Norwalk virus gastroenteritis among Israeli soldiers: lack of evidence for flyborne transmission.

BACKGROUND: Paired sera collected from subjects before and after a fly-control intervention trial conducted in the Israel Defense Force (IDF) were tested for seroconversion to Norwalk virus (NV) to examine the role of NV as a cause of diarrhea in this population and to ascertain whether flies might also be implicated in transmission. MATERIALS AND METHODS: An enzyme-linked immunosorbent assay (ELISA), using recombinant NV capsid proteins (rNV) as antigen was employed to determine the seroconversion rate in a sample of 444 subjects. RESULTS: During 11-week field training cycles, 18% of IDF soldiers who were tested had an NV infection defined as a > or = 4-fold rise in antibody, yielding a cumulative incidence of nearly one infection (0.95) per soldier per year. The rate of seroconversion was nearly twice as high among soldiers who recalled having diarrhea as among those who did not, but the rates did not differ significantly between soldiers in the fly intervention areas and those in the control areas. CONCLUSION: NV is a common cause of enteric infections and diarrhea among Israeli soldiers who serve under field conditions, but unlike infections with Shigella and enterotoxigenic Escherichia coli, transmission of NV cannot be interrupted with an aggressive program of fly-control.

Prospective cohort studies of shigellosis during military field training.

Epidemiological and clinical features of shigellosis occurring among cohorts of Israeli recruits followed-up for 3-6 months during the summer field training of years 1993-1997 were studied. The incidence rate of culture-proven shigellosis was the highest (78 cases per 1,000 recruits) in 1996 and the lowest (13 cases per 1,000 recruits) in 1995. Shigella sonnei (152 isolates) and Shigella flexneri (151 isolates) were the most common species. Fifty percent of the patients with shigellosis had fever (>37.5 degrees C), compared to only 18% of the subjects with other diarrheal diseases (P < 0.001). The duration of illness was longer among subjects with shigellosis than among those with other diarrheal diseases (P < 0.001). Illness due to Shigella flexneri was more severe than illness caused by Shigella sonnei.

Cryptosporidium infection in Bedouin infants assessed by prospective evaluation of anticryptosporidial antibodies and stool examination.

An enzyme-linked immunosorbent assay system using oocyst lysate as antigen was used to detect serum- specific antibody responses to Cryptosporidium parvum between 1989 and 1994 in consecutive sera obtained at birth, and at the age of 6, 12, and 23 months, from 52 infants living in a Bedouin town located in the south of Israel. The serologic tests revealed high levels of immunoglobulin G anti-Cryptosporidium at birth that dropped significantly by the age of 6 months and then rose continuously to a geometric mean titer of 481 at age 23 months. The serum immunoglobulin M Cryptosporidium antibodies rose continuously from nearly undetectable levels at birth to a geometric mean titer of 471 (157-fold increase) at age 23 months. All the subjects already showed at 6 months a significant rise in immunoglobulin M. A significant rise in immunoglobulin A titers was detected in 48% and 91% of subjects at 6 and 23 months, respectively. By monthly surveillance, microscopy using the modified Ziehl-Neelsen method and confirmed by indirect immunofluorescence assay detected Cryptosporidium antigens in only 11% at age 6 months and 48% at age 23 months. The extent of exposure to Cryptosporidium immediately after birth as detected by serology is much higher than that predicted by frequent prospective assessment of stool samples.

Safety and immunogenicity of two different lots of the oral, killed enterotoxigenic escherichia coli-cholera toxin B subunit vaccine in Israeli young adults.

