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9/09/2025  |   1:00 PM - 2:00 PM   |  Breakout 5   |  University Hall

Lessons derived from >2 years congenital cytomegalovirus (cCMV) screening program: Support for widespread implementation of pooled-saliva testing for universal cCMV screening

Abstract Summary

BACKGROUND: The commonly employed targeted screening of cCMV misses the majority of infants with cCMV, especially those who are asymptomatic at birth, and at risk for late-onset sequelae, thus underestimating the true public health burden of cCMV. The development of an accurate and efficient testing strategy for universal cCMV screening remains challenging. We recently reported on the development of a new saliva pooling setup for universal screening of cCMV (Nature Medicine 2024). Here we report results and lessons derived from >2-years of its routine implementation. METHODS: This prospective study took place in 2 hospitals of Jerusalem beginning April 2022. Saliva samples of all newborns with parental consent were tested for cCMV in 8-sample pools. Positive saliva results were confirmed by urine testing. RESULTS: During the first 25 months of our universal cCMV screening program, 32,385 infants (94.3% of all live newborns) were screened for cCMV using the pooled approach. The pooling strategy proved highly efficient, with each PCR test covering an average of 6 newborns, reducing the number of required saliva tests by 83%. PCR loss of sensitivity was minor, in accordance with the theoretical prediction for an 8-sample pool. cCMV was identified in 123 newborns, with a birth prevalence of 3.8 per 1000. Over half (57.7%) of infants with cCMV identified by universal screening were asymptomatic at birth and would have been missed by targeted screening. Fifty-five percent of cases followed non-primary maternal infection. CONCLUSIONS: The study demonstrates the wide feasibility and benefits of pooled-saliva testing as an accurate and cost-sparing approach, which could revolutionize the implementation of universal cCMV screening. Beyond the clinical implications toward early diagnosis and treatment of cCMV, data derived from the implemented universal screening serves to define the burden of cCMV.

Learning Objectives

  • Describe performance parameters and operational considerations related to initiating and maintaining pooled saliva testing for universal newborn screening of cCMV
  • Describe the true burden of cCMV and the fraction of infants with cCMV who are missed by targeted screening
  • Define the attribution of cCMV to primary versus non-primary maternal infection

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Presenters


Esther Oiknine-Djian | Author

estherd@hadassah.org.il;
Esther Oiknine-Djian, PhD is the supervisor of the Clinical Virology diagnostic laboratory at Hadassah Medical Center. She has facilitated the clinical implementation of the pooling strategy during the COVID-19 pandemic and subsequently for universal newborn screening of congenital CMV. In her PhD studies at the Hebrew University of Jerusalem, under the European Marie Curie programme, she investigated a novel antiviral compound against human CMV, using cell- and unique organ culture systems.

ASHA DISCLOSURE

Financial -

Nonfinancial -

AAA DISCLOSURE

Financial - No relevant financial relationship exists.


Noa Ofek Shlomai | Author

noaofek@hadassah.org.il;
Noa Ofek Shlomai, MD is the head of the Department of Neonatology at Hadassah Ein Kerem hospital campus of Hadassah Medical Center. Her research focuses on feeding and growth in preterm infants, as well as the preterm infant’s microbiome, in relation to short term and growth outcomes. She is actively involved in the diagnosis and research of congenital CMV infection outcomes.

ASHA DISCLOSURE

Financial -

Nonfinancial -

AAA DISCLOSURE

Financial - No relevant financial relationship exists.


Tal Sido | Author

talsido@hotmail.com;
Tal Sido completed her undergraduate studies in Mathematics and is currently an MD student at the Hebrew University of Jerusalem. She works at the Hadassah Medical Center Clinical Virology laboratory, contributing to congenital CMV research at the intersection of data analysis and clinical precision.

ASHA DISCLOSURE

Financial -

Nonfinancial -

AAA DISCLOSURE

Financial - No relevant financial relationship exists.


Oren Gordon | Author

orengo@hadassah.org.il;
Oren Gordon, MD, PhD is a pediatric infectious diseases specialist at Hadassah Medical Center and principal investigator of the Bone Infection Research Laboratory at the Goldyne Savad Institute of Gene Therapy. He is actively involved in the treatment and monitoring of congenital CMV. He studies pathogen resistance and persistence at the site of infection by developing novel microbiological and molecular assays as well as utilizing state-of-the-art imaging modalities, in both animal models of infection and in human patients. As a practicing Pediatric Infectious Diseases specialist, he aims to translate findings from bench to clinical practice to benefit patients.

ASHA DISCLOSURE

Financial -

Nonfinancial -

AAA DISCLOSURE

Financial - No relevant financial relationship exists.


Colin Kunzweiler | POC-Point of Contact, Author

colin.kunzweiler@modernatx.com;
Colin Kunzweiler, PhD is a Director and Epidemiologist for Moderna’s mRNA-1647 CMV vaccine candidate. Colin supports several epidemiology efforts within Moderna’s CMV development program including long-term outcome studies, natural history studies, real-world feasibility assessments, administrative claims analyses, mathematical modeling, and literature reviews. He received his PhD in Epidemiology from the University of Illinois-Chicago School of Public Health.

ASHA DISCLOSURE

Financial - Receives Salary for Employment from Moderna Therapeutics, Inc..  

Nonfinancial - No relevant nonfinancial relationship exists.

AAA DISCLOSURE

Financial - Receives support from Moderna Therapeutics, Inc. for Colin Kunzweiler is an employee of Moderna Therapeutics, Inc. and owns stock/stock options in the company..  


