Eli Somekh

Association between Common Toll-Like Receptor 4 Mutations and Severe Respiratory Syncytial Virus Disease

BACKGROUNDnThe clinical spectrum of respiratory syncytial virus (RSV) bronchiolitis in previously healthy infants is extremely variable. Thus, it is likely that factors such as genetic heterogeneity contribute to disease severity. Toll-like receptor 4 (TLR4) and CD14 are part of a receptor complex involved in the innate immune response to RSV.nnnMETHODSnThe association of the TLR4 mutations (Asp299Gly and Thr399Ile) and the CD14/-159 polymorphism were analyzed in 99 infants hospitalized with severe RSV bronchiolitis (group I). Eighty-two ambulatory infants with mild RSV bronchiolitis (group II) and 90 healthy adults (group III) composed the 2 control groups. The TLR4 mutations and the CD14/-159 polymorphism were genotyped by use of reverse-transcriptase polymerase chain reaction and restriction fragment-length polymorphism analysis, respectively.nnnRESULTSnEach of the TLR4 mutations, either alone or in cosegregation, were associated with severe RSV bronchiolitis: the Asp299Gly and Thr399Ile mutations were significantly overrepresented in group I, compared with groups II and III. No association between the CD14/-159 polymorphism and RSV bronchiolitis was found.nnnCONCLUSIONSnThese findings suggest that TLR4 mutations, but not the CD14/-159 polymorphism, are associated with an increased risk of severe RSV bronchiolitis in previously healthy infants.

PFAPA syndrome: new clinical aspects disclosed

Background: The recently described PFAPA (Periodic Fever, Aphthous stomatitis, Pharyngitis and Adenitis) syndrome is characterised by periodic fever, aphthous stomatitis, pharyngitis and adenitis. However, there are currently relatively few data on the natural history of this syndrome. Objective: To describe the presentation, clinical course, doctors’ awareness, therapeutic response and long-term follow-up of children with PFAPA syndrome. Methods: Children with PFAPA syndrome referred over a 5-year period (from January 1999 to January 2004) were enrolled in the study. Data were gathered from medical records, parents’ interviews, physical examination and telephone calls. Results: 54 patients with PFAPA syndrome were evaluated. Our patients had a higher rate of abdominal pain (65%) and a lower rate of aphthous stomatitis (39%) than those in previous reports. Four different patterns of disease evolution were identified, including the relatively common (nu200a=u200a14, 26%) and newly described course of alternating remissions and relapses. The remissions lasted 8.5 months on average (range 4–36 months). Diagnosis was established by primary paediatricians in 30 of 54 (56%) patients. However, a substantial delay in diagnosis was apparent (mean 15 months). Episodes were curtailed by a much lower dose of prednisone or equivalent corticosteroid (mean 0.6 mg/kg/day, range 0.15–1.5 mg/kg/day) than reported previously. Tonsillectomy was successful in the prevention of recurrence of further episodes in all six patients who underwent the procedure. Conclusions: We describe several new characteristics of PFAPA syndrome in children, contributing to our knowledge of this relatively unrecognised but troublesome syndrome. Early diagnosis and appropriate treatment can markedly improve the quality of life of both patients and families.

Natural history of food allergy in infants and children in Israel

BACKGROUNDnKnowledge about the natural history of food allergy, especially sesame, is scarce.nnnOBJECTIVEnTo follow the natural history of food allergies in Israel, particularly of sesame allergy.nnnMETHODSnThe survey was conducted based on clinical records and a detailed questionnaire of children diagnosed as having food allergy.nnnRESULTSnWe found 234 children with suspected food allergy. Testing detected 283 allergies in 180 patients (77%) with confirmed diagnosis. The most common allergies were to cows milk (n = 125), eggs (n = 71), sesame (n = 30), and soy (n = 23). Of those with milk allergy, 69% were IgE mediated (group 1) and 31% were non-IgE mediated (group 2). Group 1 was more likely to have an atopic background than was group 2 (P = .003), whereas group 2 was more likely to have resolution of the allergy (35 of 39 [90%] in group 2 compared with only 32 of 86 [37%] in group 1, P < .001). Allergy to soy was found in 23 children, of whom 87% manifested with gastrointestinal symptoms and 21 (91%) were also allergic to cows milk. In 19 children (83%), the allergy resolved. Thirty children had allergy to sesame, and 73% of them had an atopic background. The allergy resolved in only 9 of these patients (30%) at a mean age of 2.8 years.nnnCONCLUSIONSnThe distribution of food allergens in Israel differs from that in other countries. Non-IgE-mediated food allergy and particularly milk and soy allergy were likely to resolve completely with time. Sesame allergy was 1 of the most frequent in this cohort, was usually IgE mediated, and tended to resolve in only a few patients.

