CASE STUDY 2 (PERTUSSIS)

Resolving paradoxes posed by individual-level versus population-level data.

C. Nadell
A strain of Vibrio cholerae; C. Nadell

Pertussis (whooping cough), caused by Bordetella species bacteria, is a leading cause of vaccine-preventable death among children worldwide and is resurgent in many developed countries despite the widespread availability and application of nominally effective vaccines. The disease is most severe (and mortality highest) in infants and young children, who often have distinctive symptoms. Among adults, the disease is typically much milder and the symptoms are easily confused with those caused by other pathogens. A popular hypothesis for the resurgence of pertussis is that vaccines are effective for at most a few years and that undiagnosed infections in teenagers and adults are responsible for much of the transmission; a second hypothesis is that current vaccines protect against disease but not infection, resulting in transmission from vaccinated hosts (see [1]).

Pertussis is resurgent in many developed countries despite the widespread availability and application of nominally effective vaccines.

The potential for transmissible infection in vaccinated hosts is strongly suggested by a series of experiments in baboons: hosts inoculated with a common pertussis vaccine were susceptible to infection when exposed to infectious baboons, and vaccinated and subsequently infected baboons were capable of transmission of bacteria [2]. Critically, in marked contrast to naive animals, vaccinated animals developed no detectable disease upon infection. These data lend credence to the hypotheses described above.

However, in apparent contradiction to those findings, a growing number of studies demonstrate that the population dynamics of pertussis are inconsistent with appreciable amounts of transmissible infection in the older age classes (e.g., [3, 4]). Wherever data have been examined, mass vaccination campaigns are associated with initial, rapid collapses in the incidence of infection, a telltale signature of population-wide ‘herd’ immunity incompatible with rapidly waning immunity or vaccines largely ineffective against transmission [3-6]. In effect, then, data gathered at different scales – at the level of individual hosts and at the host population level – present a paradoxical picture of pertussis epidemiology in vaccinated populations.

Data gathered at different scales – at the level of individual hosts and at the host population level – present a paradoxical picture of pertussis epidemiology in vaccinated populations.

Resolution of this paradox will require bridging the gap between the determinants of an individual host’s course of infection and the dynamics of transmission at the population level. At the individual-level, we need to understand the roles of age, vaccine composition, and host vaccination and infection history on severity of disease, intensity of transmission, and duration and degree of immunity induced by vaccination or infection. Once new models that accurately represent these individual-scale infection dynamics have been developed, the bridge to population level dynamics can be made mathematically explicit using well-established techniques (e.g., [7, 8]). However, the knowledge to do so does not lie within the capacity of any one research group, but will instead require new collaborations that include microbiologists, immunologists, pathologists, epidemiological ecologists and mathematicians fostered by our IDEAS RCN.

References:

  1. Jackson, D.W. and P. Rohani, Perplexities of pertussis: recent global epidemiological trends and their potential causes. Epidemiol Infect, 2013: p. 1-13.
  2. Warfel, J.M. and T.J. Merkel, Bordetella pertussis infection induces a mucosal IL-17 response and long-lived Th17 and Th1 immune memory cells in nonhuman primates. Mucosal Immunol, 2013. 6(4): p. 787-96.
  3. Rohani, P., X. Zhong, and A.A. King, Contact network structure explains the changing epidemiology of pertussis. Science, 2010. 330(6006): p. 982-5.
  4. Lavine, J.S. and P. Rohani, Resolving pertussis immunity and vaccine effectiveness using incidence time series. Expert Rev Vaccines, 2012. 11(11): p. 1319-29.
  5. Wearing, H.J. and P. Rohani, Estimating the duration of pertussis immunity using epidemiological signatures. PLoS Pathog, 2009. 5(10): p. e1000647.
  6. Blackwood, J.C., et al., Deciphering the impacts of vaccination and immunity on pertussis epidemiology in Thailand. PNAS US, 2013. 110(23): p. 9595-600.
  7. Gilchrist, M.A. and D. Coombs, Evolution of virulence: interdependence, constraints, and selection using nested models. Theor Popul Biol, 2006. 69(2): p. 145-53.
  8. King, A.A., et al., Evolution of acute infections and the invasion-persistence trade-off. Am Nat, 2009. 173(4): p. 446-55.