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OBJECTIVE: To describe maternal demographics and compare clinical characteristics of infants with congenital cytomegalovirus (cCMV) identified through diagnostic codes and laboratory data in the United States during 2018-2023. METHODS: We used a CDC-licensed subset of HealthVerity data, which contained linked pregnant people-infant claims data from publicly and privately insured individuals during 2018-2023 (2023 Quarter 3 HealthVerity Maternal Outcomes Masterset data). We identified infants with cCMV using diagnostic codes or positive laboratory test results within 45 days of birth. RESULTS: Among 744 (4.6 per 10,000 live births) infants with cCMV during 2018-2023, 599 (81%) were identified by a diagnostic code only. Among 732 linked pregnant people, 91 (12%) had a diagnosis of CMV infection during pregnancy, with a similar distribution by age group and insurance type, but a lower proportion were Black as compared to those without CMV infection during pregnancy (14% vs. 29%, respectively). Overall, 452 (61%) infants had ≥1 cCMV-related clinical sign at birth and 185 (25%) had valganciclovir prescriptions. Eighty-eight (68%) infants identified by a positive laboratory test only had no cCMV-related signs and none had valganciclovir prescriptions. CONCLUSIONS: Using healthcare claims data, we found a minimal overlap of cCMV identified by diagnostic codes and laboratory test results. A minority of linked pregnant people with infants with cCMV had a CMV diagnosis during pregnancy. cCMV surveillance will help better understand the validity of ICD codes to identify infants with cCMV, describe the spectrum of disease, and monitor use of antivirals.
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Measles and rubella are vaccine-preventable viral diseases and can be prevented by safe, highly effective vaccination with measles- and rubella-containing vaccines. Given the myriad causes of febrile exanthems, laboratory surveillance for both measles and rubella is important to document the incidence of these diseases and to track the progress and maintenance of elimination in near- and post-elimination settings. Diagnostic challenges can hinder effective surveillance and classification challenges can hinder efforts to demonstrate achievement or maintenance of elimination. In this report, we review diagnostic and classification challenges for measles and rubella in near- and post-elimination settings.
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BACKGROUND: Congenital cytomegalovirus (cCMV) is the most common infectious cause of neurodevelopmental deficits in US children. To inform patient management, it is important to define whether central nervous system (CNS) manifestations are present at birth. This study characterized neuroimaging findings in infants with cCMV identified by a universal screening study in Minnesota during February 2016-December 2022. METHODS: Newborns with cCMV infection (confirmed by urine CMV polymerase chain reaction [PCR] testing, obtained following a positive screening saliva and/or dried blood spot result) underwent a diagnostic evaluation that included a cranial ultrasound (cUS) exam, laboratory studies, ophthalmological, and audiological evaluation. Neuroimaging findings and cCMV disease classification were interpreted based on international consensus guidelines. RESULTS: Among 87 newborns with confirmed cCMV, 76 underwent cUS. Of these, 53/76 (70%) had normal examinations, while 23/76 (30%) exhibited cUS findings: for 5 infants, these were clearly cCMV disease-defining, while for 18 infants, there were findings of uncertain significance. Magnetic resonance imaging (MRI) results (nâ =â 10 infants) aligned with cUS cCMV disease-defining findings in 2 infants, while cCMV-specific abnormalities were noted by MRI in 2 of 6 infants with nondiagnostic/incidental cUS findings. Of 9 infants who had both cUS and MRI examination, the average time interval between studies was 220 days (range, 2-1061). Excluding infants with cCMV CNS disease-defining cUS abnormalities, incidental findings were observed more commonly in infants with clinical/laboratory features described in cCMV disease classification guidelines (9/13) than in newborns with completely asymptomatic infections (9/58; Pâ <â .0001). CONCLUSIONS: Among infants with cCMV identified in a universal screening study, the majority had a normal cUS. CNS disease-defining abnormalities were present in 7%, while 24% had findings of uncertain significance. We propose that many cUS findings are incidental, and not diagnostic of symptomatic cCMV infection. Although these findings may not be sufficient to define the presence of symptomatic cCMV disease involving the CNS, in our study they were more commonly observed in infants with other clinical and/or laboratory findings associated with symptomatic cCMV infection.
