Dynamics of childhood invasive meningococcal disease in Israel during a 22-year period (1989-2010).

AIM: To describe the dynamics in the incidence of childhood invasive meningococcal disease (IMD) in Israel during a 22-year period (1989-2010). METHODS: A longitudinal prospective surveillance in all 27 medical centers with pediatric services in Israel. All cases of children <15 years old with positive blood/cerebrospinal fluid (CSF) culture for Neisseria meningitidis were reported. Demographic, clinical, and bacteriological data were recorded. Meningococcal vaccine was not routinely given to Israeli children during the study period. RESULTS: The mean age ± standard deviation (SD) among the 743 cases was 40.7 ± 40.2 months. The mean yearly incidence/100,000 was 2.0 ± 0.8. Age-specific incidences were 8.7 ± 2.8, 2.9 ± 1.5, and 0.8 ± 0.5 for children <1, 1-4, and >4 years old, respectively. The overall incidence decreased significantly from 3.7 in 1989 to 1.5 in 2010. Meningitis constituted 69.2 % of all cases. The most common serogroups were: B (76.9 %), C (10.9 %), Y (8.0 %), and W(135) (2.9 %). 78.6 % of all serogroup B isolates were from children <5 years old (p < 0.01). Serogroup C was found mainly in children ≥5 years old (63.4 %). The case fatality rates (CFRs) for children <1, 1-4, >4 years old, and the total study population were 9.2, 12.3, 7.7, and 9.9 %, respectively. CFRs were higher for children without meningitis (14.9 %) compared to children with meningitis (7.9 %) (p < 0.01). CONCLUSIONS: Overall, and for serogroups B and W135, childhood IMD rates decreased significantly in Israel during the study period, without routine vaccine usage. The most common serogroup in all age groups was B, which was most prevalent in children <5 years old. No change in the trend of the overall CFR was noted during the study period.

What is the clinical relevance of respiratory syncytial virus bronchiolitis?: findings from a multi-center, prospective study.

Acute bronchiolitis (AB) is caused primarily by respiratory syncytial virus (RSV). Recent laboratory tools have implicated a variety of other pathogens; however, their clinical relevance has not been clearly defined. The purpose of this study was to determine whether the etiological agents of AB affect its course. A multicenter prospective study was performed in previously healthy children <24 months of age who presented with <4 days duration of AB. Subjects were divided into the following groups: "only RSV," "also RSV," "no RSV," and "no pathogen." The clinical severity score on admission as well as the overall severity of disease was assessed. RSV was the most common cause of AB (77.5 %). "Only RSV" or "also RSV" patients had a higher clinical score on admission compared to those with "no RSV," p < 0.001 and p < 0.02, respectively. "Only RSV" and "also RSV" patients had a higher disease severity score when compared to patients with "no RSV," 5.9 ± 1.4 vs. 5.1 ± 1.5, p < 0.001, and 5.6 ± 1.4 vs. 5.1 ± 1.5, p < 0.02, respectively. Disease severity did not vary as a function of transfer to the pediatric intensive care unit (PICU) or duration of supplemental oxygen, yet, "only RSV" was associated with a longer length of stay (LOS) than "no RSV," p < 0.02. "Only RSV"-related AB was associated with a more severe initial clinical presentation and a longer LOS. There appears to be little immediate clinical benefit to diagnosing RSV AB to the individual patient, but the application of these diagnostic methods may have significant cost-saving implications and, thus, deserves consideration by medical professionals and health policy analysts.

Brain abscess in children - epidemiology, predisposing factors and management in the modern medicine era.

