Bird and Exotic Pet Wellness Center

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Toledo, OH 43623

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PDD Update

A Note of Clarification on PDD

Susan E. Orosz, PhD, DVM, DABVP (Avian), DECZM (Avian) 

There has been discussion on some avian boards about PDD and avian bornavirus and, in particular, there may be some confusion about how contagious this disease is to our beloved birds. We are all learning together as new advances come to light. Almost 30 years ago, the condition of wasting in macaws from dilation of the proventriculus of the stomach was first described. At that time, the disease had a low incidence but if one bird showed symptoms of disease, it then appeared to spread through its flock.

Until recently, clinicians, researchers and pathologists could only make the diagnosis based on dilation of the proventriculus and a biopsy of the crop that showed a lymphocytic, plasmacytic ganglioneuritis. Clinical signs observed are variable and depend upon the competency of the immune system of the avian patient and the severity and distribution of lesions. The most common clinical signs observed are depression, anorexia, loss of body condition, regurgitation, and the passage of undigested food in the feces and these classic symptoms are associated more with New World species of psittacines.

But with the advent of new PCR technologies, our view of this disease and its suspected viral culprit is changing at a fast pace. At this point in time, it appears that avian bornavirus (ABV) is most likely the causative agent of PDD. With the development of PCR primers to test for this agent, we will understand where it locates in the body, how it may be transmitted, and the routes of infection. All this information will help us determine how contagious it is to our birds.

In a survey of 39 healthy parrots, M. Lierz from the Free University of Berlin detected ABV in 27 (45.8%) of the birds based upon blood sample testing. Data from Veterinary Molecular Diagnostic lab suggests that the rate is about 30% of birds (both healthy and ill) that they have tested. This compares favorably with the observed infection rates of Borna Disease Virus (BDV) in mammalian species. This information suggests that we need to form a much different view of PDD—the old view of a disease of low incidence but severe clinical manifestations is outdated. Current research suggests an infection of much greater frequency with a low incidence of clinical disease and a much lower incidence of severe disease.

Such a view of Avian Borna virus (ABV) compares favorably with that of BDV. The infection rate for Borna Disease virus (BDV) in mammals is reported to be >30%. In healthy horses in Germany, a mean infection rate of almost 60% was found compared to the significantly lower clinical disease case rate of approximately 5%. ABV appears to parallel BDV very closely in this regards. The vast majority of ABV-positive birds DO NOT show clinical disease. A much smaller percentage will show clinical disease, but this is quite variable. We must expand our view of clinical ABV disease to that of a continuum of a wide range of clinical symptoms. Many clinically infected birds show only mild clinical signs of disease. Those with the “classic” severe form of PDD represent the extreme of this continuum and are a small percentage of birds that are clinically diseased. But we all know that we want to avoid this in our beloved birds.

We are unsure of how the disease is spread between birds and I have discussed that birds may become infected while still in the egg. We have also had birds that are positive in a household while their friends in adjoining cages have maintained a negative ABV testing status. We must keep in mind that this is an RNA virus. ABV RNA is very unstable in the environment as it is degraded by naturally occurring RNAase enzymes very rapidly. With an agent that has been ever-present in our aviary population, unrestricted for at least 40+ years, one would expect a much higher rate of infection if it was highly contagious or highly pathogenic. Even in a stressed, confined aviary populations experiencing an acute disease outbreak, only about 50% of the birds tested positive in my experience.

Sometimes there is concern that PDD is spreading through a flock and it is unclear what is meant by this. It may be that one bird with clinical signs has been confirmed with PDD and the others have tested ABV positive. These birds would be positive by PCR testing but be normal in outward appearance. The other situation is that one bird has symptoms and then other birds develop the symptoms as well. In those cases, in what I have seen, the number of birds that show outward signs may be as high as 50%.

While this is a contagious disease, it does not appear to run through a flock of birds killing them all quickly like other viruses we have experienced (example-Pacheco’s Disease Virus). On the other hand if 30% of our birds in this country may be affected, what are we going to do with birds that are up for sale or adoption or fostering? At least some will be both avian bornavirus positive and apparently healthy. I would advocate that we do not euthanize them but think through a rational way to tell potential owners, keep the birds as stress-free as possible, and provide quality nutrition to keep them immune-competent. Not every avian bornavirus-positive bird will develop clinical disease or die from PDD, most do not. And by better understanding this disease process, we may be able to eliminate it from our birds.

