Laying the foundation for whole genome sequencing of clinical Mycobacterium tuberculosis isolates in the rural Eastern Cape area of South Africa.

Tuberculosis (TB) remains an important global health concern as efforts are likely to fall short in reaching the 2030 End TB Strategy targets of reducing TB deaths by 90% and TB incidence by 80%. Moreover, recent statistics published by the World Health Organization confirmed fears of a growing drug resistant TB (DR-TB) epidemic, which further threaten TB control. South Africa is faced with dual HIV and TB epidemics and is a hotspot for DR-TB, with one of the highest burdens of multidrug resistant TB (MDR-TB) in the world. Within South Africa, the Eastern Cape, Western Cape and KwaZulu-Natal provinces suffer the highest burden of both MDR-TB and the very hard-to-treat, extensively drug resistant TB (XDR-TB).Whole genome sequencing (WGS) allows for the complete analysis of the Mycobacterium tuberculosis (Mtb) genome and identification of all known drug resistance conferring mutations. The rapid advancement of WGS technology and its decreasing cost have made it more accessible for use in research and have opened the possibility of its application in public health, even in low resource settings. The high resolution of WGS also provides the opportunity to study the genomic variants of pathobiology, decipher transmission, detect mixed infections, investigate the emergence of drug resistance, and to discover novel mechanisms of drug resistance, thereby ensuring a better understanding of factors that drive the DR-TB epidemic. Despite the ostensible benefits and decreasing costs, WGS has not yet found its rightful place in research or care of DR-TB patients in high TB burden settings due to the limited local expertise in the extraction of high quality Mtb DNA, a critical requirement for successful WGS, and the lack of personnel with the bioinformatics skills that are required for analysis and interpretation of WGS data.The overall goal of this project is to establish a new collaboration between the Global Health Institute of the University of Antwerp (UAntwerp) (Dr Anzaan Dippenaar) and the Department of Laboratory Medicine and Pathology, Water Sisulu University (WSU), South Africa (Dr Teke Apalata) in order to lay the foundation for successful future collaborative research between these two groups in the area of Mtb WGS. In order to build capacity, advance technology transfer, and plant the seeds for future collaboration, we propose a highly cost effective and innovative blended learning capacity building approach to Mtb culturing, DNA extraction for WGS and bioinformatics analyses of WGS data. In the current pandemic situation and with foreseeable future budget restrictions, novel approaches to North-South capacity building are needed. Due to the COVID-19 global pandemic, higher education has undergone massive migrations from traditional face‐to‐face education to online teaching using diverse digitalization strategies. Current online and blended learning, however, primarily focus on providing knowledge, taking tests, and offering online support. Most university have opted to keep practica on campus and in person. In this project, we aim to expand the current blended learning to hands-on, laboratory-based training by implementing novel approaches such as the "lab-in-the-box", live-streaming online demonstrations of laboratory procedures, and online monitoring of independent implementation of laboratory procedures to ensure that the technical nuances and complexities of Mtb DNA extraction and WGS bioinformatics analyses are taught in a "COVID-proof" and cost-effective manner.

Keywords:NEXT GENERATION SEQUENCING, TUBERCULOSIS

Disciplines:Analysis of next-generation sequence data, Infectious diseases