Enterotoxigenic Escherichia coli (ETEC) is one of the leading causes of diarrhea among Israeli soldiers serving in field units. Two double-blind placebo-controlled, randomized trials were performed among 155 healthy volunteers to evaluate the safety and immunogenicity of different lots of the oral, killed ETEC vaccine consisting of two doses of whole cells plus recombinantly produced cholera toxin B subunit (rCTB). The two doses of vaccine lot E005 and the first dose of vaccine lot E003 were well tolerated by the volunteers. However, 5 (17%) vaccinees reported an episode of vomiting a few hours after the second dose of lot E003; none of the placebo recipients reported similar symptoms. Both lots of vaccine stimulated a rate of significant antibody-secreting cell (ASC) response to CTB and to colonization factor antigen I (CFA/I) after one or two doses, ranging from 85 to 100% and from 81 to 100%, respectively. The rate of ASC response to CS2, CS4, and CS5 was slightly lower than the rate of ASC response induced to CTB, CFA/I, and CS1. The second vaccine dose enhanced the response to CTB but did not increase the frequencies or magnitude of ASC responses to the other antigens. The two lots of the ETEC vaccine induced similar rates of serum antibody responses to CTB and CFA/I which were less frequent than the ASC responses to the same antigens. Based on these safety and immunogenicity data, an efficacy study of the ETEC vaccine is under way in the Israel Defense Force.

Immunity to varicella zoster virus in young Israeli adults.

BACKGROUND: Chickenpox is a highly contagious childhood infection caused by varicella zoster virus, a virus of the herpes family. Although a mild and self-limiting disease in otherwise healthy children, chickenpox can be a complicated and even life-threatening disease in adults, pregnant women and immunosuppressed individuals. Among infants whose mothers had varicella during the first trimester of pregnancy, 2-3% will develop a congenital VZV syndrome that includes a combination of scarring, limb deformation, central nervous system impairment and ocular injury. In 1974, a live attenuated virus vaccine against VZV was developed in Japan and has been thoroughly tested for safety, efficacy and long-term effects. In March 1995 the vaccine was licensed in the U.S. for use in healthy children only. OBJECTIVES: To determine the rate of immunity to VZV in young Israeli adults. METHODS: On the assumption that a randomly picked sample of 18-year-old army recruits in Israel is representative of the general Jewish population, 900 sera samples were taken for 3 years (1985,1988,1992). The sera were analyzed for IgG to VZV with a commercial ELISA kit using microwells coated with VZV antigens. RESULTS: A total of 98% of the samples tested positive for VZV antibodies. The difference in serologic values between the recruitment years was not statistically significant. CONCLUSION: The majority of the Israeli population reaches adulthood already immunized against VZV, with immigrants having slightly lower immunity rates. Nonetheless, a few dozen cases of chickenpox are diagnosed in the IDF annually. These data should be taken into account when a vaccination program is devised. Should such a program be implemented, it would be interesting to repeat the serosurvey for comparison. A shift in the peak occurrence age might necessitate the administration of a booster vaccine at an older age.

Quantitative analysis of IgG class and subclass and IgA serum response to Shigella sonnei and Shigella flexneri 2a polysaccharides following vaccination with Shigella conjugate vaccines.

It has been recently reported that a conjugate vaccine composed of the O-specific polysaccharide of S. sonnei bound to Pseudomonas aeruginosa recombinant exoprotein A (rEPA) conferred 74% protection against S. sonnei shigellosis. In the present study affinity purified Shigella antibodies were used as standards to quantify and characterize the serum antibody response to vaccination with Shigella sonnei or Shigella flexneri 2a polysaccharide conjugated to rEPA. The geometric mean concentrations of antibodies at the pre-vaccination stage were 3.8 microg/ml for IgG anti-S. sonnei LPS and 11.26 microg/ml for IgG anti-S. flexneri 2a LPS. Vaccination with S. sonnei-rEPA and S. flexneri 2a-rEPA induced the production of specific IgG antibodies to levels of 115.8 microg/ml and 126.5 microg/ml, respectively. The levels of specific antibodies above the pre-vaccination values persisted for at least 2 years. The IgG response to S. flexneri 2a-rEPA conjugate was almost entirely represented by the IgG2 subclass. The concentration of IgG1 anti-S. sonnei LPS was significantly higher than that of IgG2 14 days after vaccination with the homologous conjugate, but decreased to similar levels to those of IgG2 6, 12 and 24 months after immunization. Since the only difference between the S. sonnei and S. flexneri 2a conjugates lies in the different polysaccharides of the two Shigella serogroups (the protein rEPA, is identical in both cases), it follows that the different pattern of IgG subclass response is a result of the different structures of the two O-polysaccharides of S. sonnei and S. flexneri 2a.

