@article{fdi:010073860, title = {{Q}uadruple-first line drug resistance in {M}ycobacterium tuberculosis in {V}ietnam : what can we learn from genes ?}, author = {{H}uy {N}guyen {Q}uang and {N}hung {V}iet {N}guyen and {C}ontamin, {L}. and {T}hanh {H}oa {T}hi {T}ran and {T}huong {T}hi {V}u and {H}ung {V}an {N}guyen and {N}goc {L}an {T}hi {N}guyen and {S}on {T}hai {N}guyen and {A}nh {D}ang {D}uc and {B}aƱuls, {A}nne-{L}aure and {V}an {A}nh {T}hi {N}guyen}, editor = {}, language = {{ENG}}, abstract = {{I}n {V}ietnam, a country with high tuberculosis (137/100.000 population) and multidrug-resistant ({MDR})-{TB} burdens (7.8/100.000 population), little is known about the molecular signatures of drug resistance in general and more particularly of second line drug ({SLD}) resistance. {T}his study is specifically focused on mycobacterium tuberculosis isolates resistant to four first-line drugs ({FLD}s) that make {TB} much more difficult to treat. {T}he aim is to determine the proportion of {SLD} resistance in these quadruple drug resistant isolates and the genetic determinants linked to drug resistance to better understand the genetic processes leading to quadruple and extremely drug resistance ({XDR}). 91 quadruple (rifampicin, isoniazid, ethambutol and streptomycin) {FLD} resistant and 55 susceptible isolates were included. {S}poligotyping and 24-locus {MIRU}-{VNTR} techniques were performed and 9 genes and promoters linked to {FLD} and {SLD} resistance were sequenced. {SW} susceptibility testing was carried out on a subsample of isolates. {H}igh proportion of quadruple-{FLD} resistant isolates was resistant to fluoroquinolones (27%) and second-line injectable drugs (302%) by drug susceptibility testing. {T}he sequencing revealed high mutation diversity with prevailing mutations at positions kat{G}315, inh{A}-15, rpo{B}531, emb{B}306, rrs1401, rps{L}43 and gyr{A}94. {T}he sensitivity and specificity were high for most drug resistances (>86%), but the sensitivity was lower for injectable drug resistances (<69%). {T}he mutation patterns revealed 23.1% of pre-{XDR} and 7.7% of {XDR} isolates, mostly belonging to {B}eijing family. {T}he genotypic diversity and the variety of mutations reflect the existence of various evolutionary paths leading to {FLD} and {SLD} resistance. {N}evertheless, particular mutation patterns linked to high-level resistance and low fitness costs seem to be favored.}, keywords = {{VIET} {NAM}}, booktitle = {}, journal = {{I}nfection, {G}enetics and {E}volution}, volume = {50}, numero = {}, pages = {55--61}, ISSN = {1567-1348}, year = {2017}, DOI = {10.1016/j.meegid.2017.02.012}, URL = {https://www.documentation.ird.fr/hor/fdi:010073860}, }