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Inactivated hepatitis A virus (HAV) vaccine is given in a three-dose schedule. When rapid protection is needed, injection of immune globulin (IG) concomitantly with the first dose could provide passive protection until adequate active antibody response has developed. A possible effect of IG on the immune response to the vaccine was studied in healthy volunteers; 28 received vaccine alone, and 34 received the first dose simultaneously with 5 mL of IG. A control group received hepatitis B vaccine, and a fourth group received IG alone. Four weeks after the first vaccine dose, all subjects had detectable ELISA anti-HAV antibodies. Several weeks after each vaccine dose, the geometric mean titer of antibodies was significantly lower in those who received vaccine with IG but higher than in those who received IG alone. Results for neutralizing antibodies yielded a similar trend. If IG is given with HAV vaccine, a further booster vaccine dose may be required to ensure long-lasting immunity.

The likelihood of an epidemic of measles in 1990-92 in Israel prompted us to study the immune status against measles in a random sample of 454 recruits aged 18-19 years in order to obtain data that might be used in determining vaccination policy. This cohort had received one dose of measles vaccine at 12 months of age. The measles immunity status was studied by determination of antibody values that were measured by means of an enzyme-linked immunosorbent (ELISA) IgG antibody test. Of the recruits, 84.6% were found to have positive sera for anti-measles IgG antibodies, while 13.7% had negative sera. Eight (1.7%) subjects had borderline results. The results of this study indicate the need to administer a second dose of measles vaccine at an older age in addition to the MMR (measles, mumps, rubella) vaccine that is now given in Israel at 12 months of age. This step will help achieve the World Health Organization's target of complete eradication of measles.

Background and aims Despite the high national vaccination coverage, a large outbreak of mumps occurred in Israel, in 2009–2010, with onset and heavy transmission in ultraorthodox Jewish communities and further country-wide spread. We examined the sero-prevalence of mumps antibodies in the subpopulations subsequently affected by this large mumps outbreak, compared with the general population. Methods The study was conducted in ultraorthodox Jewish communities, in Jerusalem district (N = 251), in Bnei Brak city in Tel Aviv district (N = 453), and in the general population (N = 1846), using residual sera of 1–20 year old subjects. Mumps IgG antibodies were measured using Enzygnost anti-parotitis virus IgG ELISA kit. Results Mumps sero-positivity was significantly lower in Jerusalem: 51.8% (95% CI 51.9–61.0), and Bnei Brak: 56.5% (95% CI 45.6–57.9), than in the general population: 68.1% (95% CI 66.0–70.2). Sero-positivity increased with age, however in Jerusalem it was substantially low (46%) in the age group 10–20 years. This age group comprised a significant portion of mumps patients in the 2009–2010 outbreak. Conclusions Low immunity levels, combined with overcrowding and social mixing, were the main predisposing factors of the enhanced epidemic transmission of mumps in the ultraorthodox Jewish communities and further country-wide spread.

The relationship between H. pylori infection and anemia in childhood is still unclear. The aim of the study was to examine the association between H. pylori infection and anemia or iron deficiency in school-age children and in infants.Six- to 9-year-old Israeli Arab children (N = 202) and infants (N = 197) were examined for hemoglobin and ferritin levels. ELISA was used to detect H. pylori antigens in stool specimens collected from the participants. Household characteristics were obtained through personal interviews with the mothers.The prevalence of anemia was 15.5 versus 5.5% in H. pylori-positive and -negative school-age children, respectively and 34.5 versus 29.8% in H. pylori-positive and -negative infants, respectively. The Mantel-Haenszel age-adjusted prevalence ratio (PR) and 95% confidence intervals (CIs) were 1.6 (95%CI 1.0, 2.6). In multivariate analysis controlling for socioeconomic variables, H. pylori infection was associated with 2.8 higher prevalence of anemia only in school-age children: adjusted PR 2.8 (95% CI 0.9, 9.3). The adjusted mean difference in hemoglobin levels between H. pylori infected school-age children and uninfected ones was -0.372 gr/dL (95% CI -0.704, -0.039) (p = .04). The respective mean ferritin difference was -6.74 μg/L (95% CI -13.38, -.011) (p = .04). Such differences were not found in infants.H. pylori infection is associated with higher prevalence of anemia in school-age children independently of socioeconomic variables. Such association was not observed in infants. These findings are of clinical and public health importance.

We examined the uptake of rotavirus vaccine and its effectiveness in preventing acute gastroenteritis (AGE) in the community. Data on rotavirus vaccines purchases and AGE were extracted from the computerized database of a large health maintenance organization in Israel. The incidence of AGE requiring a physician visit during 2008–09 rotavirus season among vaccinated and non-vaccinated children were compared, and vaccine effectiveness was calculated as: (1 − Relative Risk) × 100. During the study period, the uptake of rotavirus vaccine (mostly monovalent) reached 55.1% (N = 19,108) of the studied cohort. The risk of AGE requiring a physician visit was 23.2% and 46.4% among vaccinated and unvaccinated children, respectively, yielding an effectiveness of 50.1% (95% CI: 47.5%, 52.6%). Rotavirus monovalent vaccine was highly effective in preventing AGE in the community.

BACKGROUND Mass vaccination is the principal preventive measure against a smallpox outbreak after an act of bioterrorism. Vaccination of subjects who received immunosuppressive therapies is problematic because of smallpox vaccine reactogenicity. Moreover, long-term immunity to vaccinia might be affected. OBJECTIVE The objective of the study was to examine the effect of cytotoxic chemotherapy on long-term immunity to vaccinia. METHODS In a case-control study, 67 patients with breast cancer who received cytotoxic chemotherapy and who were disease free for at least 1 year were matched with healthy controls according to age, sex, and the number of smallpox vaccinations received. Markers of immunity to smallpox were examined. Forty-one patients with breast cancer who did not receive chemotherapy were used to assess the affect of cancer and radiotherapy on immunity to smallpox. RESULTS Patients with breast cancer who received chemotherapy had lower levels of vaccinia total immunoglobulin G and immunoglobulin G1 (expressed as enzyme-linked immunosorbent assay units per milliliter), neutralizing antibodies, vaccinia:memory B cell ratio (expressed as a percentage), and interferon-gamma level (expressed as picograms per milliliter), compared with healthy control individuals. CONCLUSIONS Immunity to smallpox is reduced after receipt of chemotherapy for breast cancer. This finding should be considered when planning smallpox vaccination campaigns. The effect of immunosuppressive treatments on persistence of immunity should be tested with respect to additional vaccines or natural infections.

