TY - JOUR
T1 - Half of rifampicin-resistant Mycobacterium tuberculosis complex isolated from tuberculosis patients in Sub-Saharan Africa have concomitant resistance to pyrazinamide
AU - Union Short MDR-TB Regimen Study Group
AU - Ngabonziza, Jean Claude Semuto
AU - Diallo, Awa Ba
AU - Tagliani, Elisa
AU - Diarra, Bassirou
AU - Kadanga, Abalo Essosimna
AU - Togo, Antieme Combo George
AU - Thiam, Aliou
AU - de Rijk, Willem Bram
AU - Alagna, Riccardo
AU - Houeto, Sabine
AU - Ba, Fatoumata
AU - Dagnra, Anoumou Yaotse
AU - Ivan, Emil
AU - Affolabi, Dissou
AU - Schwoebel, Valerie
AU - Trebucq, Arnaud
AU - de Jong, Bouke Catherine
AU - Rigouts, Leen
AU - Daneau, Geraldine
N1 - FTX; DOAJ
PY - 2017
Y1 - 2017
N2 - BackgroundBesides inclusion in 1st line regimens against tuberculosis (TB), pyrazinamide (PZA) is used in 2nd line anti-TB regimens, including in the short regimen for multidrug-resistant TB (MDR-TB) patients. Guidelines and expert opinions are contradictory about inclusion of PZA in case of resistance. Moreover, drug susceptibility testing (DST) for PZA is not often applied in routine testing, and the prevalence of resistance is unknown in several regions, including in most African countries.MethodsSix hundred and twenty-three culture isolates from rifampicin-resistant (RR) patients were collected in twelve Sub-Saharan African countries. Among those isolates, 71% were from patients included in the study on the Union short-course regimen for MDR-TB in Benin, Burkina Faso, Burundi, Cameroon, Central Africa Republic, the Democratic Republic of the Congo, Ivory Coast, Niger, and Rwanda PZA resistance, and the rest (29%) were consecutive isolates systematically stored from 2014-2015 in Mali, Rwanda, Senegal, and Togo. Besides national guidelines, the isolates were tested for PZA resistance through pncA gene sequencing.ResultsOver half of these RR-TB isolates (54%) showed a mutation in the pncA gene, with a significant heterogeneity between countries. Isolates with fluoroquinolone resistance (but not with injectable resistance or XDR) were more likely to have concurrent PZA resistance. The pattern of mutations in the pncA gene was quite diverse, although some isolates with an identical pattern of mutations in pncA and other drug-related genes were isolated from the same reference center, suggesting possible transmission of these strains.ConclusionSimilar to findings in other regions, more than half of the patients having RR-TB in West and Central Africa present concomitant resistance to PZA. Further investigations are needed to understand the relation between resistance to PZA and resistance to fluoroquinolones, and whether continued use of PZA in the face of PZA resistance provides clinical benefit to the patients.
AB - BackgroundBesides inclusion in 1st line regimens against tuberculosis (TB), pyrazinamide (PZA) is used in 2nd line anti-TB regimens, including in the short regimen for multidrug-resistant TB (MDR-TB) patients. Guidelines and expert opinions are contradictory about inclusion of PZA in case of resistance. Moreover, drug susceptibility testing (DST) for PZA is not often applied in routine testing, and the prevalence of resistance is unknown in several regions, including in most African countries.MethodsSix hundred and twenty-three culture isolates from rifampicin-resistant (RR) patients were collected in twelve Sub-Saharan African countries. Among those isolates, 71% were from patients included in the study on the Union short-course regimen for MDR-TB in Benin, Burkina Faso, Burundi, Cameroon, Central Africa Republic, the Democratic Republic of the Congo, Ivory Coast, Niger, and Rwanda PZA resistance, and the rest (29%) were consecutive isolates systematically stored from 2014-2015 in Mali, Rwanda, Senegal, and Togo. Besides national guidelines, the isolates were tested for PZA resistance through pncA gene sequencing.ResultsOver half of these RR-TB isolates (54%) showed a mutation in the pncA gene, with a significant heterogeneity between countries. Isolates with fluoroquinolone resistance (but not with injectable resistance or XDR) were more likely to have concurrent PZA resistance. The pattern of mutations in the pncA gene was quite diverse, although some isolates with an identical pattern of mutations in pncA and other drug-related genes were isolated from the same reference center, suggesting possible transmission of these strains.ConclusionSimilar to findings in other regions, more than half of the patients having RR-TB in West and Central Africa present concomitant resistance to PZA. Further investigations are needed to understand the relation between resistance to PZA and resistance to fluoroquinolones, and whether continued use of PZA in the face of PZA resistance provides clinical benefit to the patients.
KW - ASPARTATE DECARBOXYLASE PAND
KW - PNCA GENE-MUTATIONS
KW - DRUG-RESISTANCE
KW - FLUOROQUINOLONES
KW - SUSCEPTIBILITY
KW - TRANSMISSION
KW - MECHANISMS
KW - DIAGNOSIS
KW - LINEAGE
KW - UPDATE
U2 - 10.1371/journal.pone.0187211
DO - 10.1371/journal.pone.0187211
M3 - A1: Web of Science-article
VL - 12
JO - PLoS ONE
JF - PLoS ONE
SN - 1932-6203
IS - 10
M1 - 0187211
ER -