Prevalence of antibodies to West Nile fever, sandfly fever Sicilian, and sandfly fever Naples viruses in healthy adults in Israel.

BACKGROUND: The arbovirus infections West Nile fever (WNF) and sandfly fever (SFF) are both endemic in the Middle East. Despite the fact that the mosquito and sandfly vectors of these viruses are still found in Israel, SFF has not been reported since 1948, whereas outbreaks of WNF occur periodically. It is suspected that some of the cases of nonspecific febrile illnesses in Israel may in fact be either WNF or SFF. AIM: To determine the extent of past arbovirus infections in subgroups of Israeli soldiers. METHODS: Sera from random samples of three groups of healthy soldiers aged 18-20 (n=273), 21-30 (n=497), and 40-55 years (n=285) were examined for IgG and IgM antibodies to West Nile virus (WNV), sandfly fever Sicilian virus (SFSV), and sandfly fever Naples virus (SFNV), using an ELISA method. RESULTS: The prevalence of antibodies increased with age for all three viruses examined, and ranged from 7.0%, 0, and 2.8%, for WNV, SFSV, AND SFNV, respectively, in soldiers aged 18-20 years, to 41.9%, 23.7%, and 30.8%, in those aged 40-55 years. The percentage of seropositives for IgG who were also IgM positive were 1.0%, 5.9%, and 3.4%, for WNV, SFSV, AND SFNV, respectively. 17.5% of the seropositives for WNV were also positive for SFSV, as compared with 5.7% among the WNV-seronegatives. Among the seropositives for WNV, 23.99% were positive for SFNV, compared with 9.1% of WNV seronegatives. 48.2% of seropositives for SFSV were positive for SFNV, as compared with 8.4% for SFSV-seronegatives. In the age agroup 40-55 years, there were significantly higher prevalence rates in those born in Israel compared with those born abroad. CONCLUSIONS: There is still significant exposure to WNV, SFSV, and SFNV in Israel. Arborviruses are probably responsible for many cases of non-specific febrile illness in this region.

Characterization and quantitative analysis of serum IgG class and subclass response to Shigella sonnei and Shigella flexneri 2a lipopolysaccharide following natural Shigella infection.

The IgG subclass response to Shigella sonnei and Shigella flexneri 2a lipopolysaccharide (LPS) was examined in subjects naturally exposed to these organisms. Affinity-purified LPS antibodies obtained using a column of Shigella LPS bound to epoxy-activated Sepharose 6B were used as standards to calibrate the serum antibody response to natural Shigella infection. The geometric mean concentrations of specific IgG in sera from those not exposed to Shigella organisms were 7.9 microg/mL against S. sonnei LPS and 18.6 microg/mL against S. flexneri 2a LPS. After natural exposure to S. sonnei or S. flexneri 2a, the concentrations rose to 30.3 and 127.9 microg/mL, respectively. IgG2 was the major component in the anti-S. flexneri subclass response, while the anti-S. sonnei response was dominated by IgG1. High levels of IgG1 antibodies before exposure to organisms from either Shigella serogroup correlated with a lower risk of developing symptomatic infection.

Double-blind vaccine-controlled randomised efficacy trial of an investigational Shigella sonnei conjugate vaccine in young adults.

