Vered Agmon

Clinical, epidemiological, and microbiological features of Vibrio vulnificus biogroup 3 causing outbreaks of wound infection and bacteraemia in Israel

Summary Background Vibrio vulnificus is a gram-negative bacterium that causes septicaemia and wound infection. Cases occur sporadically, and no previous outbreaks due to a common source or a clonal strain have been reported. In the summer and autumn of 1996 and 1997, an outbreak of invasive V vulnificus infection occurred in Israel in people who had recently handled fresh, whole fish purchased from artificial fish-ponds. Methods We reviewed clinical and epidemiological information, and undertook an environmental investigation to assess disease characteristics, modes of transmission, phenotypic characteristics of the bacterium, and fish-marketing policy. The clonal nature of 19 isolates was studied by biotyping, pulsed-field gel electrophoresis, and restriction-fragment length polymorphism (RFLP) analysis of a PCR fragment. Findings During 1996–97, 62 cases of wound infection and bacteraemia occurred. 57 patients developed cellulitis, four had necrotising fasciitis, and one developed osteomyelitis. In all cases, the fish were cultivated in inland fish-ponds. In the summer of 1996, fish-pond managers initiated a new marketing policy, in which fish were sold alive instead of being packed in ice. Phenotypically, the isolates had five atypical biochemical test results. The isolates were non-typeable by pulsed-field gel electrophoresis, and all had the same PCR-RFLP pattern which had not been seen previously. Interpretation The cause of the outbreak was a new strain of V vulnificus , classified as biogroup 3. A new fish-marketing policy that began in 1996 may have exposed susceptible people to the organism.

Nontyphoid Salmonella Bacteremia: Age-Related Differences in Clinical Presentation, Bacteriology, and Outcome

In a retrospective study, 80 episodes of nontyphoid salmonella (NTS) bacteremia in children were compared with 55 episodes in adults over a 10-year period. The study disclosed major differences in the predisposition, clinical presentation, and outcome as well as the microbiology of NTS bacteremia in relation to age. Adults were more likely than children to have predisposing diseases (95% vs. 15%, respectively; P < .0001) and to receive prior medications (95% vs. 23%, respectively; P < .0001), particularly immunosuppressive agents (58% vs. 5%, respectively; P < .0001). In most adults (67%), NTS infection presented as a primary bacteremia and was associated with a high incidence of extraintestinal organ involvement (34%) and a high mortality rate (33%). In children, NTS bacteremia was usually secondary to gastroenteritis (75%) and caused no fatalities. Although group D Salmonella (78%) and the serovar Salmonella enteritidis were the predominant isolates from adults, the emergence of infections due to group C Salmonella (46%) and the serovar Salmonella virchow in children was noted.

Virulence gene profiling and pathogenicity characterization of non-typhoidal Salmonella accounted for invasive disease in humans.

Human infection with non-typhoidal Salmonella serovars (NTS) infrequently causes invasive systemic disease and bacteremia. To understand better the nature of invasive NTS (iNTS), we studied the gene content and the pathogenicity of bacteremic strains from twelve serovars (Typhimurium, Enteritidis, Choleraesuis, Dublin, Virchow, Newport, Bredeney, Heidelberg, Montevideo, Schwarzengrund, 9,12:l,v:- and Hadar). Comparative genomic hybridization using a Salmonella enterica microarray revealed a core of 3233 genes present in all of the iNTS strains, which include the Salmonella pathogenicity islands 1–5, 9, 13, 14; five fimbrial operons (bcf, csg, stb, sth, sti); three colonization factors (misL, bapA, sinH); and the invasion gene, pagN. In the iNTS variable genome, we identified 16 novel genomic islets; various NTS virulence factors; and six typhoid-associated virulence genes (tcfA, cdtB, hlyE, taiA, STY1413, STY1360), displaying a wider distribution among NTS than was previously known. Characterization of the bacteremic strains in C3H/HeN mice showed clear differences in disease manifestation. Previously unreported characterization of serovars Schwarzengrund, 9,12:l,v:-, Bredeney and Virchow in the mouse model showed low ability to elicit systemic disease, but a profound and elongated shedding of serovars Schwarzengrund and 9,12:l,v:- (as well as Enteritidis and Heidelberg) due to chronic infection of the mouse. Phenotypic comparison in macrophages and epithelial cell lines demonstrated a remarkable intra-serovar variation, but also showed that S. Typhimurium bacteremic strains tend to present lower intracellular growth than gastroenteritis isolates. Collectively, our data demonstrated a common core of virulence genes, which might be required for invasive salmonellosis, but also an impressive degree of genetic and phenotypic heterogeneity, highlighting that bacteremia is a complex phenotype, which cannot be attributed merely to an enhanced invasion or intracellular growth of a particular strain.

Blood invasiveness of Salmonella enterica as a function of age and serotype

We explored the dual influence of the patients 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 14,951 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 < 2 years. Different patterns of age-related invasiveness were observed for the five most common NTS serotypes (Enteritidis, Typhimurium, Virchow, Hadar, Infantis). Among children < 2 years, the BIR was highest for serotype Virchow and lowest for serotype Hadar, while in persons > or = 60 years it was highest for serotypes Enteritidis and lowest for serotype Infantis. The tendency of NTS serotypes to invade the bloodstream was significantly influenced by the patients age, however the impact of age differed for various NTS serotypes.

