SCAF-TB - Saving Children and Their Families From Tuberculosis: Implementation Research to Improve TB Preventive Treatment Initiation and Completion Rates Among Contact Persons in Tajikistan and Tanzania

Despite renewed global commitments to end TB, as reinforced by the UNHLM on TB, progress remains insufficient to meet TB elimination targets. A critical barrier is the limited reach and uptake of TPT, which continues to rely heavily on facility-based models that are often inaccessible or burdensome for those at risk. A fundamental shift toward broader, community-delivered TPT is urgently needed to close this implementation gap.

One key limitation in current TBI diagnostics, such as the traditional tuberculin skin test (TST), is the requirement for a follow-up visit 48-72 hours after administration to measure the result. This return visit is usually at the clinic, typically performed by a healthcare worker (HCW), which introduces significant challenges including loss to follow-up, logistical burden, and variability in result interpretation. These issues hinder timely initiation of TPT. The SCAF-TB study aims to evaluate a novel, home-based TB infection testing model using the WHO-endorsed SIILTIBCY skin test combined with a skin patch diagnostic paired with an AI-driven smartphone application to enable community-based result interpretation. This approach eliminates the need for clinic visits and may reduce inter-reader variability by leveraging technology for standardized, home-based result reading.

Apart from that, TB screening currently depends largely on chest X-rays, which are not always easily accessible and often require visits to healthcare facilities. New, more portable screening technologies-such as the AudibleHealth AI platform, which uses machine learning to analyze cough sounds and flag potential respiratory infections such as TB-could offer an innovative alternative. This study aims to evaluate the feasibility of this tool in detecting TB patients, providing evidence on whether such digital solutions can support or enhance future TB screening strategies at community level.

Moreover, prior studies have demonstrated that shifting TPT services from healthcare facilities to community-based delivery-particularly through community health workers (CHWs)-is not only feasible but also preferred, highly acceptable to patients, and cost-effective in various settings (32). Building on this evidence, SCAF-TB will assess the effectiveness, acceptability, and scalability of this integrated, decentralized TB prevention algorithm.

Objectives The overall goal of SCAF-TB is to improve access to innovative TB preventive services among children and their families in Tanzania and Tajikistan, both settings with a high burden of TB.

The investigators will utilize a type 2 hybrid effectiveness-implementation study design, which has a dual focus on effectiveness and implementation outcomes (33, 34). This multi-country, mixed-methods study includes, an inter-reader agreement study of reading SIILTIBCY results with and without AI-assisted reading, 2) in-depth interviews of key interest-holders, 3) a comparison of TPT uptake and completion rates in close contacts between clinics with and without home-based skin testing and AI-assisted reading, and 4) budget impact assessments.

The investigators will utilize an adaptation of the RE-AIM framework. The investigators propose an integrated work stream to determine the impact of the SCAF-TB model compared to the standard of care.

This study will be conducted in high-volume primary health care facilities located in Tajikistan and Tanzania. The selection of clinics within each country will be carried out in close consultation with the respective National TB Programs (NTPs) to ensure alignment with national priorities and operational feasibility. Tajikistan and Tanzania were chosen based on a set of strategic criteria: Tajikistan represents a high-burden country for multidrug-resistant tuberculosis (MDR-TB), while Tanzania faces a significant burden of both TB and TB/HIV co-infection. Both countries have demonstrated a clear willingness through their NTPs to introduce TBI testing using SIILTIBCY. Additionally, they have programmatic access to short-course TPT regimens, which are actively prescribed within their health systems. Their national guidelines also support the initiation of TPT for contact persons regardless of age, reinforcing the feasibility of broad implementation. Importantly, both countries host KNCV-affiliated offices, which will serve as key implementing partners throughout the study.

Tajikistan, a landlocked country in Central Asia, continues to face a high burden of TB, with one of the highest incidence rates in the WHO European Region. In 2023, an estimated 8,200 people were living with TB disease in 2023 out of which 620 were estimated to be children, out of whom 273 (44%) were notified. Contributing factors include poverty, malnutrition, limited access to quality healthcare, and significant labor migration, which increases transmission risk. MDR-TB poses a growing challenge, accounting for a considerable proportion of new and retreatment patients. In response, the government, in collaboration with international partners such as the WHO and the Global Fund, is focusing on early case detection, improved diagnostics (including GeneXpert), and expanded access to MDR-TB treatment. Community-based interventions and cross-border collaboration are also being strengthened to control TB transmission and improve treatment outcomes. 52% of household contacts (or all close contacts) of all ages started on TPT out of those eligible in 2023. In Tajikistan, the study is planned to be implemented in Dushanbe, which will cover 16 medical institutions (in collaboration with Center for Protection of Population from TB in Dushanbe) and 15 city polyclinics in Dushanbe.

