Virus discovery in dogs with non-suppurative encephalitis reveals a high incidence of tick-borne encephalitis virus infections in Switzerland.

INTRODUCTION: Viral infections are a frequent cause of disseminated non-suppurative encephalitis in dogs. However, using routine diagnostic methods, the specific virus may remain unknown due to extensive or complete viral clearance or because the virus is unexpected or new. A metatranscriptomics-based approach of combining high-throughput sequencing (HTS) and bioinformatics analysis was used to investigate the viral etiology in archival cases of dogs with non-suppurative encephalitis. In formalin-fixed paraffin embedded (FFPE) brain material from the years 1976 to 2021 a high incidence of tick-borne encephalitis virus (TBEV) was detected. Moreover, canine distemper virus (CDV) was identified without typical demyelinating lesions and canine vesivirus (CaVV) was detected as an unexpected virus associated with non-suppurative encephalitis. We demonstrated the viral presence in brain tissues at the sites of inflammation by immunohistochemistry (IHC) and in situ hybridization (ISH). These results highlight the value of emerging sequencing technologies in veterinary diagnostics and expand our knowledge on the etiologies of encephalitis in dogs.

INTRODUCTION: Les infections virales sont une cause fréquente d'encéphalite non suppurée disséminée chez le chien. Cependant, en utilisant les méthodes de diagnostic de routine, le virus spécifique peut rester inconnu en raison d'une clairance virale importante ou complète ou parce que le virus est inattendu ou nouveau. Une approche métatranscriptomique combinant le séquençage à haut débit et l'analyse bioinformatique a été utilisée pour étudier l'étiologie virale dans des cas archivés de chiens atteints d'encéphalite non suppurée. Une incidence élevée du virus de l'encéphalite à tiques (TBEV) a été détectée dans le matériel cérébral fixé au formol et inclus dans la paraffine (FFPE) des années 1976 à 2021. En outre, le virus de la maladie de Carré (CDV) a été identifié sans lésions démyélinisantes typiques et le vésivirus canin (CaVV) a été détecté comme un virus inattendu associé à une encéphalite non suppurative. Nous avons démontré la présence virale dans les tissus cérébraux au niveau des sites d'inflammation par immunohistochimie (IHC) et hybridation in situ (ISH). Ces résultats soulignent la valeur des technologies de séquençage émergentes dans le diagnostic vétérinaire et élargissent nos connaissances sur les étiologies de l'encéphalite chez les chiens.

The effectiveness of parallel gamma-interferon testing in New Zealand's bovine tuberculosis eradication programme.

In bovine tuberculosis (bTB) eradication programmes, especially where prevalence is low, sensitivity of testing in infected herds must be maximised to reduce the possibility of recrudescence of prior infection and the risk to other herds via animal movement. The gamma-interferon (γ-IFN) assay applied in parallel with intradermal tuberculin testing has been shown to increase test sensitivity. The aim of this work was to substantiate this effect in the field. A retrospective observational study was conducted on 239 New Zealand cattle breeding and dairy herds with bTB infection between 1 July 2011 and 1 September 2015 to evaluate the outcomes of new policy introduced in 2011. The investigation defined the number and proportion of reactors (animals testing positive and slaughtered) found with lesions of bTB in intradermal caudal fold testing (CFT) and parallel γ-IFN testing, at the breakdown test or first whole herd test after breakdown, WHT(1), and at the final or projected final whole herd test, WHT(F). Parallel γ-IFN testing was used in 26.8% of the 239 herds at WHT(1), and 430 animals in 49 herds were deemed reactors. One hundred and sixty (37.2%) of these reactors from 32 herds were found to have bTB lesions, despite having been negative to caudal fold testing. These 160 infected animals accounted for 29.6% of all infection found at WHT(1). At WHT(F), parallel γ-IFN testing was conducted on 93 herds and detected a total of 122 reactors in 49 herds, in addition to those found by CFT. Twenty-one of these reactors, from 13 herds, had bTB lesions at slaughter, accounting for 67.7% of all reactors found with bTB at WHT(F). Eleven of these 13 herds would have had their movement restrictions revoked based on a negative herd CFT alone, and could potentially have caused outward transmission of bTB to other herds, as well as experiencing recrudescent breakdowns. We conclude that γ-IFN testing in infected herds, in parallel with intradermal tuberculin testing, is a valuable tool in a bTB eradication programme, as it enables higher test sensitivity at both herd and animal level. The use of the γ-IFN test over a risk cohort early in a breakdown assists in removal of early infection and some cases of anergy to intradermal tuberculin testing. Parallel γ-IFN with compulsory slaughter of reactors should be considered in breeding and dairy herds in conjunction with tuberculin testing before movement control is revoked, and will assist in achieving TB freedom on a herd level and nationally.

