Long-Term Health Risks for Children and Young Adults after Infective Gastroenteritis

TOC Summary: Prior episodes increase risk for long-term adverse health effects

Mortality following Campylobacter infection: a registry-based linkage study

BACKGROUND: Campylobacteriosis is one of the most commonly identified causes of bacterial diarrheal disease and a common cause of gastroenteritis in travellers from developed nations. Despite the widespread occurrence, there is little information on Campylobacter mortality. METHODS: Mortality among a cohort of Campylobacter cases were compared with the general population 0–1, 1–3, 3–12 and more than 12 month after the onset of the illness. The cases were sub-grouped according to if they had been infected domestically or abroad. RESULTS: The standardized mortality ratio for cases infected domestically was 2.9 (95% CI: 1.9–4.0) within the first month following the illness. The risk then gradually diminished and approached 1.0 after one year or more have passed since the illness. This initial excess risk was not attributable to any particular age group (such as the oldest). In contrast, for those infected abroad, a lower standardized mortality ratio 0.3 (95% CI: 0.04–0.8) was shown for the first month after diagnosis compared to what would be expected in the general population. CONCLUSION: Infection with Campylobacter is associated with an increased short-term risk of death among those who were infected domestically. On the contrary, for those infected abroad a lower than expected risk of death was evident. We suggest that the explanation behind this is a "healthy traveler effect" among imported cases, and effects of a more frail than average population among domestic cases

Intussusception among Japanese children: an epidemiologic study using an administrative database

<p>Abstract</p> <p>Background</p> <p>The epidemiology of intussusception, including its incidence, can vary between different countries. The aim of this study was to describe the epidemiology of childhood intussusception in Japan using data from a nationwide inpatient database.</p> <p>Methods</p> <p>We screened the database for eligible cases ≤ 18 years of age, who were coded with a discharge diagnosis of intussusception (International Classification of Diseases, 10th revision: K-561) between July to December in 2007 and 2008. We then selected cases according to Level 1 of the diagnostic certainty criteria developed by the Brighton Collaboration Intussusception Working Group. We examined the demographics, management, and outcomes of cases, and estimated the incidence of intussusception.</p> <p>Results</p> <p>We identified 2,427 cases of intussusception. There were an estimated 2,000 cases of infantile intussusception annually in Japan, an incidence of 180-190 cases per 100,000 infants. The median age at diagnosis was 17 months, and two-thirds of the patients were male. Treatment with an enema was successful in 93.0% of cases (2255/2427). The remainder required surgery. Secondary cases accounted for 3.1% (76/2427). Median length of hospital stay was 3 days. Of the 2,427 cases, we found 2 fatal cases associated with intussusception.</p> <p>Conclusions</p> <p>This is currently the largest survey of childhood intussusception in Asia using a standardized case definition. Our results provide an estimate of the baseline risk of intussusception in Japan, and it is higher than the risk observed in other countries.</p

A recurrent mitochondrial p.Trp22Arg NDUFB3 variant causes a distinctive facial appearance, short stature and a mild biochemical and clinical phenotype

Background Isolated Complex I deficiency is the most common paediatric mitochondrial disease presentation, associated with poor prognosis and high mortality. Complex I comprises 44 structural subunits with at least 10 ancillary proteins; mutations in 29 of these have so far been associated with mitochondrial disease but there are limited genotype-phenotype correlations to guide clinicians to the correct genetic diagnosis. Methods Patients were analysed by whole-exome sequencing, targeted capture or candidate gene sequencing. Clinical phenotyping of affected individuals was performed. Results We identified a cohort of 10 patients from 8 families (7 families are of unrelated Irish ancestry) all of whom have short stature (C, p.Trp22Arg NDUFB3 variant. Two sibs presented with primary short stature without obvious metabolic dysfunction. Analysis of skeletal muscle from three patients confirmed a defect in Complex I assembly. Conclusions Our report highlights that the long-term prognosis related to the p.Trp22Arg NDUFB3 mutation can be good, even for some patients presenting in acute metabolic crisis with evidence of an isolated Complex I deficiency in muscle. Recognition of the distinctive facial features—particularly when associated with markers of mitochondrial dysfunction and/or Irish ancestry—should suggest screening for the p.Trp22Arg NDUFB3 mutation to establish a genetic diagnosis, circumventing the requirement of muscle biopsy to direct genetic investigations

Genotypic diversity and phenotypic spectrum of infantile liver failure syndrome type 1 due to variants inLARS1

