‘Holiday Sickness’ – reported exploratory outcome of over 500 United Kingdom holidaymakers with Travellers diarrhoea

Aims: To ascertain any predictors of potential food poisoning pathogens and development of post-infective irritable bowel syndrome (IBS) in UK travellers. An analysis was undertaken on prospectively collected data on 527 patients reporting symptoms of suspected food poisoning between June 2012 and June 2015. Main outcome measures: Positive stool sample indicative of food poisoning pathogens and diagnosis of post-infective IBS. Results: Data on 527 patients were examined. The large majority of patients did not provide a stool sample on return from holiday (n = 430, 81.6%) as few visited a Doctor locally or in the UK. Only 18 patients (18.6%, 95% confidence interval [CI] 11.4–27.7) who provided a stool sample were positive for microbiological food poisoning pathogens. Univariate analysis indicated a significant relationship between a positive stool sample and whether the individual sought any medical assistance at the resort (odds ratio [OR] 0.24, 95% CI 0.08–0.70) and whether they took any treatment (including self-medicated), (OR 0.21, 95% CI 0.06–0.67). Of the 527 patients only 30 (5.7%, 95% CI 3.9–8.1) experienced post-infective IBS. Univariate regression indicated a significant relationship between experiencing Per Rectal (PR) bleeding and a diagnosis of post-infective IBS (OR 3.64, 95% CI 1.00–10.49). Univariate regression also indicated an increase in the risk of developing post-infective IBS with increasing duration of symptoms (OR 1.04, 95% CI 1.02–1.05). No significant relationship was found between a positive stool sample and developing post-infective IBS (P = 0.307). Conclusions: Very few patients provide a stool sample after experiencing holiday sickness abroad. Of those that do, only a small proportion have a positive stool sample indicative of a food poisoning microorganism. Around 6% of individuals were diagnosed with post-infective IBS. Those individuals with PR bleeding and symptoms persisting for longer durations were significantly more at risk of developing post-infective IBS, whilst medical aid and treatment abroad was found to reduce the odds of a positive stool sample

Neutrophil dysfunction triggers inflammatory bowel disease in G6PC3 deficiency

From Wiley via Jisc Publications RouterHistory: received 2019-12-09, rev-recd 2020-08-28, accepted 2020-08-29, pub-electronic 2020-09-15, pub-print 2021-06Article version: VoRPublication status: PublishedFunder: Medical Research Council Clinical Research Training Fellowship; Grant(s): MR/N001427/1Funder: European Society of Paediatric Infectious Diseases FellowshipFunder: Wellcome Trust; Id: http://dx.doi.org/10.13039/100010269; Grant(s): 202865/Z/16/ZAbstract: The glucose‐6‐phosphatase catalytic subunit 3 (G6PC3) encodes a ubiquitously expressed enzyme that regulates cytoplasmic glucose availability. Loss‐of‐function biallelic G6PC3 mutations cause severe congenital neutropenia and a diverse spectrum of extra‐hematological manifestations, among which inflammatory bowel disease (IBD) has been anecdotally reported. Neutrophil function and clinical response to granulocyte colony‐stimulating factor (G‐CSF) and hematopoietic stem cell transplantation (HSCT) were investigated in 4 children with G6PC3 deficiency‐associated IBD. G6PC3 deficiency was associated with early‐onset IBD refractory to treatment with steroids and infliximab. The symptoms of IBD progressed despite G‐CSF treatment. In vitro studies on the patients’ blood showed that neutrophils displayed higher levels of activation markers (CD11b, CD66b, and CD14), excessive IL‐8 and reactive oxygen species, and increased apoptosis and secondary necrosis. Secondary necrosis was exaggerated after stimulation with Escherichia coli and could be partially rescued with supplemental exogenous glucose. HSCT led to normalization of neutrophil function and remission of gastrointestinal symptoms. We conclude that neutrophils in G6PC3 deficiency release pro‐inflammatory mediators when exposed to gut bacteria, associated with intestinal inflammation, despite treatment with G‐CSF. HSCT is an effective therapeutic option in patients with G6PC3 deficiency‐associated IBD refractory to immune suppressants

