{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T11:27:30Z","timestamp":1767180450310,"version":"build-2238731810"},"update-to":[{"DOI":"10.1371\/journal.pmed.1004285","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2023,9,20]],"date-time":"2023-09-20T00:00:00Z","timestamp":1695168000000}}],"reference-count":29,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2023,9,6]],"date-time":"2023-09-06T00:00:00Z","timestamp":1693958400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Unitaid","award":["2017-20-EGPAF-CAP-TB"],"award-info":[{"award-number":["2017-20-EGPAF-CAP-TB"]}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/P022081\/1"],"award-info":[{"award-number":["MR\/P022081\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosmedicine.org"],"crossmark-restriction":false},"short-container-title":["PLoS Med"],"abstract":"\n Background<\/jats:title>\n Over 1 million children aged 0 to 14 years were estimated to develop tuberculosis in 2021, resulting in over 200,000 deaths. Practical interventions are urgently needed to improve diagnosis and antituberculosis treatment (ATT) initiation in children aged 0 to 14 years and to increase coverage of tuberculosis preventive therapy (TPT) in children at high risk of developing tuberculosis disease. The multicountry CaP-TB intervention scaled up facility-based intensified case finding and strengthened household contact management and TPT provision at HIV clinics. To add to the limited health-economic evidence on interventions to improve ATT and TPT in children, we evaluated the cost-effectiveness of the CaP-TB intervention.<\/jats:p>\n <\/jats:sec>\n \n Methods and findings<\/jats:title>\n We analysed clinic-level pre\/post data to quantify the impact of the CaP-TB intervention on ATT and TPT initiation across 9 sub-Saharan African countries. Data on tuberculosis diagnosis and ATT\/TPT initiation counts with corresponding follow-up time were available for 146 sites across the 9 countries prior to and post project implementation, stratified by 0 to 4 and 5 to 14 year age-groups. Preintervention data were retrospectively collected from facility registers for a 12-month period, and intervention data were prospectively collected from December 2018 to June 2021 using project-specific forms. Bayesian generalised linear mixed-effects models were used to estimate country-level rate ratios for tuberculosis diagnosis and ATT\/TPT initiation. We analysed project expenditure and cascade data to determine unit costs of intervention components and used mathematical modelling to project health impact, health system costs, and cost-effectiveness.<\/jats:p>\n Overall, ATT and TPT initiation increased, with country-level incidence rate ratios varying between 0.8 (95% uncertainty interval [UI], 0.7 to 1.0) and 2.9 (95% UI, 2.3 to 3.6) for ATT and between 1.6 (95% UI, 1.5 to 1.8) and 9.8 (95% UI, 8.1 to 11.8) for TPT. We projected that for every 100 children starting either ATT or TPT at baseline, the intervention package translated to between 1 (95% UI, \u22121 to 3) and 38 (95% UI, 24 to 58) deaths averted, with a median incremental cost-effectiveness ratio (ICER) of US$634 per disability-adjusted life year (DALY) averted. ICERs ranged between US$135\/DALY averted in Democratic of the Congo and US$6,804\/DALY averted in Cameroon. The main limitation of our study is that the impact is based on pre\/post comparisons, which could be confounded.<\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n In most countries, the CaP-TB intervention package improved tuberculosis treatment and prevention services for children aged under 15 years, but large variation in estimated impact and ICERs highlights the importance of local context.<\/jats:p>\n <\/jats:sec>\n \n Trial registration<\/jats:title>\n \n This evaluation is part of the TIPPI study, registered with ClinicalTrials.gov (\n NCT03948698<\/jats:ext-link>\n ).