Dynamics of Persistent Oral Cytomegalovirus Shedding During Primary Infection in Ugandan Infants

J Infect Dis. 2016 Dec 1;214(11):1735-1743. doi: 10.1093/infdis/jiw442. Epub 2016 Sep 20.

Abstract

Cytomegalovirus (CMV) infection occurs frequently in young children, who, when infected, are then a major source of transmission. Oral CMV shedding by 14 infants with primary infection was comprehensively characterized using quantitative polymerase chain reaction weekly for ≥9 months. Three phases of oral shedding were identified: expansion, transition, and clearance. Viral expansion occurred over a median of 7 weeks, with a median doubling time of 3 days. During the transition phase, expansion slowed over a median of 6 weeks before peak viral load was reached. Clearance was slow (22-day median half-life), and shedding did not resolve during observation for any infant. Mathematical modeling demonstrated that prolonged oral CMV expansion is explained by a low within-host reproduction number (median, 1.63) and a delayed immune response that only decreases the infected cell half-life by 44%. Thus, the prolonged oral CMV shedding observed during primary infection can be explained by slow viral expansion and inefficient immunologic control.

Keywords: cytomegalovirus; epidemiology; immunology; mathematical model; theoretical biology; transmission.

MeSH terms

  • Child, Preschool
  • Cohort Studies
  • Cytomegalovirus / isolation & purification*
  • Cytomegalovirus Infections / pathology*
  • Cytomegalovirus Infections / virology*
  • Female
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Models, Theoretical
  • Mouth / virology*
  • Pregnancy
  • Real-Time Polymerase Chain Reaction
  • Time Factors
  • Uganda
  • Virus Shedding*