A Comparison of Postelimination Measles Epidemiology in the United States, 2009-2014 Versus 2001-2008.

BACKGROUND: Measles, a vaccine-preventable disease that can cause severe complications, was declared eliminated from the United States in 2000. The last published summary of US measles epidemiology was during 2001-2008. We summarized US measles epidemiology during 2009-2014. METHODS: We compared demographic, vaccination, and virologic data on confirmed measles cases reported to the Centers for Disease Control and Prevention during January 1, 2009-December 31, 2014 and January 1, 2001-December 31, 2008. RESULTS: During 2009-2014, 1264 confirmed measles cases were reported in the United States, including 275 importations from 58 countries and 66 outbreaks. The annual median number of cases and outbreaks during this period was 130 (range, 55-667 cases) and 10 (range, 4-23 outbreaks), respectively, compared with an annual median of 56 cases (P = .08) and 4 outbreaks during 2001-2008 (P = .04). Among US-resident case-patients during 2009-2014, children aged 12-15 months had the highest measles incidence (65 cases; 8.3 cases/million person-years), and infants aged 6-11 months had the second highest incidence (86 cases; 7.3 cases/million person-years). During 2009-2014, 865 (74%) of 1173 US-resident case-patients were unvaccinated and 188 (16%) had unknown vaccination status; of 917 vaccine-eligible US-resident case-patients, 600 (65%) were reported as having philosophical or religious objections to vaccination. CONCLUSIONS: Although the United States has maintained measles elimination since 2000, measles outbreaks continue to occur globally, resulting in imported cases and potential spread. The annual median number of cases and outbreaks more than doubled during 2009-2014 compared with the earlier postelimination years. To maintain elimination, it will be necessary to maintain high 2-dose vaccination coverage, continue case-based surveillance, and monitor the patterns and rates of vaccine exemption.

A Measles Outbreak in an Underimmunized Amish Community in Ohio.

BACKGROUND: Although measles was eliminated in the United States in 2000, importations of the virus continue to cause outbreaks. We describe the epidemiologic features of an outbreak of measles that originated from two unvaccinated Amish men in whom measles was incubating at the time of their return to the United States from the Philippines and explore the effect of public health responses on limiting the spread of measles. METHODS: We performed descriptive analyses of data on demographic characteristics, clinical and laboratory evaluations, and vaccination coverage. RESULTS: From March 24, 2014, through July 23, 2014, a total of 383 outbreak-related cases of measles were reported in nine counties in Ohio. The median age of case patients was 15 years (range, <1 to 53); a total of 178 of the case patients (46%) were female, and 340 (89%) were unvaccinated. Transmission took place primarily within households (68% of cases). The virus strain was genotype D9, which was circulating in the Philippines at the time of the reporting period. Measles-mumps-rubella (MMR) vaccination coverage with at least a single dose was estimated to be 14% in affected Amish households and more than 88% in the general (non-Amish) Ohio community. Containment efforts included isolation of case patients, quarantine of susceptible persons, and administration of the MMR vaccine to more than 10,000 persons. The spread of measles was limited almost exclusively to the Amish community (accounting for 99% of case patients) and affected only approximately 1% of the estimated 32,630 Amish persons in the settlement. CONCLUSIONS: The key epidemiologic features of a measles outbreak in the Amish community in Ohio were transmission primarily within households, the small proportion of Amish people affected, and the large number of people in the Amish community who sought vaccination. As a result of targeted containment efforts, and high baseline coverage in the general community, there was limited spread beyond the Amish community. (Funded by the Ohio Department of Health and the Centers for Disease Control and Prevention.).

High Concentrations of Measles Neutralizing Antibodies and High-Avidity Measles IgG Accurately Identify Measles Reinfection Cases.