\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1371\/journal.pmed.1004285","type":"journal-article","created":{"date-parts":[[2023,9,6]],"date-time":"2023-09-06T13:32:05Z","timestamp":1694007125000},"page":"e1004285","update-policy":"https:\/\/doi.org\/10.1371\/journal.pmed.corrections_policy","source":"Crossref","is-referenced-by-count":8,"title":["Cost-effectiveness analysis of interventions to improve diagnosis and preventive therapy for paediatric tuberculosis in 9 sub-Saharan African countries: A modelling study"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9775-6581","authenticated-orcid":true,"given":"Nyashadzaishe","family":"Mafirakureva","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sushant","family":"Mukherjee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mikhael","family":"de Souza","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cassandra","family":"Kelly-Cirino","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9769-494X","authenticated-orcid":true,"given":"Mario J. P.","family":"Songane","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer","family":"Cohn","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5826-0169","authenticated-orcid":true,"given":"Jean-Fran\u00e7ois","family":"Lemaire","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martina","family":"Casenghi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5825-9347","authenticated-orcid":true,"given":"Peter J.","family":"Dodd","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2023,9,6]]},"reference":[{"key":"pmed.1004285.ref001","doi-asserted-by":"crossref","first-page":"e898","DOI":"10.1016\/S2214-109X(17)30289-9","article-title":"The global burden of tuberculosis mortality in children: a mathematical modelling study","volume":"5","author":"PJ Dodd","year":"2017","journal-title":"Lancet Glob Health"},{"key":"pmed.1004285.ref002","volume-title":"Global tuberculosis report","author":"World Health Organization","year":"2021"},{"key":"pmed.1004285.ref003","article-title":"Global, regional, and national causes of under-5 mortality in 2000\u201319: an updated systematic analysis with implications for the Sustainable Development Goals Lancet Child Adolesc Health","author":"J Perin","year":"2021"},{"key":"pmed.1004285.ref004","doi-asserted-by":"crossref","first-page":"1531","DOI":"10.1164\/rccm.201904-0772OC","article-title":"Tuberculosis Diagnosis in Children Using Xpert Ultra on Different Respiratory Specimens","volume":"200","author":"HJ Zar","year":"2019","journal-title":"Am J Respir Crit Care Med"},{"key":"pmed.1004285.ref005","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/S1473-3099(12)70245-1","article-title":"Assessment of the Xpert MTB\/RIF assay for diagnosis of tuberculosis with gastric lavage aspirates in children in sub-Saharan Africa: a prospective descriptive study","volume":"13","author":"M Bates","year":"2013","journal-title":"Lancet Infect Dis"},{"key":"pmed.1004285.ref006","doi-asserted-by":"crossref","first-page":"e1350","DOI":"10.1542\/peds.2006-0519","article-title":"A refined symptom-based approach to diagnose pulmonary tuberculosis in children","volume":"118","author":"BJ Marais","year":"2006","journal-title":"Pediatrics"},{"key":"pmed.1004285.ref007","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1016\/S0140-6736(20)30166-5","article-title":"The risk of tuberculosis in children after close exposure: a systematic review and individual-participant meta-analysis","volume":"395","author":"L Martinez","year":"2020","journal-title":"Lancet"},{"key":"pmed.1004285.ref008","volume-title":"Module 1: prevention: tuberculosis preventive treatment","author":"World Health Organization","year":"2020"},{"key":"pmed.1004285.ref009","doi-asserted-by":"crossref","first-page":"e1329","DOI":"10.1016\/S2214-109X(18)30401-7","article-title":"Potential effect of household contact management on childhood tuberculosis: a mathematical modelling study","volume":"6","author":"PJ Dodd","year":"2018","journal-title":"The Lancet Global Health"},{"key":"pmed.1004285.ref010","unstructured":"World Health Organization. Global Tuberculosis Report. 