Modeling Insights into Haemophilus influenzae Type b Disease, Transmission, and Vaccine Programs

Michael L. Jackson¹

, Charles E. Rose, Amanda Cohn, Fatima Coronado, Thomas A. Clark, Jay D. Wenger, Lisa Bulkow, Michael G. Bruce, Nancy E. Messonnier, and Thomas W. Hennessy

Author affiliations: Centers for Disease Control and Prevention, Atlanta, Georgia, USA

Abstract

In response to the 2007–2009 Haemophilus influenzae type b (Hib) vaccine shortage in the United States, we developed a flexible model of Hib transmission and disease for optimizing Hib vaccine programs in diverse populations and situations. The model classifies population members by age, colonization/disease status, and antibody levels, with movement across categories defined by differential equations. We implemented the model for the United States as a whole, England and Wales, and the Alaska Native population. This model accurately simulated Hib incidence in all 3 populations, including the increased incidence in England/Wales beginning in 1999 and the change in Hib incidence in Alaska Natives after switching Hib vaccines in 1996. The model suggests that a vaccine shortage requiring deferral of the booster dose could last 3 years in the United States before loss of herd immunity would result in increasing rates of invasive Hib disease in children <5 years of age.

Routine use of Haemophilus influenzae type b (Hib) conjugate vaccines has dramatically reduced the incidence of Hib disease in children <5 years of age in numerous populations (1–4). Vaccination programs have also led to herd immunity through reduced Hib transmission, as shown by declines in the prevalence of oropharyngeal Hib colonization among vaccinated children and unvaccinated children and adults (2,4–6). However, even successful vaccination programs have not eliminated Hib colonization (7,8). Thus, the continued success of Hib control programs depends on maintaining age-appropriate Hib vaccine coverage. Such coverage can, however, be threatened by changes in vaccine supply, as indicated by the 2007–2009 Hib vaccine shortage in the United States (9,10).

To manage that shortage, the Centers for Disease Control and Prevention and partner organizations recommended that providers defer giving the 12–15-month booster dose to all children except those at high risk for invasive Hib disease (9). This recommendation was based on expert opinion about the predicted effects of a shortage initially expected to last <9 months (9). When it became clear that the shortage would last longer, we sought to develop a model of Hib transmission and disease to predict the effects of continued booster dose deferral and to guide vaccine policy. Such a model could also be useful for optimizing the introduction of Hib vaccines into new populations. Furthermore, it could provide insights into the dynamics of Hib transmission and colonization, which would inform the uncertainty over the types of Hib vaccines that are most appropriate for populations at high risk for invasive Hib disease, such as Alaska Natives (11). We present the model and show its application to various populations and vaccination scenarios.