Modeling the potential impact of vaccination on the epidemiology of congenital cytomegalovirus infection

Abstract

Background Understanding the potential for vaccination to change cytomegalovirus (CMV) epidemiology is important for developing CMV vaccines and designing clinical trials. Methods We constructed a deterministic, age-specific and time-dependent mathematical model of pathogen transmission, parameterized using CMV seroprevalence from the United States and Brazil, to predict the impact of vaccination on congenital CMV infection. Findings Concurrent vaccination of young children and adolescents would result in the greatest reductions in congenital CMV infections in populations with moderate and high baseline maternal seroprevalence. Such a vaccination strategy, assuming 70% vaccine efficacy, 90% coverage and 5-year duration of protection, could ultimately prevent 30%-50% of congenital CMV infections. At equilibrium, this strategy could result in a 30% reduction in congenital CMV infections due to primary maternal infection in the United States but a 3% increase in Brazil. The potential for an increase in congenital CMV infections due to primary maternal infections in Brazil was not predicted with use of a vaccine that confers protection for greater than 5 years. Interpretation Modeling suggests that vaccination strategies that include young children will result in greater declines in congenital CMV infection than those restricted to adolescents or women of reproductive age. Our study highlights the critical need for better understanding of the relative contribution of type of maternal infection to congenital CMV infection and disease, the main focus of vaccine prevention.

Priorities for CMV vaccine development

“…For rubella vaccine, vaccinating male and female toddlers was superior to vaccinating only seronegative women in reducing viral circulation and the incidence of congenital disease. Preliminary modeling of the effect of various immunization strategies predicts that even a CMV vaccine with a relatively short duration of efficacy of a few years administered to 12–18 month-olds would substantially reduce cCMV incidence 37, 38 .…”

Investigating spatiotemporal dynamics and synchrony of influenza epidemics in Australia: An agent-based modelling approach

“…For instance, a 2007 study estimated that the annual cost of seasonal influenza to the health system in Australia was AU$828-884 million [1]. Effective strategies for mitigating outbreaks should include a suitable combination of immunisation, vaccination, and palliative care [2,3,4] and planning these strategies requires reliable forecasting through simulation of various "what if?" scenarios.…”

Reduced Frequencies of Polyfunctional CMV-Specific T Cell Responses in Infants with Congenital CMV Infection

“…Moreover, children with congenital or postnatal CMV infection may shed virus in the urine for prolonged periods, increasing the risk of primary CMV infection in their seronegative pregnant caretakers [3-5]. One possible CMV vaccine strategy is to immunize infants to prevent CMV infection, reduce viral shedding after primary infection, or to reduce the risk of severe congenital infection during pregnancy later in life, which has been a rationale for universal rubella immunization [6-8]. Another strategy is to vaccinate infants with congenital CMV infection as immunotherapy with or without antiviral agents, which has been the basis of CMV vaccine clinical trials in seropositive women or stem cell transplant recipients [6, 9, 10].…”