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Volume 25, Number 3—March 2019
Dispatch

Drug-Resistant Tuberculosis, Lebanon, 2016 – 2017

Salam El Achkar, Christine Demanche, Marwan Osman, Rayane Rafei, Mohamad Bachar Ismail, Hiam Yaacoub, Claire Pinçon, Stéphanie Duthoy, Frédérique De Matos, Cyril Gaudin, Alberto Trovato, Daniela M. Cirillo, Monzer Hamze, and Philip SupplyComments to Author 
Author affiliations: Université de Lille, CNRS, INSERM, Centre Hospitalier Universitaire, Institut Pasteur de Lille, U1019–UMR 8204–Centre d’Infection et d’Immunité de Lille, Lille, France (S. El Achkar, C. Demanche, C. Pinçon, P. Supply); Université Libanaise, Tripoli, Lebanon (S. El Achkar, M. Osman, R. Rafei, M.B. Ismail, M. Hamze); Genoscreen, Lille (S. Duthoy, F. De Matos, C. Gaudin); IRCCS San Raffaele Scientific Institute, Milan, Italy (A. Trovato, D.M. Cirillo); Ministry of Public Health, Beirut, Lebanon (H. Yaacoub)

Main Article

Table 2

Genotypic and phenotypic drug susceptibility profiles of drug-resistant TB cases, Lebanon*

Category
Drug resistance classification
MDR

XDR
Patient ID
14
48
125†
74
168
185
TB drug
RIF Gene rpoB S450L S450L S450L S450L S450L S450L
Phenotypic            
INH Genes katG S315T F129S‡ S315T S315T   S315T
inhA         C-15T  
Phenotypic            
PZA Gene pncA   Y103Stop InserA192 A46P   H71Q
Phenotypic ND ND ND ND ND ND
EMB Gene embB Q497R M306V M306V Q497R Q497R M306V
Phenotypic            
SM Genes rpsL K43R   K88R K43R   K43R
rrs         A908C  
Phenotypic            
AMI/KAN Gene rrs         A1401G A1401G
Phenotypic            
FQ Gene gyrA   S91P§   D94A S91P D94Y
Phenotypic            
CAP Genes tlyA       InserC313    
rrs         A1401G A1401G
Phenotypic ND ND ND ND ND ND
ETH
Genes ethA Deleted¶   141 nt del# Deleted¶ DelG632 DelG1338
inhA         C-15T  
Phenotypic
ND
ND
ND

ND
ND
ND
MIRU-VNTR type** 100-32 19431-157 21404-32 10156-32 21416-15 ?-15
M. tuberculosis complex lineage†† 2 (Beijing) 4 (Euro-American) 3 (Delhi-CAS) 2 (Beijing) 4 (H37Rv-like) 4 (Haarlem)

*Only genes with detected resistance-associated mutations are shown. No mutation was detected in targets associated with linezolid or bedaquiline and clofazimine resistance. Mutations are shown as amino acid changes with the corresponding codon position, nucleotide changes in promoter regions, or inserted or deleted base (inser or del with position in coding sequence) resulting in a frameshift. Bold text shows mutations concordantly detected by whole-genome sequencing and Deeplex-MycTB (GenoScreen, https://www.genoscreen.fr) in samples subjected to both assays. Other mutations are those detected in samples analyzed by Deeplex-MycTB only. Drug resistance predictions are based on reference data from available scientific literature (8–10), and for pncA also on data from Yadon et al. (14). Black represents phenotypic resistance to the different drugs and gray represents phenotypic susceptibility. For phenotypic testing, levofloxacin was the only fluoroquinolone tested. AMI, amikacin; CAP, capreomycin; EMB, ethambutol; ETH, ethionamide; FQ, fluoroquinolones; KAN, kanamycin; INH, isoniazid; ND, not done; PZA, pyrazinamide; RIF, rifampin; SM, streptomycin.
†Deeplex-MycTB result obtained on a primary specimen (sputum). The other results were obtained on indirect samples (primary cultures).
‡Mutation described in association with isoniazid resistance once before by Wang et al. (11). This mutation is not detectable by Anyplex testing.
§Detected as a minority variant, at 5.2% in this sample (see text). Percentages of fixation of other mutations within individual samples range from 80.6% to 100%.
¶Putative deletion, as inferred by absence of reads mapped specifically on the corresponding gene target, in contrast to all other, well covered targets.
#Internal deletion, resulting in a frameshift, from gene position 859 to 999.
**According to MIRU-VNTRPlus website (http://www.miru-vntrplus.org) nomenclature (15). For patient 185, a question mark in the genotype reflects the absence of a detectable allele in locus 4052.
††According to Deeplex-MycTB (spoligotyping and phylogenetic SNPs) and MIRU-VNTRPlus identification, confirmed by whole-genome sequencing results, when done.

Main Article

Page created: February 19, 2019
Page updated: February 19, 2019
Page reviewed: February 19, 2019
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