journal.pone.0... ¹⁹19. Demissie M, Getahun H, Lindtjørn B. Community tuberculosis care through "TB clubs" in rural North Ethiopia. Soc Sci Med. 2003 May;56(10):2009-18. http://dx.doi.org/10.1016/S0277-9536(02)00182-X PMID:12697193
http://dx.doi.org/10.1016/S0277-9536(02)... ²¹21. Keus K, Houston S, Melaku Y, Burling S. Field research in humanitarian medical programmes. Treatment of a cohort of tuberculosis patients using the Manyatta regimen in a conflict zone in South Sudan. Trans R Soc Trop Med Hyg. 2003 Nov-Dec;97(6):614-8. http://dx.doi.org/10.1016/S0035-9203(03)80048-2 PMID:16134258
http://dx.doi.org/10.1016/S0035-9203(03)... ²²22. Ong'ang'o JR, Mwachari C, Kipruto H, Karanja S. The effects on tuberculosis treatment adherence from utilising community health workers: a comparison of selected rural and urban settings in Kenya.. PLoS ONE 2014;9(2):e88937. http://dx.doi.org/10.1371/journal.pone.0088937 PMID:24558452
http://dx.doi.org/10.1371/journal.pone.0... ²⁴24. Lönnroth K, Aung T, Maung W, Kluge H, Uplekar M. Social franchising of TB care through private GPs in Myanmar: an assessment of treatment results, access, equity and financial protection. Health Policy Plan. 2007 May;22(3):156-66. http://dx.doi.org/10.1093/heapol/czm007 PMID:17434870
http://dx.doi.org/10.1093/heapol/czm007... Complexity was characterized by contextual interactions that were susceptible to policy timing,¹³13. Cantalice Filho JP. Efeito do incentivo alimentício sobre o desfecho do tratamento de pacientes com tuberculose em uma unidade primária de saúde no município de Duque de Caxias, Rio de Janeiro. J Bras Pneumol. 2009 Oct;35(10):992-7. http://dx.doi.org/10.1590/S1806-37132009001000008 PMID:19918632 Portuguese.
http://dx.doi.org/10.1590/S1806-37132009... ¹⁸18. Datiko DG, Lindtjørn B. Health extension workers improve tuberculosis case detection and treatment success in southern Ethiopia: a community randomized trial.. PLoS ONE 2009;4(5):e5443. http://dx.doi.org/10.1371/journal.pone.0005443 PMID:19424460
http://dx.doi.org/10.1371/journal.pone.0... ²⁰20. van den Boogaard J, Lyimo R, Irongo CF, Boeree MJ, Schaalma H, Aarnoutse RE, et al. Community vs. facility-based directly observed treatment for tuberculosis in Tanzania's Kilimanjaro Region.. Int J Tuberc Lung Dis 2009 Dec;13(12):1524-9. PMID:19919771 ²¹21. Keus K, Houston S, Melaku Y, Burling S. Field research in humanitarian medical programmes. Treatment of a cohort of tuberculosis patients using the Manyatta regimen in a conflict zone in South Sudan. Trans R Soc Trop Med Hyg. 2003 Nov-Dec;97(6):614-8. http://dx.doi.org/10.1016/S0035-9203(03)80048-2 PMID:16134258
http://dx.doi.org/10.1016/S0035-9203(03)... ²⁴24. Lönnroth K, Aung T, Maung W, Kluge H, Uplekar M. Social franchising of TB care through private GPs in Myanmar: an assessment of treatment results, access, equity and financial protection. Health Policy Plan. 2007 May;22(3):156-66. http://dx.doi.org/10.1093/heapol/czm007 PMID:17434870
http://dx.doi.org/10.1093/heapol/czm007... staffing capabilities and attitudes,¹²12. Mathew A, Binks C, Kuruvilla J, Davies PD. A comparison of two methods of undertaking directly observed therapy in a rural Indian setting. Int J Tuberc Lung Dis. 2005 Jan;9(1):69-74. PMID:15675553 ¹⁶16. Khortwong P, Kaewkungwal J. Thai health education program for improving TB migrant's compliance. J Med Assoc Thai. 2013 Mar;96(3):365-73. PMID:23539943 ¹⁷17. Badar D, Ohkado A, Naeem M, Khurshid-ul-Zaman S, Tsukamoto M. Strengthening tuberculosis patient referral mechanisms among health facilities in Punjab, Pakistan.. Int J Tuberc Lung Dis 2011 Oct;15(10):1362-6. http://dx.doi.org/10.5588/ijtld.10.0620 PMID:22283896
http://dx.doi.org/10.5588/ijtld.10.0620... ¹⁹19. Demissie M, Getahun H, Lindtjørn B. Community tuberculosis care through "TB clubs" in rural North Ethiopia. Soc Sci Med. 2003 May;56(10):2009-18. http://dx.doi.org/10.1016/S0277-9536(02)00182-X PMID:12697193
http://dx.doi.org/10.1016/S0277-9536(02)... ²²22. Ong'ang'o JR, Mwachari C, Kipruto H, Karanja S. The effects on tuberculosis treatment adherence from utilising community health workers: a comparison of selected rural and urban settings in Kenya.. PLoS ONE 2014;9(2):e88937. http://dx.doi.org/10.1371/journal.pone.0088937 PMID:24558452
http://dx.doi.org/10.1371/journal.pone.0... ²³23. Lee S, Khan OF, Seo JH, Kim DY, Park KH, Jung SI, et al. Impact of physician's education on adherence to tuberculosis treatment for patients of low socioeconomic status in Bangladesh. Chonnam Med J. 2013 Apr;49(1):27-30. http://dx.doi.org/10.4068/cmj.2013.49.1.27 PMID:23678474
http://dx.doi.org/10.4068/cmj.2013.49.1.... relationships¹³13. Cantalice Filho JP. Efeito do incentivo alimentício sobre o desfecho do tratamento de pacientes com tuberculose em uma unidade primária de saúde no município de Duque de Caxias, Rio de Janeiro. J Bras Pneumol. 2009 Oct;35(10):992-7. http://dx.doi.org/10.1590/S1806-37132009001000008 PMID:19918632 Portuguese.
http://dx.doi.org/10.1590/S1806-37132009... ¹⁶16. Khortwong P, Kaewkungwal J. Thai health education program for improving TB migrant's compliance. J Med Assoc Thai. 2013 Mar;96(3):365-73. PMID:23539943 ¹⁹19. Demissie M, Getahun H, Lindtjørn B. Community tuberculosis care through "TB clubs" in rural North Ethiopia. Soc Sci Med. 2003 May;56(10):2009-18. http://dx.doi.org/10.1016/S0277-9536(02)00182-X PMID:12697193
http://dx.doi.org/10.1016/S0277-9536(02)... ²³23. Lee S, Khan OF, Seo JH, Kim DY, Park KH, Jung SI, et al. Impact of physician's education on adherence to tuberculosis treatment for patients of low socioeconomic status in Bangladesh. Chonnam Med J. 2013 Apr;49(1):27-30. http://dx.doi.org/10.4068/cmj.2013.49.1.27 PMID:23678474
http://dx.doi.org/10.4068/cmj.2013.49.1.... and resources.¹⁸18. Datiko DG, Lindtjørn B. Health extension workers improve tuberculosis case detection and treatment success in southern Ethiopia: a community randomized trial.. PLoS ONE 2009;4(5):e5443. http://dx.doi.org/10.1371/journal.pone.0005443 PMID:19424460
http://dx.doi.org/10.1371/journal.pone.0... ¹⁹19. Demissie M, Getahun H, Lindtjørn B. Community tuberculosis care through "TB clubs" in rural North Ethiopia. Soc Sci Med. 2003 May;56(10):2009-18. http://dx.doi.org/10.1016/S0277-9536(02)00182-X PMID:12697193
http://dx.doi.org/10.1016/S0277-9536(02)... ²³23. Lee S, Khan OF, Seo JH, Kim DY, Park KH, Jung SI, et al. Impact of physician's education on adherence to tuberculosis treatment for patients of low socioeconomic status in Bangladesh. Chonnam Med J. 2013 Apr;49(1):27-30. http://dx.doi.org/10.4068/cmj.2013.49.1.27 PMID:23678474
http://dx.doi.org/10.4068/cmj.2013.49.1.... ²⁴24. Lönnroth K, Aung T, Maung W, Kluge H, Uplekar M. Social franchising of TB care through private GPs in Myanmar: an assessment of treatment results, access, equity and financial protection. Health Policy Plan. 2007 May;22(3):156-66. http://dx.doi.org/10.1093/heapol/czm007 PMID:17434870
http://dx.doi.org/10.1093/heapol/czm007... No empiric quality measures of implementation fidelity were described.

Two studies incorporated qualitative data from focus groups and in-depth interviews.¹⁹19. Demissie M, Getahun H, Lindtjørn B. Community tuberculosis care through "TB clubs" in rural North Ethiopia. Soc Sci Med. 2003 May;56(10):2009-18. http://dx.doi.org/10.1016/S0277-9536(02)00182-X PMID:12697193
http://dx.doi.org/10.1016/S0277-9536(02)... ²²22. Ong'ang'o JR, Mwachari C, Kipruto H, Karanja S. The effects on tuberculosis treatment adherence from utilising community health workers: a comparison of selected rural and urban settings in Kenya.. PLoS ONE 2014;9(2):e88937. http://dx.doi.org/10.1371/journal.pone.0088937 PMID:24558452
http://dx.doi.org/10.1371/journal.pone.0... Although context, sampling and data collection were outlined and the findings appeared supported by data, there was no discussion of reflexivity and no detailed description of the analyses. None of the studies we investigated incorporated long-term observational or ethnographic approaches.