Disease characteristics, treatment patterns, and outcomes of follicular lymphoma in patients 40 years of age and younger: an analysis from the National Lymphocare Study†.

BACKGROUND: Follicular lymphoma (FL) is the most common indolent non-Hodgkin lymphoma, with median age at diagnosis in the seventh decade. FL in young adults (YAs), defined as diagnosis at ≤40 years, is uncommon. No standard approaches exist guiding the treatment of YA FL, and little is known about their disease characteristics and outcomes. To gain further insights into YA FL, we analyzed the National LymphoCare Study (NLCS) to describe characteristics, initial treatments, and outcomes in this population versus patients aged >40 years. PATIENTS AND METHODS: Using the NLCS database, we stratified FL patients by age: 18-40 (YA), 41-60, 61-70, 71-80, and >80 years. Survival probability was estimated using Kaplan-Meier methodology. We examined associations between age and survival using hazard ratios and 95% confidence intervals (CIs) from multivariable Cox models. RESULTS: Of 2652 eligible FL patients in the NLCS, 164 (6%) were YAs. Of YA patients, 69% had advanced disease, 80% had low-grade histology, and 50% had good-risk disease according to the Follicular Lymphoma International Prognostic Index (FLIPI). Nineteen percent underwent observation, 12% received rituximab monotherapy, and 46% received chemoimmunotherapy [in 59% of these: R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone)]. With a median follow-up of 8 years, overall survival (OS) at 2, 5, and 8 years was 98% (95% CI 93-99), 94% (95% CI 89-97), and 90% (95% CI 83-94), respectively. Median progression-free survival (PFS) was 7.3 years (95% CI 5.6-not reached). CONCLUSIONS: In one of the largest cohorts of YA FL patients treated in the rituximab era, disease characteristics and outcomes were similar to patients aged 41-60 years, with favorable OS and PFS in YAs. Longer-term outcomes and YA-specific survivorship concerns should be considered when defining management. These data may not support the need for more aggressive therapies in YA FL. CLINICAL TRIAL NUMBER: Roche/Genentech ML01377 (U2963n).

Recurrent bovine tuberculosis in New Zealand cattle and deer herds, 2006-2010.

A retrospective cohort study was conducted to identify risk factors for bovine tuberculosis (bTB) recurrence in New Zealand cattle and deer herds identified as bTB-infected from 1 June 2006 to 1 November 2010. A Cox proportional hazards model identified a positive relationship between the daily hazard of bTB recurrence and: (1) the number of prior bTB episodes for two episodes [hazard ratio (HR) 3·22, 95% confidence interval (CI) 1·21-8·60], and for five episodes (HR 89·5, 95% CI 13·8-580), (2) more than one positive bTB case animal at the index episode (HR 2·25, 95% CI 1·19-4·25) and (3) the presence of cleared test-positives at the final test of the index episode. The proportional hazards assumption was violated for the latter variable so a time-dependent covariate was introduced. Up to 2 years post-clearance, the daily hazard of bTB recurrence was greater in herds with test-positives at the final test (HR 2·59, 95% CI 1·30-5·13), but this effect was not observed more than 2 years' post-clearance (HR 1·05, 95% CI 0·28-3·91). We conclude that unresolved infection contributes to further bTB episodes in the first 2 years after herd clearance.

