The Journal of Applied Rabbit Research
Volume 12, Supplement 1 ( 1989 )

Special Issue devoted to
Viral Hemorrhagic Disease -

A major New Disease Problem of Rabbits

Published by OSU Rabbit Research Center
Oregon State University , Corvallis, Oregon 97331

Special Issue devoted to Viral Hemorrhagic Disease

This special issue of the Journal of Applied Rabbit Research is being presented to outline a very serious potential health problem in rabbits. The disease "viral hemorrhagic disease of rabbits" has already killed millions of rabbits on both the Asian and European continents during the last 4 years, with over 32 million rabbits lost in Italy alone. The disease has spread very rapidly once introduced into a country, suggesting that the domestic rabbit population is very susceptible.

During this period of time the American continent has managed to stay free of the disease, but this changed in just the last 4 months when a single focus of infection occurred near Mexico City in Mexico. From that single focus it has spread to 159 locations in Mexico. Now the great concern is, will it spread to the United States and Canada in North America and into Central and South America? By alerting the rabbit raisers in these countries and their governments to the seriousness of this disease, it is hoped that the disease can be eradicated in Mexico and prevented in those countries in both North and South America that are currently free of the disease. Recommendations to help prevent the entry of the disease into the United States and into your rabbitry are presented at the end of Dr Patton’s paper contained in this issue. Everyone concerned with rabbits should pay particular attention to these recommendations.

The OSU Rabbit Research Centre has contacted both the United States Department of Agriculture, which is responsible for the importation of animals, and the Federal Food and Drug Administration, which is responsible for inspecting foreign meat shipments. Both organisations are studying the situation to determine what should be done. Alerting your own US Congressman to this threat to your livelihood or hobby may be helpful in achieving importation bans before it is too late.

Updates on the situation will be published in future issues of the Journal of Applied Rabbit Research.

Another special issue, containing the proceedings of the Second North American Rabbit Congress, will be published later this year. The Journal is available from OSU Rabbit Research Center at a subscription cost of $15 per year.

This special issue is being distributed free of charge. If you would like additional copies to distribute at club meeting etc. please write to Dr N M Patton, OSU Rabbit Research Center, Oregon State University, Corvallis, OR, 97331, or call Harriet Johnson at 503-745-2263.

Viral Hemorrhagic Disease of Rabbits

N.M.Patton D.V.M., Ph.D.

An extremely serious disease of rabbits occurred in Mexico in the late part of 1988. This disease, called viral hemorrhagic disease of rabbits (VHD) is having a devastating effect on domestic rabbits in that country. Because of the proximity of Mexico to the United States, there is great concern among regulatory agencies in both countries that the disease will spread to the USA. If that should happen, the struggling commercial rabbit industry, backyard rabbitries, and show and pet rabbit raisers may all be adversely affected. A report on VHD in China was presented at the 4th World Congress in Budapest in the fall of 1988. An abstract of the report is found in this special issue.

History of Viral Hemorrhagic Disease of Rabbits

Viral hemorrhagic disease of rabbits was first reported from China (Liu et al.,1984). However, it may have been observed in Germany prior to that time (Loliger, 1988). The disease has now been reported in many European countries as well as several Asian countries. It is difficult to determine the direction of spread as China first saw it in Angora rabbits imported from Germany. Whether they were already infected with the virus or became infected after arriving in China was never determined (Weiyan et al 1988). In addition, there is a great deal of intercontinental movement of both live rabbits and rabbit meat between China and Europe. Thus the original direction of spread may never be known. The result is the same, however, in that both continents have been experiencing the devastating results of this disease in recent years. Interestingly, in Europe it has been a particular problem in small, backyard-type rabbitries.

Viral hemorrhagic disease of rabbits had never been observed or at least reported on the American continent until December, 1988. The first report was in a United States Department of Agriculture field bulletin. It described an outbreak of VHD in Mexico. No one knew how the outbreak started, but it was suspected that the initial virus may have come in with a shipment of frozen rabbit meat from China. Eighteen thousand kilograms of frozen rabbit meat was imported into Mexico and delivered to a supermarket chain just outside of Mexico City. It was speculated that one of the workers handling the meat may have transmitted the virus to his own rabbits which then became the first focus of infection. By the end of February the disease had spread to 159 separate rabbitries in Mexico with one focus only 400 miles from the Texas border. The incidence of the disease by week is as follows:

