Tuberculosis (TB) is a leading infectious cause of morbidity and mortality worldwide, accounting for 10 million new cases and 1.6 million deaths in 2017. The disease burden is disproportionately concentrated in low- and middle-income countries with over 95% of TB deaths contributed by these regions. In 2016, the number of new TB cases was estimated at 10 million, and nearly 40% remained undiagnosed. Limited access to health care, high treatment cost, and social stigma of TB contributed to delayed detection and poor treatment uptake. Other risk factors such as poor living conditions and overcrowding further perpetuated the transmission of TB, which, in turn, leads to social and economic insecurity. Cambodia is one of the countries with the world's highest burden of TB, with an estimated incidence of active TB of 326 (95% CI: 224-447) per 100,000 population in 2017. Through the years, TB control programs in Cambodia has achieved significant milestones made possible by committed partners and focused efforts at the grassroots, national, and international level. In 2016, the TB incidence was approximately half of that in the year 2000, and a similar decline was observed in the TB mortality rate. Furthermore, the country has made notable progress in the fight against TB by achieving a treatment success rate of 94%, one of the highest among the 30 high TB burden countries.

However, the successes are impeded by a significant proportion of undiagnosed cases. Globally, it is estimated that 36% of the TB cases were undiagnosed in 2017, and a similar proportion is observed in Cambodia. Traditionally, TB cases are captured and passively notified when people with TB present themselves to a health facility. In recent years, a more proactive strategy to increase TB case notification, namely active case finding (ACF) has gained traction and is reported to be effective. Alongside passive case finding (PCF), the ACF strategy has been adopted by countries affected by the epidemic, including Cambodia, to reach people with TB effectively. Nevertheless, despite increased efforts to improve case detection, TB case finding remains a great challenge due to limited resources, geographical barriers, and social stigma. The current approaches rely solely on skilled healthcare workers and community health volunteers to find TB cases. Its utility and sustainability, in the long run, have yet to be substantially demonstrated.

Empirically, a snowball approach (seed-and-recruit mechanism) has been widely accepted to reach concealed populations such as populations who are at-risk for HIV in many countries, including Cambodia, due to its practical feasibility. A community-based peer-led strategy as such has been an inherent component in HIV responses worldwide, and successes have been reported. However, little is known about the feasibility and effectiveness of ACF with the snowball model in improving TB case notification. However, given the comparable hard-to-reach nature of HIV and TB populations, it is a concept worth exploring. In partnership with KHANA, the National Center for Tuberculosis and Leprosy Control (CENAT), and the Cambodia Anti-Tuberculosis Association (CATA), this project seeks to examine the effectiveness of different ACF strategies in increasing TB case notification in the community and its impact on treatment outcome. This project is congruent with the global plan to end TB. and the Global Fund's strategy 2017-2022 by informing sustainable and evidence-based solutions for TB control in Cambodia.

We will conduct a cluster randomized controlled trial with four arms comparing ACF with the seed-and-recruit model, other ACF approaches, and PCF approach in eight operational districts in Cambodia. The project will be carried out over two years. ACF with the seed-and-recruit model by KHANA, ACF targeting household and neighborhood contacts by CENAT, ACF targeting the older population using mobile screening units by CATA will be implemented in the intervention arms and PCF will be implemented in the control arm. These case finding strategies have been piloted in Cambodia, and they are endorsed by the national TB program in Cambodia. This study will randomize currently underserved operational districts (without active intervention, at least in the past six months from the implementation date). The interventions will be carried out as per the protocol devised by the partner organizations, respectively.

This study aims to 1) evaluate the effectiveness of an ACF strategy using a seed-and-recruit model for increasing TB case notification (case notification rate, additionality, comparing the yield in each arm with its respective historical baseline and the cumulative yield over the implementation period) in Cambodia, 2) establish the effect of ACF strategies on TB treatment outcomes, 3) evaluate number needed to screen to detect one TB case and the cost-effectiveness (costs per TB case notified) of different ACF strategies.