Effect of hypogammaglobulinemia on the incidence of community-acquired respiratory viral infections after lung transplantation.

BACKGROUND: Hypogammaglobulinemia (HGG) has been associated with an increased risk of infectious complications in lung transplant recipients, but its effect specifically on community-acquired respiratory viruses (CARVs) remains unknown. This study aimed to determine if lung transplant recipients with HGG are at an increased risk of developing CARV infection. Secondary endpoints included the effect of HGG on lung function, incidence of rejection, and mortality. METHODS: A retrospective review of all lung transplant recipients from 2008 to 2011 was performed. Patients were stratified as either having HGG after transplantation or having normal IgG titers according to their nadir IgG level. HGG was defined a serum IgG level of <700 mg/dL. CARVs included human metapneumovirus, influenza A/B, respiratory syncytial virus A/B, parainfluenza 1/2/3, rhinovirus, and adenovirus isolated from bronchoalveolar lavage/wash, sputum, or nasal swab. RESULTS: The cohort consisted of 263 patients with a mean follow-up time of 612 ± 356 days. The incidence of CARV infection was 27% in patients with normal IgG titers and 23.4% in patients with HGG (P = .62). No difference in rejection, mortality, or lung function was found between the groups. As expected, patients who ever had a CARV infection had a significantly lower 1-second forced expiratory volume % reference on their most recent spirometry than those who had not had a CARV infection (81.6% vs 86.9%; P = .027). CONCLUSIONS: Although CARV infection has been shown to affect lung graft function, these data suggests that HGG is not associated with the incidence of CARV infection.

Effectiveness of a non-surgical alternative to the Mules operation in sheep.

OBJECTIVE: To measure changes to the perineal bare area, local tissue reaction and healing responses of young sheep, following intradermal administration of cetrimide and polyvinylpyrrolidone (PVP), with and without ethanol, to the breech and tail. METHOD: A needle-less injector was used to deposit formulations containing 40 g/L cetrimide and 30 g/L PVP (group 2) or 20 g/L cetrimide, 30 g/L PVP and 15 g/L ethanol (group 3), within the dermis of the tail and the region surrounding the perineal bare breech area of groups (N = 8) of Merino weaner sheep. The dimensions of the perineal bare area (length, width and diagonal distances left and right) and tail width were recorded before and at intervals after treatment for 60 days. Observations of swelling and bruising and scab formation at the treatment sites were recorded for up to 35 days after treatment. Rectal temperatures were monitored for up to 35 days after treatment and bodyweight for up to 60 days after treatment. An untreated control group (group 1) was included. RESULTS: Comparison of day -3 and day 35 measurement data showed that both treated groups had significantly (P < 0.05) wider breech bare areas compared to the untreated controls and that group 2 sheep had significantly (P < 0.05) longer breech bare areas compared to group 3 sheep or to the untreated controls, which were not significantly different. At this time scabs were still firmly in place on many treated sheep. At day 35 there was no increase in tail bare area caused by either treatment. By day 60 there was no significant difference between the treated and control groups in either the breech or tail regions indicating that the changes present at day 35, were not permanent. Mean weight gain in the groups throughout the 60-day interval was unaffected by treatment. Intradermal treatment was associated with a significant elevation in body temperature. This effect lasted for 3 days and was associated with signs of discomfort and depressed appearance in at least some of the treated sheep. Bruising was mild to severe in all treated sheep within two days of treatment but was not evident in any sheep by day 21. Mild to moderate swelling was also associated with treatment but was not uniform across sheep in the groups. The tail of one sheep was severely swollen for several days. Swelling remained obvious in most treated sheep until day 14 but was not present at day 21. CONCLUSION: Under the conditions of this study intradermal injection of cetrimide had no permanent effect on bare area measurements on the breech or the amount of wool-bearing skin on the tail. It also caused signs of discomfort and pain that raise welfare concerns.