As we all work together to understand this disease, we will develop better protocols to help our avian friends lead healthful lives. This is what I am seeing now clinically with the birds in our area and I encourage all of us in this dialogue to find a true path of understanding. Our birds deserve this from all of us.

 

Insight ON PDD

The European Association of Avian Veterinarians hosted an exciting research forum and question and answer period from speakers concerning PDD during their Congress March 17-21 in Antwerp, Belgium. Following is a brief review of the disease, along with new developments, as noted in papers from that meeting. Proventricular Dilitation Disease (PDD)

PDD stands for proventricular dilitation disease, and refers to one of the characteristics of this disease, an enlargement of the first part of the bird’s stomach, the proventriculus. In PDD, the proventriculus is thin-walled and “flabby,” and is unable to digest food or move it properly along.

Ventrodorsal radiograph showing barium in an enlarged crop and a very dilated stomach.  

This disease was first described in macaws and was called macaw wasting disease or syndrome. These birds had wasting of the muscle mass over the pectoral region, or “chest,” with the proventriculus dilating (enlarging) as the disease progressed. The proventricular wall thinned as well. Fluoroscopic studies using barium have shown that the normal mixing pattern of food is greatly altered, so that the food is not digested or absorbed properly. Since the original description of the disease in macaws, other parrot species have been seen to be affected. Symptoms often vary between species.

The pectoral mass is dramatically reduced in this macaw. This is due to the altered mixing combined with reduced absorption of nutrients in birds with PDD so that the patient uses the muscle mass for its energy source. These changes in motility and mixing result from the accumulation of lymphocytes and plasma cells in the nerve cell bodies in the wall of the intestines.  

Diagnosis of the disease has been hampered because the true cause or causes of the disease are not known. In addition, clear evidence of the disease, found in biopsy samples or tissue samples from deceased birds, is found at the end stage of the disease. At this stage, plasma cells and lymphocytes may invade the area around nerve cell bodies or ganglia in the wall of the first part of the gastrointestinal tract—from the crop to the stomach and duodenum. These cells can also invade parts of the brain, resulting in a condition called non-suppurative encephalitis (inflammation of the brain). It appears that the accumulation of these lymphocyte and plasma cells around nerves and their cell bodies alters the gastrointestinal tract’s function and/or causes problems with the brain, depending on where these cells localize.

 

This is a microscopic view of a ganglion (a collection of nerve cells in the lining of the GI tract) with an infiltrate of lymphocytes and plasma cells. These criteria are needed for the pathologist to make a diagnosis of PDD.  Research into the Causes of PDD

Recent studies have attempted to determine if an elusive virus may be causing the accumulation of these cells. Studies of macaw chicks in the early 1990s by Drs. Richard Gough and Nigel Harcourt-Brown in the UK found some viral “ghosts” in the feces of ill birds. At Veterinary Molecular Diagnostics (VMD) in Ohio, Dr. Bob Dahlhausen has been using a viral sequence he obtained from birds with confirmed PDD for testing over the past 3 years. He, like others from Europe and the U.S., found that the virus did not live long outside the bird. Ongoing studies in his facility have suggested several possible strains of this RNA virus suspected to cause PDD.

Using a panviral microarray assay, viral RNA was extracted in several PDD positive birds to determine the genetic “fingerprint” of a possible virus. Sequencing suggested that a divergent Bornavirus was the culprit. These results from Dr. DeRisi’s lab at UC San Francisco were published in July of 2008. Similar results were found by a group at Columbia University.

Researchers meeting in Belgium have been busy isolating virus particles, growing them in culture media and trying to reinfect birds to see if they develop clinical symptoms with the same histopathologic results of lymphocytic, plasmocytic ganglioneuritis with or without non-suppurative encephalitis. In short, can they use a particular virus to cause the same tell-tale signs of PDD? Researchers from Berlin (Dr. Michael Lierz), Munich (Dr. Rinder), and Texas A & M University (Drs. Hopes and Enderbein) have been attempting virus isolation, tissue culture, and recovery with a variety of diagnostic approaches.