Perianal Abscess and Fistula-In-Ano in Infants: A Different Entity?

PURPOSEThe features of perianal abscess and fistula-in-ano in infants are different from those of older children, and there is controversy regarding their treatment. The aim of this study was to assess the efficacy of various methods used for their management.METHODSA retrospective analysis of the records was conducted for all infants younger than 24 months of age treated for perianal abscess, fistula-in-ano, or both from 1990 to 2002.RESULTSThe study included 98 infants. Perianal abscess was found in 77 patients (75 males), and fistula-in-ano in 21. No infant had an underlying illness. Drainage was performed by needle aspiration in 47 patients and by incision and drainage in 5. Following drainage, 43 patients received antibiotics. Altogether, 6 infants were treated with antibiotics alone and 19 with local care alone. Twenty-eight boys (36.4 percent) had an evolution toward fistula-in-ano. Patients who received antibiotics following drainage were less likely to develop fistula-in-ano than were patients who underwent a drainage procedure alone (27.9 percent vs. 66.7 percent, P < 0.05). All patients with fistula-in-ano were male and had been previously treated for perianal abscess (21 patients elsewhere and 28 in our department). Spontaneous cure of fistula-in-ano occurred in 42.9 percent of them (average 3.2 months), and 57.1 percent underwent fistulectomy for persistent fistula-in-ano. Cryptotomy was added when an involved crypt was found (11 patients, 39.3 percent). No recurrence of fistula-in-ano was noted after fistulectomy.CONCLUSIONSLocal treatment for perianal abscess during the early stage and drainage by needle aspiration during the progressive stage are effective. Antibiotics may be considered for patients undergoing drainage of perianal abscess. Fistula-in-ano can be managed conservatively for one to three months. For a persisting fistula, fistulectomy with cryptotomy (when abnormal anal crypts are found) is the preferred treatment.

Silent reintroduction of wild-type poliovirus to Israel, 2013 – risk communication challenges in an argumentative atmosphere

Israel has been certified as polio-free by the World Health Organization and its routine immunisation schedule consists of inactivated poliovirus vaccine (IPV) only. At the end of May 2013, the Israeli Ministry of Health (MOH) has confirmed the reintroduction of wild-type poliovirus 1 into the country. Documented ongoing human-to-human transmission necessitated a thorough risk assessment followed by a supplemental immunisation campaign using oral polio vaccine (OPV). The unusual situation in which ongoing poliovirus transmission was picked up through an early warning system of sewage monitoring without active polio cases, brought about significant challenges in risk communication. This paper reviews the challenges faced by the MOH and the communication strategy devised, in order to facilitate and optimise the various components of the public health response, particularly vaccination. Lessons learned from our recent experience may inform risk communication approaches in other countries that may face a similar situation as global polio eradication moves towards the End game.

Reduction in Antibiotic Use Following a Cluster Randomized Controlled Multifaceted Intervention: The Israeli Judicious Antibiotic Prescription Study

