Stochastic Simulation of Endemic Salmonella enterica Serovar Typhi: The Importance of Long Lasting Immunity and the Carrier State

Abstract

BackgroundTyphoid fever caused by Salmonella enterica serovar Typhi (S. Typhi) remains a serious burden of disease, especially in developing countries of Asia and Africa. It is estimated that it causes 200,000 deaths per year, mainly in children. S. Typhi is an obligate pathogen of humans and although it has a relatively complex life cycle with a long lived carrier state, the absence of non-human hosts suggests that well targeted control methods should have a major impact on disease. Newer control methods including new generations of vaccines offer hope but their implementation would benefit from quantitative models to guide the most cost effective strategies. This paper presents a quantitative model of Typhoid disease, immunity and transmission as a first step in that process.Methodology/Principal FindingsA stochastic agent-based model has been developed that incorporates known features of the biology of typhoid including probability of infection, the consequences of infection, treatment options, acquisition and loss of immunity as a result of infection and vaccination, the development of the carrier state and the impact of environmental or behavioral factors on transmission. The model has been parameterized with values derived where possible from the literature and where this was not possible, feasible parameters space has been determined by sensitivity analyses, fitting the simulations to age distribution of field data. The model is able to adequately predict the age distribution of typhoid in two settings.Conclusions/SignificanceThe modeling highlights the importance of variations in the exposure/resistance of infants and young children to infection in different settings, especially as this impacts on design of control programs; it predicts that naturally induced clinical and sterile immunity to typhoid is long lived and highlights the importance of the carrier state especially in areas of low transmission.

Predicting the Impact of Vaccination on the Transmission Dynamics of Typhoid in South Asia: A Mathematical Modeling Study

“…For example, we found that the age distribution of typhoid cases in Dhaka, Bangladesh was consistent with a higher basic reproductive number ( R 0 ∼7) in this setting [29]. Furthermore, we estimated the rate of waning immunity to clinical disease ( ε ) to be very low, consistent with another recent modeling study [21]. However, this may be due to the relatively high incidence of typhoid infection in this population leading to continual boosting of immunity through reinfections.…”

Phylodynamics without trees: estimating R0 directly from pathogen sequences

“…(2). This is consistent with other studies: an R 0 of 2.8 was estimated in Vellore (India) [24]; a value of 3.4 was found for the reproduction number from an untreated clinical infection in [25]. However in Dhaka, Bangladesh, R 0 for typhoid fever was estimated at 7 [24] (but not all cases of S. typhi cause typhoid fever).…”

Prevalence ofSalmonellaExcretion in Stool: A Community Survey in 2 Sites, Guinea-Bissau and Senegal

“…Therefore, determining the prevalence of excreters, including asymptomatic carriers, in any population is important for modeling transmission dynamics and the potential impact of vaccination for this disease [44,45]. The role of S. Typhi carriers in the persistence of typhoid fever in endemic regions has been observed in parts of Chile [46] and Vietnam [47], and the impact of carriers on incident typhoid fever cases is consistent with output from stochastic modeling of typhoid fever transmission [48]. Less information has been documented on the factors that contribute to iNTS transmission.…”