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Rabies

Rabies Virus Diagnosis and Detection In Suspect Animals

Based upon a recent commercial press release, CDC has received many inquiries concerning a new rapid test for rabies diagnosis in animals. Below you’ll find answers to questions on rabies diagnosis in animals and current public health recommendations.

General questions and answers about rabies.


How is rabies diagnosed in an animal?
How long does animal rabies testing take?
How accurate is the direct fluorescent antibody (DFA) test for rabies?
How many animals are tested each year and how many are positive for rabies?
How does rabies virus get from a bite wound to the saliva?
How long can rabies virus be present in an animal’s saliva before it shows signs of rabies?
How much rabies virus is required to cause infection?
How are veterinary diagnostic test kits regulated in the United States?

 

How is rabies diagnosed in an animal?

After exposure, and the movement of rabies virus from the peripheral nervous system to the brain, an animal becomes ill with typical clinical signs of the disease which can include fever, general illness, difficulty swallowing, increased salivation, aggressiveness, or lethargy.

Rabies is diagnosed using the direct fluorescent antibody (DFA) test, which looks for the presence of rabies virus antigens in brain tissue. The test requires that the animal be euthanized.

A diagnosis of rabies can be made after detection of rabies virus from any part of the affected brain, but in order to rule out rabies, the test must include tissue from at least two locations in the brain, preferably the brain stem and cerebellum.

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How long does animal rabies testing take?

The test itself takes about 2 hours, but it takes time to remove the brain samples from an animal suspected of having rabies and to ship these samples to a state public health or veterinary diagnostic laboratory for diagnosis. In the United States, the results of a rabies test are typically available within 24 to 72 hours after an animal is collected and euthanized.

Because rabies exposure to suspect animals is a medical urgency, but not an emergency, testing within this time period is more than adequate for determining if a person was exposed to a rabid animal, and requires rabies postexposure prophylaxis.

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How accurate is the direct fluorescent antibody (DFA) test for rabies?

During the 50 years the DFA has been used in the United States, there has been no indication it has failed to provide accurate clinical information on the rabies status of an animal for the purposes of treating an exposed person. 

Because of its high sensitivity and specificity, in comparison to virus isolation methods, the DFA test is the “gold standard” diagnostic method for rabies and has been rigorously evaluated by international, national, and state health laboratories. The DFA test is currently the only recommended diagnostic method for routine rabies determination in animals in the United States.

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How many animals are tested each year and how many are positive for rabies?

Approximately 120,000 animals or more are tested for rabies each year in the United States, and approximately 6% are found to be rabid. The proportion of positive animals depends largely on the species of animal and ranges from <1% in domestic animals to >10% of wildlife species.

Based on routine public health surveillance and pathogenesis studies, we have learned that it is not necessary to euthanize and test all animals that bite or otherwise potentially expose a person to rabies.  For animals with a low probability of rabies such as dogs, cats, and ferrets, observation periods (10 days) may be appropriate to rule out the risk of potential human rabies exposure (more information on rabies exposure).

Consultation with a local or state health official following a potential exposure can help determine the best course of action based on current public health recommendations.

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How does rabies virus get from a bite wound to the saliva?

When an animal is infected with rabies virus, most often when the bite of another rabid animal transfers rabies virus-laden saliva into the bite wound, rabies virus moves via nerves from the wound to the spinal cord and brain. Rabies virus travels exclusively through nerve cells and is not found in blood, urine, or feces.

Once the virus reaches the brain and replicates, it moves to peripheral organs, specifically the salivary glands where it can be excreted and transmitted to another animal. This pattern of virus spread to and within the central nervous system before excretion in the saliva is the process that makes examination of the brain stem critical to rabies diagnosis. Viral antigen is widespread in the brain of most rabid animals, but because spread may also be irregular or unilateral, especially in larger animals, a negative finding for rabies can be made only if a complete cross-section of the brain stem and cerebellum are examined.

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How long can rabies virus be present in an animal’s saliva before it shows signs of rabies?

Extensive studies on dogs, cats, and ferrets show that the rabies virus can be excreted in the saliva of infected animals several days before illness is apparent. Such extensive studies have not been done for wildlife species but it is known that wildlife species do excrete rabies virus in their saliva before the onset of signs of illness. The excretion of virus may be intermittent, and the relative amount of excreted virus may vary greatly over time, before and after the onset of clinical signs. 

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How much rabies virus is required to cause infection?

The dynamics of rabies virus infection are multifaceted and depend in part on the route of exposure, rabies virus variant, and host immune factors. During clinical disease, millions of viral particles may be found intermittently in the saliva. In theory, only a single rabies particle or virion is required to result in a productive infection. The mass of a single virion has been estimated to be approximately 221 thousand kilodaltons. A small proportion of this amount includes viral RNA which accounts for less than 2% of the mass of a single virion.

Any rabies test proposed on living animals would need to be extremely sensitive to detect very minute quantities of protein or nucleic acid. In addition, several repeat tests would be needed over time to ensure that rabies virus excretion is not missed since viral shedding in the saliva is inconsistent.  For example, more than 2 billion rabies virions would need to be present in a sample if a test had a sensitivity that was limited to detecting virus in the microgram (1,000,000th of a gram) range. 

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How are veterinary diagnostic test kits regulated in the United States?

In general, if a given diagnostic product contains all materials needed to run a particular test, including instructions on interpretation of results, and if the intent of the manufacturer is to provide a self-contained, point-of-care product, such an application may be considered a diagnostic kit, and is under regulation by the United States Department of Agriculture (USDA), Animal and Plant Health Inspection Service (APHIS), Center for Veterinary Biologics. 

More information is available at the Center for Veterinary Biologics web site.

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Page last modified: March 4, 2009
Page last reviewed: March 4, 2009
Content Source: National Center for Zoonotic, Vector-Borne, & Enteric Diseases (ZVED)