Louping ill virus: an endemic tick-borne disease of Great Britain.

In Europe and Asia, Ixodid ticks transmit tick-borne encephalitis virus (TBEV), a flavivirus that causes severe encephalitis in humans but appears to show no virulence for livestock and wildlife. In the British Isles, where TBEV is absent, a closely related tick-borne flavivirus, named louping ill virus (LIV), is present. However, unlike TBEV, LIV causes a febrile illness in sheep, cattle, grouse and some other species, that can progress to fatal encephalitis. The disease is detected predominantly in animals from upland areas of the UK and Ireland. This distribution is closely associated with the presence of its arthropod vector, the hard tick Ixodes ricinus. The virus is a positive-strand RNA virus belonging to the genus Flavivirus, exhibiting a high degree of genetic homology to TBEV and other mammalian tick-borne viruses. In addition to causing acute encephalomyelitis in sheep, other mammals and some avian species, the virus is recognized as a zoonotic agent with occasional reports of seropositive individuals, particularly those whose occupation involves contact with sheep. Preventative vaccination in sheep is effective although there is no treatment for disease. Surveillance for LIV in Great Britain is limited despite an increased awareness of emerging arthropod-borne diseases and potential changes in distribution and epidemiology. This review provides an overview of LIV and highlights areas where further effort is needed to control this disease.

Outbreak of sarcoptic mange in alpacas (Vicugna pacos) and control with repeated subcutaneous ivermectin injections.

An outbreak of sarcoptic mange was investigated in an alpaca herd. Clinical disease occurred 2 months after the introduction of four alpacas with dry seborrhoeic skin lesions, the cause of which was not investigated. Initially a group of females was affected, despite repeated topical treatment with ivermectin at a dose of 0.5mg/kg bodyweight. One female died and post-mortem examination indicated sarcoptic mange as the cause of death. Infection with Sarcoptes scabiei was also demonstrated on microscopic examination of skin scrapes taken from clinically affected cohorts. Later in the outbreak, a separate group of male alpacas was also affected. Treatment using subcutaneous ivermectin injections at a dose of 0.2mg/kg, administered at 14-day intervals, was evaluated. During this course of treatment, another female died. A successful response in the other alpacas was eventually reached following 12 treatments of the female group and 8 treatments of the male group.

Outbreak of tuberculosis caused by Mycobacterium bovis in golden Guernsey goats in Great Britain.

An outbreak of caprine tuberculosis caused by Mycobacterium bovis was disclosed in June 2008, affecting goats of the golden Guernsey breed kept on 10 separate smallholdings in south-west Wales and the west of England. Following the initial diagnosis at postmortem examination, 30 goats that reacted positively to the single intradermal comparative cervical tuberculin (SICCT) test, together with five in-contact animals, were euthanased and subjected to postmortem examination and mycobacterial culture. Spoligotyping and variable number tandem repeat analysis of isolates showed that they were all of the same genotype, endemic to south-west Wales. Retrospective movement tracings identified a goat herd in south-west Wales, by then completely dispersed, as the probable common source of infection. There was a perfect correlation between the SICCT test and culture results in all slaughtered goats. Grossly visible tubercular lesions were observed at postmortem examination in all but one reactor.

Health-related quality of life after pancreatic islet transplantation: a longitudinal study.

BACKGROUND: Pancreatic islet transplantation (PIT) has proven effective in achieving insulin independence, but to date, the impact of PIT on health-related quality of life (HRQL) has not been studied. METHODS: Ten patients who have undergone PIT at our institution were administered three HRQL questionnaires: the Hypoglycemia Fear Survey, the 36-Item Short Form Health Survey (SF-36), and a fatigue questionnaire. HRQL was assessed before PIT, then 3, 6, and 12 months after PIT. Responses were compared by analysis of variance and paired Student's t tests. RESULTS: Hypoglycemia Fear Survey responses demonstrated that hypoglycemia-related anxiety and hypoglycemia-related behavior modification occurred less frequently after PIT (P=0.003 and 0.0001, respectively). The total scores of the hypoglycemia questionnaire were also significantly improved after PIT, from a median score of 156 points before transplantation to 55 points 3 months after PIT (P=0.004), 38 points 6 months after PIT (P=0.001), and 69 points 12 months after PIT (P=0.04). The median scores of all SF-36 components also improved after PIT. No significant changes were seen in the fatigue symptoms as assessed by the fatigue questionnaire. CONCLUSION: PIT recipients have less anxiety about the symptoms and consequences of hypoglycemia. PIT recipients also indicate that their behavior requires significantly less modification to prevent or treat hypoglycemia after PIT compared with before PIT. Further investigation is needed to determine whether PIT improves generic measures of HRQL.

