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

Bryan T Mayer1, Laura Matrajt1, Corey Casper1,2,3,4,5,6

  • 1Vaccine and Infectious Disease Division.

Insights

Primary cytomegalovirus (CMV) infection in infants involves prolonged oral shedding. This shedding is driven by slow viral expansion and a delayed immune response, highlighting inefficient immunologic control in young children.

Area of Science:

  • Virology
  • Pediatric Infectious Diseases
  • Immunology

Background:

  • Cytomegalovirus (CMV) is frequently acquired by young children.
  • Infected children are a significant source of CMV transmission.
  • Understanding CMV shedding dynamics in primary infection is crucial for public health.

Purpose of the Study:

  • To comprehensively characterize oral cytomegalovirus (CMV) shedding during primary infection in infants.
  • To identify distinct phases of oral CMV shedding.
  • To investigate the factors contributing to prolonged viral shedding using mathematical modeling.

Main Methods:

  • Quantitative polymerase chain reaction (qPCR) was used to monitor oral CMV shedding weekly in 14 infants with primary infection for at least 9 months.
  • Three phases of shedding (expansion, transition, clearance) were identified.
  • Mathematical modeling was employed to analyze viral dynamics and immune response.

Main Results:

  • Oral CMV shedding exhibited three distinct phases: expansion (median 7 weeks, doubling time 3 days), transition, and slow clearance (median half-life 22 days).
  • Shedding did not resolve in any infant during the observation period.
  • Mathematical modeling indicated prolonged expansion is due to a low within-host reproduction number (median 1.63) and a delayed immune response reducing infected cell half-life by only 44%.

Conclusions:

  • Primary CMV infection in infants is characterized by prolonged oral shedding.
  • Slow viral expansion and inefficient immunologic control, marked by a delayed immune response, explain the extended shedding duration.
  • These findings underscore the importance of understanding viral kinetics and host immunity in pediatric CMV infections.