2020. Available from: https:\/\/www.who.int\/publications\/i\/item\/9789240013131"},{"key":"pmed.1004285.ref011","volume-title":"Module 5: management of tuberculosis in children and adolescents","year":"2022"},{"key":"pmed.1004285.ref012","doi-asserted-by":"crossref","first-page":"207","DOI":"10.5588\/ijtld.12.0160","article-title":"Effectiveness of active case-finding strategies in tuberculosis control in Kampala, Uganda","volume":"17","author":"E Mupere","year":"2013","journal-title":"Int J Tuberc Lung Dis"},{"key":"pmed.1004285.ref013","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1097\/INF.0000000000001342","article-title":"Cost-effectiveness of Diagnostic Algorithms for Tuberculosis in Children Less Than 5 Years of Age","volume":"36","author":"AK Debes","year":"2017","journal-title":"Pediatr Infect Dis J"},{"key":"pmed.1004285.ref014","doi-asserted-by":"crossref","first-page":"e058388","DOI":"10.1136\/bmjopen-2021-058388","article-title":"Xpert Ultra stool testing to diagnose tuberculosis in children in Ethiopia and Indonesia: a model-based cost-effectiveness analysis","volume":"12","author":"N Mafirakureva","year":"2022","journal-title":"BMJ Open"},{"key":"pmed.1004285.ref015","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1136\/thoraxjnl-2011-200933","article-title":"Modelling the cost-effectiveness of strategies to prevent tuberculosis in child contacts in a high-burden setting","volume":"68","author":"AM Mandalakas","year":"2013","journal-title":"Thorax"},{"key":"pmed.1004285.ref016","doi-asserted-by":"crossref","first-page":"100707","DOI":"10.1016\/j.eclinm.2020.100707","article-title":"Cost-effectiveness of scaling up short course preventive therapy for tuberculosis among children across 12 countries","volume":"31","author":"Y Jo","year":"2021","journal-title":"EClinicalMedicine"},{"key":"pmed.1004285.ref017","article-title":"The global impact of household contact management for children on multidrug-resistant and rifampicin-resistant tuberculosis cases, deaths, and health-system costs in 2019: a modelling study","author":"PJ Dodd","year":"2022","journal-title":"Lancet Glob Health"},{"key":"pmed.1004285.ref018","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/S1473-3099(16)30474-1","article-title":"Mortality in children diagnosed with tuberculosis: a systematic review and meta-analysis","volume":"17","author":"HE Jenkins","year":"2017","journal-title":"Lancet Infect Dis"},{"key":"pmed.1004285.ref019","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1136\/thoraxjnl-2016-209421","article-title":"The impact of HIV and antiretroviral therapy on TB risk in children: a systematic review and meta-analysis","volume":"72","author":"PJ Dodd","year":"2017","journal-title":"Thorax"},{"key":"pmed.1004285.ref020","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1183\/09031936.00070812","article-title":"Contact investigation for tuberculosis: a systematic review and meta-analysis","volume":"41","author":"GJ Fox","year":"2013","journal-title":"Eur Respir J"},{"key":"pmed.1004285.ref021","article-title":"The effectiveness of contact investigation among contacts of tuberculosis patients: a systematic review and meta-analysis","author":"K Velen","year":"2021","journal-title":"Eur Respir J"},{"key":"pmed.1004285.ref022","doi-asserted-by":"crossref","first-page":"1631","DOI":"10.1093\/cid\/ciab652","article-title":"Vikela Ekhaya: A Novel, Community-based, Tuberculosis Contact Management Program in a High Burden Setting","volume":"74","author":"AW Kay","year":"2022","journal-title":"Clin Infect Dis"},{"key":"pmed.1004285.ref023","doi-asserted-by":"crossref","first-page":"e1774","DOI":"10.1016\/S2214-109X(22)00414-4","article-title":"Global impact of COVID-19 on childhood tuberculosis: an analysis of notification data","volume":"10","author":"L Ranasinghe","year":"2022","journal-title":"Lancet Glob Health"},{"key":"pmed.1004285.ref024","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1186\/s12889-020-08741-2","article-title":"Integrating pediatric TB services into child healthcare services in Africa: study protocol for the INPUT cluster-randomized stepped wedge trial.","volume":"20","author":"L Denoeud-Ndam","year":"2020","journal-title":"BMC Public Health"},{"key":"pmed.1004285.ref025","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1186\/s40814-022-00996-3","article-title":"Feasibility of a randomized clinical trial evaluating a community intervention for household tuberculosis child contact management in Cameroon and Uganda","volume":"8","author":"A Vasiliu","year":"2022","journal-title":"Pilot Feasibility Stud"},{"key":"pmed.1004285.ref026","doi-asserted-by":"crossref","first-page":"38","DOI":"10.5588\/ijtld.21.0257","article-title":"How much does TB screening cost? 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