Tamar Sela

Community-Based Safety, Immunogenicity, and Transmissibility Study of the Shigella sonnei WRSS1 Vaccine in Israeli Volunteers

ABSTRACT 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 × 103 CFU, 2 × 104 CFU, and 4 × 105 CFU) were tested with cohorts of 15 adult volunteers. The vaccine was generally well tolerated at the 103- and 104-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 105-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 106 peripheral blood mononuclear cells (PBMC) for the 103-, 104-, and 105-CFU doses, respectively. The IgG means were 40, 46, and 135 ASC per 106 PBMC, respectively. The 104-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 104-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.

Control of Streptococcus pneumoniae serotype 5 epidemic of severe pneumonia among young army recruits by mass antibiotic treatment and vaccination.

Abstract During an outbreak of severe pneumonia among new army recruits, an epidemiological investigation combined with repeated nasopharyngeal/oropharyngeal cultures from sick and healthy contacts subjects was conducted. Fifteen pneumonia cases and 19 influenza-like illness cases occurred among 596 recruits over a 4-week period in December 2005. Pneumonia attack rates reached up to 5.5%. A single pneumococcus serotype 5 clone was isolated from blood or sputum cultures in 4 patients and 30/124 (24.1%) contacts. Immunization with 23-valent polysaccharide vaccine supplemented with a 2-dose azithromycin mass treatment rapidly terminated the outbreak. Carriage rates dropped to <1%, 24 and 45 days after intervention.

A Cluster of Ecthyma Outbreaks Caused by a Single Clone of Invasive and Highly Infective Streptococcus pyogenes

BACKGROUND Ecthyma is an invasive, ulcerated skin infection. Four ecthyma outbreaks occurred in different infantry units in the Israeli Defense Force from October 2004 through February 2005. Morbidity attack rates in the first 3 outbreaks were 89% (49 of 55 soldiers), 73% (32 of 44), and 82% (37 of 45). In the fourth outbreak, in which early intervention (antimicrobial treatment and improvement of hygiene) was applied, the attack rate was 25% (10 of 40 soldiers). In the first outbreak cluster, 4 soldiers experienced poststreptococcal glomerulonephritis, and 5 cases of systemic sequelae were recorded (1 case of severe septic shock, 3 cases of pneumonia, and 1 case of septic olecranon bursitis). METHODS Streptococcus pyogenes and Staphylococcus aureus were isolated from ecthyma sores, oropharynx, and anterior nares of affected and unaffected soldiers involved in all 4 outbreaks. RESULTS Although the S. aureus isolates had different genomic profiles, >90% of S. pyogenes isolates were identified as belonging to a single clone, emm type 81, T type 8. Epidemiological investigation revealed that the hygiene levels of the soldiers and their living conditions were probably the most important cause for the difference in attack rates, wound severity, and systemic sequelae found between and within the units. CONCLUSIONS Our study demonstrates the possible ramifications of the combination of a virulent and highly infective S. pyogenes strain and poor living conditions, and it emphasizes the importance of early intervention in such conditions.

Safety and Immunogenicity of Two Different Lots of the Oral, Killed Enterotoxigenic Escherichia coli-Cholera Toxin B Subunit Vaccine in Israeli Young Adults

ABSTRACT 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.

Transmission of Streptococcus pneumoniae in adults may occur through saliva.

Of 742 army recruits tested for pneumococcal nasopharyngeal/oropharyngeal carriage, 6·6% were positive. Frequent sharing of a drinking glass/bottle was a common, strong and independent risk factor for pneumococcal carriage. Our findings strongly suggest, for the first time, that in young adults, transmission of pneumococci may occur via saliva and this should be considered when conducting an outbreak investigation and carriage studies.

Prospective Cohort Studies of Shigellosis During Military Field Training

Abstract 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  °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.

Dynamics of pneumococcal acquisition and carriage in young adults during training in confined settings in Israel.

Background Outbreaks and sporadic cases of pneumococcal illness occur among young adults in confined settings. Our aim was to characterize pneumococcal acquisition and carriage among healthy young adults in Israel during military training in confined settings. Methods During the years 2007–2008, an observational longitudinal study was conducted in three cohorts of healthy soldiers, during a 7-month basic training period. Epidemiological data, oropharyngeal and nasopharyngeal cultures were sampled on 5 occasions: before and 3, 6, 12 and 24 weeks after start of training. Samples were processed within 2–18 hours. Relatedness of isolates was investigated by capsular typing of all isolates and pulsed-field gel electrophoresis to determine acquisition and transmission. Carriage and acquisition patterns were analyzed and multivariable logistic regression analysis was performed to assess the impact of time on acquisition after mixing, controlling for other covariates. Results Pneumococci were recovered on 202 of 1872 visits among 742 individuals, including 40 different serotypes. Mean carriage prevalence increased in all visits following training initiation. Acquisition during training was high, as 36.9% of individuals acquired pneumococci at least once during training, and for almost one fourth of the whole population this occurred during the first 6 weeks. Significant clustering was noted. Sharing drinking glass/bottle was found to be a significant and common risk factor for pneumococcal acquisition. Conclusions Pneumococcal acquisition is highly frequent when young adults live in close contact in confined settings, especially early after mixing.

