Document text
ACIP CMV Vaccine Workgroup
Cytomegalovirus (CMV) and congenital CMV (cCMV)
Epidemiology and Disease Burden
Tatiana M. Lanzieri, MD, MPH
ACIP CMV WG Co -Lead
April 15th, 2025
Measles, Rubella and CMV Epidemiology TeamViral Vaccine Preventable Diseases BranchDivision of Viral DiseasesNational Center for Immunization & Respiratory Diseases
Review epidemiology and disease burden of CMV and cCMVObjectives
More than 16,000 children born with cCMV infection in
the U.S. every year – 4.5 per 1,000 live births
Frequencies based on unpublished review of 30 unique cohorts of children with cCMV identified through newborn screening followed up through childhood.OutcomeAnnual
number of
affected
children%
Neonatal death 80 0.5
cCMV disease† 2800 17
Long -term outcomes (selected)
Sensorineural hearing loss 825 5
Cognitive impairment 495 3
Motor impairment 165 1
Neonatal signs
Rash (purpura/petechiae)
Enlarged liver and/or spleen (hepatosplenomegaly)
Small head (microcephaly)
Laboratory diagnosis
PCR or culture positive on urine, blood, cerebrospinal
fluid collected within 21 days of life
Most newborns with cCMV infection have no
clinical signs at birth and are not diagnosedcCMV disease
Congenital Cytomegalovirus ( cCMV ) Infection and Disease 2024 Case Definition | CDC
US landscape on cCMV screening and surveillance
ME
WI VT NH
ND MN IL MI NY MA WA ID MT
SD IA IN OH PA NJ CT RI OR NV WY
NE MO KY WV VA MD DE CA UT CO
KS AR TN NC SC AZ NM
OK LA MS AL GA AK
TX FL HIcCMV surveillance (n=13)
Universal screening (n= 2)
Targeted -hearing screening (n= 11)
Symptom- based screening (n=3)
Last updated February 2025
State -specific cCMV prevalence estimates, United States
Adapted from Lutz et al. Updated National and State -Specific Prevalence of Congenital Cytomegalovirus Infection, United States, 2018- 2022. J Public Health Manag Pract . 2024cCMV infection prevalence (per 1,000 live births)
CMV IgG Seroprevalence, United States
National Health and Nutrition Examination Surveys (NHANES)
213642495464
293843505758
0255075
1-5 6-11 12-19 20-29 30-39 40-49CMV prevalence (%)
Age (years)
Lanzieri et al. Seroprevalence of cytomegalovirus among children 1 to 5 years of age in the United States from the National H ealth and Nutrition Examination
Survey of 2011 to 2012. Clin Vaccine Immunol 2015
Lanzieri et al. Cytomegalovirus Seroprevalence Among US Children Aged 1 to 5 Years: The National Health and Nutrition Examina tion Surveys, 2017- March 2020
Pre -Pandemic Dataset. Clin Infect Dis 2022
Bate et al. Cytomegalovirus seroprevalence in the United States: the national health and nutrition examination surveys, 1988 -2004. Clin Infect Dis 2010Increase with older age
Persons 6- 49 years:
No significant changes from
1988- 1994 to 1999-2004
Children 1 -5 years:
Increased from 21% to 29% between 2011 -2012 and 2017- 2020
pre-pandemic1988- 1994
1999- 20042011- 2012
2017- 2020NHANES cycles
CMV IgG Seroprevalence, United States,
NHANES, 1999 -2004*
0255075100
1-5 6-11 12-19 20-29 30-39 40-49CMV prevalence (%)
Age (years)Non -Hispanic Black females
Hispanic females
Non -Hispanic White females
*Except for 1 -5 years (2017- 2020 pre -pandemic dataset)
Lanzieri et al. Cytomegalovirus Seroprevalence Among US Children Aged 1 to 5 Years: The National Health and Nutrition Examina tion Surveys, 2017- March 2020 Pre -Pandemic Dataset.
