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Proventricular Dilatation Disease and Avian Borna Virus

Macawnutz

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This is a recent article written by my vet. I thought I would share it here.



Proventricular Dilatation Disease and Avian Borna Virus

Peter S. Sakas DVM, MS
Niles Animal Hospital and Bird Medical Center
www.nilesanimalhospital.com
http://www.gccbc.org/Bulletins/GCCBC Nov Dec 2013 Bulletin.pdf

Proventricular Dilatation Disease (PDD)

Proventricular dilatation disease (PDD) is a suspected viral disease that has been given many other names over the years, including macaw wasting disease (as it was thought to be prevalent in this species), neuropathic ganglioneuritis, and lymphoplasmocytic ganglioneuritis. The disease has been identified in a wide variety of birds, including 80 species of psittacines, toucans, honey creepers, weaver finches, water fowl, raptors and passerines. An epornitic of this disease is currently occurring in imported and captive-bred psittacine birds in North America and Europe.

PDD was experimentally reproduced and transmitted by exposing susceptible adult psittacine birds to a viral suspension derived from affected birds. The incubation period is variable, ranging from several weeks to more than 3 months.

PDD causes damage to the nerves supplying the GI tract, leading to segmental dysfunction of the crop, esophagus, proventriculus, and small intestine. It has also been found to affect the central nervous system and peripheral nerves. Common clinical signs of PDD include depression, gastrointestinal dysfunction (chronic weight loss, crop stasis, constant or intermittent regurgitation, dilatation of the proventriculus, ventriculus, and small intestine, malabsorption, and sometimes there is passage of whole seeds or portions of undigested food in the droppings), and central nervous system signs (ataxia, abnormal head movements, tremors, seizures, and proprioceptive and motor deficits). Neurologic signs may be present terminally. Some birds will show only gastrointestinal dysfunction, some will show only CNS signs, and some will show a combination of both.

Other infected birds will be asymptomatic but shed the virus continually, serving as the cause of outbreaks in susceptible birds in an aviary or pet retail facility. In some outbreaks, numerous cases of PDD will occur simultaneously. Sometimes, several birds will die in an outbreak and the problem will appear to resolve, only to reappear years later. It is more common, however, for many of the birds exposed to an affected bird to remain asymptomatic.

Definitive diagnosis can be achieved through the histologic demonstration of lymphoplasmacytic infiltrates within nerves, ganglia, and through the absence of normal myenteric plexi, especially within the nerve tissue of the gastrointestinal tract. Most frequently, the diagnosis is made through postmortem submission of a complete set of tissues, including proventriculus, ventriculus, brain, and spinal cord tissue. At necropsy, emaciation, pectoral muscle atrophy, and dilatation of the GI tract, including the proventriculus, are observed. Some gross necropsies of birds with PDD may appear normal, and histologic changes can be easily missed, as well.

Antemortem diagnosis of PDD is difficult, since no specific diagnostic test is still available commercially at the time of this writing. (We will speak about Avian Borna Virus in an upcoming section). Rather, diagnosis is based upon observing the characteristic clinical signs and ruling out other conditions that may produce those signs. Plain and contrast radiographs are useful for demonstrating gastric abnormalities in affected birds. Common radiographic findings are proventricular dilatation or distension and increased barium transit time. However, practitioners should not automatically assume that a bird with a dilated proventriculus has PDD, since other conditions may also produce this radiographic change. Further, the proventriculus of neonates is normally dilated and should not be misinterpreted as indicating PDD. Conditions that demonstrate clinical signs similar to PDD include GI foreign bodies and impactions, gastroenteritis, and heavy metal toxicoses.

Antemortem diagnosis is further hampered by the fact that proventricular and ventricular biopsies are not generally recommended due to the risk they pose and the tremendous distension produced by the condition. Full-thickness crop biopsies have shown some promise in the detection of PDD and are commonly used as a definitive test. However, they are helpful only if the results are positive; since false negative results can occur. Because it is important to include nerve tissue samples in this type of biopsy, the crop should be sampled in an area that has at least one large blood vessel and associated ganglia. Further, the biopsy size should be at least 1 cm x 1 cm, and it should be taken from the left midlateral aspect of the crop. In several studies, changes consistent with PDD were reliably detected in 68–78% of the crop biopsies collected from positive birds. Typically, birds were observed to have lymphoplasmacytic infiltrates in the crop without concomitant lesions in the proventriculus and/or ventriculus. Unfortunately, PDD cases have been seen where there are lesions everywhere else, except the crop!

