West Nile virus infection: Essential facts for small-animal practitioners

The media buzz may have quieted considerably, but West Nile virus continues to cause illness and death nationwide and is here to stay. Within six years of the initial detection of this exotic mosquito-borne virus in New York, it has spread to all continental states, through Canada and Mexico, and into Central America. What's more, West Nile virus continues to surprise infectious disease experts and epidemiologists. It was predicted that West Nile virus cases would wane dramatically after initial outbreaks in naïve regions, but flare-ups have occurred in some parts of the country.

Morbidity and mortality from West Nile virus infection are certainly most prevalent in birds, followed by horses and people, but the virus has an unusual ability to infect myriad species, including dogs and cats. Fortunately, West Nile virus infection appears to rarely cause disease in dogs and has been documented even less frequently in cats. The Centers for Disease Control and Prevention (CDC) has fielded a staggering number of inquiries about the virus in pets. Do you know the correct answers to your clients' questions about West Nile virus?

THE STORY OF WEST NILE VIRUS

This flavivirus was historically known to cause sporadic outbreaks of febrile disease in Africa and the Middle East. It was first identified in the West Nile district of Uganda in 1937.1 Few cases of neurologic involvement or of West Nile virus-induced disease in species other than humans were reported. However, in the mid- to late 1990s, a more aggressive, neurovirulent strain of West Nile virus appeared in the Mediterranean, causing morbidity and mortality not only in people but also in horses and birds.2-5 Genetic analyses suggest that the strain of West Nile virus that was brought to New York and first detected in the fall of 1999 was a descendant of an avian West Nile virus isolate from Israel.6,7 Despite aggressive mosquito control efforts and hopes that the cold northeastern winter would eradicate West Nile virus, never before seen on the American continents, it has become established in the environment and has spread rapidly. It is thought to spread through multiple means, such as insects blowing in the wind and migratory birds, although no one knows exactly how it spreads.

ECOLOGY AND EPIDEMIOLOGY

The ability of West Nile virus to infect a wide variety of species is probably the biggest factor not only in its successful establishment but also in the patchy, unpredictable character of West Nile virus activity, which is explosive in some regions and nearly silent in others. West Nile virus is maintained in nature in a bird-mosquito cycle, but thousands of species of birds and mosquitoes exist, and their distribution varies with local ecology, season, and climate fluctuations such as drought. Birds vary dramatically in their ability to replicate West Nile virus (and, thus, to pass it on to feeding mosquitoes),8 and some mosquitoes are much more efficient at transmitting West Nile virus.9-11 Furthermore, mosquito species vary in their feeding habits, which range from specific to comparatively unselective. Mosquitoes that feed on both birds and mammals are referred to as bridging vectors, since they provide a link for mammalian exposure to the bird-mosquito cycle of West Nile virus. Variations in feeding preferences of local bridging vector mosquitoes may explain why some areas of the nation have seen a high intensity of both equine and human cases, while in other regions, there have been sizeable outbreaks in one species yet relatively few cases in the other.

WEST NILE VIRUS IN CATS AND DOGS

Many viruses encountered in small-animal veterinary practice can infect only a few or even a single mammalian species. As demonstrated by laboratory and field data, West Nile virus has the unusual ability to establish infection in a variety of animals, ranging from alligators to wolves—and including dogs and cats.

Infection and contagion

Studies performed at Colorado State University revealed that both dogs and cats readily become infected after being bitten by West Nile virus-infected mosquitoes.12,13 Fortunately, it appears that the risk of the virus spreading to owners, other animals, or veterinarians working with infected dogs and cats is minimal; West Nile virus replicates to fairly low levels in the tissues of these animals, and no virus was detected in saliva.12 Of course, proper precautions should be taken with patients that potentially have zoonotic diseases. In cases of West Nile virus, particular care should be used in handling blood from affected animals.

In one experiment, cats fed West Nile virus-infected mice developed systemic viral infections and later seroconverted.12 This study suggests that cats allowed outdoors are at additional risk for contracting West Nile virus, not only from greater exposure to mosquitoes but also through predation. Birds or other small animals weakened by West Nile virus infection may be particularly easy targets for hunting cats. Therefore, hunting and scavenging should be discouraged or prevented to avoid infection through oral exposure.

Enough virus was measured in the bloodstream of some cats12 to possibly infect the most susceptible species of mosquitoes,9 but the level of West Nile viremia in most of the cats was below the amount thought to be necessary to infect feeding mosquitoes.12-14 Thus, like horses,15,16 dogs and cats can generally be considered incidental hosts of West Nile virus, contributing little, if at all, to the environmental maintenance of the virus. Additionally, all animals in the studies cleared West Nile virus from their bloodstreams within days and mounted an antibody response—no evidence of prolonged or persistent infection was found in any of the dogs or cats studied.