Control of endoparasites in horses with a gel containing moxidectin and praziquantel.

A gel formulation containing moxidectin (20 g/kg) and praziquantel (125 g/kg) reduced the geometric mean faecal strongyle egg count in horses to below 100 eggs per gram of faeces (epg) for at least 12 weeks despite their being exposed continuously to reinfection from pasture grazed by treated and untreated horses. The geometric mean egg count of horses treated with a proprietary paste containing abamectin (3.7 g/kg) and praziquantel (46.2 g/kg) increased steadily from six weeks after the treatment, peaking at over 820 epg after 12 weeks. Relative to the efficacy of the abamectin/praziquantel treatment, the reduction in mean faecal egg count compared with the pretreatment counts was significantly (P<0.05) better in the horses treated with moxidectin and praziquantel from eight weeks after the treatment. Both products eliminated tapeworms from horses in a non-invasive modified critical trial.

Efficacy of moxidectin and other anthelmintics against small strongyles in horses.

OBJECTIVE: To compare the efficacy of moxidectin to ivermectin, oxibendazole and morantel against some gastrointestinal nematodes in horses. DESIGN: Faecal egg count reduction after treatment. PROCEDURE: A farm was selected where the population of small strongyles in horses was known to be resistant to oxibendazole. Horses were allocated to treatment groups based on faecal egg counts. After treatment, faecal samples were taken up to 109 days after treatment and faecal egg counts estimated. Faecal cultures were used to estimate the contribution of small and large strongyles to the faecal egg counts at each sampling. RESULTS: Moxidectin (0.4 mg/kg) suppressed faecal egg counts for 109 days after treatment in most horses compared to 40 days with ivermectin (0.2 mg/kg), 13 days with morantel (9.4 mg/kg) and less than 13 days with oxibendazole (10 mg/kg). Most of the faecal egg count was attributable to small strongyles based on faecal culture, although Strongylus vulgaris was present in some samples in low numbers. Oxibendazole resistance in small strongyles was confirmed and a less than expected efficacy of morantel was also seen. CONCLUSION: Moxidectin was highly effective in reducing faecal egg counts after treatment for at least 12 weeks and up to 16 weeks in most horses. These horses were infected with a population of small strongyles known to be resistant to oxibendazole and possibly morantel. The duration of the reduction in faecal egg counts after treatment with moxidectin (0.4 mg/kg) was at least twice that of ivermectin (0.2 mg/kg) and greater than four times that for morantel and oxibendazole.

Persistent efficacy of abamectin and doramectin against gastrointestinal nematodes of cattle.

OBJECTIVE: To assess the persistent activity of injectable formulations of abamectin and doramectin against gastrointestinal nematodes of cattle. DESIGN: Controlled slaughter study assessing residual efficacy. PROCEDURE: Nematode-free calves were treated with abamectin or doramectin (each at a dose of 200 micrograms/kg) and infections then induced with repeated doses of infective larvae of Trichostrongylus axei, Haemonchus placei, Ostertagia ostertagi and Cooperia species. The duration of challenge ranged from 14 to 28 days. The calves were slaughtered at either 38/39 or 45/46 days after the treatments and nematodes recovered from the gastro-intestinal tract. RESULTS: Significant reductions in numbers of O ostertagi occurred for both abamectin and doramectin treatments (> 93%) relative to counts in untreated calves, when challenge was administered up to 21 days after treatment. For T axei and Cooperia spp significant reductions occurred when the challenge occurred for 14 days after treatment (99%). Although differences from untreated animals were not significant, the results for H placei suggested high efficacy (> 85%) for up to 21 days for doramectin and up to 28 days for abamectin. CONCLUSIONS: There was no significant difference between abamectin and doramectin for any parasite at any challenge point, indicating that there is equivalent persistent activity of doramectin and abamectin against important gastrointestinal nematodes of cattle.