Subject(s)
Cytomegalovirus Infections , Magnetic Resonance Imaging , Neonatal Screening , Humans , Cytomegalovirus Infections/diagnostic imaging , Cytomegalovirus Infections/congenital , Infant, Newborn , Minnesota , Neonatal Screening/methods , Female , Male , Ultrasonography , Echoencephalography , NeuroimagingABSTRACT
OBJECTIVE: To examine the association between congenital cytomegalovirus (cCMV) and autism spectrum disorder (ASD) administrative diagnoses in US children. METHODS: Cohort study using 2014 to 2020 Medicaid claims data. We used diagnosis codes to identify cCMV (exposure), ASD (outcome), and covariates among children enrolled from birth through ≥4 to <7 years. Covariates include central nervous system (CNS) anomaly or injury diagnosis codes, including brain anomaly, microcephaly within 45 days of birth, cerebral palsy, epilepsy, or chorioretinitis. We used Cox proportional hazards regression models to estimate hazard ratios and 95% confidence intervals, overall and stratified by sex, birth weight and gestational age outcome (low birth weight or preterm birth), and presence of CNS anomaly or injury. RESULTS: Among 2 989 659 children, we identified 1044 (3.5 per 10 000) children with cCMV and 74 872 (25.0 per 1000) children with ASD. Of those with cCMV, 49% also had CNS anomaly or injury diagnosis codes. Children with cCMV were more likely to have ASD diagnoses (hazard ratio: 2.5; 95% confidence interval: 2.0-3.2, adjusting for birth year, sex, and region). This association differed by sex and absence of CNS anomaly or injury but not birth outcome. CONCLUSIONS: Children with (versus without) cCMV diagnoses in Medicaid claims data, most of whom likely had symptomatic cCMV, were more likely to have ASD diagnoses. Future research investigating ASD risk among cohorts identified through universal cCMV screening may help elucidate these observed associations.
Subject(s)
Autism Spectrum Disorder , Cytomegalovirus Infections , Humans , Autism Spectrum Disorder/epidemiology , Autism Spectrum Disorder/diagnosis , Female , Male , Cytomegalovirus Infections/congenital , Cytomegalovirus Infections/epidemiology , Cytomegalovirus Infections/diagnosis , Child, Preschool , United States/epidemiology , Infant, Newborn , Infant , Child , Cohort Studies , Proportional Hazards Models , MedicaidABSTRACT
Measles, a highly contagious respiratory virus with the potential to cause severe complications, hospitalization, and death, was declared eliminated from the United States in 2000; however, with ongoing global transmission, infections in the United States still occur. On March 7, 2024, the Chicago Department of Public Health (CDPH) confirmed a case of measles in a male aged 1 year residing in a temporary shelter for migrants in Chicago. Given the congregate nature of the setting, high transmissibility of measles, and low measles vaccination coverage among shelter residents, measles virus had the potential to spread rapidly among approximately 2,100 presumed exposed shelter residents. CDPH immediately instituted outbreak investigation and response activities in collaboration with state and local health departments, health care facilities, city agencies, and shelters. On March 8, CDPH implemented active case-finding and coordinated a mass vaccination campaign at the affected shelter (shelter A), including vaccinating 882 residents and verifying previous vaccination for 784 residents over 3 days. These activities resulted in 93% measles vaccination coverage (defined as receipt of ≥1 recorded measles vaccine dose) by March 11. By May 13, a total of 57 confirmed measles cases associated with residing in or having contact with persons from shelter A had been reported. Most cases (41; 72%) were among persons who did not have documentation of measles vaccination and were considered unvaccinated. In addition, 16 cases of measles occurred among persons who had received ≥1 measles vaccine dose ≥21 days before first known exposure. This outbreak underscores the need to ensure high vaccination coverage among communities residing in congregate settings.
Subject(s)
Disease Outbreaks , Measles Vaccine , Measles , Transients and Migrants , Humans , Measles/epidemiology , Measles/prevention & control , Chicago/epidemiology , Male , Infant , Adult , Young Adult , Child, Preschool , Adolescent , Child , Measles Vaccine/administration & dosage , Transients and Migrants/statistics & numerical data , Female , Middle Aged , Mass Vaccination/statistics & numerical dataABSTRACT
Cytomegalovirus (CMV) is the most common infectious cause of congenital malformation and a leading cause of developmental disabilities such as sensorineural hearing loss (SNHL), motor and cognitive deficits. The significant disease burden from congenital CMV infection (cCMV) led the US National Institute of Medicine to rank CMV vaccine development as the highest priority. An average of 6.7/1000 live births are affected by cCMV, but the prevalence varies across and within countries. In contrast to other congenital infections such as rubella and toxoplasmosis, the prevalence of cCMV increases with CMV seroprevalence rates in the population. The true global burden of cCMV disease is likely underestimated because most infected infants (85-90 %) have asymptomatic infection and are not identified. However, about 7-11 % of those with asymptomatic infection will develop SNHL throughout early childhood. Although no licensed CMV vaccine exists, several candidate vaccines are in development, including one currently in phase 3 trials. Licensure of one or more vaccine candidates is feasible within the next five years. Various models of CMV vaccine strategies employing different target populations have shown to provide substantial benefit in reducing cCMV. Although CMV can cause end-organ disease with significant morbidity and mortality in immunocompromised individuals, the focus of this vaccine value profile (VVP) is on preventing or reducing the cCMV disease burden. This CMV VVP provides a high-level, comprehensive assessment of the currently available data to inform the potential public health, economic, and societal value of CMV vaccines. The CMV VVP was developed by a working group of subject matter experts from academia, public health groups, policy organizations, and non-profit organizations. All contributors have extensive expertise on various elements of the CMV VVP and have described the state of knowledge and identified the current gaps. The VVP was developed using only existing and publicly available information.