Blood chemistry may also be useful, since serum amylase and lipase levels are elevated in some patients, and hypoalbuminemia may be present. Other possible indications of PDD are elevated CPK and feather changes.

Treatment for PDD is usually unrewarding, but there has been success with the use of Celebrex in affected birds, given once daily and is now considered the treatment of choice. Celebrex does not eliminate the disease, but as it inhibits the lymphoplasmocytic infiltration around the nerves, it aids in the resolution of symptoms. In addition, careful nursing may prolong the life of an affected bird. Strict isolation is recommended. The mates, offspring, and siblings of birds that have been definitively diagnosed with PDD through histologic evaluation should be considered at extra risk of developing the disease and should be carefully monitored, but they should not be euthanized. Until a vaccine or an accurate diagnostic test is developed that can detect the presence of the virus or an antibody response to it, birds that have been exposed to PDD should be isolated or kept in single-bird households where there is no risk of exposure to other birds.

Avian Borna Virus (ABV)

In 2008, researchers of PDD identified the presence of a novel borna virus in the brains of PDD affected birds. Before ABV was discovered, Borna Disease Virus (BDV) had been identified as a cause of encephalitis in mammals. In recent veterinary literature, ABV has been considered the cause of PDD in birds. However, there is a disagreement amongst various groups of veterinarians that this is actually the case, leading to much confusion in the avicultural community.

Avian Borna Virus does cause neurological disease in birds. It passes in the droppings and is especially highly concentrated in the urine. There is even some consideration that it may pass from the hen to the chicks (called vertical transmission) and passage can also occur in the nest. There are at least five forms of the ABV virus (genotypes) and some have more virulent potential. It does not damage the cell and causes minimal disruption. It may be incorporated into the cell structure and in this way cause lifelong infections with no link to PDD.

Despite this link between PDD and ABV by several researchers, it is very much open to question. ABV testing provides inconsistent, discordant and ambiguous results. An in-house review of 200 tests in both suspect and healthy birds between 2010 and 2013, indicated that current non-pathology based diagnostic testing has limited or no value. (Van Sant AAV 2013) Samples from the same patient, collected and processed in the same way were found to show different results from different laboratories. (Van Sant AAV 2012) Birds that may eventually die from PDD may be consistently negative on polymerase chain reaction (PCR) ABV assays even when serial samples are collected, as well as be negative for ABV by culture and PCR-based testing at the time of death. (Van Sant AAV 2013) Alternatively, clinical patients included those with ABV infections that have died and shown no documentable lesions consistent with PDD. (Van Sant AAV 2013). The research that identified the “link” between PDD and ABV found ABV in 60% of the birds with PDD. Looked at another way, this means that 35% of the ABV birds DID NOT have PDD. Not really compelling evidence for that link!

A number of commercial tests are offered in the US but these different protocols are not published or standardized and at least five commercial diagnostic laboratories offer PCR-based testing for ABV. They all differ in preferred submission protocol with most requesting feces or blood samples, but another may request a pharyngeal swab and still another utilize feather shafts (which has a great propensity to be contaminated by environmental contact). (Van Sant AAV 2013) Some laboratories stress the need the process and submit samples quickly, but do not consistently advise overnight shipping on ice (which would be ideal).

All but one laboratory have reported ABV results as indicative of PDD, which is inaccurate. Some of the laboratories have adjusting their reporting as the link between PDD and ABV has now being disputed, however, some laboratories continue to report ABV results as PDD positive.

