A single dose of typhoid conjugate vaccine (TCV) offers safe, effective protection against typhoid two years after vaccination in all children, and sustained protection for older children at three to five years post immunisation, according to a report by researchers at the Oxford Vaccine Group and the International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b). But it also shows a decline in protection at the later timepoints among children vaccinated at younger ages.
The TyVOID study, published in the Lancet, measured the effectiveness of a single dose TCV in Bangladeshi children over a five-year period and confirmed the high vaccine protection (80-96%) within two years of vaccination in all children.
Three to five years after vaccination, the study found a three-fold increase in typhoid incidence in children who received TCV in 2018/2019 and those who received it in 2021, suggesting a decline in vaccine effectiveness, most pronounced in the very young. The data suggested children vaccinated at two years or older were still well protected (59-85%) at 3-5 years post vaccination however, a more significant decline in protection was seen in children vaccinated at under two years of age, suggesting that a booster dose for these children might be needed for sustained protection.
Xinxue Liu, Associate Professor of Medical Statistics and Epidemiology at the Oxford Vaccine Group, and one of the senior authors of the study, said: 'Typhoid is a serious and life-threatening enteric fever that remains a substantial public health issue for children and adolescents in low- and middle-income countries. TCV offers the best chance to reduce the burden of typhoid, helping to reduce transmission and limiting further evolution of drug-resistant strains. This study provides additional information for policy makers on longer-term TCV protection and the importance of continued investigation and updated guidance.'
Dr Firdausi Qadri, Senior Scientist at the Infectious Diseases Division at the International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), and first author on the study, said: 'This TyVOID study followed the original TyVAC cluster randomised controlled trial population for another two and a half years after unmasking in 2021. The results indicate a decay in antibody concentrations in different age groups and suggest that a booster dose around school entry age for children vaccinated while younger than 2 years could be considered, to sustain the protection from TCV through the school years when children are at greatest risk of typhoid.'
Professor Sir Andrew Pollard, Director of the Oxford Vaccine Group, said: 'The current recommendation by WHO is a single dose of TCV for infants and children from 6 months of age. Epidemiological studies in different countries across Asia and Africa showed that the incidence of typhoid fever is much higher in children younger than 16 years than it is in adults, with the peak of cases seen in those aged 5-9 years. Whether a single dose of TCV provides long-term protection continues to be a top research priority to advise policy makers.'
Typhoid fever continues to place a substantial disease burden on low-income and middle-income countries marked by inadequate sanitation and limited access to clean water and contaminated food. There are estimated to be over 7 million cases and 93,000 deaths annually worldwide. In Bangladesh, typhoid fever was ranked fourth among the causes of under-5 mortality in 2019. In addition, the escalation of antimicrobial resistance, underscored by the emergence of extensively drug-resistant strains in Asia, has reduced available treatment options and increased the public health threat from this disease. In a multicenter disease burden study, STRATAA, Bangladesh had the highest rates of cholera.
The first typhoid conjugate vaccine (TCV; Bharat Biotech International) received WHO prequalification in 2017 and in 2018 WHO recommended vaccines as an important tool in typhoid prevention and control. In 2025, TCV will be used in vaccination campaigns in children all over Bangladesh.
This report, funded by the Bill and Melinda Gates foundation, confirms the need for further studies to monitor the typhoid burden following the TCV rollout, and to provide additional vaccine protection duration data from high-burden settings as well as effect on the antibiotic resistance pattern, which is crucial for WHO to update their position.
The paper, '5-year vaccine protection following a single dose of Vi-tetanus toxoid conjugate vaccine in Bangladeshi children (TyVOID): a cluster randomised trial', is published in the Lancet.