Subject(s)
Cytomegalovirus Infections , Cytomegalovirus Vaccines , Hearing Loss, Sensorineural , Infant , Humans , Child, Preschool , Cytomegalovirus , Asymptomatic Infections , Seroepidemiologic Studies , Cytomegalovirus Infections/epidemiology , Cytomegalovirus Infections/prevention & control , Hearing Loss, Sensorineural/congenital , Hearing Loss, Sensorineural/epidemiologyABSTRACT
The study objective was to identify communication messages that parents of children diagnosed with congenital cytomegalovirus (cCMV) infection reported as essential and helpful. We performed a secondary analysis of focus groups and interviews conducted with 41 parents of children with cCMV who had enrolled in a long-term follow-up cCMV study at an academic medical center. Three groups of parents who had children with cCMV participated in the study: parents with children symptomatic at birth, parents with children asymptomatic at birth who later developed sensorineural hearing loss, and parents with children asymptomatic at birth who remained asymptomatic into adulthood. Using a health marketing approach, we identified six general themes from the focus group sessions: initial diagnosis, likely health outcome(s), comfort and coping, symptom watch, resources, and prevention. Receiving the initial diagnosis was shocking for many parents, and they wanted to know how their child would or could be affected. They valued access to the information, follow-up visits for early detection of hearing loss and other developmental delays, and support from other parents. Parents wished to obtain this information from their pediatrician but felt that experts offered more up-to-date knowledge about prognosis, monitoring, and treatment. With more U.S. states implementing cCMV screening strategies which would lead to more infant diagnoses, it will be necessary for providers to meet parents' expectations and communication needs.
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BACKGROUND: To assess demographics and outcomes up to 3 years of age among children with cytomegalovirus (CMV) infection in California neonatal intensive care units (NICUs) during 2010-2021. METHODS: The California Perinatal Quality Care Collaborative (CPQCC) collects data on all very low birth weight (VLBW, birth weight ≤ 1500 g) and acutely ill infants with birth weight > 1500 g across 92% of NICUs in California. VLBW infants and those with neurological conditions are referred to a statewide high-risk infant follow-up (HRIF) program. CMV infection was defined as a positive culture or PCR identified during the NICU hospitalization. RESULTS: During 2010-2021, CMV reporting rates averaged 3.5/1000 VLBW infants (n = 205) and 1.1/1000 infants >1500 g (n = 128). Among all 333 infants with CMV, 314 (94%) were discharged home alive, 271 (86%) were referred for HRIF and 205 (65%) had ≥1 visit. Whereas infants born to mothers <20 years of age had highest CMV reporting rates and those born to Hispanic mothers comprised 49% of all infected infants, they had the highest loss of follow-up. At the 12-month visit (n = 152), 19 (13%) infants with CMV had bilateral blindness and 18 (12%) had hearing loss. At the 24-month visit, 5 (5%) of 103 had severe cerebral palsy. CONCLUSIONS: Among infants admitted to the NICU, those with CMV diagnoses may over represent infants with more severe CMV disease and outcomes. The CPQCC and HRIF program findings may help inform implementation of surveillance for congenital CMV infection in other U.S. states and guide strategies to reduce disparities in access to services.
