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.
Subject(s)
Disease Outbreaks , Molecular Typing , Salmonella typhi/classification , Typhoid Fever/epidemiology , Typhoid-Paratyphoid Vaccines/administration & dosage , Vaccination/methods , Anti-Bacterial Agents/pharmacology , Clinical Trials as Topic , Drug Resistance, Bacterial , Genotype , Humans , India/epidemiology , Molecular Epidemiology , Polymorphism, Single Nucleotide , Quinolones/pharmacology , Salmonella typhi/genetics , Salmonella typhi/isolation & purification , Typhoid Fever/microbiologyABSTRACT
BACKGROUND: Typhoid fever remains an important cause of illness and death in the developing world. Uncertainties about the protective effect of Vi polysaccharide vaccine in children under the age of 5 years and about the vaccine's effect under programmatic conditions have inhibited its use in developing countries. METHODS: We conducted a phase 4 effectiveness trial in which slum-dwelling residents of Kolkata, India, who were 2 years of age or older were randomly assigned to receive a single dose of either Vi vaccine or inactivated hepatitis A vaccine, according to geographic clusters, with 40 clusters in each study group. The subjects were then followed for 2 years. RESULTS: A total of 37,673 subjects received a dose of a study vaccine. The mean rate of vaccine coverage was 61% for the Vi vaccine clusters and 60% for the hepatitis A vaccine clusters. Typhoid fever was diagnosed in 96 subjects in the hepatitis A vaccine group, as compared with 34 in the Vi vaccine group, with no subject having more than one episode. The level of protective effectiveness for the Vi vaccine was 61% (95% confidence interval [CI], 41 to 75; P<0.001 for the comparison with the hepatitis A vaccine group). Children who were vaccinated between the ages of 2 and 5 years had a level of protection of 80% (95% CI, 53 to 91). Among unvaccinated members of the Vi vaccine clusters, the level of protection was 44% (95% CI, 2 to 69). The overall level of protection among all residents of Vi vaccine clusters was 57% (95% CI, 37 to 71). No serious adverse events that were attributed to either vaccine were observed during the month after vaccination. CONCLUSIONS: The Vi vaccine was effective in young children and protected unvaccinated neighbors of Vi vaccinees. The potential for combined direct and indirect protection by Vi vaccine should be considered in future deliberations about introducing this vaccine in areas where typhoid fever is endemic. (ClinicalTrials.gov number, NCT00125008.)
Subject(s)
Polysaccharides, Bacterial/immunology , Typhoid Fever/prevention & control , Typhoid-Paratyphoid Vaccines/immunology , Adolescent , Adult , Antibodies, Bacterial/blood , Child , Child, Preschool , Developing Countries , Hepatitis A Vaccines/adverse effects , Humans , Immunoglobulin G/blood , India , Paratyphoid Fever/epidemiology , Polysaccharides, Bacterial/adverse effects , Population Surveillance , Salmonella typhi/immunology , Treatment Outcome , Typhoid Fever/epidemiology , Typhoid Fever/immunology , Typhoid-Paratyphoid Vaccines/adverse effectsABSTRACT
An outbreak of febrile illness occurred in Kolkata (formerly Calcutta), India, which led to an increased utilization of treatment centre facilities during August – September 2005. The etiological agent was confirmed to be dengue by analysing 308 acute-phase clinical specimens for virus-specific IgM antibodies.