Israel Medical Association Journal

This mini review includes two case descriptions. It introduces the use of chicken egg yolk antibody (IgY) solutions in the prevention and cure of viral and bacterial infections. Application for the protection against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), rotavirus, and influenza viruses, as well as for the eradication of Pseudomonas aeruginosa, caries, various enteric bacteria and other pathogens, and toxins have been developed. This approach is a fast, reliable, safe, and tested method for producing molecular shield and protection against emerging pathogens and epidemics. In the current pandemic situation caused by coronavirus disease-2019 (COVID-19), this method of passive immunization could be applied for rapid protection against modifiable agents. The specific IgY antibodies start to accumulate into egg yolks about 3 weeks after the immunization of the chicken. The product can be collected safely, as the antigen is not found in the eggs. This method for microbial safety uses natural means and commonly used food substances, which have been tested and could be produced for both blocking epidemics and applying personalized medicine

Background: The recommendation of the U.S. Centers for Disease Control and Prevention regarding universal screening for Group B Streptococcus (GBS) at 35–37 weeks gestational age in pregnancy is not accepted in Israel. The National Council for Obstetrics, Neonatology and Genetics recommends intrapartum prophylaxis, mainly based on risk factors, to prevent early neonatal GBS infection. This policy is based on past studies demonstrating low colonization rates of the bacteria in Israeli pregnant women and very low neonatal sepsis rates.

Objectives: To determine the applicability of the high-risk group prophylaxis policy for Arab Israeli pregnant women.

Methods: Vaginorectal swabs from Arab Israeli pregnant women who attended the labor ward between October 2015 and February 2016, were obtained before any pelvic examination for GBS identification using Quidel’s AmpliVue® GBS assay. Women who tested positive received intrapartum antibiotic prophylaxis to prevent neonatal infection. Obstetric data were collected from each woman from a standardized questionnaire. Data regarding the delivery and neonates were collected as well.

Results: The study comprised 188 Arab pregnant women who met the inclusion criteria and signed a consent form to participate in the study. Of these, 59 had positive tests, and a carriage rate of 31%. No neonatal colonization of GBS was found.

Conclusions: The carrier rate in Arab pregnant women in northern Israel is higher than the national average, at least partially due to the more sensitive method of GBS detection used in the present study.

Background: Children and adolescents are commonly referred to an orthopedic surgeon to assess knee malalignment.

Objectives: To assess the prevalence of genu varum and valgum among adolescents, and to identify correlates of these conditions.

Methods: A medical database of 47,588 candidates for military service presenting to the northern recruitment center during an 11 year period was analyzed to identify clinical knee alignment. Based on the standing skin surface intercondylar distance (ICD) or intermalleolar distance (IMD), the prevalence rates of genu varum (ICD ≥ 3 cm) and genu valgum (IMD ≥ 4 cm) were calculated. The association of gender, body mass index (BMI), and place of residence to knee alignment was studied.

Results: The rates of genu varum and valgum were 11.4% (5427) and 5.6% (2639), respectively. Genu varum was significantly more prevalent among males than females (16.2% vs. 4.4%, P < 0.001). It was also more prevalent among underweight subjects and less prevalent among overweight and obese subjects (P < 0.001). Genu valgum was significantly more prevalent among females than males (9.4% vs. 2.9%) and in overweight and obese subjects compared to those with normal BMI, while less prevalent in underweight subjects (P < 0.001). Multivariate analysis revealed that genu varum was independently positively associated with male gender, underweight, and living in a rural area. Genu valgum was independently positively associated with female gender, overweight, and obesity.

Conclusions: This study establishes a modern benchmark for the cutoff and prevalence of genu varum and valgum as well as associations with gender and BMI.

Background: Once a well-recognized entity, occult bacteremia (OB) is no longer a significant or serious bacterial infection. First following the introduction of the Haemophilus influenzae type B vaccine and now with the implementation of the conjugate pneumococcal vaccine (PCV), the number of cases has declined significantly. This has led to a change in many published guidelines to avoid taking blood cultures in fully vaccinated children presenting with fever. In Israel, the introduction of the PCV13 is now widespread. 

Objectives: To assess the incidence and outcome of OB, specifically by Streptococcus pneumoniae, in a single large pediatric medical center. 

Methods: We conducted a retrospective review of all cases of pneumococcal bacteremias in the years 2008–2013 and specifically those considered occult. 

Results: Of 355 cases of bacteremia diagnosed during the study period, 164 were caused by S. pneumoniae and 20 (12.8%) were considered occult. None of the OB cases had any complications. OB was not found in children over the age of 36 months. There was a change in the serotypes involving pneumococcal OB. 

Conclusions: OB is uncommon in the PCV-vaccinated population and the serotypes involved have changed.

 

Background: Legg-Calvé-Perthes disease (LCPD) is an idiopathic hip osteonecrosis prevalent in children < age 15 years. The etiology remains incompletely understood, partly because of multiple potential environmental risk factors and partly because of lack of genetic markers. It has been hypothesized that hyperactivity may induce mechanical stress and/or vascular damage at a fragile joint. 

Objectives: To assess children with LCPD for markers of attention deficit hyperactivity disorder (ADHD) relative to their unaffected comparably aged siblings to exclude the contribution of hyperactive behavior versus environmental and/or genetic factors in LCPD. 

