Population structure and antimicrobial resistance patterns of
Salmonella
Typhi and Paratyphi A amid a phased municipal vaccination campaign in Navi Mumbai, India
Authors: da Silva Kesia Esther , Date Kashmira , Hirani Nilma , LeBoa Christopher , Jayaprasad Niniya , Borhade Priyanka , Warren Joshua , Shimpi Rahul , Hoffman Seth A. , Mikoleit Matthew , Bhatnagar Pankaj , Cao Yanjia , Haldar Pradeep , Harvey Pauline , Zhang Chenhua , Daruwalla Savita , Dharmapalan Dhanya , Gavhane Jeetendra , Joshi Shrikrishna , Rai Rajesh , Rathod Varsha , Shetty Keertana , Warrier Divyalatha S. , Yadav Shalini , Chakraborty Debjit , Bahl Sunil , Katkar Arun , Kunwar Abhishek , Yewale Vijay , Dutta Shanta , Luby Stephen P. , Andrews Jason R. 
Published: July 2023

We performed whole-genome sequencing of 174
Salmonella
Typhi and 54
Salmonella
Paratyphi A isolates collected through prospective surveillance in the context of a phased typhoid conjugate vaccine introduction in Navi Mumbai, India. We investigate the temporal and geographical patterns of emergence and spread of antimicrobial resistance. We evaluated the relationship between the spatial distance between households and genetic clustering of isolates. Most isolates were non-susceptible to fluoroquinolones, with nearly 20% containing ≥3 quinolone resistance-determining region mutations. Two H58 isolates carried an IncX3 plasmid containing bla
SHV-12
, associated with ceftriaxone resistance, suggesting that the ceftriaxone-resistant isolates from India independently evolved on multiple occasions. Among
S
. Typhi, we identified two main clades circulating (2.2 and 4.3.1 [H58]); 2.2 isolates were closely related following a single introduction around 2007, whereas H58 isolates had been introduced multiple times to the city. Increasing geographic distance between isolates was strongly associated with genetic clustering (odds ratio [OR] = 0.72 per km; 95% credible interval [CrI]: 0.66–0.79). This effect was seen for distances up to 5 km (OR = 0.65 per km; 95% CrI: 0.59–0.73) but not seen for distances beyond 5 km (OR = 1.02 per km; 95% CrI: 0.83–1.26). There was a non-significant reduction in odds of clustering for pairs of isolates in vaccination communities compared with non-vaccination communities or mixed pairs compared with non-vaccination communities. Our findings indicate that
S
. Typhi was repeatedly introduced into Navi Mumbai and then spread locally, with strong evidence of spatial genetic clustering. In addition to vaccination, local interventions to improve water and sanitation will be critical to interrupt transmission.

IMPORTANCE

Enteric fever remains a major public health concern in many low- and middle-income countries, as antimicrobial resistance (AMR) continues to emerge. Geographical patterns of typhoidal
Salmonella
spread, critical to monitoring AMR and planning interventions, are poorly understood. We performed whole-genome sequencing of
S
. Typhi and
S
. Paratyphi A isolates collected in Navi Mumbai, India before and after a typhoid conjugate vaccine introduction. From timed phylogenies, we found two dominant circulating lineages of
S
. Typhi in Navi Mumbai-lineage 2.2, which expanded following a single introduction a decade prior, and 4.3.1 (H58), which had been introduced repeatedly from other parts of India, frequently containing “triple mutations” conferring high-level ciprofloxacin resistance. Using Bayesian hierarchical statistical models, we found that spatial distance between cases was strongly associated with genetic clustering at a fine scale (<5 km). Together, these findings suggest that antimicrobial-resistant
S
. Typhi frequently flows between cities and then spreads highly locally, which may inform surveillance and prevention strategies.