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Transmission of drug resistant tuberculosis in Mozambique

I Barilar(1,2) T Fernando(3) C Utpatel(1) C Abujate(3) C M Madeira(3) B Jose(4) C Mutaquiha(4) K Kranzer(5,6,7,10) T Niemann(1,2) N Ismael(3) L D Araujo(1) T Wirth(8,9) S Niemann(1,2,11) S Viegas(3)

1:Molecular and Experimental Mycobacteriology, Research Center Borstel, Borstel Germany; 2:German Center for Infection Research, Partner Site Hamburg-Lübeck-Borstel-Riems, Borstel, Germany; 3:Instituto Nacional de Saúde, Marracuene, Mozambique; 4:National Tuberculosis Control Program, Directorate of Public Health, Ministry of Health, Maputo, Mozambique; 5:Biomedical Research and Training Institute, Harare, Zimbabwe; 6:Department of Clinical Research, Faculty of Infectious and Tropical Diseases, London; 7:Division of Infectious Diseases and Tropical Medicine, University Hospital, LMU Munich, Munich, Germany; 8:EPHE, PSL University, Paris, France; 9:Institut de Systématique, Evolution, Biodiversité, ISYEB, Muséum national d’Histoire naturelle, CNRS, Sorbonne Université, EPHE, Université des Antilles, Paris, France.; 10:School of Hygiene & Tropical Medicine, London, UK; 11:Department of Human, Biological and Translational Medical Sciences, School of Medicine, University of Namibia, Windhoek, Namibia

With an estimated tuberculosis (TB) incidence of 368/100,000 and more than 4000 new rifampicin resistant (RR) or multidrug resistant (MDR) cases occurring every year, Mozambique is severely affected by the TB epidemic. However, detailed data on the drivers of the drug resistant (DR) TB epidemic in the country is not available.

To address this question, we performed whole genome sequencing (WGS) of 809 DR Mycobacterium tuberculosis complex (Mtbc) strains submitted to the National Tuberculosis Reference Laboratory in Maputo, Mozambique between 2015 and 2021. WGS data were used to perform phylogenetic lineage classification, DR profiling and transmission cluster analysis (12 SNP threshold).

628 strains were classified as MDR, out of which 21 % were pre-extensively drug resistant (XDR) due to a fluoroquinolone (FQ) resistance. 61 strains had a bedaquiline (BDQ) resistance with increasing prevalence over the study period. The cluster rate was high reaching 94% and 96% among pre-XDR and XDR Mtbc strains, respectively. Several large clusters with up to 72 isolates were detected. Particularly interesting were two outbreak clones. The first comprised 36 Ancestral 1 Beijing strains (2.2.2), which all had a FQ resistance and four an additional BDQ resistance. The second formed by 38 S-type strains (, all with the RR rpoB I491F not detected by conventional molecular DR tests. Out of these, 19 were BDQ resistant, and 13 XDR.

In conclusion, transmission appears to be a main driver of DR-TB epidemic in Mozambique. Furthermore, public action has to be taken to control the emergence of pre-XDR/XDR-TB and "diagnostics escape" strains.

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