Transaminitis after pancreatic islet transplantation.

BACKGROUND: An asymptomatic, self-limited transaminitis uniformly follows pancreatic islet transplantation (PIT) performed through portal vein (PV) infusion. The underlying cause and significance of this transaminitis is unclear. STUDY DESIGN: Records of all patients with insulin-dependent diabetes mellitus who had undergone PIT at our institution were reviewed. All PITs were performed in conjunction with a remote pancreatic islet isolation center and done through percutaneous transhepatic PV infusion. Alanine aminotransferase (ALT) levels, serum glucose concentrations, insulin requirements, and color-flow Doppler ultrasonography examinations of the right upper quadrant were assessed before and after PIT. RESULTS: Eleven patients have undergone a total of 26 PITs. An elevated ALT level occurred in all 11 patients (100%) after the first PIT, with the median post-PIT peak ALT level reaching 187 IU/L. Transaminitis was less frequent and less marked after the second PIT. A negative correlation between viability of the pancreatic islets transplanted (r = -0.44, p = 0.03) and a positive correlation between the ratio of maximum to initial PV pressure (r = 0.41, p = 0.04) were seen with the subsequent ALT peak. Color-flow Doppler ultrasonography examinations showed no occurrences of PV thrombosis or intrahepatic hematoma. Finally, the degree of transaminitis did not correlate with post-PIT insulin requirements, indicating that post-PIT transaminitis cannot be used to measure allograft rejection or function. CONCLUSIONS: Transaminitis after PIT is common and self-limited. Post-PIT transaminitis does not signal acute rejection or serious procedure-related complications such as PV thrombosis or intrahepatic hematoma.

The effect of pancreatic islet transplantation on progression of diabetic retinopathy and neuropathy.

INTRODUCTION: Pancreatic islet transplantation (PIT) has only become an effective treatment for type 1 diabetes mellitus within the past 4 years. As a result, the long-term effects of PIT on progression of diabetic neuropathy and retinopathy are unknown. The benefit of halting or improving diabetic neuropathy and retinopathy is of particular interest since most PIT recipients have not developed the advanced complications of diabetes. Herein, we describe the improvement and stabilization of diabetic neuropathy and retinopathy in 12 PIT recipients. PATIENTS AND METHODS: Between January 1, 2002, and June 30, 2004, there have been 12 patients who have received PIT. Currently, there are eight patients who have sufficient follow-up to assess the progression of diabetic retinopathy and neuropathy. To assess for disease progression, patients were examined by a single ophthalmologist and single neurologist throughout the study period. Eye exams were performed using a slit-lamp exam while neurological status was assessed using electromyelograms and clinical exams. RESULTS: All PIT recipients had decreases in hemoglobin A(1)C and increases in serum C-peptide. All study patients had stabilization of their retinopathic disease. One patient demonstrated improvement of retinopathy at 1 year posttransplant. Fifty percent of patients demonstrated improvement or stabilization of their diabetic neuropathy. One patient had mild reinnervation of the fingers and wrist extensors by clinical exam 1 year posttransplant. Four patients exhibited an average decrease of 19% in sural nerve conduction velocities. CONCLUSION: Our series has demonstrated that all PIT recipients have had stabilization of their diabetic retinopathy and that 50% of patients exhibited stabilization or even improvement of their diabetic neuropathy.

Protection against vertical transmission in bovine neosporosis.

