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. 2022 May;22(5):679-691.
doi: 10.1016/S1473-3099(21)00627-7. Epub 2022 Feb 3.

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

Ruthie Birger  1 , Marina Antillón  2 , Joke Bilcke  3 , Christiane Dolecek  4 , Gordon Dougan  5 , Andrew J Pollard  6 , Kathleen M Neuzil  7 , Isabel Frost  8 , Ramanan Laxminarayan  9 , Virginia E Pitzer  10
Affiliations

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

Ruthie Birger et al. Lancet Infect Dis. 2022 May.

Abstract

Background: Multidrug 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.

Methods: We 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.

Findings: The 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.

Interpretation: Our results indicate the benefits of prioritising TCV introduction for countries with a high avertable burden of antimicrobial-resistant typhoid fever.

Funding: The Bill & Melinda Gates Foundation.

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Conflict of interest statement

Declaration of interests RB is now employed by Merck Sharp & Dohme. AJP has received grants from National Institute for Health Research, the Bill & Melinda Gates Foundation, Wellcome Trust, and Astra Zeneca outside of the submitted work; chairs the UK Department of Health's Joint Committee on Vaccination and Immunisation; and is a member of WHO's 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 Article; and is a member of the WHO's 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 Joint Committee on Vaccination and Immunisation, Department of Health, or WHO. All other authors declare no competing interests.

Figures

Figure 1
Figure 1
Estimated prevalence of antimicrobial resistance among typhoid fever cases in 73 countries eligible for Gavi support (A) Mean prevalence of fluoroquinolone non-susceptibility for each country. (B) Bar plots of the mean prevalence and 95% CI of fluoroquinolone non-susceptibility for each country. (C) Mean prevalence of multidrug resistance for each country. (D) Bar plots of the mean prevalence and 95% CI of multidrug resistance for each country. Data sources are listed in the appendix (pp 2, 5–6).
Figure 2
Figure 2
Predicted effect of vaccination on the incidence of fluoroquinolone non-susceptible and multidrug-resistant cases of typhoid fever (A) Percentage of fluoroquinolone non-susceptible cases of typhoid fever averted over 10 years following introduction of routine immunisation with typhoid conjugate vaccines plus a catch-up campaign for each country. (B) Bar plots of the mean reduction and 95% prediction interval of fluoroquinolone non-susceptibility for each country. (C) Percentage of multidrug resistant cases of typhoid fever averted over 10 years following introduction of routine immunisation with typhoid conjugate vaccines plus a catch-up campaign for each country. (D) Bar plots of the mean reduction and 95% prediction interval of multidrug resistance for each country.
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