TY - JOUR
T1 - Safety and Efficacy of a Typhoid Conjugate Vaccine in Malawian Children
AU - Patel, Priyanka D.
AU - Patel, Pratiksha
AU - Liang, Yuanyuan
AU - Meiring, James E.
AU - Misiri, Theresa
AU - Mwakiseghile, Felistas
AU - Tracy, J. Kathleen
AU - Masesa, Clemens
AU - Msuku, Harrison
AU - Banda, David
AU - Mbewe, Maurice
AU - Henrion, Marc
AU - Adetunji, Fiyinfolu
AU - Simiyu, Kenneth
AU - Rotrosen, Elizabeth
AU - Birkhold, Megan
AU - Nampota, Nginache
AU - Nyirenda, Osward M.
AU - Kotloff, Karen
AU - Gmeiner, Markus
AU - Dube, Queen
AU - Kawalazira, Gift
AU - Laurens, Matthew B.
AU - Heyderman, Robert S.
AU - Gordon, Melita A.
AU - Neuzil, Kathleen M.
PY - 2021/9/16
Y1 - 2021/9/16
N2 - BACKGROUNDTyphoid fever caused by multidrug-resistant H58 Salmonella Typhi is an increasing public health threat in sub-Saharan Africa.METHODSWe 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.RESULTSThe 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.CONCLUSIONSAmong 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)
AB - BACKGROUNDTyphoid fever caused by multidrug-resistant H58 Salmonella Typhi is an increasing public health threat in sub-Saharan Africa.METHODSWe 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.RESULTSThe 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.CONCLUSIONSAmong 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)
U2 - 10.1056/nejmoa2035916
DO - 10.1056/nejmoa2035916
M3 - Article
SN - 0028-4793
VL - 385
SP - 1104
EP - 1115
JO - New England Journal of Medicine
JF - New England Journal of Medicine
IS - 12
ER -
