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Published on: July 6, 2013
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.
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.
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.