Adva Gadoth | Author

adva.gadoth@modernatx.com;
Adva Gadoth, PhD is an Associate Director and Epidemiologist for Moderna’s early stage and latent virus vaccines, including cytomegalovirus (CMV), herpes simplex virus (HSV), and mpox clinical development programs. Adva also supports epidemiologic evidence generation and non-interventional study implementation for Moderna’s global public health efforts, building off years of experience conducting complex cohort and disease surveillance studies in low- and middle-income countries. She received her PhD in Epidemiology from the University of California, Los Angeles (UCLA).

ASHA DISCLOSURE

Financial -

Nonfinancial -

AAA DISCLOSURE

Financial - No relevant financial relationship exists.


Laura Hendrix | Author

Laura.Hendrix@modernatx.com;
Laura Hendrix is a Senior Manager in the Real-World Analytics team at Moderna, providing biostatistical and epidemiological expertise to support the latent virus program and other therapeutic areas. With an MS in Epidemiology from the London School of Hygiene & Tropical Medicine, she brings 15 years of experience across academic and industry settings, specializing in evidence generation to inform clinical development and regulatory strategies.

ASHA DISCLOSURE

Financial -

Nonfinancial -

AAA DISCLOSURE

Financial - No relevant financial relationship exists.


John Diaz-Decaro | Author

John.Diaz-Decaro@modernatx.com;
John Diaz-Decaro is a Senior Director and Lead Epidemiologist at Moderna, where he leads epidemiologic strategy for the development of vaccines targeting Epstein-Barr virus (EBV) and other latent viruses. His work supports clinical development for Moderna’s EBV and CMV vaccine programs. Dr. Diaz-Decaro plays a key role in advancing non-interventional studies to assess disease burden, including EBV-associated conditions such as infectious mononucleosis, multiple sclerosis and post-transplant lymphoproliferative disorder. He also contributes to Moderna’s CMV epidemiology research portfolio supporting work on studies focused on investigating infant outcomes associated with congenital CMV, as well as CMV transmission dynamics in daycare settings.

ASHA DISCLOSURE

Financial -

Nonfinancial -

AAA DISCLOSURE

Financial - No relevant financial relationship exists.


Yosefa Hefter | Author

YosefaH@medisonpharma.com;
Yosefa Hefter, MD is a medical affairs manager at Medison Pharma, focusing on vaccines. Yosefa is a pediatric infectious diseases physician. She received her MD from the Albert Einstein College of Medicine and completed post-graduate training at New York Medical College and Children’s National Hospital. Prior to joining Medison in 2021, she served as a clinical reviewer in the Office of Vaccines Research and Review at the US Food and Drug Administration.

ASHA DISCLOSURE

Financial -

Nonfinancial -

AAA DISCLOSURE

Financial - No relevant financial relationship exists.


Moran Yassour | Author

Moranya@mail.huji.ac.il;
Moran Yassour, PhD is an Associate Professor and Principal Investigator at the Hebrew University of Jerusalem, jointly appointed at the Faculty of Medicine and the School of Computer Science and Engineering. As an expert in data science, she has analyzed large-scale data derived from pooled universal screening of congenital CMV. Dr. Yassour earned her Ph.D. in Computational Biology from the Hebrew University of Jerusalem and completed her postdoctoral training at the Broad Institute of MIT and Harvard, and Harvard Medical School. In her lab, she combines computational analyses with experimental approaches to study host-microbiome interactions, aiming to uncover mechanisms that shape the microbiome in infancy and its long-term health implications. Dr. Yassour is a recipient of the Azrieli Faculty Fellowship and other honors recognizing her contributions to microbiology research and computational biology.

ASHA DISCLOSURE

Financial -

Nonfinancial -

AAA DISCLOSURE

Financial - No relevant financial relationship exists.


Smadar Eventov Friedman | Author

smadaref@hadassah.org.il;
Smadar Eventov Friedman, MD, PhD is the head of the Division of Neonatology at Hadassah Medical Center and a Professor at the Hebrew University of Jerusalem. Her current main research focuses on congenital CMV, including universal screening, advanced laboratory diagnostic techniques, biomarkers and demographic characteristics of maternal infection. Together with Prof. Wolf she has implemented universal congenital CMV screening at the two hospital campuses of Hadassah Medical Center.

ASHA DISCLOSURE

Financial -

Nonfinancial -

AAA DISCLOSURE

Financial - No relevant financial relationship exists.


Dana Wolf | Primary Presenter, Author

danaw@ekmd.huji.ac.il;
Dana Wolf, MD is the Director of Clinical Virology at Hadassah Medical Center and a Professor at the Hebrew University of Jerusalem. She leads research projects focusing on human CMV transmission and correlates of protection. She has discovered new prognostic prenatal biomarkers which predict the severity of congenital CMV infection in the fetus and the newborn. She has developed and implemented, in collaboration with the Division of Neonatology, a new saliva-pooling setup for universal newborn screening of congenital CMV. She is currently characterizing neonatal and maternal infection parameters. She is a member of national and international advisory committees, including the Israeli Advisory Committee on Immunization Practices and Epidemic Preparedness Team, and the European Society for Virology Executive Board.

ASHA DISCLOSURE

Financial - Receives Grants for Independent contractor from GSK.   Receives Grants for Independent contractor from Moderna.   Receives Consulting fee,Grants for Membership on advisory committee or review panels,Independent contractor from MSD.   Receives Consulting fee for Membership on advisory committee or review panels from Roche.   Receives Grants for Independent contractor from Sanofi.   Receives Consulting fee for Membership on advisory committee or review panels from Takeda.  

Nonfinancial - No relevant nonfinancial relationship exists.

AAA DISCLOSURE

Financial - Receives support from MSD Moderna Takeda Roche GSK and Sanofi for MSD- received research grant, served in advisory committees Moderna - received research grant Takeda - served in advisory committee Roche - served in advisory committee GSK and Sanofi - were co-participants in a European research consortium in which I participated .