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Published in: BMC Infectious Diseases 1/2021

Open Access 01-12-2021 | Isoniazid | Research

Transmission patterns of rifampicin resistant Mycobacterium tuberculosis complex strains in Cameroon: a genomic epidemiological study

Authors: Matthias Merker, Nkongho F. Egbe, Yannick R. Ngangue, Comfort Vuchas, Thomas A. Kohl, Viola Dreyer, Christopher Kuaban, Jürgen Noeske, Stefan Niemann, Melissa S. Sander

Published in: BMC Infectious Diseases | Issue 1/2021

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Abstract

Background

Determining factors affecting the transmission of rifampicin (RR) and multidrug-resistant (MDR) Mycobacterium tuberculosis complex strains under standardized tuberculosis (TB) treatment is key to control TB and prevent the evolution of drug resistance.

Methods

We combined bacterial whole genome sequencing (WGS) and epidemiological investigations for 37% (n = 195) of all RR/MDR-TB patients in Cameroon (2012–2015) to identify factors associated with recent transmission.

Results

Patients infected with a strain resistant to high-dose isoniazid, and ethambutol had 7.4 (95% CI 2.6–21.4), and 2.4 (95% CI 1.2–4.8) times increased odds of being in a WGS-cluster, a surrogate for recent transmission. Furthermore, age between 30 and 50 was positively correlated with recent transmission (adjusted OR 3.8, 95% CI 1.3–11.4). We found high drug-resistance proportions against three drugs used in the short standardized MDR-TB regimen in Cameroon, i.e. high-dose isoniazid (77.4%), ethambutol (56.9%), and pyrazinamide (43.1%). Virtually all strains were susceptible to fluoroquinolones, kanamycin, and clofazimine, and treatment outcomes were mostly favourable (87.5%).

