Clinical application of whole-genome sequencing in the management of extensively drug-resistant tuberculosis: a case report.

BACKGROUND: Whole-genome sequencing (WGS)-based prediction of drug resistance in Mycobacterium tuberculosis has the potential to guide clinical decisions in the design of optimal treatment regimens. METHODS: We utilized WGS to investigate drug resistance mutations in a 32-year-old Tanzanian male admitted to Kibong'oto Infectious Diseases Hospital with a history of interrupted multidrug-resistant tuberculosis treatment for more than three years. Before admission, he received various all-oral bedaquiline-based multidrug-resistant tuberculosis treatment regimens with unfavourable outcomes. RESULTS: Drug susceptibility testing of serial M. tuberculosis isolates using Mycobacterium Growth Incubator Tubes culture and WGS revealed resistance to first-line anti-TB drugs, bedaquiline, and fluoroquinolones but susceptibility to linezolid, clofazimine, and delamanid. WGS of serial cultured isolates revealed that the Beijing (Lineage 2.2.2) strain was resistant to bedaquiline, with mutations in the mmpR5 gene (Rv0678. This study also revealed the emergence of two distinct subpopulations of bedaquiline-resistant tuberculosis strains with Asp47f and Glu49fs frameshift mutations in the mmpR5 gene, which might be the underlying cause of prolonged resistance. An individualized regimen comprising bedaquiline, delamanid, pyrazinamide, ethionamide, and para-aminosalicylic acid was designed. The patient was discharged home at month 8 and is currently in the ninth month of treatment. He reported no cough, chest pain, fever, or chest tightness but still experienced numbness in his lower limbs. CONCLUSION: We propose the incorporation of WGS in the diagnostic framework for the optimal management of patients with drug-resistant and extensively drug-resistant tuberculosis.

Burden, clinical features and outcomes of post-tuberculosis lung disease in sub-Saharan Africa: a protocol for a systematic review and meta-analysis.

INTRODUCTION: Tuberculosis (TB) is significantly associated with multiple postinfectious, non-communicable diseases after microbiological cure. For example, those with a history of TB disease have a higher risk of developing chronic lung diseases at a younger age. However, the extent and nature of post-TB complications are not well described. Here, we present a protocol for a systematic review and meta-analysis, which aims to synthesise literature on the burden of post-TB lung disease (PTLD) in sub-Saharan Africa, describe phenotypes, long-term outcomes and the health-related quality of life of people with PTLD. METHODS AND ANALYSIS: A systematic search will be conducted using PubMed, EMBASE, Web of Science, African Journals Online and the Cochrane Library of Systematic Reviews. Papers published in English and French languages that report the prevalence, clinical features, quality of life and long-term outcomes of people with PTLD in sub-Saharan Africa will be considered. We will assess and critically appraise the methodological quality of all studies using the modified covidence. Qualitative and quantitative (network and meta-analysis) synthesis will be performed and STATA V.16 will be used to estimate the burden of PTLD. ETHICS AND DISSEMINATION: Ethical approval is not required for this systematic review and meta-analysis. Our results will be published in peer-reviewed journals. PROSPERO REGISTRATION NUMBER: CRD42021274018.