Clin Infect Dis 2022
Bate et al. Cytomegalovirus seroprevalence in the United States: the national health and nutrition examination surveys, 1988 -2004. Clin Infect Dis 2010
CMV IgG Seroprevalence, United States,
NHANES, 1999 -2004*
0255075100
1-5 6-11 12-19 20-29 30-39 40-49CMV prevalence (%)
Age (years)Non -Hispanic Black females
Hispanic females
Non -Hispanic White females
*Except for 1 -5 years (2017- 2020 pre -pandemic dataset)
Lanzieri et al. Cytomegalovirus Seroprevalence Among US Children Aged 1 to 5 Years: The National Health and Nutrition Examina tion Surveys, 2017- March 2020 Pre -Pandemic Dataset.
Clin Infect Dis 2022
Bate et al. Cytomegalovirus seroprevalence in the United States: the national health and nutrition examination surveys, 1988 -2004. Clin Infect Dis 201036%77%81%
20-29
Risk of vertical transmission and cCMV disease according
to timing and type of maternal infection
Transmission rate
(%)Symptomatic at
birth* (%)SNHL or
neurodevelopmental
abnormality* (%)
Primary infection †
Periconception 21.0 1.3 -
First trimester 36.8 9.1 22.8
Second trimester 40.3 0.3 0.1
Third trimester 66.2 0.4 0.0
Non -primary infection 3.4§3 of 7§§3 of 7§§
Chatzakis et al. Timing of primary maternal cytomegalovirus infection and rates of vertical transmission and fetal consequences. AJOG 2 020
Simonazzi et al. Perinatal outcomes of non -primary maternal CMV infection: a 15 -year experience. Fetal Diagn Ther 2017.†Primary maternal infection in CMV -seronegative women was defined as seroconversion or low avidity IgG; pooled rates of
vertical transmission following primary maternal infection from 10 studies, 2942 fetuses
*Pooled rates of cCMV disease from 10 studies, 796 infected fetuses
§ Transmission rate from 1 study including 205 pregnant women diagnosed with non- primary infection
§§ Sample too small, 6 in the first trimester and 1 unknown timing
10
Risk of vertical transmission and cCMV disease according
to timing and type of maternal infection
Transmission rate
(%)Symptomatic at
birth* (%)SNHL or
neurodevelopmental
abnormality* (%)
Primary infection †
Periconception 21.0 1.3 -
First trimester 36.8 9.1 22.8
Second trimester 40.3 0.3 0.1
Third trimester 66.2 0.4 0.0
Non -primary infection 3.4§3 of 7§§3 of 7§§
Chatzakis et al. Timing of primary maternal cytomegalovirus infection and rates of vertical transmission and fetal consequences. AJOG 2 020
Simonazzi et al. Perinatal outcomes of non -primary maternal CMV infection: a 15 -year experience. Fetal Diagn Ther 2017.†Primary maternal infection in CMV -seronegative women was defined as seroconversion or low avidity IgG; pooled rates of
vertical transmission following primary maternal infection from 10 studies, 2942 fetuses
*Pooled rates of cCMV disease from 10 studies, 796 infected fetuses
§ Transmission rate from 1 study including 205 pregnant women diagnosed with non- primary infection
§§ Sample too small, 6 in the first trimester and 1 unknown timing
11
Incidence of CMV primary infection and reinfection varies
across populations
CountryAnnual rate
Population
(Assessment)Primary (PI)
IgG seroconversionReinfection (R)
IgG seroconversion
to new CMV strains
US 0.4-7% 10%PI: pregnant women, IgG seroconversion, low IgG avidity or viral
shedding in clinical trials and other studies (1,2,3,4)
