Olivia Oxlade1, Andrea Benedetti1, Mênonli Adjobimey2, Hannah Alsdurf1, Severin Anagonou3, Victoria J Cook4, Dina Fisher5, Greg J Fox6, Federica Fregonese1, Panji Hadisoemarto7, Philip C Hill8, James Johnston4, Faiz Ahmad Khan1, Richard Long9, Nhung V Nguyen10, Thu Anh Nguyen11, Joseph Obeng12, Rovina Ruslami7, Kevin Schwartzman1, Anete Trajman13, Chantal Valiquette1, Dick Menzies14. 1. McGill International TB Centre, Research Institute of the McGill University Health Centre, McGill University, Montreal, QC, Canada. 2. Centre National Hospitalier Universitaire de Pneumo-Pthisiologie de Cotonou, Cotonou, Benin. 3. National Tuberculosis Program, Cotonou, Benin. 4. Provincial TB Services, BC Centre for Disease Control, Vancouver, BC, Canada; Division of Respiratory Medicine, Department of Medicine, University of British Columbia, Vancouver, BC, Canada. 5. University of Calgary, Calgary, AB, Canada. 6. The Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia. 7. TB-HIV Research Center, Faculty of Medicine, Universitas Padjadjaran, Bandung, Indonesia; Department of Public Health, Faculty of Medicine, Universitas Padjadjaran, Bandung, Indonesia. 8. Centre for International Health, Faculty of Medicine, University of Otago, Otago, New Zealand. 9. Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada. 10. The National Lung Hospital, Hanoi, Vietnam. 11. The Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia; The Woolcock Institute of Medical Research in Vietnam, Hanoi, Vietnam. 12. Ministry of Health, Accra, Ghana. 13. McGill International TB Centre, Research Institute of the McGill University Health Centre, McGill University, Montreal, QC, Canada; Federal University of Rio de Janeiro, Rio de Janeiro, Brazil. 14. McGill International TB Centre, Research Institute of the McGill University Health Centre, McGill University, Montreal, QC, Canada. Electronic address: dick.menzies@mcgill.ca.
Abstract
BACKGROUND: Reaching the UN General Assembly High-Level Meeting on Tuberculosis target of providing tuberculosis preventive treatment to at least 30 million people by 2022, including 4 million children under the age of 5 years and 20 million other household contacts, will require major efforts to strengthen health systems. The aim of this study was to evaluate the effectiveness and cost-effectiveness of a health systems intervention to strengthen management for latent tuberculosis infection (LTBI) in household contacts of confirmed tuberculosis cases. METHODS: ACT4 was a cluster-randomised, open-label trial involving 24 health facilities in Benin, Canada, Ghana, Indonesia, and Vietnam randomly assigned to either athree-phase intervention (LTBI programme evaluation, local decision making, and strengthening activities) or control (standard LTBI care). Tuberculin and isoniazid were provided to control and intervention sites if not routinely available. Randomisation was stratified by country and restricted to ensure balance of index patients with tuberculosis by arm and country. The primary outcome was the number of household contacts who initiated tuberculosis preventive treatment at each health facility within 4 months of the diagnosis of the index case, recorded in the first or last 6 months of our 20-month study. To ease interpretation, this number was standardised per 100 newly diagnosed index patients with tuberculosis. Analysis was by intention to treat. Masking of staff at the coordinating centre and sites was not possible; however, those analysing data were masked to assignment of intervention or control. An economic analysis of the intervention was done in parallel with the trial. ACT4 is registered at ClinicalTrials.gov, NCT02810678. FINDINGS: The study was done between Aug 1, 2016, and March 31, 2019. During the first 6 months of the study the crude overall proportion of household contacts initiating tuberculosis preventive treatment out of those eligible at intervention sites was 0·21. After the implementation of programme strengthening activities, the proportion initiating tuberculosis preventive treatment increased to 0·35. Overall, the number of household contacts initiating tuberculosis preventive treatment per 100 index patients with tuberculosis increased between study phases in intervention sites (adjusted rate difference 60, 95% CI 4 to 116), while control sites showed no statistically significant change (-12, -33 to 10). There was a difference in rate differences of 72 (95% CI 10 to 134) contacts per 100 index patients with tuberculosis initiating preventive treatment associated with the intervention. The total cost for the intervention, plus LTBI clinical care per additional contact initiating treatment was estimated to be CA$1348 (range 724 to 9708). INTERPRETATION: A strategy of standardised evaluation, local decision making, and implementation of health systems strengthening activities can provide a mechanism for scale-up of tuberculosis prevention, particularly in low-income and middle-income countries. FUNDING: Canadian Institutes of Health Research.
RCT Entities:
BACKGROUND: Reaching the UN General Assembly High-Level Meeting on Tuberculosis target of providing tuberculosis preventive treatment to at least 30 million people by 2022, including 4 million children under the age of 5 years and 20 million other household contacts, will require major efforts to strengthen health systems. The aim of this study was to evaluate the effectiveness and cost-effectiveness of a health systems intervention to strengthen management for latent tuberculosis infection (LTBI) in household contacts of confirmed tuberculosis cases. METHODS: ACT4 was a cluster-randomised, open-label trial involving 24 health facilities in Benin, Canada, Ghana, Indonesia, and Vietnam randomly assigned to either a three-phase intervention (LTBI programme evaluation, local decision making, and strengthening activities) or control (standard LTBI care). Tuberculin and isoniazid were provided to control and intervention sites if not routinely available. Randomisation was stratified by country and restricted to ensure balance of index patients with tuberculosis by arm and country. The primary outcome was the number of household contacts who initiated tuberculosis preventive treatment at each health facility within 4 months of the diagnosis of the index case, recorded in the first or last 6 months of our 20-month study. To ease interpretation, this number was standardised per 100 newly diagnosed index patients with tuberculosis. Analysis was by intention to treat. Masking of staff at the coordinating centre and sites was not possible; however, those analysing data were masked to assignment of intervention or control. An economic analysis of the intervention was done in parallel with the trial. ACT4 is registered at ClinicalTrials.gov, NCT02810678. FINDINGS: The study was done between Aug 1, 2016, and March 31, 2019. During the first 6 months of the study the crude overall proportion of household contacts initiating tuberculosis preventive treatment out of those eligible at intervention sites was 0·21. After the implementation of programme strengthening activities, the proportion initiating tuberculosis preventive treatment increased to 0·35. Overall, the number of household contacts initiating tuberculosis preventive treatment per 100 index patients with tuberculosis increased between study phases in intervention sites (adjusted rate difference 60, 95% CI 4 to 116), while control sites showed no statistically significant change (-12, -33 to 10). There was a difference in rate differences of 72 (95% CI 10 to 134) contacts per 100 index patients with tuberculosis initiating preventive treatment associated with the intervention. The total cost for the intervention, plus LTBI clinical care per additional contact initiating treatment was estimated to be CA$1348 (range 724 to 9708). INTERPRETATION: A strategy of standardised evaluation, local decision making, and implementation of health systems strengthening activities can provide a mechanism for scale-up of tuberculosis prevention, particularly in low-income and middle-income countries. FUNDING: Canadian Institutes of Health Research.
Authors: Jennifer M Ross; Yongquan Xie; Yaqi Wang; James K Collins; Cody Horst; Jessie B Doody; Paulina Lindstedt; Jorge R Ledesma; Adrienne E Shapiro; Prof Simon I Hay; Hmwe H Kyu; Abraham D Flaxman Journal: EClinicalMedicine Date: 2021-11-21