Mona Marin

An updated varicella case definition and classification from the Council of State and Territorial Epidemiologists became effective in 2024, emphasizing laboratory confirmation by requiring that confirmed cases be laboratory confirmed or epidemiologically linked to a laboratory-confirmed case, in addition to meeting clinical criteria. We assessed the impact of the changes using varicella reports in Minnesota from January 1, 2024, through May 31, 2025. Of 737 reports, 61.2% (n = 451) met the new definition and 61.9% (n = 456) met the old definition; 12.1% (n = 89) changed classifications. The proportion of cases classified as confirmed decreased by 17.5%, while those classified as probable increased by 28.0%; changes were primarily driven by the requirement to link reports to a laboratory-confirmed case. Reports not classified (ie, undefined; 26.9%; n = 198) mostly lacked rash descriptions. The updated definition improves jurisdictions’ ability to classify cases accurately, thus strengthening national surveillance by reflecting current varicella epidemiology. Improved reporting of rash description, epidemiologic information, and increased laboratory testing are needed to improve surveillance.

Background: The most recent assessment of antibodies against measles, mumps, rubella, and varicella-zoster viruses (MeV, MuV, RuV, VZV) in the United States was conducted in 2009–2010. Regular assessments are essential to measure the impact of immunization programs, identify immunity gaps, and inform vaccination strategies. We report updated estimates of national seroprevalence. Methods: We used a CDC-developed immunoglobulin G multiplex bead assay to quantitatively detect antibodies against MeV, MuV, RuV, and VZV among participants aged 6–59 years in the 2017–March 2020 National Health and Nutrition Examination Survey. We estimated seroprevalence overall and by sociodemographic characteristics and assessed independent predictors of seropositivity using logistic regression models with weighted procedures for complex survey design. Results: Overall seroprevalence was 95.2% (95% CI, 94.0%–96.3%) against MeV, 87.8% (95% CI, 86.5%–89.2%) against MuV, 95.6% (95% CI, 94.5%–96.5%) against RuV, and 97.2% (95% CI, 96.4%–98.0%) against VZV and remained high across advancing age groups. Younger age and non-Hispanic Black race and ethnicity were independent predictors for MeV, MuV, and RuV seropositivity; sex, birthplace, and health insurance status were independent predictors for seropositivity for at least one of the viruses. Conclusions: Nationally, seroprevalence for MeV, MuV, RuV, and VZV antibodies remains high among persons aged 6–59 years, and our findings indicate robust antibody responses are maintained decades after vaccination or natural infection. Maintaining high population immunity through vaccination is critical to prevent cases and outbreaks of all 4 vaccine-preventable diseases.

Introduction: Preventing varicella-zoster virus infection is important in the management of human immunodeficiency virus (HIV)-positive persons. Varicella remains endemic worldwide, and HIV-positive persons can experience greater morbidity than the general population. We summarized the global literature on the safety and immunogenicity of the varicella vaccine in HIV-positive children. Methods: Systematic review of original reports on varicella vaccination of HIV-positive children, published through December 31, 2024, including assessment of safety, immunologic responses and effectiveness after vaccination. Results: Eighteen articles were analyzed. Local reactions were the most common adverse events, albeit infrequent (<21% and <10% of vaccinees after dose 1 and 2, respectively). Systemic reactions were also infrequent, consisting mostly of low-grade fever. A vaccine-related rash, reported in <5% of vaccinees, had fewer lesions and a shorter duration than typical varicella. Serious adverse events were reported only when the vaccine was inadvertently administered to children with severe HIV immunosuppression. Varicella vaccination had no clinically significant impact on plasma HIV RNA or CD4+ T-cell count after either dose. An antibody response was reported in 60%–79% of HIV-positive vaccinees after dose 2 and often declined more rapidly than in uninfected children. Cell-mediated immunity was detected in 67%–83% after dose 2. No significant differences in adverse events or short-term immune response after vaccination correlated with past or current CD4+ T-cell status. Conclusions: The varicella vaccine had a favorable safety profile and induced specific immune responses in most nonseverely immunocompromised HIV-positive children. The vaccine remains contraindicated for persons with severe HIV infection. Robust data on the durability of immune response and long-term effectiveness are needed.

Background: A third dose of measles, mumps, and rubella vaccine (MMR3) may be administered in outbreak and nonoutbreak settings. However, data on long-term immunogenicity to the mumps component of MMR are limited. We examined durability of mumps antibody response among adults up to 11 years after receipt of MMR3. Methods: Persons who received MMR3 at ages 18–28 years had sera collected before (baseline), 1 month, 1, 5, and 9–11 years after vaccination. Mumps antibodies were assessed by plaque reduction neutralization, immunoassay (EIA), and immunoglobulin G (IgG) avidity. Neutralizing antibodies were assessed against the vaccine strain (Genotype A) and a wild-type virus from Genotype G. Participants with neutralizing antibody titers <31 for Genotype A and <8 for Genotype G, and with EIA index values <1.10 were considered potentially susceptible. Results: Among participants with data for all visits after MMR3 (40%, n = 262/655), susceptibility based on Genotype A titers increased from 15.7% (41/262) at baseline to 30.5% (80/262) 9–11 years after vaccination while susceptibility based on Genotype G titers remained relatively stable (30.2%–24.2%). The proportion of participants seronegative for mumps IgG by EIA increased from 0% (0/255) at baseline to 7.5% (19/255) 9–11 years after vaccination. The avidity index increased from 52% to 67% through Year 5 (P < .0001). Conclusions: By 9–11 years after receipt of MMR3, many participants had mumps antibody levels that predicted susceptibility to infection, comparable to those observed before receipt of MMR3. The antibody titers to Genotype G remained consistently lower than the titers to the vaccine strain.

