Estimating the Impact of Vaccination on Antimicrobial-Resistant Typhoid Fever in Gavi-73 Countries

Background: Multidrug resistance (MDR) and fluoroquinolone non-susceptibility (FQNS) are major concerns for the epidemiology and treatment of typhoid fever. The recent development and licensure of typhoid conjugate vaccines (TCVs) provide an opportunity to limit the transmission and burden of antimicrobial-resistant (AMR) typhoid fever. Methods: We combined output from mathematical models of typhoid transmission with estimates of antimicrobial resistance to predict the burden of AMR typhoid fever across Gavi-73 countries. We considered FQNS and MDR separately. The impact of vaccination was predicted based on forecasts of vaccine coverage. We explored how the potential impact of vaccination on the proportion of cases that were AMR varied depending on key model parameters. Findings: The introduction of routine immunization with TCV at 9 months of age with a catch-up campaign to 15 years of age was predicted to avert 46-74% of all typhoid fever cases in Gavi-73 countries. Vaccination was predicted to reduce the relative prevalence of AMR typhoid fever by 16% (95% prediction interval (PI): 0-49%). TCV introduction with a catch-up campaign was predicted to avert 42.5 million (95% PI: 24.8-62.8 million) cases and 506,000 (95% PI: 187,000-1.9 million) deaths due to FQNS typhoid fever and 21.2 million (95% PI: 16.4-26.5 million) cases and 342,000 (95% PI: 135,000-1.5 million) deaths from MDR typhoid fever over 10 years following introduction. Interpretation: Our results indicate the benefits of prioritizing TCV introduction for countries with a high avertable burden of FQNS and MDR typhoid fever. Funding: The Bill & Melinda Gates Foundation. Declaration of Interest: AJP chairs the UK Department of Health’s (DoH) Joint Committee on Vaccination and Immunisation (JCVI) and and is a member of the World Health Organization’s (WHO) Strategic Advisory Group of Experts. VEP has received reimbursement from Merck and Pfizer for travel expenses to Scientific Input Engagements unrelated to the subject of this manuscript and is a member of the World Health Organization’s (WHO) Immunization and Vaccine-related Implementation Research Advisory Committee. The views expressed in this manuscript are those of the authors and do not necessarily reflect the views of the JCVI, the DoH, or the WHO.