There are huge differences between the laboratories, their testing protocol, their standards, impacting the reliability of their results. Dr. Fern Van Sant had tested apparently healthy birds as part of routine viral screening to board at her clinic. She had sent samples from 282 birds to an east coast university laboratory (the laboratory we use at Niles Animal Hospital and Bird Medical Center). Most were clinically normal birds and only eight birds were positive for ABV. Her colleagues urged her to use another laboratory as the “expected” background infection rate was 30%. She switched and her results were about 64% positive. She then retested these birds at the original east coast university laboratory and their original results were confirmed and they could not duplicate the positives from the new laboratory. (Van Sant AAV 2013) This shows the importance of dealing with a quality laboratory with an excellent testing protocol and high standards…not a “knock off” lab.

Although researchers and veterinarians assume ABV is the cause of PDD, increasing data suggests this data may not be absolute (Van Sant AAV 2013) Why is it that ABV is so prevalent in the psittacine population with a low incidence of fatal PDD? There have also been fatal cases of PDD with no traces of ABV. The theory that all PDD is caused by ABV may not be completely supported by fact. (Van Sant 2013)
If ABV is even a cause of some cases of PDD, in naturally occurring infections it appears that some event must occur to cause a virus that can be documented in clinically normal animals to cause lethal changes recognized as PDD. (Van Sant AAV 2013) This factor is not consistently predicted by a PCR-based assay for ABV. (Van Sant AAV 2013) We clearly lack the ability to test reliably for ABV and relate the test result to reliable prognostic information.

ABV and PDD

Unfortunately, there have been several parrots tested positive for ABV without clinical signs of PDD and they were prematurely euthanized. As it turned out their tissues were histologically negative for the presence of PDD. ABV should not be referred to as the cause of PDD. It is of questionable value to test any psittacine bird for ABV and the only definitive diagnosis of a live bird for PDD is a crop biopsy with histopathological analysis. If any bird tests positive for ABV it should be retested 90 days later, and persistently positive birds should be considered immunocompromised. PDD is not the only disease possibly associated with the immunocompromised state.

What to Do With the ABV Positive Bird?

If there is only one bird that tests positive for APV in the household it should be isolated from other susceptible birds. The disease is shed intermittently in the urine and feces so it would be a source of infection to other birds.

There have been many instances where an infected bird has been in contact with another bird which is negative and that bird remains negative for months to years. Even after the death of an infected bird, it still remains negative. The virus is not resistant in the environment and is susceptible to most detergents and disinfectants. Some people have kept positive and negative birds in the same room, but through the practice of good hygiene, good ventilation, good husbandry, and nutrition, they have prevented the spread of disease.

Positive birds in an aviary setting are a challenge. It can be difficult to separate pairs, and often positive mates do not transmit disease to their negative mates. But as transmission is fecal-oral there still is the potential for infection. In addition, there is evidence that the infection can pass from the hen to chick, so incubator hatching cannot definitively stop the spread of infection to the chick.

As the different genotypes vary in virulence, having one genotype is not protective against another. So a positive bird, exposed to another bird with another genotype could develop serious illness. So having one ABV-positive bird does not mean you can in another ABV-positive bird without risk.
There is no recommendation to euthanize ABV positive birds. There is no one test or combination of tests that can reliably predict the progression from ABV exposure and shedding to clinical PDD. There is no prophylactic treatment to prevent progression to disease.

The current recommendation is to separate positive birds from negative birds, remembering that to be negative there must be multiple negative test results. (It is recommended that if there are three negative PCR tests, the bird is considered negative).

The birds should be kept in a clean, well-ventilated area, and minimize stress. If there are negative and positive birds in the household, owners should wash their hands between birds, use a foot bath or disinfect their shoes when going from infected to non-infected rooms. Care for the negative birds before handling the positive birds. Although a contagious disease, the organism is easily destroyed in the environment.

This discussion was based on several sources:
“Essentials of Avian Medicine: A Practitioner’s Guide” Peter S Sakas DVM
AAHA Press (2002)
“Bornavirus Positive! Now What?” Sharman Hoppes DVM
“The Rabbit Hole of Avian Borna Virus Testing” Fern Van Sant DVM

Personal Communications with Branson Ritchie DVM
I am deeply indebted to Dr. Van Sant for her willingness to share her manuscript and presentation with me and to Dr. Ritchie whose eagerness to help me at any time, his wise counsel, and friendship through the years is deeply treasured by me personally. PSS
 

Hankmacaw

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Good info Sarah. I hope everyone takes a few minutes to read this.
 

gibsongrrrl

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Very good info. Dr van sant is actually right down the road from me. Would love to discuss more of this with her. Thank you for posting. I'd really love to know which labs are which, as I've heard that one has a high rate of false positives
 

Ziggymon

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The Ohio lab (don't remember its name) is the one that is notorious for its false positives.

