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

Abstract

BackgroundMulti-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. Principal findingsWhole 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.

SalmonellaTyphi acquires diverse plasmids from other Enterobacteriaceae to develop cephalosporin resistance

“…The only exception is the previously reported ceftriaxone resistant S. Typhi from Gurgaon, India which originated from lineage 4.3.1.1[13]. In contrast to the above observations, isolates from Bangladesh, Democratic Republic of Congo (DRC) and Philippines clustered with the non-H58 phylogenetic lineages(26)(27)(28)(29).…”

Antimicrobial Resistance in Typhoidal Salmonella: Surveillance for Enteric Fever in Asia Project, 2016–2019

“…A declining trend of MDR typhoid in South Asia has been reported, with the exception of Pakistan, where drug resistance continues to be high [ 10 ]. In Bangladesh, a decline in the isolation rate of MDR strains was reported between 2004–2016 [ 11 ], with a similar observation being reported from India and Nepal [ 12–16 ]. Some suggest that with a significant decrease in MDR strains, cheaper and more effective first-line antibiotics may re-emerge as drugs of choice for the treatment of typhoid fever in these countries [ 12 ], although this idea needs to be evaluated in clinical practice before any change in treatment recommendations are proposed.…”

Genomic profiling of antimicrobial resistance genes in clinical isolates of Salmonella Typhi from patients infected with Typhoid fever in India

“…H58 lineage I (genotype 4.3.1.1) was present in 13.53% (18/133) of the isolates, whereas H58 lineage II (genotype 4.3.1.2) was dominant in the majority of the isolates (70/133, 52.63%). The H58 lineage II isolates appeared to be dominant in Nepal, India and Pakistan 12,51,52 , whereas it was rare in nearby country Bangladesh 56 . In contrast, H58 lineage I (genotype 4.3.1.1) isolates were dominant (31.2%) in Bangladesh compared to India (13.53%).…”

“…Genotype-associated sequence types (ST), mutation patterns in the genes encoding DNA gyrase (gyrA and gyrB) or topoisomerase (parC and parE) and known plasmid Inc types in S. Typhi.clusters and reference strain. The isolates belonging to genotype 3.3.2 were clustered in two clades, each with a different mutation (S83Y; D87Y) in the Quinolone Resistance Determining Region (QRDR) of gene gyrA as conveyed in Bangladesh56 . QRDR double mutation in gyrA (S83F) and parE (L416F) was commonly observed in the cluster of genotype 3.3.1 which is linked with travel to West Africa54 .…”