RT Journal Article
SR Electronic
T1 Transmission of pre-XDR and XDR-TB in the Mumbai Metropolitan Region, India
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.02.02.429364
DO 10.1101/2021.02.02.429364
A1 Viola Dreyer
A1 Ayan Mandal
A1 Prachi Dev
A1 Matthias Merker
A1 Ivan Barilar
A1 Christian Utpatel
A1 Kayzad Nilgiriwala
A1 Camilla Rodrigues
A1 Derrick W. Crook
A1 the CRyPTIC Consortium
A1 Nerges Mistry
A1 Stefan Niemann
YR 2021
UL http://biorxiv.org/content/early/2021/02/22/2021.02.02.429364.abstract
AB Multidrug-resistant (MDR) and extensively drug resistant (XDR) Mycobacterium tuberculosis complex (MTBC) strains are a great challenge for tuberculosis (TB) control in India. Still, factors driving the MDR/XDR epidemic in India are not well defined.To address this, whole genome sequencing (WGS) data from 1 852 MTBC strains obtained from patients from a tertiary care hospital laboratory in Mumbai were used for phylogenetic strain classification, resistance prediction, and cluster analysis (12 allele distance threshold). Factors associated with pre-XDR/XDR-TB were defined by odds ratios and a multivariate logistic regression model.Overall, 1 017 MTBC strains were MDR, out of which 57.8 % (n=591) were pre-XDR, and 17.9 % (n=183) were XDR. Lineage 2 (L2) strains represented 41.7 % of the MDR, 77.2 % of the pre-XDR, and 86.3 % of the XDR strains, and were significantly associated with pre-XDR/XDR-TB (P < 0.001). Cluster rates were high among MDR (78 %) and pre-XDR/XDR (85 %) strains with three dominant L2 strain clusters (Cl 1-3) representing half of the pre-XDR and two thirds of the XDR-TB cases. Cl 1 strains accounted for 52.5 % of the XDR MTBC strains. Transmission could be confirmed by identical mutation patterns of particular pre-XDR/XDR strains.As a conclusion high rates of pre-XDR/XDR strains among MDR-TB patients require rapid changes in treatment and control strategies. Transmission of particular pre-XDR/XDR L2 strains is the main driver of the pre-XDR/XDR-TB epidemic. Accordingly, control of the epidemic in the region requires measures with stopping transmission especially of pre-XDR/XDR L2 strains.Competing Interest StatementThe authors have declared no competing interest.