Impact of an Innovative Childhood TB Diagnostic Approach Decentralized to District Hospital and Primary Health Care Levels on Childhood Tuberculosis Case Detection and Management in High Tuberculosis Incidence Countries (TB-Speed Decentralisation)

Impact of an Innovative Childhood TB Diagnostic Approach Decentralized to District Hospital and Primary Health Care Levels on Childhood Tuberculosis Case Detection and Management in High Tuberculosis Incidence Countries

The TB-Speed Decentralisation study aims to increase childhood Tuberculosis (TB) case detection at district hospital (DH) and Primary health Care (PHC) levels using adapted and child-friendly specimen collection methods, i.e. Nasopharyngeal Aspirate (NPA) and stool samples, sensitive microbiological detection tests (Ultra) close to the point-of-care (Omni/G1(Edge)), reinforced training on clinical diagnosis, and standardized CXR quality and interpretation using digital radiography.

The TB-Speed Decentralisation study will evaluate the impact of an innovative patient care level diagnostic approach deployed at DH and PHC levels, namely the DH focused and the PHC focused decentralization strategies. This is aimed at, improving case detection in 6 high TB incidence in low/moderate resource countries: Cambodia, Cameroon, Côte d'Ivoire, Mozambique, Sierra Leone, and Uganda, and compare effectiveness and cost-effectiveness of the two different decentralization approaches.

The hypothesis is that, in countries with high and very high TB incidence (100-299 and ≥300 cases/100,000 population/year, respectively), a systematic approach to the screening for and diagnosis of TB in sick children presenting to the health system will increase childhood TB case detection, especially PTB, which represents the majority of the disease burden (>75% of case). The study also hypothesizes that sputum collection using battery-operated suction machines and microbiological TB diagnosis using Omni/G1 (Edge) can be decentralized to PHC level, thus enabling TB diagnosis and treatment in children at PHC level.

Study Overview

• Status: Completed
• Conditions: Tuberculosis in Children
• Intervention / Treatment: Other: Decentralization of Childhood TB Diagnosis

Detailed Description

This will be an operational research study using:

• a before and after cross-sectional design to assess the impact of decentralizing an innovative childhood TB diagnostic approach
• a cross-sectional and nested cohort design to compare two different decentralization strategies at DH and PHC levels.
• quantitative and qualitative methods The intervention will be at two levels: at patient care level where an innovative childhood TB diagnostic approach will be implemented, and at health systems level where two distinct decentralization strategies will be implemented. The patient care level TB diagnostic approach consists of systematic TB screening, clinical evaluation, NPA and stool or sputum testing using Xpert Ultra, and optimised CXR reading. The two decentralization strategies are the DH-focused and the PHC-focused implementation of the innovative childhood TB diagnostic approach. Two districts per participating countries will be randomly assigned to implement the DH or PHC-focused strategies.

The study will also include a nested cohort at both the DH and PHC during the intervention phase for a selected sub-set of children with presumptive TB and all children with a diagnosis of TB that consent to participate. This prospective cohort will enable to further document study endpoints related to follow up (TB treatment outcome) and to document TB diagnosis by assessing spontaneous resolution or resolution under TB treatment.

The study will comprise an observation phase followed by an intervention phase in participating districts. During the last month of the observation phase, each district will be randomly assigned to implement either DH or PHC-focused decentralisation. There will be no patient level randomisation.

During this 3-month observation phase, the study will 1) describe the childhood TB diagnosis data and practices; 2) describe the referral processes and outcomes of referrals for TB diagnosis and treatment where feasible and 3) assess existing challenges in childhood TB diagnosis and treatment, as well as readiness (including potential challenges) for the study intervention implementation. There will be no interference with the routine TB childhood diagnosis processes.

Mixed-methods (quantitative and qualitative) will be used including the collection of retrospective and prospective aggregated data by study nurses from facility registers, the implementation of a self-administered questionnaire among all healthcare workers (HCWs), the observation of consultations and care provided, and the conduct of individual interviews with HCWs and key informants.

