Study systems include
Massachusetts (current era)
Norway (current era)
Copenhagen (prevaccine era)
Lavine, J.S., King, A.A., Bjornstad, O.N. 2011. Natural immune boosting in pertussis dynamics and the potential for long-term vaccine failure. PNAS doi: 10.1073/pnas.1014394108.
Lavine, J., Broutin, H., Harvill, E. and Bjornstad, O. 2011. Imperfect vaccine-induced immunity and whooping cough transmission to infants. Vaccine 29:11-16. doi: 10.1016/j.vaccine.2010.10.029
Roy, S., Lavine, J., Chiaromonte, F., Terwee J., VandeWoude, S., Bjornstad, O. and Poss, M. 2009. Multivariate Statistical Analyses Demonstrate Unique Host Immune Responses to Single and Dual Lentiviral Infection. PLoS One 4(10): e7359 doi:10.1371/journal.pone.0007359.
Lavine, J. S., Poss, M., and Grenfell, B. T. 2008. Directly transmitted viral diseases: modeling the dynamics of transmission. Trends in Microbiology 16:165-172.
1) Reemergence of pertussis in developed countries
In the past century we have witnessed the start of a global and largely successful experiment in controlling childhood disease outbreaks through mass vaccination campaigns. Diseases like measles, diphtheria, and rubella used to have such high incidence that everyone expected to get them; now they are a rarity even among families who do not vaccinate. Despite the successes, there have also been some surprises, such as the recent reemergence of pertussis, or whooping cough, particularly in teenagers and adults.
Part of the reason for this may be that although immunity to pertussis is not life-long, it can be boosted by re-exposure to small amounts of pertussis antigen. In collaboration with Ottar Bjornstad and Aaron King, I have developed a differential equation model that incorporates boosting of immunity. Our initial work shows that this model predicts the shift in age-incidence and recent increase in cases in highly vaccinated countries while taking into account clinical accounts of the duration of immunity to pertussis.
2) Population dynamical implications of immune system kinetics
I am currently interested in understanding the population level impacts of waning and boosting of immunity. We make the immunologically sound assumption that upon contact with a low dose of pathogen, a host with primed immunity has a quick and robust immune boosting response, but is unlikely to become highly symptomatic or transmissible. We have found that this predicts vaccine failure in the presence of high vaccine coverage due to a shift from stable dynamics with stochastically dominated fluctuations, to large, cyclic outbreaks. This research has lead me to my current work on the following two questions.
- Can we parameterize and validate this model to help explain the variable dynamics exhibited by pertussis globally, and in particular the shifts between cyclic and stable dynamics in prevaccine era Copenhagen (work with Ottar Bjornstad, Aaron King and Viggo Andreasen).
- Can we identify the key parameters (such as duration of immunity, transmission coefficient, birth rate, boosting coefficient etc.) and their boundaries that allow this model to exhibit different dynamical regimes, and thereby identify diseases other than pertussis for which this phenomenon may prevent successful disease control.
3) Estimating transmission dynamics and duration of vaccine-induced immunity from time series data
Using 20 years of case histories, including vaccine histories, provided by the Massachusetts Department of Public Health, I have been able to tease apart age-specific patterns of transmission, using wavelet phase analysis. Additionally, we are able to observe a decrease in the time between last vaccination in subsequent infection over the course of the past ten 15 years (work done in collaboration with Ottar Bjornstad, Helene Broutin, and Eric Harvill). I am also working on applying these same methods to detailed vaccine history and case data from Norway, in collaboration with Ottar Bjornstad, Birgitte Freiesleben (University of Oslo), and the Norwegian Institute for Public Health.