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

JCS Ngabonziza, AB Diallo, E Tagliani, B Diarra, AE Kadanga, ACG Togo, A Thiam, WB De Rijk, R Alagna, S Houeto, F Ba, AY Dagnra, E Ivan, D Affolabi, V Schwoebel, A Trebucq, BC De Jong, L Rigouts, G Daneau, the Union short MDRTB regimen study group

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Background: Besides inclusion in 1 st line regimens against tuberculosis (TB), pyrazinamide (PZA) is used in 2 nd 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. © 2017 Ngabonziza et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Original languageEnglish
Article numbere0187211
JournalPLoS One
Volume12
Issue number10
DOIs
Publication statusPublished - 2017

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Mycobacterium tuberculosis complex
Pyrazinamide
rifampicin
Africa South of the Sahara
Rifampin
Sub-Saharan Africa
Mycobacterium tuberculosis
tuberculosis
Tuberculosis
Rwanda
fluoroquinolones
Central Africa
mutation
genes
Genes
Burundi
drugs
Democratic Republic of the Congo
Burkina Faso
Benin

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Ngabonziza, JCS., Diallo, AB., Tagliani, E., Diarra, B., Kadanga, AE., Togo, ACG., ... group, T. U. S. MDRTB. R. S. (2017). Half of rifampicin-resistant Mycobacterium tuberculosis complex isolated from tuberculosis patients in Sub-Saharan Africa have concomitant resistance to pyrazinamide. PLoS One, 12(10), [e0187211]. https://doi.org/10.1371/journal.pone.0187211

Half of rifampicin-resistant Mycobacterium tuberculosis complex isolated from tuberculosis patients in Sub-Saharan Africa have concomitant resistance to pyrazinamide. / Ngabonziza, JCS; Diallo, AB; Tagliani, E; Diarra, B; Kadanga, AE; Togo, ACG; Thiam, A; De Rijk, WB; Alagna, R; Houeto, S; Ba, F; Dagnra, AY; Ivan, E; Affolabi, D; Schwoebel, V; Trebucq, A; De Jong, BC; Rigouts, L; Daneau, G; group, the Union short MDRTB regimen study.

In: PLoS One, Vol. 12, No. 10, e0187211, 2017.

Research output: Contribution to journalArticle

Ngabonziza, JCS, Diallo, AB, Tagliani, E, Diarra, B, Kadanga, AE, Togo, ACG, Thiam, A, De Rijk, WB, Alagna, R, Houeto, S, Ba, F, Dagnra, AY, Ivan, E, Affolabi, D, Schwoebel, V, Trebucq, A, De Jong, BC, Rigouts, L, Daneau, G & group, TUSMDRTBRS 2017, 'Half of rifampicin-resistant Mycobacterium tuberculosis complex isolated from tuberculosis patients in Sub-Saharan Africa have concomitant resistance to pyrazinamide', PLoS One, vol. 12, no. 10, e0187211. https://doi.org/10.1371/journal.pone.0187211
Ngabonziza, JCS ; Diallo, AB ; Tagliani, E ; Diarra, B ; Kadanga, AE ; Togo, ACG ; Thiam, A ; De Rijk, WB ; Alagna, R ; Houeto, S ; Ba, F ; Dagnra, AY ; Ivan, E ; Affolabi, D ; Schwoebel, V ; Trebucq, A ; De Jong, BC ; Rigouts, L ; Daneau, G ; group, the Union short MDRTB regimen study. / Half of rifampicin-resistant Mycobacterium tuberculosis complex isolated from tuberculosis patients in Sub-Saharan Africa have concomitant resistance to pyrazinamide. In: PLoS One. 2017 ; Vol. 12, No. 10.
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abstract = "Background: Besides inclusion in 1 st line regimens against tuberculosis (TB), pyrazinamide (PZA) is used in 2 nd 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. {\circledC} 2017 Ngabonziza et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.",
author = "JCS Ngabonziza and AB Diallo and E Tagliani and B Diarra and AE Kadanga and ACG Togo and A Thiam and {De Rijk}, WB and R Alagna and S Houeto and F Ba and AY Dagnra and E Ivan and D Affolabi and V Schwoebel and A Trebucq and {De Jong}, BC and L Rigouts and G Daneau and group, {the Union short MDRTB regimen study}",
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T1 - Half of rifampicin-resistant Mycobacterium tuberculosis complex isolated from tuberculosis patients in Sub-Saharan Africa have concomitant resistance to pyrazinamide

AU - Ngabonziza, JCS

AU - Diallo, AB

AU - Tagliani, E

AU - Diarra, B

AU - Kadanga, AE

AU - Togo, ACG

AU - Thiam, A

AU - De Rijk, WB

AU - Alagna, R

AU - Houeto, S

AU - Ba, F

AU - Dagnra, AY

AU - Ivan, E

AU - Affolabi, D

AU - Schwoebel, V

AU - Trebucq, A

AU - De Jong, BC

AU - Rigouts, L

AU - Daneau, G

AU - group, the Union short MDRTB regimen study

PY - 2017

Y1 - 2017

N2 - Background: Besides inclusion in 1 st line regimens against tuberculosis (TB), pyrazinamide (PZA) is used in 2 nd 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. © 2017 Ngabonziza et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

AB - Background: Besides inclusion in 1 st line regimens against tuberculosis (TB), pyrazinamide (PZA) is used in 2 nd 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. © 2017 Ngabonziza et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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DO - 10.1371/journal.pone.0187211

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SN - 1932-6203

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ER -