Seroprevalence of anti-HBs antibodies at young adulthood, before and after a booster vaccine dose, among medical personnel vaccinated in infancy

BACKGROUND Questions remain regarding the long-term protection provided by childhood HBV vaccination. The goals of this study were to assess HBV seroprevalence among medical personnel purportedly vaccinated in infancy; to investigate the immune response after a booster dose given in young adulthood; and to identify predictors of non-responders. METHODS Between 2011 and 2013 we studied Israeli male military recruits purportedly vaccinated in infancy. All subjects were born after January 1st 1992 and were undergoing medic training. We collected personal data and blood samples at baseline, and administered a dose of HBV vaccine. Subjects were retested one month later and received a second dose. A third blood draw was conducted one month after the second dose. Data collected at baseline were used as predictor variables of seropositivity (anti-HBs≥10mIU/ml). RESULTS 617 subjects were available for baseline analysis and 539 for paired observations at one month. Baseline seropositivity was 33.7%. Subjects who received post-infancy vaccine doses had a seropositivity rate double that of those denying additional doses (RR 2.22, 95% CI 1.55-3.18). One month after the first booster dose, the overall cumulative population seropositivity reached 87.7%. One month after the second vaccine dose, population seropositivity was 97.9%. Heavy smokers were 5 times less likely to demonstrate detectable antibodies after a single booster dose (OR 0.196, 95% CI 0.060-0.641, P=0.007). CONCLUSIONS This population-based study is important for informing public health vaccination policy. Our results strongly indicate that among cohorts vaccinated in infancy, two doses in adulthood will provide maximal protective antibody levels, while one dose will provide sufficient population protection.

Phenotypic Characteristics of Enterotoxigenic Escherichia coli Associated with Acute Diarrhea Among Israeli Young Adults

Enterotoxigenic Escherichia coli (ETEC) is a major cause of diarrhea among infants and children in developing countries, as well as among travelers to these areas. The major virulence factors of ETEC are the colonization factor antigens (CFAs) and a heat-labile enterotoxin (LT) and/or a heat-stable enterotoxin (ST). Among Israeli recruits serving under military field conditions, 107 of all examined isolates expressed LT or ST, and CFAs could be characterized in 68% of the isolates, in which CFAs of the CFA/II group and CS6 were the most prevalent. Additionally, 31% of the 107 ETEC isolates showed resistance to three or more of the antimicrobial agents examined, and the percentage of resistant isolates expressing LT was significantly higher than those expressing ST or LT+ST. These results may be important for development of an effective vaccine and for facilitation of an empirical choice of antibiotic treatment or prophylaxis for travelers diarrhea in this area.

Smoking initiation among Israeli adolescents: A 24-year time-to-event analysis

INTRODUCTION Preventing smoking initiation will protect future generations from smoking-attributable death and disease. This study examines the correlates and patterns of initiation among Israeli youth using time-to-event analysis and other methods. METHODS Twenty-four consecutive representative samples (1986-2009) of new military recruits (N=50,254) were analyzed. Cox regression and Kaplan-Meier analysis were used to identify factors associated with smoking initiation, and logistic regression was used to identify factors associated with smoking status. RESULTS The most hazardous age for smoking initiation was seventeen, subsequent to the mean age of smoking initiation (males: 15.7, females: 16.0). Age of initiation and age of greatest hazard for initiation declined among recruits between the years 1986 and 2009. Earlier smoking initiation among boys and girls was significantly associated with low education levels (<12years) (males: HR=2.98, CI: [2.79, 3.18]; females: HR=3.35, CI: [2.96, 3.80]), low paternal education levels, Russian birthplace, and religion. Earlier initiation in boys was associated with high fitness levels and low/medium socio-economic status. Earlier initiation in girls was associated with being Western-born and ever-use of contraception. CONCLUSIONS Smoking initiation among Israeli youth recruited to the armed forces is associated with individual and family characteristics, particularly low education levels. Time-to-event analysis complements traditional means of understanding smoking initiation by identifying ages at which initiation hazard is high.