High-resolution genotyping of the endemic Salmonella Typhi population during a Vi (typhoid) vaccination trial in Kolkata

Abstract

Background: Typhoid fever, caused by Salmonella enterica serovar Typhi (S. Typhi), is a major health problem especially in developing countries. Vaccines against typhoid are commonly used by travelers but less so by residents of endemic areas.

Methodology: We used single nucleotide polymorphism (SNP) typing to investigate the population structure of 372 S. Typhi isolated during a typhoid disease burden study and Vi vaccine trial in Kolkata, India. Approximately sixty thousand people were enrolled for fever surveillance for 19 months prior to, and 24 months following, Vi vaccination of one third of the study population (May 2003-December 2006, vaccinations given December 2004).

Principal findings: A diverse S. Typhi population was detected, including 21 haplotypes. The most common were of the H58 haplogroup (69%), which included all multidrug resistant isolates (defined as resistance to chloramphenicol, ampicillin and co-trimoxazole). Quinolone resistance was particularly high among H58-G isolates (97% Nalidixic acid resistant, 30% with reduced susceptibility to ciprofloxacin). Multiple typhoid fever episodes were detected in 22 households, however household clustering was not associated with specific S. Typhi haplotypes.

Conclusions: Typhoid fever in Kolkata is caused by a diverse population of S. Typhi, however H58 haplotypes dominate and are associated with multidrug and quinolone resistance. Vi vaccination did not obviously impact on the haplotype population structure of the S. Typhi circulating during the study period.

Figure 1. S. Typhi haplotypes identified by SNP typing.

Rooted phylogenetic tree indicating S. Typhi haplotypes defined by assayed SNPs, scale as indicated. Haplotypes identified among 372 Kolkata isolates are labeled in black, the number of detected isolates for each haplotype is indicated by bars according to the scale at the bottom. Bars are coloured to indicate major haplotypes, as in Figures 2, 3. The H58 haplogroup is highlighted in grey, and is further divided into two major lineages I and II as indicated.

Figure 2. Temporal distribution of S. Typhi haplotypes.

Monthly frequency of S. Typhi coloured by haplotype (haplotypes defined in Figure 1). Vaccines were administered in December 2004 (indicated by arrows) to approximately two thirds of the study population. (A) S. Typhi isolated from typhoid fever patients in geographical clusters assigned to Vi vaccine. (B) S. Typhi isolated from typhoid fever patients in geographical clusters assigned to hepatitis A vaccine.

Figure 3. Spatial distribution of S. Typhi haplotypes.

Maps of the study site, illustrating the division of the site into 80 geographical clusters randomly assigned to receive Vi or control (hepatitis A) vaccine. The location of each typhoid fever patient's residence is indicated by a star, coloured by the haplogroup of the corresponding S. Typhi isolate. (A) S. Typhi isolated before administration of vaccine (May 2003–November 2004). (B) S. Typhi isolated after administration of vaccine (January 2005–December 2006).