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OBJECTIVEMonogenic diabetes is rare but is an important diagnosis in pediatric diabetes clinics. These patients are often not identified as this relies on the recognition of key clinical features by an alert clinician. Biomarkers (islet autoantibodies and C-peptide) can assist in the exclusion of patients with type 1 diabetes and allow systematic testing that does not rely on clinical recognition. Our study aimed to establish the prevalence of monogenic diabetes in U.K. pediatric clinics using a systematic approach of biomarker screening and targeted genetic testing. RESEARCH DESIGN AND METHODSWe studied 808 patients (79.5% of the eligible population) <20 years of age with diabetes who were attending six pediatric clinics in South West England and Tayside, Scotland. Endogenous insulin production was measured using the urinary C-peptide creatinine ratio (UCPCR). C-peptide-positive patients (UCPCR ‡0.2 nmol/mmol) underwent islet autoantibody (GAD and IA2) testing, with patients who were autoantibody negative undergoing genetic testing for all 29 identified causes of monogenic diabetes. RESULTSA total of 2.5% of patients (20 of 808 patients) (95% CI 1.6-3.9%) had monogenic diabetes (8 GCK, 5 HNF1A, 4 HNF4A, 1 HNF1B, 1 ABCC8, 1 INSR). The majority (17 of 20 patients) were managed without insulin treatment. A similar proportion of the population had type 2 diabetes (3.3%, 27 of 808 patients). CONCLUSIONSThis large systematic study confirms a prevalence of 2.5% of patients with monogenic diabetes who were <20 years of age in six U.K. clinics. This figure suggests that ∼50% of the estimated 875 U.K. pediatric patients with monogenic diabetes have still not received a genetic diagnosis. This biomarker screening pathway is a practical approach that can be used to identify pediatric patients who are most appropriate for genetic testing.

BackgroundPoultry represent an important source of foodborne enteropathogens, in particular thermophilic Campylobacter species. Many of these organisms colonize the intestinal tract of broiler chickens as harmless commensals, and therefore, often remain undetected prior to slaughter. The exact reasons for the lack of clinical disease are unknown, but analysis of the gastrointestinal microbiota of broiler chickens may improve our understanding of the microbial interactions with the host.MethodsIn this study, the fecal microbiota of 31 market-age (56-day old) broiler chickens, from two different farms, was analyzed using high throughput sequencing. The samples were then screened for two emerging human pathogens, Campylobacter concisus and Helicobacter pullorum, using species-specific PCR.ResultsThe gastrointestinal microbiota of chickens was classified into four potential enterotypes, similar to that of humans, where three enterotypes have been identified. The results indicated that variations between farms may have contributed to differences in the microbiota, though each of the four enterotypes were found in both farms suggesting that these groupings did not occur by chance. In addition to the identification of Campylobacter jejuni subspecies doylei and the emerging species, C. concisus, C. upsaliensis and H. pullorum, several differences in the prevalence of human pathogens within these enterotypes were observed. Further analysis revealed microbial taxa with the potential to increase the likelihood of colonization by a number of these pathogens, including C. jejuni.ConclusionDepletion of these taxa and the addition of taxa that compete with these pathogens, may form the basis of competitive exclusion strategies to eliminate them from the gastrointestinal tract of chickens.

Summary Poultry meat has been associated frequently and consistently with the transmission of enteric pathogens, including Salmonella and Campylobacter. This association has resulted in the development of HACCP‐based intervention strategies. These strategies (hurdles) begin with elite breeder flocks and filter down the production pyramid. These hurdles include those already established, such as biosecurity, vaccination, competitive exclusion, pre‐ and probiotics, feed and water control, and those more experimental, such as bacteriophage or immunoglobulin therapy. The reduction in enteropathogens entering the processing plant, which employs critical control points, further reduce the exposure of consumers to these organisms. The synergistic application of hurdles will result in an environment that is restrictive and detrimental to enteropathogen colonization and contamination.

Two Enteritidis PT4 isolates which differed in inherent tolerance to heat, acid, H2O2 and the ability to survive on surfaces were used to infect mice, day-old chicks or laying hens. The acid-, heat-, H2O2- and surface-tolerant isolate was more virulent in mice and more invasive in laying hens, particularly in reproductive tissue. However, no significant differences were observed in behaviour in chicks. Both PT4 isolates were able to infect chicks housed in the same room as infected birds, although the heat-tolerant isolate survived significantly better than the heat-sensitive one in aerosols.