In one prospective randomized controlled trial, the study communities were randomly allocated to intervention and control groups to limit selection bias.¹⁸18. Datiko DG, Lindtjørn B. Health extension workers improve tuberculosis case detection and treatment success in southern Ethiopia: a community randomized trial.. PLoS ONE 2009;4(5):e5443. http://dx.doi.org/10.1371/journal.pone.0005443 PMID:19424460
http://dx.doi.org/10.1371/journal.pone.0... Three quasi-randomized trials determined assignment by residence.¹²12. Mathew A, Binks C, Kuruvilla J, Davies PD. A comparison of two methods of undertaking directly observed therapy in a rural Indian setting. Int J Tuberc Lung Dis. 2005 Jan;9(1):69-74. PMID:15675553 ¹⁶16. Khortwong P, Kaewkungwal J. Thai health education program for improving TB migrant's compliance. J Med Assoc Thai. 2013 Mar;96(3):365-73. PMID:23539943 ¹⁹19. Demissie M, Getahun H, Lindtjørn B. Community tuberculosis care through "TB clubs" in rural North Ethiopia. Soc Sci Med. 2003 May;56(10):2009-18. http://dx.doi.org/10.1016/S0277-9536(02)00182-X PMID:12697193
http://dx.doi.org/10.1016/S0277-9536(02)... No before-and-after studies used controls to account for any secular change. None of the articles described blinding measures and three specified a lack of blinding for assessors¹¹11. Heck MA, da Costa JS, Nunes MF. Prevalência de abandono do tratamento da tuberculose e fatores associados no município de Sapucaia do Sul (RS), Brasil, 2000-2008. Rev Bras Epidemiol. 2011 Sep;14(3):478-85. http://dx.doi.org/10.1590/S1415-790X2011000300012 PMID:22069015 Portuguese.
http://dx.doi.org/10.1590/S1415-790X2011... ²⁴24. Lönnroth K, Aung T, Maung W, Kluge H, Uplekar M. Social franchising of TB care through private GPs in Myanmar: an assessment of treatment results, access, equity and financial protection. Health Policy Plan. 2007 May;22(3):156-66. http://dx.doi.org/10.1093/heapol/czm007 PMID:17434870
http://dx.doi.org/10.1093/heapol/czm007... or participants.²⁰20. van den Boogaard J, Lyimo R, Irongo CF, Boeree MJ, Schaalma H, Aarnoutse RE, et al. Community vs. facility-based directly observed treatment for tuberculosis in Tanzania's Kilimanjaro Region.. Int J Tuberc Lung Dis 2009 Dec;13(12):1524-9. PMID:19919771

All of the results reported in thirteen studies were apparently defined a priori.¹⁰10. Satti H, McLaughlin MM, Omotayo DB, Keshavjee S, Becerra MC, Mukherjee JS, et al. Outcomes of comprehensive care for children empirically treated for multidrug-resistant tuberculosis in a setting of high HIV prevalence. PLoS ONE. 2012;7(5):e37114. http://dx.doi.org/10.1371/journal.pone.0037114 PMID:22629356
http://dx.doi.org/10.1371/journal.pone.0... ¹⁶16. Khortwong P, Kaewkungwal J. Thai health education program for improving TB migrant's compliance. J Med Assoc Thai. 2013 Mar;96(3):365-73. PMID:23539943 ¹⁸18. Datiko DG, Lindtjørn B. Health extension workers improve tuberculosis case detection and treatment success in southern Ethiopia: a community randomized trial.. PLoS ONE 2009;4(5):e5443. http://dx.doi.org/10.1371/journal.pone.0005443 PMID:19424460
http://dx.doi.org/10.1371/journal.pone.0... ²⁰20. van den Boogaard J, Lyimo R, Irongo CF, Boeree MJ, Schaalma H, Aarnoutse RE, et al. Community vs. facility-based directly observed treatment for tuberculosis in Tanzania's Kilimanjaro Region.. Int J Tuberc Lung Dis 2009 Dec;13(12):1524-9. PMID:19919771 ²²22. Ong'ang'o JR, Mwachari C, Kipruto H, Karanja S. The effects on tuberculosis treatment adherence from utilising community health workers: a comparison of selected rural and urban settings in Kenya.. PLoS ONE 2014;9(2):e88937. http://dx.doi.org/10.1371/journal.pone.0088937 PMID:24558452
http://dx.doi.org/10.1371/journal.pone.0... ²⁴24. Lönnroth K, Aung T, Maung W, Kluge H, Uplekar M. Social franchising of TB care through private GPs in Myanmar: an assessment of treatment results, access, equity and financial protection. Health Policy Plan. 2007 May;22(3):156-66. http://dx.doi.org/10.1093/heapol/czm007 PMID:17434870
http://dx.doi.org/10.1093/heapol/czm007... The remaining two studies accounted for modification of the results reported due to limited follow-up data, which had impaired the assessment of cure²¹21. Keus K, Houston S, Melaku Y, Burling S. Field research in humanitarian medical programmes. Treatment of a cohort of tuberculosis patients using the Manyatta regimen in a conflict zone in South Sudan. Trans R Soc Trop Med Hyg. 2003 Nov-Dec;97(6):614-8. http://dx.doi.org/10.1016/S0035-9203(03)80048-2 PMID:16134258
http://dx.doi.org/10.1016/S0035-9203(03)... or treatment outcome beyond referrals.¹⁷17. Badar D, Ohkado A, Naeem M, Khurshid-ul-Zaman S, Tsukamoto M. Strengthening tuberculosis patient referral mechanisms among health facilities in Punjab, Pakistan.. Int J Tuberc Lung Dis 2011 Oct;15(10):1362-6. http://dx.doi.org/10.5588/ijtld.10.0620 PMID:22283896
http://dx.doi.org/10.5588/ijtld.10.0620...

Funding sources included nongovernmental organizations,¹⁰10. Satti H, McLaughlin MM, Omotayo DB, Keshavjee S, Becerra MC, Mukherjee JS, et al. Outcomes of comprehensive care for children empirically treated for multidrug-resistant tuberculosis in a setting of high HIV prevalence. PLoS ONE. 2012;7(5):e37114. http://dx.doi.org/10.1371/journal.pone.0037114 PMID:22629356
http://dx.doi.org/10.1371/journal.pone.0... ¹¹11. Heck MA, da Costa JS, Nunes MF. Prevalência de abandono do tratamento da tuberculose e fatores associados no município de Sapucaia do Sul (RS), Brasil, 2000-2008. Rev Bras Epidemiol. 2011 Sep;14(3):478-85. http://dx.doi.org/10.1590/S1415-790X2011000300012 PMID:22069015 Portuguese.
http://dx.doi.org/10.1590/S1415-790X2011... ²⁰20. van den Boogaard J, Lyimo R, Irongo CF, Boeree MJ, Schaalma H, Aarnoutse RE, et al. Community vs. facility-based directly observed treatment for tuberculosis in Tanzania's Kilimanjaro Region.. Int J Tuberc Lung Dis 2009 Dec;13(12):1524-9. PMID:19919771 ²⁴24. Lönnroth K, Aung T, Maung W, Kluge H, Uplekar M. Social franchising of TB care through private GPs in Myanmar: an assessment of treatment results, access, equity and financial protection. Health Policy Plan. 2007 May;22(3):156-66. http://dx.doi.org/10.1093/heapol/czm007 PMID:17434870
http://dx.doi.org/10.1093/heapol/czm007... health departments¹⁸18. Datiko DG, Lindtjørn B. Health extension workers improve tuberculosis case detection and treatment success in southern Ethiopia: a community randomized trial.. PLoS ONE 2009;4(5):e5443. http://dx.doi.org/10.1371/journal.pone.0005443 PMID:19424460
http://dx.doi.org/10.1371/journal.pone.0... or international¹⁵15. Anuwatnonthakate A, Limsomboon P, Nateniyom S, Wattanaamornkiat W, Komsakorn S, Moolphate S, et al. Directly observed therapy and improved tuberculosis treatment outcomes in Thailand.. PLoS ONE 2008;3(8):e3089. http://dx.doi.org/10.1371/journal.pone.0003089 PMID:18769479
http://dx.doi.org/10.1371/journal.pone.0... ¹⁷17. Badar D, Ohkado A, Naeem M, Khurshid-ul-Zaman S, Tsukamoto M. Strengthening tuberculosis patient referral mechanisms among health facilities in Punjab, Pakistan.. Int J Tuberc Lung Dis 2011 Oct;15(10):1362-6. http://dx.doi.org/10.5588/ijtld.10.0620 PMID:22283896
http://dx.doi.org/10.5588/ijtld.10.0620... ¹⁹19. Demissie M, Getahun H, Lindtjørn B. Community tuberculosis care through "TB clubs" in rural North Ethiopia. Soc Sci Med. 2003 May;56(10):2009-18. http://dx.doi.org/10.1016/S0277-9536(02)00182-X PMID:12697193
http://dx.doi.org/10.1016/S0277-9536(02)... or local¹⁶16. Khortwong P, Kaewkungwal J. Thai health education program for improving TB migrant's compliance. J Med Assoc Thai. 2013 Mar;96(3):365-73. PMID:23539943 academic institutes or were not specified.¹¹11. Heck MA, da Costa JS, Nunes MF. Prevalência de abandono do tratamento da tuberculose e fatores associados no município de Sapucaia do Sul (RS), Brasil, 2000-2008. Rev Bras Epidemiol. 2011 Sep;14(3):478-85. http://dx.doi.org/10.1590/S1415-790X2011000300012 PMID:22069015 Portuguese.
http://dx.doi.org/10.1590/S1415-790X2011...

