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Background: Tuberculosis (TB) is the leading infectious killer worldwide, with approximately 1.8 million deaths in 2015. While effective treatment exists, implementation of active case finding (ACF) methods to identify persons with active TB in a timely and cost-effective manner continues to be a major challenge in resource-constrained settings. Limited qualitative work has been conducted to gain an in-depth understanding of implementation barriers.Methods: Qualitative research was conducted to inform the development of three ACF strategies for TB to be evaluated as part of the Kharitode cluster-randomised trial being conducted in a rural province of South Africa. This included 25 semi-structured in-depth interviews among 8 TB patients, 7 of their household members and 10 clinic health workers, as well as 4 focus group discussions (2 rural and 2 main town locations) with 6-8 participants each (n = 27). Interviews and focus group discussions explored the context, advantages and limitations, as well as the implications of three ACF methods. Content analysis was utilised to document salient themes regarding their feasibility, acceptability and potential effectiveness.Results: Study participants (TB patients and community members) reported difficulty identifying TB symptoms and seeking care in a timely fashion. In turn, all stakeholder groups felt that more proactive case finding strategies would be beneficial. Clinic-based strategies (including screening all patients regardless of visit purpose) were seen as the most acceptable method based on participants' preference ranking of the ACF strategies. However, given the resource constraints experienced by the public healthcare system in South Africa, many participants doubted whether it would be the most effective strategy. Household outreach and incentive-based strategies were described as promising, but participants reported some concerns (e.g. stigma in case of household-based and ethical concerns in the case of incentives). Participants offered insights into how to optimise each strategy, tailoring implementation to community needs (low TB knowledge) and realities (financial constraints, transport, time off from work).Conclusions: Findings suggest different methods of TB ACF are likely to engage different populations, highlighting the utility of a comprehensive approach.Trial Registration: Clinicaltrials.gov ( NCT02808507 ). Registered June 1, 2016. The participants in this formative study are not trial participants. [ABSTRACT FROM AUTHOR]