Fetal Neuropathology in Zika Virus-Infected Pregnant Female Rhesus Monkeys.

The development of interventions to prevent congenital Zika syndrome (CZS) has been limited by the lack of an established nonhuman primate model. Here we show that infection of female rhesus monkeys early in pregnancy with Zika virus (ZIKV) recapitulates many features of CZS in humans. We infected 9 pregnant monkeys with ZIKV, 6 early in pregnancy (weeks 6-7 of gestation) and 3 later in pregnancy (weeks 12-14 of gestation), and compared findings with uninfected controls. 100% (6 of 6) of monkeys infected early in pregnancy exhibited prolonged maternal viremia and fetal neuropathology, including fetal loss, smaller brain size, and histopathologic brain lesions, including microcalcifications, hemorrhage, necrosis, vasculitis, gliosis, and apoptosis of neuroprogenitor cells. High-resolution MRI demonstrated concordant lesions indicative of deep gray matter injury. We also observed spinal, ocular, and neuromuscular pathology. Our data show that vascular compromise and neuroprogenitor cell dysfunction are hallmarks of CZS pathogenesis, suggesting novel strategies to prevent and to treat this disease.

Immune-mediated Equine Vasculopathies.

Immune-mediated vasculopathies occur secondary to infection or another noninfectious stimulus. Potential triggers include heterologous antigens including viruses, injected proteins and drugs; or auto-antigens including immunoglobulins or other endogenous proteins. Although these conditions are rare in horses, immune-mediated vasculopathies can cause considerable morbidity, with variable clinical signs depending on severity and organ system affected. Examples include purpura hemorrhagica, systemic lupus erythematosus, drug-induced vasculitis, paraneoplastic vasculitis, and idiopathic immune-mediated vasculitis. Diagnosis is presumptive or based on histopathology of skin biopsies if cutaneous signs are present. Treatment relies on removing the inciting cause, immunosuppression, and supportive care.

Detection of Chlamydia and Chlamydia-like organisms in bovine placental tissue.

This study aimed to investigate the presence of Chlamydia spp. and Parachlamydia acanthamoebae in bovine placental tissue originating from abortion and non-abortion cases in Belgium. Placentas of 164 late term bovine abortions (last trimester of gestation) and 41 non-abortion (collected after calving) cases were analysed by PCR for Chlamydia spp., Chlamydia abortus, C. psittaci and P. acanthamoebae. Additionally, a subset of 101 (75 abortion and 26 non-abortion cases) of these placenta samples were also analysed by histopathology to detect possible Chlamydia-induced lesions. In 5.4% (11/205) of the cases, Chlamydia spp. were detected, and three of those cases were positive for C. psittaci. Parachlamydia acanthamoebae was detected in 36% (75/205) of the cases, being 44% (n = 72) in abortions and 7.3% (n = 3) in non-abortions cases (p < .001). None of the cases was positive for C. abortus. Purulent and/or necrotizing placentitis with or without vasculitis was observed in 18.8% (19/101) of the histopathologically analysed placenta samples. In 5.9% (6/101) of the cases, placentitis was observed along with vasculitis. In the abortion cases, 24% (18/75) of the samples showed purulent and/or necrotizing placentitis, while purulent and/or necrotizing placentitis was visible in 3.9% (1/26) of the non-abortion cases. Placental lesions of inflammation and/or necrosis were present in 44% (15/34) of the cases where P. acanthamoebae was detected, while inflammation and/or necrosis was present in 20.9% (14/67) of the negative cases (p < .05). The detection of Chlamydia spp. and especially P. acanthamoebae, in combination with correlated histological lesions such as purulent and/or necrotizing placentitis and/or vasculitis in placental tissue following abortion, suggests a potential role of this pathogen in cases of bovine abortion in Belgium. Further in-depth studies are necessary to unravel the role of these species as abortifacient agents in cattle and to include them in bovine abortion monitoring programmes.

Sheep-Associated Malignant Catarrhal Fever: Role of Latent Virus and Macrophages in Vasculitis.