Table 4 and Table 5 show the results on study-specific biases (available at: http://www.who.int/bulletin/volumes/93/10/14-147231).

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Table 4
Assessment of non-randomized studies on interventions to improve adherence to treatment for paediatric tuberculosis in low- and middle-income countries

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Table 5
Risk of bias in randomized control and quasi-randomized control studies on interventions to improve adherence to treatment for paediatric tuberculosis in low- and middle-income countries online

Meta-analysis

Treatment success rates for the paediatric participants in both the treatment and comparison groups were reported for 11 studies.¹⁰10. Satti H, McLaughlin MM, Omotayo DB, Keshavjee S, Becerra MC, Mukherjee JS, et al. Outcomes of comprehensive care for children empirically treated for multidrug-resistant tuberculosis in a setting of high HIV prevalence. PLoS ONE. 2012;7(5):e37114. http://dx.doi.org/10.1371/journal.pone.0037114 PMID:22629356
http://dx.doi.org/10.1371/journal.pone.0... ¹²12. Mathew A, Binks C, Kuruvilla J, Davies PD. A comparison of two methods of undertaking directly observed therapy in a rural Indian setting. Int J Tuberc Lung Dis. 2005 Jan;9(1):69-74. PMID:15675553 ¹⁴14. Marques AM, da Cunha RV. A medicação assistida e os índices de cura de tuberculose e de abandono de tratamento na população indígena Guaraní-Kaiwá no Município de Dourados, Mato Grosso do Sul, Brasil. Cad Saude Publica. 2003 Sep-Oct;19(5):1405-11. http://dx.doi.org/10.1590/S0102-311X2003000500019 PMID:14666222 Portuguese.
http://dx.doi.org/10.1590/S0102-311X2003... ¹⁶16. Khortwong P, Kaewkungwal J. Thai health education program for improving TB migrant's compliance. J Med Assoc Thai. 2013 Mar;96(3):365-73. PMID:23539943 ¹⁸18. Datiko DG, Lindtjørn B. Health extension workers improve tuberculosis case detection and treatment success in southern Ethiopia: a community randomized trial.. PLoS ONE 2009;4(5):e5443. http://dx.doi.org/10.1371/journal.pone.0005443 PMID:19424460
http://dx.doi.org/10.1371/journal.pone.0... ²⁰20. van den Boogaard J, Lyimo R, Irongo CF, Boeree MJ, Schaalma H, Aarnoutse RE, et al. Community vs. facility-based directly observed treatment for tuberculosis in Tanzania's Kilimanjaro Region.. Int J Tuberc Lung Dis 2009 Dec;13(12):1524-9. PMID:19919771 ²²22. Ong'ang'o JR, Mwachari C, Kipruto H, Karanja S. The effects on tuberculosis treatment adherence from utilising community health workers: a comparison of selected rural and urban settings in Kenya.. PLoS ONE 2014;9(2):e88937. http://dx.doi.org/10.1371/journal.pone.0088937 PMID:24558452
http://dx.doi.org/10.1371/journal.pone.0... ²³23. Lee S, Khan OF, Seo JH, Kim DY, Park KH, Jung SI, et al. Impact of physician's education on adherence to tuberculosis treatment for patients of low socioeconomic status in Bangladesh. Chonnam Med J. 2013 Apr;49(1):27-30. http://dx.doi.org/10.4068/cmj.2013.49.1.27 PMID:23678474
http://dx.doi.org/10.4068/cmj.2013.49.1.... These studies were included in the meta-analysis and together represented 1279 children - excluding those in any external comparison groups. In three of the four studies excluded from the meta-analysis, the interventions investigated appeared to bring improved rates of treatment success, for all age groups.¹³13. Cantalice Filho JP. Efeito do incentivo alimentício sobre o desfecho do tratamento de pacientes com tuberculose em uma unidade primária de saúde no município de Duque de Caxias, Rio de Janeiro. J Bras Pneumol. 2009 Oct;35(10):992-7. http://dx.doi.org/10.1590/S1806-37132009001000008 PMID:19918632 Portuguese.
http://dx.doi.org/10.1590/S1806-37132009... ²¹21. Keus K, Houston S, Melaku Y, Burling S. Field research in humanitarian medical programmes. Treatment of a cohort of tuberculosis patients using the Manyatta regimen in a conflict zone in South Sudan. Trans R Soc Trop Med Hyg. 2003 Nov-Dec;97(6):614-8. http://dx.doi.org/10.1016/S0035-9203(03)80048-2 PMID:16134258
http://dx.doi.org/10.1016/S0035-9203(03)... ²⁴24. Lönnroth K, Aung T, Maung W, Kluge H, Uplekar M. Social franchising of TB care through private GPs in Myanmar: an assessment of treatment results, access, equity and financial protection. Health Policy Plan. 2007 May;22(3):156-66. http://dx.doi.org/10.1093/heapol/czm007 PMID:17434870
http://dx.doi.org/10.1093/heapol/czm007... The results of the other excluded study¹⁷17. Badar D, Ohkado A, Naeem M, Khurshid-ul-Zaman S, Tsukamoto M. Strengthening tuberculosis patient referral mechanisms among health facilities in Punjab, Pakistan.. Int J Tuberc Lung Dis 2011 Oct;15(10):1362-6. http://dx.doi.org/10.5588/ijtld.10.0620 PMID:22283896
http://dx.doi.org/10.5588/ijtld.10.0620... indicated that the intervention led to increased referral rates.

Meta-analysis revealed a threefold improvement in odds of treatment success for children receiving the interventions (Fig. 2; OR: 3.02; 95% CI: 2.19-4.15). There was no evidence of statistical heterogeneity (I2: 0%). A funnel plot showed symmetry for the large, high-powered studies but potential publication bias for the smaller studies (Fig. 3; available at: http://www.who.int/bulletin/volumes/93/09/14-147231). Sensitivity analysis did not modify the overall results (available from the corresponding author). Baseline risk factors reported for poor adherence outcomes are outlined in Box 2.

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Fig. 2
Effect on the odds of treatment success of interventions to improve adherence to treatment for paediatric tuberculosis in low- and middle-income countries, 1996-2011

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Fig. 3
Funnel plot to evaluate publication bias of studies on interventions to improve adherence to treatment for paediatric tuberculosis in low- and middle-income countries online

Box 2. Reported risk factors for poor tuberculosis treatment adherence outcomes in paediatric patients

Patient-related

Female sex¹²12. Mathew A, Binks C, Kuruvilla J, Davies PD. A comparison of two methods of undertaking directly observed therapy in a rural Indian setting. Int J Tuberc Lung Dis. 2005 Jan;9(1):69-74. PMID:15675553
Male sex¹⁴14. Marques AM, da Cunha RV. A medicação assistida e os índices de cura de tuberculose e de abandono de tratamento na população indígena Guaraní-Kaiwá no Município de Dourados, Mato Grosso do Sul, Brasil. Cad Saude Publica. 2003 Sep-Oct;19(5):1405-11. http://dx.doi.org/10.1590/S0102-311X2003000500019 PMID:14666222 Portuguese.
http://dx.doi.org/10.1590/S0102-311X2003... ²³23. Lee S, Khan OF, Seo JH, Kim DY, Park KH, Jung SI, et al. Impact of physician's education on adherence to tuberculosis treatment for patients of low socioeconomic status in Bangladesh. Chonnam Med J. 2013 Apr;49(1):27-30. http://dx.doi.org/10.4068/cmj.2013.49.1.27 PMID:23678474
http://dx.doi.org/10.4068/cmj.2013.49.1....

Condition-related

Human immunodeficiency virus-positive²⁰20. van den Boogaard J, Lyimo R, Irongo CF, Boeree MJ, Schaalma H, Aarnoutse RE, et al. Community vs. facility-based directly observed treatment for tuberculosis in Tanzania's Kilimanjaro Region.. Int J Tuberc Lung Dis 2009 Dec;13(12):1524-9. PMID:19919771
Smear-negative tuberculosis²⁰20. van den Boogaard J, Lyimo R, Irongo CF, Boeree MJ, Schaalma H, Aarnoutse RE, et al. Community vs. facility-based directly observed treatment for tuberculosis in Tanzania's Kilimanjaro Region.. Int J Tuberc Lung Dis 2009 Dec;13(12):1524-9. PMID:19919771 ²³23. Lee S, Khan OF, Seo JH, Kim DY, Park KH, Jung SI, et al. Impact of physician's education on adherence to tuberculosis treatment for patients of low socioeconomic status in Bangladesh. Chonnam Med J. 2013 Apr;49(1):27-30. http://dx.doi.org/10.4068/cmj.2013.49.1.27 PMID:23678474
http://dx.doi.org/10.4068/cmj.2013.49.1....

Treatment-related

Tuberculosis retreatment²⁴24. Lönnroth K, Aung T, Maung W, Kluge H, Uplekar M. Social franchising of TB care through private GPs in Myanmar: an assessment of treatment results, access, equity and financial protection. Health Policy Plan. 2007 May;22(3):156-66. http://dx.doi.org/10.1093/heapol/czm007 PMID:17434870
http://dx.doi.org/10.1093/heapol/czm007...

