Avian Borna Virus: PDD or really AAG? – Dr Orosz
A disease that needs some changes of thinking
PDD = Avian Ganglio Neuritis
New insights into PDD
- Originally reported in macaw species (macaw wasting disease)
- Reported in more than 50 species of psittacine birds including
African greys, macaws, conures, lovebirds, amazons, cockatoos,
cockatiels, parakeets
- disease of captive birds
- appears to be widespread
- 30-50% of population affected
- depends on locale and testing
Clinical disease is variable – how it presents is variable, old world vs
new world
- distribution of lesions in CNS, PNS, ANS
- severity of lesions
‘Classic’ Disease – gastro tract, most often observed in New World
species.
Classic presentation:
- depression, anorexia, loss of body condition, regurgitation, loss of
pectoral mass, undigested stuff in feces
Pathology view, end stage
- no suppurative
- lymphocytic, plasmatcytic
- ganglioneuritis
PCR: presence avian bornavirus (ABV)
- sometimes, but not all the time
Historically viruses proposed: adenovirus, coronavirus, Eastern equine
encephalitis, togavirus paramyxovirus, deno-like viruses, Enteroviruses
Reoviruses documented in PDD
2007 suspected paramyxovirus like dx, blood PDD positive birds
2 independent reports BVD in summer of 2008, with a 3rd group shortly
after
Correlation of Borna Virus Disease (BVD) with avian cases of PDD
Newcastle is a paramyxovirus
Virus Chip
- interrogated confirmed PDD and control case series
- samples independently collected on 2 continents
- Microarray tissues screened for most known viral pathogens
- Novel Borna virus signature detected
Texas A&M researchers
- ABV was cultured from confirmed PDD case
- Infected 3 healthy cockatiels with ABV
- 2/3 birds developed clinical PDD
- ABV was detected in 3/3 cloacal swas
- 3/3 birds histopathy lesions
BDV – very conserved, 2 genotypes identified
ABV – more diverse
- currently 6 genotyes known
- relationship between genotype, specific host disease unknown at
this time
- BDV and ABV share similar structure
BVD is mammalian form
ABV presents in healthy birds
- causes a viremia without clinical disease
- Blood ABV testing:
o Europe 46% healthy birds are ABV positive
o 30% infection rate in US
- 33% BVD infection rate in healthy humans
Incubation period unknown
Sexually transmitted in the vitolene membrane of the egg
Psittacine nursery outbreak, 20 days
Cockatiels – loss of body weight and condition by 20-30 days post
infection
Determined, release P40 (glyco) protein with bornavirus infection,
ganglia or nuclei. P40 protein released
Research Rossie Group
- injected protein into normal cockatiels
- birds developed symptoms of PDD but did not have ABV
- PDD is actually an autoinflammatory response/disease
Birds can have PDD without ABV
The virus gets into the body, it depends on the immune system of the
bird – if the virus attacks the glyco proteins and where, the symptoms
develop.
 Like Guillain barre disease – THIS IS IMPORTANT LOOK IT UP
Infectious agent:
- ABV or other neurotropic viruses
- Causes release, protein
Histopathologic lesions compatible with autoimmune dx
- Invasion, T lymphocytes, plasma cells
{Paramyxovirus and ABV gene blast are so close it’s scary – federal
government might be concerned}
- inflammation in glial cells
- leakage of proteins
- CAN, ANS, associated, GI dysfunction and neurological signs,
cerebrum and cerebellum
- PNS: spinal cord
ANS:
- Parasympathetic
o Long preganglionic fiber
o Short postganglionic, organ wall
o Mixing and digestion
- Sympathetic
o Both are long
o Ganglia outside of the organ
Vagus Nerve
- Nuclei that innervate:
o Nucleus ambiguous
o Dorsal nucleus, GI tract -> colon
o Taste fibers
o Spinal nucleus: sensory, face, motor jaw
ABV: Autonomic NS
- Dorsal vegal nucleus
o Lesions
- smooth muscle atrophy/neurogenic atrophy
- Atony, dilatation, impaction – crop, proventriculus, ventriculus,
intestines
- Adrenal gland
o Lymphocytes, medulla
o Clusters near cortex
o Often used for histopathology
- Cerebrum
o Lymphocytic perivascular cuffing
o Glial cells affected
o Site determines the neurologic signs
- Cerebellum
o Glia + granular cell layer
o Disruption/loss Purkinje cell layer
o Glia + molecular cell layer
Proprioception
- Conscious proprioception – know where the body is
- Fascilus gracilus and cuneatus – tracts to go conscious centers