Naphthalophos combinations with benzimidazoles or levamisole as effective anthelmintics for sheep.

OBJECTIVE: To investigate the relative efficacy and safety of the anthelmintic naphthalophos in sheep, either given alone or in combination with benzimidazole (fenbendazole and albendazole) or levamisole anthelmintics. DESIGN: A parasitological study using faecal egg count reduction tests, a validating slaughter trial and field safety trials. PROCEDURE: Faecal egg count reduction tests were carried out on 13 farms. Naphthalophos and combinations of naphthalophos with levamisole and fenbendazole were included in the drench tests. On one property a controlled efficacy study was carried out to validate faecal egg count reduction test findings. In this trial, sheep were slaughtered 10 days after treatment and the remaining parasites recovered from the gastro-intestinal tract. Safety trials were carried out on eight farms where approximately 50,000 sheep were treated with naphthalophos and albendazole that were tank mixed in the backpack. RESULTS: The efficacy of naphthalophos alone in faecal egg count reduction tests ranged from 59 to 98% with one test showing > or = 95% reduction. The efficacy of naphthalophos and levamisole ranged from 74 to 100%, with 5 farms showing > or = 95% reduction. The efficacy of naphthalophos and fenbendazole ranged between 88 and 100% with > or = 95% reduction achieved on 10 farms. The controlled efficacy study showed a good correlation between the faecal egg count reduction tests and numbers of parasites recovered, except for Nematodirus where the faecal egg count reduction test overestimated efficacy. The mortality rate in the safety trials was 0.05%, with most fatalities occurring on one farm. CONCLUSION: The combination of naphthalophos and fenbendazole was more effective than a combination of naphthalophos and levamisole, and will provide a sufficiently safe drench rotation option.

Pyrethroid resistance in Australian field populations of the sheep body louse, Bovicola (Damalinia) ovis.

Synthetic pyrethroid (SP) resistance has developed in Australian field populations of the sheep body louse, Bovicola (Damalinia) ovis. Laboratory bioassays were used to measure the susceptibility of lice to cypermethrin and the other registered SPs. Results of these bioassays indicated resistance to cypermethrin, deltamethrin, cyhalothrin and alphacypermethrin. So far, high-level resistance has been diagnosed in only a few strains. The toxicological responses of these strains were clearly separated from those of the majority of louse strains tested. Furthermore, these strains had survived immersion in commercial SP dips. The level of resistance described in some strains was sufficient to cause pour-on products to fail despite the fact that the LC50s of these strains fell within the normal range of field responses.

Resistance to synthetic pyrethroid pour-on insecticides in strains of the sheep body louse Bovicola (Damalinia) ovis.

Groups of sheep infested with strains of Bovicola (Damalinia) ovis were obtained from flocks either with a history of failure to control lice with synthetic pyrethroid (SP) pour-on insecticides, or from farms where SP compounds were not used. The sheep were treated according to the manufacturer's recommendations with registered "off-shears" SP formulations. All treatments were applied under ideal conditions with doses calculated on an individual body weight basis and applied to the dorsal mid-line from the base of the neck to the butt of the tail. Treated sheep were kept in pens and maintained in separate groups. The pour-on SP treatments significantly reduced the lice population but failed to eliminate the infestation in 7 of 13 experiments in sheep carrying strains of lice with resistance factors of greater than 4 to at least one of the SP compounds. Failures occurred with all three of the SP pour-ons currently registered for lice control in NSW and with both water-based and organic solvent-based formulations.

Age-related marrow changes in the pelvis: MR and anatomic findings.

