Safety and Efficacy of a Typhoid Conjugate Vaccine in Malawian Children.
Child
Child, Preschool
Double-Blind Method
Female
Follow-Up Studies
Humans
Incidence
Infant
Intention to Treat Analysis
Malawi
Male
Meningococcal Vaccines
/ adverse effects
Polysaccharides, Bacterial
/ adverse effects
Salmonella typhi
Typhoid Fever
/ epidemiology
Typhoid-Paratyphoid Vaccines
/ adverse effects
Vaccines, Conjugate
Journal
The New England journal of medicine
ISSN: 1533-4406
Titre abrégé: N Engl J Med
Pays: United States
ID NLM: 0255562
Informations de publication
Date de publication:
16 09 2021
16 09 2021
Historique:
entrez:
15
9
2021
pubmed:
16
9
2021
medline:
30
9
2021
Statut:
ppublish
Résumé
Typhoid fever caused by multidrug-resistant H58 We conducted a phase 3, double-blind trial in Blantyre, Malawi, to assess the efficacy of Vi polysaccharide typhoid conjugate vaccine (Vi-TCV). We randomly assigned children who were between 9 months and 12 years of age, in a 1:1 ratio, to receive a single dose of Vi-TCV or meningococcal capsular group A conjugate (MenA) vaccine. The primary outcome was typhoid fever confirmed by blood culture. We report vaccine efficacy and safety outcomes after 18 to 24 months of follow-up. The intention-to-treat analysis included 28,130 children, of whom 14,069 were assigned to receive Vi-TCV and 14,061 were assigned to receive the MenA vaccine. Blood culture-confirmed typhoid fever occurred in 12 children in the Vi-TCV group (46.9 cases per 100,000 person-years) and in 62 children in the MenA group (243.2 cases per 100,000 person-years). Overall, the efficacy of Vi-TCV was 80.7% (95% confidence interval [CI], 64.2 to 89.6) in the intention-to-treat analysis and 83.7% (95% CI, 68.1 to 91.6) in the per-protocol analysis. In total, 130 serious adverse events occurred in the first 6 months after vaccination (52 in the Vi-TCV group and 78 in the MenA group), including 6 deaths (all in the MenA group). No serious adverse events were considered by the investigators to be related to vaccination. Among Malawian children 9 months to 12 years of age, administration of Vi-TCV resulted in a lower incidence of blood culture-confirmed typhoid fever than the MenA vaccine. (Funded by the Bill and Melinda Gates Foundation; ClinicalTrials.gov number, NCT03299426.).
Sections du résumé
BACKGROUND
Typhoid fever caused by multidrug-resistant H58
METHODS
We conducted a phase 3, double-blind trial in Blantyre, Malawi, to assess the efficacy of Vi polysaccharide typhoid conjugate vaccine (Vi-TCV). We randomly assigned children who were between 9 months and 12 years of age, in a 1:1 ratio, to receive a single dose of Vi-TCV or meningococcal capsular group A conjugate (MenA) vaccine. The primary outcome was typhoid fever confirmed by blood culture. We report vaccine efficacy and safety outcomes after 18 to 24 months of follow-up.
RESULTS
The intention-to-treat analysis included 28,130 children, of whom 14,069 were assigned to receive Vi-TCV and 14,061 were assigned to receive the MenA vaccine. Blood culture-confirmed typhoid fever occurred in 12 children in the Vi-TCV group (46.9 cases per 100,000 person-years) and in 62 children in the MenA group (243.2 cases per 100,000 person-years). Overall, the efficacy of Vi-TCV was 80.7% (95% confidence interval [CI], 64.2 to 89.6) in the intention-to-treat analysis and 83.7% (95% CI, 68.1 to 91.6) in the per-protocol analysis. In total, 130 serious adverse events occurred in the first 6 months after vaccination (52 in the Vi-TCV group and 78 in the MenA group), including 6 deaths (all in the MenA group). No serious adverse events were considered by the investigators to be related to vaccination.
CONCLUSIONS
Among Malawian children 9 months to 12 years of age, administration of Vi-TCV resulted in a lower incidence of blood culture-confirmed typhoid fever than the MenA vaccine. (Funded by the Bill and Melinda Gates Foundation; ClinicalTrials.gov number, NCT03299426.).
Identifiants
pubmed: 34525285
doi: 10.1056/NEJMoa2035916
pmc: PMC8202713
doi:
Substances chimiques
Meningococcal Vaccines
0
Polysaccharides, Bacterial
0
Typhoid-Paratyphoid Vaccines
0
Vaccines, Conjugate
0
Vi polysaccharide vaccine, typhoid
0
Banques de données
ClinicalTrials.gov
['NCT03299426']
Types de publication
Clinical Trial, Phase III
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1104-1115Subventions
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : NIDDK NIH HHS
ID : T32 DK067872
Pays : United States
Organisme : Bill and Melinda Gates Foundation
ID : OPP1151153
Informations de copyright
Copyright © 2021 Massachusetts Medical Society.
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