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Back to Journal »Veterinary Medicine: Research and Reports» Volume 10
The pathology of cockatiels experimentally infected with Bornavirus-2 with non-steroidal anti-inflammatory drugs failed to improve
Author Escandon P, Heatley JJ, Tizard I, Guo J, Shivaprasad HL, Musser JMB
Published on November 22, 2019, the 2019 volume: 10 pages 185-195
DOI https://doi.org/10.2147/VMRR.S229936
Single anonymous peer review
Editor approved for publication: Professor Young Lyoo
Paulina Escandon,1,2 J Jill Heatley,1,3 Ian Tizard,1,2 Jianhua Guo,1,2 HL Shivaprasad,4 Jeffrey MB Musser1,2 1Schubot Exotic Bird Health Center, College of Veterinary Medicine, Texas A&M University, College Station, TX 77843, USA; 2Department of Veterinary Pathobiology, College of Veterinary Medicine, Texas A&M University, Texas 77743, USA; 3Department of Small Animal Clinical Sciences, College of Veterinary Medicine, Texas A&M University, Texas, USA State University City 77743; 4 California Animal Health and Food Safety Laboratory System-Tulare, University of California, Tulare, USA 7743, USA Phone +1 979 458 9946 Fax +1 979 458 0321 Email [email protected ] Purpose: Psittacine Bonavirus is the pathogen of Psittacine Bonavirus syndrome, also known as and includes preventricular dilatation disease or PDD, macaw wasting disease, enteric ganglion neuritis and encephalitis, and avian ganglion neuritis. It has been suggested that non-steroidal anti-inflammatory drugs may be able to improve this disease. Therefore, this study investigated the effects of two commonly used non-steroidal anti-inflammatory drugs, celecoxib and meloxicam, on cockatiels experimentally inoculated with Parrot Bornavirus-2 (PaBV-2). Materials and methods: 27 cockatiels were randomly divided into 3 groups, 9 birds in each group, and matched according to historical PaBV shedding, weight and gender. Cockatiels are inoculated with cell culture-derived PaBV-2 through intranasal and intramuscular routes. Starting 23 days after vaccination, the chickens in each group received oral placebo, meloxicam (1.0 mg/kg) or celecoxib (10.0 mg/kg) once a day. Results: Within 33-79 days after vaccination, 2 chickens died and 6 chickens were euthanized based on neurological or gastrointestinal signs consistent with psittacine Bonavirus syndrome: 2 chickens in the placebo group and 1 chicken in the placebo group The chicken died and 1 chicken was euthanized. One bird died in the meloxicam treatment group, and 3 birds in the celecoxib treatment group were euthanized. Among the 8 chickens, 2 chickens in the meloxicam treatment group and 2 chickens in the celecoxib treatment group found black intestinal contents at autopsy. On the 173rd (±2) day after vaccination, the remaining 19 birds were euthanized. Autopsy and histopathology revealed that 23 cockatiels had characteristic lesions of psittaci-Bonavirus syndrome. All three groups of birds had histopathological lesions. RT-PCR and immunohistochemistry were used to detect PaBV RNA and PaBV nucleoprotein. There was no statistical difference between the groups, and there was no statistical difference between the three treatment groups. Conclusion: Treatment with meloxicam and celecoxib does not seem to change clinical manifestations, virus shedding, gross lesions, histopathology, or virus distribution. Treatment with non-steroidal anti-inflammatory drugs may cause gastrointestinal toxicity in cockatiels experimentally inoculated with PaBV-2. Keywords: meloxicam, celebrex, ventricular dilatation, psittacine Bonavirus syndrome, avian Bonavirus