Disease

Clinical disease from West Nile virus infection in cats is rare but has been documented.17 In fact, an apparently stray, seizing cat in New Jersey was among the first animals found to be infected with West Nile virus when the virus was first detected in 1999.18 Brief episodes of febrility, lethargy, or decreased appetite occurred in several of the cats in the laboratory studies after infection through mosquito bites, but most cats did not display any signs of disease.12,19

Clinical signs were not observed in any dogs infected in the laboratory,12-14,19 but a small number of clinical West Nile virus cases in dogs and other Canidae have been reported as the virus has spread (Bunning ML, United States Air Force; Vandeventer S, Iowa State University; Austgen LE, Colorado State University: Unpublished data, 2005).17,20,21 One large serologic study detected antibody against West Nile virus in more than 26% of 442 dogs and 9% of 138 cats from a combination of shelters and privately owned populations tested,22 indicating that exposure to West Nile virus is common.

The finding of high seroprevalence, combined with the rarity of clinical disease, suggests that the overwhelming number of exposed dogs and cats likely suffer no or mild illness as a result of West Nile virus infection. However, it is important to consider that West Nile virus-induced disease in companion animals may go largely unrecognized until more information about clinical presentation and diagnosis becomes available.

Although few cases have been analyzed, West Nile virus in dogs seems to present much as it does in horses, with signs attributable to any combination of meningitis, encephalitis, and myelitis. The most commonly affected regions of the central nervous system are the meninges, dorsal horn, brainstem, and cerebellar Purkinje cells, but the virus may be found in other areas, including the cortex. Clinical signs are nonspecific and vary greatly with the extent and location of central nervous system involvement; diagnosis cannot be made from clinical signs alone. The most frequent clinical findings in dogs with West Nile virus infection are

• Ataxia, particularly caudal; may ascend

• Weakness or paresis

• An altered mental state, such as listlessness, hyperesthesia, or somnolence

• Muscle tremors or focal twitching

• Pain—may not be localizable; varieties include myalgic, meningeal, and abdominal

• Fever

In horses and people, fever tends to peak at or before the onset of neurologic signs and has often resolved by the time of clinical evaluation. The same is likely true in dogs and cats and some other mammals kept as pets.

Diagnosis

West Nile virus-induced disease may resemble many other conditions in dogs and cats, including bacterial meningitis, distemper, rabies, fungal or rickettsial infections, systemic lupus erythematosus, or primary neurologic disease. Rank West Nile virus infection in your differential diagnoses based not only on clinical signs, but in light of the intensity of West Nile virus activity in your region. Among other resources, local information compiled by the U.S. Geological Survey and the CDC can be easily accessed at westnilemaps.usgs.gov. At this site, the avian, veterinary, and human maps will probably be most helpful, because many regions lack good mosquito and sentinel surveillance programs. Counts of West Nile virus-positive avian fatalities have been shown to provide the best estimator of the intensity of viral activity. However, many county health departments have elected to cease testing birds after the first positive result each year, so cumulative avian fatalities are unknown in these regions.

Antemortem diagnosis (Table 1) of West Nile virus infection can be challenging. West Nile virus is typically already cleared from the bloodstream by the time horses and people present for medical care. So if this is also true in dogs and cats, serum virus isolation is not likely to be effective. Single-sample tests of neutralizing antibody are rarely meaningful because of the high incidence of seroconversions secondary to subclinical West Nile virus infections in pets.22,23 Thus, paired acute and convalescent serologic testing for neutralizing antibody is currently considered the gold standard for antemortem diagnosis of West Nile virus infection. The neutralizing antibody test can be performed in any species, but it requires special facilities and, thus, is not offered by most laboratories. Data on the clinical utility of single-sample cerebrospinal fluid testing in horses24 and people2 conflict, and little is known about this method of West Nile virus infection diagnosis in other animals. Therefore, cerebrospinal fluid samples should be considered adjunctive to tests for serum antibodies in dogs and cats.

Table 1: Antemortem Diagnostic Testing for West Nile Virus Infection in Small Animals

The species of origin should be emphasized on the sample label so that serum is not mistakenly subjected to another species' IgM antibody testing, which is species-specific. IgM antibody testing is widely available for horses and people, but canine IgM assays are currently offered only by the Veterinary Medical Diagnostic Laboratory at the University of Missouri College of Veterinary Medicine and by the Michigan State University Diagnostic Center for Population and Animal Health (Virology/Serology section).