SUMMARYThe DNAs ofShigella sonneiorShigella dysenteriaetype 1 strains isolated in outbrealis of shigellosis or in sporadic cases were analysed by restriction fragment length polymorphism (RFLP). Southern blots of the DNAs of 36S. sonneiisolates digested by 8 restriction enzymes were hybridized with anEscherichia colirRNA probe. TheS. sonneistrains were unexpectedly diverse in their RFLP. Antibiotypes of the same isolates showed clusters of strains corresponding to the various outbreaks. On the other hand, RFLP analysis suggested concomitant multiple sources of infection rather than a common source and thereby introduced a new insight in the epidemiology of shigellosis. RFLP was also used to traceS. dysenteriaetype 1 transmission in a recent cluster of clinical cases. Although antibiotic resistance patterns indicated the presence of more than one strain, RFLP analysis showed that the six isolates were identical clones and suggested the loss of an R episome after one person-to-person passage.

The appearance of antigen-specific immunoglobulin A (IgA) antibody-secreting cells (ASCs) following natural infection with Shigella sonnei during a common-source outbreak caused by this organism was evaluated in a modified enzyme-linked immunosorbent assay (ELISPOT). A mean IgA ASC value of 2,131.6/10(6) cells against homologous S. sonnei lipopolysaccharide (LPS) was detected in blood samples obtained from patients with bacteriologically proven S. sonnei shigellosis 5 and 10 days after the onset of disease. In the same blood samples, the level of ASC measured against heterologous antigen (Shigella flexneri serotype 2a LPS) was significantly lower than that of the homologous antigen (mean value, 33.12/10(6) cells). Furthermore, the mean number of activated B cells that secreted anti-S. sonnei LPS antibodies was significantly higher among patients with S. sonnei shigellosis than it was among patients with non-Shigella diarrhea (2.5/10(6) cells; standard error, 1.0) and healthy subjects (5.1/10(6) cells; standard error, 2.3) (P less than 0.05). The anti-LPS IgA ASC activity was easily detected within 5 days of the onset of disease, a point at which the levels of anti-S. sonnei LPS IgG and even IgA antibodies were hardly detectable in serum.

To study the determinants of amniocentesis underutilization among Israeli Arab Muslim women.Pregnant women referred for amniocentesis (n = 476) were identified through family health centers (FHCs). Data on sociodemographic characteristics, knowledge of prenatal testing, and attitudes toward termination of pregnancy (TOP) were collected through interviews and from medical records.Of all women eligible for amniocentesis free of charge, only 17.9% (95% CI: 14.7-21.6) underwent the test. Women referred as a result of advanced maternal age underwent the test less often than those referred for other indications [13.5% and 25.0%, respectively, (p = 0.002)]. In multivariate analyses, determinants for amniocentesis underutilization among women referred for advanced maternal age were: being religious [OR 2.71 (95% CI 1.04-7.01)], perceiving amniocentesis a risky procedure [OR 3.25 (95% CI 1.28-8.20)], spouse's opposing TOP [OR 3.73 (95% CI 1.48-9.37)], less advanced age [OR 0.74 (95% CI 0.58-0.94)] and being a housewife [OR 2.59 (95% CI 0.96-6.95)]. In women referred for other reasons poor accessibility [OR 5.49 (95% CI 1.50-20.05)], perceiving amniocentesis a risky procedure [OR 3.45 (95% CI 1.17-10.17)] and spouse's opposing TOP [OR 7.47 (95% CI 2.46-22.63)] were the significant determinants.Any program aimed at increasing amniocentesis uptake among Muslim women should be directed to both partners and should emphasize the low risk for miscarriage following the test.

This study was undertaken to estimate the magnitude of Bordetella pertussis infections in a highly vaccinated population in Israel in order to evaluate the relationship between clinical notification data and serology-based evidence of infection. A cross-sectional survey was conducted on a total of 1982 serum samples from the National Serum Bank, collected from January 2000 through December 2001, in order to monitor high levels of pertussis toxin (PT) IgG antibody indicative of recent B. pertussis infection, by standardized methods. The estimation yielded an infection incidence rate of 2448 per 100,000 population (≥3 years of age) for the year 2000 compared to an annual incidence of reported pertussis of 5.6 per 100,000 for the same period. The peaks of estimated incidence of infection were found in the groups of 15–19-year olds (5245 per 100,000) and older than 60 years (6469 per 100,000), whereas the majority of clinical pertussis cases were reported for the 10–14-year olds (20.5 per 100,000). The findings clearly show that despite a high vaccination coverage rate (>93%), there is still a considerable circulation of B. pertussis , particularly in adolescents and elderly. Population-based serosurveillance for pertussis offers the potential to assist interpretation of trends independent of notification and diagnostic bias.

A means for determining immune status against shigellosis would significantly improve the design and evaluation of interventional and other epidemiologic studies. Previous case-control studies have indicated the potential role of humoral antilipopolysaccharide antibodies. To test this proposition, 190 soldiers serving in a field unit were monitored prospectively for 2.5 months for shigellosis. Blood samples were taken at the beginning of the follow-up period and tested for serological evidence of prior exposure to Shigella sonnei and Shigella flexneri. The risk for acquiring S. sonnei shigellosis was 3.7 times higher for individuals lacking homologous antibodies (P less than 0.02). The risk for acquiring S. flexneri shigellosis was 2.4 times higher for individuals lacking antibodies, although a low attack rate for S. flexneri resulted in numbers too small to achieve statistical significance. While the importance of the serum antilipopolysaccharide antibodies in protection against the disease remains unclear, these findings demonstrate that they are strong markers of acquired immunity. Serological markers should be incorporated in epidemiologic studies of shigellosis and in the design and evaluation of future trials of potential anti-Shigella vaccines.

