ParamyxoviirusesSeptember 21,22, 2010

rinderpest and the beginning of modern veterinary medicineGiovanni Maria Lancisi

Viruses with -ve RNA genomesParamyxoviridaeRhabdoviridaeOrthomyxoviridaeFiloviridaeBunyaviridaerabies virusvesicular stomatitis virusinfluenzavirusesEbola virusHaantan virusParamyxovirusesPneumovirusesMorbillivirusesparainfluenza virusrespiratorysyncytial viruscanine distemperNewcastle disease virusHendraNipahHenipah

ParamyxovirusesEnvelopedGenome - single negative stranded RNA moleculeHelical nucleocapsid with herring-bone appearance

A paramyxo virionFusionProtein (F)(syncytia whenon cell)herring-bonenucleocapsidHN (paramyxo)H (morbilli)G(pneumo)

Receptor binding and penetration

GenusReceptor attachmentMain Penetration or Fusion proteinParamyxovirus(PI3)HNF (cleaved by cellular proteases)Pneumovirus(BRSV)G (no neuraminidase)F (cleaved by cellular proteases)

Morbillivirus(CDV)H (no neuraminidase)F (cleaved by cellular proteases)

Syncytium (pl. syncytia) formationactivatedfusion proteinbuddingvirusuninfectedcellssyncytium

Syncytiasyncytia

Eosinophilic cytoplasmic inclusion bodies

Importance of type of immunityneutralizing and fusion preventing antibodies are protectivenon-neutralizing antibodies can exacerbate disease (children vaccinated with formalin inactivated vaccine)Th1 better than Th2CMI

Respiratory disease by Paramyxo and Pneumovirusesbovine parainfluenzavirus 3 (PI3)respiratory syncytial virus (BRSV)dogsPI2birdsNewcastle disease virus (clinical features depend on strain)

MorbillivirusesRinderpestPestes des petit ruminantsCanine distemper virusMorbilliviruses of marine mammalsMeaslesHendra virus (equine morbillivirus)Nipah virus

canine distemper viruscomplex disease - enteric, respiratory, lymphoid, neuraleffects wide range of carnivore speciesCanidae (main reservoir)Procyonidae (raccoons)Mustelidae (ferrets, mink)Ailuronidae (pandas)Felidae (Panthera not domestic cats)marine mammals

Pathogenesisinfectionasymptomatic incubation period (7-10 days)GI and respiratory signs, infection of epithelial cellsrecoverydeathacute neurological signsrecoverydeathchronic neurological signsdeathold dog encephalitis

Acute neurological diseaseVirus replicates in neurons and glial cellsDemyelination in white matter in absence of inflammationNo virus replication in oligodendroglial cells but suppression of myelin synthesisImmunological recovery - Lymphocytic infiltration, intrathecal antibody synthesis

Chronic diseaseWith immunological recovery - inflammation in demyelinating lesions - progressive disease

Long-term persistence in CNSNon-cytolytic replicationCell to cell spread without budding - no antigens on surface

Virus reactivation or immune-mediated damage

Clinical signsasymptomatic (most dogs)partial immunitygeneralfever, depression, anorexia, discharge from eyes/nose, entericvomiting, diarrhoearespiratorycoughing, sneezing, dyspneaneuralweakness, ataxia, incoordination, epileptic seizures, myoclonus, chewing gum fitsotherhyperkeratosis of nose and foot padsold dog encephalitisvisual defects, compulsive circling, head pressing

Diagnosis of distemperclinical signsLaboratoryPCRSerologySerum + CSF (NO EDTA)Paired samplesImmunohistochemistry

Ante-mortem diagnosis by immunohistochemistry (Haines and Clark, WCVM)

Prevention of distemperInactivated vaccinesModified liveUSE ONLY IN DOMESTIC DOGS!Vectored vaccine (Recombitek, Merial)Heterotypic vaccine (measles)

A case of distemper in SaskatoonIn December a 4-5 month old American Pitbull cross was brought to a Saskatoon animal shelter as a stray. The puppy was vaccinated with DA2PCPV and was adopted out on December 23. The puppy was returned to the shelter on December 29 as he was coughing. On January 3, the attendant described the pup as acting weird - head pressing, stumbling and twitching were observed. Within the next week several dogs at the shelter developed respiratory signs. For the next several days about 10 dogs a day were brought to the WCVM clinic with signs of distemper. All dogs at the shelter were euthanised and it was closed for traffic.