In the United States, approximately 9% of the measles cases reported from 2012 to 2014 occurred in vaccinated individuals. Laboratory confirmation of measles in vaccinated individuals is challenging since IgM assays can give inconclusive results. Although a positive reverse transcription (RT)-PCR assay result from an appropriately timed specimen can provide confirmation, negative results may not rule out a highly suspicious case. Detection of high-avidity measles IgG in serum samples provides laboratory evidence of a past immunologic response to measles from natural infection or immunization. High concentrations of measles neutralizing antibody have been observed by plaque reduction neutralization (PRN) assays among confirmed measles cases with high-avidity IgG, referred to here as reinfection cases (RICs). In this study, we evaluated the utility of measuring levels of measles neutralizing antibody to distinguish RICs from noncases by receiver operating characteristic curve analysis. Single and paired serum samples with high-avidity measles IgG from suspected measles cases submitted to the CDC for routine surveillance were used for the analysis. The RICs were confirmed by a 4-fold rise in PRN titer or by RT-quantitative PCR (RT-qPCR) assay, while the noncases were negative by both assays. Discrimination accuracy was high with serum samples collected ≥3 days after rash onset (area under the curve, 0.953; 95% confidence interval [CI], 0.854 to 0.993). Measles neutralizing antibody concentrations of ≥40,000 mIU/ml identified RICs with 90% sensitivity (95% CI, 74 to 98%) and 100% specificity (95% CI, 82 to 100%). Therefore, when serological or RT-qPCR results are unavailable or inconclusive, suspected measles cases with high-avidity measles IgG can be confirmed as RICs by measles neutralizing antibody concentrations of ≥40,000 mIU/ml.

Measles - United States, January 1-May 23, 2014.

Measles is a highly contagious, acute viral illness that can lead to serious complications and death. Although measles elimination (i.e., interruption of year-round endemic transmission) was declared in the United States in 2000, importations of measles cases from endemic areas of the world continue to occur, leading to secondary measles cases and outbreaks in the United States, primarily among unvaccinated persons. To update national measles data in the United States, CDC evaluated cases reported by states from January 1 through May 23, 2014. A total of 288 confirmed measles cases have been reported to CDC, surpassing the highest reported yearly total of measles cases since elimination (220 cases reported in 2011). Fifteen outbreaks accounted for 79% of cases reported, including the largest outbreak reported in the United States since elimination (138 cases and ongoing). The large number of cases this year emphasizes the need for health-care providers to have a heightened awareness of the potential for measles in their communities and the importance of vaccination to prevent measles.

Outbreak of measles among persons with prior evidence of immunity, New York City, 2011.

BACKGROUND: Measles was eliminated in the United States through high vaccination coverage and a public health system able to rapidly respond to measles. Measles may occur among vaccinated individuals, but secondary transmission from such individuals has not been documented. METHODS: Suspected patients and contacts exposed during a measles outbreak in New York City in 2011 were investigated. Medical histories and immunization records were obtained. Cases were confirmed by detection of measles-specific immunoglobulin M and/or RNA. Tests for measles immunoglobulin G (IgG), IgG avidity, measurement of measles neutralizing antibody titers, and genotyping were performed to characterize the cases. RESULTS: The index patient had 2 doses of measles-containing vaccine; of 88 contacts, 4 secondary patients were confirmed who had either 2 doses of measles-containing vaccine or a past positive measles IgG antibody. All patients had laboratory confirmation of measles infection, clinical symptoms consistent with measles, and high-avidity IgG antibody characteristic of a secondary immune response. Neutralizing antibody titers of secondary patients reached >80 000 mIU/mL 3-4 days after rash onset and that of the index was <500 mIU/mL 9 days after rash onset. No additional cases of measles occurred among 231 contacts of secondary patients. CONCLUSIONS: This is the first report of measles transmission from a twice-vaccinated individual with documented secondary vaccine failure. The clinical presentation and laboratory data of the index patient were typical of measles in a naive individual. Secondary patients had robust anamnestic antibody responses. No tertiary cases occurred despite numerous contacts. This outbreak underscores the need for thorough epidemiologic and laboratory investigation of suspected cases of measles regardless of vaccination status.

Elimination of endemic measles, rubella, and congenital rubella syndrome from the Western hemisphere: the US experience.

