Almost 30 years ago, macaw owners and their veterinarians saw a new disease in their pet birds, with muscle wasting and regurgitation. The disease also caused dilation of the proventriculus of the stomach, and the disease became known by the name PDD, or proventricular dilatation disease. While the cause of this disease was unknown, it was suspected to be a virus. Until recently, clinicians, researchers and pathologists could only make the diagnosis of PDD based on dilation of the proventriculus and a biopsy of the crop or pathology slides that showed a lymphocytic, plasmacytic ganglioneuritis.
Clinical signs observed are variable and depend upon the competency of the individual bird’s immune system. The most common clinical signs observed are depression, anorexia, loss of body condition, regurgitation, and the passage of undigested food in the feces. These classic symptoms are more commonly associated with New World species of parrots (Amazons, macaws, conures, Pionus, parrotlets, etc).
But with the advent of PCR technology, our view of this disease and its suspected viral culprit is changing. At this point, it appears that avian bornavirus (ABV) is most likely the causative virus that results in the symptoms of PDD.
Avian Bornavirus & PDD
In a survey of 39 healthy parrots, Dr. Michael Lierz Dipl ECZM (Wildlife Animal Health), Justus, Liebig University, Gissen, Germany, detected ABV in 27 of the birds (45.8%) based upon blood sample testing. Data from Veterinary Molecular Diagnostics (VMD, Inc, in Milford, Ohio) 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. (Bornaviruses are widespread and affect both birds and mammals.)
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to form a much different view of PDD — the old view of a disease of low incidence but severe clinical manifestations is outdated.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. In other words, it appears that many parrots have the virus, but only a small percentage exhibit serious disease.
Such a view of Avian Bornavirus (ABV) compares favorably with that of BDV. The infection rate for Borna Disease virus (BDV) in mammals is reported to be less than 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 regard. 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.
Research into the Role of Avian Bornavirus & PDD
There are a number of studies currently looking at Avian Bornavirus, but I think that the most exciting is that from Giacomo Rossi, DVM, Ph.D. Recent studies from Dr. Rossi’s lab at Camerino University, Italy, help us understand the mechanism of the disease. One of the troubling aspects to the data to date is that some birds are positive for the virus on PCR analysis but do not show symptoms. Only a smaller number of birds that have the virus on PCR analysis have symptoms. How could this be? At the 2009 European Association of Avian Veterinarians conference in Belgium, Drs. Rossi and Stefano Pesaro, DVM, PhD, presented a study indicating that cockatiels could show the same symptoms of PDD if injected only with proteins from the birds’ own nerves, not the bornavirus.
In their subsequent studies, Drs. Rossi and Pesaro observed under an electron microscope that macrophages attacked nerves that had become infected with virus and there was leakage of proteins- ganglioside proteins from these damaged nerves. This caused an auto-immune reaction – the macrophages were attacking their body’s own nerves. This reaction and inflammation that resulted from this immune attack produced the symptoms of the disease. The exact symptoms were a consequence of the parts of the central nervous system that was invaded by the virus with its subsequent leakage of the ganglioside proteins.
As a neuroanatomist, I understood that this was a neurologic disease because I observed a large number of bird patients over the years with PDD. From my observations, I knew that New World bird species most commonly have symptoms affected by the disruption of innervation to one of the cranial nerves of the brainstem – the vagus nerve. The vagus nerve supplies the first part of the intestinal tract – from the crop, stomach including the proventriculus to the duodenum, and the heart. When the vagus nerve did not work properly, there was disruption of the normal motility of the GI tract and a thinning of the wall of the GI tract.
Old World species (African greys, cockatoos, cockatiels, Eclectus, etc.) normally have symptoms of ataxia that mimic seizures to the untrained eye. They have a different part of the brain affected! But all of the nerves or the cell bodies in the brain, when affected, have the invasion of lymphocytes. Those collections of lymphocytes are what the pathologist is looking for under the microscope to make the diagnosis of PDD. This “lymphocytic ganglioneuritis” is the hallmark of PDD.
However, according to Dr Rossi’s lab group, these lymphocytes go there because of the leakage of those ganglioside proteins! That sets up an autoimmune reaction and immune complexes. It is not the virus but the leakage of the proteins from these immune complexes that causes the symptoms. The celebrex often used to treat the symptoms of the disease acts to reduce this autoimmune reaction and helps reduce symptoms. But some birds improve while others do not! This may relate to the immune system of the individual patient and the autoimmune reaction—just like in people who get Guillain Barré Syndrome, a disorder affecting the peripheral nervous system. So, by better understanding this autoimmune reaction, new strategies for treatment can emerge and provide hope to manage this syndrome better.
As we all work together to understand this disease, we will develop better protocols to help our avian friends lead healthful lives. Our birds deserve this from all of us.