High-Resolution Genotyping of the Endemic Salmonella Typhi Population during a Vi (Typhoid) Vaccination Trial in Kolkata

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Abstract
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. 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). 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. 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. Typhoid fever is caused by the bacterium Salmonella enterica serovar Typhi (S. Typhi) and 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. We used single nucleotide polymorphism (SNP) typing to investigate the population structure of 372 S. Typhi bacteria isolated from typhoid patients during a typhoid disease burden study and Vi anti-typhoid vaccine trial in Kolkata, India. Approximately sixty thousand people were enrolled for fever surveillance for 19 months prior to, and 24 months following, vaccination of one third of the study population against typhoid (May 2003–December 2006, vaccinations given December 2004). We detected a diverse population of S. Typhi, including 21 different genetic forms (haplotypes) of the bacteria. The most common (69%) were of a haplogroup known as H58, which included all multidrug resistant isolates (bacteria resistant to the antibiotics chloramphenicol, ampicillin and co-trimoxazole). Resistance to quinolones, a class of antibiotics commonly used to treat typhoid fever, was particularly high among a subgroup of H58 (H58-G). Vi vaccination did not obviously impact on the haplotype distribution of the S. Typhi circulating during the study period.

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