Date----------------------------------Foci of Infection

December 18-24, 1988------------------------2
December 25-31, 1988------------------------4
January 1-7, 1989------------------------------7
January 8-14, 1989---------------------------17
Jan 15-21, 1989--------------------------------26
Jan 22-28, 1989--------------------------------40
Jan 29-Feb 4, 1989----------------------------32
Feb 5-11, 1989---------------------------------28

Clinical and Pathological Signs

Adult rabbits seem to be most commonly affected with VHD, but it can also be seen in young rabbits older than 8 weeks. There appears to be a wide range of morbidity (those rabbits being affected). It can be as low as 30% or as high as 80%. Of rabbits affected the mortality reaches 95-100%. In other words, if the rabbit gets VHD, it will almost always die. The incubation period is very short, apparently 24-72 hours. The route of entry of the virus into the host has not been completely determined, but it apparently can invade the respiratory tract , the digestive tract or come in through scratches or abrasions in the skin. Experimentally, the virus has produced the disease when introduced orally, intramuscularly or by intraperitonial injection. It has been suggested that the virus can be transmitted by aerosols, direct contact, equipment, in the meat or by-products and possibly by insects or rodents.

There seem to be three forms of the disease: the peracute form is when all that is seen is a dead rabbit in the cage; the acute form of the disease is when the rabbit shows depression, goes off feed, and has difficulty in breathing. This rabbit dies in one to two days and exhibits incoordination, shaking and evidence of pain prior to death. It may also show a mucus blood stained nasal discharge. When the rabbits are first observed, the rectal temperature may increase 2-3 degrees F (normal rectal temperature 103 degrees F). The third form of the disease seems to be much milder. The rabbits appear sick but then recover and are immune to reinfection.

Consistent pathological lesions are found during post mortem examination of affected rabbits . As the name of the disease (viral hemorrhagic disease) suggests, the most commonly observed findings are hemorrhages throughout the body organs (Xu, 1986). The lungs seem to be consistently involved with petechial (pinpoint) to echymotic (bean size) hemorrhages all over their surface. These same hemorrhages may be seen in the bronchi and bronchioles of the lung and in the trachea. The mucus membranes of the nose and throat may also show hemorrhages. Hemorrhages are commonly seen in the liver, kidneys, spleen, heart, lymph nodes and sometimes along the digestive tract. There may also be an encephalitis.

The second major consistent lesion is seen in the liver. The liver is extremely swollen, brownish red in colour and very friable (tissue breaks apart easily). Examination of the liver under a microscope reveals many areas of necrosis (dead cells) and inflammation. Vascular thrombosis (blood clots in the vessels) is also found. The other affected organs are also swollen with gross and microscopic hemorrhages and tissue damage. Intranuclear inclusion bodies are observed in liver, spleen and kidney cells (Maracato et al 1988).

Etiology

The cause of VHD is under intense study by scientists in a number of countries. The agent is apparently a virus. Classification of the virus seems to be difficult, but it apparently is more like a parvovirus than any of the other types, so it is being called parvovirus-like. Parvovirus has been incriminated in the hemorrhagic diarrheal-type disease outbreak in dogs in recent years. A complete discription of the virus is found in a report presented at the 4th World Rabbit Congress (Weiyan et al 1988)

Treatment and Prevention

Viral hemorrhagic disease develops so quickly and kills so rapidly that the treatment does not appear to be practical. Therefore, most efforts are being concentrated on prevention. In Mexico a slaughter and quarantine method of control is being attempted. All rabbitries diagnosed with the disease are quarantined with sale of rabbits prohibited. All rabbits are then killed by government officials and the owner paid endemnity for the rabbits, or given new rabbits 4 weeks later. In China a formalized vaccine has been developed that apparently shows good promise. (Weiyan et al 1988) . The immunity developed after vaccination may be as long as six months. A vaccine, would of course, be very helpful in stopping outbreaks of VHD in countries not experiencing the disease.

Prevention is helped by good sanitation and disinfection procedures. Using a viricidal disinfectant on all equipment both inside and outside the rabbitry seems to be beneficial. Restrictions of visitors or some kind of visitor disinfection procedure may become necessary to prevent entrance of the disease. Certainly the quarantine of rabbits taken to shows or fairs becomes an absolute necessity. A one week quarantine for any returning or newly acquired rabbit would be appropriate as the incubation period seems to be quite short (2-3 days).