Malignant catarrhal fever (MCF) is a sporadic, generally fatal disease caused by gammaherpesviruses in susceptible dead-end hosts. A key pathological process is systemic vasculitis in which productively infected cytotoxic T cells play a major role. Nonetheless, the pathogenesis of MCF vasculitis is not yet clear. We hypothesized that it develops due to an interaction between virus-infected cells and immune cells, and we undertook a retrospective in situ study on the rete mirabile arteries of confirmed ovine gammaherpesvirus-2 (OvHV-2)-associated MCF cases in cattle, buffalo, and bison. Our results suggest that the arteritis develops from an adventitial infiltration of inflammatory cells from the vasa vasorum, and recruitment of leukocytes from the arterial lumen that leads to a superimposed infiltration of the intima and media that can result in chronic changes including neointimal proliferation. We found macrophages and T cells to be the dominant infiltrating cells, and both could proliferate locally. Using RNA in situ hybridization and immunohistology, we showed that the process is accompanied by widespread viral infection, not only in infiltrating leukocytes but also in vascular endothelial cells, medial smooth muscle cells, and adventitial fibroblasts. Our results suggest that OvHV-2-infected T cells, monocytes, and locally proliferating macrophages contribute to the vasculitis in MCF. The initial trigger or insult that leads to leukocyte recruitment and activation is not yet known, but there is evidence that latently infected, activated endothelial cells play a role in this. Activated macrophages might then release the necessary pro-inflammatory mediators and, eventually, induce the characteristic vascular changes.

Meningoencephalitis, Vasculitis, and Abortions Caused by Chlamydia pecorum in a Herd of Cattle.

A cow dairy (n = 2000) in close proximity to a sheep flock had third-trimester abortions and fatalities in cows and calves over a 14-month period. Eighteen of 33 aborted fetuses (55%) had multifocal random suppurative or mononuclear meningoencephalitis with vasculitis. Seventeen of these affected fetuses had intracytoplasmic bacteria in endothelial cells, and 1 fetus with pericarditis had similar bacteria within mesothelial cells or macrophages. Immunohistochemistry for Chlamydia spp. or polymerase chain reaction (PCR) for Chlamydia pecorum or both, performed on brain or pooled tissue, were positive in all 14 tested fetuses that had meningoencephalitis and in 4/4 calves and in 3/4 tested cows that had meningoencephalitis and thrombotic vasculitis. In 1 calf and 11/11 fetuses, C. pecorum PCR amplicon sequences were 100% homologous to published C. pecorum sequences. Enzootic chlamydiosis due to C. pecorum was the identified cause of the late term abortions and the vasculitis and meningoencephalitis in fetuses, calves, and cows. C. pecorum, an uncommon bovine abortogenic agent, is a differential diagnosis in late-term aborted fetuses with meningoencephalitis, vasculitis, and polyserositis.

Immersion Foot Syndrome in 6 Equids Exposed to Hurricane Floodwaters.

Prolonged exposure to water, known as immersion foot syndrome in humans, is a phenomenon first described in soldiers during World War I and characterized by dermal ischemic necrosis. In this report, we describe the pathologic findings of a condition resembling immersion foot syndrome in 5 horses and 1 donkey with prolonged floodwater exposure during Hurricane Harvey. At necropsy, all animals had dermal defects ventral to a sharply demarcated "water line" along the lateral trunk. In 5 animals, histologic examination revealed moderate to severe perivascular dermatitis with vasculitis and coagulative necrosis consistent with ischemia. The severity of the lesions progressed from ventral trunk to distal limbs and became more pronounced in the chronic cases. The pathophysiology of immersion foot syndrome is multifactorial and results from changes in the dermal microvasculature leading to thrombosis and ischemia. Prompt recognition of this disease may lead to appropriate patient management and decreased morbidity.

Lumpy Skin Disease Is Characterized by Severe Multifocal Dermatitis With Necrotizing Fibrinoid Vasculitis Following Experimental Infection.

