Assessing the Impact of a Vi-polysaccharide Conjugate Vaccine in Preventing Typhoid Infection Among Bangladeshi Children: A Protocol for a Phase IIIb Trial.

Theiss-Nyland K., Qadri F., Colin-Jones R., Zaman K., Khanam F., Liu X., Voysey M., Khan A., Hasan N., Ashher F., Farooq YG., Pollard AJ., Clemens JD.

BACKGROUND: Typhoid fever illnesses are responsible for more than 100 000 deaths worldwide each year. In Bangladesh, typhoid fever is endemic, with incidence rates between 292-395 per 100 000 people annually. While considerable effort has been made to improve access to clean water and sanitation services in the country, there is still a significant annual typhoid burden, which particularly affects children. A typhoid conjugate vaccine (Vi-TCV) was recently prequalified by the World Health Organization and recommended for use, and offers the potential to greatly reduce the typhoid burden in Bangladesh. METHODS: This study is a double-blind, cluster-randomized, controlled trial of Vi-TCV in a geographically defined area in Dhaka, Bangladesh. At least 32 500 children from 9 months to <16 years of age will be vaccinated and followed for 2 years to assess the effectiveness and safety of Vi-TCV in a real-world setting. All cluster residents will also be followed to measure the indirect effect of Vi-TCV in this community. ETHICS AND DISSEMINATION: This protocol has been approved by the International Centre for Diarrhoeal Disease Research, Bangladesh; a University of Oxford research review; and both ethical review committees. Informed written consent and assent will be obtained before enrollment. Vi-TCV has been shown to be safe and effective in previous, smaller-scale studies. The results of this study will be shared through a series of peer-reviewed journal articles. The findings will also be disseminated to the local government, stakeholders within the community, and the population within which the study was conducted. CONCLUSIONS: This trial is the largest and only cluster-randomized control trial of Vi-TCV ever conducted, and will describe the effectiveness of Vi-TCV in an endemic population. The results of this trial may provide important evidence to support the introduction of TCVs in countries with a high burden of typhoid. CLINICAL TRIALS REGISTRATION: ISRCTN11643110.

DOI

10.1093/cid/ciy1107

Type

Journal

Clin Infect Dis

Publication Date

07/03/2019

Volume

68

Pages

S74 - S82

Keywords

Bangladesh, cluster randomized controlled trial, protocol, typhoid vaccine, Adolescent, Bangladesh, Child, Child, Preschool, Clinical Trials, Phase III as Topic, Double-Blind Method, Female, Humans, Infant, Male, Polysaccharides, Bacterial, Randomized Controlled Trials as Topic, Typhoid Fever, Typhoid-Paratyphoid Vaccines, Vaccine Potency, Vaccines, Conjugate

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