Ongoing African measles virus genotype outbreak in Tel Aviv district since April, Israel, 2012.

A measles outbreak is affecting the Tel Aviv district, Israel, since April 2012. As of 10 September, 99 cases were confirmed, including 63 (64%) migrants of Eritrean and Sudanese origin. All genotyped cases had the African B3 genotype*. The mean age of migrant and non-migrant cases was 6.0±9.6 and 30.2±24.2 years, respectively (p<0.001). The majority of both migrant and non-migrant cases was unvaccinated. This is the second African measles B3 genotype outbreak within the World Health Organization European region in 2012.

Measles outbreaks affecting children in Jewish ultra-orthodox communities in Jerusalem.

In 2003 and 2004 two measles outbreaks occurred in Jewish ultra-orthodox communities in Jerusalem. The index case of the first outbreak (March 2003) was a 2-year-old unvaccinated child from Switzerland. Within 5 months, 107 cases (mean age 8.3+/-7.5 years) emerged in three crowded neighbourhoods. The first cases of the second outbreak (June 2004) were in three girls aged 4-5 years in one kindergarten in another community. By November 2004, 117 cases (mean age 7.3+/-6.5 years) occurred. The virus genotypes were D8 and D4 respectively. Altogether, 96 households accounted for the two outbreaks, with two or more patients per family in 79% of cases. Most cases (91.5%) were unvaccinated. Immunization coverage was lower in outbreak than in non-outbreak neighbourhoods (88.3% vs. 90.3%, P=0.001). Controlling the outbreaks necessitated a culture-sensitive approach, and targeted efforts increased MMR vaccine coverage (first dose) to 95.2%. Despite high national immunization coverage (94-95%), special attention to specific sub-populations is essential.

Prevalence of mumps antibodies in the Israeli population in relation to mumps vaccination policy and incidence of disease.

We examined the prevalence of mumps antibodies in the Israeli population in relation to mumps vaccination policy and past and subsequent incidence of disease. The levels of specific IgG antibodies against mumps were tested in 3330 residual sera collected during 1997-1998 from an age-stratified population sample. Against the background of a consistent MMR vaccination coverage of >90%, the age- and sex-adjusted seropositivity to mumps was 77.0%. No significant differences between genders were found. Seropositivity in the 10-13 years age group, born just before the introduction of the MMR vaccine, was the lowest (59%). These birth cohorts were the target of an outbreak of mumps in 2005 that occurred among high-school students and military recruits. A trend of waning immunity was observed between the first and second vaccine doses. The seroepidemiological data demonstrate that immunity levels below the herd immunity threshold, along with social mixing and crowded conditions facilitated the occurrence of mumps outbreaks. Periodical serosurveys are an essential component in the evaluation of the vaccination policy against mumps.

Standardization of measles, mumps and rubella assays to enable comparisons of seroprevalence data across 21 European countries and Australia.

The aim of the European Sero-Epidemiology Network is to establish comparability of the serological surveillance of vaccine-preventable diseases in Europe. The designated reference laboratory (RL) for measles, mumps, rubella (MMR) prepared and tested a panel of 151 sera by the reference enzyme immunoassay (rEIA). Laboratories in 21 countries tested the panel for antibodies against MMR using their usual assay (a total of 16 different EIAs) and the results were plotted against the reference results in order to obtain equations for the standardization of national serum surveys. The RL also tested the panel by the plaque neutralization test (PNT). Large differences in qualitative results were found compared to the RL. Well-fitting standardization equations with R2> or =0.8 were obtained for almost all laboratories through regression of the quantitative results against those of the RL. When compared to PNT, the rEIA had a sensitivity of 95.3%, 92.8% and 100% and a specificity of 100%, 87.1% and 92.8% for measles, mumps and rubella, respectively. The need for standardization was highlighted by substantial inter-country differences. Standardization was successful and the selected standardization equations allowed the conversion of local serological results into common units and enabled direct comparison of seroprevalence data of the participating countries.

Use of rubella seroepidemiological data for assessment of previous vaccination policy and for decision making in response to epidemics in Israel.

We examined the prevalence of rubella antibodies in a representative sample of the Israeli population. Three thousand three hundred and twenty-six sera collected during 1997 and 1998, from an age-stratified general population sample were tested for specific IgG antibodies against rubella. The sero-positivity rates to rubella were higher among females as compared with males (89.1% versus 82.3%, respectively (p < 0.001). This difference was the result of much lower sero-positivity rates among males in the age group 13-17, with the lowest value (56.3%) among subjects aged 16. Male subjects of this age group were in 2000 the target of an outbreak of rubella among 18-19-year old male recruits of the Israel Defense Force. The data of this study served to assess previous exposure to the wild virus or vaccine strains, to identify pockets of low level of immunity and contributed to decision making in response to the onset of a rubella outbreak.