Conclusions

Viral hemorrhagic disease is a new, devastating rabbit disease that could have a major impact on rabbits in the United States and Canada. Millions of rabbits worldwide have already succumbed to this disease ( a reported 32 million in Italy alone) and perhaps millions more will be affected if strict measures are not implemented. Immediate consideration should be given to a cessation of importation of all frozen rabbit meat and live rabbits into the United States. Examination of wild rabbits on both sides of the Mexican - American border should be conducted. If this virus enters the wild rabbit population it could easily spread across the border and it may become impossible to eradicate.

Individual rabbit raisers need to examine all sanitation and disinfection procedures to see if they are adequate to prevent the entrance of the disease. Visitors to a rabbitry should be carefully screened as to where they have been recently and their contact with other rabbits. The old adage that “an ounce of prevention is worth a pound of cure” would certainly apply to VHD.

References.

Liu, S.J. et al A new viral disease in rabbits, 1988. Animal Husb. and Vet. Med. 16:253-255 (in Chinese)

Loliger, H.C. 1988. Personal Communications

Marcato, P., C. Benazzi,C.Vecchi and L. Salde, 1988. L’epatite necrotica infettiva del coniglio. Rivisto di Coniglicoltura 25:59-64 (In Italian)

Weiyan, X., D.Nianxing and L.Shengiang. 1988. A new virus isolated from hemorrhagic disease in rabbits. Proceedings 4th World Rabbit Congress, Budapest, Hungary (Pathology Section) pp 456-461

Xu, F.N., W.P.Shen and S.J. Liu, 1988. Study of the pathology of viral hemorrhagic disease in rabbits. Vet. Bulletin 45:5261

L’EPATITE NECROTICA INFETTIVA DEL CONIGLIO

Marcato, C. Benazzi, C. Vecchi, L. Salde, P. Simond, P. Aiello and G. Tumino.

Rivista di Coniglicoltura 25:59-64 (Sept 1988)

(Reviewed By N.M. Patton)

This article, written in Italian, calls the new viral disease attacking rabbits, “infectious necrotic hepatitis of rabbits”. Regardless of the name, the description and excellent photographs illustrate what has been called viral hemorrhagic disease in Mexico and China. The authors illustrate the gross and microscopic features of this disease which has spread throughout Italy. Ultrastructural alterations of damaged liver cells support the viral etiology of the disease. The severe hepatic damage is accompanied by intravascular coagulation . Multiple hemorrhagic foci were found in various organs. Necrosis of the lymphoid tissue, regressive changes of the central nervous system, nephrosis, anemia and leucocytosis were also observed.

The authors were able to transmit the disease to healthy rabbits by inoculating suspensions of liver or lung tissue taken from diseased rabbits. They also mentioned that there were a great number of similarities between the disease seen in Italy and that which has been recently described in China.

A NEW VIRUS ISOLATED FROM HEMORRHAGIC DISEASE IN RABBITS

I. Weigan, D. Nianxing and L. Shengjiang

Proceedings of the 4th World Rabbit Congress (Pathology Section)
Budapest, Hungary , 1988 pp 456-461

(reviewed by N.M. Patton)

This paper deals primarily with the virus that was isolated in the Chinese outbreak of what they call “rabbit hemorrhagic disease”. They report that the disease was first observed in China in 1984 and may have been bought in with a shipment of German Angora rabbits. The disease could not be controlled by various antibiotics or sulfonamides and was therefore suspected to be viral in nature. This suspicion was confirmed by laboratory isolation of the virus. They describe the symptoms and lesions attributed to this disease, but concentrate on the clinical pathology and properties of the virus.

They describe hemagglutination tests and the inhibition of these tests by specific antisera. Suspensions of liver and spleen cells from infected rabbits would agglutinate human red blood cells. The agglutinating activity associated with the virus was destroyed by heating to 50 degrees C or by reducing the ph to 3.0 but the pathogenicity of the virus was not diminished. (in other words it is still infective to rabbits).

The physical properties of the virus were described. It was a nonenveloped, DNA virus with 32 capsomers. It measured 32-34 nanometers in diameter when observed with an electron microscope. It was not denatured by heating and probably belonged to the Parvovirus classification. The authors suggested it be called parvovirus-like.

(The lead author, when presenting this paper in Budapest, talked about a vaccine trial that had recently been conducted in China using a formalin inactivated type of vaccine. The virus was grown on tissue culture prior to inactivation and inocculation into rabbits. He suggested that 1 milllimeter of the vaccine injected subcutaneously produced a protective titer in rabbits in three days. The immune protection had a six month duration).

LETTER TO THE EDITOR

March 6th, 1989 Del Astado de Mexico A.C.