However, a very interesting proposal was presented by Dr. Rossi’s group from the University of Camerino, Italy. His research has taken an entirely different approach to investigating this syndrome, focusing on the response of the brain to viral infection. His research suggests that viruses with similar action can result in a similar clinical effect. It is not the particular virus, but the action caused by the virus that produces the symptoms of PDD. Dr. Rossi’s studies suggest that there is an accumulation of a specific ganglioside protein in the cell bodies of the vagus nerve—the one that controls movement of the proximal GI tract. These ganglioside proteins can also accumulate in other portions of the brain. It may be that when these start to accumulate, the lymphocytes attempt to react to these proteins and that further degrades normal neural function. Their work suggests that it is the bird’s own response to the ganglioside proteins that cause the clinical signs. They used just the ganglioside proteins and injected them into several cockatiels. All cockatiels developed the clinical symptoms and histologic features of PDD after 1 month.

In looking at Bornavirus as a possible cause, studies from horses, sheep, and rodents (rats, mice, hamsters, gerbils, rabbits, and guinea pigs) provide clues about the actions of this virus. It has been shown that Bornavirus can persist without apparent disease in horses, cats, and sheep in Europe. This may be for birds as well. In the US, studies at VMD show that a number of psittacine birds test positive for the disease, but show no clinical signs. Researchers in Europe suggest the same may be true in psittacine birds there as well.

Data in the infection of adult rats suggest that viremia and fecal shedding do not play a significant role in spreading the disease. In other words, Bornavirus in rats is rarely spread in feces. However it is spread, Bornavirus appears to move rapidly to nerve terminals where the viral particles can move up the axons of the nerves. The accumulation of the particles may cause accumulation of these specific ganglioside proteins, and hence, the lymphocytes and plasma cells. This may help to explain why celebrex is helpful in many of our avian patients. Celebrex is a selective Cox-2 inhibitor and reduces inflammation in nervous tissue. By reducing inflammation, it may reduce these proteins and the cells that accumulate, helping to reduce symptoms.

PDD’s Effects on Birds 

PDD can be devastating and cause death to the patient, but may cause varying signs that come and go or maybe never occur. Birds may be positive on viral testing but be normal in appearance (asymptomatic) or have occasional bouts. Some birds may show clinical signs but when the crop or stomach is biopsied, the histopathologic findings that must be present to call it PDD are not there.

Many birds with PDD may have diarrhea with undigested food in their droppings. Some may regurgitate hours after eating. These birds may waste over time with reduced pectoral muscle mass and a pronounced keel. This tends to be more common in young macaws and adult Amazons.

Other birds may exhibit neurologic signs—they may appear to seizure but often bob, have trouble placing their feet so appear to move them and their legs stiffly, and revert to baby behaviors. Some birds may go blind. The birds that tend to have neurologic signs are cockatoos and African grey parrots. Eclectus may have GI and/or neurologic signs. But not all birds follow the rules. Never consider euthanizing a bird that appears normal but has a positive test result by PCR. Studies at VMD, the University of California at San Francisco, and Columbia University suggest there are a number of distinct genetic subgroups. These subgroups may affect the nervous system of different species of birds differently, which could explain why the signs vary.

Conclusion

There is still much to be learned to understand the origin of this disease. With that information, diagnostic and treatment options may be gained to improve the health of our wonderful psittacine birds.

At The Bird & Exotic Pet Wellness Center, Dr. Orosz has been involved with understanding, diagnosing and treating this disease since it was first described. She started her veterinary career at a veterinary hospital in California, which was one of the first to describe the disease. She has been working with Dr. Dahlhausen at VMD to further understand this disease, characterize the suspected Bornavirus link to the symptoms, and help improve diagnostics.

Dr Dahlhausen has devoted a large amount of time and effort as an avian veterinarian and researcher to characterize the disease. Samples can be sent to his lab, Veterinary Molecular Diagnostics through your veterinarian or by us at The Bird and Exotic Pet Wellness Center.  From a therapeutic point of view, Dr Dahlhausen was the first to use Celebrex as one of the treatment modalities. We have been working together to develop effective therapies for psittacine birds and to help our clients better understand this disease. Appointments and phone consultations can be made by calling The Bird and Exotic Pet Wellness Center at 419.843.3137.

 

Copyright, Susan E. Orosz, 2009