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. 2015 Apr 23;11(4):e1004138.
doi: 10.1371/journal.pcbi.1004138. eCollection 2015 Apr.

A change in vaccine efficacy and duration of protection explains recent rises in pertussis incidence in the United States

Manoj Gambhir  1 , Thomas A Clark  2 , Simon Cauchemez  3 , Sara Y Tartof  4 , David L Swerdlow  5 , Neil M Ferguson  6
Affiliations

A change in vaccine efficacy and duration of protection explains recent rises in pertussis incidence in the United States

Manoj Gambhir et al. PLoS Comput Biol. .

Abstract

Over the past ten years the incidence of pertussis in the United States (U.S.) has risen steadily, with 2012 seeing the highest case number since 1955. There has also been a shift over the same time period in the age group reporting the largest number of cases (aside from infants), from adolescents to 7-11 year olds. We use epidemiological modelling and a large case incidence dataset to explain the upsurge. We investigate several hypotheses for the upsurge in pertussis cases by fitting a suite of dynamic epidemiological models to incidence data from the National Notifiable Disease Surveillance System (NNDSS) between 1990-2009, as well as incidence data from a variety of sources from 1950-1989. We find that: the best-fitting model is one in which vaccine efficacy and duration of protection of the acellular pertussis (aP) vaccine is lower than that of the whole-cell (wP) vaccine, (efficacy of the first three doses 80% [95% CI: 78%, 82%] versus 90% [95% CI: 87%, 94%]), increasing the rate at which disease is reported to NNDSS is not sufficient to explain the upsurge and 3) 2010-2012 disease incidence is predicted well. In this study, we use all available U.S. surveillance data to: 1) fit a set of mathematical models and determine which best explains these data and 2) determine the epidemiological and vaccine-related parameter values of this model. We find evidence of a difference in efficacy and duration of protection between the two vaccine types, wP and aP (aP efficacy and duration lower than wP). Future refinement of the model presented here will allow for an exploration of alternative vaccination strategies such as different age-spacings, further booster doses, and cocooning.

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Conflict of interest statement

Manoj Gambhir is a paid employee of IHRC, inc.

Figures

Fig 1
Fig 1. Incidence of disease and vaccination coverage in the United States.
The time varying incidence of disease in the US, summed over all ages, between 1950 and 2009, annotated for significant events relating to vaccination policy. The blue solid line illustrates the DTP3 (first three DTP doses) vaccine coverage level over time.
Fig 2
Fig 2. Incidence of disease in the United States, compared with modeled values.
The time varying incidence of disease cases in the model and the US data (log scale) after 1990. The black dots are US disease incidence data, and the shaded regions represent the credible intervals (50% and 95%) obtained through model parameter estimation of model 8. The model has been run beyond the time over which it was trained to illustrate its continued correspondence with the 2010–2012 data (red crosses).
Fig 3
Fig 3. Cross-sectional incidence of disease over age of population.
Annual age-dependent (to age 30 years) incidence of pertussis disease cases for the years 1994–2012 in 2 year intervals. Gray shaded envelopes indicate 50%, 90%, 95%, and 99% credible intervals from the model parameter and uncertainty estimation. Black points (1994–2008) indicate disease incidence data collected by the NNDSS. The red crosses on the 2010 and 2012 plots also represent NNDSS incidence data; however, the model was not fitted to these data and so model outputs represent out-of-sample predicted age-dependent incidence curves.
Fig 4
Fig 4. Case-control study results compared with modeled values.
Vaccine Effectiveness (VE) as measured in the case-control study of Misegades et al [22] from 2010 in California (black crosses) compared with VE values generated by simulations of the case-control study using the model fitted to the incidence and these VE data (gray region). The gray shaded region represents the 95% credible interval of the model outputs. The dotted curve lying above the 2010 data and simulations was calculated by simulating a 1990 case-control study, and shows significantly slower waning of the VE value.
Fig 5
Fig 5. Epidemiological model diagram.
The compartmental model for pertussis infection and disease used, modified from the basic model of Aguas et al [44]. There are two infected compartments for primary (I 1) and secondary (or higher) infection (I 2). We assume that surveillance systems only capture those who are experiencing primary infection. Once an individual has recovered from primary or secondary infection, induced immunity may wane, whereupon they will re-enter the susceptible state. Rates of flow between compartments are defined in Table 3.
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References

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