Background: In the United States, 2 doses of measles-mumps-rubella (MMR)–containing vaccines are recommended routinely during childhood; a third dose may be given under certain circumstances. We present observed seroprotection rates and estimate long-term dynamics of measles, mumps, and rubella neutralizing antibody (nAb) levels among 2- and 3-dose MMR (MMR2 and MMR3, respectively) vaccinees. Methods: Persons who received MMR2 at age 4–12 years or MMR3 at age 18–31 years were enrolled in 1994–1995 and 2009–2010, respectively. Per cohort, sera were collected before vaccination (baseline) and at various intervals ranging from 1 month to 10 years postvaccination to assess nAb levels. Annual changes in nAb levels per virus and cohort were estimated through 10 years postvaccination using generalized estimating equations. Models were stratified by baseline nAb levels. Results: Among MMR2 participants (n = 621), 93.7%, 73.4%, and 83.9% had protective nAb levels against measles, mumps, and rubella, respectively, at the 10-year visit; among MMR3 participants (n = 665), 90.5%, 69.1%, and 100% had protective nAb levels, respectively, at the 9–11-year visit. Estimated nAb levels declined annually across both cohorts, all viruses, and baseline nAb strata, though patterns and magnitude varied. More than one-quarter of participants had mumps nAb levels below the presumed seroprotection threshold at the terminal visits. Conclusions: These findings indicate that even when MMR antibodies wane, protection against disease is largely retained. Waning of mumps antibodies was greater than for measles and rubella in both 2- and 3-dose vaccinees, likely because a greater proportion failed to mount a robust initial response.

Background: A third dose of measles-mumps-rubella vaccine (MMR) may be administered for various reasons, but data on long-term immunity are limited. We assessed neutralizing antibody levels against measles and rubella among adults up to 11 years after receipt of a third MMR dose. Methods: In this longitudinal study, healthy adults who received a third MMR dose as young adults (ages 18–28 years) were recalled around 5 years and 9–11 years after the third dose. Measles and rubella antibody levels were assessed by plaque-reduction and immunocolorimetric neutralization assays, respectively. Antibody concentrations <120 mIU/mL and <10 U/mL were considered potentially susceptible to measles and rubella, respectively. Geometric mean concentrations (GMCs) and 95% confidence intervals (CIs) over time were estimated from generalized estimating equation models. Results: Approximately 5 and 9–11 years after receipt of the third dose, 405 and 304 adults were assessed, respectively. Measles GMC was 428 mIU/mL (95% CI, 392–468 mIU/mL) 5 years postvaccination, declining to 381 mIU/mL (95% CI, 339–428 mIU/mL) 11 years postvaccination. At the last follow-up visit (9–11 years postvaccination), 10% of participants were potentially susceptible to measles infection. Rubella GMCs were stable throughout the follow-up period (63 U/mL to 65 U/mL); none of the participants was susceptible to rubella at the last follow-up visit. Conclusions: Eleven years after receiving a third MMR dose, measles and rubella neutralizing antibody levels remained high in adults. However, on the basis of waning antibody levels, some adults may become susceptible to measles infection over time despite receipt of 3 vaccine doses.

The clinical presentation of varicella in unvaccinated persons, with skin vesicles and scabs, has facilitated the use of rapid diagnostic methods for confirming disease. Polymerase chain reaction (PCR) assays are the diagnostic method of choice. The sharp decline in unmodified cases of varicella due to the US varicella vaccination program has led to fewer healthcare providers being familiar with varicella presentation and an increased reliance on laboratory diagnosis to confirm suspected cases. The mild, atypical presentation of the disease in vaccinated persons (fewer skin lesions, mostly maculopapular) has made it more challenging for providers to recognize and also to collect samples to detect the virus. Nonetheless, PCR is highly sensitive and specific in confirming modified disease if adequate samples are provided. While a positive PCR result is confirmatory, interpreting a negative result can prove to be more challenging in determining whether suspected varicella is falsely negative or attributable to other causes. Enhanced education of healthcare providers is critical for adequate specimen collection from modified varicella cases. In addition, more sensitive commercial serologic assays are needed in the United States for varicella immunity testing in the vaccine era.

Varicella poses an occupational risk and a nosocomial risk for susceptible healthcare personnel and patients, respectively. Patients with varicella are thought to be infectious from 1 to 2 days before rash onset until all lesions are crusted, typically 4–7 days after onset of rash. We searched Medline, Embase, Cochrane Library and CINAHL databases to assess evidence of varicella-zoster virus (VZV) transmission before varicella rash onset. Few articles (7) contributed epidemiologic evidence; no formal studies were found. Published articles reported infectiousness at variable intervals before rash onset, between <1 day to 4 days prior to rash, with 1–2 patients for each interval. Laboratory assessment of transmission before rash was also limited (10 articles). No culture-positive results were reported. VZV DNA was identified by PCR before rash onset in only one study however, PCR does not indicate infectivity of the virus. Based on available medical literature, VZV transmission before rash onset seems unlikely, although the possibility of pre-rash, respiratory transmission cannot be entirely ruled out.