Christian Schnier

Sole ulcers in Finnish dairy cattle.

The Finnish Healthy Hooves project was set up to determine the frequency of, and risk factors for various hoof lesions in Finnish dairy herds. Data were collected in the years 2003 and 2004. A large dataset of over 74,000 cow-level observations recorded by hoof trimmers was merged with production data from the Finnish Agricultural Data Processing Centre Ltd. Ultimately, data from a single lactation from each of 16,792 cows in 703 herds were used for the analyses in this paper. Three-level hierarchical logistic models with hoof trimmer and farms (within hoof trimmer) as random effects were fit to data sets of tie stall (TS) and loose housing (LH) herds separately. The outcome of interest was the presence or absence of a sole ulcer in one or more legs of a cow during the lactation of interest. Cows examined once had a risk of sole ulcer 5.23% in tie stall herds and 7.58% in LH herds. As the number of examinations increased the odds of a diagnosis of sole ulcer increased substantially (2 and 3+ examinations had odds ratios (ORs) of 1.42 and 3.42 in TS herds and 2.77 and 6.89 in LH herds). Breed had a large effect on the risk of sole ulcer with Holsteins 2.89 times more likely to be affected than Ayrshires in TS herds and 2.94 times in LH herds. In TS herds, the presence of other hoof lesions such as haemorrhages (OR = 2.97), heel-horn erosions (OR = 2.10) and corkscrew claw (OR = 2.83) increased the risk of a sole ulcer developing. In LH herds, only haemorrhages (OR = 1.80) were a significant risk factor when parity was > or = 2. In TS herds, use of mats (compared to hard flooring) significantly reduced the risk of sole ulcers (OR = 0.49). The effect of parity on the risk of sole ulcer was greatest when parity > or = 4 but this effect was only significant in tie stalls (OR = 1.86). When analyses were restricted to cows with parity > or = 2, similar results were obtained for the risk factors identified above. In addition, parity became highly significant in TS and LH (OR 2.31 and 2.23, respectively when parity was 4+). In TS herds, herd average milk production was significantly associated with a decrease risk of sole ulcer (OR = 1.28 per 1000 kg decrease) but there was no effect of production at the cow level (measured as deviation from the herd mean). No significant effects of production were observed in LH herds.

Efficacy of two vaccine formulations against contagious bovine pleuropneumonia (CBPP) in Kenyan indigenous cattle

A live, attenuated vaccine is currently the only viable option to control of CBPP in Africa. It has been suggested that simple modifications to current vaccines and protocols might improve efficacy in the field. In this report we compared the current vaccine formulation with a buffered preparation that maintains Mycoplasma viability at ambient temperature for a longer time. Groups of animals were vaccinated with the two formulations and compared with non vaccinated groups. Half of the animals in each group were challenged 3 months post vaccination, the other half after 16 months. Protection levels were measured using the pathology index, calculated from post mortem scores of lesions from animals killed during the course of clinical disease. In the challenge at 3 months post vaccination, the protection levels were 52% and 77% for the modified and current vaccine preparations, respectively. At 16 months post vaccination, the protection levels were 56% and 62% for the modified and current vaccine preparations, respectively. These findings indicate that there are no differences in protection levels between the two vaccines. Because of its longer half life after reconstitution, the modified vaccine might be preferred in field situations where the reconstituted vaccine is likely not to be administered immediately.

Influence of Host Immunity on Parasite Diversity in Theileria parva

ABSTRACT We examined the influence of host immunity on the genotypic diversity of the intracellular transforming cattle parasite Theileria parva. By tracking the emergence of discrete parasite genotypes in an animal challenged with a bulk stabilate following immunization with its major component clone, we observed a profound modulation of genotypic frequencies in the breakthrough schizont population. In particular, no incidences of the immunizing clone were observed and a progressive decline was apparent in the relatedness of breakthrough genotypes to it. These observations were reflected in the genotypic profile of transmissible parasite stages that emerged in the erythrocyte fraction of the animal and in parasite progeny generated by tick pickup. In a separate experiment, genotypic profiles of breakthrough parasite populations were observed to vary between unrelated immune animals selected on the basis of the major histocompatibility complex (MHC) class I phenotype, a known determinant of the specificity of the immune response. Furthermore, immunization and challenge of calves with molecularly distinct but cross-protective parasite populations revealed that infection results in transmissible erythrocyte forms in spite of a protective immune response. These observations suggest that immunity does not prevent transmission of challenge parasites and that its impact on the parasite at a population level is influenced by herd MHC diversity.

