title: Pseudo-outbreak of pre-extensively drug-resistant (Pre-XDR) tuberculosis in Kinshasa: collateral damage caused by false detection of fluoroquinolone resistance by GenoType MTBDRsl.
abstract: Fluoroquinolones are the core drugs for the management of multidrug-resistant tuberculosis (MDR-TB). Molecular drug susceptibility testing methods provide considerable advantages for scaling up programmatic management and surveillance of drug-resistant TB. We describe here the misidentification of fluoroquinolone resistance by the GenoType MTBDRsl (MTBDRsl) (Hain Lifescience GmbH, Nehren, Germany) line probe assay (LPA) encountered during a feasibility and validation study for the introduction of this rapid drug susceptibility test in Kinshasa, Democratic Republic of Congo. The double gyrA mutation 80Ala and 90Gly represented 57% of all fluoroquinolone mutations identified from MDR-TB patient sputum samples, as confirmed by DNA sequencing. This double mutation was previously found to be associated with susceptibility to fluoroquinolones, yet it leads to absent hybridization of a wild-type band in the MTBDRsl and is thus falsely scored as resistance. Our findings suggest that MTBDRsl results must be interpreted with caution when the interpretation is based solely on the absence of a wild-type band without confirmation by visualization of a mutant band. Performance of the MTBDRsl LPA might be improved by replacing the gyrA wild-type probes by additional probes specific for well-documented gyrA mutations that confer clinically relevant resistance.
authors.affiliation: National Tuberculosis Program, Kinshasa, Democratic Republic of Congo Institut National de Recherche Bio-Médicale, Kinshasa, Democratic Republic of Congo Institute of Tropical Medicine, Antwerp, Belgium meckkay2002@yahoo.fr.
authors.forename: Michel K
authors.initials: MK
authors.lastname: Kaswa
authors.affiliation: Institut National de Recherche Bio-Médicale, Kinshasa, Democratic Republic of Congo.
authors.forename: Muriel
authors.initials: M
authors.lastname: Aloni
authors.affiliation: Institut National de Recherche Bio-Médicale, Kinshasa, Democratic Republic of Congo.
authors.forename: Léontine
authors.initials: L
authors.lastname: Nkuku
authors.affiliation: National Tuberculosis Program, Kinshasa, Democratic Republic of Congo.
authors.forename: Brian
authors.initials: B
authors.lastname: Bakoko
authors.affiliation: National Tuberculosis Program, Kinshasa, Democratic Republic of Congo.
authors.forename: Rossin
authors.initials: R
authors.lastname: Lebeke
authors.affiliation: National Tuberculosis Program, Kinshasa, Democratic Republic of Congo.
authors.forename: Albert
authors.initials: A
authors.lastname: Nzita
authors.affiliation: Institut National de Recherche Bio-Médicale, Kinshasa, Democratic Republic of Congo.
authors.forename: Jean Jacques
authors.initials: JJ
authors.lastname: Muyembe
authors.affiliation: Institute of Tropical Medicine, Antwerp, Belgium New York University, New York, New York, USA.
authors.forename: Bouke C
authors.initials: BC
authors.lastname: de Jong
authors.affiliation: Institute of Tropical Medicine, Antwerp, Belgium.
authors.forename: Pim
authors.initials: P
authors.lastname: de Rijk
authors.affiliation: KU Leuven, Leuven, Belgium.
authors.forename: Jan
authors.initials: J
authors.lastname: Verhaegen
authors.affiliation: Institute of Tropical Medicine, Antwerp, Belgium.
authors.forename: Marleen
authors.initials: M
authors.lastname: Boelaert
authors.affiliation: University of Antwerp, Antwerp, Belgium.
authors.forename: Margareta
authors.initials: M
authors.lastname: Ieven
authors.affiliation: Institute of Tropical Medicine, Antwerp, Belgium.
authors.forename: Armand
authors.initials: A
authors.lastname: Van Deun
mesh_terms: D000995:Antitubercular Agents / Q000494:pharmacology*; D027081:DNA Gyrase / Q000235:genetics; D004269:DNA, Bacterial / Q000737:chemistry / Q000235:genetics; D015023:Democratic Republic of the Congo / Q000453:epidemiology; D004196:Disease Outbreaks; D005189:False Positive Reactions; D024841:Fluoroquinolones / Q000494:pharmacology*; D060005:Genotyping Techniques / Q000379:methods*; D006801:Humans; D020125:Mutation, Missense; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000235:genetics; D017354:Point Mutation; D017422:Sequence Analysis, DNA; D013183:Sputum / Q000382:microbiology; D018088:Tuberculosis, Multidrug-Resistant / Q000453:epidemiology* / Q000382:microbiology
chemical_list: D000995:Antitubercular Agents; D004269:DNA, Bacterial; D024841:Fluoroquinolones; D027081:DNA Gyrase