The association between various sociodemographic variables and the presence of anti-Shigella sonnei lipopolysaccharide (LPS) antibodies was examined in a random sample (N = 383) of male Israeli conscripts. Of the male conscripts, 190 (49.6%) had pre-existing antibodies against S. sonnei LPS (defined as HA titres of greater than or equal to 1:10 after treatment of sera with 2-mercaptoethanol). Univariate analysis revealed a significant positive association between the presence of humoral anti-S. sonnei LPS antibodies and sociodemographic variables including Eastern origin (p = 0.007), low socioeconomic status (p = 0.0016), and the number of siblings (p = 0.023). When multiple logistic regression was used to control simultaneously for the effects of the other variables, ethnic origin emerged as the strongest correlate of anti-S. sonnei LPS antibodies. On the other hand, the association of the sociodemographic variables in subjects suffering from S. sonnei infection during their military service, was in the opposite direction (p less than 0.001 for both socioeconomic status and ethnicity). These findings suggest differences between subpopulations in acquired immunity to S. sonnei due to differences in exposure to the homologous organism prior to military service.

SUMMARYThe European Sero-Epidemiology Network 2 (ESEN2) aimed to compare serological results of vaccine-preventable diseases across Europe. To ensure direct inter-country comparability of hepatitis A virus antibody (anti-HAV) measurements, a standardization panel of 150 sera was developed by a designated reference laboratory and tested by participating national laboratories using assays of choice; each country's results were subsequently regressed against those of the reference laboratory. Quantitatively, the assays were generally highly correlated (R2>0·90). Nevertheless, qualitative comparisons indicated that results obtained with different assays may differ despite the usage of well-established international and local standards. To a great extent standardization successfully alleviated such differences. The generated standardization equations will be used to convert national serological results into common units to enable direct international comparisons of HAV seroprevalence data. The results of this study are expected to contribute to the evaluation and potential improvement of the currently employed immunization strategies for hepatitis in Europe.

To standardize serological surveillance to compare rubella susceptibility in Australia and 16 European countries, and measure progress towards international disease-control targets.Between 1996 and 2004, representative serum banks were established in 17 countries by collecting residual sera or community sampling. Serum banks were tested in each country and assay results were standardized. With a questionnaire, we collected information on current and past rubella vaccination programmes in each country. The percentage of seronegative (4 IU/ml) children (2-14 years of age) was used to evaluate rubella susceptibility, and countries were classified by seronegativity as group I (5%), group II (5-10%) or group III (10%). The proportion of women of childbearing age without rubella protection (or = 10 IU/ml) was calculated and compared with WHO targets of5%.Only Romania had no rubella immunization programme at the time of the survey; the remaining countries had a two-dose childhood schedule using the measles, mumps and rubella (MMR) vaccine. The percentage of susceptible children defined five countries as group I, seven as group II and four as group III. Women of childbearing age without rubella protection were5% in only five countries.Despite the low reported incidence in many countries, strengthening the coverage of the routine two-dose of MMR vaccine among children is needed, especially in group III countries. Catch-up campaigns in older age groups and selective targeting of older females are needed in many countries to ensure necessary levels of protective immunity among women of childbearing age.

The existing limited data on diarrheal diseases in Israel indicate higher rates and more severe illness among Arab children compared to Jewish children.To determine the incidence and risk factors of diarrheal diseases in 3-5 year old Israeli Arab children from villages of Northern Israel.We carried out a follow-up study in 343 children who attended 9 kindergartens from 3 villages of Northern Israel. Daily surveillance was conducted on children's absenteeism from the kindergartens. The causes of absenteeism were recorded based on information received from parents' interviews. During the summer vacation, the follow-up was based on biweekly interviews. We also performed a nested case control study to identify potential risk factors of diarrheal disease; data were obtained through mothers' interviews.During the follow-up period, 100 new episodes of diarrhea were recorded yielding an incidence rate of 0.51 episodes/12 child-months, while 55% of the episodes were associated with visits to the clinic. In the multivariate analysis, the risk of diarrheal diseases was increased in males (OR 2.31 95% CI 1.3-4), in children aged 4 years or less compared to older children (OR 1.76 95% CI 1.01-3.06), and when the mother's education was 8 years or less (OR 1.88, 95% CI 1.08-3.26). Having siblings younger than 5 years old was associated with a reduced risk of diarrheal diseases (OR 0.57 95% CI 0.3-0.9).The incidence rate of diarrheal diseases among Israeli Arab toddlers attending kindergartens in villages from northern Israel is high. The risk factors of diarrheal disease in this population are significantly associated with features of the child and his family rather than environmental characteristics of the community or kindergarten.

Preexisting serum immunoglobulin (Ig) A and IgG titers against colonization factors and heat-labile toxin of enterotoxigenic Escherichia coli (ETEC) were examined in young adults who subsequently developed ETEC-associated diarrhea and in healthy matched controls. The data suggest an inverse association between the antibody titers against colonization factors, but not heat-labile toxin, and development of ETEC-associated diarrhea.

Herpes simplex virus types-1 (HSV-1) and Varicella-zoster virus (VZV) are herpes viruses that share many characteristics. However, HSV-1 spreads by close contact while VZV spreads mainly by the airborne route. In this study we compared the dynamics and correlates of transmission of these viruses in the same population. In 2000–2001, 1555 sera from an age-stratified general population sample were tested using commercial ELISA kits to measure type-specific HSV-1 and varicella IgG antibodies. The VZV seroprevalence increased rapidly with age reaching 50% seropositivity by the age of 3 years, while HSV-1 reached 50% seropositivity at the age of 14 years. The highest VZV force of infection was in the 3.5–5.5-year age group followed by the 5.5–10.5 years age group, while for HSV-1 the age specific force of infection was substantially lower and stable over the various age groups. Multivariate analysis revealed that HSV-1 seroprevalence was significantly, independently associated with age, country of birth, country of origin, ethnicity, socio-economic status and VZV sero-status. Only age, country of origin and HSV-1 sero-status were found to be associated with VZV seropositivity. In developed countries such as Israel the transmission of VZV is much quicker and less dependent on socioeconomic status as compared with HSV-1.