In this study we were interested to determine whether infection of cattle prior to pregnancy would afford any protection to the foetus if the dams were challenged with Neospora caninum at mid-gestation. The experiment comprised four groups of cattle: group 1, uninfected controls; group 2, inoculated with N. caninum tachyzoites 6 weeks prior to mating and then challenged with N. caninum at mid-gestation; group 3, naive cattle challenged with N. caninum at mid-gestation and group 4 were infected with N. caninum prior to mating and left unchallenged throughout pregnancy. Positive cell-mediated and humoral immune responses to N. caninum were recorded in groups 2 and 4 prior to pregnancy and in groups 2, 3 and 4 following challenge at mid-gestation. However there was a marked down regulation of the cell-mediated immune response in all groups around mid-gestation. There was a significant increase in rectal temperature response in animals in group 3 compared to group 2 following challenge but no other clinical symptoms of disease were recorded and all cattle proceeded to calving. At calving, pre-colostral blood samples were negative for antibodies to N. caninum in all the calves born to dams in groups 1, 2 and 4. In contrast, all the calves born to dams in group 3 had high levels of specific antibody to N. caninum indicating that they had been exposed to the parasite in utero. At post-mortem N. caninum DNA was detected in CNS, thymus and placental cotyledon samples in calves from group 3. All tissue samples from calves in the other 3 groups were negative for N. caninum DNA with the exception of one calf from group 2 where specific DNA was detected in a sample of spinal cord. These results suggest that the immune response generated in the dams in group 2 prior to pregnancy had protected against vertical transmission of the parasite following challenge at mid-gestation.

Neosporosis. Aspects of epidemiology and host immune response.

Neospora caninum is a recently recognized protozoan parasite which has been described as causing a neuromuscular paralysis in dogs and is emerging as a major cause of bovine infertility and abortion worldwide. The parasite is known to infect a range of warm blooded animals but the disease predominates in dogs and cattle. It is not yet known if N. caninum can infect and cause disease in people. The dog has recently been identified as the definitive host and the parasite may be transmitted through the ingestion of oocysts or congenitally from mother to fetus. N. caninum is known to infect red foxes (Vulpes vulpes) and coyotes (Canis latrans) and the role of wildlife species as reservoirs of infection requires further investigation. Little is known about the range of parasite genotypes within the environment or the variation in virulence between different strains. RAPD-PCR analysis of geographically distinct bovine and canine isolates has revealed little genetic variation. Epidemiological studies from different areas of the world have investigated the importance of N. caninum as an abortifacient agent and longitudinal studies have shown the high rate (approximately 80%) of congenital transmission within infected herds. Information on the rates of repeat abortion due to neosporosis are less well defined however current estimates put this at 5% suggesting that cattle may develop some form of protective immunity against N. caninum-induced abortion. Diagnosis of the disease is based upon detection of the parasite in the tissues, most commonly using immunohistochemistry with additional information provided by serology. However, although positive fetal serology is a strong indicator of exposure to the parasite, care should be taken in the interpretation of maternal serology. As we understand more about the epidemiology of neosporosis we are also better able to interpret the results of diagnostic tests. The mere presence of the parasite does not necessarily infer that this was the primary cause of abortion. CD4+ T-cells, interferon gamma and macrophages have all been found to significantly inhibit multiplication of N. caninum tachyzoites. The nature of a protective immune response and its modulation in the pregnant animal is discussed.

Lack of cytomegalovirus transmission after pancreatic islet transplantation.

In spite of antiviral prophylaxis, the transmission rate of cytomegalovirus (CMV) after solid organ transplantation remains high. In contrast, CMV transmission has never been reported following pancreatic islet transplantation (PIT). Eleven (seven CMV seronegative, four CMV seropositive) recipients underwent a total of 26 PITs. Following PIT recipients were monitored clinically and tested monthly for CMV antigenemia. Valganciclovir was given to all patients for 100 days after each PIT. Follow-up ranged from 6 to 24 months (median 14.5 months). Pancreatic islet grafts were procured from 18 CMV seropositive and 8 seronegative donors (69% and 31% of donors, respectively). In total there were 6 R+D+, 3 R+D-, 12 R-D+, and 5 R-D-PITs. No patient developed CMV antigenemia or symptoms consistent with CMV infection at any time following PIT. Routine posttransplant testing of PIT recipients demonstrated that neither CMV transmission nor CMV infection occurred after PIT.

Characterisation of the lymphoproliferation in rabbits experimentally affected with malignant catarrhal fever.