- If lymphocites are in the way, they can’t tell where they are – will
fall, stumble, etc
ABV(AAG) Clinical signs – CNS
- often in old world species
- +/- GI tract signs
- CNS signs only -> histopathology: GI tract lesions
- +/- cortical blindness (can see but can’t interpret images
properly)
- ataxia, incoordination
- proprioceptive & motor deficits
- progressive paresis
- less commonly paralysis and seizures
ABV(AAG) PNS Anatomy
- Thoracolumbar spinal cord greatly affected
o Focal microgliosis
o Swollen axons, myelin degeneration
o Peripheral neuritis in birds
o May be contributory to feather and self mutilation disorders
PDD diagnosis, ABV testing
- presumptive diagnosis – history, clinical signs, radiological
evidence of disease
- Definitive diagnosis – characteristic lymphoplasmocytic
ganlioneuritis
o Crop
o Ventricular
o Biopsy
- majority of testing just shows if bird has borna, NOT PDD. Use as
clue
ABV RT- PCR
-Tested 791 blood and/or cloacal swab samples up through 2008
- 34.3% were positive
- present in all major species
ABV detected in: highest concentration in retina, brain, and spinal cord
-
Significant percentage of avian population affected
A continuum of clinical diseases exists
A wasting bird represents an extreme case
Majority of birds DO NOT SHOW clinical disease
- Clinical disease, intermittent or more continuous – can
exhibit symptoms only during certain times of the year,
especially during hormonal periods. As a sexually
transmitted the disease, the virus has to be activated
by the gonadal hormones to then pass down the
disease to the chick via the egg membrane. OR virus is
passed vent to vent or via eating feces of infected bird.
- More commonly during hormonal periods
- CNS
o Hyperexcitable
o Wobbly
o Blindness (can be reversed if properly treated)
Anything that is neurotropic as a virus can potentially cause the
problem
AAG IS A RETAINED VIRUS
Virus can’t live for long outside of its environment – is NOT
airborne
Treatment: [has to be based on the symptoms that the bird has]
- ANS signs:
o Altered GI tract function, bacterial overgrowth
 Often clostridium
o Avian gastric yeasts
o Reduced/altered motility
- GI signs
o Often affects liver function – commonly treated with milk
thistle and dandelion
- Bacterial showers?
- Inflammation, liver
o Doxycycline
o NSAIDS
o Ginger
o Onsior
- Treatment for CNS signs
o Celebrex
o Onsior
o Amantidine
o Gabapentin (control seizures)
o Adjunct to decrease inflammation
 Depo Lupron (shot)
 Reduction of hormonal behaviors
o Cortical Blindness
 Celebrex
 B complex vitamins
 Omega 3 PUFAs – eggs, walnuts, pumpkin, flax seed
- Treatment for PNS signs
o Neuritis = pain: tramadol, NSAIDs, nerve/ring/line blocks
OLD concept of ABV parallels early BDV:
- low incidence of infection
- fatal clinical disease
- strong pathogen
- 1890 epidemic, fatal neurological dx, military horses in borna
Germany
- BVD was thought to be a deadly virus to all
NEW concept of BVD
- High incidence – 60% avg infection rate, healthy horses/etc
- Low disease prevalence, 5-10% clinical disease
- Pathogenicity inversely related to prevalence of infection
BVD:
- High prevalence of silent infections
- Low level of clinical disease
ANY AGENT CAUSES RELEASE of P40 PROTEIN
Gullian Barre Pathophysiology
- Autoimmune dx triggered by bacterial or viral infection
- Gangliosides are immune targets
- Different gangliosides predominate, different areas
o Peripheral nerves
o Ganglia
Gullian Barre Clinical Manifestations
- Depends on subtype
- Numbness, pain
- Parasthesias
- Weakness of the limbs
- Weakness plateaus about 4 weeks
Avian AutoImmune Ganglioneuritis
- Better description of the pathologic process
- T lymphocytes, plasma cells invade where P40 proteins released
- Like G Barre, varies by location
- Severity depends, immune health individual
- Site of infection varies based on ganglioside targets
- When affects peripheral nerves:
o Possible feather damage
o Possible self mutilation
- can get neurogenic atrophy from damaged peripheral nerves
- cachexia from poor absorption – feather changes should also
occur
- Autonomic ganglia – dorsal vagal nucleus
o Can be very localized, just the crop/stomach/heart etc
New approaches are immune directed – immune modulating
therapeutic approach
Birds can’t HEAL from AAG, but they can get better – symptoms can get
treated, but the actual infection can never leave the body