IMPORTANCE: To verify the elimination of endemic measles, rubella, and congenital rubella syndrome (CRS) from the Western hemisphere, the Pan American Health Organization requested each member country to compile a national elimination report. The United States documented the elimination of endemic measles in 2000 and of endemic rubella and CRS in 2004. In December 2011, the Centers for Disease Control and Prevention convened an external expert panel to review the evidence and determine whether elimination of endemic measles, rubella, and CRS had been sustained. OBJECTIVE: To review the evidence for sustained elimination of endemic measles, rubella, and CRS from the United States through 2011. DESIGN, SETTING, AND PARTICIPANTS: Review of data for measles from 2001 to 2011 and for rubella and CRS from 2004 to 2011 covering the US resident population and international visitors, including disease epidemiology, importation status of cases, molecular epidemiology, adequacy of surveillance, and population immunity as estimated by national vaccination coverage and serologic surveys. MAIN OUTCOMES AND MEASURES: Annual numbers of measles, rubella, and CRS cases, by importation status, outbreak size, and distribution; proportions of US population seropositive for measles and rubella; and measles-mumps-rubella vaccination coverage levels. RESULTS: Since 2001, US reported measles incidence has remained below 1 case per 1,000,000 population. Since 2004, rubella incidence has been below 1 case per 10,000,000 population, and CRS incidence has been below 1 case per 5,000,000 births. Eighty-eight percent of measles cases and 54% of rubella cases were internationally imported or epidemiologically or virologically linked to importation. The few cases not linked to importation were insufficient to represent endemic transmission. Molecular epidemiology indicated no endemic genotypes. The US surveillance system is adequate to detect endemic measles or rubella. Seroprevalence and vaccination coverage data indicate high levels of population immunity to measles and rubella. CONCLUSIONS AND RELEVANCE: The external expert panel concluded that the elimination of endemic measles, rubella, and CRS from the United States was sustained through 2011. However, international importation continues, and health care providers should suspect measles or rubella in patients with febrile rash illness, especially when associated with international travel or international visitors, and should report suspected cases to the local health department.

Comparison of the sensitivity of laboratory diagnostic methods from a well-characterized outbreak of mumps in New York city in 2009.

A mumps outbreak in upstate New York in 2009 at a summer camp for Orthodox Jewish boys spread into Orthodox Jewish communities in the Northeast, including New York City. The availability of epidemiologic information, including vaccination records and parotitis onset dates, allowed an enhanced analysis of laboratory methods for mumps testing. Serum and buccal swab samples were collected from 296 confirmed cases with onsets from September through December 2009. All samples were tested using the Centers for Disease Control and Prevention (CDC) capture IgM enzyme immunoassay (EIA) and a real-time reverse transcription-PCR (rRT-PCR) that targets the short hydrophobic gene. A subset of the samples (n = 205) was used to evaluate 3 commercial mumps IgM assays and to assess the sensitivity of using an alternative target gene (nucleoprotein) in the rRT-PCR protocol. Among 115 cases of mumps with 2 documented doses of measles, mumps, and rubella (MMR) vaccine, the CDC capture IgM EIA detected IgM in 51% of serum samples compared to 9% to 24% using three commercial IgM assays. The rRT-PCR that targeted the nucleoprotein gene increased RNA detection by 14% compared to that obtained with the original protocol. The ability to detect IgM improved when serum was collected 3 days or more after symptom onset, whereas sensitivity of RNA detection by rRT-PCR declined when buccal swabs were collected later than 2 days after onset. Selection of testing methods and timing of sample collection are important factors in the ability to confirm infection among vaccinated persons. These results reinforce the need to use virus detection assays in addition to serologic tests.

Mumps outbreak in Orthodox Jewish communities in the United States.

