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Efficacy of Typhoid Conjugate Vaccine: Final Analysis of a Four-Year, Randomised Controlled Trial in Malawian Children

19 Pages Posted: 7 Apr 2023

See all articles by Priyanka D. Patel

Priyanka D. Patel

University of Malawi - Malawi-Liverpool-Wellcome Trust Clinical Research Programme

Yuanyuan Liang

University of Maryland - Department of Epidemiology and Public Health

James E. Meiring

University of Sheffield - Department of Infection, Immunity & Cardiovascular Disease

Nedson Chasweka

University of Malawi - Malawi-Liverpool-Wellcome Trust Clinical Research Programme

Pratiksha Patel

University of Malawi - Malawi-Liverpool-Wellcome Trust Clinical Research Programme

Theresa Misiri

University of Malawi - Malawi-Liverpool-Wellcome Trust Clinical Research Programme

Felistas Mwakisighile

University of Malawi - Malawi-Liverpool-Wellcome Trust Clinical Research Programme

Richard Wachepa

University of Malawi - Malawi-Liverpool-Wellcome Trust Clinical Research Programme

Happy C. Banda

University of Malawi - Malawi-Liverpool-Wellcome Trust Clinical Research Programme

Florence Shumba

University of Malawi - Malawi-Liverpool-Wellcome Trust Clinical Research Programme

Gift Kawalazira

Blantyre District Council - District Health Office

Queen Dube

Queen Elizabeth Central Hospital; Ministry of Health (Malawi)

Nginache Nampota-Nkomba

Kamuzu University of Health Sciences - Blantyre Malaria Project

Osward M. Nyirenda

Kamuzu University of Health Sciences - Blantyre Malaria Project

Tsion Girmay

University of Maryland - Center for Vaccine Development and Global Health

Shrimati Datta

University of Maryland - Center for Vaccine Development and Global Health

Leslie P. Jamka

University of Maryland - Center for Vaccine Development and Global Health

J. Kathleen Tracy

University of Maryland - Center for Vaccine Development and Global Health

Matthew B. Laurens

University of Maryland - Department of Pediatrics; University of Maryland - Center for Vaccine Development and Global Health

Robert S. Heyderman

University of Malawi - Malawi-Liverpool-Wellcome Trust Clinical Research Programme; University College London - Division of Infection and Immunity

Kathleen M. Neuzil

University of Maryland - Center for Vaccine Development and Global Health

Melita A. Gordon

University of Malawi - Malawi-Liverpool-Wellcome Trust Clinical Research Programme

More...

Abstract

Background: Randomised controlled trials of typhoid conjugate vaccines among children in Africa and Asia demonstrate high short-term efficacy. Data on durability of protection beyond two years, particularly in younger children, are limited. We present the final analysis of a randomised controlled trial in Malawi, encompassing more than 4 years of follow-up.

Methods: In a phase 3 double-blinded efficacy trial, healthy children aged 9 months-12 years were randomly assigned in a 1:1 ratio to receive a single dose of Vi polysaccharide conjugated to tetanus toxoid vaccine (Vi-TT) or meningococcal capsular group A conjugate (MenA) vaccine. We conducted passive surveillance for febrile illness from vaccination (February-September 2018) through September 2022. The primary outcome was first episode of blood culture-confirmed typhoid fever.

Results: Between 21 February-27 September 2018, 28,130 children were vaccinated; 14,069 were assigned to receive Vi-TT and 14,061 assigned to receive MenA. After a median follow-up of 4·3 years (interquartile range: 4·2-4·5), 24 children in the Vi-TT group (39·7 cases/100,000 person-years) and 110 children in the MenA group (182·7 cases/100,000 person-years) were diagnosed with a first episode of blood culture-confirmed typhoid fever. In the intention-to-treat population, efficacy of Vi-TT was 78·3% (95% confidence interval (CI): 66·3%- 86·1%), and the number of children needed to vaccinate to prevent one case was 163. Over 4 years, vaccine efficacy was estimated to fall by 1.3% per year (p=0·77). Efficacies by age-group were 70·6% (95% CI: 6·4%- 93·0%) in children aged 9 months to <2 years, 79.6% (95% CI: 45·8%-93·9%) in children 2 to <5 years, and 79·3% (95% CI: 63·5%-89·0%) in children 5-12 years.

Conclusions: A single dose of Vi-TT is durably efficacious in preventing blood culture-confirmed typhoid fever for >4 years among children aged 9 months-12 years.

Trial Registration: ClinicalTrials.gov number NCT03299426.

Funding: This study was funded by a grant from the Bill & Melinda Gates Foundation (OPP1151153).