BACKGROUND: The aim of this double-blind randomised vaccine-controlled trial was to assess the efficacy of a conjugate vaccine composed of Shigella sonnei O-specific polysaccharide bound to Pseudomonas aeruginosa recombinant exoprotein A (S sonnei-rEPA) and of an oral, live-attenuated Escherichia coli/S flexneri 2a (EcSf2a-2) hybrid vaccine among military recruits in Israel at high risk of exposure to Shigella spp. We report here our preliminary findings on the efficacy of S sonnei-rEPA; we have not documented sufficient cases to assess the efficacy of EcSf2a-2. METHODS: Between April, 1993, and August, 1994, male Israeli Military recruits aged 18-22 years were asked to take part in our study. We enrolled 1446 soldiers from seven separate field sites (groups A-G). Soldiers were randomly allocated one injection of S sonnei-rEPA and four doses of oral placebo (n = 576), four oral doses of EcSf2a-2 and one injection of saline placebo (n = 580), or one injection of meningococcal tetravalent control vaccine and four doses of oral placebo (n = 290). Because there were no cases of S flexneri 2a, the EcSf2a-2 and meningococcal vaccines were the control group. We defined S sonnei shigellosis as diarrhoea with a positive faecal culture for S sonnei. Each group of soldiers was followed up for 2.5-7.0 months. The primary endpoint was protective efficacy of S sonnei-rEPA against S sonnei shigellosis. FINDINGS: Cases of culture-proven S sonnei shigellosis occurred in four groups of soldiers (groups A-D), which comprised 787 volunteers (312 received S sonnei-rEPA, 316 received EcSf2a-2, and 159 received meningococcal control vaccine). In groups A-C, cases of shigellosis occurred 70-155 days after vaccination, whereas in group D cases occurred after 1-17 days. In groups A-C, the attack rate of shigellosis was 2.2% in recipients of S sonnei-rEPA compared with 8.6% in controls (protective efficacy 74% [95% CI 28-100], p = 0.006). S sonnei-rEPA also showed significant protection against shigellosis in group D (43% [4-82], p = 0.039). Prevaccination and postvaccination ELISA measurements of antibody to S sonnei lipopolysaccharide among recipients of S sonnei-rEPA showed that the vaccinees who developed S sonnei shigellosis had significantly lower serum IgG and IgA responses to the homologous lipopolysaccharide than those who did not (p = < 0.05). INTERPRETATION: One injection of S sonnei-rEPA confers type-specific protection against S sonnei shigellosis. The high antibody concentration induced by the conjugate vaccine in volunteers who did not develop shigellosis suggests that there is an association between serum antibody titre and protection.

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.

Safety and immunogenicity of investigational Shigella conjugate vaccines in Israeli volunteers.

The safety and immunogenicity of investigational conjugates, composed of the O-specific polysaccharides of Shigella sonnei and Shigella flexneri type 2a covalently bound to Pseudomonas aeruginosa recombinant exoprotein A (rEPA), were evaluated in 192 Israeli soldiers. None had significant local reactions or fever. Fourteen days after injection, 90% of S. sonnei-rEPA recipients and 73 to 77% of S. flexneri-rEPA recipients had a fourfold or greater increase in serum immunoglobulin G (IgG) and IgA anti-lipopolysaccharide (anti-LPS) levels; at 2 years, these remained higher than at prevaccination (P < 0.01). There was a fourfold or greater increase in IgM anti-LPS in 20% of vaccinees at 2 weeks, but levels returned to prevaccination values at 6 to 12 months. IgG was the highest and most sustained class of LPS antibodies. Reinjection at day 42 did not boost antibody levels. Eighteen of 23 (78%) who received S. sonnei-rEPA and 13 of 19 (68%) who received S. flexneri-rEPA. had significant IgA-secreting cell responses. Significant IgG antibody-secreting cell responses were detected in 19 of 23 (83%) and 11 of 19 (58%) volunteers following vaccination with S. sonnei-rEPA and S. flexneri 2a-rEPA, respectively. On the basis of these data, further evaluation of the Shigella conjugates for protective efficacy in field trials in Israel was started.

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.

Detection of antibodies to Shigella lipopolysaccharide in urine after natural Shigella infection or vaccination.

