Implementation of targeted next-generation sequencing for the diagnosis of drug-resistant tuberculosis in low-resource settings: a programmatic model, challenges, and initial outcomes

Abstract

Targeted next-generation sequencing (tNGS) from clinical specimens has the potential to become a comprehensive tool for routine drug-resistance (DR) prediction of Mycobacterium tuberculosis complex strains (MTBC), the causative agent of tuberculosis (TB). However, TB mainly affects low- and middle-income countries, in which the implementation of new technologies have specific needs and challenges. We propose a model for programmatic implementation of tNGS in settings with no or low previous sequencing capacity/experience. We highlight the major challenges and considerations for a successful implementation. This model has been applied to build NGS capacity in Namibia, an upper middle-income country located in Southern Africa and suffering from a high-burden of TB and TB-HIV, and we describe herein the outcomes of this process.

Multidrug-resistant tuberculosis: latest opinions on epidemiology, rapid diagnosis and management

“…Only primary quantitative studies were selected from the search output. The title of the study, year of study, study setting, study design, MDR-TB confirmed number of cases, MDR-TB/HIV co-infection proportion, and the outcome explored were characteristics retrieved from the studies (Table 1 ) [ 9 – 13 , 14 ▪▪ , 15 – 21 , 22 ▪▪ , 23 , 24 ▪▪ , 25 – 29 , 30 ▪ , 31 ▪ , 32 – 36 , 37 ▪▪ , 38 – 48 , 49 ▪▪ , 50 ▪ ].…”

Targeted genome sequencing for tuberculosis drug susceptibility testing in South Africa: a proposed diagnostic pipeline

“…The difficulties faced in implementing tNGS are ubiquitous amongst all low- and middle-income countries. A recent strategy that has been successfully implemented in Nigeria utilised a model comprising preparation, implementation, and sustainability phases [ 37, 38 ]. The preparation phase involved site and staff identification, establishing a timeline with achievable goals, with effective co-ordination, communication and contracting.…”

“…The benefits associated with tNGS extend beyond TB diagnostics [ 37, 38 ]. The implementation of NGS and tNGS infrastructure will upskill the molecular workforce of the country.…”

Current Uses and Future Perspectives of Genomic Technologies in Clinical Microbiology

“…The design of primers or probes for enrichment necessitates an in-depth understanding of the genomic characteristics of the organisms under investigation. An inaccurate selection of target regions can result in incomplete or biased results [56,57]. Furthermore, data analysis and interpretation can be complex, especially when dealing with diverse microbial populations.…”

“…A programmatic model for the implementation of tNGS has been put into action in Namibia, an upper middle-income country located in Southern Africa. Namibia faces a significant burden of tuberculosis (TB) [56]. The overarching goal of integrating tNGS into routine practices in high-TB-incidence countries, such as Namibia, is to enhance the clinical management of TB cases and establish effective surveillance mechanisms for resistance to new treatment regimens.…”