Periodic Reporting for period 1 - Decide-TB (Validation of treatment decision algorithms for childhood tuberculosis at low levels of healthcare in high burden countries - effectiveness, implementation, and integration into policy and practices)
Periodo di rendicontazione: 2023-04-01 al 2024-09-30
The End TB Strategy, adopted in 2014, aims to end the TB epidemic by 2035 by reducing TB deaths by 95%. Achieving this goal requires innovative health technologies, better TB prevention and care approaches, and rapid adoption of research-based policies, especially for the most vulnerable populations including children. Annually, 1.2 million children under 15 develop TB, with over 250,000 deaths, occurring in a vast majority in undiagnosed/untreated children. Only 44% of paediatric TB cases are reported, and for children under 5, this drops to 35%. Low case detection is largely due to the paucibacillary nature of the disease and challenges in respiratory sample collection contributing to the low microbiological yield in children. Children with inadequate immunity [e.g. children living with HIV (CLHIV), or those with severe acute malnutrition (SAM)] or severe pneumonia are at higher risk of underdiagnosis and of dying from TB.
The World Health Organization (WHO) has prioritized improved diagnostics in the field of child TB. Currently, in the absence of highly sensitive TB diagnostic tool for children, most children are started on treatment only on the basis of high clinical suspicion. Treatment Decision Algorithms (TDAs) assign scores to clinical and radiographic features or microbiological tests and recommend TB treatment initiation above a pre-defined total score. TDAs enable rapid and uniform treatment decision-making. In 2022, WHO conditionally recommended TDAs for diagnosing pulmonary TB in children under 10 years and suggested two TDAs for use in settings with and without chest X-ray (CXR). Decentralizing childhood TB services is essential to increase access to TB diagnosis and will require strengthening clinical skills and treatment decision-making capacity. Data on the diagnostic accuracy of TDAs, their feasibility, acceptability by end-users, effectiveness, and cost-effectiveness are crucial to update the current WHO policy and operational handbook, national policies, and clinical curricula. A comprehensive TDA-based approach could integrate other specific TDAs developed for CLHIV and those with SAM if they outperform the WHO-suggested TDAs. It would also integrate a disease severity assessment step to enable shorter treatment for non-severe TB cases. These tools should align with healthcare workers’ practices at primary and district levels, supported by digital innovations like clinical decision support systems (CDSS) to improve decentralized TB care quality and delivery.
In this context, the general objective of the Decide-TB project is to generate evidence for the implementation of a comprehensive TDA-based approach for TB in children living in high TB-burden and resource-limited countries, at DH and PHC levels, and to facilitate integration of this evidence within practices and policies.
The World Health Organization (WHO) has prioritized improved diagnostics in the field of child TB. Currently, in the absence of highly sensitive TB diagnostic tool for children, most children are started on treatment only on the basis of high clinical suspicion. Treatment Decision Algorithms (TDAs) assign scores to clinical and radiographic features or microbiological tests and recommend TB treatment initiation above a pre-defined total score. TDAs enable rapid and uniform treatment decision-making. In 2022, WHO conditionally recommended TDAs for diagnosing pulmonary TB in children under 10 years and suggested two TDAs for use in settings with and without chest X-ray (CXR). Decentralizing childhood TB services is essential to increase access to TB diagnosis and will require strengthening clinical skills and treatment decision-making capacity. Data on the diagnostic accuracy of TDAs, their feasibility, acceptability by end-users, effectiveness, and cost-effectiveness are crucial to update the current WHO policy and operational handbook, national policies, and clinical curricula. A comprehensive TDA-based approach could integrate other specific TDAs developed for CLHIV and those with SAM if they outperform the WHO-suggested TDAs. It would also integrate a disease severity assessment step to enable shorter treatment for non-severe TB cases. These tools should align with healthcare workers’ practices at primary and district levels, supported by digital innovations like clinical decision support systems (CDSS) to improve decentralized TB care quality and delivery.
In this context, the general objective of the Decide-TB project is to generate evidence for the implementation of a comprehensive TDA-based approach for TB in children living in high TB-burden and resource-limited countries, at DH and PHC levels, and to facilitate integration of this evidence within practices and policies.