Clinical rubella reinfection during pregnancy in a previously vaccinated woman.

We report a documented case of clinically apparent rubella reinfection during pregnancy with rubelliform rash and fever followed by lymphodenopathy at the 18th week of gestation, in a previously vaccinated woman with haemagglutination inhibition (HI) antibody titre of 1:32. The serological tests results (including neutralizing antibodies) demonstrated a significant rise in her rubella specific IgG level with strongly positive IgM reactivity. In addition, rubella-specific IgG antibody avidity testing displayed high avidity index (53-88%) typical of rubella reinfection. Umbilical cord blood, drawn by sonographic-guided cordocentesis at 24 weeks' gestation, was found to be negative for rubella-specific IgM antibody. The pregnancy was continued to term, and a healthy infant was born.

Placental transfer of maternal rubella antibodies to full-term and preterm infants.

Premature infants are vulnerable to infections, partly because of the low transplacental transfer of maternal antibodies. The present study investigated the placental transfer of maternal rubella-specific antibodies to full-term and preterm infants. The study group consisted of 133 healthy, native Israeli mothers and their 159 newborns. Of these, 69 were full-term infants (gestational age > 37 weeks) of 69 mothers, and 90 were preterm infants (gestational age < 35 weeks) of 64 mothers. Antibody titers against rubella were measured in maternal and umbilical cord blood samples by hemagglutination inhibition and microneutralization techniques. There was no significant difference in the level of protection and in geometrical mean titers by hemagglutination between the full-term and preterm groups. Conversely, significant differences in geometric mean titers of neutralizing antibodies were found between full-term and preterm infants, e.g., 65.9 and 39.8, respectively (P < 0.001). Very low birth weight preterm infants are at greater risk of rubella infection during the first year of life, due to the diminished transfer of neutralizing maternal antibodies. Therefore, earlier vaccination of this group may be beneficial.

Subclinical rubella reinfection during pregnancy followed by transmission of virus to the fetus.

We report a documented case of rubella reinfection during pregnancy in a previously vaccinated woman with residual antibody titre to rubella of 15 IU/ml. The reinfection occurred following an exposure to rubella virus (contact with 6-year-old daughter with clinical rubella) between the 7th and 10th week of pregnancy which resulted in transmission of the virus to the fetus. Umbilical cord blood drawn by cordocentesis was found to be strongly positive for rubella IgM antibody. After termination of the pregnancy rubella virus was isolated in cell culture from fetal tissues.

Rubella in pregnancy in Israel: 15 years of follow-up and remaining problems.

Despite extensive vaccination programs introduced in Israel since 1973, rubella virus continues to pose a threat to pregnant women. Screening for antibodies from women of childbearing age between 1980 and 1994 showed a decrease in seronegativity from 15.4% to 7% between the years 1980 and 1988, followed by an increase to 9.6% in 1991-92 due in part to the large wave of immigration from the former USSR, and a decrease back to 6.9% in 1993-94. The morbidity fluctuated, with peaks in 1983, 1987 and 1991, yielding a total of 219 cases in the target population of women of childbearing age. Additional problems encountered were reinfections, vaccine failures, and false positive results in screening. During the study period we confirmed 35 cases of reinfections in pregnancy, 19 of which resulted in delivery of healthy babies. In two of four cases of abortion following reinfection that we could follow, the fetus was infected. Immunization of 15-month-old babies introduced in 1989 and the new policy of two-dose vaccination introduced in 1995 are expected to further reduce the spread of rubella virus in the coming years.

Serological evidence for hepatitis E virus infection in Israel.