AIMS: Brain abscess is rare in children. Predisposing factors are found in almost 85% of cases. Overall, 25% of brain abscesses develop in children, mostly in the 4-7 years age group. Our study aimed to characterize children with brain abscesses treated in our hospital, identify risk factors, pathogens and short-term outcome. METHODS: A retrospective cohort of 20 years period, (1989-2009) included 27 children (0-18 years). Medical records were analysed for age, gender, presenting symptoms and signs, predisposing factors, laboratory tests, imaging, microbiology results, treatment and outcome. RESULTS: Of all the children, 63% (17/27) were male patients; mean age was 7.9 years and 52% were referred from other hospitals. Predisposing factors were identified in 81%, congenital heart disease and otitis were rare and sinusitis was found in 22% of the children. Main symptoms and signs included headaches, fever, neurological signs convulsions, (41%, 81%, 78% and 41% respectively). In 30% of cases, cultures were sterile. All patients were operated in addition to antibiotic treatment. Outcome was good with low mortality rate (3.7%). CONCLUSIONS: Manifestations of brain abscess may be subtle. A high index of suspicion and early imaging are warranted, different predisposing factors may reflect early intervention for congenital heart diseases. Mortality is rare in the modern medicine era.

Isolation of mesenchymal stem cells from G-CSF-mobilized human peripheral blood using fibrin microbeads.

Adult mesenchymal stem cells (MSC) that are able to differentiate into various mesenchymal cell types are typically isolated from bone marrow, but their significant presence in human peripheral blood (PB) is controversial. Fibrin microbeads (FMB) that bind matrix-dependent cells were used to isolate MSC from the mononuclear fraction of mobilized PB of adult healthy human donors treated with a granulocyte colony-stimulating factor. Isolation by plastic adherence resulted in a negligible number of MSC in all samples tested, whereas FMB-based isolation yielded spindle-shaped cell samples that could further expand on plastic or on FMB in eight out of the 11 samples. The yield of these cells at days 17-18 after the harvest was approximately 0.5% of the initial cell number. The isolated cells were grown on plastic and characterized by FACS analysis and immunohistochemistry for specific markers. Following culturing and first passage, the FMB-isolated cells stained positive for mesenchymal stromal cell markers CD90 and CD105, expressed vimentin and fibronectin and were negative for hematopoietic markers CD45 and CD34. These cells could differentiate into osteoblasts, adipocytes and chondrocytes. This study indicates that FMB may have special advantage in isolating MSC from sources such as mobilized PB, where the number of such cells is scarce.

Clinical features and epidemiology of invasive Kingella kingae infections in southern Israel.

OBJECTIVE: To characterize the clinical spectrum and epidemiology of invasive Kingella kingae infections in children living in southern Israel. DESIGN: Five-year observational, descriptive study. POPULATION: Children in whom K. kingae was isolated from blood or other normally sterile body fluid. RESULTS: Twenty-five patients with invasive K. kingae infection (13 male and 12 female) were identified. Twenty-four of these children were younger than 2 years. The annual incidence was 14.3, 27.4, and 31.9 cases per 100,000 children < or = 4 years, < or = 24 months, and < or = 12 months, respectively. Seventeen (68%) of 25 patients sought treatment between July and December. Concomitant upper respiratory tract infection or stomatitis was observed in 14 (56%) of the patients, suggesting a respiratory or buccal source for the infection. Four children were bacteremic: 2 of them suffered from a lower respiratory tract infection, and the remaining 2 had bacteremia with no evident focal infection. Twenty-one children had skeletal infections and none of them was bacteremic; 16 had septic arthritis, 3 had osteomyelitis, 1 had both osteomyelitis and septic arthritis of the adjacent joint, and 1 had dactylitis of the hand. Involvement of the ankle was unusually frequent among children with septic arthritis, whereas the calcaneus was involved in 3 of the 4 children with osteomyelitis. Antibiotic treatment resulted in full recovery in all cases, and only 2 patients with septic arthritis required surgical drainage. CONCLUSION: Kingella kingae is a much more common cause of invasive infection in young children than has been previously recognized. The disease has a clear seasonal pattern, usually affects the skeletal system, frequently involves unusual bones and joints, and follows a benign course.

Outpatient treatment of serious community-acquired pediatric infections using once daily intramuscular ceftriaxone.