Lumpy skin disease is a high-consequence disease in cattle caused by infection with the poxvirus lumpy skin disease virus (LSDV). The virus is endemic in most countries in Africa and an emerging threat to cattle populations in Europe and Asia. As LSDV spreads into new regions, it is important that signs of disease are recognized promptly by animal caregivers. This study describes the gross, microscopic, and ultrastructural changes that occur over time in cattle experimentally challenged with LSDV. Four calves were inoculated with wildtype LSDV and monitored for 19 to 21 days. At 7 days after inoculation, 2 of the 4 cattle developed multifocal cutaneous nodules characteristic of LSD. Some lesions displayed a targetoid appearance. Histologically, intercellular and intracellular edema was present in the epidermis of some nodules. Occasional intracytoplasmic inclusion bodies were identified in keratinocytes. More severe and consistent changes were present in the dermis, with marked histiocytic inflammation and necrotizing fibrinoid vasculitis of dermal vessels, particularly the deep dermal plexus. Chronic lesions consisted of full-thickness necrosis of the dermis and epidermis. Lesions in other body organs were not a major feature of LSD in this study, highlighting the strong cutaneous tropism of this virus. Immunohistochemistry and electron microscopy identified LSDV-infected histiocytes and fibroblasts in the skin nodules of affected cattle. This study highlights the noteworthy lesions of LSDV and how they develop over time.

Equine pastern vasculitis in a horse associated with a multidrug-resistant Pseudomonas aeruginosa isolate.

BACKGROUND: Equine pastern vasculitis is an uncommon disorder in horses. Underlying causes are difficult to assess, especially bacterial infections. CLINICAL SUMMARY: A 13-year-old French saddle gelding horse presented for evaluation of a six weeks history of pastern dermatitis. Histopathological examination of skin biopsy samples revealed small vessel vasculitis. A pure growth of a multidrug-resistant Pseudomonas aeruginosa (MRPA) was obtained from a deep skin biopsy. Clinical remission was observed after a six week course of enrofloxacin and lesions did not recur. CONCLUSIONS AND CLINICAL IMPORTANCE: To the best of the authors' knowledge, this is the first report of a pastern vasculitis associated with MRPA and successfully treated with a six week course of enrofloxacin.

Histologic Changes Associated With Placental Separation in Gilts Infected with Porcine Reproductive and Respiratory Syndrome Virus.

The placenta is a vital organ providing the developing fetus with nutrient and gas exchange, thermoregulation, and waste elimination necessary for fetal development, as well as producing hormones to maintain pregnancy. It is hypothesized that fetal pig death in porcine reproductive and respiratory syndrome may be attributed to pathology of the maternal-fetal interface leading to premature placental separation. This study was designed to evaluate the chronologic progression of porcine reproductive and respiratory syndrome virus (PRRSV)-induced lesions at the maternal-fetal interface, with particular focus on placental separation in experimentally challenged third-trimester gilts. Fifteen gilts were inoculated with a virulent strain of PRRSV-2 on gestation day 86 ± 0.4. On multiple days postinoculation, 3 gilts along with 1 sham-inoculated control per time point were euthanized, and uterine and fetal placental tissues corresponding to each fetus were collected for histopathologic evaluation. The presence of any fetal lesion was 23 times more likely in compromised (meconium-stained and decomposed) compared with viable fetuses ( P < .001). In PRRSV-infected gilts, endometritis was more severe than placentitis, and the severity of endometrial inflammation and vasculitis increased progressively from 2 to 14 days postinoculation. Neither placental vasculitis nor a chronologic progression in the severity of placental detachment was observed. Severe placental detachment was more frequently present in PRRSV-infected compared with noninfected samples and was most significantly associated with placental inflammation, compared with other uterine lesions, viral load, or termination day. The results of this study suggest that placental separation by itself is not sufficient to significantly compromise fetal viability in reproductive porcine reproductive and respiratory syndrome.

Bartonella henselae in a dog with ear tip vasculitis.