HLA-DQA1*05 carriage associated with development of anti-drug antibodies to infliximab and adalimumab in patients with Crohn's Disease

Anti-tumor necrosis factor (anti-TNF) therapies are the most widely used biologic drugs for treating immune-mediated diseases, but repeated administration can induce the formation of anti-drug antibodies. The ability to identify patients at increased risk for development of anti-drug antibodies would facilitate selection of therapy and use of preventative strategies.This article is freely available via Open Access. Click on Publisher URL to access the full-text

REVIEW OF CELIAC DISEASE PRESENTATION IN A PEDIATRIC TERTIARY CENTRE

ABSTRACT BACKGROUND: Celiac disease is an immune-mediated disorder with a multiform presentation and therefore a challenging diagnosis. OBJECTIVE: Our purpose is to identify the epidemiological, clinical, laboratory and histologic characteristics of children with celiac disease at diagnosis and on follow-up. METHODS: Children with previously established or newly diagnosed celiac disease, admitted in a tertiary centre in a two-year period (2014-2016) were recruited. Data was collected retrospectively from electronic medical records and clinical notes, and subsequently analysed with SPSS version 20.0. RESULTS: A total of 159 patients, out of 312, were included. Age ranged from 1 to 17 years (mean ± SD: 8.5±4.5 years, 69% girls). Disease presentation was classical in 60%, non-classical in 25%, subclinical in 10% and 5% classified as potential celiac disease. Non-classical and subclinical profiles had a higher mean age at presentation but not statistically significant (P-value 0.24). The most frequent gastrointestinal features at presentation were abdominal pain (58%), diarrhea (43%) and bloating (27%). A positive family history for celiac disease was present in 24% (n=35). We found anaemia in 23%, low ferritin in 63% and a moderate to severe deficiency of 25-hydroxyvitamin D in 62%. celiac disease -specific serologic testing and esophagogastroduodenoscopy were performed in 99%. Histology revealed modified Marsh 2 or 3 enteropathy in 94%, the remaining had normal histology but positive human leukocyte antigen typing. Clinical improvement at 12 months of gluten-free diet was complete in 51% and partial in 49%. IgA tTG normalized after 12-30 months of gluten-free diet in 45%. On growth assessment at diagnosis and after 12-28 months of gluten-free diet, 100% had height increase (mean ±SD: 7.11±4.43 cm) and 96% weight gain (mean ±SD: 5.60±4.91 kg). CONCLUSION: Our findings outline the diverse clinical presentations of pediatric celiac disease that should be considered irrespective of age. Increased clinician’s awareness will enable an early diagnosis and treatment, with subsequent symptom and nutritional status improvement

COVID-19 outbreak: a potential threat to routine vaccination programme activities in Nigeria

COVID-19 is an infectious disease caused by the most recently discovered coronavirus (SARS-CoV-2). The virus and disease were unknown before the outbreak began in the city of Wuhan, China, in December 2019. Nigeria and other sub-Sahara Africa countries like the rest of the world introduced several lockdown measures as part of their public health response to mitigate the spread of the virus. This, however, was not without the likelihood of consequences considering the weak health systems. The access and supply side of vaccination was more likely to have been affected by the lockdown measures. When vaccination services are disrupted even for brief periods during emergencies, the risk of outbreak-prone vaccine-preventable diseases increases, leading to excess morbidity and mortality. This highlights the importance of maintaining essential services such as vaccination in times of emergency. There is therefore an urgent need to ensure that children are protected against those diseases for which vaccines already exist. The COVID-19 outbreak has posed a new hindrance to vaccination activities in Nigeria and across Sub-Saharan Africa with associated threat to surveillance of vaccine-preventable diseases. Achieving and sustaining high levels of vaccination coverage during this period must, therefore, be a priority for all health systems

Spontaneous adverse drug reaction reporting during the seasonal malaria chemoprevention campaign in 2022