Pediatric patients with serious infections are usually hospitalized for parenteral antibiotic treatment. We studied prospectively 74 pediatric patients with community-acquired serious infections and used once daily intramuscular ceftriaxone. Seventeen patients (23%) were initially hospitalized and 57 (77%) patients were treated entirely as outpatients. An initial intramuscular dose of 75 mg/kg was followed by daily doses of 50 mg/kg (maximum, 1.5 g). Infections treated included periorbital/buccal cellulitis, other cellulitis, urinary tract infections, pneumonia, osteomyelitis, mastoiditis, suppurative arthritis and orbital cellulitis. Organisms were recovered from cultures of 37 (50%) patients and 6 (8%) patients were bacteremic. Bacteria included Gram-positive (mostly Staphylococcus aureus) and Gram-negative (mostly enteric bacilli and Haemophilus influenzae organisms). No serious side effects were observed. Of 74 patients 72 (97%) were cured and improvement was usually observed within 24 hours. Two patients did not improve: one with chronic Pseudomonas mastoiditis; and one with lung abscess. Based on previous experience it is estimated that 376 hospitalization days were saved. All 72 successfully treated patients and their parents resumed normal activity within 72 hours of starting therapy. Our data suggest that ceftriaxone can be used for outpatient treatment of some infectious diseases.

Safety and immunogenicity of oral tetravalent human-rhesus reassortant rotavirus vaccine in neonates.

We conducted a prospective randomized double blind study to determine: (1) the safety and immunogenicity of live oral tetravalent human-rhesus rotavirus reassortant vaccine in neonates; and (2) whether a second dose at the age of 6 to 8 weeks enhances the immunogenicity. Two hundred forty healthy neonates were enrolled and received vaccine (183) or placebo (57) on the second day of life. At the age of 6 to 8 weeks 133 received placebo and 88 received a second dose of vaccine. Medical events were noted within 10 days from vaccine administration in 6 of 183 (3.3%) vaccine recipients vs. 0 of 57 placebo recipients (P = 0.34) after the first dose and in 8 of 88 (9%) vs. 4 of 133 (3%) after the second dose (P = 0.069); none was severe and all were of short duration. Seroresponse of any type (detectable IgA or 4-fold increase of titer to rhesus rotavirus was 9% for the placebo, vs. 52 and 46% for those who received one and two doses of vaccine, respectively. However, neutralizing antibodies against human serotypes 1, 2 and 3 were not raised successfully in vaccinated infants when compared with placebo recipients. The same pattern was found when geometric mean titers were compared. Vaccine take was better when cord blood titers were low. At the age of 1 year the vaccinees had more often high titers for antirhesus rotavirus antibodies (> 640) than the placebo recipients (49% vs. 0%; P < 0.001). NO difference was found between the groups in neutralizing antibodies to human serotypes 1, 2 and 3 rotavirus.(ABSTRACT TRUNCATED AT 250 WORDS)

The use of prophylactic furazolidone to control a nosocomial epidemic of multiply resistant Salmonella typhimurium in pediatric wards.

The nosocomial spread of enteric pathogens is often difficult to control in overcrowded pediatric wards. During 1983 and 1984, despite cohorting of patients and enforced hand washing, more than 200 cases of nosocomial multiply resistant Salmonella typhimurium phage type R-9 were observed on two adjacent pediatric wards. Most cases occurred during the summer months. After 19 new cases were detected early in the summer of 1985, oral administration of furazolidone throughout their entire hospital stay (2.5 mg/kg twice daily) was recommended for all subsequently hospitalized infants. Among the 114 (65%) infants who were appropriately treated, only one additional case (1%) was detected. In contrast 11 (19%) cases occurred among the 59 infants who were inappropriately treated: 5 of 35 (14%) of those who were not treated and 6 of 24 (25%) in whom treatment with furazolidone was delayed greater than 24 hours (P less than 0.001 between the appropriately and inappropriately treated groups). In pediatric wards where infection control measures cannot be optimally applied, prophylactic furazolidone administration may be helpful in preventing the spread of enteric pathogens.

Rotavirus diarrhea in Jewish and Bedouin children in the Negev region of Israel: epidemiology, clinical aspects and possible role of malnutrition in severity of illness.