Vaccination of Cattle with the N Terminus of LppQ of Mycoplasma mycoides subsp. mycoides Results in Type III Immune Complex Disease upon Experimental Infection

ABSTRACT Contagious bovine pleuropneumonia (CBPP) is a serious respiratory disease of cattle caused by Mycoplasma mycoides subsp. mycoides. Current vaccines against CBPP induce short-lived immunity and can cause severe postvaccine reactions. Previous studies have identified the N terminus of the transmembrane lipoprotein Q (LppQ-N′) of M. mycoides subsp. mycoides as the major antigen and a possible virulence factor. We therefore immunized cattle with purified recombinant LppQ-N′ formulated in Freunds adjuvant and challenged them with M. mycoides subsp. mycoides. Vaccinated animals showed a strong seroconversion to LppQ, but they exhibited significantly enhanced postchallenge glomerulonephritis compared to the placebo group (P = 0.021). Glomerulonephritis was characterized by features that suggested the development of antigen-antibody immune complexes. Clinical signs and gross pathological scores did not significantly differ between vaccinated and placebo groups. These findings reveal for the first time the pathogenesis of enhanced disease as a result of antibodies against LppQ during challenge and also argue against inclusion of LppQ-N′ in a future subunit vaccine for CBPP.

Exploring farmer preferences for contagious bovine pleuropneumonia vaccination: A case study of Narok District of Kenya

Contagious bovine pleuropneumonia (CBPP) is an economically important disease in most of sub-Saharan Africa. A conjoint analysis and ordered probit regression models were used to measure the preferences of farmers for CBPP vaccine and vaccination attributes. This was with regard to inclusion or not of an indicator in the vaccine, vaccine safety, vaccine stability as well as frequency of vaccination, vaccine administration and the nature of vaccination. The analysis was carried out in 190 households in Narok District of Kenya between October and December 2006 using structured questionnaires, 16 attribute profiles and a five-point Likert scale. The factors affecting attribute valuation were shown through a two-way location interaction model. The study also demonstrated the relative importance (RI) of attributes and the compensation value of attribute levels. The attribute coefficient estimates showed that farmers prefer a vaccine that has an indicator, is 100% safe and is administered by the government (p<0.0001). The preferences for the vaccine attributes were consistent with expectations. Preferences for stability, frequency of vaccination and nature of vaccination differed amongst farmers (p>0.05). While inclusion of an indicator in the vaccine was the most important attribute (RI=43.6%), price was the least important (RI=0.5%). Of the 22 household factors considered, 15 affected attribute valuation. The compensation values for a change from non inclusion to inclusion of an indicator, 95-100% safety, 2h to greater than 2h stability and from compulsory to elective vaccination were positive while those for a change from annual to biannual vaccination and from government to private administration were negative. The study concluded that the farmers in Narok District had preferences for specific vaccine and vaccination attributes. These preferences were conditioned by various household characteristics and disease risk factors. On average the farmers would need to be compensated or persuaded to accept biannual and private vaccination against CBPP. There is need for consideration of farmer preferences for vaccine attribute levels during vaccine formulations and farmer preferences for vaccination attribute levels when designing delivery of vaccines.

Cattle immunized against the pathogenic L-α-glycerol-3-phosphate oxidase of Mycoplasma mycoides subs. mycoides fail to generate neutralizing antibodies and succumb to disease on challenge.

Highlights • Cattle were vaccinated with Mycoplasma mycoides mycoides (Mmm) recombinant l-α-glycerol-3-phosphate oxidase.• A mouse mAb to l-α-glycerol-3-phosphate oxidase was generated.• Mouse mAb blocked H2O2 release by Mmm, but cattle antisera did not.• Cattle were not protected after challenge.