At the beginning of the intervention phase, a 3-months preparation period will set up the health facilities for decentralization by providing equipment, materials, and reagents, training health workers in childhood TB care, in NPA and stool collection and testing on Ultra, setting up G1 (Edge) at PHC or G4 at DH if not already available and digital CXR and CXR quality control. Existing health care workers will be trained in childhood TB care according to the National Tuberculosis Program (NTP) guidelines, and also in NPA and stool collection and testing on Ultra for study purposes.

Implementation of the innovative childhood TB diagnostic approach at the selected DH and PHC will start as soon as sites are equipped and HCWs trained in childhood TB care and NPA and stool collection, and will implement continued capacity building at sites, regular clinical mentoring visits with NTP or their representative, and continued CXR quality control.

The 6-month prospective cohort follow-up study will be initiated immediately and will consecutively include every tenth child with presumptive TB and all children diagnosed with TB.

Individual data collection will be initiated as soon as the innovative childhood TB diagnostic approach including NPA and stool sample collection and Ultra testing is implemented in the site and will be conducted throughout the intervention phase to document secondary endpoints. Aggregated data for TB screening will be collected throughout the study.

Feasibility, acceptability, and compliance to the intervention protocol will be assessed by mixed methods including a repeat self-administered questionnaire among all HCWs, observations of consultations and care provided, and individual interviews with HCWs, National TB program & local health authorities representatives, and beneficiaries. i.e. parents/guardians.

• Study Type: Interventional
• Enrollment (Actual): 3106
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Cambodia
  • Angroka, Cambodia
    • Angroka Rh
  • Angroka, Cambodia
    • Taphem Hc
  • Angroka, Cambodia
    • Tropang Andert Hc
  • Batheay, Cambodia
    • Batheay Rh
  • Batheay, Cambodia
    • Choeung Chnok Hc
  • Batheay, Cambodia
    • Tumnub Hc
  • KUS, Cambodia
    • KUS HC
  • Nhaeng Nhang, Cambodia
    • Nhaeng Nhang Hc
  • Phaav, Cambodia
    • Phaav HC
  • Sambour, Cambodia
    • Sambour Hc
• Cameroon
  • Bafia, Cameroon
    • Csi Messngssang
  • Bafia, Cameroon
    • HD BAFIA
  • Balamba, Cameroon
    • Csi Balamba Bafia
  • Batchenga, Cameroon
    • Cma Batchenga
  • Bokito, Cameroon
    • Cma Bokito Bafia
  • Essong, Cameroon
    • Csi Essong
  • Kiiki, Cameroon
    • Cma Kiiki Bafia
  • Obala, Cameroon
    • Cma Fomakap
  • Obala, Cameroon
    • Csi Ngogo
  • Obala, Cameroon
    • Obala Hosp
• Côte D'Ivoire
  • Banteapleu, Côte D'Ivoire
    • Dr Banteapleu
  • Dakpadou, Côte D'Ivoire
    • Csu Dakpadou
  • Daleu, Côte D'Ivoire
    • Csr Daleu
  • Danane, Côte D'Ivoire
    • H G de Danane
  • Kouan-houle, Côte D'Ivoire
    • Csu Kouan-Houle
  • Mahapleu, Côte D'Ivoire
    • Csu Mahapleu
  • Medon, Côte D'Ivoire
    • Csr Medon
  • Sago, Côte D'Ivoire
    • CMS SAGO
  • Sahoua, Côte D'Ivoire
    • Dr de Sahoua
  • Sassandra, Côte D'Ivoire
    • H G Sassandra
• Mozambique
  • Chiaquelane, Mozambique
    • Chiaquelane
  • Chibonzane, Mozambique
    • Chibonzane
  • Chidenguele, Mozambique
    • Chidenguele
  • Chokwe, Mozambique
    • Chalocuane
  • Chokwe, Mozambique
    • HOKWE
  • Chokwe, Mozambique
    • Hosp Rural Chokwe
  • Macuacua, Mozambique
    • MACUACUA
  • Manjacaze, Mozambique
    • Hospital Rural de Manjacaze
  • Manjacaze, Mozambique
    • Laranjeira
• Sierra Leone
  • BO, Sierra Leone
    • Bo Govt Hosp
  • BO, Sierra Leone
    • New Police barracks
  • Babara, Sierra Leone
    • Babara Chc
  • Gbinti, Sierra Leone
    • Gbinti Chc
  • Gerihun, Sierra Leone
    • Gerihun Chc
  • Koribondo, Sierra Leone
    • Koribondo Chc
  • Mange, Sierra Leone
    • Mange Chc
  • Njala, Sierra Leone
    • Njala University Chc
  • Petifu, Sierra Leone
    • Petifu Chc
  • Port Loko, Sierra Leone
    • Port Loko Govt Hosp
• Uganda
  • Buyamba, Uganda
    • Buyamba Hc Iii
  • Kambuga, Uganda
    • Kambuga Hospital
  • Kanungu, Uganda
    • Kanungu Hciv
  • Kanyantorogo, Uganda
    • Kanyantorogo Hciii
  • Lwamaggwa, Uganda
    • Lwamaggwa Hc Iii
  • Lwanda, Uganda
    • Lwanda Hc Iii
  • Manya, Uganda
    • St Bernards Manya Hc Iii
  • Matanda, Uganda
    • Matanda Hciii
  • Nyamirama, Uganda
    • Nyamirama HC III
  • Rakai, Uganda
    • Rakai Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 14 years (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Sick children seeking care at Oupatient Department of District Hospital or Primary Health Center
• Age <15 years