Social and/or economic related

Low-socioeconomic level²⁴24. Lönnroth K, Aung T, Maung W, Kluge H, Uplekar M. Social franchising of TB care through private GPs in Myanmar: an assessment of treatment results, access, equity and financial protection. Health Policy Plan. 2007 May;22(3):156-66. http://dx.doi.org/10.1093/heapol/czm007 PMID:17434870
http://dx.doi.org/10.1093/heapol/czm007...

Health system related

Distance from care source¹²12. Mathew A, Binks C, Kuruvilla J, Davies PD. A comparison of two methods of undertaking directly observed therapy in a rural Indian setting. Int J Tuberc Lung Dis. 2005 Jan;9(1):69-74. PMID:15675553

Discussion

In our review of interventions to promote paediatric tuberculosis treatment adherence in low- and middle-income countries, we found evidence that such interventions can result in clinically important improvements in tuberculosis treatment success. Diverse interventions addressing education, psychosocial support, care delivery, health system strengthening and social protection are reportedly feasible and effective in facilitating treatment completion.

Several studies followed collaborative strategies. For example, there was evidence of social franchise programmes communicating with the media, tuberculosis villages communicating with local leaders, tuberculosis clubs communicating with neighbours, health centres communicating with referral facilities and health providers engaging in motivational communication with patients.

We used systematic methods to identify and analyse a broad range of studies, without language limitations and with solicitation of input from the authors of relevant articles in an attempt to minimize search bias. We provided detailed descriptions and syntheses of interventions - which were often multi-component and complex - that had been implemented among children in low- and middle-income countries. Our summary findings may help guide future intervention planning and evaluation. Our reviews did, however, have several limitations. For example, few studies included specific details on the nature of their paediatric programme, and no data on individual patients were available. Given the generally small sample sizes, the reported confidence intervals for the effects of individual interventions were often broad. Despite this, all but one of the 11 studies included in the meta-analysis had odds ratios that indicated that the investigated intervention improved the rate of treatment success, and the four largest of these studies provided unequivocal evidence of such benefit.

Heterogeneity in the context and measurement of adherence, outcome definition and reporting limit the value of between-study comparisons. In high-income countries, multi-component interventions are common and often found to be superior to single-component interventions.²⁶26. Roter DL, Hall JA, Merisca R, Nordstrom B, Cretin D, Svarstad B. Effectiveness of interventions to improve patient compliance: a meta-analysis. Med Care. 1998 Aug;36(8):1138-61. http://dx.doi.org/10.1097/00005650-199808000-00004 PMID:9708588
http://dx.doi.org/10.1097/00005650-19980... Several of the relevant studies included in our reviews also attempted to target several adherence factors simultaneously, by using complex interventions. Such complex interventions make it difficult to attribute the results to particular intervention categories or components. One of the studies we reviewed was of an intervention that included education, improved dosing and appointment convenience, patient tracing, reduction of out-of-pocket costs and a deposit that was refunded on treatment completion.¹²12. Mathew A, Binks C, Kuruvilla J, Davies PD. A comparison of two methods of undertaking directly observed therapy in a rural Indian setting. Int J Tuberc Lung Dis. 2005 Jan;9(1):69-74. PMID:15675553 It may be that only when implemented together do these elements succeed.

Recognizing the interconnected nature of WHO's five adherence dimensions and intervention categories for long-term therapies,²2. Adherence to long-term therapies: evidence for action.; Geneva: World Health Organization 2003. we have summarized contextual factors affecting the adherence interventions we investigated in a framework (Fig. 4). The themes highlighted in this figure are intended to be illustrative across dimensions and intervention categories. For instance, factors that may adversely affect tuberculosis treatment adherence that span psychosocial and educational categories - e.g. low literacy and limited self-efficacy - are shown in the figure alongside adherence-promoting factors such as family education and patient empowerment. The contextual framework may aid further collaborative studies and analyses of adherence-targeted interventions.

Thumbnail

Fig. 4
Contextual framework showing factors that may promote or threaten adherence to treatment for paediatric tuberculosis in low- and middle-income countries

Through qualitative analysis, we identified three areas where studies described - or failed to describe - children's unique features that can affect adherence intervention delivery. First, few studies described paediatric-specific disease epidemiology and use of paediatric-inclusive outcomes. Several authors reported an unexpectedly high prevalence of paediatric tuberculosis that warranted management as a public health problem.¹⁴14. Marques AM, da Cunha RV. A medicação assistida e os índices de cura de tuberculose e de abandono de tratamento na população indígena Guaraní-Kaiwá no Município de Dourados, Mato Grosso do Sul, Brasil. Cad Saude Publica. 2003 Sep-Oct;19(5):1405-11. http://dx.doi.org/10.1590/S0102-311X2003000500019 PMID:14666222 Portuguese.
http://dx.doi.org/10.1590/S0102-311X2003... ¹⁸18. Datiko DG, Lindtjørn B. Health extension workers improve tuberculosis case detection and treatment success in southern Ethiopia: a community randomized trial.. PLoS ONE 2009;4(5):e5443. http://dx.doi.org/10.1371/journal.pone.0005443 PMID:19424460
http://dx.doi.org/10.1371/journal.pone.0... ²¹21. Keus K, Houston S, Melaku Y, Burling S. Field research in humanitarian medical programmes. Treatment of a cohort of tuberculosis patients using the Manyatta regimen in a conflict zone in South Sudan. Trans R Soc Trop Med Hyg. 2003 Nov-Dec;97(6):614-8. http://dx.doi.org/10.1016/S0035-9203(03)80048-2 PMID:16134258
http://dx.doi.org/10.1016/S0035-9203(03)... However, most of the studies that we screened simply excluded children and 54 studies that would otherwise have been eligible for our analyses had to be excluded because they failed to report paediatric outcomes separately. Even for the eligible studies, adherence outcomes were not explicitly adapted for paediatric patients - although paediatric-specific treatment toxicity was recognized in one study.¹⁰10. Satti H, McLaughlin MM, Omotayo DB, Keshavjee S, Becerra MC, Mukherjee JS, et al. Outcomes of comprehensive care for children empirically treated for multidrug-resistant tuberculosis in a setting of high HIV prevalence. PLoS ONE. 2012;7(5):e37114. http://dx.doi.org/10.1371/journal.pone.0037114 PMID:22629356
http://dx.doi.org/10.1371/journal.pone.0...

Second, several reports noted challenges in paediatric tuberculosis diagnosis and care. Children can pose diagnostic dilemmas that complicate epidemiological and outcome estimates.¹⁰10. Satti H, McLaughlin MM, Omotayo DB, Keshavjee S, Becerra MC, Mukherjee JS, et al. Outcomes of comprehensive care for children empirically treated for multidrug-resistant tuberculosis in a setting of high HIV prevalence. PLoS ONE. 2012;7(5):e37114. http://dx.doi.org/10.1371/journal.pone.0037114 PMID:22629356
http://dx.doi.org/10.1371/journal.pone.0... ²¹21. Keus K, Houston S, Melaku Y, Burling S. Field research in humanitarian medical programmes. Treatment of a cohort of tuberculosis patients using the Manyatta regimen in a conflict zone in South Sudan. Trans R Soc Trop Med Hyg. 2003 Nov-Dec;97(6):614-8. http://dx.doi.org/10.1016/S0035-9203(03)80048-2 PMID:16134258
http://dx.doi.org/10.1016/S0035-9203(03)... One study noted that paediatric lymph-node biopsies could not be safely performed locally.²¹21. Keus K, Houston S, Melaku Y, Burling S. Field research in humanitarian medical programmes. Treatment of a cohort of tuberculosis patients using the Manyatta regimen in a conflict zone in South Sudan. Trans R Soc Trop Med Hyg. 2003 Nov-Dec;97(6):614-8. http://dx.doi.org/10.1016/S0035-9203(03)80048-2 PMID:16134258
http://dx.doi.org/10.1016/S0035-9203(03)... Another considered how children's difficulty with sputum production may contribute to low detection rates¹⁸18. Datiko DG, Lindtjørn B. Health extension workers improve tuberculosis case detection and treatment success in southern Ethiopia: a community randomized trial.. PLoS ONE 2009;4(5):e5443. http://dx.doi.org/10.1371/journal.pone.0005443 PMID:19424460
http://dx.doi.org/10.1371/journal.pone.0... while a different study specified distinct sputum collection techniques for younger children.¹⁰10. Satti H, McLaughlin MM, Omotayo DB, Keshavjee S, Becerra MC, Mukherjee JS, et al. Outcomes of comprehensive care for children empirically treated for multidrug-resistant tuberculosis in a setting of high HIV prevalence. PLoS ONE. 2012;7(5):e37114. http://dx.doi.org/10.1371/journal.pone.0037114 PMID:22629356
http://dx.doi.org/10.1371/journal.pone.0... Dosing instructions that were adapted for paediatric treatment were also recommended.¹⁰10. Satti H, McLaughlin MM, Omotayo DB, Keshavjee S, Becerra MC, Mukherjee JS, et al. Outcomes of comprehensive care for children empirically treated for multidrug-resistant tuberculosis in a setting of high HIV prevalence. PLoS ONE. 2012;7(5):e37114. http://dx.doi.org/10.1371/journal.pone.0037114 PMID:22629356
http://dx.doi.org/10.1371/journal.pone.0... Key comorbidities in children - e.g. malnutrition²¹21. Keus K, Houston S, Melaku Y, Burling S. Field research in humanitarian medical programmes. Treatment of a cohort of tuberculosis patients using the Manyatta regimen in a conflict zone in South Sudan. Trans R Soc Trop Med Hyg. 2003 Nov-Dec;97(6):614-8. http://dx.doi.org/10.1016/S0035-9203(03)80048-2 PMID:16134258
http://dx.doi.org/10.1016/S0035-9203(03)... - may benefit from dedicated attention.