We conducted a 1-year prospective study in the Negev region of southern Israel to determine the epidemiologic and clinical patterns of rotavirus diarrhea. A total of 605 patients were studied, 392 Bedouins and 213 Jews, 441 of whom had diarrhea (449 episodes) and 164 did not. Rotavirus was the most common organism detected in children with diarrhea (63 of 444; 14%) but was rarely found in controls (3 of 163; 2%) (P less than 0.001). In 22% (12 of 54) of the rotavirus-positive patients, at least one other organism was also detected. The rate of rotavirus detection decreased as age increased, from 18% in the first year to 8% in the third year of life. Hospitalization with rotavirus diarrhea occurred more frequently in the summer. However, during winter, when diarrhea was less prevalent in the community, the proportion of cases associated with rotavirus was higher. Compared with controls, malnourished children were more likely to be hospitalized. However, rotavirus was detected in similar proportions among well-nourished and malnourished cases with diarrhea. The most prevalent rotavirus serotype was type 1 (in 69%), followed by types 4 and 2 (18 and 13%, respectively). We estimated that during the study period, approximately 2% of all Bedouin infants vs. only 0.2% of Jewish infants were hospitalized with rotavirus disease in their first year of life. Clinical signs and symptoms and stool appearance were not useful in predicting rotavirus detection. Malnutrition seems to be an important indicator of disease severity, which may explain why the toll of rotavirus-associated morbidity and mortality is particularly high among children in developing countries.

Clinical and epidemiologic significance of coagulase-negative staphylococci bacteremia in a tertiary care university Israeli hospital.

OBJECTIVES: To characterize the clinical significance of coagulase-negative staphylococci (CNS) bacteremia. DESIGN: Prospective cohort study. SETTING: A 900-bed hospital in Haifa, Israel, from November 1996 to March 1997. RESULTS: Of 137 episodes of positive blood cultures for CNS, 41 (30%) were considered as true infection. Twenty-seven of 119 episodes associated with only 1 blood culture positive for CNS (23%) met the definition of infection as compared with 14 of 18 episodes (78%) associated with 2 or more blood cultures positive for CNS (P <.001). Methicillin resistance was significantly more frequent among Staphylococcus epidermidis isolates of episodes of true bacteremia than of episodes of contamination (15 of 22 [68%] vs. 11 of 33 [33%], respectively; P =.02). S hominis was isolated only in episodes considered as contamination (P =.01). It was estimated that CNS represents 24% of all nosocomial bloodstream pathogens. When CNS were isolated in the first 48 hours of hospitalization, an intravascular device was more frequently associated with episodes of true bacteremia than in those considered as contamination (7 of 7 [100%] vs. 10 of 57 [18%], respectively; P <.001). The mortality rate among patients with true CNS bacteremia was 16%. CONCLUSION: Some laboratory parameters may help identify episodes of true CNS bacteremia, which appears to be more common than previously considered.

Evaluation of an enzyme immunoassay for the detection of Cryptosporidium spp. in stool specimens from infants and young children in field studies.

Diagnosis of Cryptosporidium is made by the identification of oocysts in stool specimens. Screening in field studies relies mainly on acid-fast staining followed by microscopic examination. The more sensitive immunofluorescent antibody (IFA) staining method is time-consuming, may involve technical difficulties, and is extremely costly as a screening procedure in field studies. We evaluated the diagnostic utility of a commercially available enzyme immunoassay (EIA), which detects Cryptosporidium-specific antigen, in 204 unprocessed stool specimens obtained from patients less than three years of age from a field study in southern Israel. When compared with the routine screening procedure applied in this field study (screening by acid-fast staining and microscopy after concentration, and confirmation of positive results by IFA), both the sensitivity and specificity were 98%. Of 139 specimens negative by microscopy, 13 (9.3%) were positive by the EIA. Eleven of these were confirmed by inhibition with antibody to Cryptosporidia-specific antigen. The EIA is an important tool for identifying Cryptosporidium in fecal specimens in field studies since it is sensitive, specific, simple to use, and unaffected by the presence of a preservative.

