Efficacy and safety of vi-tetanus toxoid conjugated typhoid vaccine (PedaTyph™) in Indian children: School based cluster randomized study

Abstract

Vi polysaccharide typhoid vaccines cannot be used in children <2 years owing to poor immunogenic and T cell independent properties. Conjugate vaccine prepared by binding Vi to tetanus toxoids (Vi-TT) induces protective levels even in children <2 years. We evaluated efficacy and safety following vaccination with a Vi-TT vaccine in children 6 months to 12 years of age. Overall, 1765 subjects were recruited from two registered municipal urban slums of southern Kolkata. Most of the children of the slum dwellers attended the schools in the locality which was selected with permission from the school authority. Schools were randomly divided into vaccinated (Test group) and unvaccinated group (Control group). Children and their siblings of test group received 2-doses of PedaTyph TM vaccine at 6 weeks interval. Control group received vaccines as per national guidelines. Adverse events (AEs) were examined after 30 minutes, 1 month and clinical events were observed till 12 months post-vaccination. Incidence of culture positive typhoid fever in the control group was 1.27% vis-a-vis none in vaccine group during 12 months. In subgroup evaluated for immunogenicity, an antibody titer value of 1.8 EU/ml (95% CI: 1.5 EU/ml, 2.2 EU/ml), 32 EU/ml (95% CI: 27.0 EU/ml, 39.0 EU/ml) and 14 EU/ml (95% CI: 12.0 EU/ml, 17.0 EU/ml) at baseline, 6 weeks and 12 months, respectively was observed. Sero-conversion among the sub-group was 100% after 6 weeks of post-vaccination and 83% after 12 months considering 4-fold rise from baseline. The efficacy of vaccine was 100 % (95% CI: 97.6%, 100%) in the first year of follow-up with minimal AEs post vaccination. Vi conjugate typhoid vaccine conferred 100% protection against typhoid fever in 1765 children 6 months to 12 years of age with high immunogenicity in a subgroup from the vaccine arm.

Estimation of Incidence of Typhoid and Paratyphoid Fever in Vientiane, Lao People’s Democratic Republic

“…A recent systematic review of global typhoid fever incidence studies showed that annual incidence in studies carried out at sites in Asia in the period 2000-2013 ranged from 15 per 100,000 population in China 22 to 1,279 per 100,000 population in India. 23 The overall annual typhoid fever incidence across Asian studies in this systematic review was 190 per 100,000 population. 24 Furthermore, a sister study to ours performed in Yangon, Myanmar, for the period 2015-2016 estimated annual typhoid fever and paratyphoid fever incidence there at 391 and 107 per 100,000 population, respectively, albeit with wide uncertainty bounds.…”

Low and declining attack rates of imported typhoid fever in the Netherlands 1997–2014, in spite of a restricted vaccination policy

“…A new conjugate vaccine is in development in India, which could be a good alternative for high risk travelers in the future [21, 22]. In recent years there have been a number of reported multi-year outbreaks of multi-drug resistant typhoid fever [23–26].…”

Vaccines for preventing typhoid fever

“…Vi‐TT , a new conjugated Vi‐polysaccharide linked to tetanus toxoid carrier protein, has been licensed in India in two preparations: Peda Typh (two doses, children six months and above; Mitra 2016 IND ) and Typbar‐TCV (one dose, children six months and above; Jin 2017 ; Mohan 2015 ). WHO has approved Typbar‐TCV for infants and children over six months of age in endemic areas ( WHO 2018a ).…”