Implementation of whole genome sequencing for tuberculosis diagnostics in a low-middle income, high MDR-TB burden country

在低收入、耐多药结核病高负担国家实施结核病诊断的全基因组测序

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作者:Monica Vogel # ,Christian Utpatel # ,Caroline Corbett # ,Thomas A Kohl # ,Altyn Iskakova # ,Sevim Ahmedov ,Uladzimir Antonenka ,Viola Dreyer ,Ainura Ibrahimova ,Chynara Kamarli ,Dilorom Kosimova ,Vanessa Mohr ,Evgeni Sahalchyk ,Meerim Sydykova ,Nagira Umetalieva ,Abdylat Kadyrov ,Gulmira Kalmambetova ,Stefan Niemann ,Harald Hoffmann

Abstract

Whole genome sequencing (WGS) is revolutionary for diagnostics of TB and its mutations associated with drug-resistances, but its uptake in low- and middle-income countries is hindered by concerns of implementation feasibility. Here, we provide a proof of concept for its successful implementation in such a setting. WGS was implemented in the Kyrgyz Republic. We estimated needs of up to 55 TB-WGS per week and chose the MiSeq platform (Illumina, USA) because of its capacity of up to 60 TB-WGS per week. The project's timeline was completed in 93-weeks. Costs of large equipment and accompanying costs were 222,065 USD and 8462 USD, respectively. The first 174 WGS costed 277 USD per sequence, but this was skewed by training inefficiencies. Based on real prices and presuming optimal utilization of WGS capacities, WGS costs could drop to 167 and 141 USD per WGS using MiSeq Reagent Kits v2 (500-cycles) and v3 (600-cycles), respectively. Five trainings were required to prepare the staff for autonomous WGS which cost 48,250 USD. External assessment confirmed excellent performance of WGS by the Kyrgyz laboratory in an interlaboratory comparison of 30 M. tuberculosis genomes showing complete agreeance of results.

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