Device-associated, device-day infection rates in an Israeli adult general intensive care unit.

Surveillance is an essential element of hospital infection control programs. Previous studies have shown that interhospital comparison of intensive care unit (ICU) nosocomial infections (NI) may be best made by comparing ICU-type-specific, device-associated infection rates and that these adjusted rates vary by ICU type. The aim of this study was to evaluate whether significant structural improvements introduced in an adult general ICU were associated with changes in the NI rates in this unit. In addition, we compared these rates with those of ICUs reported by the National Nosocomial Infections Surveillance (NNIS) System of the Centers for Diseases Control and Prevention. During a 12-month period 337 patients were surveyed. There were 20 ventilator-associated pneumonias (VAP)/1000 ventilator (VEN)-days, 12 bloodstream infections (BSI)/1000 central vascular catheter (CVC)-days and 14 urinary tract infection (UTI)/1000 indwelling urinary catheter (IUC)-days. Structural changes and reduction in device utilization ratios were not followed by change in NI rates in this unit. VAP and BSI rates were comparable to those reported for neurosurgical and burn ICUs, respectively, in the NNIS System, despite a much higher device utilization ratios. The present study provides specific surveillance data for further interhospital comparison with similar types of ICUs.

Cost benefit analysis of Haemophilus influenzae type b vaccination programme in Israel.

STUDY OBJECTIVE: The recent availability of Haemophilus influenzae type b (HIB) conjugate vaccines prompted an examination of the costs and benefits of four and three dose HIB prevention programmes targeting all newborns in Israel. MEASUREMENTS AND MAIN RESULTS: A four dose programme would reduce the number of childhood (aged 0-13) HIB cases from 184.2 to 31.3 per year, yielding a benefit ($1.03 million) to cost ($3.55 million) ratio of just 0.29/l for health services only, based on a vaccine price of $7.74 per dose. When benefits resulting from a reduction in mild handicaps and severe neurological sequelae are included, the benefit ($4.48 million) to cost ratio rises to 1.26/l and it reaches 1.45/l when the $0.66 million indirect benefits of reduced work absences and mortality are also included. Break even vaccine costs are $2.24 when health service benefits only are considered and $11.21 when all the benefits are included. CONCLUSION: In the absence of other projects with higher benefit to cost ratios, Israel should start to provide a nationwide HIB vaccination programme since the monetary benefits to society of such a programme will exceed the costs to society. A barrier to implementation may occur, however, because the costs of the programme exceed the benefits to the health services alone.

Partitioning of dioxins, dibenzofurans, and coplanar PCBS in blood, milk, adipose tissue, placenta and cord blood from five American women.

Partitioning of dioxins, dibenzofurans and the dioxin-like coplanar PCBs was determined by congener-specific high resolution gc-ms analysis of compounds in 6 tissue samples each from 5 women. Samples were whole blood obtained prior to delivery; maternal adipose tissue, cord blood and placenta obtained during cesarean section delivery; and whole blood and milk taken at the time of first obstetrical follow-up examination, one to two months following delivery. All women lived in upstate New York. Specimens were collected in late 1995 and early 1996. Mean measured levels of total PCDDs, PCDFs and coplanar PCBs were 352 pg/g for adipose tissue, 526 pg/g for predelivery blood, 182 pg/g for placenta, 165 pg/g for cord blood, 352 pg/g for postpartum blood and 220 pg/g for milk. Mean total TEQ levels were 11.6 pg/g TEQ for adipose tissue, 12.1 pg/g TEQ for predelivery blood, 10.5 pg/g TEQ for placenta, 5.8 pg/g TEQ for cord blood, 10.0 pg/g TEQ for postpartum blood and 10.2 pg/g TEQ for milk.

[Articular involvement as a presenting symptom of malignancy in childhood].