Exclusion Criteria:

- None

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: District Hospital focused decentralization strategy; In this strategy, the patient care level innovative childhood TB diagnostic approach will be implemented at the DH level. PHCs in this district, will only conduct systematic TB screening.	Other: Decentralization of Childhood TB Diagnosis; The patient care level TB diagnostic approach consists of systematic TB screening, clinical evaluation, NPA and stool or sputum testing using Xpert Ultra, and optimised CXR reading will be implemented at DH and PHC levels
Experimental: Primary Health Center focused decentralization strategy; In this strategy, the patient care level innovative childhood TB diagnostic approach will be done at the PHC.	Other: Decentralization of Childhood TB Diagnosis; The patient care level TB diagnostic approach consists of systematic TB screening, clinical evaluation, NPA and stool or sputum testing using Xpert Ultra, and optimised CXR reading will be implemented at DH and PHC levels

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Children diagnosed with TB	Proportion of TB cases detected among sick children routinely attending outpatient services before and after the intervention	Day 0

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
TB case detection	Proportion of TB cases (confirmed and unconfirmed) detected among children identified as presumptive TB	Month 6
TB treatment uptake and time to TB treatment initiation - 1	Proportion of children initiating TB treatment among those diagnosed as TB	Month 6
TB treatment uptake and time to TB treatment initiation - 2	Time from positive TB screening to TB treatment initiation	Month 6
Cost-effectiveness from the health services perspective	Incremental-Cost Effectiveness Ratio (ICER) of the diagnostic approach	Month 22
Acceptability by health care providers, NTPs and health authorities, and beneficiaries	Perceptions and experience of the intervention by healthcare workers (HCWs), the NTP and health authorities, and the beneficiaries (parents/guardians)	Day 0
Fidelity of the implementation of the diagnostic approach as compared to the protocol and study procedures - 1	Changes in the intervention implementation as compared to 1) study standard implementation procedures and 2) country implementation procedures. These changes could be related to NTP guidelines dispositions, adaptation to local context and constraints not initially planned per standard and country implementation procedures	Month 6
Fidelity of the implementation of the diagnostic approach as compared to the protocol and study procedures - 2	Proportion of clinical mentoring visits performed per study procedures; proportion of health facilities implementing NPA and stool sample collection and performing sample processing and Ultra testing per study procedures	Month 22
Performance of the diagnostic approach at patient level	Sensitivity and specificity of the diagnostic approach as compared to the reference diagnosis based on the Case Definitions for Classification of Intrathoracic Tuberculosis in Children for clinical research	Month 6
TB treatment outcome	TB treatment outcome as defined by WHO	Month 6
Diagnostic performance of CXR reading by clinicians at DH and PHC levels	Sensitivity and specificity of CXR reading by clinicians at DH and PHC to detect lesions suggestive of TB as compared to the reference reading (independent reading by external radiologist experts)	Month 6
