Impact of newborn screening for SCID on the management of congenital athymia.

BACKGROUND: Newborn screening (NBS) programs for severe combined immunodeficiency facilitate early diagnosis of severe combined immunodeficiency and promote early treatment with hematopoietic stem cell transplantation, resulting in improved clinical outcomes. Infants with congenital athymia are also identified through NBS because of severe T-cell lymphopenia. With the expanding introduction of NBS programs, referrals of athymic patients for treatment with thymus transplantation have recently increased at Great Ormond Street Hospital (GOSH) (London, United Kingdom). OBJECTIVE: We studied the impact of NBS on timely diagnosis and treatment of athymic infants with thymus transplantation at GOSH. METHODS: We compared age at referral and complications between athymic infants diagnosed after clinical presentation (n = 25) and infants identified through NBS (n = 19) who were referred for thymus transplantation at GOSH between October 2019 and February 2023. We assessed whether age at time of treatment influences thymic output at 6 and 12 months after transplantation. RESULTS: The infants referred after identification through NBS were significantly younger and had fewer complications, in particular fewer infections. All deaths occurred in the group of those who did not undergo NBS, including 6 patients before and 2 after thymus transplantation because of preexisting infections. In the absence of significant comorbidities or diagnostic uncertainties, timely treatment was achieved more frequently after NBS. Treatment when younger than age 4 months was associated with higher thymic output at 6 and 12 months after transplantation. CONCLUSION: NBS contributes to earlier recognition of congenital athymia, promoting referral of athymic patients for thymus transplantation before they acquire infections or other complications and facilitating treatment at a younger age, thus playing an important role in improving their outcomes.

How Worried Are You about Food Fraud? A Preliminary Multi-Country Study among Consumers in Selected Sub-Saharan African Countries.

Food fraud is an old, recurring, and global threat to public health. It poses a serious threat to food security in sub-Saharan Africa (SSA). Despite the prevalence of food fraud in SSA, little is known about how food fraud is viewed by consumers. This study aims to provide an overview of consumers' concerns about food fraud in SSA. A multi-country survey was conducted in October 2022-31 January 2023, and 838 valid responses were returned. To reduce the large and correlated dataset, Principal Component Analysis (PCA) was used. Five components were derived from PCA: (i) Staple foods; (ii) Premium food and drink products; (iii) Trust in reliable sources; (iv) Trust in less reliable sources; and (v) Trust in food vendors. The findings revealed Ghanaian (mean rank = 509.47) and Nigerian (mean rank = 454.82) consumers tended to score higher on the measure of food fraud concern suggesting that they were less confident in the safety and quality of the food they consume. Demographic characteristics including age, number of children, personal and family experience of food fraud and PCA components such as 'Staple foods', 'Trust in reliable sources', and 'Trust in food vendors' significantly predicted the model. This is the first preliminary study to provide empirical findings on consumers' concerns about food fraud in SSA. Practical and policy recommendations for the region are suggested. This includes (i) modelling the AfriFoodinTegrity in West Africa across other major regions such as Central, East, and Southern Africa; (ii) establish a regional sub-Saharan Africa Rapid Alert System for Food and Feed (SSA-RASFF) platform; and (iii) food safety and food fraud reports could be incorporated into SSA-RASFF portal for information sharing.

Exploring dark kitchens in Brazilian urban centres: A study of delivery-only restaurants with food delivery apps.

Dark kitchen is a delivery-only restaurant that operates without direct contact with the consumer, has no premises for local consumption and sells exclusively through online platforms. The main objective of this work is to identify and characterise dark kitchens in three urban centres featured in the most used food delivery app in Brazil. To this end, data collection was conducted in two phases. In the first phase, through data mining, we collected information from restaurants in three cities (Limeira, Campinas and São Paulo - Brazil) that were provided in the food delivery app. A total of 22,520 establishments were searched from the central point of each of the cities. In the second phase, the first 1,000 restaurants in each city were classified as dark kitchens, standard, or undefined restaurants. A thematic content analysis was conducted to further distinguish the dark kitchen models. Of the restaurants evaluated, 1,749 (65.2%) were classified as standard restaurants, 727 (27.1%) as dark kitchens, and 206 (7.7%) as undefined. In terms of the characteristics of dark kitchens, they were more dispersed and located further away from the central points compared to standard restaurants. Meals in dark kitchens were cheaper than in standard restaurants, and had a lower number of user reviews. Most of the dark kitchens in São Paulo served Brazilian dishes, while in the smaller cities, Limeira and Campinas, it was mainly snacks and desserts. Six different models of dark kitchen were identified: Independent dark kitchen; shell-type (hub); franchise; virtual kitchen in a standard restaurant (different menu); virtual kitchen in a standard restaurant (similar menu but different name); and home-based dark kitchen. The modelling approach and methodology used to classify and identify dark kitchens is considered a contribution to science as it allows a better understanding of this fast growing sector of the food industry. This in turn can help to develop management strategies and policies for the sector. Our study is also of value to regulators to determine their proliferation through urban planning and to promote appropriate guidelines for dark kitchens as they differ from standard restaurants.