Conclusion

Pre-existing resistance to high-dose isoniazid, and ethambutol is associated with recent transmission of RR/MDR strains in our study. A possible contributing factor for this observation is the absence of universal drug susceptibility testing in Cameroon, likely resulting in prolonged exposure of new RR/MDR-TB patients to sub-optimal or failing first-line drug regimens.
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Literature
2.
go back to reference Aung KJM, Van Deun A, Declercq E, Sarker MR, Das PK, Hossain MA, et al. Successful “9-month Bangladesh regimen” for multidrug-resistant tuberculosis among over 500 consecutive patients. Int J Tuberc Lung Dis. 2014;18:1180–7.CrossRef Aung KJM, Van Deun A, Declercq E, Sarker MR, Das PK, Hossain MA, et al. Successful “9-month Bangladesh regimen” for multidrug-resistant tuberculosis among over 500 consecutive patients. Int J Tuberc Lung Dis. 2014;18:1180–7.CrossRef
3.
go back to reference Moodley R, Godec TR. Short-course treatment for multidrug-resistant tuberculosis: the STREAM trials. Eur Respir Rev. 2016;25:29–35.CrossRef Moodley R, Godec TR. Short-course treatment for multidrug-resistant tuberculosis: the STREAM trials. Eur Respir Rev. 2016;25:29–35.CrossRef
6.
go back to reference Van Deun A, Maug AKJ, Salim MAH, Das PK, Sarker MR, Daru P, et al. Short, highly effective, and inexpensive standardized treatment of multidrug-resistant tuberculosis. Am J Respir Crit Care Med. 2010;182:684–92.CrossRef Van Deun A, Maug AKJ, Salim MAH, Das PK, Sarker MR, Daru P, et al. Short, highly effective, and inexpensive standardized treatment of multidrug-resistant tuberculosis. Am J Respir Crit Care Med. 2010;182:684–92.CrossRef
7.
go back to reference Kuaban C, Noeske J, Rieder HL, Aït-Khaled N, Abena Foe JL, Trébucq A. High effectiveness of a 12-month regimen for MDR-TB patients in Cameroon. Int J Tuberc Lung Dis. 2015;19:517–24.CrossRef Kuaban C, Noeske J, Rieder HL, Aït-Khaled N, Abena Foe JL, Trébucq A. High effectiveness of a 12-month regimen for MDR-TB patients in Cameroon. Int J Tuberc Lung Dis. 2015;19:517–24.CrossRef
8.
go back to reference Piubello A, Harouna SH, Souleymane MB, Boukary I, Morou S, Daouda M, et al. High cure rate with standardised short-course multidrug-resistant tuberculosis treatment in Niger: no relapses. Int J Tuberc Lung Dis. 2014;18:1188–94.CrossRef Piubello A, Harouna SH, Souleymane MB, Boukary I, Morou S, Daouda M, et al. High cure rate with standardised short-course multidrug-resistant tuberculosis treatment in Niger: no relapses. Int J Tuberc Lung Dis. 2014;18:1188–94.CrossRef
9.
go back to reference Lange C, Duarte R, Fréchet-Jachym M, Guenther G, Guglielmetti L, Olaru ID, et al. Limited benefit of the new shorter multidrug-resistant tuberculosis regimen in Europe. Am J Respir Crit Care Med. 2016;194:1029–31.CrossRef Lange C, Duarte R, Fréchet-Jachym M, Guenther G, Guglielmetti L, Olaru ID, et al. Limited benefit of the new shorter multidrug-resistant tuberculosis regimen in Europe. Am J Respir Crit Care Med. 2016;194:1029–31.CrossRef
11.
go back to reference Nunn AJ, Phillips PPJ, Meredith SK, Chiang C-Y, Conradie F, Dalai D, et al. A trial of a shorter regimen for rifampin-resistant tuberculosis. N Engl J Med. 2019;380:1201–13.CrossRef Nunn AJ, Phillips PPJ, Meredith SK, Chiang C-Y, Conradie F, Dalai D, et al. A trial of a shorter regimen for rifampin-resistant tuberculosis. N Engl J Med. 2019;380:1201–13.CrossRef
12.
go back to reference Ahmad Khan F, Salim MAH, du Cros P, Casas EC, Khamraev A, Sikhondze W, et al. Effectiveness and safety of standardised shorter regimens for multidrug-resistant tuberculosis: individual patient data and aggregate data meta-analyses. Eur Respir J. 2017;50(1):1700061.CrossRef Ahmad Khan F, Salim MAH, du Cros P, Casas EC, Khamraev A, Sikhondze W, et al. Effectiveness and safety of standardised shorter regimens for multidrug-resistant tuberculosis: individual patient data and aggregate data meta-analyses. Eur Respir J. 2017;50(1):1700061.CrossRef
13.
go back to reference Kendall EA, Fofana MO, Dowdy DW. Burden of transmitted multidrug resistance in epidemics of tuberculosis: a transmission modelling analysis. Lancet Respir Med. 2015;3:963–72.CrossRef Kendall EA, Fofana MO, Dowdy DW. Burden of transmitted multidrug resistance in epidemics of tuberculosis: a transmission modelling analysis. Lancet Respir Med. 2015;3:963–72.CrossRef
