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Clinical Trial
. 2021 Sep 16;385(12):1104-1115.
doi: 10.1056/NEJMoa2035916.

Safety and Efficacy of a Typhoid Conjugate Vaccine in Malawian Children

Priyanka D Patel  1 , Pratiksha Patel  1 , Yuanyuan Liang  1 , James E Meiring  1 , Theresa Misiri  1 , Felistas Mwakiseghile  1 , J Kathleen Tracy  1 , Clemens Masesa  1 , Harrison Msuku  1 , David Banda  1 , Maurice Mbewe  1 , Marc Henrion  1 , Fiyinfolu Adetunji  1 , Kenneth Simiyu  1 , Elizabeth Rotrosen  1 , Megan Birkhold  1 , Nginache Nampota  1 , Osward M Nyirenda  1 , Karen Kotloff  1 , Markus Gmeiner  1 , Queen Dube  1 , Gift Kawalazira  1 , Matthew B Laurens  1 , Robert S Heyderman  1 , Melita A Gordon  1 , Kathleen M Neuzil  1 ; TyVAC Malawi Team
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Free PMC article
Clinical Trial

Safety and Efficacy of a Typhoid Conjugate Vaccine in Malawian Children

Priyanka D Patel et al. N Engl J Med. .
Free PMC article

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.).

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Figures

Figure 1:
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.
See this image and copyright information in PMC

References

    1. Global Burden of Disease Collaborative Network. GBD 2020 Cause and Risk Summaries: Typhoid fever — level 4 cause. Seattle, United States: Institute for Health Metrics and Evaluation (IHME). 2020; Available from: http://www.healthdata.org/results/gbd_summaries/2019/typhoid-fever-level...
    1. Antillón M, Warren JL, Crawford FW, et al.The burden of typhoid fever in low- and middle-income countries: a meta-regression approach. PLoS Negl Trop Dis 2017;11(2):1–21. - PMC - PubMed
    1. Marks F, von Kalckreuth V, Aaby P, et al.Incidence of invasive salmonella disease in sub-Saharan Africa: a multicentre population-based surveillance study. Lancet Global Health 2017;5(3):e310–23. - PMC - PubMed
    1. Breiman RF, Cosmas L, Njuguna H, et al.Population-based incidence of typhoid fever in an urban informal settlement and a rural area in Kenya: implications for typhoid vaccine use in Africa. PLoS One 2012;7(1):e29119. - PMC - PubMed
    1. Meiring JE, Patel P, Patel P, Gordon MA. Typhoid conjugate vaccines: making vaccine history in Africa. Expert Review of Vaccines 2018;17(8):673–676. - PubMed

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