Study of Akabane disease in an Iranian dairy herd: a re-emerging disease.

Akabane virus is a teratogenic pathogen transmitted by Culicoides spp. to ruminants. The virus induces anomalies in the central nervous system in the developing fetus, resulting in arthrogryposis-hydranencephaly (A-H) syndrome. During three outbreaks of the disease (2002, 2013, and 2020), 77 calves were born in Varamin, Iran, with A-H syndrome. The presenting neurologic signs were categorized into three main groups, as common, less common, and uncommon signs. The common signs were unawareness of the surroundings, blindness, deep depression, partial failure of suckling, and unintelligent behavior. The less commonly noted signs were hyperexcitability, regurgitation, head pressing, compulsive walking, and kicking, while the uncommon signs comprised protrusion of the tongue, making sounds resembling barking, carnivore-like milk drinking, and deafness. Arthrogryposis, dome-shaped skull, kyphosis, torticollis, lordosis, scoliosis, and spina bifida were the diagnosed skeletal defects. Upon necropsy, hydranencephaly, hydrocephaly, and microencephaly were seen in the calves presenting neurologic signs, while astrocytosis, astrogliosis, focal gliosis, perivascular, perineuronal, and submeningeal edema, perivascular cuffing, non-suppurative meningitis, non-suppurative encephalitis and lymphoplasmacytic infiltration, and perivascular and parenchymal hemorrhage were seen in samples obtained from the brains. RT-PCR detected Akabane virus in the brain tissues of the affected calves. This is the first clinical study of Akabane disease in calves in Iran.

Ultrasonographic approach and findings in calves with hydranencephaly.

BACKGROUND: Teratogenic viral infections may proceed to hydranencephaly in cattle. Post-mortem and antemortem diagnosis can be achieved by necropsy or ultrasonography, CT-scan and MRI techniques. OBJECTIVES: The aim of this study was to determine how effective ultrasonography approach is in detecting hydranencephaly in calves. METHODS: In this study, ultrasonography images were obtained from brains of nine Holstein claves, of the same age, with neurological signs (due to Akabane virus infection), approaching from the caudal part of the temporal bone. To confirm the obtained images, the same approach was used to obtain images from a normal calf of the same age. The thickness of the temporal bone was measured and compared in seven affected and the healthy calves, using CT-scan images. RESULTS: In ultrasonographic images, temporal bone (as a hyperechoic structure) and temporal cortical mantle (as an echogenic structure) were noted in the right and left side of the skull. The medial part of the image showed presence of fluid in an anechoic region, instead of brain parenchyma. Falx cerebri was also seen as a floating hyperechoic line in the middle part in all patients. There was no statistically significant difference between the thickness of temporal bone in normal and affected calves (p = 0.502). All findings were confirmed by necropsy. CONCLUSIONS: Transtemporal approach is a novel and easy approach to study the brain in calves. This is the first study on the hydranencephalic brains of claves, using ultrasonography by transtemporal approach.

First genomic detection of Peaton virus in a calf with hydranencephaly in Israel.

Simbu serogroup are arbo- viruses which are mainly transmitted by Culicoides. Two members of the Simbu serogroup, Akabane and Shuni viruses, have been isolated from congenitally malformed ruminants in Israel. A recent serosurvey revealed that Israeli ruminants have been exposed to several additional Simbu viruses, including Shamonda and Sathuperi that seems to be circulating in Israel. In April 2017, an apparently healthy one-month-old male calf was transferred to the Kimron Veterinary Institute. A few days later, the calf was reported to be slow to respond to its surroundings and was not able to feed on its own. Blindness was observed upon clinical examination. RNA of the small, medium and large segments of Simbu serogroup viruses were amplified and sequenced from the testis tissues and from the Cerebrospinal fluid (CSF). During post-mortem examination, hydranencephaly was defined. Phylogenetic analysis of all three segments of Simbu serogroup viruses showed that the sequences detected in the Israeli calf were virtually identical to Peaton virus (PEAV). PEAV was also detected in two pools of Culicoides imicola trapped at two different locations in Israel. This is the first genomic detection of PEAV outside Australia and Japan. These results are of epidemiological significance, as they demonstrate that PEAV is circulating in Israel and affects cattle. Consequently, these results are also of relevance to a potential spread of Simbu serogroup viruses into Europe.