Malignant catarrhal fever (MCF) in rabbits caused by the three Herpesviruses: alcelaphine herpesvirus-1 (AHV-1), ovine herpesvirus-2 (OHV-2) and hippotragine herpesvirus-1 (HipHV-1) induced hyperplasia of lymphoid tissues and accumulations of mononuclear lymphoid cells in non-lymphoid tissues. However, certain lymph nodes were affected preferentially. The lymphoid cells in non-lymphoid tissues were CD43+ T-cells which showed evidence of in situ multiplication. A more detailed phenotypic analysis of splenocytes and lymph node cells in AHV-1 infected rabbits suggested that the hyperplasia was probably due to the expansion of CD8+ T-cells. On the basis of these data and the observations of other authors, that no or very little viral expression can be detected in lesions of MCF affected animals, we propose that the pathogenesis of MCF results from a dysregulation of a secretory T-cell activator. The variable pathology induced by the three viruses may reflect a quantitative or qualitative differences in this proposed activator.

Phenotype, growth regulation and cytokine transcription in Ovine Herpesvirus-2 (OHV-2)-infected bovine T-cell lines.

The causal agent of sheep-associated malignant catarrhal fever (MCF), Ovine Herpesvirus-2 (OHV-2), can be propagated in IL-2-dependent lymphoblastoid cell lines derived from diseased cattle and deer providing a useful model for the investigation of the pathogenesis of MCF. In this study, five interleukin-2 (IL-2)-dependent cell lines were established from affected cattle to examine their growth regulation and cytokine transcription. All cell lines expressed CD2, CD5 and CD25. Three of the cell lines were CD4+ and one CD8+, whereas one cell was of mixed CD4 and CD8 phenotye. The growth of these cell lines was reduced when cultured with antibody against CD25, the IL-2 receptor alpha subunit. All cell lines showed a lack of response to Con A and their cell growth was inhibited by Cyclosporin A which is known to inhibit cytokine promoters. It was decided therefore, to examine the cell lines for the presence of mRNA of different cytokines. The results showed that the cell lines transcribed message for IFNgamma, TNFalpha, IL-4 and IL-10 whereas no mRNA for IL-2 or IL-1beta was detected. In conclusion, the OHV-2-immortalised cell lines resemble anergic T-cells which may be activated giving rise to the characteristic lesions of MCF.

Craniofacial growth in bilateral cleft lip and palate patients following secondary premaxillary setback.

Data of an experimental group of bilateral cleft lip and palate patients (BCLP) who had undergone premaxillary setback at a mean age of 10.2 years were compared with a control group of standard cephalometric values for the white population, and with cephalometric data of BCLP patients from the Oslo Cleft Lip and Palate Archive who did not have premaxillary setback. Cephalometric lateral skull radiographs were taken at a mean age of 16.6 years when most facial growth is completed. Overall, the most marked difference between the two cleft samples was a slightly more concave profile in the experimental BCLP group, mainly due to clockwise rotation of the maxillary plane. Other differences were a longer face and a larger mandible in the experimental group.

Maternal and fetal immune responses of cattle inoculated with Neospora caninum at mid-gestation.

The humoral and cell-mediated immune responses of pregnant cattle and their fetuses were examined at intervals after infection with Neospora caninum tachyzoites at mid-gestation (day 140). All cattle seroconverted and interferon gamma was detected in supernatants of peripheral blood mononuclear cells stimulated with specific antigen. At day 14 post-inoculation (pi), specific cell proliferation responses were detected in the lymph node draining the site of inoculation and in the uterine lymph node. The peak response was recorded in the majority of maternal lymph nodes by day 28 pi and cells from the maternal retropharyngeal lymph node, which in part drains the central nervous system, showed no specific activity to N. caninum until day 42 pi. This changing pattern of immune responsiveness may reflect parasite invasion and development within different host tissues. Fetal lymph node cells showed mitogen responsiveness from day 14 pi (day 154 of gestation) and also showed N. caninum-specific cell proliferation and interferon-gamma responses by day 28 pi (day 168 of gestation). At day 42 pi, specific cell-mediated immune responses were not apparent; however, N. caninum-specific fetal IgG and IgM antibodies were detected.

The pathogenesis of neosporosis in pregnant cattle: inoculation at mid-gestation.