Third, several studies acknowledged the need to consider the preferences and social role of children and adolescents, who may need tailored interventions. In one study involving the use of directly observed, short-term treatment, children and women were more likely than men to select community-based over facility-based treatment, when given the option.²⁰20. van den Boogaard J, Lyimo R, Irongo CF, Boeree MJ, Schaalma H, Aarnoutse RE, et al. Community vs. facility-based directly observed treatment for tuberculosis in Tanzania's Kilimanjaro Region.. Int J Tuberc Lung Dis 2009 Dec;13(12):1524-9. PMID:19919771 Another study adapted an intervention, for use among children, according to household and social needs. This intervention included supporting the children in returning to school.¹⁰10. Satti H, McLaughlin MM, Omotayo DB, Keshavjee S, Becerra MC, Mukherjee JS, et al. Outcomes of comprehensive care for children empirically treated for multidrug-resistant tuberculosis in a setting of high HIV prevalence. PLoS ONE. 2012;7(5):e37114. http://dx.doi.org/10.1371/journal.pone.0037114 PMID:22629356
http://dx.doi.org/10.1371/journal.pone.0... As one study commented, tuberculosis - and tuberculosis treatment - can cut the economic productivity of adolescents and young adults, who tend to have relatively high burdens of the disease.¹²12. Mathew A, Binks C, Kuruvilla J, Davies PD. A comparison of two methods of undertaking directly observed therapy in a rural Indian setting. Int J Tuberc Lung Dis. 2005 Jan;9(1):69-74. PMID:15675553

Based on our review and identified themes, future studies need to: (i) assess interventions in low- and middle-income countries that explicitly analyse paediatric-inclusive and paediatric-distinct needs and outcomes, (ii) use mixed-method approaches that can assess the pathways linking context-dependent factors with outcomes, (iii) use longitudinal evaluations that investigate the sustainability of the effectiveness and benefits of interventions and the potential burdens posed by interventions, and (iv) incorporate and address cost-effectiveness, resource implications and potential scalability.

Our findings indicate the potential usefulness of diverse interventions to increase the rate of treatment completion among paediatric tuberculosis patients and improve outcomes in resource-poor settings.

Acknowledgements

We thank members of the International Society of Paediatric Oncology's Paediatric Oncology in Developing Countries Abandonment of Treatment Working Group (SIOP PODC).

References

¹
Guidance for national tuberculosis programmes on the management of tuberculosis in children. 2nd ed. Geneva: World Health Organization; 2014.
²
Adherence to long-term therapies: evidence for action.; Geneva: World Health Organization 2003.
³
Pefura Yone EW, Kengne AP, Kuaban C. Incidence, time and determinants of tuberculosis treatment default in Yaounde, Cameroon: a retrospective hospital register-based cohort study. BMJ Open. 2011;1(2):e000289. http://dx.doi.org/10.1136/bmjopen-2011-000289 PMID:22116091
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¹¹
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» http://dx.doi.org/10.1590/S1415-790X2011000300012
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Mathew A, Binks C, Kuruvilla J, Davies PD. A comparison of two methods of undertaking directly observed therapy in a rural Indian setting. Int J Tuberc Lung Dis. 2005 Jan;9(1):69-74. PMID:15675553
¹³
Cantalice Filho JP. Efeito do incentivo alimentício sobre o desfecho do tratamento de pacientes com tuberculose em uma unidade primária de saúde no município de Duque de Caxias, Rio de Janeiro. J Bras Pneumol. 2009 Oct;35(10):992-7. http://dx.doi.org/10.1590/S1806-37132009001000008 PMID:19918632 Portuguese.
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Datiko DG, Lindtjørn B. Health extension workers improve tuberculosis case detection and treatment success in southern Ethiopia: a community randomized trial.. PLoS ONE 2009;4(5):e5443. http://dx.doi.org/10.1371/journal.pone.0005443 PMID:19424460
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Demissie M, Getahun H, Lindtjørn B. Community tuberculosis care through "TB clubs" in rural North Ethiopia. Soc Sci Med. 2003 May;56(10):2009-18. http://dx.doi.org/10.1016/S0277-9536(02)00182-X PMID:12697193
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van den Boogaard J, Lyimo R, Irongo CF, Boeree MJ, Schaalma H, Aarnoutse RE, et al. Community vs. facility-based directly observed treatment for tuberculosis in Tanzania's Kilimanjaro Region.. Int J Tuberc Lung Dis 2009 Dec;13(12):1524-9. PMID:19919771
²¹
Keus K, Houston S, Melaku Y, Burling S. Field research in humanitarian medical programmes. Treatment of a cohort of tuberculosis patients using the Manyatta regimen in a conflict zone in South Sudan. Trans R Soc Trop Med Hyg. 2003 Nov-Dec;97(6):614-8. http://dx.doi.org/10.1016/S0035-9203(03)80048-2 PMID:16134258
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Ong'ang'o JR, Mwachari C, Kipruto H, Karanja S. The effects on tuberculosis treatment adherence from utilising community health workers: a comparison of selected rural and urban settings in Kenya.. PLoS ONE 2014;9(2):e88937. http://dx.doi.org/10.1371/journal.pone.0088937 PMID:24558452
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²³
Lee S, Khan OF, Seo JH, Kim DY, Park KH, Jung SI, et al. Impact of physician's education on adherence to tuberculosis treatment for patients of low socioeconomic status in Bangladesh. Chonnam Med J. 2013 Apr;49(1):27-30. http://dx.doi.org/10.4068/cmj.2013.49.1.27 PMID:23678474
» http://dx.doi.org/10.4068/cmj.2013.49.1.27
²⁴
Lönnroth K, Aung T, Maung W, Kluge H, Uplekar M. Social franchising of TB care through private GPs in Myanmar: an assessment of treatment results, access, equity and financial protection. Health Policy Plan. 2007 May;22(3):156-66. http://dx.doi.org/10.1093/heapol/czm007 PMID:17434870
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Roter DL, Hall JA, Merisca R, Nordstrom B, Cretin D, Svarstad B. Effectiveness of interventions to improve patient compliance: a meta-analysis. Med Care. 1998 Aug;36(8):1138-61. http://dx.doi.org/10.1097/00005650-199808000-00004 PMID:9708588
» http://dx.doi.org/10.1097/00005650-199808000-00004

Publication Dates

Publication in this collection
Oct 2015

History

Received
11 Sept 2014
Reviewed
01 May 2015
Accepted
07 May 2015

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[1] ¹
Guidance for national tuberculosis programmes on the management of tuberculosis in children. 2nd ed. Geneva: World Health Organization; 2014.

[2] ²
Adherence to long-term therapies: evidence for action.; Geneva: World Health Organization 2003.

[3] ³
Pefura Yone EW, Kengne AP, Kuaban C. Incidence, time and determinants of tuberculosis treatment default in Yaounde, Cameroon: a retrospective hospital register-based cohort study. BMJ Open. 2011;1(2):e000289. http://dx.doi.org/10.1136/bmjopen-2011-000289 PMID:22116091
» http://dx.doi.org/10.1136/bmjopen-2011-000289

[4] ⁴
Higgins JPT, Green S, editors. Cochrane handbook for systematic reviews of interventions version 5.1.0 [updated March 2011]. Oxford: The Cochrane Collaboration; 2011. Available from: Available from: www.cochrane-handbook.org [cited 2015 May 13].
» www.cochrane-handbook.org

[5] ⁵
Enhancing the quality and transparency of health research [Internet]. Oxford: Equator Network; 2013. Available from: Available from: http://www.equator-network.org/ [cited 2014 Apr 25].
» http://www.equator-network.org/

[6] ⁶
Armijo-Olivo S, Stiles CR, Hagen NA, Biondo PD, Cummings GG. Assessment of study quality for systematic reviews: a comparison of the Cochrane Collaboration Risk of Bias Tool and the Effective Public Health Practice Project Quality Assessment Tool: methodological research. J Eval Clin Pract. 2012 Feb;18(1):12-8. http://dx.doi.org/10.1111/j.1365-2753.2010.01516.x PMID:20698919
» http://dx.doi.org/10.1111/j.1365-2753.2010.01516.x

[7] ⁷
Petticrew M, Anderson L, Elder R, Grimshaw J, Hopkins D, Hahn R, et al. Complex interventions and their implications for systematic reviews: a pragmatic approach. J Clin Epidemiol. 2013 Nov;66(11):1209-14. http://dx.doi.org/10.1016/j.jclinepi.2013.06.004 PMID:23953085
» http://dx.doi.org/10.1016/j.jclinepi.2013.06.004

[8] ⁸
Critical appraisal skills programme [Internet]. Oxford: CASP UK; 2014. Available from: Available from: http://www.casp-uk.net/ [cited 2014 Apr 22].
» http://www.casp-uk.net/

[9] ⁹
Moher D, Liberati A, Tetzlaff J, Altman DG; PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009 Jul 21;6(7):e1000097. http://dx.doi.org/10.1371/journal.pmed.1000097 PMID:19621072
» http://dx.doi.org/10.1371/journal.pmed.1000097

[10] ¹⁰
Satti H, McLaughlin MM, Omotayo DB, Keshavjee S, Becerra MC, Mukherjee JS, et al. Outcomes of comprehensive care for children empirically treated for multidrug-resistant tuberculosis in a setting of high HIV prevalence. PLoS ONE. 2012;7(5):e37114. http://dx.doi.org/10.1371/journal.pone.0037114 PMID:22629356
» http://dx.doi.org/10.1371/journal.pone.0037114