In its first large-scale smallpox vaccination campaign in the 20(th) century, Israel has experienced an exceptionally high rate of failure to achieve clinical take following vaccination. It was hypothesized that this failure rates might be attributed to the unique vaccination technique adopted in Israel, of using beveled needles rather than bifurcated needles.We retrospectively identified two cohorts vaccinated in the defined dates during the Israeli revaccination campaign, in which beveled needles and bifurcated needles were used alternately, and studied the impact of different covariates on clinical vaccination outcome measures.Of 116 subjects that were vaccinated within the defined dates, 46 were vaccinated using bifurcated needles, and 70 by beveled needles. 'Take' rates in subjects vaccinated up to 20 years earlier was 77.5%, compared with 97.2% among those vaccinated in the more distant past (p = 0.001). In multivariate analyses, vaccination 'take' was independently associated with a shorter time from previous vaccination (p = 0.013), but not with gender, birth country, vaccinator or the vaccination technique used.The low take rates observed in the Israeli smallpox revaccination campaign could not be attributed to the unique local vaccination technique, and was most likely induced by a higher rate of residual immunity among vaccinees, compared with the US, as well as by the lower vaccine concentrations used in Israel. In countries and circumstances when bifurcated needles are not sufficiently available, the beveled needle technique may be considered an appropriate alternative.

A seroepidemiological study was performed to evaluate immunity to diphtheria and to determine the correlates of diphtheria toxoid antibody levels among children and adults in Israel. In total, 3185 sera from an age-stratified sample of children and adults, obtained in 2000–2001, were tested for diphtheria toxoid antibodies by an in-house double-antigen ELISA. A level of ≤0.01 IU /mL (no immune protection or seronegativity) was found in 168 (5.3%) of the 3185 subjects, 639 (20.1%) had antibody levels of 0.011–0.099 IU /mL (basic immunity or low seropositivity), and 2378 (74.7%) had antibody levels ≥0.1 IU /mL (full protection or seropositivity). Seronegativity increased significantly in subjects aged >50 years, reaching levels of 9.7%, 12.6% and 18.9% in the groups aged 50–54, 55–59 and >60 years, respectively (p 0.001), with rates of basic immunity following a similar pattern. Subjects born abroad had higher seronegativity rates than those born in Israel (7.7%vs. 4.9%; p 0.019). No difference in diphtheria toxoid antibody levels was found according to other demographical variables, such as gender, Jewish or Arab ethnicity, urban or rural settlements, and the subjects’ place of residence. The level of immunity to diphtheria among children and adults in Israel was satisfactory, with the exception of individuals aged >50 years. The risk of diphtheria outbreaks is low, but sporadic cases may occur among individuals lacking basic immunity against the disease.

The threat of using variola virus in a bioterrorist attack urged different countries to renew the production of traditional vaccines and develop new generations of smallpox vaccines. Manufacturers try to combine smallpox vaccine past experience with technological advances in vaccine development to achieve protection similar to that of the traditional vaccines with a higher level of safety and fewer contraindications. In light of the reported immunogenicity and reactogenicity of the stockpiled smallpox vaccines employed in the last immunization campaigns of "first responders", we review recently accumulated data on the assessment of new smallpox vaccine candidates and discuss their role in possible vaccination policies.

Tick-borne relapsing fever (TBRF) is an acute febrile illness. In Israel, TBRF is caused by Borrelia persica and is transmitted by Ornithodoros tholozani ticks. We examined the safety and efficacy of postexposure treatment to prevent TBRF.In a double-blind, placebo-controlled trial, 93 healthy subjects with suspected tick exposure (52 with signs of tick bites and 41 close contacts--those without signs but with a similar risk of contact with ticks) were randomly assigned to receive either doxycycline (Dexxon, in a dose of 200 mg the first day and then 100 mg per day for four days) or placebo after presumed exposure to TBRF. Cases of TBRF were defined by fever and a positive blood smear. Serologic analysis for cross-reactivity to Borrelia burgdorferi and polymerase chain reaction (PCR) for the borrelia glpQ gene were also performed.After randomization, 47 subjects (26 with signs of tick bites and 21 close contacts) received doxycycline. Forty-six other subjects (26 with signs of tick bites and 20 close contacts) received placebo. All 10 cases of TBRF identified by a positive blood smear were in the placebo group of subjects with signs of a tick bite (P0.001). These findings suggested a 100 percent efficacy of preemptive treatment (95 percent confidence interval, 46 to 100 percent). PCR for the borrelia glpQ gene was negative at baseline for all subjects and subsequently positive in all subjects with fever and a positive blood smear. Seroconversion was detected in eight of nine cases of TBRF. PCR and serum samples were negative for all of the other subjects tested. No major treatment-associated adverse effects were identified.Treatment with doxycycline is safe and efficacious in preventing TBRF after suspected exposure to ticks in a high-risk environment. (ClinicalTrials.gov number, NCT00237016 [ClinicalTrials.gov].).

This large-scale study provides up-to-date estimates of Varicella zoster virus (VZV) age-specific seroprevalence and characteristics of VZV transmission in a representative sample of the Israeli population. In 2000–2001, 1,642 sera collected from an agestratified general population sample were tested for VZV antibodies using an indirect IgG ELISA system. The age-weighted VZV overall estimate was 90.2%. Seropositivity increased rapidly with age, from 68.9% at age 4 to 94.4% at age 7 and 96.6% at age 12 years. The highest force of infection was in the 4–5 years age group (0.548 per susceptible year) followed by the 6–9 years age group. Multivariate analysis revealed that VZV seroprevalence estimates were significantly associated with age and place of origin. The highest seroprevalence estimate was found among subjects of Eastern origin. The seroepidemiology of VZV in Israel shows a pattern corresponding to that described for developed European countries. This study indicates that the highest force of infection is in pre-school children. Knowledge of pre-vaccination seroepidemiology is important to evaluate the effect of vaccination programs on the epidemiology of the disease.