Thank you for posting this, Sarah.
 

Macawnutz

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I'd really love to know which labs are which, as I've heard that one has a high rate of false positives

I agree. It has also been brought to my attention from members here that not all labs test for all genotypes. That would also be helpful information in choosing which lab to use.
 

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Clear as mud now right Sarah?:) It really is enough to drive you completely insane. When I took Letti and Leo in, I asked Dr. Sladky where he stood on testing for ABV as a normal procedure for well birdie exams and he said that he thought it was pointless unless the bird was showing clinical signs of PDD unless you wanted to drive yourself nuts. So, we skipped that particular test...although I probably wouldn't have bothered even if he would have suggested it. I'm so surprised when vets think it's a good idea to test for it without a good reason.
 

Macawnutz

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My fear is how narrow minded some vets can become once an ABV test is positive. It seems they stop looking for answers as they feel they have found them.

Had I done the ABV when it was recommended to me by my first vet and it came back positive..... would I have ever found that Korbel had AGY? Probably not.
 

jmfleish

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My fear is how narrow minded some vets can become once an ABV test is positive. It seems they stop looking for answers as they feel they have found them.

Had I done the ABV when it was recommended to me by my first vet and it came back positive..... would I have ever found that Korbel had AGY? Probably not.
Yep, you've got another really good point there. I wish we were throwing more money at it and finding out more about it...it's a very scary prospect.
 

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My fear is how narrow minded some vets can become once an ABV test is positive. It seems they stop looking for answers as they feel they have found them.

Had I done the ABV when it was recommended to me by my first vet and it came back positive..... would I have ever found that Korbel had AGY? Probably not.
Totally agree. I would definitely recommend any bird that tests positive for ABV and/or has neurological symptoms or vomiting also have blood tests done for metal tox because it presents so similarly. I've seen quite a few birds that came in with PDD symptoms that ended up testing pos for metal tox and responded to treatment for that. Even my own bird, whose proventriculus was slightly enlarged on xray after an incident where she vomited and couldn't keep food down for a few hours until she let go of the hugest poo bomb I have ever seen. I then found the paint chips from her cage in her droppings and requested she be tested for lead and zinc after being on meds for PDD treatment with no improvement. she was back to normal within 3 days of starting chelation treatment.
 

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When I took Letti and Leo in, I asked Dr. Sladky where he stood on testing for ABV as a normal procedure for well birdie exams and he said that he thought it was pointless unless the bird was showing clinical signs of PDD
That is Dr. W's take on it also.
 

Macawnutz

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Totally agree. I would definitely recommend any bird that tests positive for ABV and/or has neurological symptoms or vomiting also have blood tests done for metal tox because it presents so similarly. I've seen quite a few birds that came in with PDD symptoms that ended up testing pos for metal tox and responded to treatment for that. Even my own bird, whose proventriculus was slightly enlarged on xray after an incident where she vomited and couldn't keep food down for a few hours until she let go of the hugest poo bomb I have ever seen. I then found the paint chips from her cage in her droppings and requested she be tested for lead and zinc after being on meds for PDD treatment with no improvement. she was back to normal within 3 days of starting chelation treatment.

Korbel was 10 weeks old. He was vomiting constantly when ever he had food in him to vomit. He could not swallow and went from 1030 to 730 grams in a few weeks. He had a foot twitch and could not sleep. We had him tested for everything and then repeated tests. He had as many as 20 fecal gram stains and just as many crop swabs. I continued to refuse the ABV knowing it would give me no comfort with either outcome. The vets urged me to put him down saying I was allowing him to suffer but I knew there was something being missed. My last visit to that vet was to do the ABV test, I begged for them to do another crop swab explaining I felt it was yeast....... Why AGY finally showed on that last crop swab is beyond me but me but it saved his life.

