Lymphohistiocytic Meningoencephalitis Research Articles

Myxobolus lentisuturalis infection in a farmed population of goldfish Carassius auratus from the USA.

Myxobolus lentisuturalis is a myxozoan parasite of piscine muscle that has been described in goldfish Carassius auratus and Prussian carp Carassius gibelio. This report documents a naturally occurring infection of M. lentisuturalis in a population of farmed goldfish in the USA. Postmortem examination was performed on 4 affected goldfish. Gross findings included large cystic cavities along the dorsal midline filled with caseous exudate. Histopathology revealed myxozoan plasmodia and spores in the epaxial muscles with varying degrees of granulomatous and necrotizing myositis accompanied by lymphohistiocytic meningoencephalitis. Spore morphology and dimensions were consistent with M. lentisuturalis, as observed by light microscopy. PCR and sequence analysis of the small subunit ribosomal DNA of infected muscle samples from 2 goldfish confirmed the parasite to have 99-100% nucleotide identity to M. lentisuturalis sequences recovered from similar cases of this parasite infecting goldfish in China and Italy and Prussian carp in China. This is the first reported case of M. lentisuturalis in the USA and furthers the understanding of the pathogenicity of this under-described parasite.

Genuine lethal infection of a wood pigeon (Columba palumbus) with high pathogenicity avian influenza H5N1, clade 2.3.4.4b, in Germany, 2022

Despite the increasing frequency of avian influenza (AI) cases in wild birds in Europe during the last decade, doves and pigeons were not recognized to be part of the AI epidemiology. Here we describe a natural, lethal HPAIV infection of subtype H5N1, clade 2.3.4.4b, in a wood pigeon (Columba palumbus) in Germany, 2022. The animal was housed in a bird sanctuary that suffered an HPAI-outbreak with multiple bird species affected. The pigeon’s post mortem findings were dominated by an acute lymphohistiocytic meningoencephalitis as well as neuronal necrosis in the grey matter of the cerebral hemispheres and in the brain stem. Influenza A viral antigen was associated to these alterations with a striking ependymal and periventricular distribution most probably indicating intraventicular liquorogenic spread of the virus. In addition, typical severe multifocal to coalescing necrotizing pancreatitis was evident. Occasionally, vascular endothelial cells showed an intense viral antigen staining. Examination of oropharyngeal and cloacal swabs and of various tissues by real-time RT-PCR corroborated systemic infection with highly pathogenic (HP) AIV of subtype H5N1. Viral loads soared in brain and pancreas samples. Full genome sequencing directly from brain tissue confirmed the assignment of the virus to clade 2.3.4.4b of the goose/Guangdong lineage bearing a polybasic hemagglutinin cleavage site. Our results demonstrate the principal susceptibility of wood pigeons to HPAIV H5N1 resulting in a sporadic infection. Considering the wide distribution and roaming of wild, feral, and racing pigeons with often close contact to humans, thorough investigation of suspected cases including pathological manifestation is advisable.

Pathogenesis of Equid Alphaherpesvirus 1 Infection in the Central Nervous System of Mice.

Equid alphaherpesvirus 1 (EHV-1) causes myeloencephalopathy in horses and occasionally in non-equid species. Although mouse models have been developed to understand EHV-1 pathogenesis, few EHV-1 strains have been identified as highly neurovirulent to mice. The aim of this study was to evaluate the pathogenesis of 2 neurovirulent EHV-1 strains in mice, and to characterize the inflammatory cells and expression of chemokines and the apoptosis marker caspase-3 in the brain of infected mice. C57BL/6J mice were inoculated intranasally with EHV-1 strains A4/72 or A9/92 and evaluated on 1, 2, and 3 days post inoculation (DPI). EHV-1-infected mice showed severe neurological signs at 3 DPI. Ultrastructural analysis revealed numerous viral nucleocapsids and fewer enveloped virions within degenerated and necrotic neurons and in the surrounding neuropil. Histologically, at 3 DPI, there was severe diffuse neuronal degeneration and liquefactive necrosis, prominent microgliosis, and perivascular cuffing composed of CD3+ cells (T cells) and Iba-1+ cells (macrophages), mainly in the olfactory bulb and ventral portions of the brain. In these areas, moderate numbers of neuroglial cells expressed CCL5 and CCL2 chemokines. Numerous neurons, including those in less affected areas, were immunolabeled for cleaved caspase-3. In conclusion, neurovirulent EHV-1 strains induced a fulminant necrotizing lymphohistiocytic meningoencephalitis in mice, with microgliosis and expression of chemokines and caspase-3. This model will be useful for understanding the mechanisms underlying the extensive neuropathology induced by these viral infections.

