Typhoid Vaccine Clinical Trial in Nepal: Phase III Results

Typhoid causes 11-21 million cases and 117,000-161,000 deaths annually worldwide. It is a huge public health problem in Kathmandu, the Capital of Nepal, where it is responsible for approximately 45 percent of all bloodstream infections in children.

The incidence of typhoid in Kathmandu is highest in the months of July and August and lowest during the winter months. The annual incidence of typhoid in Kathmandu varies between 297 and 449 per 100,000 population. Moreover, the increased public health threat of typhoid has occurred due to emergence of antibiotic resistance, not just in Nepal, but also in other countries in South Asia, including India, Bangladesh and Pakistan.

Background of the Study

The use of typhoid vaccines for preventing typhoid fever was recommended by the World Health Organization (WHO) way back in 2008. However, although several typhoid vaccines have been developed since then, none of them were successful in preventing typhoid fever.

In recent years, a new generation of typhoid conjugate vaccines has been developed in which a Salmonella typhi antigen is conjugated (attached) to a tetanus-toxin protein that acts as a carrier for the antigen. One of these typhoid conjugate vaccines has been found to be highly immunogenic, safe and efficacious in both children and adults. However, data from clinical trials in typhoid endemic areas is still lacking. The present clinical trial attempted to fill this lacuna in knowledge.

Key Features of the Study

• This was a Phase III, double-blind, randomized, controlled trial, meaning that it was very well-designed, highly rigorous and adhered to stringent protocol
• The clinical trial was conducted in Lalitpur Metropolitan City in the Kathmandu Valley in Nepal
• The study period was from 20^th November 2017 to 9^th April 2018
• 20,019 healthy children between the ages of 9 months and 16 years were included in the trial
• The children were assigned to the following two groups:
• Experimental Group: This group received the tetanus-toxoid conjugated Vi polysaccharide typhoid vaccine (Typbar-TCV) manufactured by Bharat Biotech International, Hyderabad, India
• Control Group: This group received the meningococcal capsular group A conjugate vaccine (MenAfriVac) manufactured by Serum Institute of India, Pune, India
• The total follow-up period after vaccination was 2 years

Key Findings of the Study

• The typhoid vaccine protected 81.6 percent of the vaccinated children against typhoid fever
• The typhoid vaccine generated a very strong immune response - protective antibodies were detected in 99.1 percent of vaccinated children
• Adverse reactions were present in less than 5 percent of vaccinated children

Summary

• A single dose of the typhoid vaccine was highly immunogenic and efficacious
• A single dose of the typhoid vaccine led to a reduction of 82 percent in the incidence of typhoid fever
• The immunogenicity of the typhoid vaccine was very high and elicited antibodies within 1 month of vaccination
• The typhoid vaccine was safe as adverse reactions were minimal

Conclusion

It may be concluded that the typhoid conjugate vaccine is a highly immunogenic, safe and effective vaccine for vaccinating children living in endemic areas, who are at high risk of developing typhoid fever.

Funding Source

The study was funded by the Bill & Melinda Gates Foundation, Seattle, Washington, USA.

Reference :

1. Phase 3 Efficacy Analysis of a Typhoid Conjugate Vaccine Trial in Nepal - (https://www.nejm.org/doi/full/10.1056/NEJMoa1905047)

Source: Medindia