Typhoid Vaccine Clinical Trial in Nepal: Phase III Results

Phase III clinical trial of a typhoid conjugate vaccine conducted over 20,000 children in Kathmandu, Nepal, is highly immunogenic, safe and effective for vaccinating children at high risk.

Highlights:

A Phase III clinical trial of a new typhoid conjugate vaccine was conducted in over 20,000 children in Nepal
The vaccine was highly immunogenic, as well as safe and effective for vaccination of children at high risk
The vaccine has the potential to significantly reduce the global burden of typhoid

Phase III clinical trial of a new typhoid conjugate vaccine in Nepal showed that a single dose of the vaccine was immunogenic and effectively protected children against Salmonella typhi, the causative agent of typhoid.

The study has been published in the New England Journal of Medicine (NEJM), a publication of the Massachusetts Medical Society, Waltham, MA, USA.

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‘A Phase III clinical trial of a typhoid conjugate vaccine conducted in Nepal was highly immunogenic, safe and effective for vaccination of children at high risk of contracting typhoid.’
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Typhoid: Major Public Health Problem in Nepal

Typhoid fever - also called enteric fever – is characterized by high fever and diarrhea and is caused by the bacterium Salmonella typhi, which attacks the gut and is spread through contaminated food and water.

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.

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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.

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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

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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:

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

Source-Medindia