[11] ¹¹
Heck MA, da Costa JS, Nunes MF. Prevalência de abandono do tratamento da tuberculose e fatores associados no município de Sapucaia do Sul (RS), Brasil, 2000-2008. Rev Bras Epidemiol. 2011 Sep;14(3):478-85. http://dx.doi.org/10.1590/S1415-790X2011000300012 PMID:22069015 Portuguese.
» http://dx.doi.org/10.1590/S1415-790X2011000300012

[12] ¹²
Mathew A, Binks C, Kuruvilla J, Davies PD. A comparison of two methods of undertaking directly observed therapy in a rural Indian setting. Int J Tuberc Lung Dis. 2005 Jan;9(1):69-74. PMID:15675553

[13] ¹³
Cantalice Filho JP. Efeito do incentivo alimentício sobre o desfecho do tratamento de pacientes com tuberculose em uma unidade primária de saúde no município de Duque de Caxias, Rio de Janeiro. J Bras Pneumol. 2009 Oct;35(10):992-7. http://dx.doi.org/10.1590/S1806-37132009001000008 PMID:19918632 Portuguese.
» http://dx.doi.org/10.1590/S1806-37132009001000008

[14] ¹⁴
Marques AM, da Cunha RV. A medicação assistida e os índices de cura de tuberculose e de abandono de tratamento na população indígena Guaraní-Kaiwá no Município de Dourados, Mato Grosso do Sul, Brasil. Cad Saude Publica. 2003 Sep-Oct;19(5):1405-11. http://dx.doi.org/10.1590/S0102-311X2003000500019 PMID:14666222 Portuguese.
» http://dx.doi.org/10.1590/S0102-311X2003000500019

[15] ¹⁵
Anuwatnonthakate A, Limsomboon P, Nateniyom S, Wattanaamornkiat W, Komsakorn S, Moolphate S, et al. Directly observed therapy and improved tuberculosis treatment outcomes in Thailand.. PLoS ONE 2008;3(8):e3089. http://dx.doi.org/10.1371/journal.pone.0003089 PMID:18769479
» http://dx.doi.org/10.1371/journal.pone.0003089

[16] ¹⁶
Khortwong P, Kaewkungwal J. Thai health education program for improving TB migrant's compliance. J Med Assoc Thai. 2013 Mar;96(3):365-73. PMID:23539943

[17] ¹⁷
Badar D, Ohkado A, Naeem M, Khurshid-ul-Zaman S, Tsukamoto M. Strengthening tuberculosis patient referral mechanisms among health facilities in Punjab, Pakistan.. Int J Tuberc Lung Dis 2011 Oct;15(10):1362-6. http://dx.doi.org/10.5588/ijtld.10.0620 PMID:22283896
» http://dx.doi.org/10.5588/ijtld.10.0620

[18] ¹⁸
Datiko DG, Lindtjørn B. Health extension workers improve tuberculosis case detection and treatment success in southern Ethiopia: a community randomized trial.. PLoS ONE 2009;4(5):e5443. http://dx.doi.org/10.1371/journal.pone.0005443 PMID:19424460
» http://dx.doi.org/10.1371/journal.pone.0005443

[19] ¹⁹
Demissie M, Getahun H, Lindtjørn B. Community tuberculosis care through "TB clubs" in rural North Ethiopia. Soc Sci Med. 2003 May;56(10):2009-18. http://dx.doi.org/10.1016/S0277-9536(02)00182-X PMID:12697193
» http://dx.doi.org/10.1016/S0277-9536(02)00182-X

[20] ²⁰
van den Boogaard J, Lyimo R, Irongo CF, Boeree MJ, Schaalma H, Aarnoutse RE, et al. Community vs. facility-based directly observed treatment for tuberculosis in Tanzania's Kilimanjaro Region.. Int J Tuberc Lung Dis 2009 Dec;13(12):1524-9. PMID:19919771

[21] ²¹
Keus K, Houston S, Melaku Y, Burling S. Field research in humanitarian medical programmes. Treatment of a cohort of tuberculosis patients using the Manyatta regimen in a conflict zone in South Sudan. Trans R Soc Trop Med Hyg. 2003 Nov-Dec;97(6):614-8. http://dx.doi.org/10.1016/S0035-9203(03)80048-2 PMID:16134258
» http://dx.doi.org/10.1016/S0035-9203(03)80048-2

[22] ²²
Ong'ang'o JR, Mwachari C, Kipruto H, Karanja S. The effects on tuberculosis treatment adherence from utilising community health workers: a comparison of selected rural and urban settings in Kenya.. PLoS ONE 2014;9(2):e88937. http://dx.doi.org/10.1371/journal.pone.0088937 PMID:24558452
» http://dx.doi.org/10.1371/journal.pone.0088937

[23] ²³
Lee S, Khan OF, Seo JH, Kim DY, Park KH, Jung SI, et al. Impact of physician's education on adherence to tuberculosis treatment for patients of low socioeconomic status in Bangladesh. Chonnam Med J. 2013 Apr;49(1):27-30. http://dx.doi.org/10.4068/cmj.2013.49.1.27 PMID:23678474
» http://dx.doi.org/10.4068/cmj.2013.49.1.27

[24] ²⁴
Lönnroth K, Aung T, Maung W, Kluge H, Uplekar M. Social franchising of TB care through private GPs in Myanmar: an assessment of treatment results, access, equity and financial protection. Health Policy Plan. 2007 May;22(3):156-66. http://dx.doi.org/10.1093/heapol/czm007 PMID:17434870
» http://dx.doi.org/10.1093/heapol/czm007

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Higgins JPT, Altman DG, Sterne JAC, on behalf of the Cochrane Statistical Methods Group and the Cochrane Bias Methods Group. Chapter 8: Assessing risk of bias in included studies. In: Higgins JPT, Green S, editors. Cochrane handbook for systematic reviews of interventions. London: The Cochrane Collaboration; 2011. pp. 8.13-8.18.

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Roter DL, Hall JA, Merisca R, Nordstrom B, Cretin D, Svarstad B. Effectiveness of interventions to improve patient compliance: a meta-analysis. Med Care. 1998 Aug;36(8):1138-61. http://dx.doi.org/10.1097/00005650-199808000-00004 PMID:9708588
» http://dx.doi.org/10.1097/00005650-199808000-00004

