West Nile fever in Israel 1999-2000: from geese to humans.

West Nile virus (WNV) caused disease outbreaks in Israel in the 1950s and the late 1970s. In 1998 an outbreak of WNV in goose farms and evidence of infection in dead migratory birds were reported. Consequently, human diagnostic services for WNV were resumed, including virus isolation, serology, and RT-PCR. Risk factors for infection were assessed by a serological survey in 1999, which revealed a seroprevalence of (a) 86% in people who had close contact with sick geese, (b) 28% in people in areas along bird migration routes, and (c) 27% in the general population. Following two fatal cases in Tel Aviv in September 1999 and one encephalitis case in the southern Eilot region, a regional serological survey was initiated there. The survey revealed two more WNV-associated acute encephalitis cases, an IgG seroprevalence of 51%, and an IgM seroprevalence of 22%. In the summer of 2000, acute cases of WN disease were identified in the central and northern parts of Israel, involving 439 people. The outbreak started in mid-August, peaked in September, and declined in October, with 29 fatal cases, primarily in the elderly. During the outbreak, diagnosis was based on IgM detection. Four virus isolates were subsequently obtained from preseroconverted frozen sera. Sequence and phylogenetic analysis of 1662 bases covering the PreM, M, and part of the E genes revealed two lineages. One lineage was closely related to a 1999 Israeli bird (gull) isolate and to a 1999 New York bird (flamingo) isolate, and the other lineage was closely related to a 1997 Romanian mosquito isolate and to a 1999 Russian human brain isolate.

Gender differences in the reactogenicity of measles-mumps-rubella vaccine.

BACKGROUND: In trials comparing different formulations of measles vaccine, excess non-specific mortality occurred in female children who received high titer vaccine. These findings suggest a gender-specific effect of measles vaccine. OBJECTIVES: To determine whether gender differences exist in the rates of adverse reactions and morbidity in the month following immunization with measles-containing vaccine, and to evaluate whether there is a gender-specific association between the humoral immune response to measles vaccination and post-vaccination morbidity. METHODS: Parents completed questionnaires on the health status of 755 infants aged 15-20 months, during the month preceding and the month following the measles-mumps-rubella vaccination. Blood samples were tested for measles antibody titers in a subsample of 237 infants. RESULTS: After controlling background morbidity in the infants, the relative risk of fever and rash following vaccination was 2.35 in females and 1.36 in males. The geometric mean antibody titers against measles were similar in both sexes and there was no significant association between antibody titer and post-vaccination morbidity in either sex. CONCLUSIONS: Our findings demonstrate higher rates of adverse effects in females following vaccination with MMR vaccine, irrespective of the humoral response. This study emphasizes the need to consider possible gender differences when evaluating new vaccines.

Measles immunity and response to revaccination of a young adult population in Israel.

In order to evaluate the true immune status and the effect of revaccination on a young adult population, we collected serum samples from 289 military recruits who were vaccinated during an outbreak in 1991. Most vaccinees, age 18-25 years, had apparently been immunized once before as infants. Sera collected just prior to the vaccination and 14 and 28 days afterwards were tested for measles antibodies by hemagglutination inhibition (HI) and enzyme-linked immunosorbent assay (ELISA)-IgM. Before vaccination, 46 (15.9%) of the subjects had no HI antibodies, (< 1:4) and 48 (16.6%) had borderline (1:4) HI titer. Following vaccination, only ten (3.5%) remained negative and 19 (6.6%) had borderline titer. The increase in HI antibody titer was inversely proportional to the prevaccination titer, and 159 subjects (55.0%) showed no increase at all. The geometric mean titer (GMT) rose from 9.14 to 21.47. Among the prevaccination-negative subjects (HI < 1:4) 28 (60.9%) reached a postvaccination titer of > or = 1:8, and eight (17.4%) reached a titer of 1:4. Twelve (26.1%) of the negative subjects seroconverted and developed IgM, 16 (35%) seroconverted without IgM, and 18 (39%) remained negative and did not develop IgM. A group of eight vaccinees with prevaccination titer of > or = 1:4 developed IgM. Some were probably infected by the circulating wild-type virus prior to the vaccination. Thus, a total number of 20 of the 289 subjects studied (6.9%) had true negative preimmune status as judged by the IgM test. However, the vaccination campaign prevented further measles cases, apparently by increasing the population's immunity, particularly in individuals with very low titers or without measles antibodies.

