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Predicting the Impact of Typhoid Conjugate Vaccines on Antimicrobial Resistance.

ABSTRACT: BACKGROUND:Empiric prescribing of antimicrobials in typhoid-endemic settings has increased selective pressure on the development of antimicrobial-resistant Salmonella enterica serovar Typhi. The introduction of typhoid conjugate vaccines (TCVs) in these settings may relieve this selective pressure, thereby reducing resistant infections and improving health outcomes. METHODS:A deterministic transmission dynamic model was developed to simulate the impact of TCVs on the number and proportion of antimicrobial-resistant typhoid infections and chronic carriers. One-way sensitivity analyses were performed to ascertain particularly impactful model parameters influencing the proportion of antimicrobial-resistant infections and the proportion of cases averted over 10 years. RESULTS:The model simulations suggested that increasing vaccination coverage would decrease the total number of antimicrobial-resistant typhoid infections but not affect the proportion of cases that were antimicrobial resistant. In the base-case scenario with 80% vaccination coverage, 35% of all typhoid infections were antimicrobial resistant, and 44% of the total cases were averted over 10 years by vaccination. Vaccination also decreased both the total number and proportion of chronic carriers of antimicrobial-resistant infections. The prevalence of chronic carriers, recovery rates from infection, and relative fitness of resistant strains were identified as crucially important parameters. CONCLUSIONS:Model predictions for the proportion of antimicrobial resistant infections and number of cases averted depended strongly on the relative fitness of the resistant strain(s), prevalence of chronic carriers, and rates of recovery without treatment. Further elucidation of these parameter values in real-world typhoid-endemic settings will improve model predictions and assist in targeting future vaccination campaigns and treatment strategies.

SUBMITTER: Kaufhold S

PROVIDER: S-EPMC6405272 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Predicting the Impact of Typhoid Conjugate Vaccines on Antimicrobial Resistance.

Kaufhold Samantha S Yaesoubi Reza R Pitzer Virginia E VE

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 20190301 Suppl 2

<h4>Background</h4>Empiric prescribing of antimicrobials in typhoid-endemic settings has increased selective pressure on the development of antimicrobial-resistant Salmonella enterica serovar Typhi. The introduction of typhoid conjugate vaccines (TCVs) in these settings may relieve this selective pressure, thereby reducing resistant infections and improving health outcomes.<h4>Methods</h4>A deterministic transmission dynamic model was developed to simulate the impact of TCVs on the number and pr ...[more]

PMID: 30845324

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Project description:BackgroundSeveral prolonged typhoid fever epidemics have been reported since 2010 throughout eastern and southern Africa, including Malawi, caused by multidrug-resistant Salmonella Typhi. The World Health Organization recommends the use of typhoid conjugate vaccines (TCVs) in outbreak settings; however, current data are limited on how and when TCVs might be introduced in response to outbreaks.MethodologyWe developed a stochastic model of typhoid transmission fitted to data from Queen Elizabeth Central Hospital in Blantyre, Malawi from January 1996 to February 2015. We used the model to evaluate the cost-effectiveness of vaccination strategies over a 10-year time horizon in three scenarios: (1) when an outbreak is likely to occur; (2) when an outbreak is unlikely to occur within the next ten years; and (3) when an outbreak has already occurred and is unlikely to occur again. We considered three vaccination strategies compared to the status quo of no vaccination: (a) preventative routine vaccination at 9 months of age; (b) preventative routine vaccination plus a catch-up campaign to 15 years of age; and (c) reactive vaccination with a catch-up campaign to age 15 (for Scenario 1). We also explored variations in outbreak definitions, delays in implementation of reactive vaccination, and the timing of preventive vaccination relative to the outbreak.ResultsAssuming an outbreak occurs within 10 years, we estimated that the various vaccination strategies would prevent a median of 15-60% of disability-adjusted life-years (DALYs). Reactive vaccination was the preferred strategy for WTP values of $0-300 per DALY averted. For WTP values > $300, introduction of preventative routine TCV immunization with a catch-up campaign was the preferred strategy. Routine vaccination with a catch-up campaign was cost-effective for WTP values above $890 per DALY averted if no outbreak occurs and > $140 per DALY averted if implemented after the outbreak has already occurred.ConclusionsCountries for which the spread of antimicrobial resistance is likely to lead to outbreaks of typhoid fever should consider TCV introduction. Reactive vaccination can be a cost-effective strategy, but only if delays in vaccine deployment are minimal; otherwise, introduction of preventive routine immunization with a catch-up campaign is the preferred strategy.

Dataset Information

Predicting the Impact of Typhoid Conjugate Vaccines on Antimicrobial Resistance.

Publications

Predicting the Impact of Typhoid Conjugate Vaccines on Antimicrobial Resistance.

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