His ABV test came back negative. The vet called and explained that meant very little and I should test him again. I did test him again after that but not at that clinic. My current vet sent it in for me even though he and I both knew I had no reason too.
 

gibsongrrrl

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Korbel was 10 weeks old. He was vomiting constantly when ever he had food in him to vomit. He could not swallow and went from 1030 to 730 grams in a few weeks. He had a foot twitch and could not sleep. We had him tested for everything and then repeated tests. He had as many as 20 fecal gram stains and just as many crop swabs. I continued to refuse the ABV knowing it would give me no comfort with either outcome. The vets urged me to put him down saying I was allowing him to suffer but I knew there was something being missed. My last visit to that vet was to do the ABV test, I begged for them to do another crop swab explaining I felt it was yeast....... Why AGY finally showed on that last crop swab is beyond me but me but it saved his life.

His ABV test came back negative. The vet called and explained that meant very little and I should test him again. I did test him again after that but not at that clinic. My current vet sent it in for me even though he and I both knew I had no reason too.
I totally remember that. So glad he's a big healthy boy now :heart: Vets are great and do their very best, but when we are the ones that live with them and see them everyday, our instincts are observations are just as important as their knowledge. I am so glad both of us pushed for further testing of our FIDs :hug8:
 

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Interesting article Sarah. One thing that does stick out, is that until AVs and Labs begin working together and decide upon a definitive set of standards for testing, it is questionable as to how much progress will be made in developing an accurate test and an effective treatment for this horrible disease. :(
 

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I am very upset currently, as Kimi's necropy resultd are starting to come in, and its very interesting. I had him sent to texas a and m for the necropy, as my vet is the type to jump on the abv = too bad, so sad bandwagon.

So far they have not been able to find abv in his brain, which is where the virus typically is found in higher amounts. So they did a full autopsy, and they are still waiting on thise results.

Am i kinda pissed right now? Yes. I am very interested in the results, now. Ugh.
 

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I am very upset currently, as Kimi's necropy resultd are starting to come in, and its very interesting. I had him sent to texas a and m for the necropy, as my vet is the type to jump on the abv = too bad, so sad bandwagon.

So far they have not been able to find abv in his brain, which is where the virus typically is found in higher amounts. So they did a full autopsy, and they are still waiting on thise results.

Am i kinda pissed right now? Yes. I am very interested in the results, now. Ugh.
You may not necessarily find any results of PDD on necropsy alone. You have to have a histopathology done as well. I'm assuming if you sent the body to Texas A&M for necropsy and told them you were specifically looking for PDD, that they would do the histo as well.
 

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Yes, that's what they are doing, as well. So, we shall see.
 

95talongirl

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This was posted to the PDD group on yahoo. Latest report on what's going on with ABV. Just did a copy/paste from the email, as my computer doesn't have word. LOL! (I believe this was published in May, 2014)


Avian Bornavirus Primer
Sharman M. Hoppes, DVM, Dipl. ABVP (Avian Practice); Texas A&M University College of Veterinary Medicine andChristal Pollock, DVM, Dipl. ABVP (Avian Practice); Lafeber Company Veterinary Consultant
Reviewers:Ian Tizard, BVMS, PhD, Dipl. ACVM, ScD; Texas A&M University College of Veterinary Medicine andNeil Forbes, BVetMed DECAMS FRCVS; Great Western Exotics, Swindon, United Kingdom
Key words: Bornavirus, ganglioneuritis, proventricular dilatation disease, PDD, psittacine, parrot
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macawsimported into the United States and Germany. During the early years, this disease was often referred to as “macaw wasting disease” (Payne 2012). Since that time, proventricular dilatation disease has been identified in over 50 different avian species including passerines like thecanary(Serinus canaria), honeycreepers, weaver finches, waterfowl, toucans, birds of prey, and psittacine birds (Hoppes 2013, Payne 2012, Smith 2010, Weissenböck 2009). Proventricular dilatation disease has been reported in captive parrots in North America, Latin America, Europe, Australia, Africa, Japan, and the Middle East (Sassa 2013, Last 2012, Doneley 2007).
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Polyuria, hypotension, and cardiac abnormalities have also been reported. Avian bornavirus infection damages the Purkinje cells, which can potentially cause arrhythmias however this is usually a postmortem finding.
Table 1.Potential signs of neuropathic ganglioneuritis in the psittacine bird
Gastrointestinal singsCentral or peripheral nervous system signs