R: post -partum women, IgG seropositive with seroconversion to new
strains (5)
Brazil 20% 9-35%Pregnant women, IgG seronegative during 1st trimester or seropositive
at first prenatal visit (6,7)
R: range for non -transmitters vs. transmitters mothers
1 Hughes et al. A Trial of Hyperimmune Globulin to Prevent Congenital Cytomegalovirus Infection. N Engl J Med 2021
2 Hyde et al. Cytomegalovirus seroconversion rates and risk factors: implications for congenital CMV. Rev Med Virol 2010
3 Colugnati et al. Incidence of cytomegalovirus infection among the general population and pregnant women in the United States. BMC Infec t Dis 2007
4 Das et al. Safety, efficacy, and immunogenicity of a replication -defective human cytomegalovirus vaccine, V160, in cytomegalov irus-seronegative women: a double -blind, randomised ,
placebo -controlled, phase 2b trial. Lancet Infect Dis 2023
5 Ross et al. Cytomegalovirus reinfections in healthy seroimmune women. JID 2010
6 Mussi -Pinhata et al. Seroconversion for cytomegalovirus infection during pregnancy and fetal infection in a highly seropositive population: “the BraCHS study.” JID 2018
7 Yamamoto et al. Human cytomegalovirus reinfection is associated with intrauterine transmission in a highly cytomegalovirus -imm une maternal population. AJOG 2010
Proportions of cCMV infections due to non- primary maternal infection (NPI)
vary with maternal seroprevalence but risk of cCMV infection is higher when
mother is CMV seronegative before pregnancy
Country, years
(n° infants screened)Maternal
CMV IgG
seroprevalencecCMV infection
prevalence
per 1,000 live birthsRisk of cCMV
among seronegative
vs. seropositive
motherProportion
attributable to NPI
France, 2013- 2015
(12,000)61% 3.70.86% vs. 0.2%
(4x)52%
Brazil, 2013- 2017
(12,000)97% 5.72.8% vs. 0.5%
(6x)90%
Leruez -Ville et al. Risk Factors for Congenital CMV Infection Following Primary and Nonprimary Maternal Infection: A Prospective Neonatal Screening Study Using PCR in Saliva. CID 2017
Yamamoto et al. Contribution of Congenital CMV Infection to Permanent Hearing Loss in a Highly Seropositive Population: The Braz ilian CMV Hearing and Maternal Secondary Infection Study. CID 2020
Mussi -Pinhata et al. Seroconversion for Cytomegalovirus Infection During Pregnancy and Fetal Infection in a Highly Seropositive Population: "The BraCHS Study“. JID 2018
25%
(n=4,000)
75%
(n=12,000)About 12,000 cCMV infections in the U.S. every year
may be attributable to primary maternal infections*
* Using 3,667,758 live births in US 2022 NVSS - Birth Data (cdc.gov) , stratified by maternal age group and birth order
Unpublished estimates based on CMV seroprevalence data from NHANES; other studies 25 -50% cCMV infections attributed to primary maternal infections.cCMV infections due to
PRIMARY infectioncCMV infections due to
NON- PRIMARY infection
Stowell et al. Cross -sectional study of cytomegalovirus shedding and immunological markers among seropositive children and their mothers. BMC Infect Dis. 2014.
Cannon et al. Repeated measures study of weekly and daily cytomegalovirus shedding patterns in saliva and urine of healthy cy tomegalovirus -seropositive children. BMC Infect Dis. 2014.
Cannon et al. Review of cytomegalovirus shedding in bodily fluids and relevance to congenital cytomegalovirus infection. Rev Med Virol 2011.