We describe the first community-based evaluation of Shigella sonnei strain WRSS1, a live, oral candidate vaccine attenuated by a 212-bp deletion in the virG (or icsA ) plasmid virulence gene. Three single-dose regimens of WRSS1 (5 × 10 3 CFU, 2 × 10 4 CFU, and 4 × 10 5 CFU) were tested with cohorts of 15 adult volunteers. The vaccine was generally well tolerated at the 10 3 - and 10 4 -CFU doses. There were no fevers and there was one report of moderate diarrhea in 30 vaccinees; five additional vaccinees reported mild diarrhea. At the 10 5 -CFU dose, there were two reports of low-grade fevers and four reports of moderate diarrhea. The geometric means for immunoglobulin A (IgA) antibody-secreting cells (ASC) against lipopolysaccharide (LPS) were 30, 75, and 193 ASC per 10 6 peripheral blood mononuclear cells (PBMC) for the 10 3 -, 10 4 -, and 10 5 -CFU doses, respectively. The IgG means were 40, 46, and 135 ASC per 10 6 PBMC, respectively. The 10 4 -CFU dose of WRSS1 gave the best balance of safety and immunogenicity, since all vaccinees had a significant IgA ASC response and 73% had a response of more than 50 ASC. The anti-LPS seroconversion rate (threefold) for IgA was 60% and the IgG rate was 27% for the 10 4 -CFU cohort. Each vaccinee and a cohabitating household contact delivered daily perianal stool swabs for bacteriological culture. WRSS1 colonized vaccinees for a median of 5 days, and one individual excreted WRSS1 intermittently for 23 days. None of the 45 household contacts were colonized with WRSS1 after a cumulative 192 days of cohabitation with colonized vaccinees, suggesting that adventitious vaccine spread was not common in the community setting.

Relapsing fever caused by Borrelia persica is an acute tick-borne disease infecting people in the Middle East. A PCR test targeting the glycerophosphodiester phosphodiesterase (GlpQ) gene was used to detect infection in the blood of suspected relapsing fever patients. The assay detected infection in all 19 patients from Israel who were spirochetemic by blood smear examination and in two additional patients with clinical relapsing fever who were negative by smear examination. Patients were positive by PCR of blood only at the febrile stage and not during the incubation period prior to the appearance of clinical symptoms. Of 52 tick-bitten subjects who were tested and followed-up after being bitten by ticks, 10 developed symptoms of relapsing fever and all became positive by PCR following an earlier negative test. Partial sequencing of the 16S rRNA gene supported by phylogenetic analysis indicated that infection was caused by B. persica or a closely related species. A phylogenetic analysis of the GlpQ sequence showed that it was different yet closely related to other relapsing fever Borrelia spp. present in the Old World. The GlpQ PCR was positive also with the relapsing fever spirochetes B. recurrentis and B. crocidure but not with the Lyme disease agent B. burgdorferi DNA. A second modified GlpQ PCR was able to discriminate between probable B. persica and B. recurrentis and B. crocidurae infection. This study describes the first molecular assay for the diagnosis of relapsing fever caused by B. persica.

The purpose of the present study is to explore the possibility that plant lectins can be used for the development of rapid and inexpensive technique for differentiation of mycobacterial species. The method is based on interaction between mycobacteria and lectins as visualized by agglutination in a microtiter plate. We employed 18 mycobacterium species and determined the minimal lectin concentration (MLC) of 23 different lectins. For some of the bacteria as a high as 1000 microg/ml of one or more lectins were required to induce agglutination, while for other strains as low as 1.95 microg/ml of the lectin were needed. A unique pattern of agglutination was observed for each species over a range of 62-1000 microg/ml lectin concentrations. There were little or no variations in MLC within strains (intraspecies) of each of two species tested. In contrast, there were marked interspecies variations in MLC. Analysis of the MLC showed that the highest score of interspecies differences with 23 lectins was obtained at 125 microg/ml lectin concentration. At this concentration it was found that the pattern of agglutinations with only two lectins was sufficient to differentiate mycobacterium species from each other. Because the bacteria-lectin interaction is adaptable to various methods of visualization, our findings may set the stage for developing a rapid and reliable tool to differentiate mycobacterium species.

An increase in gastroenteritis outbreaks due to Norovirus has been reported worldwide. We investigated a large-scale outbreak affecting 246 residents and 33 staff members in six nursing homes in the Tel-Aviv district, Israel, during 3 weeks in 2002. Person-to-person spread was noticed in all nursing homes. The spread of disease could not be attributed to social interactions. Among the elderly residents, the hospitalization rate was 10·2% and the case-fatality rate was 2·0%. Bacteriological cultures were negative. Overall, 7 out of 15 stool specimens were positive for Norovirus by RT–PCR. All were sequenced and found to be 90% identical. The characteristics of this outbreak and the RT–PCR results suggest that illness was caused by Norovirus. Due to the high case-fatality rate of Norovirus gastroenteritis, there should be a high index of suspicion when encountering a gastroenteritis outbreak among the elderly. This will enable prompt action to stop the spread of illness.

