Safety and Efficacy of a Typhoid Conjugate Vaccine in Malawian Children

Priyanka D Patel, Pratiksha Patel, Yuanyuan Liang, James E Meiring, Theresa Misiri, Felistas Mwakiseghile, J Kathleen Tracy, Clemens Masesa, Harrison Msuku, David Banda, Maurice Mbewe, Marc Henrion, Fiyinfolu Adetunji, Kenneth Simiyu, Elizabeth Rotrosen, Megan Birkhold, Nginache Nampota, Osward M Nyirenda, Karen Kotloff, Markus Gmeiner, Queen Dube, Gift Kawalazira, Matthew B Laurens, Robert S Heyderman, Melita A Gordon, Kathleen M Neuzil, TyVAC Malawi Team, Priyanka D Patel, Pratiksha Patel, Yuanyuan Liang, James E Meiring, Theresa Misiri, Felistas Mwakiseghile, J Kathleen Tracy, Clemens Masesa, Harrison Msuku, David Banda, Maurice Mbewe, Marc Henrion, Fiyinfolu Adetunji, Kenneth Simiyu, Elizabeth Rotrosen, Megan Birkhold, Nginache Nampota, Osward M Nyirenda, Karen Kotloff, Markus Gmeiner, Queen Dube, Gift Kawalazira, Matthew B Laurens, Robert S Heyderman, Melita A Gordon, Kathleen M Neuzil, TyVAC Malawi Team

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.).

Copyright © 2021 Massachusetts Medical Society.

Figures

Figure 1:. Disposition of participants (CONSORT flow…
Figure 1:. Disposition of participants (CONSORT flow diagram)
*MenA group A meningococcal †Randomization deviation: Two participants received the same PID. The second participant who received a duplicate PID was assigned a new PID after randomization and excluded from per-protocol analysis.
Figure 2.
Figure 2.
Kaplan-Meier Estimates of the Cumulative Incidence of Blood Culture-Positive Typhoid Fever, By Vaccine Group, Intention to Treat Population.

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Source: PubMed

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