The purpose of the present study was to explore the possibility of detecting antibodies to Shigella sonnei lipopolysaccharide (LPS) in urine after infection or vaccination. Urinary immunoglobulin A (IgA) and IgG antibodies and specific IgA secretory protein against S. sonnei LPS were measured by enzyme-linked immunosorbent assay (ELISA), after adjustment for urine concentration. A significant antibody level was defined as one above a cutoff value calculated from the geometric mean + 2 standard deviations of urinary anti-S. sonnei LPS levels in 43 healthy hepatitis B vaccinees (controls). Of 11 culture-proven cases of S. sonnei shigellosis, at convalescence 9 (82%) had significantly elevated levels of urinary antibodies to the homologous LPS. The S. sonnei conjugate vaccine, composed of S. sonnei O-specific polysaccharide covalently bound to recombinant exoprotein A of Pseudomonas aeruginosa, elicited a significant urine IgA or IgG anti-LPS response in 60% (6 of 10), 56% (9 of 16) 43% (16 of 37), and 14% (3 of 21) of the volunteers at 2 weeks, 6 weeks, 6 months, and 12 months after vaccination, respectively. The specificity of the urine antibody response to S. sonnei LPS was documented by the total lack of response in subjects who received parenteral Shigella flexneri 2a-recombinant exoprotein A conjugate (69 urine samples) or meningoccal tetravalent control vaccines (4 urine samples). All the volunteers who lacked a significant response to S. sonnei LPS in serum also lacked such response in urine samples. Seventy-four percent of the volunteers with a significant IgA or IgG anti-LPS response in serum at convalescence or 14 days after vaccination showed a similar response in urine. The ratio of the titer of secretory protein bound to IgA anti-S. sonnei LPS in urine to that in serum was 303 times higher than the ratio of anti-S. sonnei LPS total IgA titer in urine to that in serum, indicating that the urine IgA is of secretory origin. These findings suggest the possible use of urinary Shigella LPS antibodies as markers of systemic and secretory immune responses after natural infection or vaccination. At this stage, because of its limited sensitivity, the detection by ELISA of Shigella LPS antibodies in urine cannot replace the same assay in serum as a definitive test in an individual with a negative result.

Ethnic differences in the prevalence of anti-hepatitis C antibodies and hepatitis B surface antigen in Israeli blood donors by age, sex, country of birth and origin.

The presence of anti-hepatitis C virus (HCV) antibodies frequently indicates both persistent infection and infectivity. Consequently, blood donors found to be anti-HCV positive, are excluded from the donor pool. The aim of this study was to compare age, sex and ethnic differences in the prevalence of anti-HCV antibodies with that of hepatitis B surface antigen (HBsAg) among immigrant and Israeli-born blood donors. Anti-HCV antibodies were assayed by a second-generation enzyme-immunoassay (EIA) and HBsAg by a standard EIA in a sample of 136,977 blood donors in Israel during 1992. The overall age-adjusted prevalence of anti-HCV antibodies was 0.66% in men and 0.55% in women, and for HBsAg, 0.85% and 0.44%, respectively. There was a significant increase in the prevalence of anti-HCV antibody with age, and significant differences by country of birth, with the highest prevalence found among those born in the former USSR and eastern Europe. This contrasted with the findings for the prevalence of HBsAg, where the highest rates were among those born in northern Africa. Among Israeli-born donors, differences in the prevalence of anti-HCV antibodies by parental country of origin were minimal and much less than for HBsAg. Hence the prevalence of anti-HCV antibodies in Israel is strongly associated with age and country of birth but not with country of origin. There is little evidence of substantial vertical or intrafamilial transmission of HCV infection in Israel.

The effect of using short versus detailed self-administered questionnaires on the estimate of illicit drug use among young adults.

We compared two study instruments in use in the Israel Defence Forces to ascertain the prevalence of illicit drug use: a short versus a detailed self-administered anonymous questionnaire. A relatively lower estimate of illicit drug use was found among subjects that answered the short questionnaire. The difference was noted for lifetime prevalence of illicit drug use for women but not for men (6.5% of women reported ever use of illicit drugs using the detailed questionnaire versus 2.1% of women using the short questionnaire, p = 0.002); for prevalence of infrequent illicit drug use (3.3% of men and 3.4% of women reported less than monthly use of illicit drugs using the detailed questionnaire versus 0.2% of men and none of the women with the short questionnaire; p = 0.004 and p < 0.001, respectively), but not for frequent use (i e monthly or more). There was no difference in the percent of subjects that admitted that they knew where to get drugs. We conclude that the short questionnaire in routine use for more than a decade is a useful instrument when compared with the detailed questionnaire, in that the yield of important information such as frequent illicit drug use is similar. This is achieved with the benefit of greater convenience and ease of application to large samples at a lower cost.

Safety and immunogenicity of the oral E. coli K12-S. flexneri 2a vaccine (EcSf2a-2) among Israeli soldiers.