BACKGROUND: Bartonella henselae, a Gram-negative, zoonotic, alpha-proteobacteria has been previously implicated in association with cutaneous vasoproliferative lesions (bacillary angiomatosis), nodular panniculitis and multifocal erythema (erythema multiforme) in dogs. OBJECTIVE: Describe clinical, microbiological and histological lesions in a dog with ear margin vasculitis and B. henselae infection. ANIMALS: A 12-month-old, specific pathogen-free intact female beagle dog maintained in a vector-free laboratory animal resource facility. METHODS AND MATERIALS: Bartonella and Rickettsia serological evaluation, Bartonella and Rickettsia PCR, Bartonella alpha-proteobacteria growth medium (BAPGM) enrichment blood culture/PCR, histopathological investigation and confocal immunohistochemical evaluation. RESULTS: Serological investigation (seroreversion) and PCR testing of aural tissue biopsies failed to support Rickettsia rickettsii as a cause of the aural vasculitis; however, B. henselae, genotype San Antonio 2 DNA was amplified and sequenced from both ear tip margins and from normal-appearing abdominal skin. Seroconversion to B. henselae was documented retrospectively by IFA testing. Bartonella henselae organisms were visualized by confocal immunostaining within all three biopsies. Histopathology revealed small vessel necrotizing vasculitis and dermal necrosis. Bartonella henselae seroreversion and complete resolution of skin lesions occurred in conjunction with administration of oral doxycycline and enrofloxacin for six weeks. CONCLUSIONS AND CLINICAL IMPORTANCE: Bartonella henselae is an emerging zoonotic pathogen that has been associated with leucocytoclastic vasculitis in humans and may have had a contributing or causative role in the development of the cutaneous aural margin vasculitis in this beagle.

Wooden Breast Myodegeneration of Pectoralis Major Muscle Over the Growth Period in Broilers.

Wooden breast (WB) myopathy of broiler chickens is a myodegenerative disease of an unknown etiology and is macroscopically characterized by a hardened consistency of the pectoralis major muscle. Our aim was to describe the development and morphology of WB over the growth period in broilers. Additionally, the effect of restricted dietary selenium on the occurrence of WB was examined by allocating the birds in 2 dietary groups: restricted and conventional level of selenium. The experiment included 240 male broilers that were euthanized at ages of 10, 18, 24, 35, 38, or 42 days and evaluated for WB based on abnormal hardness of the pectoralis major muscle. The severity and the distribution of the lesion and presence of white striping were recorded. The first WB cases were seen at 18 days; 13/47 birds (28%) were affected and the majority exhibited a mild focal lesion. In subsequent age groups the WB prevalence varied between 48% and 73% and the lesion was usually diffuse and markedly firm. White striping often coexisted with WB. Histological evaluation performed on 111 cases revealed a significant association of myodegeneration and lymphocytic vasculitis with WB. Vasculitis and perivascular cell infiltration were restricted to the veins. Restricted dietary selenium did not affect the occurrence of WB ( P = .44). Our results indicate that WB starts focally and spreads to form a diffuse and more severe lesion.

EAR AND TAIL LESIONS ON CAPTIVE WHITE-TAILED DEER FAWNS (ODOCOILEUS VIRGINIANUS): A CASE STUDY.

During the 2008-2011 time period, undiagnosed lesions were observed in 21 of 150 white-tailed deer fawns (Odocoileus virginianus) that were part of a captive deer herd at Mississippi State University. Clinical findings in healthy and diseased fawns from 0 to 90 days of age included bite and scratch marks followed by moderate to severe ear and tail necrosis. Gross necropsy findings of necrotizing ulcerative dermatitis correlated with histopathologic findings that included focally severe multifocal vasculitis, vascular necrosis, and thrombosis. This article is a clinical description of these previously unreported lesions associated with tissue necrosis in young captive white-tailed deer.

Anthrax vaccine associated deaths in miniature horses.

During a widespread anthrax outbreak in Canada, miniature horses were vaccinated using a live spore anthrax vaccine. Several of these horses died from an apparent immune-mediated vasculitis temporally associated with this vaccination. During the course of the outbreak, other miniature horses from different regions with a similar vaccination history, clinical signs, and necropsy findings were found.

