Evaluation of Typhoid Conjugate Vaccine Effectiveness in Ghana (TyVEGHA) Using a Cluster-Randomized Controlled Phase IV Trial: Trial Design and Population Baseline Characteristics
Andrea Haekyung Haselbeck,
Birkneh Tilahun Tadesse,
Juyeon Park,
Malick M. Gibani,
Ligia María Cruz Espinoza,
Ariane Abreu,
Craig Van Rensburg,
Michael Owusu-Ansah,
Sampson Twuamsi-Ankrah,
Michael Owusu,
Isaac Aguna,
Valentina Picot,
Hyonjin Jeon,
Ellen Higginson,
Sunju Park,
Zenaida R. Mojares,
Justin Im,
Megan E. Carey,
Farhana Khanam,
Susan Tonks,
Gordon Dougan,
Deokryun Kim,
Jonathan Sugimoto,
Vittal Mogasale,
Kathleen M. Neuzil,
Firdausi Qadri,
Yaw Adu-Sarkodie,
Ellis Owusu-Dabo,
John Clemens,
Florian Marks
Affiliations
Andrea Haekyung Haselbeck
International Vaccine Institute, Seoul 08826, Korea
Birkneh Tilahun Tadesse
International Vaccine Institute, Seoul 08826, Korea
Juyeon Park
International Vaccine Institute, Seoul 08826, Korea
Malick M. Gibani
Department of Infectious Disease, Imperial College of Medicine, London SW7 2AZ, UK
Ligia María Cruz Espinoza
International Vaccine Institute, Seoul 08826, Korea
Ariane Abreu
International Vaccine Institute, Seoul 08826, Korea
Craig Van Rensburg
International Vaccine Institute, Seoul 08826, Korea
Michael Owusu-Ansah
School of Public Health, Kwame Nkrumah University of Science and Technology, Kumasi 00000, Ghana
Sampson Twuamsi-Ankrah
School of Public Health, Kwame Nkrumah University of Science and Technology, Kumasi 00000, Ghana
Michael Owusu
School of Public Health, Kwame Nkrumah University of Science and Technology, Kumasi 00000, Ghana
Isaac Aguna
School of Public Health, Kwame Nkrumah University of Science and Technology, Kumasi 00000, Ghana
Valentina Picot
Fondation Mérieux, 69002 Lyon, France
Hyonjin Jeon
International Vaccine Institute, Seoul 08826, Korea
Ellen Higginson
Cambridge Institute for Therapeutic Immunology and Infectious Disease, University of Cambridge, Cambridge CB2 0SL, UK
Sunju Park
International Vaccine Institute, Seoul 08826, Korea
Zenaida R. Mojares
International Vaccine Institute, Seoul 08826, Korea
Justin Im
International Vaccine Institute, Seoul 08826, Korea
Megan E. Carey
Cambridge Institute for Therapeutic Immunology and Infectious Disease, University of Cambridge, Cambridge CB2 0SL, UK
Farhana Khanam
International Centre for Diarrhoeal Disease Research, Dhaka 1212, Bangladesh
Susan Tonks
Cambridge Institute for Therapeutic Immunology and Infectious Disease, University of Cambridge, Cambridge CB2 0SL, UK
Gordon Dougan
Cambridge Institute for Therapeutic Immunology and Infectious Disease, University of Cambridge, Cambridge CB2 0SL, UK
Deokryun Kim
International Vaccine Institute, Seoul 08826, Korea
Jonathan Sugimoto
Seattle Epidemiologic Research and Information Center, Cooperative Studies Program, Office of Research and Development, United States Department of Veterans Affairs, Seattle, WA 98174, USA
Vittal Mogasale
International Vaccine Institute, Seoul 08826, Korea
Kathleen M. Neuzil
Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, MD 21201, USA
Firdausi Qadri
International Centre for Diarrhoeal Disease Research, Dhaka 1212, Bangladesh
Yaw Adu-Sarkodie
School of Public Health, Kwame Nkrumah University of Science and Technology, Kumasi 00000, Ghana
Ellis Owusu-Dabo
School of Public Health, Kwame Nkrumah University of Science and Technology, Kumasi 00000, Ghana
John Clemens
International Vaccine Institute, Seoul 08826, Korea
Florian Marks
International Vaccine Institute, Seoul 08826, Korea
Typhoid fever remains a significant health problem in sub-Saharan Africa, with incidence rates of >100 cases per 100,000 person-years of observation. Despite the prequalification of safe and effective typhoid conjugate vaccines (TCV), some uncertainties remain around future demand. Real-life effectiveness data, which inform public health programs on the impact of TCVs in reducing typhoid-related mortality and morbidity, from an African setting may help encourage the introduction of TCVs in high-burden settings. Here, we describe a cluster-randomized trial to investigate population-level protection of TYPBAR-TCV®, a Vi-polysaccharide conjugated to a tetanus-toxoid protein carrier (Vi-TT) against blood-culture-confirmed typhoid fever, and the synthesis of health economic evidence to inform policy decisions. A total of 80 geographically distinct clusters are delineated within the Agogo district of the Asante Akim region in Ghana. Clusters are randomized to the intervention arm receiving Vi-TT or a control arm receiving the meningococcal A conjugate vaccine. The primary study endpoint is the total protection of Vi-TT against blood-culture-confirmed typhoid fever. Total, direct, and indirect protection are measured as secondary outcomes. Blood-culture-based enhanced surveillance enables the estimation of incidence rates in the intervention and control clusters. Evaluation of the real-world impact of TCVs and evidence synthesis improve the uptake of prequalified/licensed safe and effective typhoid vaccines in public health programs of high burden settings. This trial is registered at the Pan African Clinical Trial Registry, accessible at Pan African Clinical Trials Registry (ID: PACTR202011804563392).
