Dissecting the indirect effects caused by vaccines into the basic elements

Abstract

Vaccination directly protects vaccinated individuals, but it also has the potential for indirectly protecting the unvaccinated in a population (herd protection). Unintended negative consequences such as the re-manifestation of infection, mainly expressed as age shifts, result from vaccination programs as well. We discuss the necessary conditions for achieving optimal herd protection (i.e., high quality vaccine-induced immunity, substantial effect on the force of infection, and appropriate vaccine coverage and distribution), as well as the conditions under which age shifts are likely to occur. We show examples to illustrate these effects. Substantial ambiguity in observing and quantifying these indirect vaccine effects makes accurate evaluation troublesome even though the nature of these outcomes may be critical for accurate assessment of the economic value when decision makers are evaluating a novel vaccine for introduction into a particular region or population group. More investigation is needed to identify and develop successful assessment methodologies for precisely analyzing these outcomes.

Keywords: age shift; clustering; externalities; force of infection; herd protection; rebound effects; serotype replacement; vaccination.

Figure 1.

Modeled phases of varicella infection after vaccination (used with permission from Brisson et al.²) Brisson M, Edmunds WJ. Med Decis Making, 23(1), pp. 76–82, copyright ©2003 by (SAGE Publications). Reprinted by Permission of SAGE Publications. (1) Pre-vaccination phase; (2) Honeymoon phase (Rn < 1); (3) Post-honeymoon epidemic (Rn > 1); (4) New equilibrium.

Figure 2.

Effect of “clustering” on the outbreak probability of measles (used with permission from Salathe et al.) Salathe M, Bonhoeffer S., J R Soc Interface, 5(29), pp. 1505–8, copyright ©2008 by (The Royal Society Publishing). Reprinted by Permission of The Royal Society PublishingBlack bars = probability of measles outbreak without opinion formation Gray bars = probability of measles outbreak with opinion formation.

Figure 3.

Complex relationship between pertussis vaccination and herd protection (used with permission from Arinaminpathy et al.) Reprinted from PNAS USA, 109(49), Arinaminpathy N, Lavine JS, Grenfell BT., Self-boosting vaccines and their implications for herd immunity, pp. 20154–9, Copyright (2012), with permission from PNAS USA.

Figure 4.

Observed age shift in cases of hepatitis A in Catalonia, Spain (used with permission from Lopalco et al.) Reprinted from Vaccine, 19(4–5), Lopalco PL, Salleras L, Barbuti S, et al., Hepatitis A and B in children and adolescents–what can we learn from Puglia (Italy) and Catalonia (Spain)?, pp. 470–474, Copyright (2001), with permission from Elsevier.

Figure 5.

Stylized diagram for evaluating the effects of vaccination.