  • Weight loss





  • Scant feces

  • Ataxia, weakness


  • Tremors

  • Seizure activity

  • Blindness

  • Abnormal head movements

Figure 1.Maldigestion/malabsorption diarrhea in a parrot fed a seed-based diet. Photo credit:Dr. Gregory A. Rich.Click image to enlarge.

Figure 2.Radiographic evidence of proventricular dilatation (arrow). Photo credit: Dr. Sharman Hoppes.Click image to enlarge.
*Editor’s Note: Although death would seem to be the most objective of parameters, there are camps of PDD study that disagree vehemently with the statement that symptomatic avian bornavirus disease is invariably fatal and there are reports of birds with chronic disease living long, long lives.↑ top
Schubot Exotic Bird Health Centerthat have tested positive for ABV via PCR and serology for over 7 years that continue to be clinically healthy. Other individuals consistently tested negative for up to 6 years before becoming acutely ill. These birds only tested positive on PCR and serology at the terminal stages of disease.
PCR:Reverse transcription (RT) polymerase chain(PCR) testingof droppings, feathers, and blood has been evaluated in psittacine birds (Table 2) (Hoppes 2013, de Kloet 2011, Dahlhausen 2010). Positive ABV PCR test results do not mean the bird has or ever will develop clinical disease, and most PCR testing does not differentiate between ABV genotypes. Due to intermittent shedding, one negative PCR test result also cannot rule out ABV infection, particularly if the sample is not properly stored.
Serology:Serological testing has also been frustratingly inconclusive, with some ABV-infected birds failing to develop a detectable antibody response within weeks of dying of neuropathic ganglioneuritis (Table 2) (Herzog 2010). In other individuals there appears to be a positive correlation between the level of antibodies produced and the development of disease. Tests used to detect ABV titers have included indirect immunofluorescence, ELISA, and Western blot assay (Hoppes 2013).
Histopathology: Although crop biopsies are rarely performed in our practice (Hoppes), a crop biopsy is routinely performed by some avian veterinarians in suspect PDD birds. Surgical removal of a small, vascular, full thickness segment of the crop wall is approximately 70% reliable in identifying histologic signs consistent with neuropathic ganglioneuritis. Crop biopsy results also depend on the presence of segmental disease in the tiny piece of tissue collected. Additionally most birds without gastrointestinal signs are almost always negative via crop biopsy.
Current recommendation: A combination of cloacal or feather RT-PCR with a serologic assay may offer the best chance of identifying ABV infection.Birds with a high ABV load via PCR combined with high antibody titers appear to have the highest risk of developing clinical disease (Heffels-Redmann 2012), however there is there is no one combination of tests that can be used to reliably predict the progression from ABV exposure and shedding to clinical disease at this time. Multiple tests must be performed before a bird can be considered ABV negative. Ideally three negative PCR test results are needed for a bird to be considered negative.
Table 2.Laboratories in the United States that perform avian bornavirus diagnostic testing
PCRSerology
Avian BiotechXX
The Schubot CenterX
Veterinary Molecular DiagnosticsX


Figure 3.Profound emaciation in a cockatoo with neuropathic ganglioneuritis. Photo credit:Dr. Isabelle Langlois.Click image to enlarge.
Histopathologically there may be a lymphoplasmacytic ganglioneuritis involving the brain, spinal cord, peripheral nerves, splanchnic nerves, heart, and adrenal gland. In some instances, lesions can also be detected in the lungs or kidneys. Lesions may only be present in the brain and spinal cord in some neurologic cases.
Avian bornavirus can consistently be detected by PCR analysis in the tissues of birds that die of neuropathic ganglioneuritis. The virus may be found in all major organs or may be limited to the brain, spinal cord, and peripheral nerves. The vitreous humor can also be a source of ABV, even in apparently healthy carrier birds (Hoppes 2013).
 
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