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

• Published in: PLoS computational biology 2017-09, Vol.13 (9), p.e1005719-e1005719
• Main Authors: van Boven, Michiel, van de Kassteele, Jan, Korndewal, Marjolein J, van Dorp, Christiaan H, Kretzschmar, Mirjam, van der Klis, Fiona, de Melker, Hester E, Vossen, Ann C, van Baarle, Debbie
• Format: Article
• Language: English
• Subjects: Activation; Adolescent; Adult; Adults; Age; Aged; Aged, 80 and over; Antibody response; Biology and Life Sciences; Child; Child, Preschool; Children; Congenital diseases; Cross-Sectional Studies; Cytomegalovirus; Cytomegalovirus Infections - epidemiology; Cytomegalovirus Infections - transmission; Cytomegalovirus Infections - virology; Disease control; Epidemiology; Estimates; Female; Females; Funding; Health aspects; Health care; Herpes viruses; Humans; Infant; Infant, Newborn; Infections; Infectious diseases; Influenza; Male; Males; Mathematical models; Medicine and Health Sciences; Middle Aged; Parameter estimation; People and Places; Population; Population (statistical); Population studies; Prevalence; Public health; Research and Analysis Methods; Saliva; Seroepidemiologic Studies; Serology; Sex; Social research; Software; Statistical analysis; Studies; Urine; Vaccines; Virus Activation; Viruses; Womens health; Young Adult
• ISSN: 1553-7358; 1553-734X; 1553-7358
• DOI: 10.1371/journal.pcbi.1005719

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.