Jennifer S. Rota

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.

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.

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.

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, 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 Viruses in the United States, 1997–2001

From 1997 to 2001, sequence data from 55 clinical specimens were obtained from confirmed measles cases in the United States, representing 21 outbreaks and 34 sporadic cases. Sequence analysis indicated the presence of 11 of the recognized genotypes. The most common genotypes detected were genotype D6, usually identified from imported cases from Europe, and genotype D5, associated with importations from Japan. A number of viruses belonging to genotype D4 were imported from India and Pakistan. Overall, viral genotypes were determined for 13 chains of transmission with an unknown source of virus, and seven different genotypes were identified. Therefore, the diversity of Measles virus genotypes observed in the United States from 1997 to 2001 reflected multiple imported sources of virus and indicated that no strain of measles is endemic in the United States.

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.

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 Peoples 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.

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.