Evidence of extensive renewed Schmallenberg virus circulation in Belgium during summer of 2016 - increase in arthrogryposis-hydranencephaly cases expected.

A seroprevalence study carried out between June and September 2016 in the Belgian sheep population showed a significant increase in overall (from 25% to 62%) and between-herd (from 60% to 96%) seroprevalence against Schmallenberg virus (SBV) during this period, indicating the most extensive recirculation of SBV since its original emergence in 2011. SBV recirculation was confirmed by the detection of SBV RNA-positive Culicoides obsoletus complex midges collected in the region of Antwerp in August 2016, reaching a minimum infection rate of 3%. The recirculation of SBV in the largely unprotected ruminant population during summer 2016 will likely cause an increase in the number of arthrogryposis-hydranencephaly cases in newborn ruminants during the coming months.

Doenças hereditárias e defeitos congênitos diagnosticados em búfalos (Bubalus bubalis) no Brasil / Hereditary diseases and congenital defects diagnosed in water buffalo (Bubalus bubalis) in Brazil

A review on hereditary diseases and/or congenital defects diagnosed in water buffaloes in Brazil is performed. The epidemiological, clinical and pathological aspects of each disease or group of diseases are briefly described. Hereditary diseases include acantholytic mechanobullous dermatosis, arthrogryposis, myotonia, hydranencephaly, chondrodysplasia, and albinism. Congenital defects of unknown cause include megaesophagus, heart defects (patent ductus arteriosus), dermatosparaxia, and different defects of the reproductive system. The breeds most affected by genetic diseases are those from Asian Continent (Murrah and Jafarabadi), probably as a result of inbreeding in Brazilian herds due the prohibition of importation of breeding buffalo from that continent. The diagnosis of two hereditary diseases, arthrogryposis and myotonia, in Rio Grande do Sul (southern Brazil) and Pará (nothern Brazil) suggests that the undesirable genes are widespread in the buffalo population. The identification of these genes by molecular techniques associated with the buffalo breeding with correct sanitary, zootechnical, and reproductive control practices can decrease the negative effects of genetic diseases in the Brazilian buffalo herd.

É realizada uma revisão sobre as doenças hereditárias e/ou defeitos congênitos diagnosticados em búfalos no Brasil. São descritos brevemente os aspectos epidemiológicos, clínicos e patológicos de enfermidades hereditárias ou provavelmente hereditárias já observadas no Brasil, como dermatose mecanobolhosa, artrogripose, miotomia, hidranencefalia, condrodisplasia e albinismo; e dos defeitos congênitos que não tem uma causa ainda comprovada como megaesôfago, defeitos cardíacos (persistência do ducto arterioso), dermatosparaxia, defeitos no sistema reprodutivo e outros defeitos. Observou-se que as raças mais afetadas por enfermidades de natureza genética são as que têm origem no Continente Asiático (Murrah e Jafarabadi), provavelmente em consequência da consanguinidade existente nos rebanhos devido a proibição da importação de reprodutores, sêmen e embriões daquele continente. O diagnóstico de duas dessas doenças, artrogripose e miotomia hereditária no Rio Grande do Sul e no Pará, demonstra que os genes indesejáveis estão disseminados na população de búfalos no país e que a identificação desses genes por meio de técnicas moleculares associada à criação desta espécie com maior controle sanitário, reprodutivo e zootécnico pode minimizar os prejuízos decorrentes dessas enfermidades à bubalinocultura.