Parrot Bornaviruses 1–8 (PaBV-1-8) is a pathogen that causes progressively fatal avian nervous system syndrome, called Parrot Bornavirus syndrome, which is a complex clinical problem that may include anterior ventricular dilatation disease or PDD, Macaw wasting disease, enteric ganglion neuritis and encephalitis, avian ganglion neuritis or neurological dysfunction. 1-5 Parrot Bona Virus Syndrome mainly affects captive birds of the psittacidae and cactus families, such as cockatoos, cockatiels, lovebirds, conures, parakeets (except parrots), especially macaws , But it has also been diagnosed in more than 80 species of birds. 6-8 After infection, the tissues of the virus are widely distributed. Parrot Bornavirus and viral RNA are detected in the brain, eyes, retinal nerves, spinal cord, heart, adrenal glands, kidneys and intestines. 9,10 The disease is characterized by infection of the central and peripheral nervous system and other organs with PaBV, which leads to lymphoplasmacytic infiltration of these tissues, and ultimately leads to neurological diseases and gastrointestinal dysfunction. 8-14
There is currently no effective treatment for PaBV infection or Parrot Bornavirus syndrome. Experimentally, IFN-α inhibited viral infection and reduced the viral load in quail cell culture15, while ribavirin inhibited transcription and reduced the viral load in cultured duck embryo fibroblasts. 16,17 Symptomatic treatment and management is currently the only recommended treatment for psittaci Bonavirus syndrome7. ,18 According to the clinical and pathological signs of PaBV infection, the disease may be caused by an inflammatory response to the virus in the brain, nerves and other tissues. 10-12 Therefore, non-steroidal anti-inflammatory drugs (NSAIDs) and immunosuppressants can inhibit or reduce inflammation caused by PaBV infection and reduce the severity of clinical diseases. 7,18
It has been reported that the use of non-steroidal anti-inflammatory drugs can reduce the severity of clinical symptoms in birds affected by PDD. 7 Celecoxib and meloxicam are non-steroidal anti-inflammatory drugs commonly used for symptomatic treatment of birds diagnosed with psittacine Bonavirus syndrome. 18-21 However, meloxicam did not reduce the severity of clinical symptoms. Signs of cockatiels experimentally infected with PaBV-4 may actually exacerbate the progression of the disease. twenty two
Due to differences in the reported results, controlled studies on the effectiveness of NSAIDs are limited, and there is a lack of studies comparing celecoxib and meloxicam in the treatment of PaBV-infected birds. Therefore, the purpose of this study is to evaluate celecoxib and meloxicam The effect of treatment on clinical symptoms, viral shedding and pathology in cockatiels infected with PaBV-2. We hypothesize that taking NSAIDs will reduce the severity of illness in infected cockatiels.
PaBV-2 was isolated from the brain of an experimentally infected cockatiel (Nymphicus hollandicus). 14 The growth of the virus used for vaccination is as described above. 23 In short, duck embryo fibroblast cell culture was inoculated with the stock virus and maintained in Dulbecco's modified Eagle medium (Gibco®, Life Technologies Co., Thermo Fisher Scientific, Waltham, MA, USA) and 10% embryonic fibroblasts. Bovine serum (Gibco®, Life Technologies Co) in an atmosphere of 37°C and 5% CO2. After 3 days of incubation, the cells were harvested, divided into 1.0 mL aliquots, and stored at -80°C. As described below, through RNA extraction and RT-PCR analysis, and then sequence analysis of the PCR products, it is confirmed that the virus is PaBV-2. A combined intranasal and intramuscular administration of infected cells containing 8 × 104 viral foci forming units was used to inoculate birds.
Three meloxicam 15.0 mg tablets (Lupin, Pharmaceuticals, Inc. Baltimore, MD, USA) were crushed by using a mortar and pestle, and the powder was dissolved in 1 mL of deionized water to produce a concentration of 1.0 mg/ mL of a suspension of meloxicam. Add 10 ml of Ora-Plus (Perrigro® Co., Dublin, Ireland) suspension carrier, and then add Ora-Sweet (Perrigro® Co.) to the suspension to obtain a final volume of 45.0 mL. The contents of 9 celecoxib 50.0 mg capsules (Pfizer Inc., Mission, KS, USA) were added to 1.0 mL deionized water to prepare a suspension containing 10.0 mg/mL celecoxib. Add 10 ml of Ora-Plus suspension carrier, then add Ora-Sweet to the suspension, the final volume is 45.0 mL. All solutions are stored at 4ºC and freshly prepared every 30 days. Before administration, all solutions were warmed to room temperature.