BACKGROUND: By 2005, vaccination had reduced the annual incidence of mumps in the United States by more than 99%, with few outbreaks reported. However, in 2006, a large outbreak occurred among highly vaccinated populations in the United States, and similar outbreaks have been reported worldwide. The outbreak described in this report occurred among U.S. Orthodox Jewish communities during 2009 and 2010. METHODS: Cases of salivary-gland swelling and other symptoms clinically compatible with mumps were investigated, and demographic, clinical, laboratory, and vaccination data were evaluated. RESULTS: From June 28, 2009, through June 27, 2010, a total of 3502 outbreak-related cases of mumps were reported in New York City, two upstate New York counties, and one New Jersey county. Of the 1648 cases for which clinical specimens were available, 50% were laboratory-confirmed. Orthodox Jewish persons accounted for 97% of case patients. Adolescents 13 to 17 years of age (27% of all patients) and males (78% of patients in that age group) were disproportionately affected. Among case patients 13 to 17 years of age with documented vaccination status, 89% had previously received two doses of a mumps-containing vaccine, and 8% had received one dose. Transmission was focused within Jewish schools for boys, where students spend many hours daily in intense, face-to-face interaction. Orchitis was the most common complication (120 cases, 7% of male patients ≥12 years of age), with rates significantly higher among unvaccinated persons than among persons who had received two doses of vaccine. CONCLUSIONS: The epidemiologic features of this outbreak suggest that intense exposures, particularly among boys in schools, facilitated transmission and overcame vaccine-induced protection in these patients. High rates of two-dose coverage reduced the severity of the disease and the transmission to persons in settings of less intense exposure.

Two case studies of modified measles in vaccinated physicians exposed to primary measles cases: high risk of infection but low risk of transmission.

In 2009, measles outbreaks in Pennsylvania and Virginia resulted in the exposure and apparent infection of 2 physicians, both of whom had a documented history of vaccination with >2 doses of measles-mumps-rubella vaccine. These physicians were suspected of having been infected with measles after treating patients who subsequently received a diagnosis of measles. The clinical presentation was nonclassical in regard to progression, duration, and severity. It is hypothesized that the 2 physicians mounted vigorous secondary immune responses typified by high avidity measles immunoglobulin G antibody and remarkably high neutralizing titers in response to intense and prolonged exposure to a primary measles case patient. Both of the physicians continued to see patients, because neither considered that they could have measles. Despite surveillance for cases among contacts, including unvaccinated persons, no additional cases were identified.

Measles in the United States during the postelimination era.

BACKGROUND: Measles affected entire birth cohorts in the prevaccine era but was declared eliminated in the United States in 2000 because of a successful measles vaccination program. METHODS: We reviewed US surveillance data on confirmed measles cases reported to the Centers for Disease Control and Prevention and data on national measles-mumps-rubella (MMR) vaccination coverage during postelimination years 2001-2008. RESULTS: During 2001-2008, a total of 557 confirmed cases of measles (annual median no. of cases, 56) and 38 outbreaks (annual median no. of outbreaks, 4) were reported in the United States; 232 (42%) of the cases were imported from 44 countries, including European countries. Among case-patients who were US residents, the highest incidences of measles were among infants 6-11 months of age and children 12-15 months of age (3.5 and 2.6 cases/1 million person-years, respectively). From 2001 through 2008, national 1-dose MMR vaccine coverage among children 19-35 months of age ranged from 91% to 93%. From 2001 through 2008, a total of 285 US-resident case-patients (65%) were considered to have preventable measles (ie, the patients were eligible for vaccination but unvaccinated). During 2004-2008, a total of 68% of vaccine-eligible US-resident case-patients claimed exemptions for personal beliefs. CONCLUSIONS: The United States maintained measles elimination from 2001 through 2008 because of sustained high vaccination coverage. Challenges to maintaining elimination include large outbreaks of measles in highly traveled developed countries, frequent international travel, and clusters of US residents who remain unvaccinated because of personal belief exemptions.

Measles outbreak associated with an international youth sporting event in the United States, 2007.