Determination of immunity to measles virus in young adults: comparative evaluation of a commercial enzyme immunoassay and the hemagglutination inhibition techniques.

BACKGROUND: Determination of the immune status against measles in young adults requires careful evaluation of the laboratory methods because of waning immunity. The hemagglutination inhibition (HI) test and enzyme-linked immunosorbent assay (ELISA) may lack the sensitivity required to detect very low levels of antibodies. In addition, the correlation between ELISA-IgG assays and the degree of protection from measles is not well defined. OBJECTIVES: (a) Evaluation of a commonly used measles ELISA-IgG test kit in comparison with the hemagglutination inhibition (HI) test which corresponds strongly to virus neutralization; (b) determination of false negative rates of the ELISA-IgG and the HI tests; (c) evaluation of the ELISA-IgG test kit as a quantitative assay. STUDY DESIGN: One hundred and eighty serum samples collected from 60 vaccinated young adults immediately before vaccination and 14 and 28 days postvaccination, were tested comparatively by HI and by a commercial ELISA-IgG kit. For evaluation of false negative rates, postvaccination sera of a cohort of 48 vaccinees with negative HI or ELISA-IgG prevaccination sera were tested for IgM. Sixty-three of the samples were also titrated by the ELISA-IgG kit using serial dilutions, for comparison with HI titers. RESULTS: Using the HI test as a reference method, the ELISA-IgG kit was found to have overall accuracy of 81%, sensitivity of 80% and specificity of 84%. The false negative and the false positive rates were 20% and 16%, respectively. In contrast, when we used postvaccination IgM test to distinguish between true and false prevaccination negatives in both the HI and ELISA-IgG tests, we found that the false negative rates were 75.6% by ELISA and 72.5% by HI, and false positive rates were 2.4% and 0%, respectively. Serum titers determined by the ELISA-IgG test were generally 5-10-fold higher than the corresponding HI titers, but without a consistent correlation. CONCLUSIONS: Both the ELISA-IgG and the HI tests frequently failed to detect residual immunity. The two tests also did not correlate well with each other suggesting that different antigenic determinants of the virus are involved in each assay and therefore the HI test should not be used as a reference method for evaluation of the sensitivity of ELISA IgG kits.

Decay of maternally derived measles antibody in a highly vaccinated population in southern Israel.

The introduction of live attenuated measles vaccine in Israel during 1967 dramatically decreased the incidence of measles. However, cases still occur in periodic outbreaks and epidemics, with an increasing proportion of infants and children younger than 2 years of age. We examined the decay of maternally derived measles antibody during the first year of life in the Jewish population of Israel which represents a highly vaccinated population with immunization rates exceeding 90%. We used sera of healthy full term infants born in 1988 and 1989. Fifty specimens for each of the following age groups were used: 0 (cord blood), 2, 4, 6, 7 and 12 months. Three assays for each specimen were used: enzyme-linked immunosorbent assay (ELISA); hemagglutination-inhibition test (HI); and neutralization test (NT). Good correlation among all 3 tests was found. All cord blood specimens were positive by at least 2 assays. Seropositivity rates declined rapidly with age. Fifty percent of all 4-month-old infants and < 30% of all 6-month-old infants were positive by 1 test or more; at 12 months of age none of the tested specimens was positive by HI or NT and only 1 of 50 infants was positive by ELISA. In infants younger than 6 months of age, 5 (22%) of 23 specimens negative both by ELISA and by HI were positive by NT, but in 6-month-olds, only 2 (7%) of 28 negative by ELISA and HI were positive by NT, and in 12-month-olds none was positive. The results from southern Israel are similar to those obtained in North America and provide evidence that infants older than 6 months of age in a well-immunized population may be poorly protected against measles. On the basis of this information and epidemiologic data, the Israel Ministry of Health has recommended lowering the immunization age for measles, mumps and rubella from 15 months to 12 months.