Porencephaly and hydranencephaly in six dogs.

A retrospective study was performed to identify dogs with cerebrospinal fluid-filled cavitatory lesions on MRI. Six dogs were included and the lesions were classified. In the three dogs in the present study with hydranencephaly, unilateral but complete loss of the temporal and parietal lobes was noted and had almost complete loss of the occipital and frontal lobes of a cerebral hemisphere. In the three dogs with porencephaly, there was unilateral incomplete loss of the parietal lobe and one dog had additional partial loss of the temporal and frontal lobes. Two of the dogs with porencephaly had seizures; the third showed no associated clinical signs. The dogs with hydranencephaly had mentation changes and circled compulsively. The two porencephalic dogs with seizures were treated with phenobarbitone. One of the dogs with hydranencephaly showed increased frequency and duration of circling; one dog's clinical signs did not progress and the third dog was euthanased due to increasing aggression. The dog with increased circling had ventriculoperitoneal shunt placement and the circling frequency reduced.

Congenital hydranencephaly and cerebellar hypoplasia in water buffalo in southern Brazil.

Seven cases of hydranencephaly and cerebellar hypoplasia in a water buffalo herd are described. The herd of 133 females was divided for mating into 4 groups and mated with different bulls. The disease was observed in the offspring of 5 cows from only 1 group over a period of 6 years. These cows had all mated with the same bull during that period. All affected calves were unable to suckle, showed intention tremors, involuntary movements of the ears, depression, and blindness. Some calves were recumbent and others showed wide-based stance and inability to walk. At necropsy, all affected calves had similar lesions consisting of hydranencephaly and cerebellar hypoplasia. Histologically, the cavities were surrounded by normal-looking nervous tissue. The occurrence of the disease in the offspring of only 1 out of 6 bulls in different years, the similar lesions in all 7 calves affected, and the negative serology and immunohistochemistry for Bovine virus diarrhea virus and Bluetongue virus highly suggest that the disease is hereditary.

Epizootic congenital hydranencephaly and abortion in cattle due to bluetongue virus serotype 8 in the Netherlands.

An outbreak of hydranencephaly in aborted foetuses and newborn calves occurred following the 2007 epidemic of bluetongue serotype 8 (BTV8\net2006) in the Netherlands. In total 35 aborted foetuses and 20 live-born calves, submitted from September 2007 to May 2008, were examined pathologically. Foetuses with gestational ages between 4 and 9 months (mean 6.8 month) showed varying stages of cerebral malformation. Initial stages were cavitations in the cerebral hemispheres with massive destruction of neuroparenchyma, calcium deposits, and a phagocytic inflammatory response. Later stages showed distinct hydranencephaly, the cerebral hemispheres being almost completely replaced by fluid-filled sacs. In seven cases the cerebellum was affected as well, but brainstem structures were intact. Newborn calves with clinical signs of abnormal behaviour ('dummy calves'), circling, head pressing, incoordination, and blindness were seen from the end of January 2008. The calves were born between 2nd January and 16th March 2008. The calves were euthanized after 1 day up to 14 weeks (mean 4-7 weeks). Brain malformations in these calves were confined to the cerebrum and consisted of varying degrees of hydranencephaly. Spleen tissue was PCR-positive for bluetongue virus (BTV) in 21 of 35 foetuses and in 1 of 20 calves. A higher percentage of PCR-positives was found in foetuses aborted in early gestation than in late gestation, suggesting clearance of BTV during gestation. Fifteen of 33 dams of PCR-negative hydranencephalic foetuses or calves could be traced and all were BTV-seropositive, indicating a previous BTV infection. The timing of hydranencephaly cases in live-born calves during the first months of 2008 was consistent with infection in early gestation during the prior transmission season. Vertical transmission and teratogenic potential have previously been described for modified-live vaccines for bluetongue but are highly unusual for field strains of BTV, which raises the issue whether BTV8\net2006 or its ancestor has been cell- or laboratory-adapted in the past.