BACKGROUND: Despite elimination of endemic measles in the United States (US), outbreaks associated with imported measles continue to occur. In 2007, the initiation of a multistate measles outbreak was associated with an imported case occurring in a participant at an international youth sporting event held in Pennsylvania. METHODS: Case finding and contact tracing were conducted. Control measures included isolating ill persons and administering postexposure prophylaxis to exposed persons without documented measles immunity. Laboratory evaluation of suspected cases and contacts included measles serologic testing, viral culture, detection of viral RNA by reverse-transcription polymerase chain reaction, and viral genotyping. RESULTS: The index case occurred in a child from Japan aged 12 years. Contact tracing among 1250 persons in 8 states identified 7 measles cases; 5 (71%) cases occurred among persons without documented measles vaccination. Epidemiologic and laboratory investigation supported a single chain of transmission, linking the outbreak to contemporaneous measles virus genotype D5 transmission in Japan. Of the 471 event participants, 193 (41%) lacked documentation of presumed measles immunity, 94 (49%) of 193 were US-resident adults, 19 (10%) were non-US-resident adults (aged >18 years), and 80 (41%) were non-US-resident children. DISCUSSION: Measles outbreaks associated with imported disease are likely to continue in the US. Participants in international events, international travelers, and persons with routine exposure to such travelers might be at greater risk of measles. To reduce the impact of imported cases, high measles, mumps, and rubella vaccine coverage rates should be maintained throughout the US, and support should continue for global measles control and elimination.

Recent resurgence of mumps in the United States.

BACKGROUND: The widespread use of a second dose of mumps vaccine among U.S. schoolchildren beginning in 1990 was followed by historically low reports of mumps cases. A 2010 elimination goal was established, but in 2006 the largest mumps outbreak in two decades occurred in the United States. METHODS: We examined national data on mumps cases reported during 2006, detailed case data from the most highly affected states, and vaccination-coverage data from three nationwide surveys. RESULTS: A total of 6584 cases of mumps were reported in 2006, with 76% occurring between March and May. There were 85 hospitalizations, but no deaths were reported; 85% of patients lived in eight contiguous midwestern states. The national incidence of mumps was 2.2 per 100,000, with the highest incidence among persons 18 to 24 years of age (an incidence 3.7 times that of all other age groups combined). In a subgroup analysis, 83% of these patients reported current college attendance. Among patients in eight highly affected states with known vaccination status, 63% overall and 84% between the ages of 18 and 24 years had received two doses of mumps vaccine. For the 12 years preceding the outbreak, national coverage of one-dose mumps vaccination among preschoolers was 89% or more nationwide and 86% or more in highly affected states. In 2006, the national two-dose coverage among adolescents was 87%, the highest in U.S. history. CONCLUSIONS: Despite a high coverage rate with two doses of mumps-containing vaccine, a large mumps outbreak occurred, characterized by two-dose vaccine failure, particularly among midwestern college-age adults who probably received the second dose as schoolchildren. A more effective mumps vaccine or changes in vaccine policy may be needed to avert future outbreaks and achieve the elimination of mumps.

Identical genotype B3 sequences from measles patients in 4 countries, 2005.

Surveillance of measles virus detected an epidemiologic link between a refugee from Kenya and a Dutch tourist in New Jersey, USA. Identical genotype B3 sequences from patients with contemporaneous cases in the United States, Canada, and Mexico in November and December 2005 indicate that Kenya was likely to have been the common source of virus.

Review of the temporal and geographical distribution of measles virus genotypes in the prevaccine and postvaccine eras.

Molecular epidemiological investigation of measles outbreaks can document the interruption of endemic measles transmission and is useful for establishing and clarifying epidemiological links between cases in geographically distinct clusters. To determine the distribution of measles virus genotypes in the prevaccine and postvaccine eras, a literature search of biomedical databases, measles surveillance websites and other electronic sources was conducted for English language reports of measles outbreaks or genetic characterization of measles virus isolates. Genotype assignments based on classification systems other than the currently accepted WHO nomenclature were reassigned using the current criteria. This review gives a comprehensive overview of the distribution of MV genotypes in the prevaccine and postvaccine eras and describes the geographically diverse distribution of some measles virus genotypes and the localized distributions of other genotypes.

Subacute sclerosing panencephalitis: more cases of this fatal disease are prevented by measles immunization than was previously recognized.