Food fraud and mitigating strategies of UK food supply chain during COVID-19.

Covid-19 had shown the vulnerability of the food supply chain and fraudsters may take advantage of the pandemic whilst the population needed a continuous supply of safe and quality food. The lack of monitoring and policing in the food supply chain may encourage fraudsters to upscale their operations. Previous studies had warned of a surge in fraudulent products due to COVID-19. This raised the question on whether food fraud had increased during the pandemic? This study aims to investigate food fraud during COVID-19 and how the food supply chain develops mitigating strategies against fraudulent activities. A mixed-method approach including survey and semi-structured interviews were conducted among UK food businesses. Two hundred and two agri-food businesses responded to the survey and 15 semi-structured interviews were conducted. The majority of the food businesses did not experience an increase of food fraud activities during COVID-19. Two thematic domains and ten sub-themes were identified from the data set. There was a heightened sense of anticipation and preparation for increased fraudulent activities during the pandemic. The main risk mitigating strategies included horizon scanning; developing and maintaining supplier relationship and assurance; understanding product characteristics, testing capabilities, conducting vulnerability assessments and training. Practical and cost-effective strategies for small and medium food businesses were recommended. This is the first empirical study on food fraud and mitigating strategies of the UK food supply chain during the pandemic. Our findings provide evidence for informing the policies and practices of the food regulatory authorities as well as best practices to protect the UK food supply chain against food fraud during exogenous shocks like COVID-19.

Rituximab-induced hypogammaglobulinemia and infection risk in pediatric patients.

BACKGROUND: Rituximab is a B-cell depleting agent used in B-cell malignancies and autoimmune diseases. A subset of adult patients may develop prolonged and symptomatic hypogammaglobulinemia following rituximab treatment. However, this phenomenon has not been well delineated in the pediatric population. OBJECTIVES: This study sought to determine the prevalence, risk factors, and clinical significance of hypogammaglobulinemia following rituximab therapy in children. METHODS: This was a multicenter, retrospective cohort study that extracted clinical and immunological data from pediatric patients who received rituximab. RESULTS: The cohort comprised 207 patients (median age, 12.0 years). Compared to baseline values, there was a significant increase in hypogammaglobulinemia post-rituximab therapy, with an increase in prevalence of hypo-IgG (28.7%-42.6%; P = .009), hypo-IgA (11.1%-20.4%; P = .02), and hypo-IgM (20.0%-62.0%; P < .0001). Additionally, low IgG levels at any time post-rituximab therapy were associated with a higher risk of serious infections (34.4% vs 18.9%; odds ratio, 2.3; 95% CI, 1.1-4.8; P = .03). Persistent IgG hypogammaglobulinemia was observed in 27 of 101 evaluable patients (26.7%). Significant risk factors for persistent IgG hypogammaglobulinemia included low IgG and IgA levels pre-rituximab therapy. Nine patients (4.3%) within the study were subsequently diagnosed with a primary immunodeficiency, 7 of which received rituximab for autoimmune cytopenias. CONCLUSIONS: Hypogammaglobulinemia post-rituximab treatment is frequently diagnosed within the pediatric population. Low IgG levels are associated with a significant increase in serious infections, and underlying primary immunodeficiencies are relatively common in children receiving rituximab, thus highlighting the importance of immunologic monitoring both before and after rituximab therapy.

Paediatric eosinophilic oesophagitis in New Zealand: A 3-year prospective study.