Subject(s)
Cytomegalovirus Infections , Intensive Care Units, Neonatal , Infant, Newborn , Infant , Pregnancy , Female , Child , Humans , Child, Preschool , Birth Weight , Cytomegalovirus Infections/epidemiology , Infant, Very Low Birth Weight , CaliforniaABSTRACT
BACKGROUND: Congenital cytomegalovirus (cCMV) is not a nationally notifiable condition, and little is known about how U.S. health departments (HDs) currently conduct cCMV surveillance. METHODS: We surveyed U.S. HDs that conduct cCMV surveillance or screening activities identified through a web-based assessment. Meetings were held with each HD to enhance our understanding of survey responses. RESULTS: Ten states are systematically collecting cCMV case data to track cCMV cases during early infancy and to provide resources and services to families. Cases are ascertained using cCMV diagnostic codes, reported diagnosis, or laboratory results. Data elements collected for each case include demographics (all 10 states), clinical signs (8 states), laboratory data (4 states), treatment (4 states), and long-term outcomes (1 state). Annual number of cases reported by HDs ranged from 3 to 47 cases/year in seven states, which was much lower than the expected number of cCMV cases. All 10 HDs have the ability to analyze data collected and four disseminate findings. Major challenges of surveillance reported by HDs were lack of standardized case definitions, personnel constraints, and limited funding. CONCLUSIONS: A comprehensive account of cCMV disease burden is severely limited by low case ascertainment and paucity of data on long-term outcomes. A standardized public health case definition for cCMV would improve consistency in measuring disease prevalence across jurisdictions and over time. Surveillance for cCMV has the potential to increase disease awareness and inform strategies to prevent cCMV-associated disabilities.
Subject(s)
Cytomegalovirus Infections , Cytomegalovirus , Humans , United States/epidemiology , Cytomegalovirus Infections/epidemiology , Cytomegalovirus Infections/diagnosis , Surveys and Questionnaires , PrevalenceABSTRACT
A young man with X-linked severe combined immunodeficiency developed a persistent vaccine-derived rubella virus (VDRV) infection, with the emergence of cutaneous granulomas more than fifteen years after receipt of two doses of measles-mumps-rubella (MMR) vaccine. Following nasopharyngeal swab (NP) collection, VDRV was detected by real-time polymerase chain reaction (RT-qPCR) and sequencing, and live, replication-competent VDRV was isolated in cell culture. To assess duration and intensity of viral shedding, sequential respiratory samples, one cerebrospinal fluid sample, and two urine samples were collected over 15 months, and VDRV RNA was detected in all samples by RT-qPCR. Live VDRV was cultured from nine of the eleven respiratory specimens and from one urine specimen. To our knowledge, this was the first reported instance of VDRV cultured from respiratory specimens or from urine. To assess potential transmission to close contacts, NP specimens and sera were collected from all household contacts, all of whom were immunocompetent and previously vaccinated with MMR. VDRV RNA was not detected in any NP swabs from the contacts, nor did serologic investigations suggest VDRV transmission to any contacts. This report highlights the need to understand the prevalence and duration of VDRV shedding in granuloma patients and to estimate the risk of VDRV transmission to immune and non-immune contacts.
Subject(s)
Severe Combined Immunodeficiency , X-Linked Combined Immunodeficiency Diseases , Male , Humans , Rubella virus , Measles-Mumps-Rubella Vaccine/adverse effects , Granuloma/geneticsABSTRACT
OBJECTIVES: To assess the 6-month incidence of laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, postnatal care, hospitalization, and mortality among infants born to people with laboratory-confirmed SARS-CoV-2 infection during pregnancy by timing of maternal infection. METHODS: Using a cohort of liveborn infants from pregnancies with SARS-CoV-2 infections in the year 2020 from 10 United States jurisdictions in the Surveillance for Emerging Threats to Mother and Babies Network, we describe weighted estimates of infant outcomes from birth through 6 months of age from electronic health and laboratory records. RESULTS: Of 6601 exposed infants with laboratory information through 6 months of age, 1.0% (95% confidence interval: 0.8-1.1) tested positive, 19.1% (17.5-20.6) tested negative, and 80.0% (78.4-81.6) were not known to be tested for SARS-CoV-2. Among those ≤14 days of age, SARS-CoV-2 infection occurred only with maternal infection ≤14 days before delivery. Of 3967 infants with medical record abstraction, breastmilk feeding initiation was lower when maternal infection occurred ≤14 days before delivery compared with >14 days (77.6% [72.5-82.6] versus 88.3% [84.7-92.0]). Six-month all-cause hospitalization was 4.1% (2.0-6.2). All-cause mortality was higher among infants born to people with infection ≤14 days (1.0% [0.4-1.6]) than >14 days (0.3% [0.1-0.5]) before delivery. CONCLUSIONS: Results are reassuring, with low incidences of most health outcomes examined. Incidence of infant SARS-CoV-2, breastmilk feeding initiation, and all-cause mortality differed by timing of maternal infection. Strategies to prevent infections and support pregnant people with coronavirus disease 2019 may improve infant outcomes.
