Journal Article

Population structure and antimicrobial resistance patterns of Salmonella Typhi isolates in urban Dhaka, Bangladesh from 2004 to 2016

Holt, Kathryn E., Dyson, Zoe A., Chowdhury, Emran Kabir, Klemm, Elizabeth J., Dougan, Gordon, Khanam, Farhana, Rahman, Sadia Isfat Ara, Qadri, Firdausi

2020

Overview

Multi-drug resistant typhoid fever remains an enormous public health threat in low and middle-income countries. However, we still lack a detailed understanding of the epidemiology and genomics of S. Typhi in many regions. Here we have undertaken a detailed genomic analysis of typhoid in urban Dhaka, Bangladesh to unravel the population structure and antimicrobial resistance patterns in S. Typhi isolated between 2004-2016. Whole genome sequencing of 202 S. Typhi isolates obtained from three study locations in urban Dhaka revealed a diverse range of S. Typhi genotypes and AMR profiles. The bacterial population within Dhaka were relatively homogenous with little stratification between different healthcare facilities or age groups. We also observed evidence of exchange of Bangladeshi genotypes with neighboring South Asian countries (India, Pakistan and Nepal) suggesting these are circulating throughout the region. This analysis revealed a decline in H58 (genotype 4.3.1) isolates from 2011 onwards, coinciding with a rise in a diverse range of non-H58 genotypes and a simultaneous rise in isolates with reduced susceptibility to fluoroquinolones, potentially reflecting a change in treatment practices. We identified a novel S. Typhi genotype, subclade 3.3.2 (previously defined only to clade level, 3.3), which formed two localized clusters (3.3.2.Bd1 and 3.3.2.Bd2) associated with different mutations in the Quinolone Resistance Determining Region (QRDR) of gene gyrA. Our analysis of S. Typhi isolates from urban Dhaka, Bangladesh isolated over a twelve year period identified a diverse range of AMR profiles and genotypes. The observed increase in non-H58 genotypes associated with reduced fluoroquinolone susceptibility may reflect a change in treatment practice in this region and highlights the importance of continued molecular surveillance to monitor the ongoing evolution of AMR in Dhaka. We have defined new genotypes and lineages of Bangladeshi S. Typhi which will facilitate the identification of these emerging AMR clones in future surveillance efforts.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Age groups / Agglutination tests / Analysis / Anti-Bacterial Agents - pharmacology / Antibacterial agents / Antibiotics / Antimicrobial agents / Antimicrobial resistance / Archives & records / Bangladesh - epidemiology / Biology and Life Sciences / Clones / Computer and Information Sciences / Countries / Deoxyribonucleic acid / DNA / DNA sequencing / DNA, Bacterial - genetics / Drug resistance / Drug Resistance, Bacterial - genetics / Epidemiology / Fever / Fluoroquinolones / Funding / Gene sequencing / Genes / Genetic aspects / Genetic research / Genome, Bacterial / Genomes / Genomic analysis / Genomics / Genotype / Genotypes / Health aspects / Health care facilities / Health facilities / Health risks / Humans / Identification / Infectious diseases / Internationality / Medicine and Health Sciences / Microbial drug resistance / Multidrug resistance / Mutation / Novels / Pathogens / People and Places / Polymorphism, Single Nucleotide / Population / Population structure / Profiles / Public health / Public health movements / Rahman, Zoe / Retrospective Studies / Salmonella / Salmonella Infections - epidemiology / Salmonella Infections - microbiology / Salmonella Infections - transmission / Salmonella typhi - drug effects / Salmonella typhi - genetics / Salmonella typhi - isolation & purification / Sanitation / Stratification / Structure (Literature) / Supervision / Surveillance / Time Factors / Travel / Tropical diseases / Typhoid / Typhoid fever / Urban areas / Urban Population / Waterborne diseases / Whole genome sequencing