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Introduction: Children with peanut allergy are at increased risk of developing tree nut allergies, which can be severe and for most lifelong. Introduction of peanut in the first year of life can reduce the risk of peanut allergy, however, prevention strategies for tree nut allergies have not been established. We aimed to test the efficacy and safety of a novel strategy, a supervised multi-nut oral food challenge (OFC) compared to standard care for tree nut allergy prevention in infants at high risk of developing tree nut allergy, TreEAT. Methods and analysis: TreEAT is a 2-armed, open-label, randomised, controlled trial (RCT). Infants (n=212) aged 4-11months with peanut allergy will be randomised 1:1 at peanut allergy diagnosis to either a hospital-based multi-tree nut (almond, cashew, hazelnut and walnut) OFC using multi-nut butter or standard care (home introduction of individual tree nuts). All infants will be assessed at age 18months, with questionnaires and SPT to peanut and tree nuts. Peanut and tree nut OFCs will be performed as required to determine allergy status for each nut. The primary outcome is tree nut allergy at age 18 months. Secondary outcomes include peanut allergy resolution, proportion and severity of adverse events related to tree nut ingestion, number and frequency of tree nuts ingested, quality of life and parental anxiety and allergy related healthcare visits from randomisation to 18 months of age. Analyses will be performed on an intention-to-treat basis. Ethics and dissemination TreEAT was approved by the Royal Children’s Hospital Human Research Ethics Committee (#70489). Outcomes will be presented at scientific conferences and disseminated through publication. Trial registration number: ClinicalTrials.gov ID: NCT04801823

Research Letter There are few data on long-term effects and quality of life impact of peanut OIT. PPOIT was shown to induce 8-week sustained unresponsiveness that persists to 3-years post-treatment after ad libitum peanut ingestion. PPOIT provides lasting benefits for children with peanut allergy, with long-lasting improvement in health-related quality of life.

Cumulative evidence shows that peanut oral immunotherapy (OIT) is effective at inducing desensitization through downregulation of effector pathways in the allergic reaction cascade; however, only a subset of patients achieve sustained unresponsiveness (remission), which requires redirection of the underlying allergic response toward tolerance. A recent meta-analysis of peanut OIT randomized trials found that OIT is associated with a threefold greater risk of anaphylaxis and twofold greater risk of epinephrine use than allergen avoidance. Strategies to reduce adverse events associated with OIT and improve the ability for OIT to induce sustained unresponsiveness are required to improve the benefit-risk of peanut OIT.

IntroductionEgg allergy is the most common food allergy in children but recent studies have shown persistence or delayed resolution into adolescence. As there is currently no effective long-term treatment, definitive treatments that improve quality of life and prevent fatalities for food allergies are required. We have previously shown that a novel treatment comprising a combination of the probiotic Lactobacillus rhamnosus CGMCC 1.3724 with peanut oral immunotherapy (OIT) is highly effective at inducing sustained unresponsiveness, with benefit persisting to 4 years after treatment cessation in the majority of initial treatment responders. In this study, we plan to extend the probiotic food OIT platform to another allergen, namely egg. We describe the protocol for a phase 2, dual-centre, randomised, controlled trial evaluating the effectiveness of probiotic and egg OIT at inducing desensitisation or sustained unresponsiveness (remission) in participants with egg allergy compared with placebo.Methods and analysis80 participants aged 5–30 years of age with current egg allergy confirmed by double-blind placebo-controlled food challenge at study screening will be recruited from Australia and Singapore. There are two intervention arms—probiotic and egg OIT (active) or placebo. Interventions are administered once daily for 18 months. The primary outcome is the proportion of participants who attain 8-week sustained unresponsiveness in the active group versus placebo group.Ethics and disseminationThis study has been approved by the Human Research Ethics Committees at the Royal Children’s Hospital (HREC 2019.082) and the National Healthcare Group Domain Specific Review Board (2019/00029). Results will be published in peer-reviewed journals and disseminated via presentations at international conferences.Trial registration numberACTRN12619000480189.

Fecal microbial transplantation (FMT) has been shown to be more effective than antimicrobial therapy in the treatment of recurrent Clostridium difficile infection (CDI) in adults, with a randomized control trial (RCT) showing resolution of symptoms and clearance of CDI in 81% of subjects compared to 31% with standard antibiotic therapy (1). This article is protected by copyright. All rights reserved.

Background The prevalence of school students at risk of anaphylaxis in Victoria is unknown and has not been previously studied. Similarly, rates of adrenaline autoinjector usage in the school environment have yet to be determined given increasing prescription rates. Objectives We sought to determine time trends in prevalence of school children at risk of anaphylaxis across all year levels and the annual usage rate of adrenaline autoinjectors in the school setting relative to the number of students at risk of anaphylaxis. Methods Statewide surveys from more than 1,500 government schools including more than 550,000 students were used and prevalence rates (%) with 95% CIs were calculated. Results The overall prevalence of students at risk of anaphylaxis has increased 41% from 0.98% (95% CI, 0.95-1.01) in 2009 to 1.38% (95% CI, 1.35-1.41) in 2014. There was a significant drop in reporting of anaphylaxis risk with transition from the final year of primary school to the first year of secondary school, suggesting a change in parental reporting of anaphylaxis risk among secondary school students. The number of adrenaline autoinjectors activated per 1000 students at risk of anaphylaxis ranged from 6 to 8 per year, with consistently higher activation use in secondary school students than in primary school students. Conclusions Statewide prevalence of anaphylaxis risk has increased in children attending Victorian government schools. However, adrenaline autoinjector activation has remained fairly stable despite known increase in the rates of prescription.