Israel is suspected to be endemic for hepatitis E virus (HEV) because of its geographic location and the large-scale immigration from endemic countries. Although no cases of local HEV infection have been diagnosed, a serological survey would provide indirect evidence for such infection. We examined sera from 1,416 healthy subjects, including 1,139 Jews from various regions of Israel and 277 Arabs, most of whom reside in the West Bank of the Jordan River. In addition, we tested 13 non-A, non-B, and non-C viral hepatitis patients. Sera were screened for antibody to hepatitis E virus (anti-HEV) by a newly developed enzyme immunoassay (EIA) and by immunoblots for both IgG and IgM anti-HEV activity. Positive samples were confirmed by neutralization. The seroprevalence found by EIA was 2.81% and 1.81% in the Jewish and Arab populations, respectively. More than a 2-fold higher prevalence in males compared to females and an increase with age were found in both populations. However, these differences were nonsignificant. The geographical distribution was even throughout the country, except for two clusters of 3 and 4 seropositive individuals possibly reflecting past foci of infection. Eight of 37 EIA-positive sera were positive for IgG, and 3 were positive for IgM by the immunoblot assay. Among hepatitis patients (9 acute and 4 chronic), one patient with chronic hepatitis was positive for both IgG and IgM. Our study provides indirect evidence that Israel is endemic for HEV.(ABSTRACT TRUNCATED AT 250 WORDS)

Activity of two synthetic amphiphilic peptides and magainin-2 against herpes simplex virus types 1 and 2.

The in vitro antiviral activity of two amphiphilic synthetic peptides, modelin-1 (mod-1) and modelin-5 (mod-5), and of the natural antibacterial peptide magainin-2 (mag-2) against herpes simplex viruses type 1 (HSV-1) and 2 (HSV-2) were evaluated. The peptides were incubated with the virus, i.e. direct inactivation, and their effects examined by means of plaque reduction assay and/or reduction in virus yield. Only mod-1 displayed a strong antiviral effect against HSV-1 and HSV-2, with 50% effective dose (ED50) values of 4.6 and 4.1 micrograms/mL, respectively. Mag-2, mod-5 and a mixture of both had no significant inhibitory effect. Addition of mod-1 up to a concentration of 100 micrograms/mL to the culture medium had no significant cytotoxic effect on host vero cells, as measured by the trypan blue-exclusion method. It showed, however, considerable hemolytic activity against human red blood cells. Experiments including acyclovir (ACV) as a reference viral inhibitor indicated that the mode of action of mod-1 is different from that of ACV. In contrast to ACV, the peptide inactivates the virus following a very short incubation before vero cell infection, suggesting some kind of direct interaction of the peptide with the viral envelope, rather than inhibition of viral DNA replication or gene expression. Our results suggest that mod-1 may be an effective topical antiviral agent against herpes viruses.

A new serotype of the outer capsid protein VP4 shared by an unusual human rotavirus strain Ro1845 and canine rotaviruses.

The VP4 protein of human rotavirus (HRV) strain Ro1845 and canine rotavirus strains K9 and CU-1 exhibited greater than 98% amino acid identity within their group, but showed less identity with VP4 proteins of other HRV and animal rotavirus strains, the simian rotavirus strain RRV VP4 being most similar to them (90% amino acid identity). To exclude the possibility that these three strains were members of the RRV VP4 serotype P3, neutralization studies were performed using antisera to reassortant viruses containing the VP4 gene from each of Ro1845, CU-1 and RRV. The result established close antigenic similarity among the VP4 proteins of Ro1845, K9 and CU-1 and revealed only a marginal degree of similarity between the VP4 proteins of these three strains and that of strain RRV. These sequence and serological data suggest that the VP4 proteins of Ro1845, K9 and CU-1 represent a new P serotype which we propose to assign P13.

Identification of feline- and canine-like rotaviruses isolated from humans by restriction fragment length polymorphism assay.

Restriction fragment length polymorphism assay of reverse-transcribed and polymerase chain reaction-amplified rotavirus gene segment 9 was developed to differentiate human serotype 3 rotaviruses from animal serotype 3 rotaviruses. On the basis of similarities or differences in HinfI and DdeI restriction profiles, unusual group A serotype 3 human rotaviruses that belonged to subgroup I were shown to be of feline and canine origin. By this approach, the new human rotavirus isolates 5193, AU-387, AU-720, AU-785 and AU-1115 were shown to resemble certain feline-like human rotaviruses. Similar results were previously obtained by Nakagomi et al. (O. Nakagomi, A. Hoshima, Y. Aboudy, I. Shif, M. Mochizuki, T. Nakagomi, and T. Gotlieb-Stematsky. J. Clin. Microbiol. 28:1198-1203, 1990) by using RNA-RNA cross hybridization with established feline rotaviruses. The restriction fragment length polymorphism assay can provide fast and valuable information on the interspecies transmission of rotaviruses in nature.

Uniformity of serotype and electropherotype in local human rotavirus isolates during each of three successive cold seasons.