Parasitological and clinical-pathological findings in twelve outbreaks of acute trypanosomiasis in dairy cattle in Rio de Janeiro state, Brazil

In Brazil, infection in cattle was first reported in the state of Pará, in 1944, and the presence of the parasite has already been recorded in several states. The purpose of this study was to report the clinical-pathological aspects of a natural infection by T. vivax in dairy cattle in the state of Rio de Janeiro. Twelve outbreaks of the infection were diagnosed in 11 municipalities from April 2016 to October 2018. All properties had acquired cattle from states where the disease had already been recorded and it was found that needles for oxytocin administration had been shared. These outbreaks were studied by visiting the properties to perform anamnesis, clinical exams and collection of material for laboratory diagnosis. Laboratory diagnosis was performed through parasitological, molecular and histopathological techniques. Animals with confirmed diagnosis for T. vivax showed anemia, lack of appetite, decreased milk production, weight loss, weakness, abortion, diarrhea and neurological signs. The main histological lesions found were meningoencephalitis and lymphohistiocytic myocarditis. In the central nervous system, the lesions were more severe in the brain compared to the spinal cord, being progressively more severe in the rostro-dorsal direction. Also, they were more accentuated in the white matter compared to the gray matter. Due to nonspecific clinical signs, laboratory tests were key for diagnosis. Trypanosomiasis in cattle herds in the state of Rio de Janeiro, Brazil, is of great concern because of its potential to cause economic losses.

An improved animal model for herpesvirus encephalitis in humans.

Herpesviral encephalitis caused by Herpes Simplex Virus 1 (HSV-1) is one of the most devastating diseases in humans. Patients present with fever, mental status changes or seizures and when untreated, sequelae can be fatal. Herpes Simplex Encephalitis (HSE) is characterized by mainly unilateral necrotizing inflammation effacing the frontal and mesiotemporal lobes with rare involvement of the brainstem. HSV-1 is hypothesized to invade the CNS via the trigeminal or olfactory nerve, but viral tropism and the exact route of infection remain unclear. Several mouse models for HSE have been developed, but they mimic natural infection only inadequately. The porcine alphaherpesvirus Pseudorabies virus (PrV) is closely related to HSV-1 and Varicella Zoster Virus (VZV). While pigs can control productive infection, it is lethal in other susceptible animals associated with severe pruritus leading to automutilation. Here, we describe the first mutant PrV establishing productive infection in mice that the animals are able to control. After intranasal inoculation with a PrV mutant lacking tegument protein pUL21 and pUS3 kinase activity (PrV-ΔUL21/US3Δkin), nearly all mice survived despite extensive infection of the central nervous system. Neuroinvasion mainly occurred along the trigeminal pathway. Whereas trigeminal first and second order neurons and autonomic ganglia were positive early after intranasal infection, PrV-specific antigen was mainly detectable in the frontal, mesiotemporal and parietal lobes at later times, accompanied by a long lasting lymphohistiocytic meningoencephalitis. Despite this extensive infection, mice showed only mild to moderate clinical signs, developed alopecic skin lesions, or remained asymptomatic. Interestingly, most mice exhibited abnormalities in behavior and activity levels including slow movements, akinesia and stargazing. In summary, clinical signs, distribution of viral antigen and inflammatory pattern show striking analogies to human encephalitis caused by HSV-1 or VZV not observed in other animal models of disease.

Comparative histopathological characteristics of highly pathogenic avian influenza (HPAI) in chickens and domestic ducks in 2008 Korea.

