Estimating the effect of vaccination on antimicrobial-resistant typhoid fever in 73 countries supported by Gavi: a mathematical modelling study

Virginia E Pitzer,Gordon Dougan,Kathleen M Neuzil,Joke Bilcke,Christiane Dolecek,Isabel Frost,Marina Antillón,Andrew J Pollard,Ramanan Laxminarayan,Ruthie Birger

doi:10.1016/s1473-3099(21)00627-7

Abstract

SummaryBackgroundMultidrug resistance and fluoroquinolone non-susceptibility (FQNS) are major concerns for the epidemiology and treatment of typhoid fever. The 2018 prequalification of the first typhoid conjugate vaccine (TCV) by WHO provides an opportunity to limit the transmission and burden of antimicrobial-resistant typhoid fever.MethodsWe combined output from mathematical models of typhoid transmission with estimates of antimicrobial resistance from meta-analyses to predict the burden of antimicrobial-resistant typhoid fever across 73 lower-income countries eligible for support from Gavi, the Vaccine Alliance. We considered FQNS and multidrug resistance separately. The effect of vaccination was predicted on the basis of forecasts of vaccine coverage. We explored how the potential effect of vaccination on the prevalence of antimicrobial resistance varied depending on key model parameters.FindingsThe introduction of routine immunisation with TCV at age 9 months with a catch-up campaign up to age 15 years was predicted to avert 46–74% of all typhoid fever cases in 73 countries eligible for Gavi support. Vaccination was predicted to reduce the relative prevalence of antimicrobial-resistant 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 caused by 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 multidrug-resistant typhoid fever over 10 years following introduction.InterpretationOur results indicate the benefits of prioritising TCV introduction for countries with a high avertable burden of antimicrobial-resistant typhoid fever.FundingThe Bill & Melinda Gates Foundation.

Highlights

Despite global improvements in sanitation and hygiene, typhoid fever, caused by the pathogen Salmonella enterica serovar Typhi (S Typhi), remains a major source of morbidity and mortality
The prevalence of fluoroquinolone non-susceptibility (FQNS) tended to be high in Asia and lower (
Half of the avertable cases of typhoid with FQNS were in India (21·1 million, 95% PI 6·3–41·3 million), whereas the greatest number of avertable cases with multidrug resistance occurred in Nigeria (5·2 million, 95% PI 2·4–9·3 million); countryspecific estimates of cases, deaths, and disability-adjusted life years (DALYs) averted are available in the appendix

Summary

Introduction

Despite global improvements in sanitation and hygiene, typhoid fever, caused by the pathogen Salmonella enterica serovar Typhi (S Typhi), remains a major source of morbidity and mortality. TCV vaccination with a catch-up campaign up to age 15 years was predicted to avert 42·5 million (95% PI 24·8–62·9 million) cases of typhoid fever with FQNS and 21·2 million (95% PI 16·4–26·5 million) cases with multidrug resistance over 10 years (appendix pp 16–21). Half of the avertable cases of typhoid with FQNS were in India (21·1 million, 95% PI 6·3–41·3 million), whereas the greatest number of avertable cases with multidrug resistance occurred in Nigeria (5·2 million, 95% PI 2·4–9·3 million); countryspecific estimates of cases, deaths, and DALYs averted are available in the appendix (pp 16–21). Over 90% of the total avertable cases of antimicrobial-resistant typhoid fever occurred in south Asia (60%) and sub-Saharan Africa (33%; table 3). Vaccination was predicted to avert 56·9% (95% PI 35–74) of cases and 61·3% (95% PI 36–75) of DALYs in Pakistan (table 3)

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Results

Conclusion