AIM: Eosinophilic oesophagitis (EoE) is a rare, chronic, relapsing immune/antigen-mediated disease characterised by symptoms of oesophageal dysfunction, with a paucity of data among New Zealand (NZ) children. This 3-year prospective study aimed to characterise EoE diagnosed nationally and to describe initial treatment strategies adopted. METHODS: Information on new diagnoses of paediatric EoE was obtained via the New Zealand Paediatric Surveillance Unit, through monthly questionnaires. RESULTS: From February 2014 to January 2017, 73 new cases (74% male) of EoE were reported, including 74% NZ European, 10% Asian, 7% Maori, 5% Middle-Eastern and 3% Pacific peoples. Median age of symptom onset was 4 years; dysphagia (48%) was the most common, followed by vomiting/regurgitation (40%), food impaction (19%) and epigastric pain (16%). A co-morbid history of other allergic conditions was present in 62% of patients, and 41% had a first degree relative with atopy. Seventy-nine percent of patients had abnormal endoscopic findings, most commonly linear furrows and white plaques; none had strictures. Median eosinophil count per high-powered field was 40 and 50 in the mid and distal oesophagus, respectively. Fifty-four percent of patients were initially managed with dietary manipulation alone (four required elemental feeds, five nasogastric tubes). Fifty-four percent of patients were treated with swallowed corticosteroids and 7% with prednisone. One patient was also treated with a leukotriene receptor antagonist. CONCLUSION: This first prospective study on paediatric patients with EoE in NZ finds similar demographics and disease characteristics as in other populations despite our unique ethnic population. Long-term prospective observational data should significantly improve our knowledge of this rare condition.

Diagnosis and management of severe combined immunodeficiency in Australia and New Zealand.

This consensus document outlines the recommendations from the Australasian Society of Clinical Immunology and Allergy Transplantation and Primary Immunodeficiency group for the diagnosis and management of patients with severe combined immunodeficiency. It also provides a proposed framework for the early investigation, management and supportive care prior to haematopoietic stem cell transplantation.

Human interleukin-2 receptor ß mutations associated with defects in immunity and peripheral tolerance.

Interleukin-2, which conveys essential signals for immunity, operates through a heterotrimeric receptor. Here we identify human interleukin-2 receptor (IL-2R) ß chain (IL2RB) gene defects as a cause of life-threatening immune dysregulation. We report three homozygous mutations in the IL2RB gene of eight individuals from four consanguineous families that cause disease by distinct mechanisms. Nearly all patients presented with autoantibodies, hypergammaglobulinemia, bowel inflammation, dermatological abnormalities, lymphadenopathy, and cytomegalovirus disease. Patient T lymphocytes lacked surface expression of IL-2Rß and were unable to respond to IL-2 stimulation. By contrast, natural killer cells retained partial IL-2Rß expression and function. IL-2Rß loss of function was recapitulated in a recombinant system in which IL2RB mutations caused reduced surface expression and IL-2 binding. Stem cell transplant ameliorated clinical symptoms in one patient; forced expression of wild-type IL-2Rß also increased the IL-2 responsiveness of patient T lymphocytes in vitro. Insights from these patients can inform the development of IL-2-based therapeutics for immunological diseases and cancer.

Paediatric food-induced anaphylaxis hospital presentations in New Zealand.

AIM: Globally, rates of paediatric food-induced anaphylaxis (FIA) are increasing. Little data is available regarding the epidemiology of FIA among New Zealand (NZ) children. This study investigated the incidence of paediatric (0-14 years) FIA hospital presentations in NZ over a 10-year period. METHODS: Ministry of Health public hospital discharge data from 2006 to 2015 were analysed using FIA-related International Classification of Diseases codes (T78.0 - anaphylactic shock due to adverse food reaction and T78.2 - anaphylactic shock unspecified and free text qualifier) to identify acute hospital presentations. RESULTS: The overall annualised FIA hospital presentation rate was 16.2 per 100 000 children. Subgroup analysis indicated a significantly higher rate in males (19.1/100 000) than in females (13.1/100 000), and among children aged less than 2 years of age (50.5/100 000) compared with older children. Rates among Asian and Pacific children were higher than Maori and NZ European children. In 67.7% of cases, a single specific allergen was suggested by the information provided; among these cases, nuts (48%), specifically peanuts (26%), were the most commonly reported allergen, followed by cow's milk (21%). Time trend analysis showed a 2.8-fold increase in the overall annualised rate for the 10-year period. CONCLUSION: These findings are consistent with other international studies indicating increasing rates of FIA in children. These data will provide information for a review of NZ paediatric allergy services to ensure current international standards with regard to the equitable delivery of timely, appropriate and accessible care are being met. Reasons for differences by gender, age and ethnicity require further investigation.

The case for a national service for primary immune deficiency disorders in New Zealand.