Methods: All children followed in the Pediatric Orthopedic Clinic, and their comparably aged siblings, were recruited. ADHD was assessed using the TOVA computerized test and DSM-IV criteria. Quality of life and sleep disorders as ancillary tests were assessed using the Child Health Questionnaire (Parent Form 50), Pediatric Outcomes Data Collection Instrument, and Pediatric Daytime Sleepiness Scale.

Results: Sixteen children with LCPD (age 9.1 ± 3.3, 75% males) were compared with their closest-aged siblings (age 9.3 ± 2.6, 30% males). Mean TOVA scores of children with LCPD (-3.79 ± 2.6) and of their non-LCPD siblings (-3.6 ± 4.04) were lower relative to the general population (0 ± 1.8, P < 0.0001). Both group means were in the ADHD range (≤ -1.8) implying that 73% of this LCPD cohort and 53% of their non-LCPD siblings performed in the ADHD range, relative to 3.6% incidence expected in the general population (P < 0.0001). Other test results were similar in both groups. 

Conclusions: Our findings in a small cohort of children with LCPD and their comparably aged siblings do not support an association between LCPD and ADHD. ADHD markers were equally high in the LCPD children and siblings. 

 

Background: Anti-red blood cell antibodies, free light chains (FLC) and prothrombotic proteins (PTP) may co-elute with intact immunogIobulin (IgG), and may be the cause of adverse reactions to intravenous immunoglobulin preparations (IVIG).

Objectives: To investigate the presence of residual amounts of these components in IVIG and their effects on ABO blood group agglutination.

Methods: Iso-agglutinin anti-A and anti-B activity was determined with a direct hemagglutination assay of red blood cell (RBC) suspensions from 1% of 46 blood donors together with the serial dilutions of five IVIG (IV1, IV2, IV3, IV4, IV5). Anti-A1 monoclonal antibody was used to confirm reactivity with the A1-reference RBC. The selected IVIG were diluted to a final concentration of 25 mg/ml in 0.15 M NaCl and 0.01 M phosphate-buffered saline (PBS), pH 7.4, with or without a further twofold dilution in a low ionic strength solution.

Results: A variation up to fivefold in the titer strength of anti-A/B activity was observed between the IVIG preparations. A2-type RBC required higher IVIG inputs when tested in 0.15 M NaCl. The differences in FLC kappa and lambda concentrations were as high as > 400 mg/L among the various IVIG. Only IV1 had a significantly high level of antiphospholipid IgG antibodies (18 U/ml). We demonstrated the presence of anti-RBC antibodies, FLC and PTP in IVIG preparations.

Conclusions: Our findings provide clear evidence that IVIG may harbor pathophysiological substrates with a potential risk for adverse effects such as iatrogenic hemolysis, FLC-associated disorders, and thromboembolism. 

Background: In the last decade the use of different types of oral immunotherapy for food-allergic patients has increased with generally satisfactory outcomes. Cow’s milk and hen’s egg, a common element in the daily diet, have received the main interest. Most of these immunotherapy regimens are performed in the hospital, causing inconvenience for both children and their parents.

Objectives: To assess the efficacy and safety of a home-based oral immunotherapy regimen with raw pasteurized egg.

Methods: The study group comprised children aged 6 years and older with allergy to hen’s egg proteins, proven by positive skin prick-tests (SPT) and/or specific immunoglobulin E (sIgE) and positive open oral food challenge (OOFC) with boiled or raw egg. Patients who met the inclusion criteria and signed the informed consent form underwent egg immunotherapy according to an established schedule.

Results: The treatment was given to 31 of the 36 recruited patients: 80.6% of the intention to treat population achieved complete tolerance to the maximum dose equivalent to one raw hen’s egg, 3.2% achieved incomplete tolerance, and 16.2% did not achieve an acceptable tolerance dose. Most of the latter patients had a positive baseline OOFC with low doses of boiled egg. The average number of reactions per treated patient was 5.8, most of them grades 1 and 2 there were no grade 4 reactions.

Conclusions: This home-based oral immunotherapy protocol proved to effectively induce tolerance to hen’s egg in most of the egg-allergic children and its safety profile was acceptable.

Background: Respiratory syncytial virus bronchiolitis is the single leading cause of pediatric admissions for infants in the first year of life, presenting regularly in epidemic proportions in the winter months and impacting in a major way on pediatric inpatient services.

Objective: To quantitate the burden of RSV[1] disease on a pediatric service with the purpose of providing a database for proper health planning and resource allocation.

Methods: We conducted a prospective 5 year study of documented RSV infections in a single pediatric service. RSV disease was confirmed by direct immunofluorescence testing of nasal swabs from all hospitalized cases of bronchiolitis.

Results: On average, 147 ± 17 cases of RSV bronchiolitis were admitted annually in the November–March RSV season, representing 7%–9% of admissions and 10%–14% of hospital days. There was a consistent male preponderance of admissions (55–64%) and 15–23% of admissions were patients less than 1 month old. In peak months RSV cases accounted for as many of 40% of the hospitalized infants and was the leading cause of over-occupancy (up to 126%) in the pediatric ward during the winter,

Conclusions: RSV infection is a major burden for pediatric inpatient services during the winter season. This recurrent and predictable “epidemic,” which regularly leads to over-occupancy, requires increased manpower (nursing) and resources (beds, pulse oximeters) to facilitate proper care. Since this annual event is not a surprise nor an unexpected peak, but rather a cyclical predictable epidemiological phenomenon, proper planning and allocation of services are crucial.