Other morbillivirusesHorse morbillivirus (Hendra virus)Nipah virusRinderpestPestes des petit ruminantes

RinderpestWild and domestic ruminants, pigsDirect contact or contaminated waterHigh feverPurulent dischargeErosion of oral mucosaBloody diarrhoea

A new disease in horses and people (1994)MacKayBrisbaneQueensland(Hendra)CairnsTownsville

At a stable in Hendra (1994)Two horses moved to stableDrama Series becomes sick and diesWithin three weeks 13 horses dieRespiratory, CNS, haemorrhages in lungStable hand and trainer become sickTrainer dies

Diagnostic investigationRule out AHS, flu, EHV-1, bacteria, toxinsSee syncytia in cultures - suspect paramyxovirusPCR for PI and pneumoviruses is negativePCR for morbillivirus +veSequence -> new virusCross reactivity between human and horse sera

Diagnostic investigationMore than 3,000 serum samples, horses and people negative5,000 samples from 46 species - negativeAntibodies in fruit batsVirus isolated

At a farm near MacKay (July 1994)Pregnant mare at pasture develops respiratory signsMoved to paddockMare develops respiratory distress, ataxia, edema ->diesStallion in next paddock, neuro. Signs, haemorrhages ->diesOwner (vet) and husband perform necropsy

Possible causesAvocado poisoningBrown snake bite

MacKay August 1994Husband becomes sickSore throat, headaches, etc. CSF - neutrophilia, no virus or bacteria identifiedResponds to antibiotics - recovers

MacKay September 1995Husband readmittedNeuro signs, seizuresTreated with acyclovir, antibiotics, anticonvulsants, corticosteroidsComa - dies three weeks laterDiagnosticCSF from 1994 - 1/4 for EMV, virus by PCRIn 1995, increase in titre from 1/16 to 1/5792Necrosis in neocortex, basal brain, brain stem, cerebellum

Equine morbillivirusHorses, people, cats, guinea pigs infectedFruit bats can be infected but no diseaseExcreted in feces, urine, infection by eating shed virus

Nipah VirusOct 98 to April 99 - 257 cases of encephalitis (100 deaths)Similar disease in pigs

Nipah diseaseFever, severe head aches, muscle painCommon - association with pigsInitially thought to be Japanese encephalitisSyncytia, paramyxovirus on EMVirus isolated, Univ. Malaya and CDCSimilar to Hendra virusSerological confirmation that virus involved in outbreak.

Porcine respiratory encephalitis syndrome, barking pig syndromeFeverCoughingRespiratory distressTrembling, head pressing, spasmsAbortions, still births

Nipah virusPigs, humans, dogs, cats, rats and horses can be infectedSerological evidence in fruit bats (reservoir?)virus from fruit bats - 20022004-5 - human cases in Bangladesh (no contact with pigs or bats, contaminated fruit?)

Why?Chou. Nipah virus outbreak in Malaysia. J Clin Virol April 2003

Control1 million pigs killedreduce pig-human contact

Nipah in BalgladeshPossible contamination of date-palm sap by Nipah virus

Nipah human to human transmission

First veterinary college Lyons, 1762**Paramyxo and Pneumo - localized respiratory disease - may be fatal in new born animals or secondary bacterial infectionsMorbillivirus devastating diseases in man and other animals - measles, Rinderpest, emerging diseases reemerging diseases in new hostsRinderpest (outbreaks in 18-19 century led to establishment of vet colleges).

*Bovine - PI3 and BRSV (along with BVD and BHV-1) - bovine respiratory disease complex. Respiratory disease on their own or predispose animals to secondary bacterial infectionenzootic pneumonia*PDS:serology (VN) - serum, CSF*In Bangladesh, a muslim country with not much of a demand for pigs, Nipah was initially transmitted by the contamination of sweet palm sap collected for recovering sugar and for fermentation. The disease now spreads directly from person to person.