Genetic diversity and stability of the porA allele as a genetic marker in human Campylobacter infection

The major outer-membrane protein (MOMP) of Campylobacter jejuni and Campylobacter coli, encoded by the porA gene, is extremely genetically diverse. Conformational MOMP epitopes are important in host immunity, and variation in surface-exposed regions probably occurs as a result of positive immune selection during infection. porA diversity has been exploited in genotyping studies using highly discriminatory nucleotide sequences to identify potentially epidemiologically linked cases of human campylobacteriosis. To understand the overall nature and extent of porA diversity and stability in C. jejuni and C. coli we investigated sequences in isolates (n=584) obtained from a defined human population (approx. 600 000) over a defined time period (1 year). A total of 196 distinct porA variants were identified. Regions encoding putative extracellular loops were the most variable in both nucleotide sequence and length. Phylogenetic analysis identified three porA allele clusters that originated in (i) predominantly C. jejuni and a few C. coli, (ii) solely C. jejuni or (iii) predominantly C. coli and a few C. jejuni. The stability of porA within an individual human host was investigated using isolates cultured longitudinally from 64 sporadic cases, 27 of which had prolonged infection lasting between 5 and 98 days (the remainder having illness of normal duration, 0–4 days), and 20 cases from family outbreaks. Evidence of mutation was detected in two patients with prolonged illness. Despite demonstrable positive immune selection in these two unusual cases, the persistence of numerous variants within the population indicated that the porA allele is a valuable tool for use in extended typing schemes

Testing Gait with Ankle-Foot Orthoses in Children with Cerebral Palsy by Using Functional Mixed-Effects Analysis of Variance

Dr Morrissey is part funded by the NIHR/HEE Senior Clinical Lecturer scheme. Tis report presents independent research part-funded by the National Institute for Health Research (NIHR) CAT SCL-2013-04-00

Incidence trend and risk factors for campylobacter infections in humans in Norway

BACKGROUND: The objectives of the study were to evaluate whether the increase in incidence of campylobacteriosis observed in humans in Norway from 1995 to 2001 was statistically significant and whether different biologically plausible risk factors were associated with the incidence of campylobacteriosis in the different counties in Norway. METHODS: To model the incidence of domestically acquired campylobacteriosis from 1995 to 2001, a population average random effect poisson model was applied (the trend model). To case data and assumed risk-factor/protective data such as sale of chicken, receiving treated drinking water, density of dogs and grazing animals, occupation of people in the municipalities and climatic factors from 2000 and 2001, an equivalent model accounting for geographical clustering was applied (the ecological model). RESULTS: The increase in incidence of campylobacteriosis in humans in Norway from 1995 to 2001 was statistically significant from 1998. Treated water was a protective factor against Campylobacter infections in humans with an IRR of 0.78 per percentage increase in people supplied. The two-level modelling technique showed no evidence of clustering of campylobacteriosis in any particular county. Aggregation of data on municipality level makes interpretation of the results at the individual level difficult. CONCLUSION: The increase in incidence of Campylobacter infections in humans from 1995 to 2001 was statistically significant from 1998. Treated water was a protective factor against Campylobacter infections in humans with an IRR of 0.78 per percentage increase in people supplied. Campylobacter infections did not appear to be clustered in any particular county in Norway

Campylobacter jejuni transcriptome changes during loss of culturability in water

Background: Water serves as a potential reservoir for Campylobacter, the leading cause of bacterial gastroenteritis in humans. However, little is understood about the mechanisms underlying variations in survival characteristics between different strains of C. jejuni in natural environments, including water. Results: We identified three Campylobacter jejuni strains that exhibited variability in their ability to retain culturability after suspension in tap water at two different temperatures (4°C and 25°C). Of the three strains C. jejuni M1 exhibited the most rapid loss of culturability whilst retaining viability. Using RNAseq transcriptomics, we characterised C. jejuni M1 gene expression in response to suspension in water by analyzing bacterial suspensions recovered immediately after introduction into water (Time 0), and from two sampling time/temperature combinations where considerable loss of culturability was evident, namely (i) after 24 h at 25°C, and (ii) after 72 h at 4°C. Transcript data were compared with a culture-grown control. Some gene expression characteristics were shared amongst the three populations recovered from water, with more genes being up-regulated than down. Many of the up-regulated genes were identified in the Time 0 sample, whereas the majority of down-regulated genes occurred in the 25°C (24 h) sample. Conclusions: Variations in expression were found amongst genes associated with oxygen tolerance, starvation and osmotic stress. However, we also found upregulation of flagellar assembly genes, accompanied by down-regulation of genes involved in chemotaxis. Our data also suggested a switch from secretion via the sec system to via the tat system, and that the quorum sensing gene luxS may be implicated in the survival of strain M1 in water. Variations in gene expression also occurred in accessory genome regions. Our data suggest that despite the loss of culturability, C. jejuni M1 remains viable and adapts via specific changes in gene expression

Chicken consumption and use of acid-suppressing medications as risk factors for Campylobacter enteritis, England.

In a case-control study of Campylobacter spp. risk factors in England during 2005-2006, we identified recent consumption of commercially prepared chicken as an important risk factor. The risk for illness associated with recent chicken consumption was much lower for persons who regularly ate chicken than in those who did not, which suggests that partial immunologic protection may follow regular chicken preparation or consumption. Chicken-related risk factors accounted for 41% of cases; acid-suppressing medication, for 10%; self-reported past Campylobacter enteritis, 2%; and recent acquisition of a pet dog, 1%. Understanding the risks associated with chicken from different sources will benefit strategies to reduce Campylobacter infections. Better characterization of immune correlates for Campylobacter infection is necessary to assess the relative importance of immunity and behavioral factors in determining risk