[An unusual case of subacute sclerosing panencephalitis].

A 25-year-old man was admitted following deterioration in behavior and onset of blindness. He soon became comatose and died 6 weeks later. Brain biopsy showed nuclear inclusion bodies resembling viral capsids, astrocytosis and perivascular lymphocytic cuffing but no demyelination. The diagnosis of subacute sclerosing panencephalitis was made on finding: measles virus antigens in both serum and cerebrospinal fluid, the identification of measles RNA sequences in brain tissue by the polymerase chain reaction, and intense, oligoclonal, IgG-banding in the CSF. However, the relatively advanced age of the patient, the absence of myoclonus and the nondistinctive EEG profile lacking synchronous bursts of high-voltage slow and sharp waves, are unusual.

Sex differences in the humoral antibody response to live measles vaccine in young adults.

BACKGROUND: Following vaccination of children using high-titre live measles vaccine, excess non-specific mortality was reported, particularly among females. Since vaccination with live measles virus results in a temporary depression of the immune response to other antigens, the female predominance in subsequent non-measles mortality may be due to sex differences in response to live measles vaccines. METHODS: In this study, the immunogenicity of standard titre live Schwarz strain measles vaccine was examined 2 and 4 weeks post-vaccination in 223 males and 66 female aged 18-20 years in Israel in 1991. RESULTS: Females had higher post-vaccination geometric mean titre (GMT) at all levels of pre-vaccination titres at both 2 and 4 weeks. Furthermore, after controlling for differences in pre-vaccination titres, overall the post-vaccination GMT for females was about 50% higher than for males (P < 0.001). CONCLUSIONS: These findings indicate that females exhibit a stronger humoral immune response to measles vaccine. Possible sex differences in immunosuppression following measles vaccination should be explored.

Measles immunity in Israeli young adults: effects of second immunization at 18 years of age.

Measles morbidity and mortality in Israel have declined since the introduction of routine vaccination, even though measles continues to occur in epidemic cycles. In this study we examined the antibody response to measles revaccination, and the effect of prior administration of immune serum globulin (ISG) on the antibody response to measles vaccine. A study group of 312 young adults in army service received the Schwartz strain measles vaccine. Serum antibody levels were studied prior to vaccination and 2 and 4 weeks after vaccination. The finding of this study show that: a) booster response occurs in those vaccinees shown to have low or undetectable prerevaccination titers of measles antibodies; b) there is no effect of administration of ISG, prior to vaccination, on the antibody response to measles vaccine; and c) at the present level of immunity to measles in the Israeli adolescent population, we still may witness periodic epidemics in populations at risk.

Cardiovascular haemodynamics of oriental hornet venom sac extract.

The effects of hornet venom sac extract on the functioning of the cardiovascular system was assessed in dogs by concomitant examination of the following parameters: Systemic blood pressure, blood pressure and the dp/dt derivative of the left ventricle of the heart, heart rate, direct measurement of the left ventricular wall thickness, cardiac output, and body temperature. The effect of adult hornet venom sac extract on the canine cardiovascular system was rapid and led to a sharp drop in the systemic blood pressure, a similar drop in the pressure and dp/dt derivative in the left ventricle, to bradycardia, immediate thickening of the left ventricular wall and to an immediate rise in the cardiac output. As for the canine temperature, this dropped immediately following the administration of venom sac extract and remained at the new low level for at least 30 min. The smaller molecular weight components (less than 10 kilodalton) in venom sac extract have been found to be responsible for the immediate effects of venom sac extract on the cardiovascular system. On the other hand the high-molecular weight components exert more delayed effects which lead to a cumulative disturbance of cardiac function.

Mastoparan induces hypothermia in mice.

The polypeptide mastoparan, isolated from the venom of the Oriental Hornet, Vespa orientalis, induces hypothermia in white mice 15 minutes after its intraperitoneal injection. The hypothermic effect is induced by mastoparan obtained from different hornet and wasp venoms. The normal murine core temperature is lowered by mastoparan from 38 degrees C to as far as 33 degrees C. This lowering lasts for one hour and is reversible.