Twenty-seven cockatiels (Nymphicus hollandicus) were used, with weights ranging from 79 to 145 grams (101 grams on average). The chickens are evaluated as healthy by physical examination and medical history. These cockatiels were quarantined for 60 days. During this period, each parrot received 3 tests for psittaci (genotype 1-4) and chlamydia within 4 weeks. And Macrorhabdus ornithogaster (poultry stomach yeast). Birds need all tests to be negative to be included in the study. In the aviary of the Schubot Exotic Bird Health Center of Texas A&M University, 14 or 13 cockatiels are housed in each cage. The light-dark cycle is 12 hours and the room temperature is 23.3 (±5.0)°C. Each chicken is fed 1/6 cups of high-quality FruitBlend (ZuPreem®, Shawnee, KS, USA) with natural fruit flavor every day, and can drink tap water at will. The animal use protocol that details the experimental protocol is reviewed and approved by the Texas A&M University Research Compliance Office and complies with the guidelines contained in the 8th edition of the "Guidelines for the Care and Use of Laboratory Animals" published by the National Academy of Sciences.
The poultry were matched according to the history of PaBV shedding, weight and sex, and were randomly divided into three groups, each with 9 birds: the first group of poultry (placebo) was vaccinated with PaBV-2, and oral treatment was started 23 days after the inoculation. Once a day, use only the delivery solution (water, Ora-plus and Ora-Sweet). Birds in group 2 (treated with meloxicam) were inoculated with PaBV-2, and oral treatment was started 23 days after inoculation, with 1.0 mg/kg meloxicam once a day. Group 3 birds (treated with celecoxib) were inoculated with PaBV-2, and oral treatment was started 23 days after vaccination, with 10.0 mg/kg celecoxib once a day. All treatments were performed before eating in the morning. Recalculate the dosage after weighing each week. The medication administrator/evaluator, laboratory technicians, and pathologists did not know the medications given to each group until the study was completed.
Observe the bird’s clinical symptoms and deviations from normal behavior every day: these include fluffy feathers, bowed heads, too quiet, almond-shaped eyes, overeating, lethargy, and reluctance to fly. Before vaccination, cloaca swabs were collected twice; body weight and physical condition score (BCS) assessed once. After virus inoculation, chickens are weighed and BCS is evaluated every week; cloaca swabs are collected every three weeks and stored at -80ºC until they are detected by RT-PCR. The physical condition score is determined by evaluating the keel and pectoral muscle area. The body condition score ranges from 1 to 5, from thin to obese. 24 If a bird meets the following predetermined criteria, it is withdrawn from the study and euthanized: weight loss> 20% of initial body weight; BCS is 1; or as recommended by the attending veterinarian.
On day 173 (±2) after experimental inoculation [Day 150 (±2) of NSAID treatment or placebo treatment], the surviving birds were anesthetized with 5% isoflurane and 100% oxygen; body weight, BCS, Cloaca swabs and urine. Urine was collected as previously described by Heatley et al. 25 After collecting the samples while the birds were still under deep anesthesia, they were killed humanely through a chamber exposed to 100% CO2. Perform a complete autopsy immediately and record the gross lesions. Paired samples of heart, liver, feather pouch, spleen, crop, stomach, ventricle, intestine, gonad, pancreas, adrenal gland, kidney, lung, spinal cord, brain, eye, aqueous humor, optic nerve, brachial plexus and sciatic nerve are collected and stored in -80ºC for later analysis by RT-PCR. The rest of each organ is placed in 10% neutral buffered formalin for histological examination and immunohistochemistry (IHC) testing.
As mentioned earlier, RT-PCR was used to detect the presence of viral RNA in tissues, urine, and cloaca swabs. 23 All samples were repeatedly tested for matrix protein and phosphoprotein. Samples with a circulation threshold (CT) ≥ 37.0 are considered negative. If the sample is positive for only one of the two proteins, the sample is retested. Use sequence detection system, version 2.4.1 (SDS 2.4) software (Life Technologies, Thermo Fisher, Carlsbad, CA, USA) to analyze the results.
