A typhoid vaccine, licensed only for use in children less than two years of age in India, could prevent over half of the infections, according to a study published in The Lancet journal. In a trial of 112 adults the Vi-conjugate typhoid vaccine has proven safe, highly immunogenic. The study provides the first efficacy data for the leading candidate vaccine being considered for widespread use in children less than 2 years, who are disproportionately affected by typhoid.
The trial uses a controlled human infection model, in which healthy volunteers are vaccinated and then deliberately exposed to the pathogen. These types of studies have been used to support the development of various vaccines as they can be rapidly deployed to assess vaccine efficacy. The Vi-conjugate vaccine studied in this trial is only licensed for use in children less than two years in India, and there are no typhoid vaccines licensed worldwide for use in children under two years old. The study provides evidence to support the development of Vi-conjugate vaccines as a control measure to reduce the burden of typhoid fever. Typhoid affects between 12.5 and 20.6 million people worldwide in regions with inadequate water quality and poor sanitation, particularly in south Asia and sub-Saharan Africa. One in 100 cases are deadly and approximately three per cent of cases become chronic carriers. Typhoid is caused by Salmonella enterica serovar Typhi (S Typhi bacteria) and is usually treated with antibiotics, but antibiotic resistance is increasing. Children are particularly susceptible to typhoid, but no vaccine is licenced for worldwide use in children less than two years, contributing to poor adoption of typhoid immunisation programmes. In the study led by the University of Oxford in UK, 112 volunteers were randomly assigned to receive a single dose of the Vi-tetanus toxoid conjugate vaccine (Typbar-TCV; Vi-TT), the pre-existing Vi-polysaccharide vaccine (TYPHIM Vi; Vi-PS), which cannot be given to young children, or a control meningococcal conjugate vaccine (MENVEO). One month post-vaccination, participants were given an oral dose of the bacteria (wild type Quailes strain of S Typhi). Participants were monitored daily for a two-week period and were given a course of antibiotics if they were diagnosed with typhoid. At the end of the two weeks, all participants, including those not diagnosed, were given a course of antibiotics. In the control group, 77 per cent of participants were diagnosed with typhoid, compared with 35 per cent Vi-TT recipients and 35 per cent Vi-PS recipients, equivalent to a vaccine efficacy of 54.6 per cent for Vi-TT and 52.0 per cent for Vi-PS. “Our study provides further evidence to support the development of Vi-conjugate vaccines as a control measure to reduce the burden of typhoid fever, and individuals living in endemic regions should not be made to wait another 60 years to receive the vaccine,” said Professor Andrew Pollard, from University of Oxford.