BACKGROUND: The most severe sequela of measles virus infection is subacute sclerosing panencephalitis (SSPE), a fatal disease of the central nervous system that generally develops 7-10 years after infection. From 1989 through 1991, a resurgence of measles occurred in the United States, with 55,622 cases of measles reported. The purpose of the present study was to identify cases of SSPE that were associated with the resurgence of measles and to calculate the risk of developing SSPE. METHODS: Brain tissue samples obtained from 11 patients with a presumptive diagnosis of SSPE were tested for the presence of measles virus RNA. Measles virus genotypes were determined by reverse-transcription polymerase chain reaction (RT-PCR) and by analysis of the sequences of the PCR products. A search of the literature was conducted to identify reports of cases of SSPE in persons residing in the United States who had measles during 1989-1991. RESULTS: The measles virus sequences derived from brain tissue samples obtained from 11 patients with SSPE confirmed the diagnosis of SSPE. For 5 of the 11 patients with SSPE who had samples tested by RT-PCR and for 7 patients with SSPE who were identified in published case reports, it was determined that the development of SSPE was associated with the measles resurgence that occurred in the United States during 1989-1991. The estimated risk of developing SSPE was 10-fold higher than the previous estimate reported for the United States in 1982. CONCLUSIONS: Vaccination against measles prevents more cases of SSPE than was originally estimated.

Genetic analysis of measles viruses isolated in the united states between 1989 and 2001: absence of an endemic genotype since 1994.

This report describes measles virus surveillance in the United States for 1989-2001. During the resurgence of measles in the United States between 1989 and 1992, only viruses of genotype D3 were isolated. In contrast, virological surveillance conducted after the resurgence period showed that at least 12 different genotypes were associated with the greatly reduced number of measles cases. Eight different genotypes were identified for 27 chains of transmission in which the source of infection was unknown. The diversity of measles virus genotypes observed in the United States between 1994 and 2001 reflected multiple imported sources of virus and indicated that no genotype of measles is endemic in the United States. Therefore, the data obtained from virological surveillance are consistent with the conclusions made by disease surveillance and epidemiological investigations that measles is no longer an endemic disease in the United States.

The laboratory confirmation of suspected measles cases in settings of low measles transmission: conclusions from the experience in the Americas.

The Americas have set a goal of interrupting indigenous transmission of measles using a strategy developed by the Pan American Health Organization (PAHO). This strategy includes recommendations for vaccination activities to achieve and sustain high immunity in the population and is complemented by sensitive epidemiological surveillance systems developed to monitor illnesses characterized by febrile rash, and to provide effective virological and serological surveillance. A key component in ensuring the success of the programme has been a laboratory network comprising 22 national laboratories including reference centres. Commercially available indirect enzyme immunoassay kits (EIA) for immunoglobulin M (IgM)-class antibodies are currently being used throughout the region. However, because there are few or no true measles cases in the region, the positive predictive value of these diagnostic tests has decreased. False-positive results of IgM tests can also occur as a result of testing suspected measles cases with exanthemata caused by Parvovirus B19, rubella and Human herpesvirus 6, among others. In addition, as countries maintain high levels of vaccination activity and increased surveillance of rash and fever, the notification of febrile rash illness in recently vaccinated people can be anticipated. Thus, managers in the measles elimination programme must be prepared to address the interpretation of a positive result of a laboratory test for measles IgM when clinical and epidemiological data may indicate that the case is not measles. The interpretation of an IgM-positive test under different circumstances and the definition of a vaccine-related rash illness in a setting of greatly reduced, or absent, transmission of measles is discussed.

The Measles Laboratory Network in the region of the Americas.

The success of measles eradication depends upon a laboratory network to rapidly analyze samples obtained as part of surveillance and case investigation. The Pan American Measles Laboratory Network was established in 1995. Major activities of the 22 participating laboratories include the rapid testing of serum samples to diagnose measles, analysis and recommendation of techniques to be used in serologic testing, training in virus isolation, and procurement and distribution of laboratory materials. In addition, a comprehensive quality-control program and an electronic communication network have been developed. Testing for rubella has also been incorporated. The Network has been crucial to the great progress made toward eradicating measles from the Western Hemisphere. The priority given to the laboratories in the Network must continue in order to ensure that the eradication goal is reached and that validation of the interruption of endemic transmission of measles is documented.