To investigate the pathogenesis of bovine neosporosis, 14 pregnant cattle were each inoculated subcutaneously with either 10(7) or 5 x 10(8) Neospora caninum (strain NC1) tachyzoites at 140 days' gestation. Serial necropsies were then carried out over an 8-week period. In the placenta, Neospora DNA and histopathological changes were observed in samples taken 14 days post-inoculation (dpi), with focal necrosis of maternal caruncular septa and fetal placental villi, serum leakage, and a maternal and fetal inflammatory response. At subsequent samplings, pathological changes in the placenta showed signs of resolution. No parasitaemia was detected in the dams in the two weeks following inoculation. In the fetus, Neospora DNA was detected at 14 dpi, and histopathological changes in the fetal central nervous system at 28 and 42 dpi consisted of small foci of necrosis and inflammation. Resolution of placental lesions during the experiment indicated that the disease was being controlled, and fetal infection, although established, did not appear to be progressing to a fatal outcome. The two doses of tachyzoites produced similar results, but the higher dose elicited earlier and more extensive lesions in the placenta and fetus. Control animals remained negative for all parameters recorded. It is concluded that in bovine neosporosis the placenta plays a central role in the pathogenesis and epidemiology of the infection, and that while primary tissue destruction by the parasite may endanger the fetus, the maternal and fetal inflammatory responses may also be damaging.

Chronic meningoencephalitis associated with Brucella sp. infection in live-stranded striped dolphins (Stenella coeruleoalba).

A chronic, non-suppurative meningoencephalitis was found in three young striped dolphins (Stenella coeruleoalba) during routine neuropathological examination of marine mammals live-stranded on the Scottish coast. In all three dolphins the lesions were associated with the isolation of a Brucella sp. from the brain and with the immunohistochemical detection of brucella antigen. Moreover, antibodies to Brucella spp. were detected in the two dolphins that were subjected to serological examination. Immunohistochemical and serological examinations for morbillivirus antigen and antibodies, respectively, were negative in all cases. Although brucella infection of marine mammals has been extensively documented in recent years, its association with lesions and disease is less well recognized. The present report provides the first description of an association between Brucella sp. infection and neuropathological changes in a cetacean species.

Experimental induction of pneumonic pasteurellosis in calves by intratracheal infection with Pasteurella multocida biotype A:3.

The study aimed to establish an experimental model to investigate the pathogenesis of lung infection by Pasteurella multocida, an important cause of bovine respiratory disease. An experimental model is required to assist the development of an effective vaccine. Sixteen 8-week-old calves were challenged intratracheally with 10(9) or 10(10) colony forming units of P. multocida in either 60 or 300 ml saline in a 2 x 2 factorial experiment. All animals became dull within 2-6h post-infection (p.i.) and two calves were killed humanely because of suspected endotoxic shock. Remaining animals showed increased respiratory rates by 15-20 h p.i. and, at 23 h p.i., calves given the high dose, high volume challenge showed higher (P < 0.05) rectal temperatures. From 24 to 36 h p.i., clinical signs decreased in a majority of animals. Plasma haptoglobin concentrations increased (P < 0.05) in calves given the high volume challenge irrespective of the number of bacteria. At post-mortem examination (4d p.i.), lung lesions, mainly in the apical lobes, were found in all calves. Histopathological examination showed areas of purulent pneumonia with a tendency to abscessation and inflamed interlobular septa characterised by accumulation of neutrophils and oedema. The clinical and pathological responses described were typical of bovine pneumonic pasteurellosis.

Clinical, pathological and epidemiological findings in three outbreaks of ovine protozoan myeloencephalitis.

Ovine protozoan myeloencephalitis is a disease of sheep associated with the apicomplexan protozoan Sarcocystis tenella. This paper describes the clinical, pathological and epidemiological findings in three affected flocks from a well-defined geographical area. Clinical signs were restricted to sheep under one year old in their first winter and were first observed at least 42 days after they had been moved off the hill grazing areas to low ground pasture, or after they were given conserved forage. The findings are discussed in relation to the timescale of the life cycle of S. tenella and it is suggested that clinical disease was precipitated by the change from a low level of exposure to infection on the hill to a high level of exposure through contaminated pasture or forage. Possible preventive strategies are discussed.