Bluetongue virus serotype 8-associated congenital hydranencephaly in calves.

Hydranencephaly, the almost complete absence of the cerebral parenchyma, induced by infection with modified live bluetongue virus (BTV) crossing the placenta has previously been reported in sheep and rarely in cattle in the USA and in South Africa. The current study describes 29 cases of hydranencephaly in bovine foetuses and 'dummy' calves up to 3 months of age in Belgium associated with natural BTV serotype 8 infection very early in gestation. Histological examination of the remaining cerebral parenchyma showed moderate to severe atrophy of the neural tissue. The lesions observed support the hypothesis of BTV-induced destruction of precursor cells. However, in several calves a slight infiltration of the walls of venules and arterioles with T lymphocytes (vasculitis) was observed as well, which seems to be responsible for at least some of the lesions. Bluetongue viral RNA was detected in 15 animals using a BTV-specific real-time RT-PCR with a much higher success rate in brain tissues compared with blood and spleen samples. Virus isolation in embryonated eggs was unsuccessful. In conclusion, hydranencephaly in calves can be associated with natural wild-type BTV-8 intra-uterine infection.

Arthrogryposis, hydranencephaly and cerebellar hypoplasia syndrome in neonatal calves resulting from intrauterine infection with Aino virus.

To determine the teratogenic potential of Aino virus (AINOV) in cattle, pregnant cows and fetal cattle were infected with a fresh isolate of AINOV. Five pregnant cows were inoculated intravenously with the virus at 122 to 162 days of gestation and allowed to give birth. All of the cows developed neutralizing antibodies to the virus, indicating that the cows had been infected with the virus; however, no clinical abnormalities were seen in their six newborn calves, and no specific antibodies to the virus were detected in the precolostral serum of calves. Five fetuses with fetal ages ranging from 132 to 156 days were inoculated in utero with the virus. One weak newborn and four stillborn calves were delivered at gestation days 256 to 263, i.e., less than the standard gestation term; they had congenital abnormalities including arthrogryposis, hydranencephaly and cerebellar hypoplasia. Antibodies specific to AINOV were detected in their precolostral serum. These results demonstrate that AINOV is a potential etiological agent of congenital malformation of cattle.

Serological evidence of akabane virus infection in northern Israel in 2001.

In February 2002 the first cases of a "blind newborn calves" syndrome with hydranencephaly appeared in Israel. Eighty-one serum samples, from 54 animals on farms where the syndrome was recorded and 27 others from unaffected farms were examined by neutralization of Akabane virus (AKAV, strain OBE-1) by the micro-titer method. Forty-seven of the 54 samples from the affected farms contained high serum neutralization titers against AKAV (mean SN titer 79.5 and +/- 44.7, standard deviation), whereas only one of the 27 samples from the unaffected farms was positive (titer of 8). These results suggest that the vector(s) of AKAV was circulating in Israel in August through December, 2001.

Prenatal sonographic diagnosis of fetal death and hydranencephaly in two Chihuahua fetuses.

Hydranencephaly and fetal death was diagnosed in two of three fetuses during the abdominal sonographic examination of a 2.5-year-old, intact female Chihuahua that had clinical signs of dystocia 63 days after mating. A cesarean section was performed and one live normal puppy was present. Two dead puppies, each with a markedly enlarged and fluid filled skull were removed.

Transorbital echoencephalography in cattle.

The purpose of this study was establishment of the criteria of transorbital echoencephalography in cattle and experimental applications to bovine practice. Quantitative investigations using magnetic resonance (MR) imaging revealed that this examination could be applied to cattle under 3 months of age. The method of transducer positioning was established in Japanese Black (J.B.) and filial (F1) cattle (turning caudally at an angle of about 16 degrees and dorsally at an angle of about 23 degrees) or in Holstein cattle (turning caudally at an angle of about 20 degrees and dorsally at an angle of about 21 degrees). Examinations in clinical calves revealed that the cerebral parenchyma and the lateral ventricle could be detected antemortem or postmortem. In this study, the diagnoses of hydrocephalus or hydranencephaly was possible using antemortem transorbital echoencephalography. Transorbital echoencephalography was especially useful as the imaging method for bovine hydranencephaly.