The tissue samples were fixed in 10% neutral buffered formalin, processed overnight, embedded in paraffin, 4 µm sections, stained with hematoxylin and eosin (H & E), and inspected by light microscopy according to standard procedures. Immunohistochemical analysis of the tissue obtained by autopsy was carried out according to the previously described method to prove the presence of PaBV nucleoprotein. 26 The reviewing pathologist used the following sequential scales to perform semi-quantitative virus scores on tissue samples: not detected (-), detected a small amount (+), detected a moderate amount (++), detected a large amount (+++) .
The Gehan-Breslow method was used to analyze the difference in survival between treatment groups. Two-way repeated measures analysis of variance (ANOVA) was used to compare weight changes between treatment groups and days over the course of the experiment. Kruskal-Wallis one-way analysis of variance was used to determine the difference between histological findings and IHC results. AP ≤ 0.05 is considered statistically significant. Sigma Plot version 10.0.1 is used to perform all statistical analysis (Systat Software, Inc., San Jose, CA, USA).
There was no significant difference in survival rates between the 3 study groups (Figure 1). In the placebo group (group 1), 2 out of 9 chickens were euthanized at 54 days and 61 days after vaccination before the end of the study. In the meloxicam treatment group (group 2), 2 out of 9 chickens were euthanized or found dead 33 days and 79 days after vaccination. In the celecoxib treatment group (group 3), 4 out of 9 chickens were euthanized or found dead at 37, 43, 45 and 74 days after vaccination. Among the 8 chickens that died before the completion of the study, 2 were found dead, one in each of the meloxicam and celecoxib treatment groups, and the remaining 6 showed neurological or gastrointestinal symptoms of PaBV infection (Table 1 ). Table 1 Cockatiels who were euthanized or found dead before the end of the study Figure 1 Cockatiels vaccinated with PaBV-2 and treated with placebo, meloxicam (1.0 mg/kg) or celecoxib (10.0 mg/kg) Survival analysis of cockatoos (Nymphicus hollandicus). Note: The Gehan-Breslow statistics of the survival curve are used to generate the survival analysis. Chickens were experimentally inoculated with PaBV-2 on day 0. On the 23rd day after vaccination (dashed arrow), the chickens were given orally once a day: placebo control group (black solid line), meloxicam (gray dashed line) and celecoxib (gray dashed line).
Table 1 Cockatiels euthanized or found dead before the end of the study
Figure 1 Survival analysis of cockatiels (Nymphicus hollandicus) vaccinated with PaBV-2 and treated with placebo, meloxicam (1.0 mg/kg) or celecoxib (10.0 mg/kg). Note: The Gehan-Breslow statistics of the survival curve are used to generate the survival analysis. Chickens were experimentally inoculated with PaBV-2 on day 0. On the 23rd day after vaccination (dashed arrow), the chickens were given orally once a day: placebo control group (black solid line), meloxicam (gray dashed line) and celecoxib (gray dashed line).
During the entire study period, there were no significant differences in body weight between the study groups. In each treatment group, significant daily differences in body weight were noted. On the 7th day after treatment with or without NSAID, all groups lost weight. Between day 7 and day 47, the body weight of the NSAID treatment group was significantly lower than the body weight before vaccination or before the start of NSAID treatment; however, from 54 days after treatment to the end of the study, their weight before vaccination or treatment was not significant. The difference. During the study period, there were no significant differences in physical condition scores between or within groups.
