Typhoid Vaccination Offers Protection for Children

With typhoid fever a growing threat in sub-Saharan Africa, vaccination offered a protective effect in children in Malawi, according to a paper published in The New England Journal of Medicine.

Investigators from the Malawi–Liverpool–Wellcome Program randomly assigned children to receive a Vi polysaccharide typhoid conjugate vaccine (Vi-TCV) or meningococcal capsular group A conjugate (MenA) vaccine in order to define the vaccine efficacy and safety outcomes after between 18 to 24 months of follow-up. The study authors said that typhoid fever is an increasing public health threat in sub-Saharan Africa, with 1.2 million annual cases and 18,703 deaths attributed to typhoid.

Their analysis took place among more than 28,000 children aged 9 months to 12 years in Blantyre, Malawi. Of that group, half were assigned to Vi-TCV and the remainder were assigned to receive the MenA vaccine. The World Health Organization (WHO) recommended typhoid conjugate vaccine (TCV) for use in all countries where the disease is endemic, the study authors noted. They also added that Vi-TCV contains 25 μg of Vi polysaccharide per 0.5-ml dose while MenA was administered at a dose of 10 μg per 0.5 ml to children 1 year of age or older and at a dose of 5 μg per 0.5 ml to children younger than 1 year of age. Both vaccines were administered with routine measles-rubella vaccines in children aged 9 to 11 months.

Between February 2018 and April 2020, there were 7776 children who presented to a passive surveillance center and who met the criteria for a blood sample, which was obtained from 7,314 children, the study authors wrote. Of those, 75 samples were positive for S. Typhi, and all were isolates of MDR, the investigators determined. Additionally, 4 were resistant to ciprofloxacin.

The study authors observed 74 confirmed cases of typhoid fever: 62 cases from the MenA group and 12 from the Vi-TCV group. The study authors noted that 1 participant from the MenA group died from severe typhoid after 7 months post-vaccination, but the protective efficacy of Vi-TCV post-vaccination was 80 percent. After 12 months, the estimated efficacy for Vi-TCV was 84 percent, which dropped to 82 at 18 months, and 78 percent at 24 months.

Rash and syncope were found in 2 boys within 30 minutes after vaccination which was said to be related to the administration, and 1 case of diarrhea was determined to be unrelated to vaccination. There were 14 serious adverse events (4 in the Vi-TCV group, and 10 in the MenA group) within 28 days after vaccination, the study authors found. And 6 months after vaccination, there were 130 recorded serious adverse events (52 in Vi-TCV group, 78 in MenA group) among 118 participants. The study authors noted that the most common serious adverse events included respiratory tract infection, gastroenteritis, and malaria.

The study authors also said that 196 children identified as HIV-infected and of those, 190 received antiretroviral therapy (89 in the Vi-TCV group, 107 in MenA). There were 6 deaths within 6 months post-vaccination, all from the MenA group, the study authors noted, but they also determined that the deaths were unrelated to vaccination.

“The efficacy of Vi-TCV was similar in children who were younger than 5 years of age and children who were 5 years of age or older at the time of vaccination, and this efficacy remained consistent throughout the observation period,” the study authors concluded. “The safety profile of Vi-TCV was reassuring, with no excess serious adverse events in the Vi-TCV group and no adverse or serious adverse events considered to be related to the vaccine.”