We explored the dual influence of the patient's age and the infecting serotype on the blood invasiveness patterns of non-Typhi Salmonella enterica (NTS). Blood invasiveness ratio (BIR) was calculated as the ratio between the number of blood and blood+stool isolates. Analysis of 14951 NTS isolates showed that the BIR increased drastically above the age of 60 years, reaching levels 3·5–7 times higher compared to age group

We report the first community-based evaluation of Shigella flexneri 2a strain SC602, a live, oral vaccine strain attenuated by deletion of the icsA ( virG ) plasmid virulence gene, given at 10 4 CFU. The primary objectives of this trial were to determine the safety and immunogenicity of the vaccine and to determine the duration of colonization. Four of 34 volunteers experienced transient fevers, and three reported diarrhea during the first 3 days of the study. Half of the volunteers mounted a positive serum immunoglobulin A (IgA) response to S. flexneri lipopolysaccharide. All but one of the volunteers excreted the vaccine in their stools for 1 to 33 days, and this excretion was often intermittent. Data from the community-based study were supplemented with an inpatient trial in which three volunteers received 10 3 and nine received 10 4 CFU. All volunteers who received 10 3 CFU excreted SC602 and had an IgA antibody-secreting cell response. Two of these had a serum IgA response. Six of the nine volunteers who received 10 4 CFU excreted SC602. One vaccinee had a transient fever and two met the definition of diarrhea. Six volunteers that received 10 4 CFU had an antibody-secreting cell response, and four had a serum IgA response. SC602 has now been tested at 10 4 CFU in a total of 58 volunteers. The cumulative results of these clinical trials, reported here and previously (Coster et al., Infect. Immun. 67: 3437-3443, 1999), have demonstrated that SC602 is a substantially attenuated candidate vaccine that can evoke protection against the most severe symptoms of shigellosis in a stringent human challenge model of disease.

BACKGROUND During the winter of 2002-2003, the Israeli health authorities launched a campaign to vaccinate first responders against smallpox. METHODS In an open study, 159 healthy, preimmunized adults, 24-52 years old, who participated in the campaign were vaccinated with the Lister strain of vaccinia virus by the multipuncture technique. The safety, immunogenicity, and reactogenicity of the vaccine were assessed. RESULTS Successful vaccination rates were 61% and 56%, on the basis of clinical take and seroconversion, respectively. Adverse events among the vaccinees were minor. Seventy-nine (88%) of the 90 vaccinees with clinical take also seroconverted ( kappa =0.779). The level of preexisting antibodies inversely correlated with the rates of clinical take and seroconversion (P

The relationship between the timing of surgery after hip fracture and the subsequent survival of the patient has been studied extensively, yet still remains a controversy. This study aims to assess the impact of operative delay on the 1-year survival of patients and on the rate of complications during the postoperative hospital stay. Medical and demographic data were extracted from the hospital records of 651 consecutive hip fracture patients over 60 years old. Information on mortality was obtained by cross-linkage with the Department of Interior population files. The multivariate survival analysis model was utilized to assess the association between the time from fracture incident to surgery and the outcome (1-year survival and postoperative complications). The hazard ratio (HR) of 1-year mortality for postponing surgery beyond 48 h was 1.63 (95%CI 1.11–2.40), as derived by the Cox proportional hazards model. Other variables found to be independently associated with decreased survival are: male gender (HR=1.54), mental deterioration (HR=2.94), postoperative mobility (HR=2.45), and severity of pre-existing diseases (HR=1.96). Occurrence of general complications during the postoperative hospital stay was a significant predictor of decreased 1-year survival (HR=1.83). These findings suggest that early (within 48 h) surgical treatment of hip fractures is associated with improved 1-year survival.

Addition of the cholera toxin B subunit to oral and intranasal proteosome-Shigella flexneri 2a lipopolysaccharide vaccines improved their immunogenicities. Enhancement of anti-O-Shigella immunoglobulin A levels was most evident in lung lavages following oral immunization and in lung and intestinal fluids when suboptimal doses were used with either immunization route.

In 1988 an outbreak of type 1 paralytic poliomyelitis occurred in Israel. Almost the entire population in the age group 0-40 years received a single dose of trivalent oral polio vaccine. We examined the serological responses to the vaccine at 2 weeks and 4 years later, in a group of 17 vaccines. Geometric mean antibody titres (GMTs) against both the type 1 epidemic and Mahoney strains had declined by about 50% from the levels found at 2 weeks after vaccination. However, they were still more than five times higher than the prevaccination levels. All vaccines had neutralizing antibody titres against both the type 1 strains of at least 1:64, well above the 1:8 titre regarded as protective. The GMTs against the type 2 and 3 strains declined to about one-third of the 2-week postvaccination levels but were also well above protective levels. These findings indicate that antibody titres against both the Mahoney and epidemic type 1 strains remained at very adequate levels over a period of at least 4 years. Thus the immunity resulting from a single booster dose of oral poliovaccine in young adults is likely to be long-lasting, a finding of particular importance for travellers on extended visits to endemic areas.

Background: Paired sera collected from subjects before and after a fly-control intervention trial conducted in the Israel Defence 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 ≥ 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 cannt be interrupted with an aggressive program of fly-control.

Summary Background: Over a period of 4 days between May 18–21, 1998, a multifocal outbreak of diarrhea, involving 175 Israel Defence Force soldiers and at least 54 civilians, occurred in the Golan Heights. Patients and Methods: Stool samples from 40 affected soldiers were collected for microbiological testing. In addition, a rapid PCR technique was employed for the direct detection of the heat-labile (LT) and heat-stable toxin (ST) genes of enterotoxigenic Escherichia coli (ETEC) in stool samples. Results: All 40 stool specimens taken from patients with diarrhea was negative by culture. However, ETEC was detected in 16 stool specimens using the rapid PCR method. The epidemiological investigation found no association between the food items consumed prior to the onset of the outbreak and the attack rate of diarrhea. A review of the water distribution system revealed that all affected military posts and civilian communities were supplied by a common water pipeline. Water sampled from various points along the distribution system showed inadequate chlorination and high concentrations of E. coli. Conclusion: This report suggests that the involvement of ETEC in the etiology of waterborne diarrheal outbreaks may be underestimated, probably due to the difficulties involved in the laboratory identification of this enteropathogen. Adoption of our rapid method for the identification of ETEC, which is applicable to routine diagnostic laboratories, facilitates pathogen detection within hours, and allows early intervention in cases of widespread diarrheal epidemics.

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.