With the rapid generation of genetic information from the Streptomyces coelicolor genome project, deciphering the relevant gene products is critical for understanding the genetics of this model streptomycete. A putative malate synthase gene (aceB) from S. coelicolor A3(2) was identified by homology-based analysis, cloned by polymerase chain reaction, and fully sequenced on both strands. The putative malate synthase from S. coelicolor has an amino acid identity of 77% with the malate synthase of S. clavuligerus, and possesses an open reading frame which codes for a protein of 540 amino acids. In order to establish the identity of this gene, the putative aceB clones were subcloned into the expression vector pET24a, and heterologously expressed in Escherichia coli BL21(DE3). Soluble cell-free extracts containing the recombinant putative malate synthase exhibited a specific activity of 1623 (nmol·mg-1·min-1), which is an increment of 92-fold compared to the non-recombinant control. Thus, the gene product was confirmed to be a malate synthase. Interestingly, the specific activity of S. coelicolor malate synthase was found to be almost 8-fold higher than the specific activity of S. clavuligerus malate synthase under similar expression conditions. Furthermore, the genomic organisation of the three Streptomyces aceB genes cloned thus far is different from that of other bacterial malate synthases, and warrants further investigation.Key words: primary metabolism, polymerase chain reaction, glyoxylate pathway.

A key step which involves the cyclization of δ-(L-α-aminoadipyl)-L-cysteinyl-D-valine to the bicyclic ring structure of isopenicillin N in the penicillin and cephalosporin biosynthetic pathway, is catalyzed by isopenicillin N synthase (IPNS). In this study, an IPNS gene from Streptomyces lipmanii NRRL 3584 (slIPNS) was cloned via PCR-based homology cloning, sequenced and expressed in Escherichia coli. Soluble slIPNS was overexpressed up to 21% of total soluble protein, and verified to be functionally active when in an IPNS enzymatic assay. Sequence comparison of the slIPNS gene obtained (excluding the consensus primer sequences) with another cloned IPNS from S. lipmanii 16884.3, revealed one three-nucleotide deletion and three closely-spaced single nucleotide deletions. Futhermore, this paper also reports the first instance of the usage of PCR as an alternative and rapid strategy for IPNS cloning using consensus primers. Key words: isopenicillin N synthase, β-lactam antibiotics, secondary metabolism, consensus primers.

With the rapid generation of genetic information from the Streptomyces coelicolor genome project, deciphering the relevant gene products is critical for understanding the genetics of this model streptomycete. A putative malate synthase gene (aceB) from S. coelicolor A3(2) was identified by homology-based analysis, cloned by polymerase chain reaction, and fully sequenced on both strands. The putative malate synthase from S. coelicolor has an amino acid identity of 77% with the malate synthase of S. clavuligerus, and possesses an open reading frame which codes for a protein of 540 amino acids. In order to establish the identity of this gene, the putative aceB clones were subcloned into the expression vector pET24a, and heterologously expressed in Escherichia coli BL21(DE3). Soluble cell-free extracts containing the recombinant putative malate synthase exhibited a specific activity of 1623 (nmol.mg-1.min-1), which is an increment of 92-fold compared to the non-recombinant control. Thus, the gene product was confirmed to be a malate synthase. Interestingly, the specific activity of S. coelicolor malate synthase was found to be almost 8-fold higher than the specific activity of S. clavuligerus malate synthase under similar expression conditions. Furthermore, the genomic organisation of the three Streptomyces aceB genes cloned thus far is different from that of other bacterial malate synthases, and warrants further investigation.

Background Wiskott-Aldrich Syndrome (WAS) is an X-linked primary immunodeficiency associated with recurrent infections, eczema, and small platelets. Patients are at risk of autoimmune complications which represent a more severe form of the WAS disease spectrum. Case history We described a 4-year-old boy who was diagnosed with WAS, in the context of mucosal bleeding and severe thrombocytopenia. The thrombocytopenia did not respond to intravenous immunoglobulins and steroids. Several months post-diagnosis, he developed left lower lobe pneumococcal pneumonia, arthritis and a vasculitic rash which was leukocytoclastic on histology. This was followed by a rise in his IgG levels (peaking at 46 g/L), abnormal liver function tests which were predominantly cholestatic, and persistently low C4 levels. Liver biopsy showed vasculitis and autoimmune cholangitis. His anti-C1q autoantibodies and rheumatoid factor were also significantly elevated. He was treated with a combination of anti-CD20 monoclonal antibody and steroids, resulting in a significant improvement in his clinical symptoms and laboratory markers. He underwent a matched sibling bone marrow transplant (BMT) and is currently well 45 days post-transplant. Discussion In conclusion, vasculitis in WAS requires prompt treatment due to the risk of severe morbidity and is a consideration for BMT.