BACKGROUNDnAntibiotic overuse is of great public health concern. This study assessed whether intervention among physicians and their treated population could achieve a sustained reduction in antibiotic use, specifically in classes known to promote antibiotic resistance among children in a community setting.nnnMETHODSnWe performed a cluster randomized controlled multifaceted trial among 52 primary care pediatricians and the 88,000 children registered in their practices. The intervention was led by local leaders and engaged the participating physicians. It included physician focus group meetings, workshops, seminars, and practice campaigns. These activities focused on self-developed guidelines, improving parent and physician knowledge, diagnostic skills, and parent-physician communication skills that promoted awareness of antibiotic resistance. The main outcome measure was the change in annual antibiotic prescription rates (APRs) of children treated by the intervention group physicians as compared with rates among those treated by control group physicians. The study comprised a 2-year pre-intervention period, a 3-year intervention period, and a 1-year follow-up period. Mixed-effect models were used to assess risk ratios to account for the clustered study design.nnnRESULTSnA decrease in the total APR among children treated by the intervention physicians compared with those treated by the control physicians was observed in the first intervention year (APR decrease among control physicians, 40%; APR decrease among intervention physicians, 22%; relative risk [RR], .76; 95% confidence interval [CI], .75-.78). This reduction crossed over all antibiotic classes but was most prominent for macrolides (macrolide prescription rate among control physicians, 58%; macrolide prescription rate among intervention physicians, 27%; RR, .58; 95% CI, .55-.62). The effect was sustained during the 4 following years. CONCLUSIONS.u2003Multifaceted intervention that engages the physicians in an educational process is effective in reducing APRs and can be sustained.nnnCLINICAL TRIALS REGISTRATIONnNCT01187758.

Chronic Urticaria in Children: Expanding the "Autoimmune Kaleidoscope"

Most cases of chronic urticaria (CU) are considered idiopathic. It has recently been accepted that autoimmunity plays a critical role in the pathogenesis of CU in some of these patients. Although urticaria is common in the pediatric population, the knowledge regarding CU-associated autoimmunity is very limited. We describe the association of CU with a wide spectrum of clinical and laboratory autoimmune disorders in 2 children and emphasize the concept that CU is another manifestation of the “autoimmune kaleidoscope.”

The Israeli public health response to wild poliovirus importation

In 2013, a silent wild poliovirus type 1 importation and sustained transmission event occurred in southern Israel. With the aim of preventing clinical poliomyelitis and ensuring virus re-elimination, the public health response to the importation event included intensification of clinical and environmental surveillance activities, enhancement of vaccine coverage, and supplemental immunisation with a bivalent oral polio vaccine against wild poliovirus types 1 and 3. A national campaign launched in August, 2013, resulted in vaccination of 943,587 children younger than 10 years (79% of the eligible target population). Expanded environmental surveillance (roughly 80% population coverage) documented a gradual disappearance of wild poliovirus type 1 in the country from September, 2013, to April, 2014. No paralytic poliomyelitis case was detected. A prompt extensive and coordinated national public health response, implemented on the basis of evidence-based decision making, successfully contained this serious importation and sustained transmission event of wild poliovirus to Israel. On April 28, 2015, WHO officially declared Israel as a polio-free country.

Novel mutations in RAG1/2 and ADA genes in Israeli patients presenting with T-B- SCID or Omenn syndrome

The relative frequency of the different forms of SCID may vary in different countries. The most frequent form in Israel is the autosomal-recessive T-B- SCID or Omenn syndrome while X-linked SCID is rare. We report our immunological and genetic analyses in multicentre study of patients presenting with either T-B- SCID or Omenn syndrome. Among 16 patients, we identified 7 novel mutations in 6 patients. In the RAG1 gene we detected two novel mutations: L454Q and 469 fs-4bpdel. In the RAG 2 gene: 3 novel mutations: D65Y, G157V, and E480X. One T-B- SCID patient was found to be a compound heterozygote for new mutations in the ADA gene: W264X and R235W. Prenatal diagnosis was performed in 8 families while others refused due to religious reasons. Identification of the new mutations expands our knowledge regarding the unique features of SCID phenotype in Israel and may help the families seeking for genetic counseling.

Benign Paroxysmal Torticollis in Infancy

We present four children with benign paroxymsal torticollis (BPT) and a review of the literature. BPT appears to be a self-limited disorder that occurs predominantly in females. The attacks of head tilting usually start in infancy, may recur at varying intervals until the age of 1 to 5 years, and may be confused with other seizures. Other symptoms, such as ataxia and vomiting, may be associated with the attacks of torticollis. Less frequently, infantile migraine also may be associated.