Hydranencephaly and cerebellar hypoplasia in two kittens attributed to intrauterine parvovirus infection.

Six weeks after vaccination with modified live feline parvovirus vaccine, a cat gave birth to five kittens, three of which died soon afterwards. The remaining two kittens (A and B) survived, but at 8 weeks of age were unable to walk and showed abnormal behaviour, with lack of menace and oculovestibular responses, and severe dysmetria. These signs suggested multifocal disease associated with the cerebrum and cerebellum. Magnetic resonance imaging demonstrated severe bilateral (kitten A) or unilateral (kitten B) hydrocephalus or hydranencephaly, combined with cerebellar agenesis (kitten A) or severe hypoplasia (kitten B). Hydranencephaly was confirmed histopathologically in both kittens. Parvovirus was isolated from the kidney of one kitten. Parvoviral DNA was amplified by the polymerase chain reaction (PCR) from paraffin wax-embedded brain of both kittens. The severe malformations observed in these kittens presumably resulted from an in-utero parvovirus infection, possibly due to vaccination, that occurred late in the first, or early in the second, trimester of pregnancy.

Teratogenicity of Aino virus in the chick embryo.

Aino virus (JaNAr 28 strain), a possible agent of a congenital anomaly of calves, was inoculated into the yolk sac of chick embryos at a dose of 10(2), 10(3), 10(4) or 10(5) TCID50 0.2 ml-1 at four, six or eight days of incubation. At 21 days of incubation all the unhatched embryos or hatched chickens in the experimental and control groups were sacrificed for pathological examination. The incidence of hydranencephaly, cerebellar hypoplasia or agenesis and arthrogryposis or scoliosis was highest (85 per cent in the chicks inoculated with 10(3) TCID50 0.2 ml-1 at eight days of incubation. The lesions were very similar to those found in congenital abnormalities in calves suspected of a natural infection with Aino virus.

Hydranencephaly, cerebellar hypoplasia, and myopathy in chick embryos infected with aino virus.

Pathogenesis of Aino virus (AIV), a suspected causative agent of congenital abnormalities of calves, has not yet been established by experimental infection of dams. To investigate the pathogenesis, 10(3) median tissue culture infective doses per 0.2 ml of AIV strain JaNAr 28 was inoculated into the yolk sac of 8-day-old chick embryos. At 4, 7, 10, and 13 days post-inoculation (PI) 20 eggs were opened and macro- and microscopic studies combined with virus recovery and immunohistochemical detection of the virus antigen were performed. At 7 to 13 days PI chick embryos manifested marked hydranencephaly, cerebellar hypoplasia, arthrogryposis, and scoliosis, with the highest incidences of 86.7%, 73.3%, 80.0%, and 20.0%, respectively. At 4 days PI the viral antigen was found in nerve cells, gitter cells in mild necrotic foci of the central nervous system (CNS), degenerative myotubules, and macrophages in the interstitium, which was associated with the early phase of AIV-induced encephalitis and polymyositis, with occasional accompanying hemorrhage and clumping of myotubular fragments. From 7 to 10 days PI, AIV antigen increased markedly in the liquefactive necrosis and in both degenerative and normal-looking myotubules in conjunction with developing hydranencephaly and arthrogryposis. The encephalitis and myositis had a tendency to mitigate by 10 days PI, coincident with a slight decrease in amount of AIV antigen. At 13 days PI there was almost no detectable AIV antigen in CNS and skeletal muscles, probably due to depletion of cells having affinity to AIV.