Subject(s)
COVID-19 , Pregnancy Complications, Infectious , Pregnancy , Female , Humans , United States/epidemiology , Infant , Infant, Newborn , SARS-CoV-2 , COVID-19/epidemiology , Pregnancy Complications, Infectious/diagnosis , Pregnancy Complications, Infectious/epidemiology , Pregnancy Complications, Infectious/prevention & control , Pregnancy Outcome/epidemiology , COVID-19 Testing , Infectious Disease Transmission, Vertical/prevention & controlABSTRACT
Among 342 US infants with congenital cytomegalovirus treated with antivirals, 114 (33%) received ganciclovir (with or without valganciclovir) and 228 (67%) received valganciclovir only, for a median of 8 and 171 days, starting at a median of 15 and 45 days of life, respectively, with neutropenia diagnosed in 25% and 17%.
Subject(s)
Cytomegalovirus Infections , Ganciclovir , Antiviral Agents/therapeutic use , Cytomegalovirus , Cytomegalovirus Infections/congenital , Cytomegalovirus Infections/drug therapy , Electronic Health Records , Ganciclovir/therapeutic use , Humans , Infant , United States , Valganciclovir/therapeutic useABSTRACT
On August 29, 2021, the United States government oversaw the emergent establishment of Operation Allies Welcome (OAW), led by the U.S. Department of Homeland Security (DHS) and implemented by the U.S. Department of Defense (DoD) and U.S. Department of State (DoS), to safely resettle U.S. citizens and Afghan nationals from Afghanistan to the United States. Evacuees were temporarily housed at several overseas locations in Europe and Asia* before being transported via military and charter flights through two U.S. international airports, and onward to eight U.S. military bases, with hotel A used for isolation and quarantine of persons with or exposed to certain infectious diseases.§ On August 30, CDC issued an Epi-X notice encouraging public health officials to maintain vigilance for measles among Afghan evacuees because of an ongoing measles outbreak in Afghanistan (25,988 clinical cases reported nationwide during January-November 2021) (1) and low routine measles vaccination coverage (66% and 43% for the first and second doses, respectively, in 2020) (2).
Subject(s)
Communicable Diseases , Measles , Communicable Diseases/epidemiology , Disease Outbreaks/prevention & control , Humans , Measles/epidemiology , Measles/prevention & control , Public Health , United States/epidemiology , VaccinationABSTRACT
From 2009-2015 to 2016-2019, the proportion of infants in the US with congenital cytomegalovirus treated with valganciclovir roughly doubled for infants enrolled with employer-sponsored insurance (from 16% to 29%) and Medicaid (from 16% to 36%). The proportion treated with valganciclovir increased for all congenital cytomegalovirus disease severity groups.
Subject(s)
Cytomegalovirus Infections , Cytomegalovirus , Antiviral Agents/therapeutic use , Cytomegalovirus Infections/diagnosis , Cytomegalovirus Infections/drug therapy , Humans , Infant , Medicaid , United States , Valganciclovir/therapeutic useSubject(s)
Infant, Premature , Infant, Very Low Birth Weight , Virus Diseases/epidemiology , Female , Humans , Infant, Newborn , Infant, Premature, Diseases/epidemiology , Infant, Small for Gestational Age , Length of Stay , Male , Microcephaly/epidemiology , Pregnancy , Prenatal Care/statistics & numerical data , Vermont/epidemiologyABSTRACT
Congenital cytomegalovirus (CMV) is a leading cause of non-genetic sensorineural hearing loss and neurodevelopmental disabilities among US children. Studies using administrative healthcare databases have identified infants with congenital CMV using diagnostic codes from the International Classification of Diseases, Ninth and Tenth Revision, Clinical Modification. Using Cerner Health Facts deidentified electronic health records, we assessed the sensitivity of CMV diagnostic codes among infants with laboratory confirmed congenital CMV infection (i.e. a positive CMV laboratory test - polymerase chain reaction, direct fluorescent antibody, or culture from urine, saliva, respiratory secretion or blood samples, or IgM serology - within 21 days of life). During 2010-2017, 668 congenital CMV cases were identified among 7,517,207 infants with encounters within 21 days of life, or 0.89 cases per 10,000 infants. The sensitivity of CMV diagnostic codes assigned within 21 and 90 days of life was 10.3% (95% CI: 8.2-12.9) and 11.1% (95% CI: 8.9-13.7), respectively.