Lack of Serologic Evidence of Neospora caninum in Humans, England

Retrospective testing of 3,232 serum samples from the general population and 518 serum samples from a high-risk group showed no evidence of human exposure to Neospora caninum in England. Results were obtained by using immunofluorescence antibody testing and ELISA to analyze frequency distribution

The feasibility of testing whether Fasciola hepatica is associated with increased risk of verocytotoxin producing Escherichia coli O157 from an existing study protocol

The parasite Fasciola hepatica is a major cause of economic loss to the agricultural community worldwide as a result of morbidity and mortality in livestock, including cattle. Cattle are the principle reservoir of verocytotoxigenic Escherichia coli O157 (VTEC O157), an important cause of disease in humans. To date there has been little empirical research on the interaction between F. hepatica and VTEC O157. It is hypothesised that F. hepatica, which is known to suppress type 1 immune responses and induce an anti-inflammatory or regulatory immune environment in the host, may promote colonisation of the bovine intestine with VTEC O157. Here we assess whether it is statistically feasible to augment a prospective study to quantify the prevalence of VTEC O157 in cattle in Great Britain with a pilot study to test this hypothesis. We simulate data under the framework of a mixed-effects logistic regression model in order to calculate the power to detect an association effect size (odds ratio) of 2. In order to reduce the resources required for such a study, we exploit the fact that the test results for VTEC O157 will be known in advance of testing for F. hepatica by restricting analysis to farms with a VTEC O157 sample prevalence of >0% and <100%. From a total of 270 farms (mean 27 cows per farm) that will be tested for VTEC O157, power of 87% can be achieved, whereby testing of F. hepatica would only be necessary for an expected 50 farms, thus considerably reducing costs. Pre-study sample size calculations are an important part of any study design. The framework developed here is applicable to the study of other co-infections

Age at first birth in women is genetically associated with increased risk of schizophrenia

Prof. Paunio on PGC:n jäsenPrevious studies have shown an increased risk for mental health problems in children born to both younger and older parents compared to children of average-aged parents. We previously used a novel design to reveal a latent mechanism of genetic association between schizophrenia and age at first birth in women (AFB). Here, we use independent data from the UK Biobank (N = 38,892) to replicate the finding of an association between predicted genetic risk of schizophrenia and AFB in women, and to estimate the genetic correlation between schizophrenia and AFB in women stratified into younger and older groups. We find evidence for an association between predicted genetic risk of schizophrenia and AFB in women (P-value = 1.12E-05), and we show genetic heterogeneity between younger and older AFB groups (P-value = 3.45E-03). The genetic correlation between schizophrenia and AFB in the younger AFB group is -0.16 (SE = 0.04) while that between schizophrenia and AFB in the older AFB group is 0.14 (SE = 0.08). Our results suggest that early, and perhaps also late, age at first birth in women is associated with increased genetic risk for schizophrenia in the UK Biobank sample. These findings contribute new insights into factors contributing to the complex bio-social risk architecture underpinning the association between parental age and offspring mental health.Peer reviewe

Genome-wide haplotype association study identifies the FRMD4A gene as a risk locus for Alzheimer's disease

Recently, several genome-wide association studies (GWASs) have led to the discovery of nine new loci of genetic susceptibility in Alzheimer's disease (AD). However, the landscape of the AD genetic susceptibility is far away to be complete and in addition to single-SNP (single-nucleotide polymorphism) analyses as performed in conventional GWAS, complementary strategies need to be applied to overcome limitations inherent to this type of approaches. We performed a genome-wide haplotype association (GWHA) study in the EADI1 study (n=2025 AD cases and 5328 controls) by applying a sliding-windows approach. After exclusion of loci already known to be involved in AD (APOE, BIN1 and CR1), 91 regions with suggestive haplotype effects were identified. In a second step, we attempted to replicate the best suggestive haplotype associations in the GERAD1 consortium (2820 AD cases and 6356 controls) and observed that 9 of them showed nominal association. In a third step, we tested relevant haplotype associations in a combined analysis of five additional case-control studies (5093 AD cases and 4061 controls). We consistently replicated the association of a haplotype within FRMD4A on Chr.10p13 in all the data set analyzed (OR: 1.68; 95% CI: (1.43-1.96); P=1.1 × 10 -10). We finally searched for association between SNPs within the FRMD4A locus and Aβ plasma concentrations in three independent non-demented populations (n=2579). We reported that polymorphisms were associated with plasma Aβ42/Aβ40 ratio (best signal, P=5.4 × 10 -7). In conclusion, combining both GWHA study and a conservative three-stage replication approach, we characterised FRMD4A as a new genetic risk factor of AD

Endogenousand exogenous transplacental infection in Neospora caninum and Toxoplasma gondii

It is clear from researching the vertical transmission of Neospora caninum in cattle that the terms 'vertical', 'congenital' and, indeed, 'transplacental' are inadequate for describing two extremely different situations that have fundamentally different immunological, epidemiological and control implications. A similar situation pertains to Toxoplasma gondii in different hosts. We advocate the use of the terms 'endogenous transplacental infection (TPI)' to define foetal infection from a recrudescent maternal infection acquired before pregnancy (and probably prenatally) and 'exogenous TPI' to define foetal infection that occurs as a result of an infection of the dam during pregnancy

Evaluation of an ELISA to assess the intensity of Fasciola hepatica infection in cattle