The clinical and laboratory features of 6 children with arthritis or arthralgia as presenting manifestations of malignancy are described. 4 of the 6 had leukemia, 1 had a neuroblastoma and 1 had histiocytosis-X. The diagnosis of malignancy was made 2 days to 2.5 months after onset of symptoms. Although all patients presented with limp, the clinical courses suggested the need to consider leukemia and the other malignancies in the differential diagnosis.

Epidemiology and clinical significance of non-tuberculous mycobacteria isolated from pulmonary specimens.

SETTING: A tertiary university medical centre in northern Israel. OBJECTIVE: To evaluate the clinical significance of non-tuberculous mycobacteria (NTM) isolated from pulmonary specimens. DESIGN: Clinical and microbiological data were collected from patient files. Cases were classified as definite, probable and possible NTM. RESULTS: Between 2004 and 2010, 215 cases with respiratory isolates of NTM were identified. Mycobacterium xenopi was the most common species (n = 84, 39.1%), followed by M. simiae (n = 52, 24.2%). A total of 170 (79.1%) cases were classified as possible and 24 (11.2%) as probable NTM. Only 21 (9.8%) cases were considered definite NTM, the majority of which were M. kansasii and M. avium complex. CONCLUSIONS: M. xenopi and M. simiae are the most prevalent species of NTM isolated from respiratory samples in northern Israel. However, most of these isolates represent colonisation. Of the relatively small number of clinically significant isolates, M. kansasii and M. avium complex were the most common.

Impact of carbapenem resistance on the outcome of patients' hospital-acquired bacteraemia caused by Klebsiella pneumoniae.

BACKGROUND: Carbapenem-resistant Enterobacteriaceae, especially Klebsiella spp., have become a major health problem recently worldwide. Since 2006 the incidence of carbapenem-resistant Klebsiella pneumoniae (CRKP) infections has increased substantially in Israel. Bloodstream infections (BSIs) caused by these strains have been associated with high rates of treatment failure and mortality. AIM: This study was designed to identify risk factors for carbapenem resistance among patients with healthcare-related (HCR) K. pneumoniae bacteraemia and predictors of mortality associated with HCR-CRKP bacteraemia compared with carbapenem-susceptible K. pneumoniae (CSKP). METHODS: In this retrospective case-control study, all cases of K. pneumoniae bacteraemia during 2006-2008 were identified. Resistance patterns, underlying morbidities, risk factors for drug resistance and mortality rates were compared for patients with CRKP and CSKP bacteraemia. FINDINGS: Two hundred and fourteen patients with CSKP bacteraemia were compared with 103 patients with CRKP bacteraemia. Severe, chronic comorbidities and prior antibiotic use were more frequent among patients with CRKP bacteraemia. On multivariate analysis prior use of macrolides and antibiotic exposure for ≥14 days remained the only independent factors associated with CRKP bacteraemia. Mortality rates of CRKP patients were significantly higher than those of CSKP patients. On multivariate analyses: bedridden status, chronic liver disease, Charlson comorbidity index ≥5, mechanical ventilation, and haemodialysis remained independently associated with mortality among patients with K. pneumoniae bacteraemia. Carbapenem resistance was not a risk factor for mortality. CONCLUSIONS: Previous antibiotic exposure is a risk factor for CRKP-BSI. Mortality among patients with K. pneumoniae bacteraemia is associated with serious comorbidities, but not with carbapenem resistance.

Distribution of fluconazole-resistant Candida bloodstream isolates among hospitals and inpatient services in Israel.

The emergence of fluconazole-resistant Candida (FRC) is worrisome, but little is known about susceptibility patterns in different nosocomial settings. We prospectively analysed Candida bloodstream isolates in 18 medical centres in Israel (six tertiary-care and 12 community hospitals). The study included 444 episodes of candidaemia (450 patient-specific isolates, 8.5% fluconazole-resistant). Institutional FRC bloodstream infection rates correlated with annual inpatient days, and were strongly associated with the presence and activity of haematology/oncology services. Infection with Candida krusei and fluconazole-resistant Candida glabrata occurred exclusively in hospitals with >600 beds. These findings suggest that empirical antifungal strategies should be tailored to the nosocomial setting.