Background Evidence for a causal relationship between presence of Helicobacter pylori (H. pylori) in gastric mucosa and development of peptic disease is based largely on intervention studies in which eradication of H. pylori led to healing of the lesion. The aim of this study was to assess the importance of H. pylori seropositivity for subsequent development of peptic disease in a prospective study design in young Israelis. Methods A nested case-control serum bank study based on a systematic sample of male and female inductees to the Israel Defense Force. Twenty-nine cases of duodenal ulcer or duodenitis of moderate or higher severity, diagnosed between 1986 and 1995, were individually matched for age, sex, ethnicity, education and year of induction, with five healthy controls each. Presence of anti-H. pylori antibodies in the frozen stored sera was determined by ELISA. Results The geometric mean titre of anti-H. pylori antibodies at baseline was significantly higher in cases (18.3 U/ml) than controls (6.9 U/ml; P = 0.009). The matched odds ratio for peptic ulcer disease by seropositivity was 3.8 (95% CI : 1.4‐10.2). A stronger association was evident for subjects diagnosed >2 years after induction than those diagnosed earlier. The population attributable fraction was 56.6% (95% CI : 15.7‐81.1). Conclusions Pre-existing infection with H. pylori, as determined by seropositivity, is an important determinant of development of duodenal ulcer or duodenitis in young Israelis, supporting the generalizability of an apparent causal association to diverse populations.

The goal of this study was to assess the susceptibility of the sub-population of over 500,000 immigrants from the former USSR who came to Israel during 1989-94 to HAV infection, and to provide military physicians with estimates of the prevalence of HBV and HCV carriage in this sub-population. 987 males aged 17-49 and 195 females aged 17-19, reporting to military recruitment offices between December 1991 and March 1992 were tested. Anti-HAV, anti-HBV antibodies and hepatitis B surface antigen (HBsAg) were detected by using standard enzyme immunoassay (EIA) tests, and anti-HCV antibodies by a second-generation EIA and confirmed by a third-generation INNO-LIA test. It was found that in the 17-19-year age-group the prevalence of anti-HAV antibodies was 37%, anti-HBV was 12.8%, HBsAg was 3.0% and anti-HCV 1.3%. All markers were higher among males. The prevalence of anti-HAV and anti-HBs antibodies increased with age among males. That of HBsAg and anti-HCV antibodies increased with age overall. In the multiple logistic regression analysis, HAV and HBV seropositivity were significantly associated with the mother's education and republic of origin. It was concluded that the prevalence of anti-HAV antibodies is similar to that among the local population, which should not be considered at a higher risk of infection during military service. On the other hand, the higher prevalence of HBsAg and anti-HCV antibodies in this sub-population should heighten the awareness of the possibility of chronic liver pathology.

Microbiological surveys in areas where diarrheal disease is endemic implicate Shigella species as etiologic agents in at least 20% of diarrheal cases. Shigella flexneri 2a is usually the most prevalent species and serotype in these areas (8, 14, 30). Shigellae are extraordinarily adept intestinal pathogens, as evidenced by their small infectious doses (7). Shigella infection is usually transmitted by the fecal-oral route and can be manifested as uncomplicated watery diarrhea. A more definitive manifestation of shigellosis is dysentery, i.e., frequent passage of small-volume stools with gross blood, mucus, and fecal leukocytes. Constitutional symptoms (e.g., fever, rectal tenesmus, and headache) also characterize severe disease. Colonoscopy of patients infected with either Shigella dysenteriae or S. flexneri reveals diffuse erythema, focal hemorrhages, and inflammatory changes resembling ulcerative colitis. Rectal biopsies taken during the early stages of infection reveal aphthoid lesions overlying small lymphoid follicles (23). These clinical findings are consistent with experimental observations made with the rabbit ileal loop model, suggesting that Shigella initiates intestinal infections by invading the follicle-associated membranous cells (28). Experiments employing polarized epithelial cells as a model of the intestinal epithelium suggest that shigellae invade enterocytes through the basolateral membrane. Internalized bacteria subsequently spread within infected cells by organizing host cell actin into a cytoskeleton-based motor (10, 22). Genetic analysis has shown that this spreading phenotype is dependent upon a plasmid-borne virulence gene designated icsA (2) or virG (22). The 120-kDa protein expressed by this plasmid-carried gene acts as a recruiter for cytosolic nucleators of filamentous actin (10). This actin is concentrated at the distal poles of septating shigellae, and the resulting comet-like tails provide a motive force for the bacteria within the cytoplasm of infected epithelial cells (36). The mobilized bacteria impinge on the inner face of the host cell plasma membrane, and they spread into contiguous epithelial cells via membrane protrusions (10). Intragastric challenge of rhesus monkeys, a primate model of intestinal shigellosis, demonstrates that icsA-mediated intercellular spread of shigellae is a key step in pathogenesis. For example, endoscopy of asymptomatic animals challenged with an icsA mutant of S. flexneri serotype 5 reveals only scattered nodular abscesses rather than the hemorrhagic ulcerations and diffuse mucosal inflammation seen in animals challenged with the virulent parent strain (32). icsA mutants are also avirulent in the Sereny guinea pig keratoconjunctivitis model of suppurative Shigella infection (13, 26). Deletion of the iuc chromosomal locus (encoding aerobactin) partially attenuates S. flexneri in the Sereny guinea pig test and in the rabbit ileal loop model (24). Intragastric inoculation with either an icsA single mutant or an icsA iuc double mutant protects rhesus monkeys against subsequent challenge with the virulent S. flexneri 5 parent strain (32, 33). Epidemiological and clinical studies indicate that an episode of shigellosis elicits substantial immunity against subsequent disease caused by the same Shigella serotype (6, 8, 15, 19). In a rational approach to Shigella vaccine development, we and others have constructed genetically attenuated vaccines designed to establish asymptomatic infections that induce protective immune responses. However, the ideal balance of safety and efficacy in attenuated Shigella vaccines has been elusive (11, 15–18, 20, 25). Current research suggests that icsA iuc mutants could serve as attenuated Shigella vaccines, and the SC602 ΔicsA Δiuc S. flexneri 2a candidate was constructed to test this combination of attenuating mutations in volunteers. Here we describe a preliminary dose selection study, two expanded dose selection studies, and an efficacy (challenge) study of SC602 that were performed in the clinical inpatient ward of the U.S. Army Medical Research Institute for Infectious Diseases (USAMRIID), Ft. Detrick, Md. (Parts of this work were previously presented at the 96th General Meeting of the American Society for Microbiology, 19 to 23 May 1996, and at the 98th General Meeting of the American Society for Microbiology, 17 to 21 May 1998.)

