Source: Masters Abstracts International, Volume: 57-05.

Adviser: Virginia Pitzer.

Background: Empiric prescribing of antimicrobials in typhoid-endemic settings has increased selective pressure on the development of antimicrobial-resistant Salmonella enterica serovar Typhi (S. 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 on the proportion of antimicrobial-resistant infections and the total number of cases averted over ten years.

Findings: The model simulation suggested that increasing vaccination coverage decreased the total number of antimicrobial-resistant infections without affecting the proportion of cases that were antimicrobial resistant. In the base case scenario with 80% vaccination coverage, 86.5% of all typhoid infections were antimicrobial resistant and 213,060 total cases were averted over ten years. Vaccination also decreased both the total number and proportion of chronic carriers of antimicrobial-resistant infections. Between 2 and 2.5% of the population became chronic carriers by the end of the simulation, with approximately 80% of those carrying antimicrobial-resistant S. Typhi. The treatment rate, the fraction of chronic carriers of antimicrobial-resistant infections in the population, the duration of vaccine-induced immunity, and the relative fitness of the resistant strains were identified as crucially important parameters.

Significance: Model predictions for the proportion of resistant infections depended strongly on the treatment rate as well as chronic carriers, while the relative fitness of the resistant strains and duration of vaccine-induced immunity were impactful on the number of cases averted. Further elucidation of these parameter values in real-world typhoid-endemic settings will improve model predictions, clarify the natural history of typhoid infections, and assist in targeting future vaccination campaigns and treatment strategies.