Investigation of a mumps outbreak among university students with two measles-mumps-rubella (MMR) vaccinations, Virginia, September-December 2006.

Following the clinical diagnosis of the first case of mumps on September 22, 2006 at the University of Virginia (UVA), 52 suspected cases were identified through active surveillance for mumps by the end of December 2006. Samples were collected from 47 students who presented with parotitis despite a documented history of two doses of measles, mumps, and rubella (MMR) vaccine. Six of 47 serum samples (13%) were positive for mumps IgM, and 46/47 specimens were positive for mumps IgG. Endpoint titration of acute phase serum samples from laboratory-confirmed cases did not provide evidence that elevated serum IgG is a consistent marker for infection among cases due to secondary vaccine failure. Buccal swab samples from 39 of the 47 students were tested by real-time reverse transcription-polymerase chain reaction (RT-PCR) and/or viral culture. Mumps virus or mumps RNA was detected in 12 of 39 buccal samples (31%). Genetic analysis of the virus from the outbreak at UVA indicated that the outbreak was not linked to the large mumps outbreak in the Midwestern US that occurred earlier in 2006. Our findings support the use of viral detection to improve laboratory diagnosis of mumps among persons who have received two doses of MMR.

Processes for obtaining nonmedical exemptions to state immunization laws.

OBJECTIVES: This study sought to determine the specific processes required for obtaining religious and philosophical exemptions to school immunization laws. METHODS: State health department immunization program managers in the 48 states that offer nonmedical exemptions were surveyed. Categories were assigned to reflect the complexity of the procedure within a state for obtaining an exemption. RESULTS: Sixteen of the states delegated sole authority for processing exemptions to school officials. Nine states had written policies informing parents who seek an exemption of the risks of not immunizing. The complexity of the exemption process, in terms of paperwork or effort required, was inversely associated with the proportion of exemptions field. CONCLUSIONS: In many states, the process of claiming a nonmedical exemption requires less effort than fulfilling immunization requirements.

New genetic group of measles virus isolated in the People's Republic of China.

Genetic and antigenic characterization of 14 wild-type measles viruses isolated from four provinces in the People's Republic of China during 1993 and 1994 was conducted. Sequence analyses of the hemagglutinin (H) and nucleoprotein (N) genes indicated that 13 of the 14 Chinese viruses comprised a previously undescribed genetic group. Viruses from this unique group were the most genetically diverse measles viruses described, so far. The Chinese viruses differed from other wild-type viruses by as much as 6.9% in the H gene and 7.0% in the N gene at the nucleotide level. One of the 14 viruses was a member of the same genetic group that contains the Edmonston strain. Antigenic analysis using monoclonal antibodies to the H protein did not detect significant differences in binding patterns between the Chinese viruses and other wild-type measles viruses. In addition, representative viruses from the unique Chinese group were neutralized by both human post-vaccination antiserum and mouse antiserum against the H protein of the Edmonston vaccine virus. Viruses closely related to these Chinese viruses were also associated with importations of measles into the United States during 1997 from Vietnam and Hong Kong suggesting that viruses from this new genetic group continue to circulate in China and possibly other parts of Asia.

Genetic analysis of measles viruses isolated in the United States, 1995-1996.

Genetic analysis was conducted on 28 wild type measles viruses isolated from outbreaks or cases in the United States during 1995-1996. These viruses were members of at least 6 distinct genetic groups. However, none of these viruses was related to the group 2 viruses that were associated with the resurgence of measles in the United States between 1989 and 1992 except for a single importation from the Philippines. The sequence data support and extend previous findings showing that transmission of group 2 viruses within the United States was interrupted after 1993. The data also suggest that all measles cases that occurred in the United States in 1995-1996 were the result of importation of virus, even in instances when the source was unknown. Molecular epidemiologic studies can provide a means to measure the success of measles control programs by helping to identify the transmission pathways of the virus.

Molecular epidemiology of measles virus: identification of pathways of transmission and implications for measles elimination.

The nucleotide sequences of either the hemagglutinin or nucleoprotein genes from wild type measles viruses isolated in the United States between 1989 and 1992 differed by < 0.5%. This suggests that the majority of viruses associated with resurgence of measles in the United States belonged to a single indigenous genotype. In contrast, wild type viruses isolated from sporadic outbreaks of measles in the United States during 1994 were genetically heterogeneous. These viruses were more closely related to wild type viruses previously circulating in Europe, Africa, or Japan and were epidemiologically linked to importations or no known source. In addition to demonstrating the utility of genetic analysis in understanding the epidemiology of measles, these data suggest that the transmission of the indigenous virus was interrupted after the 1989-1992 epidemic. Measures to further reduce the incidence of measles in the United States should include efforts to control importation and subsequent spread of measles.