Abstract Background Seasonal administration of antimalaria drug, sulphadoxine/pyrimethamine plus amodiaquine to children 3–59 months is a malaria preventive intervention used for the reduction of childhood malaria morbidity and mortality in area with highly seasonal malaria transmission like sub-Saharan Africa. This intervention has been deployed in Nigeria and other sub-Saharan African countries for years and may continue for more years to come either alone or combination with other novel interventions. Despite the importance of pharmacovigilance, there is currently a dearth of pharmacovigilance data in most African countries, especially in public health interventions like seasonal malaria chemoprevention campaigns. The availability of quality safety data is likely to improve the acceptability of this preventive intervention. Results The study identified vomiting as the most reported adverse drug reaction. Other reported reactions include weakness, fever, abdominal pain, convulsion, redness of the eyes, swollen hand/face, rash, itching, cough, headache, and excessive salivation. Using Naranjo scale, 69.2% of the reported reactions can be classified as possible; while 29.5% can be classified as probable, only 1.3% is classified as definite. 92.3% of reported adverse drug reactions were from children 12–59 months and 7.7% were from those 3–11 months. The proportion of ADRs classified according to the affected organ/system is as follows: central nervous system (10.26%), gastrointestinal (60.26%), ocular (10.26%), musculoskeletal (7.69%), and dermatological (11.53%). The study also suggests better tolerability to the seasonal malaria chemoprevention medicines with more implementation experience, as states with more implementation experiences reported fewer suspected adverse drug reactions. Conclusions The findings from this study provide additional information on possible adverse drug reactions during seasonal malaria chemoprevention campaigns. This additional information should be communicated to caregivers during the seasonal malaria chemoprevention campaigns as a way of building trust and improving acceptability of the intervention. Also, strengthening of the national pharmacovigilance system is vital to ensure improved timeliness, quality, and quantity of pharmacovigilance reporting on SMC intervention in Africa, as results from the study show low levels of pharmacovigilance reporting across the states

Reduced production of sulfated glycosaminoglycans occurs in Zambian children with kwashiorkor but not marasmus

Background: Kwashiorkor, a form of severe malnutrition with high mortality, is characterized by edema and systemic abnormalities. Although extremely common, its pathophysiology remains poorly understood, and its characteristic physical signs are unexplained. Objective: Because kwashiorkor can develop in protein-losing enteropathy, which is caused by a loss of enterocyte heparan sulfate proteoglycan (HSPG), and previous observations suggest abnormal sulfated glycosaminoglycan (GAG) metabolism, we examined whether intestinal GAG and HSPG are abnormal in children with kwashiorkor. Design: Duodenal biopsy samples collected from Zambian children with marasmus (n = 18), marasmic kwashiorkor (n = 8), and kwashiorkor (n = 15) were examined for expression of HSPG, GAGs, and immunologic markers and compared against reference samples from healthy UK control children. GAG and HSPG expression density and inflammatory cell populations were quantitated by computerized analysis. Results: The kwashiorkor group was less wasted and had a lower HIV incidence than did the other groups. All duodenal biopsy samples showed inflammation compared with the histologically uninflamed control samples. Biopsy samples from marasmic children had greater inflammation and greater CD3+ and HLA-DR (human leukocyte antigen DR)-positive cell densities than did samples from children with kwashiorkor. Expression of both HSPG and GAGs was similar between marasmic and well-nourished UK children but was markedly lower in children with kwashiorkor in both the epithelium and lamina propria. Although underglycosylated and undersulfated, epithelial syndecan-1 protein was normally expressed in kwashiorkor, which confirmed that abnormalities arise after core protein synthesis. Conclusions: Intestinal HSPG loss occurs in kwashiorkor, which may precipitate protein-losing enteropathy to cause edema. If occurring systemically, impaired HSPG expression could cause several previously unexplained features of kwashiorkor. We speculate that a genetic predisposition to reduced HSPG biosynthesis may offer a contrasting selective advantage, by both diminishing protein catabolism during transient undernutrition and protecting against specific infectious diseases. Am J Clin Nutr 2009; 89: 592-600