Most birds that died prematurely or were euthanized tended to lose weight and BCS during the study. One bird in the meloxicam group is an exception. At the time of euthanasia, this bird gained a lot of weight compared to other birds, but had a lower BCS. The autopsy results showed that the crops were highly expanded and the glandular stomach was full of feed, which was probably the cause of the weight gain (Figure 2B). Figure 2 Gross autopsy results of cockatiels (Nymphicus hollandicus) vaccinated with PaBV-2 and treated with placebo, meloxicam (1.0 mg/kg) or celecoxib (10.0 mg/kg). (A) Bird 15, Meloxicam treatment group: Euthanasia was performed on the 173rd day after vaccination. The glandular stomach is moderately dilated (yellow arrow). (B) Bird 21, celecoxib treatment group: euthanized on the 45th day after vaccination. The stomach is slightly dilated (yellow arrow), and there are undigested seeds in the intestine (gray arrow). (C) 22 birds, celecoxib treatment group: euthanized on the 74th day after vaccination. The crop is severely expanded (red arrow), the proventriculus is slightly expanded (yellow arrow), and the intestinal contents turn black (gray arrow).
Figure 2 Gross autopsy results of cockatiels (Nymphicus hollandicus) vaccinated with PaBV-2 and treated with placebo, meloxicam (1.0 mg/kg) or celecoxib (10.0 mg/kg). (A) Bird 15, Meloxicam treatment group: Euthanasia was performed on the 173rd day after vaccination. The glandular stomach is moderately dilated (yellow arrow). (B) Bird 21, celecoxib treatment group: euthanized on the 45th day after vaccination. The stomach is slightly dilated (yellow arrow), and there are undigested seeds in the intestine (gray arrow). (C) 22 birds, celecoxib treatment group: euthanized on the 74th day after vaccination. The crop is severely expanded (red arrow), the proventriculus is slightly expanded (yellow arrow), and the intestinal contents turn black (gray arrow).
The results of viral RNA detection in cloacal swab samples are summarized in Table 2. Before experimental vaccination, cloaca swabs of all birds tested negative for viral RNA, except for one cockatiel that tested positive for cloacal swabs on day -17. I was vaccinated, but was negative on days -31, 13 and 20 after vaccination. PaBV shedding was detected for the first time 42 days after inoculation in groups 2 and 3. At the end of the study, all birds that had not died or were prematurely euthanized due to humanitarian considerations had positive cloacal swabs, except for one bird in group 2, which was negative for the entire study period. By the end of the study, the cumulative number of chickens with positive cloacal swabs in groups 1, 2 and 3 were 8/9, 6/9, and 7/9, respectively. Table 2 Detection of viral RNA in cloaca samples from cockatiels (Nymphicus hollandicus) treated with PaBV-2 and placebo, meloxicam (1.0 mg/kg) or celecoxib (10.0 mg/kg)
Table 2 Detection of viral RNA in cloaca samples from cockatiels (Nymphicus hollandicus) treated with PaBV-2 and placebo, meloxicam (1.0 mg/kg) or celecoxib (10.0 mg/kg)
At the end of the study, viral RNA was detected in the midbrain, hindbrain, cerebellum, forebrain, kidney, and urine of all surviving birds, except for one. There was no significant difference in the amount of detectable viral RNA between the treatment groups.