Virology of measles virus.

Measles virus is the prototypic member of the Morbillivirus genus of the family Paramyxoviridae. The viral genomic RNA is single-stranded, nonsegmented, and of negative polarity and encodes six major structural proteins. The two viral transmembrane glycoproteins, the hemagglutinin and fusion proteins, are both required for virus-host cell membrane fusion, while attachment to host cells is mediated by the hemagglutinin. The human CD46 molecule has been identified as a cellular receptor for measles virus. Antibodies raised against either viral glycoprotein neutralize measles virus in vitro and protect against infection. Although measles virus remains a single serotype (monotypic), nucleotide sequence analyses have identified distinct lineages among recent wild type isolates. These genetic changes were manifested by detectable antigenic variation between vaccine and wild type viruses and at some point may influence strategies for control, elimination, and eventual eradication of measles virus.

Comparison of sequences of the H, F, and N coding genes of measles virus vaccine strains.

Many live-attenuated vaccines for measles virus have been developed using either the prototype Edmonston strain or other locally isolated measles strains. The attenuation methods used to develop these vaccines have differed in the type(s) of cell line(s) used, number of passages, and temperatures of incubation. To assess the extent of genetic diversity within vaccine strains and to determine the extent to which the varied passage histories may have affected the viruses, we conducted sequence analyses of the fusion, hemagglutinin, nucleoprotein, and matrix genes of Edmonston-derived and non-Edmonston-derived strains. Despite the diverse geographic origins of the vaccine viruses and the different attenuation methods used, there was remarkable sequence similarity among all strains examined. The sequences of all of the vaccine strains were very similar to the sequences of a low-passage seed of the original Edmonston strain. The most divergent sequences were from two of the non-Edmonston-derived vaccines: CAM-70, a vaccine developed from a Japanese wild-type virus, and S-191, which was developed in China.

Genetic variability of the glycoprotein genes of current wild-type measles isolates.

The glycoprotein coding sequences from three wild-type measles viruses isolated in the United States during 1988-1989 were examined by mRNA templated sequencing to determine whether contemporary strains have undergone genetic changes relative to the vaccine strain, Moraten. These studies revealed variation in the hemagglutinin (HA) gene and, to a far lesser degree, the fusion (F) gene. The F protein coding region was highly conserved with only three predicted amino acid changes. Among the predicted amino acid changes identified in the HA was a new potential glycosylation site at residue 416, located toward the carboxy-terminal end of the HA peptide. Eighty percent of the predicted amino acid changes in the HA shared by the three wild-type isolates were clustered near the five previously identified potential glycosylation sites. A linear pattern of evolutionary change was observed after comparing the predicted amino acid HA changes from the 1988-1989 viruses to those predicted in the HA protein from U.S. wild types isolated in 1977 and 1983.

Cocirculation of two distinct evolutionary lineages of influenza type B virus since 1983.

During 1988-1989 two highly distinct antigenic variants of influenza type B were recognized in hemagglutination-inhibition tests with postinfection ferret serum. These viruses were antigenically related to either B/Victoria/2/87, the most recent reference strain, or B/Yamagata/16/88, a variant that was isolated in Japan in May 1988. All influenza B viruses isolated in the United States during an epidemic in the winter of 1988-1989 were antigenically related to B/Victoria/2/87. However, in several countries in Asia, both B/Victoria/2/87-like viruses and B/Yamagata/16/88-like viruses were isolated. Sequence analysis of the hemagglutinin (HA) genes of several influenza B isolates from 1987 to 1988 indicated that the HA1 domains of the B/Yamagata/16/88-like viruses and B/VI/87-like viruses isolated in 1988 differed by 27 amino acids. Evolutionary relationships based on this sequence data indicated that the B/Yamagata/16/88-like viruses were more closely related to epidemic viruses from 1983 (B/USSR/100/83-like viruses) than to more recent reference strains such as B/Victoria/2/87. All other Asian strains, as well as selected isolates from the United States in 1988, were confirmed by sequence analysis as being genetically related to B/Victoria/2/87. These data provide clear evidence that two parallel evolutionary pathways of influenza type B have existed since at least 1983 and that viruses from each of the separate lineages were isolated from cases of influenza B in 1988. This finding is similar to earlier observations for type A H1N1 and H3N2 influenza viruses.