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1.
Figure 1

Figure 1. Stratification of pneumococcal serotypes.. From: Pneumococcal Transmission and Disease In Silico: A Microsimulation Model of the Indirect Effects of Vaccination.

Serotypes are stratified into 5 categories, based on their inclusion in different PCV formulations (PCV7, PCV10 and PCV13) and their case-to-carrier ratios. The number (N) of isolates refers to the distribution of serotypes in children <2 years of age [25]. In the model, each category is subdivided into a given number of individual model types.

Markku Nurhonen, et al. PLoS One. 2013;8(2):e56079.
2.
Figure 3

Figure 3. Model for transmission of pneumococcal carriage.. From: Pneumococcal Transmission and Disease In Silico: A Microsimulation Model of the Indirect Effects of Vaccination.

Each individual in the population belongs to one of 67 possible states: susceptible to carriage, carrier of one of the 11 model types, or simultaneous carrier of any two of the 11 model types. For simplicity, the figure presents the model for two of the 11 model types, denoted as A and B. The flow of individuals is governed by rates of clearance and acquisition, as marked at each arrow. The rates of acquisition depend on the number of carriers in the mixing group which the individual belongs to and, for already carrying individuals, also on the ranking order of the categories corresponding to the incoming and the carried type (see text). The rates of acquisition for vaccine-protected individuals are reduced by a factor (1-φc). Vaccinated individuals lose protection against carriage with a waning rate (see text) and move to an unprotected compartment. The rate of clearance μ is assumed same, regardless of the vaccination status, the type(s) and the number of types carried.

Markku Nurhonen, et al. PLoS One. 2013;8(2):e56079.
3.
Figure 4

Figure 4. Incidence of carriage and case-to-carrier ratios by serotype category in two age classes in Finland.. From: Pneumococcal Transmission and Disease In Silico: A Microsimulation Model of the Indirect Effects of Vaccination.

The stationary incidence of pneumococcal carriage (per year per 100,000 persons) is indicated on the horizontal axis by category, shown cumulatively. The serotype category-specific case-to-carrier ratios are shown on the vertical axis; note the different scales in the <5 and 5+ panels. The area of each rectangle represents the annual IPD incidence (per 100,000) in the respective serotype category. The upmost horizontal pair of panels shows the annual IPD incidence (per 100,000) before vaccination. The category-specific incidences of carriage (horizontal axis) correspond to the average pre-vaccination incidences. The other panels correspond to the projected IPD incidences after the onset of vaccination programme with PCV7, PCV10 and PCV13. The projected overall and serotype category-specific IPD incidences (indicated in green font) are obtained as averages from simulation runs based on the 50 most optimal parameter combinations. The post-vaccination panels show the average projected IPD incidence (area), the average case-to-carrier ratios (vertical axis) and the corresponding incidence of carriage (horizontal axis). The pairs of values in parentheses are the corresponding ranges of projected IPD incidences based on the 50 simulation runs.

Markku Nurhonen, et al. PLoS One. 2013;8(2):e56079.
4.
Figure 5

Figure 5. Basic reproduction matrix K.. From: Pneumococcal Transmission and Disease In Silico: A Microsimulation Model of the Indirect Effects of Vaccination.

Each column in the plot corresponds to a single carrier of a given stratum. The stratification is based on 29 age groups, presence of siblings under 7 years of age (yes/no for children <7 years of age), parental status (with/without children <7 years of age for adults 20–45 years of age), day care attendance (yes/no). Each entry indicates the average number of infectious contacts from a single carrier in stratum j (column) to a one-year age cohort of individuals in stratum i (row). Darker colours indicate higher numbers. The numbers are calculated from the distribution of social contacts extracted from the simulation and applying the most optimal parameter combintation. The column/row numbering refers to the lower limit of the age group.

Markku Nurhonen, et al. PLoS One. 2013;8(2):e56079.
5.
Figure 7

Figure 7. Thresholds for elimination of vaccine-type carriage among children less than five years of age.. From: Pneumococcal Transmission and Disease In Silico: A Microsimulation Model of the Indirect Effects of Vaccination.

The figure shows the time in years until near elimination (5% of the level of vaccine-type carriage prevalence in the pre-vaccination era) for PCV7 and PCV13 and for different combinations of the values of vaccine efficacy against carriage (horizontal axis in each plot) and coverage of vaccination (vertical axis). Left panels: The waning rate of vaccine-induced immunity against carriage is 10% per year. Right panels: the waning rate is 25% per year. Upper panels: PCV7. Lower panels: PCV13. The numbering within each panel corresponds to lower limits (in years) of the respective colour codes, with 40+ corresponding to 40 or more years until near elimination. The results were obtained using the most optimal parameter combination. For results corresponding to the 50 most optimal parameter combinations, see Figure S3.2 in File 3.

Markku Nurhonen, et al. PLoS One. 2013;8(2):e56079.
6.
Figure 6

Figure 6. Impact of vaccination on pneumococcal carriage in two age classes in Finland.. From: Pneumococcal Transmission and Disease In Silico: A Microsimulation Model of the Indirect Effects of Vaccination.

Each panel presents the projected cumulative prevalence of carriage of the five serotype categories (from V to I) as a function of time, with time 0 corresponding to the onset of the vaccination programme. The point-wise median prevalence based on the 50 most optimal parameter combinations is shown cumulatively by serotype category. For the total prevalence of all five categories, also the 5% and 95% quantiles (dashed curves) are shown. Upper panels: individuals <5 years of age. Lower panels: individuals 5+ years of age. From left to right: PCV7, PCV10, PCV13. To adjust for a changing demography, the prevalence shown in the figure is standardised according to the age distribution of Finland in 2005. In the simulation, the values of vaccine efficacy against carriage (φc) was 0.50 for all vaccine types in the respective vaccine formulation, the coverage of vaccination (pc) 0.90 and the waning rate of immunity against carriage (w) 10% per year.

Markku Nurhonen, et al. PLoS One. 2013;8(2):e56079.
7.
Figure 2

Figure 2. Age-specific prevalence of carriage and the serotype distribution.. From: Pneumococcal Transmission and Disease In Silico: A Microsimulation Model of the Indirect Effects of Vaccination.

(A) The prevalence of pneumococcal carriage in 9 age windows (<0.5, 0.5–0.99, 1.00–1.49, 1.50–1.99, 2–3, 4–5, 6–12, 13–17, 18+ years of age). The blue and red horizontal lines correspond to the model simulation using the 5 most optimal parameter combinations having the 5 highest (median) likelihood values, with the blue lines indicating the most optimal combination (Table 1). The ranges of model predictions are shown for each age window in grey colour. These correspond to the 50 most optimal parameter combinations. The point-wise intervals containing 75% of these 50 prevalence values are shown in yellow. The observed proportions (number of positive samples/number of samples) are indicated by the green line segments (there were no observations in age window 2–3 years). These data originate from 3 studies as described in the text. (B) The serotype distribution for the five serotype categories. The simulation results and the observed data are presented as in panel A. The observed data originate from a study of pneumococcal carriage in children <2 years of age (Table 1; [25]).

Markku Nurhonen, et al. PLoS One. 2013;8(2):e56079.

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