With this letter I would first like to send to you all my regards and to tell you about a recent major problem we are having in Mexico.

During the past three months the rabbit population in six states of Mexico has diminished dramatically by an unknown and very contagious outbreak of disease and until now Mexican Animal Health Authorities have not been able to identify for certain the cause of the problem. They are considering a virus problem and have called the disease “disease X”, “hemorrhagic virus disease” or "Pneumo-hepatic Syndrome" that probably came from imported Chinese frozen rabbits. The American-Mexican Commision to eradicate Aftosa fever and other animal exotic diseases has also intervened but we are still waiting for an answer. In the meantime, the government has established an emergency plan to stop the spread of the disease to other farms and other states of Mexico, mainly by prohibiting the commercialization (including meat and by products) and any movement in rabbits.

For more detailed information about this disease I would like to point out to you some major findings:

Clinical Signs

.The mortality and most serious cases have been found in adult animals. The disease is characterised by causing a sudden death in 90-95% of the total herd. The rabbits die within 72 hours after experimental infection.

.It appears that the deaths of the rabbits is related to an association of hepatic and lung dysfunction.

.The affected rabbits show symptoms of depression, sadness, anorexia and dysnea.

.The rabbits show incoordination, crying, shaking and other nervous signs just before they die.

.The death rabbits show a mucus and blood-stained nasal exudate.

.In some cases clinical signs are not observed since the affected animals die suddenly.

.In some cases we have observed a jelly-like stool from the anal area as in mucoid enteritis.

Pathology

Gross Lesions

.There is an increase in the size of the liver, spleen and kidney. There is lung congestion and edema. Echymotic hemorrhages are observed in lungs and trachea.

.Some diagnosis reports have shown petechial hemorrhages on the serosal surface of the intestine and on the epicardium and endocardium of the heart of the rabbits.

Microscopic

.Histopathological examinations have distinguished in 96% of the cases generalised hepatosis and hepatocyte dissociation

.In some cases the liver contains numerous focal areas of necrosis and accumulation of haematic pigmentation.

.In 60% of the cases there are lung lesions with atelectasis; a lower proportion have pneumonic focal areas , congestion and edema.

.The kidneys may present areas of interstitial nephritis and hemorrhagic nephrosis

.In the spleen there is lymphatic dissociation.

Due to the nature and magnitude of the problem, some institutions such as Centro de Ganaderia, Colegio de Post-graduados, Chapingo, Mexico, and “Conejos” Centro de Investigacion Cientifica del Estado de Mexico, A.C., are considering it necessary to invite a specialist to Mexico to assist us in this major problem that is putting at risk our research programs and rabbit production in Mexico.

I will be looking forward to hearing your opinion about this situation and thank you very much in advance.

Sincerely,

Raymundo Rodriguez de Lara, Ph.D.

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USDA APHIS MEXICO UPDATE (Received 1996)
Viral Hemorrhagic Disease of Rabbits in Mexico-Update

Mexico is close to eradicating viral hemorrhagic disease (VHD) of rabbits. Surveys in 1992 did not detect any new infected premises (table1) and the last new case was confirmed on April 10, 1991.

Table 1 - Summary of activities of the campaign against viral hemorrhagic disease (VHD) in Mexico.

Year----Number of Field Investigations----Affected Premises----Sacrificed Rabbits----Affected States
1988--------------------X----------------------------------61----------------------------X----------------------3
1989-----------------10,349---------------------------2,788------------------------111,180----------------15
1990-------------------1,173-------------------------------1---------------------------7,033-------------------3
1991-------------------3,298-------------------------------1---------------------------2,306-------------------1
1992---------------------657--------------------------------0------------------------------60-------------------0
Total-----------------14,818---------------------------2,838------------------------120,579-------------------
X=Data not available

As per the strategy to eradicate the disease, extensive serological surveys were continued through 1991 (fig 2) and into 1992. All seropositive animals and their contacts were depopulated, and the involved premises were cleaned and disinfected.

During the course of the eradication campaign, 120,579 rabbits have been destroyed. However, in a program of repopulation, approximately 90 per cent of these (107,301 animals) had been replaced by August 2, 1992. Out of the original 15 states affected by VHD, rabbits in 12 have been completely repopulated, and those areas continue to be free of the disease. In the near future, repopulation should be complete and the disease should be eradicated in Mexico.

(Dr Armando Mateos, Director, Mexico-United States Exotic Animal Disease Commission, Mexico City, Mexico)