Multidrug- Resistant Salmonella enterica Serovar Infantis, Israel

To determine whether rapid emergence of Salmonella enterica serovar Infantis in Israel resulted from an increase in different biotypes or spread of 1 clone, we characterized 87 serovar Infantis isolates on the genotypic and phenotypic levels. The emerging strain comprised 1 genetic clone with a distinct pulsed-field gel electrophoresis profile and a common antimicrobial drug resistance pattern.

Clinical Characteristics and Molecular Subtyping of Vibrio vulnificus Illnesses, Israel

The genetically distinct biotype 3 has penetrated Israeli freshwaters and is causing severe illness in persons who handle tilapia or carp.

Increased Incidence of Campylobacter spp. Infection and High Rates among Children, Israel

During 1999–2010, the annual incidence of Campylobacter spp. infection in Israel increased from 31.04 to 90.99 cases/100,000 population, a yearly increase of 10.24%. Children <2 years of age were disproportionally affected; incidence in this age group (356.12 cases/100,000 population) was >26-fold higher than for the 30–<50 age group.

Integrative Analysis of Salmonellosis in Israel Reveals Association of Salmonella enterica Serovar 9,12:l,v:− with Extraintestinal Infections, Dissemination of Endemic S. enterica Serovar Typhimurium DT104 Biotypes, and Severe Underreporting of Outbreaks

ABSTRACT Salmonella enterica is the leading etiologic agent of bacterial food-borne outbreaks worldwide. This ubiquitous species contains more than 2,600 serovars that may differ in their host specificity, clinical manifestations, and epidemiology. To characterize salmonellosis epidemiology in Israel and to study the association of nontyphoidal Salmonella (NTS) serovars with invasive infections, 48,345 Salmonella cases reported and serotyped at the National Salmonella Reference Center between 1995 and 2012 were analyzed. A quasi-Poisson regression was used to identify irregular clusters of illness, and pulsed-field gel electrophoresis in conjunction with whole-genome sequencing was applied to molecularly characterize strains of interest. Three hundred twenty-nine human salmonellosis clusters were identified, representing an annual average of 23 (95% confidence interval [CI], 20 to 26) potential outbreaks. We show that the previously unsequenced S. enterica serovar 9,12:l,v:− belongs to the B clade of Salmonella enterica subspecies enterica, and we show its frequent association with extraintestinal infections, compared to other NTS serovars. Furthermore, we identified the dissemination of two prevalent Salmonella enterica serovar Typhimurium DT104 clones in Israel, which are genetically distinct from other global DT104 isolates. Accumulatively, these findings indicate a severe underreporting of Salmonella outbreaks in Israel and provide insights into the epidemiology and genomics of prevalent serovars, responsible for recurring illness.

Emergence of Streptococcus pneumoniae Serotype 12F after Sequential Introduction of 7- and 13-Valent Vaccines, Israel

Israel implemented use of 7- and 13-valent pneumococcal vaccine in 2009 and 2010, respectively. We describe results of prospective, population-based, nationwide active surveillance of Streptococcus pneumoniae serotype 12F (Sp12F) invasive pneumococcal disease (IPD) dynamics in the 7 years after vaccine introduction. Of 4,573 IPD episodes during July 2009–June 2016, a total of 434 (9.5%) were caused by Sp12F. Sp12F IPD rates (cases/100,000 population) increased in children <5 years of age, from 1.44 in 2009–2010 to >3.9 since 2011–2012, followed by an increase in all ages. During 2011–2016, Sp12F was the most prevalent IPD serotype. Sp12F isolates were mostly penicillin nonsusceptible (MIC >0.06 µg/mL; MIC50 = 0.12) and predominantly of sequence type 3774), a clone exclusively found in Israel (constituting ≈90% of isolates in 2000–2009). The sharp increase, long duration, and predominance of Sp12F IPD after vaccine implementation reflect a single clone expansion and may represent more than a transient outbreak.

Curtailed short-term and long-term survival following infection with non-typhoid Salmonella in Israel

Among bacterial foodborne pathogens, non-typhoid Salmonella enterica (NTS) is a leading cause of death worldwide. This study assessed short-term and long-term mortality following NTS infection in Israel, and evaluated the effects of age, sex, source of isolation and different serotypes on mortality. The source of data was a national registry of NTS isolates submitted to the Salmonella Reference Center, Government Central Laboratories, in Jerusalem, Israel, during 1997-2006. Vital status was derived from the registry of the Israeli Ministry of the Interior. The survival of a cohort of 15,919 patients infected with the top five NTS serotypes was evaluated by calculating age-standardized mortality ratios (SMRs) and by Cox proportional hazards multivariate regressions at three follow-up time intervals: 30 days, 1 year and end of follow-up. The median follow-up time was 6.44 years (mean, 6.21 years; range, 1 day to 10.80 years). The cumulative crude mortality rates at the three time intervals were 0.68%, 1.86% and 4.40%, respectively, corresponding to increased SMRs of 16.95 (95% CI 13.9-20.46), 4.25 (95% CI 3.78-4.76), and 1.83 (95% CI 1.70-1.97), respectively. Cox regressions revealed that increasing age, extraintestinal source of isolation and NTS serotype had significant effects on mortality within all three follow-up intervals. The risk of mortality was increased for serotypes Infantis and Typhimurium, and decreased for serotypes Virchow and Hadar, as compared with serotype Enteritidis. The study revealed curtailed short-term and long-term survival following NTS infection that persisted for many years following detection by culture.