15.
go back to reference Shah NS, Auld SC, Brust JCM, Mathema B, Ismail N, Moodley P, et al. Transmission of extensively drug-resistant tuberculosis in South Africa. N Engl J Med. 2017;376:243–53.CrossRef Shah NS, Auld SC, Brust JCM, Mathema B, Ismail N, Moodley P, et al. Transmission of extensively drug-resistant tuberculosis in South Africa. N Engl J Med. 2017;376:243–53.CrossRef
16.
go back to reference Trébucq A, Schwoebel V, Kashongwe Z, Bakayoko A, Kuaban C, Noeske J, et al. Treatment outcome with a short multidrug-resistant tuberculosis regimen in nine African countries. Int J Tuberc Lung Dis. 2018;22:17–25.CrossRef Trébucq A, Schwoebel V, Kashongwe Z, Bakayoko A, Kuaban C, Noeske J, et al. Treatment outcome with a short multidrug-resistant tuberculosis regimen in nine African countries. Int J Tuberc Lung Dis. 2018;22:17–25.CrossRef
18.
go back to reference Coll F, McNerney R, Guerra-Assunção JA, Glynn JR, Perdigão J, Viveiros M, et al. A robust SNP barcode for typing Mycobacterium tuberculosis complex strains. Nat Commun. 2014;5:4812.CrossRef Coll F, McNerney R, Guerra-Assunção JA, Glynn JR, Perdigão J, Viveiros M, et al. A robust SNP barcode for typing Mycobacterium tuberculosis complex strains. Nat Commun. 2014;5:4812.CrossRef
19.
go back to reference Heep M, Brandstätter B, Rieger U, Lehn N, Richter E, Rüsch-Gerdes S, et al. Frequency of rpoB mutations inside and outside the cluster I region in rifampin-resistant clinical Mycobacterium tuberculosis isolates. J Clin Microbiol. 2001;39:107–10.CrossRef Heep M, Brandstätter B, Rieger U, Lehn N, Richter E, Rüsch-Gerdes S, et al. Frequency of rpoB mutations inside and outside the cluster I region in rifampin-resistant clinical Mycobacterium tuberculosis isolates. J Clin Microbiol. 2001;39:107–10.CrossRef
20.
go back to reference Walker TM, Ip CL, Harrell RH, Evans JT, Kapatai G, Dedicoat MJ, et al. Whole-genome sequencing to delineate Mycobacterium tuberculosis outbreaks: a retrospective observational study. Lancet Infect Dis. 2013;13:137–46.CrossRef Walker TM, Ip CL, Harrell RH, Evans JT, Kapatai G, Dedicoat MJ, et al. Whole-genome sequencing to delineate Mycobacterium tuberculosis outbreaks: a retrospective observational study. Lancet Infect Dis. 2013;13:137–46.CrossRef
23.
go back to reference Kohl TA, Harmsen D, Rothgänger J, Walker T, Diel R, Niemann S. Harmonized genome wide typing of tubercle bacilli using a web-based gene-by-gene nomenclature system. EBioMedicine. 2018;34:131–8.CrossRef Kohl TA, Harmsen D, Rothgänger J, Walker T, Diel R, Niemann S. Harmonized genome wide typing of tubercle bacilli using a web-based gene-by-gene nomenclature system. EBioMedicine. 2018;34:131–8.CrossRef
24.
go back to reference Dheda K, Gumbo T, Maartens G, Dooley KE, McNerney R, Murray M, et al. The epidemiology, pathogenesis, transmission, diagnosis, and management of multidrug-resistant, extensively drug-resistant, and incurable tuberculosis. Lancet Respir Med. 2017;5:291–360.CrossRef Dheda K, Gumbo T, Maartens G, Dooley KE, McNerney R, Murray M, et al. The epidemiology, pathogenesis, transmission, diagnosis, and management of multidrug-resistant, extensively drug-resistant, and incurable tuberculosis. Lancet Respir Med. 2017;5:291–360.CrossRef
25.
go back to reference Yang C, Luo T, Shen X, Wu J, Gan M, Xu P, et al. Transmission of multidrug-resistant Mycobacterium tuberculosis in Shanghai, China: a retrospective observational study using whole-genome sequencing and epidemiological investigation. Lancet Infect Dis. 2017;17:275–84.CrossRef Yang C, Luo T, Shen X, Wu J, Gan M, Xu P, et al. Transmission of multidrug-resistant Mycobacterium tuberculosis in Shanghai, China: a retrospective observational study using whole-genome sequencing and epidemiological investigation. Lancet Infect Dis. 2017;17:275–84.CrossRef
26.
go back to reference Lew W, Pai M, Oxlade O, Martin D, Menzies D. Initial drug resistance and tuberculosis treatment outcomes: systematic review and meta-analysis. Ann Intern Med. 2008;149:123–34.CrossRef Lew W, Pai M, Oxlade O, Martin D, Menzies D. Initial drug resistance and tuberculosis treatment outcomes: systematic review and meta-analysis. Ann Intern Med. 2008;149:123–34.CrossRef