Vaccin contre l'anthrax associé à la mort de chevaux miniatures. Durant une vaste éclosion d'anthrax au Canada, des chevaux miniatures ont été vaccinés en utilisant un vaccin à base de spores viables d'anthrax. Plusieurs chevaux sont morts d'une vasculite d'origine immunologique associée temporellement avec cette vaccination. Pendant l'éclosion, on a trouvé d'autres chevaux miniatures de régions différentes présentant une anamnèse de vaccination, de signes cliniques et de résultats d'autopsie semblables.(Traduit par Isabelle Vallières).

Cardiac lesions in 30 dogs naturally infected with Leishmania infantum chagasi.

The hearts of 30 dogs naturally infected with Leishmania infantum chagasi were evaluated histologically and immunohistochemically. Myocardial lesions were detected in all dogs, including lymphoplasmacytic myocarditis (27/30), myonecrosis (24/30), increased interstitial collagen (22/30), lepromatous-type granulomatous myocarditis (7/30), fibrinoid vascular change (3/30), and vasculitis (1/30). The parasite was detected in the hearts of 20 of 30 dogs. The number of parasitized cells correlated with the intensity of the inflammation and with the number of granulomas. The results indicate that cardiac lesions are prevalent in dogs with naturally occurring leishmaniasis even in the absence of clinical signs of cardiac disease.

Atherosclerosis associated with vasculopathic lesions in a golden retriever with hypercholesterolemia.

A 2-year-old neutered male golden retriever dog presented for lameness secondary to ulcerations of multiple digital paw pads was diagnosed with vasculitis and hypercholesterolemia. Despite treatment, ischemic necrosis progressed to include all distal extremities and the dog eventually expired due to myocardial infarction secondary to severe atherosclerosis. The rapid demise and the dermatologic lesions may have been secondary to cholesterol embolism syndrome which has never before been reported in a dog.

Athérosclérose associée à des lésions vasculopathiques chez un Golden retriever atteint d'hypercholestérolémie. Un chien Golden retriever mâle intact âgé de 2 ans a été présenté pour une boiterie secondaire à des ulcérations de plusieurs coussinets des pattes et un diagnostic de vasculite et d'hypercholestérolémie a été posé. Malgré le traitement, la nécrose ischémique a progressé pour inclure toutes les extrémités distales et le chien est finalement mort en raison d'un infarcissement du myocarde secondaire à une athérosclérose grave. Le décès rapide et les lésions dermatologiques peuvent avoir été secondaires au syndrome de l'embolisme du cholestérol, qui n'a pas encore été signalé chez un chien.(Traduit par Isabelle Vallières).

Shar-Pei autoinflammatory disease with skin necrosis due to neutrophilic vasculitis: a case report.

A 4-month-old female Shar-pei dog was admitted with apathy, anorexia, and vomiting. The patient had an appropriate vaccination protocol, with the last vaccine administered 2.5 weeks prior to the onset of clinical signs. Physical examination revealed tachycardia, fever and swelling of the tibiotarsal joints. Several diagnostic tests including complete blood cell count, biochemistry profile, urinalysis, thoracic radiographs, hind limbs radiographs, abdominal ultrasound, and infectious diseases tests, were conducted to determine the underlying cause. Shar-Pei Auto-inflammatory Disease (SPAID) was diagnosed. Additionally, the patient developed skin necrosis in the inner aspect of the tibiotarsal joints as a complication. A skin biopsy revealed cutaneous vasculopathy causing degeneration, abrupt ulceration, and ischemic necrosis with intense neutrophilic inflammation of the dermis and subcutis. Moreover, a hospital-acquired infection was identified by skin culture. Debridement of the necrotic skin was performed, and due to its' severity and extent, the wound was closed by secondary intention. A diagnostic protocol and the therapeutic dose of acetylsalicylic acid, which led to clinical improvement, are recommended here. The patient has continued to present episodic manifestations of SPAID mainly fever and swelling of the tibiotarsal joints, but there has been no recurrence of necrosis or other cutaneous lesion in the last two years.

