Lidya Chaidir1, Carolien Ruesen2, Bas E Dutilh3, Ahmad R Ganiem4, Anggriani Andryani5, Lika Apriani6, Martijn A Huynen3, Rovina Ruslami4, Philip C Hill7, Reinout van Crevel2, Bachti Alisjahbana4. 1. Infectious Disease Research Center, Faculty of Medicine, Universitas Padjadjaran, Eijkman 38, Bandung 40161, Indonesia. Electronic address: lidya.chaidir@unpad.ac.id. 2. Department of Internal Medicine, Radboud University Medical Center, Geert Grooteplein-Zuid 10, Nijmegen 6525 GA, The Netherlands. 3. Centre for Molecular and Biomolecular Informatics, Radboud University Medical Center, Geert Grooteplein 8, Nijmegen 6500 HB, The Netherlands. 4. Infectious Disease Research Center, Faculty of Medicine, Universitas Padjadjaran, Eijkman 38, Bandung 40161, Indonesia; Faculty of Medicine, Universitas Padjadjaran/Hasan Sadikin Hospital, Pasir Kaliki 38, Bandung 40161, Indonesia. 5. West Java Provincial Referral Laboratory, Sederhana 3-5, Bandung 40161, Indonesia. 6. Infectious Disease Research Center, Faculty of Medicine, Universitas Padjadjaran, Eijkman 38, Bandung 40161, Indonesia. 7. Centre for International Health, Dunedin School of Medicine, University of Otago, P.O. Box 56, Dunedin 9054, New Zealand.
Abstract
OBJECTIVES: Whole-genome sequencing (WGS) is rarely used for drug resistance testing of Mycobacterium tuberculosis in high-endemic settings. Here we present the first study from Indonesia, which has the third highest tuberculosis (TB) burden worldwide, with <50% of drug-resistant cases currently detected. METHODS: WGS was applied for strains from 322 human immunodeficiency virus (HIV)-negative adult TB patients. Phenotypic drug susceptibility testing (DST) was performed for a proportion of the patients. RESULTS: Using WGS, mutations associated with drug resistance to any TB drug were identified in 51 (15.8%) of the 322 patients, including 42 patients (13.0%) with no prior TB treatment (primary resistance). Eight isolates (2.5%) were multidrug-resistant (MDR) and one was extensively drug-resistant (XDR). Most mutations were found in katG (n=18), pncA (n=18), rpoB (n=10), fabG1 (n=9) and embB (n=9). Agreement of WGS-based resistance and phenotypic DST to first-line drugs was high for isoniazid and rifampicin but was lower for ethambutol and streptomycin. Drug resistance was more common in Indo-Oceanic lineage strains (37.5%) compared with Euro-American (18.2%) and East-Asian lineage strains (10.3%) (P=0.044), but combinations of multiple mutations were most common among East-Asian lineage strains (P=0.054). CONCLUSIONS: These data support the potential use of WGS for more rapid and comprehensive prediction of drug-resistant TB in Indonesia. Future studies should address potential barriers to implementing WGS, the distribution of specific resistance mutations, and the association of particular mutations with endemic M. tuberculosis lineages in Indonesia.
OBJECTIVES: Whole-genome sequencing (WGS) is rarely used for drug resistance testing of Mycobacterium tuberculosis in high-endemic settings. Here we present the first study from Indonesia, which has the third highest tuberculosis (TB) burden worldwide, with <50% of drug-resistant cases currently detected. METHODS: WGS was applied for strains from 322 human immunodeficiency virus (HIV)-negative adult TB patients. Phenotypic drug susceptibility testing (DST) was performed for a proportion of the patients. RESULTS: Using WGS, mutations associated with drug resistance to any TB drug were identified in 51 (15.8%) of the 322 patients, including 42 patients (13.0%) with no prior TB treatment (primary resistance). Eight isolates (2.5%) were multidrug-resistant (MDR) and one was extensively drug-resistant (XDR). Most mutations were found in katG (n=18), pncA (n=18), rpoB (n=10), fabG1 (n=9) and embB (n=9). Agreement of WGS-based resistance and phenotypic DST to first-line drugs was high for isoniazid and rifampicin but was lower for ethambutol and streptomycin. Drug resistance was more common in Indo-Oceanic lineage strains (37.5%) compared with Euro-American (18.2%) and East-Asian lineage strains (10.3%) (P=0.044), but combinations of multiple mutations were most common among East-Asian lineage strains (P=0.054). CONCLUSIONS: These data support the potential use of WGS for more rapid and comprehensive prediction of drug-resistant TB in Indonesia. Future studies should address potential barriers to implementing WGS, the distribution of specific resistance mutations, and the association of particular mutations with endemic M. tuberculosis lineages in Indonesia.
Authors: Andre Marolop Pangihutan Siahaan; Steven Tandean; Rr Suzy Indharty; Bahagia Willibrodus Maria Nainggolan; Martin Susanto Journal: Int J Surg Case Rep Date: 2022-09-08