Study	Country and study design	Care setting	Participant description	Duration, months	Period	Study arms
Study	Country and study design	Care setting	Participant description	Duration, months	Period	Intervention	Comparison
Non-randomized
Anuwatnonthakate et al.¹⁵15. Anuwatnonthakate A, Limsomboon P, Nateniyom S, Wattanaamornkiat W, Komsakorn S, Moolphate S, et al. Directly observed therapy and improved tuberculosis treatment outcomes in Thailand.. PLoS ONE 2008;3(8):e3089. http://dx.doi.org/10.1371/journal.pone.0003089 PMID:18769479 http://dx.doi.org/10.1371/journal.pone.0...	Thailand, prospective observational cohort^a	Region - all public and private facilities in four provinces	Diverse patient population including urban, rural and migrant populations. HIV co-infection rate 20%. Of the participants, 223 (3%) were aged < 15 years^b.	24	2004-2006	DOT supervised by family member or HCW	Self-administered therapy
Heck et al.¹¹11. Heck MA, da Costa JS, Nunes MF. Prevalência de abandono do tratamento da tuberculose e fatores associados no município de Sapucaia do Sul (RS), Brasil, 2000-2008. Rev Bras Epidemiol. 2011 Sep;14(3):478-85. http://dx.doi.org/10.1590/S1415-790X2011000300012 PMID:22069015 Portuguese. http://dx.doi.org/10.1590/S1415-790X2011...	Brazil, retrospective observational cross-sectional^a	City - 18 urban outpatient primary health units and five referral units supervised by Municipal Tuberculosis Control Programme	Socioeconomic and education summary not provided; HIV co-infection rate 16%. Of the participants, 57 (9%) were aged ?? 19 years.	96	2000-2004 and 2005-2008	Decentralization of tuberculosis programme actions for primary care and implementation of DOT	SOC before decentralization initiatives
Lee et al.²³23. Lee S, Khan OF, Seo JH, Kim DY, Park KH, Jung SI, et al. Impact of physician's education on adherence to tuberculosis treatment for patients of low socioeconomic status in Bangladesh. Chonnam Med J. 2013 Apr;49(1):27-30. http://dx.doi.org/10.4068/cmj.2013.49.1.27 PMID:23678474 http://dx.doi.org/10.4068/cmj.2013.49.1....	Bangladesh, prospective before-and-after study^a	Clinic - suburban primary health clinic in industrial complex near capital	Participants had low socioeconomic status, limited education and high level of illiteracy. Of the participants, 26 (7%) were aged < 18 years^b.	33	2005-2006 and 2006-2007	Patient education on the importance of treatment adherence provided, by a physician, weekly for 1 month, fortnightly for next month, then monthly. Visits scheduled to coincide with medication refills	SOC, with no standardized patient education and return visits not timed to coincide with refills
Marques and da Cunha¹⁴14. Marques AM, da Cunha RV. A medicação assistida e os índices de cura de tuberculose e de abandono de tratamento na população indígena Guaraní-Kaiwá no Município de Dourados, Mato Grosso do Sul, Brasil. Cad Saude Publica. 2003 Sep-Oct;19(5):1405-11. http://dx.doi.org/10.1590/S0102-311X2003000500019 PMID:14666222 Portuguese. http://dx.doi.org/10.1590/S0102-311X2003...	Brazil, retrospective before-and-after^a	Hospital - urban hospital	Indigenous population suffering extreme poverty, malnutrition and cultural and socioeconomic barriers to extended hospitalization. Of the participants, 244 (41%) were aged < 15 years^b.	35	1996-1998 and 1998-1999	Outpatient treatment with home-based DOT via indigenous health agents	Systematic hospitalization of patients for up to 6 months
Ong'ang'o et al.²²22. Ong'ang'o JR, Mwachari C, Kipruto H, Karanja S. The effects on tuberculosis treatment adherence from utilising community health workers: a comparison of selected rural and urban settings in Kenya.. PLoS ONE 2014;9(2):e88937. http://dx.doi.org/10.1371/journal.pone.0088937 PMID:24558452 http://dx.doi.org/10.1371/journal.pone.0...	Kenya, retrospective cohort^a	Region - sample of four urban and rural public health facilities, using and not using CHWs	Mention of stigma towards tuberculosis and cultural beliefs against conventional treatment of the disease in rural setting. Of the participants, 298 (11%) were aged < 14 years^b.	72	2005-2011	Personalized education from CHW, on treatment and risks involved in lack of adherence, plus CHW-supervised DOT at household level with ongoing CHW educational support	Nurse at health facility advised patients of treatment schedule, need for adherence and need for family support. Weekly DOT at health facility
Satti et al.¹⁰10. Satti H, McLaughlin MM, Omotayo DB, Keshavjee S, Becerra MC, Mukherjee JS, et al. Outcomes of comprehensive care for children empirically treated for multidrug-resistant tuberculosis in a setting of high HIV prevalence. PLoS ONE. 2012;7(5):e37114. http://dx.doi.org/10.1371/journal.pone.0037114 PMID:22629356 http://dx.doi.org/10.1371/journal.pone.0...	Lesotho, retrospective cohort	Community - mountainous rural and urban, inpatient and outpatient setting	Nineteen patients with suspected or confirmed MDR tuberculosis, of whom 14 (74%) were co-infected with HIV, 12 (63%) were malnourished and all were aged < 16 years.	42	2007-2011	Comprehensive approach to care for MDR tuberculosis, with or without HIV co-infection, using social support, close monitoring by CHWs and clinicians and inpatient care when warranted	Patients of MDR tuberculosis with high rates of HIV co-infection in neighbouring South Africa
van den Boogaard et al.²⁰20. van den Boogaard J, Lyimo R, Irongo CF, Boeree MJ, Schaalma H, Aarnoutse RE, et al. Community vs. facility-based directly observed treatment for tuberculosis in Tanzania's Kilimanjaro Region.. Int J Tuberc Lung Dis 2009 Dec;13(12):1524-9. PMID:19919771	United Republic of Tanzania, retrospective observational cohort^a	Region - urban and rural districts with national referral hospital, regional hospital and primary health clinics	Socioeconomic and education summary not provided. HIV co-infection rate 31%. Of the participants, 308 (11%) were aged < 15 years.	12	2007	Patient-centred treatment that allowed patients to choose between community and facility-based DOT	Conventional facility-based DOT supervised by facility-based provider
Badar et al.¹⁷17. Badar D, Ohkado A, Naeem M, Khurshid-ul-Zaman S, Tsukamoto M. Strengthening tuberculosis patient referral mechanisms among health facilities in Punjab, Pakistan.. Int J Tuberc Lung Dis 2011 Oct;15(10):1362-6. http://dx.doi.org/10.5588/ijtld.10.0620 PMID:22283896 http://dx.doi.org/10.5588/ijtld.10.0620...	Pakistan, prospective observational cohort	Province - urban, nongovernment outpatient tertiary care hospital as referring centre	Socioeconomic and education summary not provided. Of the participants, 150 (34%) were aged ?? 19 years.	9	2009	Electronic database register, designated oversight of referrals, staff referral orientation, tracking via 1-3 phone calls, communication between centres via exchanges of pre-stamped mail, scheduled meetings and phone contact and patients referred to closest facility	Patient responsible for return to referring unit
Cantalice Filho¹³13. Cantalice Filho JP. Efeito do incentivo alimentício sobre o desfecho do tratamento de pacientes com tuberculose em uma unidade primária de saúde no município de Duque de Caxias, Rio de Janeiro. J Bras Pneumol. 2009 Oct;35(10):992-7. http://dx.doi.org/10.1590/S1806-37132009001000008 PMID:19918632 Portuguese. http://dx.doi.org/10.1590/S1806-37132009...	Brazil, before-and-after^a	Clinic - urban primary health care outpatient clinic	Socioeconomic and education summary not provided. HIV co-infection rate < 5%. Of the participants, 8 (6%) were aged < 18 years^b.	57	2001-2003 and 2004-2006	Standard treatment regimen plus monthly food basket	Standard treatment regimen, including self-administered therapy
Keus et al.²¹21. Keus K, Houston S, Melaku Y, Burling S. Field research in humanitarian medical programmes. Treatment of a cohort of tuberculosis patients using the Manyatta regimen in a conflict zone in South Sudan. Trans R Soc Trop Med Hyg. 2003 Nov-Dec;97(6):614-8. http://dx.doi.org/10.1016/S0035-9203(03)80048-2 PMID:16134258 http://dx.doi.org/10.1016/S0035-9203(03)...	South Sudan, prospective observational cohort^a	Programme - humanitarian rural tuberculosis camp located in "transitional" zone between militia and local factions	Pastoral, migratory population living in conflict conditions with no health infrastructure. HIV co-infection rate < 5%. Of the participants, 84 (52%) were aged < 15 years.	9	2001	Village-based treatment in a conflict zone of South Sudan	Treatment in a less insecure area - Manyatta Region - with 2-month supervised then 3-month unsupervised regimen
Lönnroth et al.²⁴24. Lönnroth K, Aung T, Maung W, Kluge H, Uplekar M. Social franchising of TB care through private GPs in Myanmar: an assessment of treatment results, access, equity and financial protection. Health Policy Plan. 2007 May;22(3):156-66. http://dx.doi.org/10.1093/heapol/czm007 PMID:17434870 http://dx.doi.org/10.1093/heapol/czm007...	Myanmar, prospective cohort	Clinics - multiple township outpatient clinics serving low-income population	Mostly patients with low socioeconomic status, from townships in which many used private health care as the first point of contact. Of the participants, 66 (26%) were aged 16 years.	14	2004-2005	Social franchise engaging private general practitioners to deliver quality controlled tuberculosis care, including service branding, defined treatment supporter and default tracing mechanism	Continuation of previous SOC, with patient utilization of existing treatment centres and the public sector's DOT logo branding
Randomized or quasi-randomized
Datiko and Lindtjørn¹⁸18. Datiko DG, Lindtjørn B. Health extension workers improve tuberculosis case detection and treatment success in southern Ethiopia: a community randomized trial.. PLoS ONE 2009;4(5):e5443. http://dx.doi.org/10.1371/journal.pone.0005443 PMID:19424460 http://dx.doi.org/10.1371/journal.pone.0...	Ethiopia, prospective randomized	Clinics - rural outpatient setting in south of country	Patients with poor access, poverty and low health-seeking behaviours. Of the participants, 32 (10%) were aged < 14 years.	19	2006-2008	Local treatment by HEWs. HEW training in adherence support, diagnosis, referral with enhanced case finding and the problems of non-adherence. Community mobilization and education	HEWs did not receive training on diagnostic techniques or adherence support. HEWs engage in community education on symptoms of tuberculosis. DOT provided at health facility instead of within local neighbourhood
Demissie et al.¹⁹19. Demissie M, Getahun H, Lindtjørn B. Community tuberculosis care through "TB clubs" in rural North Ethiopia. Soc Sci Med. 2003 May;56(10):2009-18. http://dx.doi.org/10.1016/S0277-9536(02)00182-X PMID:12697193 http://dx.doi.org/10.1016/S0277-9536(02)...	Ethiopia, prospective quasi-randomized^a	Clinics - rural outpatient centres in north of country	Tuberculosis associated with strong community stigma, to the extent that patients may lose their work if employer is aware of diagnosis. Of the participants, 7 (5%) were aged < 15 years.	12	1998-1999	Patients organized according to residential area into clubs, each with 3-10 members, an elected leader and the same appointment dates. Weekly club meetings with emphasis on social support towards treatment completion.	Continuation of previous SOC. No tuberculosis clubs but otherwise similar treatment regimen and packages of health education as in the intervention arm
Khortwong and Kaewkungwal¹⁶16. Khortwong P, Kaewkungwal J. Thai health education program for improving TB migrant's compliance. J Med Assoc Thai. 2013 Mar;96(3):365-73. PMID:23539943	Thailand, prospective quasi-randomized^a	Clinics - urban outpatient hospital clinics	Marginalized migrant population living in crowded conditions, with high mobility. Lack of legal status or registration made most ineligible for routine health-care services. Of the participants, 4 (4%) were aged < 18 years^b.	16	2009-2010	Migrant population provided with intensive education modules, home and workplace visits and phone-call reminders, with emphasis on therapeutic health team relationships	Migrant population received continuation of previous SOC, which included optional treatment supervision by a village health volunteer
Mathew et al.¹²12. Mathew A, Binks C, Kuruvilla J, Davies PD. A comparison of two methods of undertaking directly observed therapy in a rural Indian setting. Int J Tuberc Lung Dis. 2005 Jan;9(1):69-74. PMID:15675553	India, retrospective quasi-randomized observational cohort	Clinic - outpatient clinic based in rural secondary-level mission hospital in north of country	In one of the poorest regions in India, with high rate of illiteracy. Tribal population engaged in small-scale farming, with poor road access. Of the participants, 94 (14%) were aged < 15 years but data were only reported for 61 of these.	30	2001-2003	Free drugs, visits made to the patient by the DOT supervisor - a community member - monthly during intensive phase and every 2 months thereafter. Adherence checks. Patient asked to visit clinic three times during therapy	Drugs provided at cost, family member supported DOT and accompanied patient to appointments. Monthly clinic visits in intensive phase and clinic visits every 2 months thereafter