Declaration of Interest: PDP, YL, JEM, NC, PP, TM, FM, RW, HCB, FS, GK, QD, NNN, OMN, TG, DS, LPJ, JMT, MBL, RSH, and MAG have no competing interests to declare. YL, DS, LPJ, MBL, and KMN receive funding from the TyVAC grant (OPP1151153). KMN is on the World Health Organization Strategic Advisory Group of Experts on Immunization (SAGE).

Ethical Approval: Local ethics approval was obtained from the Malawi National Health and Science Review Committee, and international ethics approval from the University of Liverpool Ethical Review Board, and the University of Maryland Baltimore Institutional Review Board. Results and safety were regularly reviewed by a Data and Safety Monitoring Board.

Keywords: Malawi, typhoid conjugate vaccine, Africa, efficacy, pediatrics

Suggested Citation

Patel, Priyanka D. and Liang, Yuanyuan and Meiring, James E. and Chasweka, Nedson and Patel, Pratiksha and Misiri, Theresa and Mwakisighile, Felistas and Wachepa, Richard and Banda, Happy C. and Shumba, Florence and Kawalazira, Gift and Dube, Queen and Nampota-Nkomba, Nginache and Nyirenda, Osward M. and Girmay, Tsion and Datta, Shrimati and Jamka, Leslie P. and Tracy, J. Kathleen and Laurens, Matthew B. and Heyderman, Robert S. and Neuzil, Kathleen M. and Gordon, Melita A., Efficacy of Typhoid Conjugate Vaccine: Final Analysis of a Four-Year, Randomised Controlled Trial in Malawian Children. Available at SSRN: https://ssrn.com/abstract=4411421 or http://dx.doi.org/10.2139/ssrn.4411421

Priyanka D. Patel

University of Malawi - Malawi-Liverpool-Wellcome Trust Clinical Research Programme ( email )

United Kingdom

Yuanyuan Liang

University of Maryland - Department of Epidemiology and Public Health ( email )

James E. Meiring

University of Sheffield - Department of Infection, Immunity & Cardiovascular Disease

Nedson Chasweka

University of Malawi - Malawi-Liverpool-Wellcome Trust Clinical Research Programme ( email )

United Kingdom

Pratiksha Patel

University of Malawi - Malawi-Liverpool-Wellcome Trust Clinical Research Programme ( email )

United Kingdom

Theresa Misiri

University of Malawi - Malawi-Liverpool-Wellcome Trust Clinical Research Programme ( email )

United Kingdom

Felistas Mwakisighile

University of Malawi - Malawi-Liverpool-Wellcome Trust Clinical Research Programme ( email )

United Kingdom

Richard Wachepa

University of Malawi - Malawi-Liverpool-Wellcome Trust Clinical Research Programme ( email )

United Kingdom

Happy C. Banda

University of Malawi - Malawi-Liverpool-Wellcome Trust Clinical Research Programme ( email )

United Kingdom

Florence Shumba

University of Malawi - Malawi-Liverpool-Wellcome Trust Clinical Research Programme ( email )

United Kingdom

Gift Kawalazira

Blantyre District Council - District Health Office ( email )

Queen Dube

Queen Elizabeth Central Hospital ( email )

Malawi

Ministry of Health (Malawi) ( email )

Nginache Nampota-Nkomba

Kamuzu University of Health Sciences - Blantyre Malaria Project ( email )

Osward M. Nyirenda

Kamuzu University of Health Sciences - Blantyre Malaria Project ( email )

Tsion Girmay

University of Maryland - Center for Vaccine Development and Global Health ( email )

Shrimati Datta

University of Maryland - Center for Vaccine Development and Global Health

685 W. Baltimore St
Room 480
Baltimore, MD 21201
United States

Leslie P. Jamka

University of Maryland - Center for Vaccine Development and Global Health

685 W. Baltimore St
Room 480
Baltimore, MD 21201
United States

J. Kathleen Tracy

University of Maryland - Center for Vaccine Development and Global Health

685 W. Baltimore St
Room 480
Baltimore, MD 21201
United States

Matthew B. Laurens

University of Maryland - Department of Pediatrics ( email )

University of Maryland - Center for Vaccine Development and Global Health ( email )

685 W. Baltimore St
Room 480
Baltimore, MD 21201
United States

Robert S. Heyderman

University of Malawi - Malawi-Liverpool-Wellcome Trust Clinical Research Programme ( email )

P.O. Box 30096, Chichiri
Blantyre 3, Malawi
Blantyre
Malawi

University College London - Division of Infection and Immunity ( email )

Kathleen M. Neuzil (Contact Author)

University of Maryland - Center for Vaccine Development and Global Health ( email )

685 W. Baltimore St
Room 480
Baltimore, MD 21201
United States

Melita A. Gordon

University of Malawi - Malawi-Liverpool-Wellcome Trust Clinical Research Programme ( email )

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