Schleiss et al. Assessment of congenital cytomegalovirus prevalence among newborns in Minnesota during the COVID -19 pandemic. JAMA Network Open 2022.Children with CMV infection excrete
large amounts of virus in saliva and
urine for months
CMV excretion peaks at 1 -2 years of age
‒1/3 of first- time mothers will be pregnant again,
with a second birth within <18 months of the first
‒More likely with day care attendance (2x)
‒Higher risk of cCMV in second -born childrenYoung children play a critical role in CMV transmission
Modeling suggest that short -duration of protection in infants can impact
transmission to pregnant mothers and decrease cCMV infections
*Protection estimated for primary infection (35% for up to 1 year)
†Screening coverage, all CMV -seronegative vaccinated
§Potential for increase in congenital CMV infections due to primary maternal infections predicted in high seroprevalence settings (Brazil) without booster at 15 -19yModel PopulationVaccine
efficacy
(%)Duration of
protection
(years)Vaccine
coverage
(%)Effect 50 years
post -vaccination
Byrne* 2m 35 1 67 85% ↓cCMV infections
Lanzieri§<1y 60 5 50 Elimination
12-18m and 15- 19y 70 5 60 30% ↓cCMV infections
20-29y 60 5 50 10% ↓ cCMV infections
Alfaro -Murillo †19-20y (CMV neg. F) 95 25 90 4% ↓ cCMV disease
<1y (CMV neg. F) 95 4 90 2% ↓cCMV disease
Model PopulationVaccine
efficacy
(%)Duration of
protection
(years)Vaccine
coverage
(%)Effect 50 years
post -vaccination
Byrne* 2m 35 1 67 85% ↓cCMV infections
Lanzieri§<1y 60 5 50 Elimination
12-18m and 15- 19y 70 5 60 30% ↓cCMV infections
20-29y 60 5 50 10% ↓ cCMV infections
Alfaro -Murillo †19-20y (CMV neg. F) 95 25 90 4% ↓ cCMV disease
<1y (CMV neg. F) 95 4 90 2% ↓cCMV diseaseModels predict different impact of vaccine in US
*Protection estimated for primary infection (35% for up to 1 year)
†Screening coverage, all CMV -seronegative vaccinated
§Potential for increase in congenital CMV infections due to primary maternal infections predicted in high seroprevalence settings (Brazil) without booster at 15 -19y
The epidemiology of CMV and cCMV is complex
In the United States, nearly 75% of cCMV infections due to primary maternal infection
Globally, most cCMV infections due to non -primary maternal infection
An effective CMV vaccine could reduce cCMV disease burden
Long- lasting immunity to ensure women are protected before pregnancy and throughout
childbearing years
Vaccination of toddlers could provide indirect protection to pregnant women Summary
ACIP Members
•Denise Jamieson (WG chair)
•Bonnie Maldonado
Liaisons
•David Kimberlin (AAP)
•Liat Greenwood Chernoff (ACNM)
•Naima Joseph (ACOG)
•Tabitha Hanson (AIM)
•Leisha Nolen (CSTE)
•Ajit Limaye (IDSA)
•Caleb Lyu (NACCHO)
•Maria Carrillo -Marquez (PIDS)Acknowledgments - ACIP CMV WG Members
Ex Officio Members
•Douglas Pratt (FDA)
•Britt Rizek (HRSA)
•Matthew Clark (IHS)
Consultants
•Andrea Ciaranello (Harvard Medical School)
•Rana Chakraborty (University of Miami)
•Sonja Rasmussen (Johns Hopkins University)
•Martina Badell (SMFM)
CDC Staff - DVD
•Tatiana Lanzieri (WG co -lead)
•David Sugerman (WG co -lead)
CDC Staff - DVD
•Tom Clark (ACIP advisor)
•Sara Oliver (ACIP advisor)
•Dan Filardo
•Jessica Leung
•Chelsea Lutz
•Lois Park
•Kelley Raines
•Ashrita Rau
•Brian WakemanAcknowledgments - ACIP CMV WG CDC Participants
CDC Staff - non-DVD
•Amimah Asif (ISD)
•Karen Pazol (ISD)
•Christine Olson (ISO)
•Elizabeth Quincer (ISO)
•Kate Woodworth (DBDID)
•Alison Fountain (DBDID)
•Naomi Tepper (DRH)
ACIP Staff
•Melinda Wharton
•Jessica MacNeil
•Leslie Lee
•Stephanie Thomas
For more information, contact CDC 1 -800- CDC-INFO (232- 4636) TTY: 1- 888- 232- 6348
www.cdc.gov
The findings and conclusions in this report are those of the authors and do not
necessarily represent the official position of the Centers for Disease Control and Prevention.