Typhoid Fever: Pathogenesis and Immunologic Control

Hornick, Richard B.; Greisman, Sheldon E.; Woodward, Theodore E.; DuPont, Herbert L.; Hawkins, A. T.; Snyder, Marshall L.

doi:10.1056/nejm197010012831406

Cited by 189 publications

(74 citation statements)

References 32 publications

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“…However, this may be due to the relatively high incidence of typhoid infection in this population leading to continual boosting of immunity through reinfections. Individuals have been known to experience more than one episode of clinical typhoid infection [30], so this finding should be interpreted cautiously. The development of clinical typhoid may depend on both the immune history of the individual as well as the infecting dose [31], but our parsimonious model does not explicitly account for the dose-response relationship.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2014

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BackgroundModeling of the transmission dynamics of typhoid allows for an evaluation of the potential direct and indirect effects of vaccination; however, relevant typhoid models rooted in data have rarely been deployed.Methodology/Principal FindingsWe developed a parsimonious age-structured model describing the natural history and immunity to typhoid infection. The model was fit to data on culture-confirmed cases of typhoid fever presenting to Christian Medical College hospital in Vellore, India from 2000–2012. The model was then used to evaluate the potential impact of school-based vaccination strategies using live oral, Vi-polysaccharide, and Vi-conjugate vaccines. The model was able to reproduce the incidence and age distribution of typhoid cases in Vellore. The basic reproductive number (R 0) of typhoid was estimated to be 2.8 in this setting. Vaccination was predicted to confer substantial indirect protection leading to a decrease in the incidence of typhoid in the short term, but (intuitively) typhoid incidence was predicted to rebound 5–15 years following a one-time campaign.Conclusions/SignificanceWe found that model predictions for the overall and indirect effects of vaccination depend strongly on the role of chronic carriers in transmission. Carrier transmissibility was tentatively estimated to be low, consistent with recent studies, but was identified as a pivotal area for future research. It is unlikely that typhoid can be eliminated from endemic settings through vaccination alone.

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Section: Discussionmentioning

confidence: 99%

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

et al. 2014

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“…Volunteer challenge studies of wild-type S. Typhi infection performed in the 1960s and 1970s suggested a key role for cellular immune responses; however, these studies were performed before the availability of modern immunologic techniques 2. Our current understanding of cellular responses during S. Typhi infection are extrapolated from murine models of S. Typhimurium infection (that cause a systemic typhoidal-like illness in mice), and from human studies with attenuated S. Typhi live vaccine strains 3.…”

Section: Introductionmentioning

confidence: 99%

Cellular and Cytokine Responses to Salmonella enterica Serotype Typhi Proteins in Patients with Typhoid Fever in Bangladesh

Bhuiyan¹,

Sayeed²,

Khanam³

et al. 2014

The American Society of Tropical Medicine and Hygiene

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We assessed interferon-gamma (IFN-γ) responses via enzyme-linked immunosorbent spot (ELISPOT) to a number of S. Typhi antigens in samples from humans with S. Typhi bacteremia and typhoid fever in Bangladesh. Compared with responses in healthy endemic zone controls, there were significantly increased IFN-γ responses at the time of clinical presentation (acute phase) and at convalescence 14–28 days later. The majority (80–90%) of IFN-γ expressing T cells were CD4+. We observed a significant increase in interleukin-17 (IL-17) positive CD4 + T cells at convalescent versus acute stage of infection using an intracellular cytokine staining assay. We also found that stimulated peripheral blood mononuclear cells (PBMCs) produced significantly increased levels of a number of cytokines at the convalescent versus acute phase of infection, including IFN-γ, MIP-1β, sCD40L, TNF-β, IL-13, and IL-9. These results suggest that S. Typhi antigens induce a predominantly Th1 response, but that elevations in other cytokines may be modulatory.

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“…Both natural exposure and live attenuated vaccines provide some protection, but volunteer infection studies [1] and naturally occurring epidemics [2] have both demonstrated repeated infection with symptomatic typhoid. A specific element of the biology is the existence of long-term carrier states involving colonization of the gall bladder and of other sites.…”

Section: Introductionmentioning

confidence: 99%

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

2013

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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.

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Typhoid Fever: Pathogenesis and Immunologic Control

Cited by 189 publications

References 32 publications

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

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

Cellular and Cytokine Responses to Salmonella enterica Serotype Typhi Proteins in Patients with Typhoid Fever in Bangladesh

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

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