Purpose: Biallelic variants in LARS1, coding for the cytosolic leucyl-tRNA synthetase, cause infantile liver failure syndrome 1 (ILFS1). Since its description in 2012, there has been no systematic analysis of the clinical spectrum and genetic findings. Methods: Individuals with biallelic variants in LARS1 were included through an international, multicenter collaboration including novel and previously published patients. Clinical variables were analyzed and functional studies were performed in patient-derived fibroblasts. Results: Twenty-five individuals from 15 families were ascertained including 12 novel patients with eight previously unreported variants. The most prominent clinical findings are recurrent elevation of liver transaminases up to liver failure and encephalopathic episodes, both triggered by febrile illness. Magnetic resonance image (MRI) changes during an encephalopathic episode can be consistent with metabolic stroke. Furthermore, growth retardation, microcytic anemia, neurodevelopmental delay, muscular hypotonia, and infection-related seizures are prevalent. Aminoacylation activity is significantly decreased in all patient cells studied upon temperature elevation in vitro. Conclusion: ILFS1 is characterized by recurrent elevation of liver transaminases up to liver failure in conjunction with abnormalities of growth, blood, nervous system, and musculature. Encephalopathic episodes with seizures can occur independently from liver crises and may present with metabolic stroke

Contribution of TAT System Translocated PhoX to Campylobacter jejuni Phosphate Metabolism and Resilience to Environmental Stresses

Campylobacter jejuni is a common gastrointestinal pathogen that colonizes food animals; it is transmitted via fecal contamination of food, and infections in immune-compromised people are more likely to result in serious long-term illness. Environmental phosphate is likely an important sensor of environmental fitness and the ability to obtain extracellular phosphate is central to the bacteria's core metabolic responses. PhoX is the sole alkaline phosphatase in C. jejuni, a substrate of the TAT transport system. Alkaline phosphatases mediate the hydrolytic removal of inorganic phosphate (Pi) from phospho-organic compounds and thereby contribute significantly to the polyphosphate kinase 1 (ppk1) mediated formation of poly P, a molecule that regulates bacterial response to stresses and virulence. Similarly, deletion of the tatC gene, a key component of the TAT system, results in diverse phenotypes in C. jejuni including reduced stress tolerance and in vivo colonization. Therefore, here we investigated the contribution of phoX in poly P synthesis and in TAT-system mediated responses. The phoX deletion mutant showed significant decrease (P<0.05) in poly P accumulation in stationary phase compared to the wild-type, suggesting that PhoX is a major contributor to the inorganic phosphate pool in the cell which is essential for poly P synthesis. The phoX deletion is sufficient for a nutrient stress defect similar to the defect previously described for the ΔtatC mutant. Additionally, the phoX deletion mutant has increased resistance to certain antimicrobials. The ΔphoX mutant was also moderately defective in invasion and intracellular survival within human intestinal epithelial cells as well as in chicken colonization. Further, the ΔphoX mutant produced increased biofilm that can be rescued with 1 mM inorganic phosphate. The qRT-PCR of the ΔphoX mutant revealed transcriptional changes that suggest potential mechanisms for the increased biofilm phenotype

NBAS variants are associated with quantitative and qualitative NK and B cell deficiency

Purpose Biallelic pathogenic NBAS variants manifest as a multisystem disorder with heterogeneous clinical phenotypes such as recurrent acute liver failure, growth retardation, and susceptibility to infections. This study explores how NBAS-associated disease affects cells of the innate and adaptive immune system. Methods Clinical and laboratory parameters were combined with functional multi-parametric immunophenotyping methods in fifteen NBAS-deficient patients to discover possible alterations in their immune system. Results Our study revealed reduced absolute numbers of mature CD56dim natural killer (NK) cells. Notably, the residual NK cell population in NBAS-deficient patients exerted a lower potential for activation and degranulation in response to K562 target cells, suggesting an NK cell–intrinsic role for NBAS in the release of cytotoxic granules. NBAS-deficient NK cell activation and degranulation was normalized upon pre-activation by IL-2 in vitro, suggesting that functional impairment was reversible. In addition, we observed a reduced number of naïve B cells in the peripheral blood associated with hypogammaglobulinemia. Conclusion In summary, we demonstrate that pathogenic biallelic variants in NBAS are associated with dysfunctional NK cells as well as impaired adaptive humoral immunity

Virulence of a T6SS Campylobacter jejuni chicken isolate from North Romania

Objectives: In this study we have investigated the in vitro and in vivo virulence characteristics of a new T6SS positive Campylobacter jejuni chicken isolate (SV12) originating from a poultry population in North Romania. A detailed phenotypic characterization was performed and compared to the T6SS negative C. jejuni 81-176 wild strain. Results: Our results indicate that the significantly higher capacity to attach and invade HCT-8 cells of C. jejuni SV12 isolate is associated with increased motility, increased resistance to bile salts and serum resistance, when compared to C. jejuni strain 81-76. Mice infected with the SV12 isolate showed statistically higher levels of colonization at both 7- and 14-days post-inoculation and in the stomach, caecum, duodenum and large intestine. Infection with the SV12 strain induced a stronger immune response as the gene transcript levels of IL-17, TNFα and IFNγ were more pronouncedly up-regulated compared to the C. jejuni strain 81-176. The present study showed that the new isolate SV12 had an enhanced virulence capacity compared to the wild strain which was evident in vivo as well. This work also provides an insight on the colonization pattern and host immune response differences between T6SS positive and T6SS negative C. jejuni