The aim of this study was to describe antibiotic resistance rates of enterotoxigenic Escherichia coli in Israel in order to facilitate the empirical choice of antibiotic treatment or prophylaxis for traveler's diarrhea and infantile diarrhea in our region. A total of 281 enterotoxigenic Escherichia coli isolates were tested: 144 from Bedouin infants and 137 from Israeli soldiers. Antibiotic-resistant isolates were prevalent in both groups, but higher resistance rates were found in the pediatric group. Strains producing heat-labile toxin showed higher resistance rates than strains producing heat-stable toxin. The results obtained in Israel preclude the use of many commonly used antibiotics for the treatment of traveler's diarrhea. Quinolones, however, are still effective.

Large outbreaks of diphtheria occurred recently in the former USSR. Between 1989 and 1994, a total of about 600,000 Soviet immigrants arrived in Israel. The immune status against diphtheria in a sample of 992 men aged 17-49 and 195 women aged 17-19, who arrived in Israel during 1990-91, was studied in order to evaluate the need for vaccination. Participants completed a self-administered questionnaire and diphtheria antitoxin antibody levels were measured by means of ELISA. At age 17-19, the prevalence of antitoxin antibody levels below the protective level of 0.01 IU/ml was 4.8% in the men and 2.1% in the women. Among the men, the percentage lacking protection declined from 4.8% at age 17-19 years to 1.6% at age 20-24, and increased to 18.2% at age 35-49. In the oldest group, the prevalence of those lacking protection was considerably higher than for the general Israeli population. In the multivariate analysis, age, mother's education and republic of origin were significantly associated with the absence of protection. Immigrants from the former USSR appear to be more susceptible to diphtheria, thus increasing the possibility of clinical disease, and it is recommended that they receive booster doses of diphtheria toxoid.

Summary 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 -r EPA) and of an oral, live-attenuated Escherichia coli/S flexneri 2a ( EcSf 2a-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 EcSf 2a-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 EcSf 2a-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 EcSf 2a-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 EcSf 2a-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.

Dear Sir: In their comprehensive and rigorous study on the etiology of anemia in Cote d'Ivoire, Righetti and others1 reported high prevalence of anemia (45–75%), inflammation, and deficiencies of iron, riboflavin, and vitamin A. The factors that were significantly and positively linked to the prevalence of anemia differed by age group: (1) infection with Plasmodium falciparum in 6- to 23-month-old children, (2) cellular iron deficiency and chronic inflammation in 6- to 8-year-old children, and (3) cellular iron deficiency in non-pregnant young women.1 Identifying modifiable risk factors like the factors reported by Righetti and others1 is highly important and can help in establishing interventions aimed at reducing the burden of anemia. Helicobacter pylori colonizes the stomach; typically, it is acquired in childhood and causes asymptomatic chronic infection, which is highly endemic in developing countries.2 A small portion of H. pylori-infected subjects develop peptic ulcers and gastric carcinoma, usually in late adulthood.2 In well-designed studies, H. pylori was found to be associated with increased likelihood of iron deficiency anemia (IDA)3,4; furthermore, anti-H. pylori therapy substantially reduced the percentage of children affected with IDA.5 In a community-based study among Arab children in Israel, we found significantly lower mean hemoglobin levels in children ages 6–9 years who were infected with H. pylori compared with their uninfected peers.6 H. pylori was also associated with low ferritin levels.6,7 In a systematic review and meta-analysis,8 we found higher prevalence of IDA in H. pylori-infected subjects than uninfected ones (pooled odds ratio = 2.8; 95% confidence interval = 1.9–4.2).8 We recommend the investigation of H. pylori infection as a potential factor that might play a role in the occurrence of anemia in this population.1 Trials on the impact of anti-H. pylori therapy on the burden of anemia and IDA could shed light on whether the association between H. pylori and these disorders is causal.

Formed before international negotiations of the revised International Health Regulations (IHR), the Middle East Consortium for Infectious Disease Surveillance (MECIDS) is a regional collaboration aimed at facilitating implementation of the revised IHR and, more broadly, improving the detection and control of infectious disease outbreaks among neighboring countries in an area of continuous dispute. Initially focused on enhancing foodborne disease surveillance, MECIDS has expanded the scope of its work to also include avian and pandemic influenza and other emerging and re-emerging infectious diseases. Here, we describe the history and governance of MECIDS, highlighting key achievements over the consortium's seven-year history, and discuss the future of MECIDS. Keywords: Middle East; cross-border collaboration; foodborne disease surveillance; avian influenza preparedness; pandemic influenza (Published: 25 January 2013) Citation: Emerg Health Threats J 2013, 6 : 19955 - http://dx.doi.org/10.3402/ehtj.v6i0.19955

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.

Shigellosis or bacillary dysentery is caused by organisms belonging to genus Shigella, divided into four species (S. dysenteriae, S. boydii, S.flexneri and S. sonnei). With the exception of S. sonnei which has a single serotype, each species is divided into several serotypes according to the O-polysaccharide antigen of the cell wall (S. dysenteriae has 12 serotypes, S. flexneri has 6 serotypes, and S. boydii has 18 serotypes). Shigella spp. are invasive organisms that penetrate into the enterocytes of the colon epithelium, escape very quickly from the phagocytic vacuole and multiplicate intracellularly. Although non-motile, shigellae can move on an actin skeleton and spread to adjacent cells. The inflammatory process is usually limited to the lamina propria and does not involve the spread of Shigella deeper, into the submucosa. Pathogenesis in Shigella spp. is associated with a constellation of genes encoded on both the chromosome and a large 140 MDa virulence plasmid. These genes can be divided into two groups: regulatory genes and structural genes. The 140 MDa plasmid encodes for all the genes essential for invasion of Shigella into the epithelium of the colon. Regulatory genes are located on the virulence plasmid or on the chromosome.