A double-blind placebo-controlled study was carried out on the safety and immunogenicity of the oral Shigella flexneri (EcSf2a-2) vaccine among Israeli soldiers. Sixty volunteers received the vaccine and 59 received placebo. Fifty-three were given the full vaccine regimen (four doses). Doses ranged between 4.1 x 10(8) and 1.1 x 10(9) c.f.u. Visits to the unit clinic for mild gastrointestinal symptoms were common after the first dose in vaccinees (13%) as compared with placebo recipients (5%), but the difference was not significant, p = 0.12. Similarly, there was no difference between the groups for either gastrointestinal or non-gastrointestinal complaints reported by questionnaire. The vaccine strain was excreted by 69% and 67% of the vaccinees one day after receiving the second and the fourth doses, respectively. As judged by antibiotic susceptibility, phage typing and restriction fragment length polymorphism (RFLP), the vaccine strain emerged as genetically stable after replication in human gut and shedding. There was neither bacteriological nor serological evidence of transmission of the vaccine from vaccinees to placebo recipients. Eighteen of 26 (69.2%) and 11 of 30 (36.7%) vaccinees had significant IgA secreting cell responses 7 and 21 days after the first dose, respectively. Significant IgA or IgG serum antibody response to S. flexneri 2a LPS was detected in 30% of the vaccinees. These results support further evaluation of EcSf2a-2 vaccine protective efficacy in field studies.

Incidence of diabetes mellitus in various population groups in Israel (1989 and 1990).

A prospective survey of all newly diagnosed insulin-dependent diabetes mellitus (IDDM) children and adolescents aged 0-17 years in Israel was conducted for the years 1989 and 1990. All diabetic clinics in Israel treating young diabetics were contacted and they returned written reports to us. Each clinic was also visited regularly by a member of the team who reviewed the individual charts to obtain data on population origin as well as medical and demographic data. A total of 187 patients were identified (164 Jews and 23 Arabs), giving a total incidence rate of 5.46/10(5). Analysis of the incidence rates by population groups showed that Arabs and Jews originating in Asia had the lowest incidence (2.77 and 4.58/10(5) respectively), followed by Jews whose fathers were born in Israel (5.61/10(5)). The highest incidence was registered for Jews originating from Europe and North America (9.34/10(5)). The female-to-male preponderance ratio was higher in the Jews originating in Asia (2.1) than in Jews originating in Europe and North America (1.2). Comparing the present data with a survey performed for the years 1975-80 we found a statistically significant increase in incidence in all population groups. Our findings strongly suggest an influence of genetic factors on the incidence of childhood IDDM.

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.

Long-term persistence of anti-diphtheria toxin antibodies among adults in Israel. Implications for vaccine policy.

Vaccination against diphtheria has essentially led to the disappearance of the disease in Israel. However, in other countries with high immunization coverage, isolated cases and small outbreaks have occurred in adults. Immunity following vaccination or natural exposure to toxigenic strains of C. diphtheriae is conferred by serum antibodies to diphtheria toxin. Since booster doses of diphtheria toxoid are recommended every ten years in adults, this raises the question of persistence of protective levels of anti-diphtheria toxin antibodies. In this study we assessed a possible age-related decline in anti-diphtheria toxin antibodies among adults in Israel. The study population comprised random samples in three age groups: 263 male recruits aged 18-19 years, 116 male reserve soldiers aged 25-35 years and 153 aged 41-51 years. Anti-diphtheria toxin antibody levels were measured by means of ELISA. Results indicate that 64.3% (95% CI = 58.5-70.1%) of those aged 18-19 had anti-diphtheria toxin levels in excess of 0.1 IU ml-1, whereas the corresponding figures for ages 25-35 and 41-51 were 32.8% (95% CI = 24.2-41.3%) and 15% (95% CI = 9.4-20.7%). However, even in the oldest age group, 95.4% (95% CI = 90.8-98.1%) had antibodies above the presumed protective level of 0.01 IU ml-1. Although these results indicate a significant age-related decline in anti-diphtheria toxin antibodies in vaccinated subjects, most had apparently protective levels. The absence of cases suggests that vaccine-induced immunity is long-lasting. However the immune status of the population should be carefully monitored.