The presence of IgM in the serum indicates recent exposure to West Nile virus. But because of the commonality of subclinical West Nile virus infections, IgM in the serum is not diagnostic unless it is accompanied by correlative clinical signs. The incubation period for West Nile virus-induced disease and the timing of the appearance of serum antibody are variable,2,16 so IgM measurements taken early in the course of disease may be negative or inconclusive, requiring repeat testing.

Diagnosing West Nile virus infection postmortem is comparatively straightforward since more definitive testing modalities can be used on tissue samples harvested at necropsy (Table 2). Because West Nile virus can reach high concentrations in some tissues and exposure to the virus during postmortem examination has resulted in human West Nile virus infection, necropsy of animals suspected of having West Nile virus infection should be performed in a laminar flow cabinet or at least in a well-ventilated area. Be sure to use a mask, gloves, disinfectants, and protective clothing and equipment. If possible, have a veterinary diagnostic laboratory perform the necropsy.

Table 2: Postmortem Diagnostic Testing for West Nile Virus Infection in Small Animals

The tissues most likely to yield West Nile virus are the heart, kidneys, and central nervous system, particularly the brainstem. If possible, a section of spinal cord should also be submitted. It is best to formalinize half of each sample and leave the other half untreated. All tissues should be chilled, not frozen, and shipped expeditiously for West Nile virus polymerase chain reaction (PCR) or immunohistochemistry testing or both; virus isolation may also be attempted. Be sure to also request rabies testing for deceased patients suspected of having West Nile virus infection.

For up-to-date information and guidance when dealing with suspected West Nile virus cases, it is advisable to consult both your state veterinary office and a reference laboratory or state diagnostic laboratory. Also, please report positive results to the public health department as diagnostic laboratories may not routinely do so.

Treatment

As with most other viral diseases, no reliable therapeutics target West Nile virus infection. If fever is present, it unlikely clears the infection: West Nile virus continues to replicate at temperatures as high as 113 F (45 C).25 Most of the damage to the central nervous system is likely attributable to the inflammatory response, rather than West Nile virus-induced cytopathology. Supportive care with fluid therapy, analgesics, and symptomatic treatments are the most important aspects of patient management. Recumbent patients will require turning every few hours, and many animals incapacitated by West Nile virus are appetent but unable to eat or drink without assistance. Antibiotics are unlikely to be beneficial if an animal is indeed suffering from West Nile virus infection, but their administration may be prudent to address other differential diagnoses and to help prevent nosocomial infection.

WEST NILE VIRUS IN BIRDS

Mortality from West Nile virus infection has been reported in a staggering number of bird species. Most data come from wild birds, but zoos with outdoor aviaries have reported considerable losses, and some pet birds have also been afflicted.17,26 Avian infection with West Nile virus differs considerably from that in mammals and is highly variable among different species of birds.8,19,26-29 Young hatchlings tend to rapidly succumb to West Nile virus infection, and some birds, particularly passerines, remain vulnerable throughout their lives. The good news is that most domestic avian species, including psittacines, are relatively resistant to severe clinical manifestations after infection with West Nile virus.8 Key points to consider:

• The clinical course of West Nile virus in birds is typically rapid. Initial lethargy and inappetence are followed by neurologic signs (head tilt; torticollis; difficulty perching, drinking, and eating) and then agonal signs.

• All organ systems of birds may be infected with high levels of virus. Unlike mammals, birds showing clinical signs likely have widespread, active viral infection.

• Some species of birds shed West Nile virus in saliva and excreta and may also spontaneously hemorrhage. These birds can infect cage mates (in the absence of a mosquito vector) and also constitute a major zoonotic risk.

• Diagnosis can be made by PCR or virus isolation from serum and sometimes from oral or cloacal swabs.30

• If pursued, treatment is typically restricted to aggressive supportive care, with the use of proper precautions by handlers. Corticosteroid therapy is generally regarded as being contraindicated since birds often have extensive, active infection. However, corticosteroids may be beneficial during convalescence.

• Some clinically affected birds recover from West Nile virus infection. Those with neurologic signs may have prolonged convalescences or permanent sequelae.

The efficacy of equine vaccines in preventing or even ameliorating disease from West Nile virus infection in birds is highly questionable.31 Fortunately, few safety concerns have arisen. Work is currently under way to develop avian-specific vaccines, but none are commercially available in the United States yet.

Laura Austgen, PhD, DVM

James L. Voss Veterinary Teaching Hospital

College of Veterinary Medicine and Biomedical Sciences

Colorado State University

Fort Collins, CO 80523

REFERENCES

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