Infectious reactivation of cytomegalovirus explaining age- and sex-specific patterns of seroprevalence.

• Main Authors: Michiel van Boven, Jan van de Kassteele, Marjolein J Korndewal, Christiaan H van Dorp, Mirjam Kretzschmar, Fiona van der Klis, Hester E de Melker, Ann C Vossen, Debbie van Baarle
• Format: Article
• Language: English
• Published: Public Library of Science (PLoS) 2017-09-01
• Series: PLoS Computational Biology
• Online Access: http://europepmc.org/articles/PMC5630159?pdf=render
• ISSN: 1553-734X; 1553-7358

Human cytomegalovirus (CMV) is a herpes virus with poorly understood transmission dynamics. Person-to-person transmission is thought to occur primarily through transfer of saliva or urine, but no quantitative estimates are available for the contribution of different infection routes. Using data from a large population-based serological study (n = 5,179), we provide quantitative estimates of key epidemiological parameters, including the transmissibility of primary infection, reactivation, and re-infection. Mixture models are fitted to age- and sex-specific antibody response data from the Netherlands, showing that the data can be described by a model with three distributions of antibody measurements, i.e. uninfected, infected, and infected with increased antibody concentration. Estimates of seroprevalence increase gradually with age, such that at 80 years 73% (95%CrI: 64%-78%) of females and 62% (95%CrI: 55%-68%) of males are infected, while 57% (95%CrI: 47%-67%) of females and 37% (95%CrI: 28%-46%) of males have increased antibody concentration. Merging the statistical analyses with transmission models, we find that models with infectious reactivation (i.e. reactivation that can lead to the virus being transmitted to a novel host) fit the data significantly better than models without infectious reactivation. Estimated reactivation rates increase from low values in children to 2%-4% per year in women older than 50 years. The results advance a hypothesis in which transmission from adults after infectious reactivation is a key driver of transmission. We discuss the implications for control strategies aimed at reducing CMV infection in vulnerable groups.