An ELISA with a diagnostic sensitivity of 98 per cent and specificity of 96 per cent was evaluated as a means of assessing the intensity of Fasciola hepatica infection in cattle. A total of 294 blood samples were collected from infected cattle at a local abattoir, and the level of infection in each animal was assessed on the basis of the extent of liver pathology and the presence of flukes; 120 blood samples were also collected from uninfected cattle kept on a farm known to be free of F hepatica. The results indicated that there was a significant correlation (P<0.001) between the ELISA values and the intensity of infection. Values between 15 and 28 per cent of a positive control sample indicated a low intensity of infection, values between 28 and 50 per cent indicated a medium intensity of infection and values above 50 per cent indicated a high intensity of infection

Diagnosis and seroepidemiology of Neospora caninum-associated bovine abortion

A round table was conducted at the VIIIth International Coccidiosis Conference on Neospora diagnosis with particular emphasis on strategies to diagnose bovine abortion. The strength and weakness of different assays for Neospora caninum infection and whether these methods have resulted in the overdiagnosis of neosporosis was discussed. It was evident that each diagnostic method, namely histology, immunohistochemistry, molecular detection and serological assays were, under certain circumstances, valuable in assessing the role N. caninum in abortion. Histological, immunohistochemical and molecular detection assays are of outstanding importance for the examination of tissues of aborted foetuses. While histology and immunohistochemistry allow direct assessment of pathomorphological changes caused by infection, molecular detection assays such as PCR are superior because of higher sensitivity and specificity in identifying N. caninum in foetal tissues. Serological tests, such as ELISA, are useful in determining whether an animal has been infected with N. caninum. Seroepidemiological approaches allow one to assess an abortion problem at a herd level and when used in conjunction with certain statistical methods are able to confirm a suspected N. caninum-associated abortion

Associations between anti-Fasciola hepatica antibody levels in bulk-tank milk samples and production parameters in dairy herds

Our primary objective was to determine the relationships between Fasciola-specific antibody levels in bulk-tank milk and measures of productivity to estimate economic losses that are associated with Fasciola infections. A bulk-tank milk-ample was collected in March 2004 from 1105 dairy herds in Flanders and the antibody levels against Fasciola hepatica (ODRf) and Ostertagia ostertagi (ODRo) were determined. The association of ODRf with four production parameters (milk yield, milk-protein %, milk-fat % and inter-calving interval) was assessed by multivariable linear-regression models. Production data were available for 463 out of the 1105 herds sampled. An increase in ODRf from the 25% quantile (0.428) to the 75% quanfile (1.064) was associated with a decrease in the annual average milk yield of 0.7 kg/(cow day) (P = 0.002), with a decrease in the average milk-fat % of 0.06% (P < 0.001) and with an increase of the mean inter-calving interval of 4.7 days (P = 0.03). No significant relationship was found with the average milk-protein %. When the relationships of ODRf and ODRo with milk yield were tested simultaneously, we saw an additive rather than synergistic effect of concurrent infections. (c) 2006 Elsevier B.V. All rights reserved

Qualitative and quantitative evaluation of coprological and serological techniques for the diagnosis of fasciolosis in cattle

The objectives of this study were (1) to evaluate available coprological and serological tests for detection of Fasciola hepatica infection in field conditions, (2) to investigate if the season when samples were collected affects the interpretation of the test results, and (3) to evaluate if the test results are associated with the level of infection. During weekly visits to an abattoir, the whole liver, a rectal faecal sample and a blood sample were collected from 100 cows in two seasons each ("spring" = February-May 2006 and "autumn" = October-December 2006). A sedimentation-flotation technique on 4 g (SF 4 g) or 10 g (SF 10 g) of faeces, a copro-antigen ELISA and two indirect serum F hepatica ELISAs (excretory-secretory (ES) and Pourquier ELISA) were performed and the test results were compared with the presence of infection and worm counts at liver necropsy. Over both seasons the sensitivity (Se) and specificity (Sp) were for the SF 4 g 43% and 100%, for the SF 10 g 64% and 93%, for the copro-antigen ELISA 94% and 93%, for the ES ELISA 87% and 90% and for the Pourquier ELISA 88% and 84%. Significant between-season differences (P 10 flukes) than that is free of infection or lightly infected (< 10 flukes). Weak (similar to 0.3) and moderate (similar to 0.6) correlations were observed within infected animals of level of infection with ES and copro-antigen ELISA results, respectively. (C) 2008 Elsevier B.V. All rights reserved

Evaluation of an enzyme-linked immunosorbent assay for detection of antibodies to Fasciola hepatica in milk

Antibodies against Fasciola hepatica were detected in serum and individual milk samples of dairy cattle using an ELISA. Percentage positivity (PP) values in milk samples were related to serum PP values and were not influenced by days into lactation. The correlation coefficient between serum and individual milk samples was highly significant (r = 0.84, P < 0.005). The correlation coefficient between herd seroprevalence and herd milk antibody prevalence was 0.96. The correlation coefficient between prevalence measured by faecal egg count and both seroprevalence and milk antibody prevalence within the herd was 0.87. The diagnostic sensitivity and specificity for milk were 92% (95% CI = 89-96) and 88% (95% CI = 85-91), respectively, when the serum test was considered as a gold standard. In conclusion, the level of antibody to E hepatica in milk is significantly correlated with the antibody level in serum and this ELISA is suitable as a means of routine veterinary diagnosis of exposure to F hepatica in cattle and an alternative to testing sera. (c) 2007 Elsevier B.V. All rights reserved