Matched population-based study examining the risk of type 2 diabetes in people with and without diagnosed hepatitis C virus infection

Meta‐analyses have found hepatitis C virus (HCV) infection to be associated with an increased risk of type 2 diabetes mellitus (T2DM). Here, we examine this association within a large population‐based study, according to HCV RNA status. A data‐linkage approach was used to examine the excess risk of diagnosed T2DM in people diagnosed with antibodies to HCV (anti‐HCV) in Scotland (21 929 anti‐HCV+ves; involving 15 827 HCV RNA+ves, 3927 HCV RNA−ves and 2175 with unknown RNA‐status) compared to that of a threefold larger general population sample matched for gender, age and postcode (65 074 anti‐HCV−ves). To investigate effects of ascertainment bias the following periods were studied: up to 1 year before (pre‐HCV)/within 1 year of (peri‐HCV)/more than 1 year post (post‐HCV) the date of HCV‐diagnosis. T2DM had been diagnosed in 2.9% of anti‐HCV+ves (including 3.2% of HCV RNA+ves and 2.3% of HCV RNA−ves) and 2.7% of anti‐HCV−ves. A higher proportion of T2DM was diagnosed in the peri‐HCV period (i.e. around the time of HCV‐diagnosis) for the anti‐HCV+ves (22%) compared to anti‐HCV−ves (10%). In both the pre‐HCV and post‐HCV periods, only those anti‐HCV+ves living in less deprived areas (13% of the cohort) were found to have a significant excess risk of T2DM compared to anti‐HCV−ves (adjusted odds ratio in the pre‐HCV period: 4.0 for females and 2.3 for males; adjusted hazard ratio in the post‐HCV period: 1.5). These findings were similarly observed for both HCV RNA+ves (chronic) and HCV RNA−ves (resolved). In the largest study of T2DM among chronic HCV‐infected individuals to date, there was no evidence to indicate that infection conveyed an appreciable excess risk of T2DM at the population level.

Identifying dementia cases with routinely-collected health data: a systematic review

Prospective, population‐based studies can be rich resources for dementia research. Follow‐up in many such studies is through linkage to routinely collected, coded health‐care data sets. We evaluated the accuracy of these data sets for dementia case identification.

Accuracy of routinely-collected healthcare data for identifying motor neurone disease cases: A systematic review

Background Motor neurone disease (MND) is a rare neurodegenerative condition, with poorly understood aetiology. Large, population-based, prospective cohorts will enable powerful studies of the determinants of MND, provided identification of disease cases is sufficiently accurate. Follow-up in many such studies relies on linkage to routinely-collected health datasets. We systematically evaluated the accuracy of such datasets in identifying MND cases. Methods We performed an electronic search of MEDLINE, EMBASE, Cochrane Library and Web of Science for studies published between 01/01/1990-16/11/2015 that compared MND cases identified in routinely-collected, coded datasets to a reference standard. We recorded study characteristics and two key measures of diagnostic accuracy—positive predictive value (PPV) and sensitivity. We conducted descriptive analyses and quality assessments of included studies. Results Thirteen eligible studies provided 13 estimates of PPV and five estimates of sensitivity. Twelve studies assessed hospital and/or death certificate-derived datasets; one evaluated a primary care dataset. All studies were from high income countries (UK, Europe, USA, Hong Kong). Study methods varied widely, but quality was generally good. PPV estimates ranged from 55–92% and sensitivities from 75–93%. The single (UK-based) study of primary care data reported a PPV of 85%. Conclusions Diagnostic accuracy of routinely-collected health datasets is likely to be sufficient for identifying cases of MND in large-scale prospective epidemiological studies in high income country settings. Primary care datasets, particularly from countries with a widely-accessible national healthcare system, are potentially valuable data sources warranting further investigation.

Use of laboratory-based surveillance data to estimate the number of people chronically infected with hepatitis B living in Scotland

It is paramount to understand the epidemiology of chronic hepatitis B to inform national policies on vaccination and screening/testing as well as cost-effectiveness studies. However, information on the national (Scottish) prevalence of chronic hepatitis B by ethnic group is lacking. To estimate the number of people with chronic hepatitis B in Scotland in 2009 by ethnicity, gender and age, the test data from virology laboratories in the four largest cities in Scotland were combined with estimates of the ethnic distribution of the Scottish population. Ethnicity in both the test data and the Scottish population was derived using a name-based ethnicity classification software (OnoMAP; Publicprofiler Ltd, UK). For 2009, we estimated 8720 [95% confidence interval (CI) 7490-10 230] people aged ⩾15 years were living with chronic hepatitis B infection in Scotland. This corresponds to 0·2% (95% CI 0·17-0·24) of the Scottish population aged ⩾15 years. Although East and South Asians make up a small proportion of the Scottish population, they make up 44% of the infected population. In addition, 75% of those infected were aged 15-44 years with almost 60% male. This study quantifies for the first time on a national level the burden of chronic hepatitis B infection by ethnicity, gender and age. It confirms the importance of promoting and targeting ethnic minority groups for hepatitis B testing.