Intervention timeline.

<p>Events in 2010 are listed on the left alongside the timeframe for the simulated interventions: (I) RDT screening, (IIa) time-of-departure prophylaxis with antimicrobial drugs, (IIb) early-initiated prophylaxis with antimicrobial drugs beginning 7 d prior to deployment, (III) two-dose OCV immunization at 36 and 22 d prior to deployment, (IVa) two-dose OCV immunization combined with time-of-departure chemoprophylaxis, and (IVb) two-dose OCV immunization combined with early-initiated chemoprophylaxis.</p

Epidemiological dynamics.

<p>We illustrate model-data concordance by plotting case observations (points) along with sample paths from stochastic realizations of the model (<i>n =</i> 100) under the status-quo scenario used for fitting. We plot instances (<i>n</i> = 79) in which transmission ensued and omit those where no epidemic occurred (<i>n</i> = 21). (<b>A</b>): Cases in the Artibonite-adjacent communes; (<b>B</b>): cases in all other communes.</p

Overall effect of vaccination on the projected incidence of typhoid over the first 10 years following vaccine introduction.

<p>The model-predicted reduction in the cumulative incidence of typhoid at coverage levels ranging from 0 to 100% is plotted for vaccine-induced immunity and efficacy assumptions corresponding to (<i>A</i>) the Ty21a live oral vaccine, (<i>B</i>) the Vi-polysaccharide (ViPS) vaccine, and (<i>C</i>) the Vi-conjugate (ViCV) vaccine administered at 6 years of age or (<i>D</i>) 9 months of age. The red line represents the model-predicted overall effect of vaccination, while the green line represents the population direct effect of vaccination. The dotted black line represents the population coverage (i.e. the proportion of the population ever vaccinated).</p

Combined impact of sanitation and vaccination on the projected weekly incidence of typhoid.

<p>The model-predicted weekly number of typhoid cases in Vellore is plotted for values of the proportion of transmission due to chronic carriers (<i>c_p</i>) from 5% to 95% and the percent of transmission that is water-borne (<i>R</i>_0,<i>w</i>/<i>R</i>₀) from 25% to 100%. Improved sanitation is modeled as a reduction in water-borne transmission (<i>R</i>_0,<i>w</i>) from baseline levels to zero over a 30-year period beginning in year 5. Vaccination is introduced in year 5 with 80% coverage as routine vaccination of 6 year olds plus a one-time catch-up campaign among 6–15 year olds using ViPS vaccines. The red line represents the overall effect of sanitation plus vaccination, while the light blue line represents the effect of improved sanitation only and the dotted blue line is the projected typhoid incidence in the absence of any intervention.</p

Fixed model parameters and parameters estimated from the best-fit model for typhoid inpatients at Christian Medical College hospital in Vellore, India.

<p>The best-fit model was not sensitive to this parameter.</p><p>Inseparable from the estimated long-cycle transmission parameter, <i>β_w</i>.</p

Model for the transmission dynamics of typhoid.

<p>(<i>A</i>) Diagram of model structure. Model parameters are defined in <a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0002642#pntd-0002642-t001" target="_blank">Table 1</a>. (<i>B</i>) Weekly incidence of observed (blue line) and model-predicted (thick red line) typhoid inpatients at Christian Medical College hospital in Vellore, India. The thin red line represents a simulated incidence time-series for the best-fit model assuming the number of cases each week is Poisson distributed with a mean equal to the model-predicted incidence. (<i>C</i>) Age distribution of observed (blue) and model-predicted (red) typhoid cases.</p

Cumulative number of typhoid cases prevented per 1,000 vaccine courses when vaccination is introduced with 80% coverage.

<p>Cumulative number of typhoid cases prevented per 1,000 vaccine courses when vaccination is introduced with 80% coverage.</p

Predicted impact of vaccination on the weekly incidence of typhoid.

<p>Vaccination is introduced in year 5 with 80% coverage as (<i>A</i>) a one-time campaign among 6–15 year olds, (<i>B</i>) routine vaccination of 6 year olds, or (<i>C</i>) routine vaccination of 6 year olds plus a one-time catch-up campaign among 6–15 year olds. The red line represents the model-predicted overall effect of vaccination, while the green line represents the population direct effect of vaccination and the dotted blue line is the projected typhoid incidence in the absence of vaccination.</p

Total cases and incidence for the Global Burden of Disease regions and subregions made up of low- and middle-income countries.

<p>Total cases are shown in millions and incidence is per 100,000 person-years.</p

Probability that each location falls into one of four incidence categories: <10, 10-<100, 100-<500, and ≥500 cases per 100,000 person-years, designated as low, medium, high, and very high incidence, respectively.

<p>Probability that each location falls into one of four incidence categories: <10, 10-<100, 100-<500, and ≥500 cases per 100,000 person-years, designated as low, medium, high, and very high incidence, respectively.</p