Institutional members access full text with Ovid®

Share this article on:

Nonprimary Maternal Cytomegalovirus Infection After Viral Shedding in Infants

Boucoiran, Isabelle, MD, MSc*; Mayer, Bryan, T., PhD; Krantz, Elizabeth, M., MS; Marchant, Arnaud, MD, PhD; Pati, Sunil, PhD, MBA§; Boppana, Suresh, MD§; Wald, Anna, MD, MPH†,¶; Corey, Larry, MD†,¶; Casper, Corey, MD, MPH†,¶,‖; Schiffer, Joshua, T., MD, MSc†,¶; Gantt, Soren, MD, PhD, MPH†,*,*

The Pediatric Infectious Disease Journal: July 2018 - Volume 37 - Issue 7 - p 627–631
doi: 10.1097/INF.0000000000001877
Original Studies

Background: Most infants with congenital Cytomegalovirus (CMV) infection are born to seropositive women as a result of maternal CMV nonprimary infection (reinfection or reactivation). Although infected children are known to transmit CMV to their seronegative mothers, the frequency and magnitude of nonprimary maternal CMV infection after exposure to viral shedding by children in their household have not been characterized.

Methods: A cohort of Ugandan newborns and their mothers were tested weekly for CMV by quantitative polymerase chain reaction of oral swabs. Infant primary infection and maternal nonprimary infection were defined by the onset of persistent high-level oral CMV shedding. Strain-specific antibody testing was used to assess maternal reinfection. Cox regression models with time-dependent covariates were used to evaluate risk factors for nonprimary maternal infection.

Results: Nonprimary CMV infection occurred in 15 of 30 mothers, all after primary infection of their infants by a median of 6 weeks (range: 1–10) in contrast to none of the mothers of uninfected infants. The median duration of maternal oral shedding lasted 18 weeks (range: 4–42) reaching a median maximum viral load of 4.69 log copies/mL (range: 3.22–5.64). Previous-week infant CMV oral quantities strongly predicted maternal nonprimary infection (hazard ratio: 2.32 per log10 DNA copies/swab increase; 95% confidence interval: 1.63–3.31). Maternal nonprimary infections were not associated with changes in strain-specific antibody responses.

Conclusions: Nonprimary CMV infection was common in mothers after primary infection in their infants, consistent with infant-to-mother transmission. Because infants frequently acquire CMV from their mothers, for example, through breast milk, this suggests the possibility of “ping-pong” infections. Additional research is needed to characterize the antigenic and genotypic strains transmitted among children and their mothers.

From the *Département d’Obstétrique-Gynécologie, Université de Montréal, CHU Sainte-Justine, Montréal, Québec, Canada; Vaccine and Infectious Disease Division

Fred Hutchinson Cancer Research Center, Seattle, Washington

Institute for Medical Immunology, Institute for Medical Immunology, Université libre de Bruxelles, Charleroi, Belgium

§Department of Pediatrics, University of Alabama Hospital, Birmingham, United Kingdom

Department of Medicine, University of Washington

Infectious Disease Research Institute, Seattle, Washington

*Department of Pediatrics, University of British Columbia, BC Children’s Hospital, Vancouver, British Columbia, Canada.

Accepted for publication August 31, 2017.

This work was supported by grants from the NIH—Roadmap KL2 Clinical Scholar Training Program KL2-RR025015-01 (S.G.), University of Washington Center for AIDS Research New Investigator Award P30-AI027757 (S.G.), P01-AI 030731 (A.W., L.C., and J.T.S.), R01-CA138165 (C.C.) and P30-CA015704 (L.C. and C.C.)—and by a Child & Family Research Institute Salary Award (S.G.).

S.G. reports research funding from VBI Vaccines Inc. The other authors have no conflicts of interest to disclose.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (www.pidj.com).

Address for correspondence: Soren Gantt, MD, PhD, MPH, BC Children’s Hospital Research Institute, 950 W 28th Ave, Rm A5-144, Vancouver, BC V5Z 4H4, Canada. E-mail: sgantt@bcchr.ca.

Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.