We compared characteristic lesions occurring in chickens and domestic ducks naturally infected with H5N1 HPAI virus in April and May 2008. Infected chickens generally exhibited pale-green, watery diarrhoea, depression, neurological signs and cyanosis of wattles and combs, and infected ducks generally exhibited neurological signs and watery diarrhoea. Gross petechial or ecchymotic haemorrhage affected the heart, proventriculus, liver, muscle, fat, and pancreas in chickens, and muscle in ducks. Necrotic foci were primarily present in the pancreas of both species and in the heart of domestic ducks. Histopathologically, chickens exhibited multifocal encephalomalacia, multifocal lymphohistiocytic myocarditis, multifocal necrotic pancreatitis and haemorrhage of several organs and tissues; ducks exhibited lymphohistiocytic meningoencephalitis with multifocal haemorrhages, multifocal necrotic pancreatitis, and severe necrotic myocarditis with mineralisation. The characteristic histopathologic findings of 2008 HPAI were multifocal encephalomalacia and necrotic pancreatitis accompanied by lymphohistiocytic myocarditis, and haemorrhage in various organs and tissues in chickens, whereas in ducks, they were severe necrotic myocarditis with mineralisation and necrotic pancreatitis, accompanied with lymphohistiocytic meningoencephalitis. The high mortality of domestic ducks may be intimately associated with heart failure resulting from increased H5N1 HPAI viral cardiotropism.

Canine Distemper Virus Infection in Fennec Fox (Vulpes zerda)

Fifteen 8-month-old fennec foxes imported from Sudan showed fever, mucopurulent ocular discharge, diarrhea, severe emaciation, seizures, and generalized ataxia, and died. Three of the 15 animals were presented for diagnostic investigation. Severe dehydration, brain congestion, and gastric ulcers were observed in all animals. In one animal, the lungs had failed to collapse and were multifocally dark red in appearance. Histopathologically, there were lymphohistiocytic meningoencephalitis with malacia, mild interstitial pneumonia, lymphoid depletion of lymphoid tissues and organs, and intestinal villous atrophy with intralesional coccidia. There were many intracytoplasmic and/or intranuclear inclusion bodies in the epithelial cells of the medullary velum, lungs, liver, kidneys, trachea, pancreas, stomach, gall bladder, urinary bladder, and ureters, and in macrophages of malacia foci and lymphocytes and macrophages of lymphoid organs. Additionally, intestinal coccidia were confirmed to be Isospora species by a fecal test. To our knowledge, this is the first report of canine distemper with intestinal coccidiosis in fennec fox.

Neurotropism of Highly Pathogenic Avian Influenza Virus A/Chicken/Indonesia/2003 (H5N1) in Experimentally Infected Pigeons (Columbia livia f. domestica)

This investigation assessed the susceptibility of experimentally infected pigeons to the highly pathogenic avian influenza virus (HPAIV) H5N1 that caused recent outbreaks of avian influenza in birds and humans in several countries of Asia. For this purpose 14 pigeons were infected ocularly and nasally with 10(8) EID50 and clinical signs were recorded and compared with five chickens infected simultaneously as positive controls. The chickens demonstrated anorexia, depression, and 100% mortality within 2 days postinoculation. Three of the pigeons died after a history of depression and severe neurological signs consisting of paresis to paralysis, mild enteric hemorrhage, resulting in a mortality of 21%. Gross lesions in these pigeons were mild and inconsistent. Occasionally subcutaneous hyperemia and hemorrhage and cerebral malacia were observed. Microscopic lesions and detection of viral antigen were confined to the central nervous system of these pigeons. In the cerebrum and to a minor extent in the brain stem a lymphohistiocytic meningoencephalitis with disseminated neuronal and glial cell necrosis, perivascular cuffing, glial nodules, and in one bird focally extensive liquefactive necrosis could be observed. The remaining nine pigeons showed neither clinical signs nor gross or histological lesions associated with avian influenza, although seroconversion against H5 indicated that they had been infected. These results confirm that pigeons are susceptible to HPAIV A/chicken/Indonesia/2003 (H5N1) and that the disease is associated with the neurotropism of this virus. Although sentinel chickens and most pigeons did not develop disease, further experiments have to elucidate whether or not Columbiformes are involved in transmission and spread of highly pathogenic avian influenza.