Each of three consecutive cold seasons (November-March) in the town of Tiberias, Israel, was dominated by one particular rotavirus serotype causing acute diarrhoea in the community: the 1987/88 season by serotype-2; 1988/89 by serotype-1 and 1989/90 by serotype-4. Each season was also characterized by a particular pattern of rotaviral RNA when visualized using electrophoresis in gels. RNA profiles of identical rota serotypes and serotypic prevalence for any given cold season were unique for the town of Tiberias and different from other localities throughout Israel. The meaning of these findings in terms of herd immunity is discussed.

Hemagglutination by a human rotavirus isolate as evidence for transmission of animal rotaviruses to humans.

Human rotavirus strain Ro1845, which was isolated in 1985 from an Israeli child with diarrhea, has a hemagglutinin that is capable of agglutinating erythrocytes from guinea pigs, sheep, chickens, and humans (group O). Hemagglutination was inhibited after incubation with hyperimmune sera or in the presence of glycophorin, the erythrocyte receptor for animal rotaviruses. These results suggest that Ro1845 is an animal rotavirus that infected a human child.

Molecular identification by RNA-RNA hybridization of a human rotavirus that is closely related to rotaviruses of feline and canine origin.

With a few exceptions subgroup I group A human rotavirus strains have short RNA patterns, whereas most animal rotavirus strains belong to subgroup I and have long RNA patterns. Thus, new isolates of subgroup I human rotaviruses with long RNA patterns are considered to have a high likelihood of being animal rotaviruses. A group of human rotaviruses represented by the AU-1 strain has recently been shown to be genetically related to a feline rotavirus (FRV-1) isolated in Japan. A human rotavirus, strain Ro1845, which is similar to the AU-1 strain in its subgroup (I), serotype (3), and electropherotype (long), was compared with various human and animal strains by RNA-RNA hybridization to determine its genogroup, a term proposed to classify rotaviruses based on their gene homology. The Ro1845 strain did not show a significant level of homology with AU-1, FRV-1, or other human strains, indicating that the Ro1845 strain is different in its genogroup not only from the AU-1 strain but also from other human strains. However, the Ro1845 strain showed a high degree of homology with another feline rotavirus (Cat97) isolated previously in Australia, suggesting that the Ro1845 strain might originate from a feline rotavirus that is genetically distinct from the Japanese FRV-1 strain. Furthermore, the Ro1845 strain as well as the Cat97 strain were related genetically to the canine rotavirus RS15 strain. Taken together, these results indicate that at least two genogroups are present in feline rotaviruses, one resembling the AU-1 strain and the other resembling the Ro1845 strain as well as canine rotaviruses.

Efficiency of isolation of human rotavirus in primary African green monkey kidney cells.

Out of 212 human rotavirus (HRV) containing fecal specimens, 173 (81.6%) yielded virus on first passage in primary African Green monkey kidney cells (AGMK), while additional 34 specimens, did not yield virus on first passage. However, following blind passages, 18 of the 34 yielded virus in passage levels 2-8, thus raising the overall isolation rate to 90.1%. The isolation rate of HRV strains obtained in embryonic Rhesus monkey kidney cell line (MA-104), was only 41.4%. ELISA tests performed on fluids from infected cell cultures proved to be an efficient tool to measure virus replication. No differences were encountered in the isolation rates between subgroup I and II strains, while viruses lacking the antigenic determinants of both subgroups did not grow at all. However, one of those unusual group A strains was isolated and grew well in AGMK cells. Primary AGMK and MA-104 cells supported the growth of tissue culture adapted virus most efficiently when compared with six human and primate cell types.

Use of polyclonal and monoclonal antibodies and analysis of viral RNA in the detection of unusual group A human rotaviruses.

Immuno-enzymatic assay employing monoclonal antibodies and viral RNA analysis by gel electrophoresis were used to classify human group A rotaviruses (HRV) into subgroups I and II. Of 249 fecal samples positive for group A rotaviruses, 29 (11%) belonged to subgroup I and 215 (85%) were identified as subgroup II. Two samples (Ro-302 and Ro-500) contained mixed infections of the two subgroups. Three isolates belonged to neither one of the two subgroups, but they did not yield enough viral RNA to allow their classification. One subgroup I isolate (Ro-1845) contained components typical of subgroup II viruses in that it was identical to serotype 3 and yielded RNA with fast-moving 10th and 11th segments. After growth in culture, the two mixed infections yielded subgroup II viruses, which were identified as serotype 1. The three unclassified isolates grew poorly in culture and could not be further analyzed. The subgroup I isolate (Ro-1845) grew well in culture and yielded virus similar to the original one.