Added value of CXR in the diagnosis of TB in children as compared to microbiology and clinical evaluation only	Proportion of children diagnosed with TB based on CXR and incremental yield of TB detection with CXR results as compared to microbiological (Ultra on NPA and stool or sputum) and clinical evaluation, respectively	Month 6
Uptake of the quality control of the CXR reading	Proportion of CXR selected for quality review assessed by the reference reviewer and time to results of the quality control to the clinic	Month 6
TB screening in outpatient children - 1	Proportion of children screened for TB among sick children attending outpatient services	Day 7
TB screening in outpatient children - 2	Proportion of children identified with presumptive TB among children screened	Day 7
Feasibility of implementing the different diagnostic approach components - 1	Proportion of children with presumptive TB enrolled in the study receiving the different components of the innovative childhood TB diagnostic approach (NPA and stool or sputum sampling attempt and success, sample testing with Ultra and results, clinical evaluation, CXR and interpretation, full diagnostic package)	Day 7
Feasibility of implementing the different diagnostic approach components - 2	Time to sample test and results delivery to clinician	Day 7
Feasibility of implementing the different diagnostic approach components - 3	Number of visits to the health facility until final diagnosis	Day 7

Collaborators and Investigators

• Sponsor: Institut National de la Santé Et de la Recherche Médicale, France
• Collaborators: UNITAID
• Investigators: Principal Investigator: Olivier Marcy, PhD, University of Bordeaux; Principal Investigator: Maryline Bonnet, PhD, Institut de Recherche pour le Developpement; Principal Investigator: Eric Wobudeya, PhD, MU-JHU Care Ltd

Publications and helpful links

General Publications

• Joshi B, De Lima YV, Massom DM, Kaing S, Banga MF, Kamara ET, Sesay S, Borand L, Taguebue JV, Moh R, Khosa C, Breton G, Mwanga-Amumpaire J, Bonnet M, Wobudeya E, Marcy O, Orne-Gliemann J; TB-Speed Decentralization study group. Acceptability of decentralizing childhood tuberculosis diagnosis in low-income countries with high tuberculosis incidence: Experiences and perceptions from health care workers in Sub-Saharan Africa and South-East Asia. PLOS Glob Public Health. 2023 Oct 11;3(10):e0001525. doi: 10.1371/journal.pgph.0001525. eCollection 2023.

Helpful Links

• TB-Speed project official website

Study record dates

Study Major Dates

• Study Start (Actual): March 7, 2020
• Primary Completion (Actual): March 31, 2022
• Study Completion (Actual): March 31, 2022

Study Registration Dates

• First Submitted: June 6, 2019
• First Submitted That Met QC Criteria: July 26, 2019
• First Posted (Actual): July 31, 2019

Study Record Updates

• Last Update Posted (Actual): March 26, 2025
• Last Update Submitted That Met QC Criteria: March 25, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: Case detection; Childhood TB; Decentralized Diagnosis approaches
• Additional Relevant MeSH Terms: Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Actinomycetales Infections; Mycobacterium Infections; Tuberculosis
• Other Study ID Numbers: C18-25

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No