title: A dynamic transmission model with age-dependent infectiousness and reactivation for cytomegalovirus in the United States: Potential impact of vaccination strategies on congenital infection.
abstract: We present an age-structured dynamic transmission model for cytomegalovirus (CMV) in the United States, based on natural history and available data, primarily aiming to combine the available qualitative and quantitative knowledge toward more complex modeling frameworks to better reflect the underlying biology and epidemiology of the CMV infection. The model structure explicitly accounts for primary infections, reactivations and re-infections. Duration of infectiousness and likelihood of reactivation were both assumed to be age-dependent, and natural reduction in the re-infection risk following primary infection was included. We used an empirical social contact matrix (POLYMOD-based) as support for CMV transmission between different age groups. The baseline model reproduced well the age-stratified seroprevalence data (National Health and Nutrition Examination Survey III) used for calibration. The model was further used to explore the potential impact of hypothetical vaccination on reducing congenital CMV infection under various vaccine profiles and vaccination scenarios. Our preliminary model-based simulations suggested that while infant vaccination may represent an attractive way to reduce congenital CMV infection over time, adolescent female vaccination with an adequate routine booster platform may, under certain conditions, provide an alternative. However, for such tools to be considered toward actual decision-making, enhanced validations based on additional studies and data would be further necessary. The modeling framework presented in this paper was designed to be sufficiently general and flexible, such that it can allow for further adaptations to reflect new knowledge or data that may become available in the future.
authors.affiliation: a GSK Vaccines; Vaccines - Non-Clinical Operations ; King of Prussia , PA , USA.
authors.forename: Cosmina
authors.initials: C
authors.lastname: Hogea
authors.forename: Ilse
authors.initials: I
authors.lastname: Dieussaert
authors.forename: Thierry
authors.initials: T
authors.lastname: Van Effelterre
authors.forename: Adrienne
authors.initials: A
authors.lastname: Guignard
authors.forename: Johann
authors.initials: J
authors.lastname: Mols
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002675:Child, Preschool; D003587:Cytomegalovirus / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000453:epidemiology / Q000635:transmission*; D022482:Cytomegalovirus Vaccines / Q000627:therapeutic use*; D005260:Female; D005544:Forecasting; D006285:Health Planning; D006801:Humans; D017589:Immunization Programs / Q000458:organization & administration*; D007117:Immunization, Secondary; D007223:Infant; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D015203:Reproducibility of Results; D016036:Seroepidemiologic Studies; D014481:United States / Q000453:epidemiology; D014611:Vaccination; D055815:Young Adult
chemical_list: D022482:Cytomegalovirus Vaccines
keywords: CMV, cytomegalovirus; FOI, force of infection; HPV, human papillomavirus; NHANES, National Health and Nutrition Examination Survey; PI, primary infection; RI, recurrent infection; age-dependence; cCMV, congenital CMV; congenital infection; cytomegalovirus; dynamic transmission model; mathematical modeling; vaccination