TY - JOUR
T1 - Use of whole genome sequencing to predict Mycobacterium tuberculosis drug resistance in Indonesia
AU - Chaidir, Lidya
AU - Ruesen, Carolien
AU - Dutilh, Bas E
AU - Ganiem, Ahmad R
AU - Andryani, Anggriani
AU - Apriani, Lika
AU - Huynen, Martijn A
AU - Ruslami, Rovina
AU - Hill, Philip C
AU - Crevel, Reinout van
AU - Alisjahbana, Bachti
N1 - Copyright © 2018. Published by Elsevier Ltd.
PY - 2019/3
Y1 - 2019/3
N2 - BACKGROUND: Whole genome sequencing (WGS) is rarely used for drug-resistance testing of Mycobacterium tuberculosis in high-endemic settings. We present the first study from Indonesia, which has the second highest tuberculosis (TB) burden worldwide, with less than 50% of drug-resistant cases currently detected.METHODS: We applied WGS in strains from 322 adult HIV-negative TB patients. Phenotypic DST was done for a portion of patients.RESULTS: Fifty-one isolates (15.8%) harboured drug resistance mutations, including 42 among 322 patients (13.0%) with no prior TB treatment. Eight (2.5%) isolates were multidrug-resistant (MDR), 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). The agreement of WGS-based resistance and phenotypic drug susceptibility testing (DST) to first-line drugs was high for isoniazid, rifampicin, and streptomycin, and less for ethambutol. Drug resistance was more common in Indo-Oceanic lineage strains (37.5%) than 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: Our data support the potential use of WGS for more rapid and comprehensive prediction ofDR-TB in Indonesia. Future studies should address potential barriers in implementing WGS, the distribution of specific resistance mutations, and associations of particular mutations with endemic M. tuberculosis lineages in Indonesia.
AB - BACKGROUND: Whole genome sequencing (WGS) is rarely used for drug-resistance testing of Mycobacterium tuberculosis in high-endemic settings. We present the first study from Indonesia, which has the second highest tuberculosis (TB) burden worldwide, with less than 50% of drug-resistant cases currently detected.METHODS: We applied WGS in strains from 322 adult HIV-negative TB patients. Phenotypic DST was done for a portion of patients.RESULTS: Fifty-one isolates (15.8%) harboured drug resistance mutations, including 42 among 322 patients (13.0%) with no prior TB treatment. Eight (2.5%) isolates were multidrug-resistant (MDR), 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). The agreement of WGS-based resistance and phenotypic drug susceptibility testing (DST) to first-line drugs was high for isoniazid, rifampicin, and streptomycin, and less for ethambutol. Drug resistance was more common in Indo-Oceanic lineage strains (37.5%) than 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: Our data support the potential use of WGS for more rapid and comprehensive prediction ofDR-TB in Indonesia. Future studies should address potential barriers in implementing WGS, the distribution of specific resistance mutations, and associations of particular mutations with endemic M. tuberculosis lineages in Indonesia.
KW - Mycobacterium tuberculosis
KW - drug resistance
KW - whole genome sequencing
KW - resistance mutations
U2 - 10.1016/j.jgar.2018.08.018
DO - 10.1016/j.jgar.2018.08.018
M3 - Article
C2 - 30172045
SN - 2213-7165
VL - 16
SP - 170
EP - 177
JO - Journal of Global Antimicrobial Resistance
JF - Journal of Global Antimicrobial Resistance
ER -