27.
go back to reference Hoek KGP, Schaaf HS, Gey van Pittius NC, van Helden PD, Warren RM. Resistance to pyrazinamide and ethambutol compromises MDR/XDR-TB treatment. S Afr Med J. 2009;99:785–7.PubMed Hoek KGP, Schaaf HS, Gey van Pittius NC, van Helden PD, Warren RM. Resistance to pyrazinamide and ethambutol compromises MDR/XDR-TB treatment. S Afr Med J. 2009;99:785–7.PubMed
28.
go back to reference Espinal MA, Kim SJ, Suarez PG, Kam KM, Khomenko AG, Migliori GB, et al. Standard short-course chemotherapy for drug-resistant tuberculosis: treatment outcomes in 6 countries. JAMA. 2000;283:2537–45.CrossRef Espinal MA, Kim SJ, Suarez PG, Kam KM, Khomenko AG, Migliori GB, et al. Standard short-course chemotherapy for drug-resistant tuberculosis: treatment outcomes in 6 countries. JAMA. 2000;283:2537–45.CrossRef
29.
go back to reference Fitzwater SP, Caviedes L, Gilman RH, Coronel J, LaChira D, Salazar C, et al. Prolonged infectiousness of tuberculosis patients in a directly observed therapy short-course program with standardized therapy. Clin Infect Dis. 2010;51:371–8.CrossRef Fitzwater SP, Caviedes L, Gilman RH, Coronel J, LaChira D, Salazar C, et al. Prolonged infectiousness of tuberculosis patients in a directly observed therapy short-course program with standardized therapy. Clin Infect Dis. 2010;51:371–8.CrossRef
30.
go back to reference Escombe AR, Moore DAJ, Gilman RH, Pan W, Navincopa M, Ticona E, et al. The infectiousness of tuberculosis patients coinfected with HIV. PLOS Med. 2008;5:e188.CrossRef Escombe AR, Moore DAJ, Gilman RH, Pan W, Navincopa M, Ticona E, et al. The infectiousness of tuberculosis patients coinfected with HIV. PLOS Med. 2008;5:e188.CrossRef
32.
go back to reference Comas I, Borrell S, Roetzer A, Rose G, Malla B, Kato-Maeda M, et al. Whole-genome sequencing of rifampicin-resistant Mycobacterium tuberculosis strains identifies compensatory mutations in RNA polymerase genes. Nat Genet. 2011;44:106–10.CrossRef Comas I, Borrell S, Roetzer A, Rose G, Malla B, Kato-Maeda M, et al. Whole-genome sequencing of rifampicin-resistant Mycobacterium tuberculosis strains identifies compensatory mutations in RNA polymerase genes. Nat Genet. 2011;44:106–10.CrossRef
33.
go back to reference Ngabonziza JCS, Diallo AB, Tagliani E, Diarra B, Kadanga AE, Togo ACG, et al. Half of rifampicin-resistant Mycobacterium tuberculosis complex isolated from tuberculosis patients in Sub-Saharan Africa have concomitant resistance to pyrazinamide. PLoS ONE. 2017;12:e0187211.CrossRef Ngabonziza JCS, Diallo AB, Tagliani E, Diarra B, Kadanga AE, Togo ACG, et al. Half of rifampicin-resistant Mycobacterium tuberculosis complex isolated from tuberculosis patients in Sub-Saharan Africa have concomitant resistance to pyrazinamide. PLoS ONE. 2017;12:e0187211.CrossRef
34.
go back to reference Cox HS, Sibilia C, Feuerriegel S, Kalon S, Polonsky J, Khamraev AK, et al. Emergence of extensive drug resistance during treatment for multidrug-resistant tuberculosis. N Engl J Med. 2008;359:2398–400.CrossRef Cox HS, Sibilia C, Feuerriegel S, Kalon S, Polonsky J, Khamraev AK, et al. Emergence of extensive drug resistance during treatment for multidrug-resistant tuberculosis. N Engl J Med. 2008;359:2398–400.CrossRef
35.
go back to reference Trébucq A, Decroo T, Van Deun A, Piubello A, Chiang C-Y, Koura KG, et al. Short-course regimen for multidrug-resistant tuberculosis: a decade of evidence. J Clin Med. 2020;9:55.CrossRef Trébucq A, Decroo T, Van Deun A, Piubello A, Chiang C-Y, Koura KG, et al. Short-course regimen for multidrug-resistant tuberculosis: a decade of evidence. J Clin Med. 2020;9:55.CrossRef
Metadata
Title
Transmission patterns of rifampicin resistant Mycobacterium tuberculosis complex strains in Cameroon: a genomic epidemiological study
Authors
Matthias Merker
Nkongho F. Egbe
Yannick R. Ngangue
Comfort Vuchas
Thomas A. Kohl
Viola Dreyer
Christopher Kuaban
Jürgen Noeske
Stefan Niemann
Melissa S. Sander
Publication date
01-12-2021
Publisher
BioMed Central
Published in
BMC Infectious Diseases / Issue 1/2021
Electronic ISSN: 1471-2334
DOI
https://doi.org/10.1186/s12879-021-06593-8

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