The main abnormalities observed at the autopsy were the expansion of the crop and the glandular stomach and the thinning of the enlarged and dilated heart wall (Figure 2A-C). However, these abnormalities are not always present, nor are they of consistent severity. Birds that were euthanized or died early in the study had more significant crop and anterior chamber expansion than birds that survived to the 173rd (±2) day after inoculation. Two chickens in group 2 and two chickens in group 3 showed black intestinal contents; these 4 birds were euthanized before the end of the study (Figure 2B and C). Occasionally other abnormalities, such as liver mottled, enlarged spleen, mild intestinal flatulence, and pale pancreas, did not have any group preference. Histopathological changes occurred in many tissues, but there were no significant differences in the severity of the lesions based on the group (Table 3). Observed pathological changes include: lymphoplasmacytic myenteric ganglion neuritis in crops, stomach, ventricle and intestine; multifocal dilatation/interstitial inflammation of renal tubules, fibrosis and/or mineralization, and scattered lymph node formation ; Lymphoplasma cell infiltration in the epicardium, myocardium and/or Purkinje cells of the heart; and lymphoplasmacytic perivascular cuffs in the central nervous system (Figure 3). Although uncommon, histopathological changes have also been observed in the liver, pancreas, lung, spleen, optic nerve, and adrenal glands. Table 3 Distribution of histological lesions in cockatiels (Nymphicus hollandicus) treated with PaBV-2 and placebo, meloxicam (1.0 mg/kg) or celecoxib (10.0 mg/kg) Figure 3 Xuanfeng inoculation The histology of the parrot (Nymphicus hollandicus) found that PaBV-2 was treated with placebo, meloxicam (1.0 mg/kg) or celecoxib (10.0 mg/kg). (A) Lymph plasma cell infiltration of crop serosa ganglia. Three birds, placebo, were euthanized 173 (±2) days after vaccination. (B) Moderate lymphoplasmic cell infiltration in the subserosa ganglia of the proventriculus. Nine birds, placebo, were euthanized 173 (±2) days after vaccination. (C) Moderate lymphoplasma cell infiltration in the subserosa ganglia of the ventricle. Bird 17, treated with meloxicam, euthanized 173 (±2) after inoculation. (D) Infiltration of lymphocytes in the renal interstitium, forming lymph nodes. Three birds, placebo, were euthanized 173 (±2) days after vaccination. (E) The lymphoplasmacytic infiltration of the epicardial ganglion of the heart. Twenty-five birds were treated with celecoxib and euthanized 173 (±2) days after vaccination.
Table 3 Distribution of histological lesions in cockatiels (Nymphicus hollandicus) treated with PaBV-2 and placebo, meloxicam (1.0 mg/kg) or celecoxib (10.0 mg/kg)
Figure 3 Histological findings of cockatiels (Nymphicus hollandicus) inoculated with PaBV-2 and treated with placebo, meloxicam (1.0 mg/kg) or celecoxib (10.0 mg/kg). (A) Lymph plasma cell infiltration of crop serosa ganglia. Three birds, placebo, were euthanized 173 (±2) days after vaccination. (B) Moderate lymphoplasmic cell infiltration in the subserosa ganglia of the proventriculus. Nine birds, placebo, were euthanized 173 (±2) days after vaccination. (C) Moderate lymphoplasma cell infiltration in the subserosa ganglia of the ventricle. Bird 17, treated with meloxicam, euthanized 173 (±2) after inoculation. (D) Infiltration of lymphocytes in the renal interstitium, forming lymph nodes. Three birds, placebo, were euthanized 173 (±2) days after vaccination. (E) The lymphoplasmacytic infiltration of the epicardial ganglion of the heart. Twenty-five birds were treated with celecoxib and euthanized 173 (±2) days after vaccination.
There was no statistical difference in the distribution or number of viral nucleoproteins among the three groups (Table 4). The virus (PABV-2) is mainly detected in the brain, heart, gastrointestinal tract and kidney, but also detected in the liver, pancreas, lung, spleen, adrenal optic nerve, caudal urinary gland, cloaca, gonad and skin/feather follicles . Skeletal muscle is the only tissue that is consistently negative for the virus. No virus was detected in any tissue of 4 chickens: 1 in group 1, 2 in group 2, and 1 in group 3. Table 4 The tissue distribution and relative amount of PaBV nuclear protein (N protein) detected by immunohistochemistry
Table 4 The tissue distribution and relative amount of PaBV nucleoprotein (N protein) detected by immunohistochemistry
Oral meloxicam 1.0 mg/kg or celecoxib 10.0 mg/kg once a day for 150 days. Clinical manifestations, virus shedding, gross lesions, virus distribution and histopathology of cockatiels inoculated with PaBV No difference was shown in any aspect. 2 Compared with untreated poultry. These results are consistent with previously published experimental studies on the use of meloxicam,22 but contradictory to reports on the treatment of clinically affected birds. 19-21 Bird species differences, virus genotype differences, and evaluation standards may be the reasons for the lack of consistency between our research and evaluation standards. Previous clinical case reports.