Tanzania, located in East Africa, remains among the high TB burden countries globally, with an estimated 122,000 people developing TB disease in 2023, including approximately 20,000 children. Key contributing factors to TB transmission in Tanzania include high HIV prevalence, poverty, undernutrition, and limited healthcare access in rural and hard-to-reach areas. In response, the Tanzanian government, supported by partners is intensifying efforts on early diagnosis through decentralized services and advanced diagnostics like GeneXpert and digital chest X-rays. Treatment for both drug-sensitive and MDR-TB has been expanded, and the country is also scaling up preventive strategies such as TPT for eligible contacts-nevertheless, just 16% of household contacts of all ages initiated TPT in 2023. Community-based TB care models and integration with HIV services are further strengthening the national response.

In Tanzania, the study will be conducted in two districts of Ilala and Kinondoni located in Dar es Salaam region. Tanzania started implementation of TPT back in 2005 whereby it was given to under-five years of age household contacts of bacteriologically confirmed TB patients and provided at TB clinics. Upon 2011, the TPT was extended to include all people living with HIV (PLHIV) and Isoniazid Preventive Therapy (IPT) was solely given as the TPT. Following the policy and guidelines reviewed in 2025, TPT is recommended for all household contacts of bacteriologically confirmed PTB patients, adults and children living with HIV, prisoners, miners, people who use drugs (PWUDs), and elders after ruling out active TB disease.

At the community level, CHWs are engaged to conduct community sensitization as well as to create demand creation for TPT to help improve health seeking behavior. It is recommended that TPT sensitization be integrated with other routine services done at the community level, including active case finding, TB contact investigation, Reproductive, Maternal, Newborn, Child, and Adolescent Health outreach services, immunization campaigns, HIV services campaigns. CHWs have been trained in how to evaluate TPT eligibility for those at risk using standardized TB screening questionnaires. Following TB screening, all presumptive TB patients are referred for TB testing at health facility level. Those who test TB negative will be eligible for TBI testing and recorded in TPT register for close monitoring and evaluation. Those who will test positive for TB will be enrolled in the TB register and initiated anti TB medication. CHWs are asked to ensure close follow-up of TPT clients (and TB patients) for drugs adherence and completion at their catchment areas of implementation.

Contact persons of bacteriologically confirmed TB patients (so called index patients) who are documented in contact registers at participating Primary Health facilities will be considered for the study. CHWs will proactively visit TB-affected households to screen eligible contacts, particularly children and vulnerable family members. CHWs will also follow up with contact persons after TPT initiation to provide necessary support and manage potential adverse reactions, to improve TPT adherence and completion rate.

In the study clinics, index patients will first agree to home-visits by a CHW. Qualifying TB index patients are defined by the Tajikistan and Tanzanian National TB guidelines and are reflected in the inclusion/exclusion criteria by country. The TB index patient's diagnosis will be kept confidential and only disclosed to household members with permission from the index patient. The consent process will document the index patient's agreement to a home visit and their consent for abstracting their clinical data. Community health teams will make up to three attempts to visit the household. All adults and children under 15 years whose parent or legal guardian consent to study participation (and the child provides assent when appropriate) will be screened for both TB and HIV at home (as per national guidelines). HIV testing will be offered and conducted in the household for all adults and children 18 months and older with unknown HIV status using a rapid HIV test (per local practice and standard of care). Children under 18 months old will be assessed for HIV exposure by both report and evaluation of personal health card. Their care relating to prevention of mother-to-child transmission (PMTCT) will be reviewed including maternal antiretroviral status, infant prophylaxis, and infant testing. If they are not up to date with testing or have been lost to follow up, the community health team will refer that infant/mother pair to the clinic.

Recruitment The visit will begin with contact tracing where the index patient is asked to list all household members. Clinic staff will then ask index patients if the household can be approached by research staff for study participation. The home visit will include (1) TB symptom screening for all children under 5 years, (2) TB disease screening using a combination of symptom screening, AudibleHealth, and portable digital CXR (if available) for all contacts ≥5 years, (3) TBI screening using SIILTIBCY in eligible contacts, (4) TPT initiation for asymptomatic child contacts under 5 years, PLHIV (regardless of age) and contacts diagnosed with TBI, and (5) clinic referral for all symptomatic child contacts under 5 years, contacts ≥5 years of age with presumptive TB or who are ineligible for SIILTIBCY testing (Figure 2). An individual is defined as having presumptive TB if they are symptomatic, screened positive by AudibleHealth, or present with any chest X-ray abnormalities suggestive of TB.

Rule-out TB For children, TB symptom screening will be conducted using the WHO endorsed pediatric symptom screen that will focus on major pediatric symptoms including fever, cough of two weeks or more, wheeze, reduced playfulness or unusual fatigue, lethargy, visible mass in the neck, weight loss or failure to thrive based on clinical report and/or the personal health card. For adults symptom screening will assess whether participants are experiencing cough of any duration, sputum, haemoptysis, fever, night sweats and weight loss (36). In addition to symptom screening to rule-out TB d