Study	Selection bias	Study design	Confounders	Blinding	Data collection method	Withdrawals and dropouts	Global rating
Anuwatnonthakate et al.¹⁵15. Anuwatnonthakate A, Limsomboon P, Nateniyom S, Wattanaamornkiat W, Komsakorn S, Moolphate S, et al. Directly observed therapy and improved tuberculosis treatment outcomes in Thailand.. PLoS ONE 2008;3(8):e3089. http://dx.doi.org/10.1371/journal.pone.0003089 PMID:18769479 http://dx.doi.org/10.1371/journal.pone.0...	Moderate	Moderate	Strong	Weak	Weak	Strong	Weak
Heck et al.¹¹11. Heck MA, da Costa JS, Nunes MF. Prevalência de abandono do tratamento da tuberculose e fatores associados no município de Sapucaia do Sul (RS), Brasil, 2000-2008. Rev Bras Epidemiol. 2011 Sep;14(3):478-85. http://dx.doi.org/10.1590/S1415-790X2011000300012 PMID:22069015 Portuguese. http://dx.doi.org/10.1590/S1415-790X2011...	Moderate	Weak	Weak	Weak	Weak	Moderate	Weak
Lee et al.²³23. Lee S, Khan OF, Seo JH, Kim DY, Park KH, Jung SI, et al. Impact of physician's education on adherence to tuberculosis treatment for patients of low socioeconomic status in Bangladesh. Chonnam Med J. 2013 Apr;49(1):27-30. http://dx.doi.org/10.4068/cmj.2013.49.1.27 PMID:23678474 http://dx.doi.org/10.4068/cmj.2013.49.1....	Moderate	Moderate	Strong	Not clear	Weak	Moderate	Moderate
Marques and da Cunha¹⁴14. Marques AM, da Cunha RV. A medicação assistida e os índices de cura de tuberculose e de abandono de tratamento na população indígena Guaraní-Kaiwá no Município de Dourados, Mato Grosso do Sul, Brasil. Cad Saude Publica. 2003 Sep-Oct;19(5):1405-11. http://dx.doi.org/10.1590/S0102-311X2003000500019 PMID:14666222 Portuguese. http://dx.doi.org/10.1590/S0102-311X2003...	Not clear	Moderate	Weak	Not clear	Weak	Weak	Weak
Ong'ang'o et al.²²22. Ong'ang'o JR, Mwachari C, Kipruto H, Karanja S. The effects on tuberculosis treatment adherence from utilising community health workers: a comparison of selected rural and urban settings in Kenya.. PLoS ONE 2014;9(2):e88937. http://dx.doi.org/10.1371/journal.pone.0088937 PMID:24558452 http://dx.doi.org/10.1371/journal.pone.0...	Moderate	Moderate	Strong	Moderate	Weak	Strong	Moderate
Satti et al.¹⁰10. Satti H, McLaughlin MM, Omotayo DB, Keshavjee S, Becerra MC, Mukherjee JS, et al. Outcomes of comprehensive care for children empirically treated for multidrug-resistant tuberculosis in a setting of high HIV prevalence. PLoS ONE. 2012;7(5):e37114. http://dx.doi.org/10.1371/journal.pone.0037114 PMID:22629356 http://dx.doi.org/10.1371/journal.pone.0...	Moderate	Weak	Weak	Not clear	Weak	Strong	Weak
van den Boogaard et al.²⁰20. van den Boogaard J, Lyimo R, Irongo CF, Boeree MJ, Schaalma H, Aarnoutse RE, et al. Community vs. facility-based directly observed treatment for tuberculosis in Tanzania's Kilimanjaro Region.. Int J Tuberc Lung Dis 2009 Dec;13(12):1524-9. PMID:19919771	Moderate	Moderate	Moderate	Weak	Weak	Moderate	Weak
Badar et al.¹⁷17. Badar D, Ohkado A, Naeem M, Khurshid-ul-Zaman S, Tsukamoto M. Strengthening tuberculosis patient referral mechanisms among health facilities in Punjab, Pakistan.. Int J Tuberc Lung Dis 2011 Oct;15(10):1362-6. http://dx.doi.org/10.5588/ijtld.10.0620 PMID:22283896 http://dx.doi.org/10.5588/ijtld.10.0620...	Not clear	Weak	Weak	Weak	Weak	Weak	Weak
Cantalice Filho¹³13. Cantalice Filho JP. Efeito do incentivo alimentício sobre o desfecho do tratamento de pacientes com tuberculose em uma unidade primária de saúde no município de Duque de Caxias, Rio de Janeiro. J Bras Pneumol. 2009 Oct;35(10):992-7. http://dx.doi.org/10.1590/S1806-37132009001000008 PMID:19918632 Portuguese. http://dx.doi.org/10.1590/S1806-37132009...	Moderate	Moderate	Moderate	Not clear	Weak	Weak	Weak
Keus et al.²¹21. Keus K, Houston S, Melaku Y, Burling S. Field research in humanitarian medical programmes. Treatment of a cohort of tuberculosis patients using the Manyatta regimen in a conflict zone in South Sudan. Trans R Soc Trop Med Hyg. 2003 Nov-Dec;97(6):614-8. http://dx.doi.org/10.1016/S0035-9203(03)80048-2 PMID:16134258 http://dx.doi.org/10.1016/S0035-9203(03)...	Moderate	Weak	Weak	Moderate	Weak	Strong	Weak
Lönnroth et al.²⁴24. Lönnroth K, Aung T, Maung W, Kluge H, Uplekar M. Social franchising of TB care through private GPs in Myanmar: an assessment of treatment results, access, equity and financial protection. Health Policy Plan. 2007 May;22(3):156-66. http://dx.doi.org/10.1093/heapol/czm007 PMID:17434870 http://dx.doi.org/10.1093/heapol/czm007...	Weak	Weak	Weak	Not clear	Weak	Strong	Weak

Study	Random sequence generation	Allocation concealment	Blinding of participants and personnel	Blinding of outcome assessors	Incomplete outcome data	Selective reporting	Other bias
Datiko and Lindtjørn¹⁸18. Datiko DG, Lindtjørn B. Health extension workers improve tuberculosis case detection and treatment success in southern Ethiopia: a community randomized trial.. PLoS ONE 2009;4(5):e5443. http://dx.doi.org/10.1371/journal.pone.0005443 PMID:19424460 http://dx.doi.org/10.1371/journal.pone.0...	Low	High	Low	High	Low	Low	Low
Demissie et al.¹⁹19. Demissie M, Getahun H, Lindtjørn B. Community tuberculosis care through "TB clubs" in rural North Ethiopia. Soc Sci Med. 2003 May;56(10):2009-18. http://dx.doi.org/10.1016/S0277-9536(02)00182-X PMID:12697193 http://dx.doi.org/10.1016/S0277-9536(02)...	High	Unclear	Unclear	High	Low	Unclear	Low
Khortwong and Kaewkungwal¹⁶16. Khortwong P, Kaewkungwal J. Thai health education program for improving TB migrant's compliance. J Med Assoc Thai. 2013 Mar;96(3):365-73. PMID:23539943	High	Unclear	Unclear	High	Low	Unclear	Low
Mathew et al.¹²12. Mathew A, Binks C, Kuruvilla J, Davies PD. A comparison of two methods of undertaking directly observed therapy in a rural Indian setting. Int J Tuberc Lung Dis. 2005 Jan;9(1):69-74. PMID:15675553	High	Unclear	High	High	High	Unclear	Low

Saúde Pública

Saúde Pública

Interventions to improve adherence to treatment for paediatric tuberculosis in low- and middle-income countries: a systematic review and meta-analysis

Interventions pour améliorer l'observance thérapeutique dans le traitement de la tuberculose chez l'enfant dans les pays à revenu faible et intermédiaire: revue systématique et méta-analyse

Intervenciones para mejorar el cumplimiento del tratamiento de la tuberculosis pediátrica en los países de ingresos bajos y medios: una revisión sistemática y un metanálisis

التدخلات الساعية إلى تحسين مستوى الالتزام بالعلاج الخاص بمرض السل لدى الأطفال في البلدان محدودة ومتوسطة الدخل: مراجعة منهجية وتحليل تجميعي

在中低收入国家采取干预措施以提高儿科结核病的治疗依从性： 系统评审和元分析

Abstract

Objective

Methods

Findings

Conclusion

Résumé

Objectif

Méthodes

Résultats

Conclusion

Resumen

Objetivo

Métodos

Resultados

Conclusión

ملخص

الغرض

摘要

目的

方法

结果

结论

Резюме

Цель.

Методы.

Результаты.

Вывод.

Introduction

Methods

Search and selection

Data extraction

Statistical analysis

Results

Interventions

Treatment adherence

Risk of bias

Meta-analysis

Discussion

Acknowledgements

References

Publication Dates

History

在中低收入国家采取干预措施以提高儿科结核病的治疗依从性：系统评审和元分析