Developing Implementation Strategies for Targeted Next-Generation Sequencing for Tuberculosis Diagnosis in Botswana: A Study Protocol

To address drug-resistant tuberculosis (TB), the World Health Organization has recommended that all countries with capacity implement targeted next-generation sequencing for genomic drug resistance testing. Targeted next-generation sequencing can quickly identify many drug resistance-conferring mutations. However, the technology is complex, costly, and relies on numerous factors including laboratory capacitation, financing, revisions of guidelines and diagnostic algorithms, high-quality sputum samples, and timely communication of results. This protocol describes a study to be conducted with the Botswana Ministry of Health to prospectively develop targeted next-generation sequencing implementation packages for TB in Botswana. We will use qualitative methods, Implementation Mapping, and other Implementation Science theories and frameworks to select implementation strategies. First, we will draw from previous research and team expertise to identify barriers and facilitators in Botswana’s TB care cascade. Second, we will interview TB stakeholders and affected persons, including staff at clinics, district offices, laboratories, policymaking entities, and civil society organizations. People affected by TB include people recently diagnosed, in treatment, who have completed treatment, and caregivers. Transcripts will be deductively analyzed to identify priority implementation outcomes and performance objectives. Third, we will use our findings to develop implementation strategies. Finally, we will workshop strategies in focus groups with stakeholders, enabling the selection of preferred implementation packages. The development of sustainable implementation strategies will be crucial to maximize the benefits of targeted next-generation sequencing for TB. Our study will generate strategies for Botswana that have applicability to other low-to-middle-income settings, and which can be further developed, validated, and trialed. Trial Registration N/A. This is not a randomized control trial or interventional study.