Major progress has been made over the first 18 months of the project. The project was launched on April 1st 2023 with an online kick off meeting which gathered all consortium members. In June 2023, consortium members gathered in Cape Town for a face-to-face 4-day workshop to make progress within WP and to discuss subsequent steps. In July 2023 NTPs from both countries organized Country clinical workshops together with UNZA, INS, and IRD. Attended by key stakeholders and members of the DTB consortium (WP4), these workshops aimed to adapt and adopt the WHO recommendation to use TDA for children and to design a comprehensive TDA-based approach for TB screening, diagnosis, and management in children based on national TB program’s perspectives. Country workshops reports were written to synthetize possible adaptation to the proposed TDAs and to describe the comprehensive TDA-based approach, as well as consideration for implementation and data collection. They were formally approved by both NTP for pilot testing.
The Decide-TB trial protocol v1.0 was developed, approved, and submitted to country ethics committees in 28/072023 (WP2). It was approved in Zambia on 24/11/2023 and in Mozambique on 12/06/2024 (WP2). Between September and December 2023, the IPD meta-analysis protocol was finalised (WP3). The site selection survey was conducted in both countries to select districts where to implement the programmatic pilot (WP6). An individual data entry module (Electronic Medical Record - EMR) for individual clinical data collection was developed (WP2 and WP4) and made available on servers at INS (Mozambique) and MOH in Zambia on the DHIS2 system (WP5). The DTB consortium members met in Paris during the Union conference in November 2023. The formative phase research was conducted from February-March 2024, in Zambia (WP2-WP6) and in June-July 2024 in Mozambique. The health economics analysis plan was finalised (WP7). Training curricula and job aides for health care workers (HCW) were developed (WP4). The DTB protocol was amended and resubmitted to ethics committees in both countries in May 2024. It was approved in July in Zambia and in October in Mozambique. The DTB trial started with data collection in the Standard of Care (SOC) phase on June 1st in Zambia and on 21st July in Mozambique. HCW were trained in data collection at SOC phase using the registers digitalized in DHIS2. Training of trainers in Zambia happened in July (WP4). The first district switched to the intervention phase on 1 September in Zambia; HCW in selected facilities were trained on childhood TB, TDAs and the EMR and started using TDAs.
The Decide-TB trial protocol v1.0 was developed, approved, and submitted to country ethics committees in 28/072023 (WP2). It was approved in Zambia on 24/11/2023 and in Mozambique on 12/06/2024 (WP2). Between September and December 2023, the IPD meta-analysis protocol was finalised (WP3). The site selection survey was conducted in both countries to select districts where to implement the programmatic pilot (WP6). An individual data entry module (Electronic Medical Record - EMR) for individual clinical data collection was developed (WP2 and WP4) and made available on servers at INS (Mozambique) and MOH in Zambia on the DHIS2 system (WP5). The DTB consortium members met in Paris during the Union conference in November 2023. The formative phase research was conducted from February-March 2024, in Zambia (WP2-WP6) and in June-July 2024 in Mozambique. The health economics analysis plan was finalised (WP7). Training curricula and job aides for health care workers (HCW) were developed (WP4). The DTB protocol was amended and resubmitted to ethics committees in both countries in May 2024. It was approved in July in Zambia and in October in Mozambique. The DTB trial started with data collection in the Standard of Care (SOC) phase on June 1st in Zambia and on 21st July in Mozambique. HCW were trained in data collection at SOC phase using the registers digitalized in DHIS2. Training of trainers in Zambia happened in July (WP4). The first district switched to the intervention phase on 1 September in Zambia; HCW in selected facilities were trained on childhood TB, TDAs and the EMR and started using TDAs.
We have designed a comprehensive TDA-based approach for use at lower level of healthcare, and started testing by NTPs in a programmatic pilot in Mozambique and Zambia. We have developed a CDSS and strengthen district information systems to collect individual data, which will contribute to monitoring and evaluation, clinical mentoring, and supervision by NTPs and to research. We started testing comprehensive TDA-based approach in the Decide-TB trial. In parallel, the diagnostic accuracy of different TDAs is being assessed through an IPD meta-analysis. Overall, the project will contribute to thorough external validation of the WHO-suggested TDAs. Preliminary results have been presented at the Union Conference in November 2024. Furthermore, key stakeholders and decision-makers have been engaged in both countries and this will continue throughout the project. It will facilitate translation of the overall integrated TDA approach into clinical and implementation practices as well as policy at national and international levels.