Circovirus in tissues of dogs with vasculitis and hemorrhage.

We characterized the complete genome of a novel dog circovirus (DogCV) from the liver of a dog with severe hemorrhagic gastroenteritis, vasculitis, and granulomatous lymphadenitis. DogCV was detected by PCR in fecal samples from 19/168 (11.3%) dogs with diarrhea and 14/204 (6.9%) healthy dogs and in blood from 19/409 (3.3%) of dogs with thrombocytopenia and neutropenia, fever of unknown origin, or past tick bite. Co-infection with other canine pathogens was detected for 13/19 (68%) DogCV-positive dogs with diarrhea. DogCV capsid proteins from different dogs varied by up to 8%. In situ hybridization and transmission electron microscopy detected DogCV in the lymph nodes and spleens of 4 dogs with vascular compromise and histiocytic inflammation. The detection of a circovirus in tissues of dogs expands the known tropism of these viruses to a second mammalian host. Our results indicate that circovirus, alone or in co-infection with other pathogens, might contribute to illness and death in dogs.

Presumed reactive polyarthritis and granulomatous vasculitis in a Mississippi sandhill crane (Grus canadensis pulla).

A 1.5-year-old female Mississippi sandhill crane (Grus canadensis pulla) was presented and managed for a polyarthritis of the intertarsal and tarsophalangeal articulations. Results of aerobic bacterial cultures, Mycoplasma species culture, and polymerase chain reaction testing of articular fluid did not identify any causative organisms. Results of radiographs and cytologic examination of articular fluid were consistent with an inflammatory, nonerosive polyarthritis. The arthritis did not improve with systemic anti-inflammatory and antibiotic treatment and with joint lavage. A large necrotic granulomatous mass was detected on the right shoulder area from which Staphylococcus aureus and Enterococcus species were isolated as opportunistic pathogens. Two days after surgical resection of the mass, the distal polyarthritis resolved. Histopathologic examination of the mass was consistent with granulomatous vasculitis with abscess formation of unknown origin. In this crane, the unresponsiveness to standard therapy, the presence of an infected and inflammatory mass, and the resolution of the polyarthritis after the resection of the mass strongly supported a diagnosis of reactive immune-mediated nonerosive polyarthritis. Analysis of this case suggests that immune-mediated idiopathic arthritis should be a differential diagnosis of distal polyarthritis in cranes and that an inciting source remote from the joints should be investigated in case of lack of response to standard therapy.

Retrospective evaluation of the etiology and clinical characteristics of peripheral edema in dogs.

BACKGROUND: The prevalence and clinical characteristics of different etiologies of peripheral edema in dogs are unknown. HYPOTHESIS/OBJECTIVES: To determine the prevalence of different etiologies of peripheral edema, describe clinical characteristics that vary among etiologies, and report survival times. ANIMALS: Five hundred twenty-seven dogs with peripheral edema. METHODS: Retrospective medical record review. Differences in clinical variables among etiology groups were assessed by Kruskal-Wallis testing with post hoc pairwise Dunn's testing and Chi-square testing with Monte Carlo simulation. RESULTS: The most common etiologies of peripheral edema in dogs were vasculitis (n = 193, 37%), lymphatic/venous obstruction (LVO; 114, 22%), and hypoalbuminemia (94, 18%). Right-sided congestive heart failure (R-CHF) was uncommon (25, 5%). Edema was localized in 377 (72%) dogs and generalized in 142 (27%) dogs, and hypoalbuminemia was more likely to cause generalized edema compared to LVO or vasculitis (P < .0001). Concurrent abdominal effusion (155, 29%) was more common than pleural (77, 15%) or pericardial (12, 2%) effusion. Abdominal and pleural effusion occurred more commonly in dogs with hypoalbuminemia or R-CHF compared to LVO or vasculitis (P < .0001). CONCLUSIONS AND CLINICAL IMPORTANCE: Distribution of edema, concurrent cavitary effusions, and clinicopathological data can help predict the underlying etiology of peripheral edema in dogs.