Safety and Efficacy of a Typhoid Conjugate Vaccine in Malawian Children

Patel, Priyanka D., Patel, Pratiksha, Liang, Yuanyuan, Meiring, James E., Misiri, Theresa, Mwakiseghile, Felistas, Tracy, J. Kathleen, Masesa, Clemens, Msuku, Harrison, Banda, David, Mbewe, Maurice, Henrion, Marc, Adetunji, Fiyinfolu, Simiyu, Kenneth, Rotrosen, Elizabeth, Birkhold, Megan, Nampota, Nginache, Nyirenda, Osward M., Kotloff, Karen, Gmeiner, Markus, Dube, Queen, Kawalazira, Gift, Laurens, Matthew B., Heyderman, Robert S., Gordon, Melita A. and Neuzil, Kathleen M. (2021) 'Safety and Efficacy of a Typhoid Conjugate Vaccine in Malawian Children'. New England Journal of Medicine, Vol 385, Issue 12, pp. 1104-1115.

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Abstract

BACKGROUND
Typhoid fever caused by multidrug-resistant H58 Salmonella Typhi is an increasing public health threat in sub-Saharan Africa.

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)

Item Type:	Article
Subjects:	QW Microbiology and Immunology > Immunotherapy and Hypersensitivity > QW 805 Vaccines. Antitoxins. Toxoids WA Public Health > Health Problems of Special Population Groups > WA 395 Health in developing countries WC Communicable Diseases > Infection. Bacterial Infections > Enteric Infections > WC 270 Typhoid fever WS Pediatrics > WS 100 General works
Faculty: Department:	Clinical Sciences & International Health > Clinical Sciences Department Clinical Sciences & International Health > Malawi-Liverpool-Wellcome Programme (MLW)
Digital Object Identifer (DOI):	https://doi.org/10.1056/NEJMoa2035916
Depositing User:	Stacy Murtagh
Date Deposited:	07 Oct 2021 16:04
Last Modified:	16 Mar 2022 02:02
URI:	https://archive.lstmed.ac.uk/id/eprint/19118

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