Primary immune deficiency disorders (PIDs) are rare conditions for which effective treatment is available. It is critical these patients are identified at an early stage to prevent unnecessary morbidity and mortality. Treatment of these disorders is expensive and expert evaluation and ongoing management by a clinical immunologist is essential. Until recently there has been a major shortage of clinical immunologists in New Zealand. While the numbers of trained immunologists have increased in recent years, most are located in Auckland. The majority of symptomatic PID patients require life-long immunoglobulin replacement. Currently there is a shortage of subcutaneous and intravenous immunoglobulin (SCIG/IVIG) in New Zealand. A recent audit by the New Zealand Blood Service (NZBS) showed that compliance with indications for SCIG/IVIG treatment was poor in District Health Boards (DHBs) without an immunology service. The NZBS audit has shown that approximately 20% of annual prescriptions for SCIG/IVIG, costing $6M, do not comply with UK or Australian guidelines. Inappropriate use may have contributed to the present shortage of SCIG/IVIG necessitating importation of the product. This is likely to have resulted in a major unnecessary financial burden to each DHB. Here we present the case for a national service responsible for the tertiary care of PID patients and oversight for immunoglobulin use for primary and non-haematological secondary immunodeficiencies. We propose that other PIDs, including hereditary angioedema, are integrated into a national PID service. Ancillary services, including the customised genetic testing service, and research are also an essential component of an integrated national PID service and are described in this review. As we show here, a hub-and-spoke model for a national service for PIDs would result in major cost savings, as well as improved patient care. It would also allow seamless transition from paediatric to adult services.

Paediatric non-IgE mediated food allergy: guide for practitioners.

AIM: Food avoidance in children is increasingly common due to concerns about allergy. We aim to review the current literature on paediatric non-IgE mediated food allergy including what is known about pathophysiology, diagnosis, management and prognosis of common and severe presentations. Considerations regarding appropriate formula selection are also presented. METHODS: Common non-IgE mediated conditions were searched through common medical databases. Thorough review of available literature was then synthesised and critically appraised. RESULTS: Current understanding of immunological mechanisms of most non-IgE mediated conditions remains elusive. Most conditions are outgrown in childhood and have a good prognosis. Dietary modification for some conditions is important to ensure safety. They are not recommended in all situations due to potentially harmful consequences. CONCLUSION: Assessment of children with concerns regarding non-IgE mediated conditions requires a thorough history and is generally not supported by reliable diagnostic tests. Caution is warranted when advising families to undertake dietary exclusions unless well supported by the evidence and ensuring benefits outweigh any potential harm.

Fatal food allergy and opportunities for risk minimisation.

IgE-mediated food allergy affects up to 6% of children and 2% of adults. Fatal food allergic reactions are rare. Management of food allergy requires accurate identification of allergen(s), risk assessment, education on allergen avoidance / management of allergic reaction, and follow up. A case of fatal allergic reaction to cashew ingestion is reported, illustrating the importance of these aspects of management.

The changing epidemiology of food allergy--implications for New Zealand.

Food allergy (FA) is recognised as an important public health problem in developed countries. Recent studies suggest a significant proportion of the general population has a definable FA. The methods used to study FA influence published estimates of incidence and prevalence. In particular, studies relying on self-assessment are likely to overestimate the condition compared to studies using a comprehensive approach including symptoms, allergy testing, rigorously conducted laboratory tests, and food challenges. Currently there are no reliable data on the prevalence of FA in New Zealand. This has had several adverse consequences including the lack of public hospital services for patients with severe allergies. In this article we summarise the epidemiological data on FA and discuss the implications for New Zealand.

Anaphylaxis management: the essential role of adrenaline (epinephrine) auto-injectors. Should PHARMAC fund them in New Zealand?

Anaphylaxis is an important life-threatening medical emergency. There is extensive evidence supporting the early use of intramuscular adrenaline for first medical responders and for self-initiated treatment, in at-risk individuals. Major patient groups identified as at ongoing risk are children and adults with severe food allergy, patients with venom allergy who have not been desensitised, and those with idiopathic anaphylaxis. Individual anaphylactic events are largely unpredictable. The most effective and safe route of administration for adrenaline is intramuscular, but it is difficult for patients and carers to achieve accurate and timely self-administration using an ampoule, needle, and syringe. The adrenaline auto-injector device which is available in New Zealand (the EpiPen) is not funded by PHARMAC, and thus only available to patients and families who are able to afford the purchase cost. It is difficult to understand the continued unwillingness of PHARMAC to fund an adrenaline auto-injector device to at-risk individuals, given the large body of information supporting its efficacy and use. The Australian model, where authorisation from a relevant specialist is required, could be used.