In this study, the black matter in the intestines of 4 cockatiels treated with NSAID may be autolyzed blood. After 10 to 56 days of NSAID treatment, all 4 cockatiels were euthanized. In a previous study, cockatiels inoculated with PaBV were treated with meloxicam. One bird’s intestine was filled with blood and turned black, while the other bird’s intestine may have black material, which may have been Dissolve blood. 22 In mammals, gastrointestinal abnormalities such as ulcers and bleeding and renal necrosis due to ischemia are the main features of NSAID toxicity; however, these have not been reported as the main side effects of NSAID use in birds. The combined effect of 27-35 PaBV-induced pathological changes and NSAID treatment may aggravate the gastrointestinal irritation and toxicity of NSAID, and may increase the risk of gastrointestinal bleeding.
The use of NSAIDs on birds infected with PaBV will not affect their body weight and BCS. The body weight and BCS of birds that showed severe clinical symptoms and were removed or died early have decreased. This is consistent with gastrointestinal dysfunction that causes chicken hunger. 7,14,22,36 Interestingly, although most chickens infected with PaBV lost weight, one chicken in the meloxicam group gained weight and removed it from the study. During the autopsy, the crops and the glandular stomach were swollen with feed. Presumably, the weight gain is due to the contents of the anterior chamber. This reinforces that poultry body weight should not only be used to assess disease progression or severity.
The survival rate and early removal of birds in the study were not statistically different between the groups; however, compared with the meloxicam treatment group or the placebo group, the celecoxib treatment group showed signs of early removal There are twice as many chickens in clinical conditions (Figure 1). Except that NSAIDs had no significant effect on the overall mortality rate, the cockatiel began to show clinical symptoms and had to be removed early (33-79 days after PaBV vaccination). The time was not affected by NSAID treatment, and was similar to that of birds inoculated with PaBV-2. The time period observed in other studies of the class. 3,9,14,22,36,37
The gross pathology showed no significant differences between the three treatment groups. All groups had clinical manifestations indicative of Bonavirus syndrome, the most typical of which was a dilated stomach, as described in the literature. 3,9,14,22,36,37 NSAID treatment is expected to reduce lesion distribution and tissue inflammation in cockatiels vaccinated with PaBV-2; however, in this study, treatment did not have any significant effect.
The shedding of PaBV-2 is not affected by NSAID administration. In fact, the treated birds tended to fall out earlier than the placebo group, although there was no significant difference. Shedding was first detected on the 42nd day after the inoculation and became more consistent on the 63rd day after the inoculation. This time period corresponds to the previous work in our laboratory. At the end of the study, only one bird did not spread the virus. Previous studies have shown that there is no 100% correlation between histopathology and virus detection between tissues and body fluids. 25,38
Throughout the study, through RT-PCR and IHC, one bird in the meloxicam treatment group was negative for the presence of PaBV. However, at autopsy, its glandular stomach expanded and contained undigested seeds. Histopathology revealed a perivascular cuff, increased glial cells in the brain, and lymph nodes in the ventricular mucosa, ganglia and serosa. The tissues tested by IHC may be negative for viral antigens, but the animals may still have subclinical or asymptomatic infections. 38 Cryptosporidium was found in the stomach of this bird, which may be a factor in some of these lesions. 39
The administration of meloxicam or celecoxib failed to change the clinical symptoms, gross or histopathological changes, viral shedding, or the progression or severity of viral RNA distribution in cockatiels infected with PaBV-2. As it may cause gastrointestinal irritation, bleeding, or other adverse side effects of non-steroidal anti-inflammatory drugs, special care should be taken when prescribing NSAIDs to birds with gastrointestinal dysfunction (such as may occur in PaBV infection).
The author thanks Debra Turner and Dr. Jordan Gentry for technical assistance. Partially supported by Schubot Exotic Bird Health Center. The open access publishing fee for this article was borne by the Texas A&M University Open Access Fund for Knowledge (OAKFund) and supported by the University Library and Office of the Vice President of Research.
All authors declare no conflicts of interest related to the research conducted.
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