Typhoid fever in Santiago, Chile: Insights from a mathematical model utilizing venerable archived data from a successful disease control program

Typhoid fever is endemic in many developing countries. In the early 20(th) century, newly industrializing countries including the United States successfully controlled typhoid as water treatment (chlorination/sand filtration) and improved sanitation became widespread. Enigmatically, typhoid remained endemic through the 1980s in Santiago, Chile, despite potable municipal water and widespread household sanitation. Data were collected across multiple stages of endemicity and control in Santiago, offering a unique resource for gaining insight into drivers of transmission in modern settings. We developed an individual-based mathematical model of typhoid transmission, with model components including distinctions between long-cycle and short-cycle transmission routes. Data used to fit the model included the prevalence of chronic carriers, seasonality, longitudinal incidence, and age-specific distributions of typhoid infection and disease. Our model captured the dynamics seen in Santiago across endemicity, vaccination, and environmental control. Both vaccination and diminished exposure to seasonal amplified long-cycle transmission contributed to the observed declines in typhoid incidence, with the vaccine estimated to elicit herd effects. Vaccines are important tools for controlling endemic typhoid, with even limited coverage eliciting herd effects in this setting. Removing the vehicles responsible for amplified long-cycle transmission and assessing the role of chronic carriers in endemic settings are additional key elements in designing programs to achieve accelerated control of endemic typhoid.