Short repetition time magnetic resonance images of the pelvis in 70 subjects (aged 1 day to 24 years) without history of bone marrow disease were retrospectively analyzed for the distribution and appearance of red and yellow marrow. The signal intensity and degree of mottling of marrow in six anatomic regions of the pelvis were observed and were assigned a grade. Anatomic correlation was provided with gross and microscopic examination of bone marrow biopsy specimens taken from selected pelvic sites in cadavers of children. Marrow signal intensity increased in all pelvic regions except the acetabulum from birth to age 24 years. Marrow heterogeneity was most prominent in the acetabulum at all ages. Patterns of bone marrow signal intensity and heterogeneity are recognized for four age groups: the infant, child, adolescent, and young adult. Regional and age-related differences in the signal intensity of pelvic marrow correlate with the percentage of fat seen microscopically in marrow.

Solid-state phosphorus-31 nuclear magnetic resonance differentiation of bone mineral and synthetic apatite used to fill bone defects.

Bioabsorption of synthetic apatite compounds used to promote bone healing and remodeling has been difficult to evaluate. In this study, solid-state phosphorus-31 nuclear magnetic resonance (NMR) has been used to characterize and quantitate bone mineral and a synthetic apatite in order to establish a model for bioabsorption studies. Pulverized solid samples of cortical rabbit bone and a synthetic fluoridated apatite were examined in vitro at variable degrees of hydration. A 9.4 T superconducting spectrometer was used to obtain 31P magic angle spinning NMR spectra and T1 relaxation times. Quantitation was attempted in mixed samples using T1 recovery data. Bone mineral and synthetic apatite could be distinguished by chemical shift and T1 relaxation time in variable hydration states, and were readily differentiated in mixtures by their T1 relaxation time. NMR estimates of relative proportions of components in mixed samples were accurate within 2% of evaluations based on weight. Solid-state 31P NMR therefore provides a suitable method for monitoring the bioabsorption of synthetic apatites.

Neonatal tuberous sclerosis: magnetic resonance appearance of subependymal tubers.

A case of tuberous sclerosis in a neonate, with cerebral and cardiac hamartomas evaluated by MR imaging, is presented. Intracranial subependymal tubers in this neonate exhibit increased signal intensity on short TR images. This differs from the signal characteristics of subependymal tubers in older patients.

Red and yellow marrow in the femur: age-related changes in appearance at MR imaging.

T1-weighted magnetic resonance (MR) images of the femur in 77 subjects, aged 1 month to 24 years, were retrospectively analyzed for the distribution and appearance of red and yellow marrow. The subjects were divided into six age groups, and the signal intensity and degree of mottling of marrow in the proximal epiphysis, proximal metaphysis, diaphysis, distal metaphysis, and distal epiphysis were observed and assigned a grade. Bone marrow with low or intermediate to slightly increased signal intensity was considered red marrow, while bone marrow with increased signal intensity was considered fatty marrow. An orderly progression of red to yellow marrow conversion in the femur was appreciated first in the diaphysis (ages 1-10 years) and then in the distal metaphysis (ages 10-20 years), with an adult pattern seen by age 24 years. The MR spectrum of red and yellow marrow differs from the existing macroscopic anatomical data because MR imaging is apparently more sensitive to the presence of microscopic fat in bone marrow.

Enhancement of mitochondrial function in sepsis.

Recent reports from our laboratory have challenged the concept that sepsis selectively damages or interferes with mitochondrial function. To address the lingering skepticism that mitochondrial assays in surviving animals might not detect this "injury," we injected rats with a lethal dose of Escherichia coli endotoxin and compared hepatic, cardiac, and skeletal muscle mitochondrial function in these animals with that of control rats. Mitochondrial function was serially determined during a four-hour postmortem period by measuring the respiratory control ratio, the adenosine diphosphate-oxygen ratio, and protein levels. Hepatic mitochondria ceased to function within 30 minutes of the time of death. Cardiac and skeletal muscle mitochondria functioned normally up to four hours after death in both septic and control animals. Mitochondria from septic animals had a significantly higher respiratory control ratio than those from control rats. Thus, sepsis appears to enhance rather than damage mitochondrial function up to four hours after death.