The NHANES is conducted by the National Center for Health Statistics (NCHS), Centers for Disease Control and Prevention (CDC), to assess the health and nutritional status of the US population. The survey uses a stratified, multistage, probability-cluster design, to provide a sample representative of the civilian noninstitutionalized US population. Survey participants undergo household interviews, standardized physical examinations, and provide biological samples for testing. Non-Hispanic blacks and Hispanics were oversampled to provide stable estimates for these groups. Informed consent was obtained from all participants, and the Institutional Review Board of NCHS, CDC approved the protocol.

Serum samples from NHANES participants aged 6–49 years during 2009–2010 were tested for immunoglobulin G (IgG) antibodies of interest. Commercially available indirect enzyme-linked immunosorbent IgG assays (IgG ELISA II; Wampole Laboratories) were used for the detection and qualitative determination of IgG antibody to MMR viruses. IgG antibodies to measles and mumps viruses were categorized based on index standard ratio (ISR) values as follows: seronegative, ISR of ≤0.90; indeterminate, ISR of 0.91–1.09; and seropositive, ISR of ≥1.10. For rubella, values of ≥10 IU were considered seropositive. Seronegative and indeterminate samples were retested with an equal number of randomly selected seropositive samples. Samples that initially tested indeterminate then positive on retesting were categorized as seropositive; negative or indeterminate samples were categorized as negative for this study. Discordant results were reconciled by 1 additional test; the final result was used. For quality assurance, a 10% random-sample repeat of the entire specimen collection set was performed. For varicella, the CDC in-house varicella whole-cell enzyme immunoassay (W-EIA) was used; IgG antibodies were categorized based on optical density (OD). Samples with OD of ≥0.250 were considered seropositive. Samples testing W-EIA negative (OD of <0.170) or indeterminate (OD of 0.170–0.249) were retested using a more sensitive glycoprotein antigen-based EIA (gpELISA) appropriate for detection of vaccine-induced antibodies [12]. Samples were considered seropositive if gpELISA-adjusted OD was ≥0.200 and considered seronegative if <0.200.

Procedures used in previous analysis of NHANES measles, mumps, rubella, and varicella data were used here [9–12]. Participants were grouped by birth year (1957–1966, 1967–1976, 1977–1986, 1987–1998, and 1999–2004) and age (6–11 years, 12–19 years, 20–29 years, 30–39 years, and 40–49 years) [9–12]. Race and Hispanic origin were based on the respondent's self-assessment and categorized as non-Hispanic white, non-Hispanic black, Mexican American, and other (subjects who did not self-select into the previous groups or reported multiple races). Separate estimates were not reported for the other race/ethnic group, but these individuals were included in all other estimates. Birthplace was coded as US and non-US. Estimates were weighted to represent the total civilian noninstitutionalized US household population and account for oversampling and nonresponse [13]. Standard errors were calculated accounting for the complex sample design using SUDAAN software (version 11.0.1). Estimates were considered unstable if the relative standard error around the percent seronegative participants was >30% or if based on <10 seronegative persons. The exact binomial method was used to calculate 95% confidence intervals (CIs) [14]. The t tests were used to assess differences between groups; P values < .05 were considered significant. No adjustments for multiple comparisons were made.

Overall seroprevalence remains high for measles, mumps, rubella, and varicella antibodies in the US population aged 6–49 years during 2009–2010. Seroprevalence was highest among those aged 6–11 years, a group likely to have been vaccinated recently. Lower estimates in older age groups (birth cohort 1967–1976) for MMR is consistent with findings from previous NHANES and could be a result of lower vaccination levels, changes in vaccine policy, and declining disease prevalence, and immunosenescence [9, 10]. US-born persons had lower mumps and higher varicella seroprevalence than non-US born persons. Lower seroprevalence among some subgroups may indicate populations at increased risk for transmission and outbreaks of these vaccine-preventable diseases.

High measles seroprevalence reflects high vaccine coverage nationally; however, 8% of persons aged 6–49 years were found to be susceptible. Susceptibility is likely to be even higher if we considered children aged <12 months. Susceptible persons remain at risk for measles in the US, primarily due to importation. During 2001–2011, 88% of the 911 reported measles cases were import-associated [15]. As long as measles remains endemic in other countries, importations will continue with the risk for sustained outbreaks among unvaccinated populations.

Seroprevalence was lower for mumps than measles and rubella. Lower seroprevalence may be explained by the lower effectiveness of the mumps component of the MMR vaccine estimated at 88% (range, 66–95%) compared with 97% (range, 67%–100%) for measles and 97% (range, 94%–100%) for rubella [1]. However, although antibody measurements are often used as surrogate measures of immunity, no serologic tests that reliably predict immunity are available for mumps. Although recent mumps outbreaks occurred in populations with high 2-dose coverage, they were limited to intense exposure settings, with limited spread outside these settings [4, 5]. To maintain control of mumps, it remains important to ensure appropriate MMR vaccination among children and persons in settings with the potential for intense exposure and transmission of mumps (eg, schools, colleges, correctional facilities, congregate living facilities, or healthcare settings) [1].

Rubella seroprevalence was high (>93%) in all subgroups. As a result, few rubella and only 4 CRS cases have been reported through national surveillance during 2005–2011 [1, 15]. The higher rubella seroprevalence during 2009–2010 in women than men likely reflects continued efforts to vaccinate susceptible women of child-bearing age as part of the efforts to maintain CRS elimination.

During 2009–2010, varicella seroprevalence was high across all age groups. Age group-specific estimates were similar to estimates from NHANES 1999–2004, except children aged 6–11 years, where seroprevalence increased from 88.9% to 98.0% [12]. Considering the low varicella incidence among children in the last decade, this increase could be directly attributed to the successful implementation of routine varicella vaccination in the US starting in 1996. By 2008, 1-dose varicella vaccination coverage among children aged 19–35 months reached 91% [16]. Fewer children will enter adolescence and adulthood susceptible to varicella and at risk of severe disease. Similar to previous studies, seroprevalence was lower in those born outside compared with inside the US [12]. Providers should continue to assess evidence of immunity for all non-US born adults, irrespective of age.

This study has several limitations. Sample sizes for subgroup estimates were limited or unstable because data was only available for 2 survey years. Hence, results for these subgroups should be interpreted with caution. Second, ELISA testing methods for measles and rubella differed from NHANES 1999–2004; therefore, the 2 survey periods were not directly comparable. Finally, NHANES does not collect disease or vaccination history so we were unable to distinguish between seropositivity due to infection versus vaccination.

Results from NHANES 2009–2010 indicate high seroprevalence to measles, mumps, rubella, and varicella in the civilian non-institutionalized US population aged 6–49 years and provides evidence to support sustained maintenance of elimination of measles, rubella, and CRS, and low mumps and varicella incidence in the US. Measles and rubella remain endemic in much of the world with ongoing risk for importation to the US. Monitoring seroprevalence is an important component of understanding risks for these diseases in the US.