Half of rifampicin-resistant Mycobacterium tuberculosis complex isolated from tuberculosis patients in Sub-Saharan Africa have concomitant resistance to pyrazinamide

被引:15
|
作者
Ngabonziza, Jean Claude Semuto [1 ,2 ]
Diallo, Awa Ba [3 ]
Tagliani, Elisa [4 ]
Diarra, Bassirou [5 ]
Kadanga, Abalo Essosimna [6 ]
Togo, Antieme Combo George [5 ]
Thiam, Aliou [3 ]
de Rijk, Willem Bram [2 ]
Alagna, Riccardo [4 ]
Houeto, Sabine [7 ]
Ba, Fatoumata [8 ]
Dagnra, Anoumou Yaotse [6 ]
Ivan, Emil [1 ]
Affolabi, Dissou [7 ]
Schwoebel, Valerie [9 ]
Trebucq, Arnaud [9 ]
de Jong, Bouke Catherine [2 ]
Rigouts, Leen [2 ,10 ]
Daneau, Geraldine [2 ,11 ]
机构
[1] Rwanda Biomed Ctr, Biomed Serv Dept, Natl Reference Lab Div, Kigali, Rwanda
[2] Inst Trop Med, Dept Biomed Sci, Mycobacteriol Unit, Antwerp, Belgium
[3] CHNU Aristide le Dantec, Mycobacteriol Unit, Bacteriol Virol Lab, Dakar, Senegal
[4] IRCCS San Raffaele Sci Inst, Div Immunol Transplantat & Infect Dis, Emerging Bacterial Pathogens Unit, Milan, Italy
[5] Univ Sci Tech & Technol Bamako, SEREFO UCRC Program, Bamako, Mali
[6] Lab Natl Reference Mycobacteries, Lome, Togo
[7] Lab Reference Mycobacteries, Cotonou, Benin
[8] Lab Reference Mycobacteries, Dakar, Senegal
[9] Int Union TB & Lung Dis, Paris, France
[10] Univ Antwerp, Dept Biomed Sci, Antwerp, Belgium
[11] Haute Ecole Francisco Ferrer, Biomed Sect, Brussels, Belgium
来源
PLOS ONE | 2017年 / 12卷 / 10期
关键词
ASPARTATE DECARBOXYLASE PAND; PNCA GENE-MUTATIONS; DRUG-RESISTANCE; FLUOROQUINOLONES; SUSCEPTIBILITY; TRANSMISSION; MECHANISMS; DIAGNOSIS; LINEAGE;
D O I
10.1371/journal.pone.0187211
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Background Besides 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. Methods Six 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. Results Over 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. Conclusion Similar 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.
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页数:15
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