Typhoid Vaccine Deployment Scenarios

We considered three scenarios under the assumption that a country has not yet implemented routine vaccination: (1) an outbreak is likely to occur over the next 10 years; (2) an outbreak is unlikely to occur (and hence, the country maintains the same pre-outbreak seasonal incidence); and (3) an outbreak has already occurred and is unlikely to happen again (and hence, the country has a higher incidence post-outbreak compared to pre-outbreak). The most likely scenario depends on the recent history of typhoid incidence and that of nearby regions. If surrounding regions have been experiencing outbreaks but the country has not yet had one, we assume that it is likely that an outbreak will occur at some point within the next 10 years (Scenario 1). For this scenario, we randomized the timing of the start of the outbreak to follow a uniform distribution over Years 0–10; we assumed only a single outbreak occurs. However, if surrounding regions are not experiencing outbreaks, it may be unlikely that an outbreak would occur (Scenario 2). If an outbreak has already occurred, as it did in Malawi, we assume another outbreak is unlikely within the next 10 years (Scenario 3).
Because the outbreak in Malawi was driven by the emergence of multi-drug resistance, typhoid incidence under the Scenario 3 (post-outbreak) is higher than the incidence under Scenario 2 (pre-outbreak). For Scenario 2, we assume typhoid fever incidence is comparable to that estimated for Blantyre for 1995–2005, whereas for Scenario 3, we assume it is comparable to that predicted for Blantyre for 2021–2031. These scenarios are comparable to previous cost-effectiveness analyses and allow us to examine whether it would be beneficial to introduce TCV in an endemic setting when typhoid fever incidence is lower (Scenario 2: pre-outbreak) or higher (Scenario 3: post-outbreak).
We simulated four alternative vaccination strategies, following previous cost-effectiveness analyses of TCV strategies and the current WHO recommendation in endemic settings [14 , 23 (link), 24 (link), 31 (link)]: no vaccination (base case), preventive routine TCV introduction at 9 months of age (in Year 0), preventive routine vaccination plus a one-time catch-up to age 15 (also in Year 0), and (for Scenario 1 only) reactive routine vaccination plus a catch-up campaign to age 15 once the outbreak was identified (Table 2). Vaccine efficacy parameters (including the initial vaccine efficacy and exponential rate of waning immunity) were estimated by fitting to data from a phase 3, double-blind, randomized active-controlled clinical trial of single-dose Typbar TCV in Blantyre, Malawi [9 (link), 23 (link)] (Table 1, Additional file 1: S1.1.2.2 Text, Fig. S2). Routine vaccination coverage was assumed to increase from 85 to 95% over the first ten years of vaccination and then remain at 95% [23 (link)]. For catch-up campaign coverage, we varied the proportion vaccinated uniformly from 60 to 90%.Table 2

Strategy comparisons for deploying typhoid conjugate vaccines to prevent or respond to an outbreak

Strategy type	Vaccination strategies
Base	No vaccination
Preventive	Routine at 9 months
Preventive	Routine + catch-up to age 15
Reactive	Routine + catch-up to age 15

Each of the scenarios examined compares four strategies: a base case (no vaccination), a preventive strategy with routine vaccination at 9 months of age (“routine”), a preventive strategy with routine vaccination and a catch-up campaign up to 15 years of age (“routine + catch-up”), and a reactive vaccination strategy with routine vaccination and a catch-up campaign