Update on vector-borne zoonoses (Proceedings)

Vector-borne infectious diseases have been identified more frequently in humans and domestic animals in recent years, and include some of the most important emerging and re-emerging infectious diseases. Infectious diseases that may be transmitted to dogs and cats via a vector include viral, bacterial/rickettsial, and protozoal diseases. The vectors most commonly are arthropods such as sandflies, mosquitos, fleas, and ticks. The epidemiology of vector-borne infections depends upon the distribution of the arthropod vector, and travel history is an important consideration when examining dogs with possible vector-borne infectious diseases.

The development of molecular diagnostic techniques has contributed to improved recognition of a number of zoonotic vector-borne infectious agents, including Bartonella and Borrelia. Improved surveillance for these diseases has also improved recognition. Human and animal travel is increasing worldwide and has contributed to emergence of many infectious diseases. Competent vectors for Plasmodium and Leishmania exist within the United States, so these infectious diseases have the potential to become a huge human health problem if they are imported here and the right conditions exist for transmission. Re-emergence can also occur when vector control programs succeed and subsequently fail to be maintained.

Habitat changes, deforestation and urbanization have contributed to emergence of a number of important vector-borne diseases in humans. Reforestation has probably contributed to emergence of Lyme borreliosis in the United States. Climate influences on host behaviour include more people and their pets staying indoors in an air-conditioned environment, which would tend to decrease the risk of vector-borne infectious disease. Humidity, rainfall, wind, and the duration of daylight are also important considerations.

Dogs can also serve as sentinels for human exposure to vector-borne infectious diseases, but in the majority of instances (perhaps with the exception of Bartonella), dogs and cats do not directly transmit these infections directly to people. Because many of these infections may be transmitted by blood transfusion, care should be taken when collecting and handling blood from dogs and cats suspected to be infected with a vector-borne infectious disease.

Coinfection with multiple zoonotic vector-borne infectious agents is a relatively common phenomenon that is being increasingly recognized. Coinfections can complicate the clinical picture, and in some situations, one organism may affect another's pathogenicity. Documentation of exposure to one vector-borne infectious agent should be a cue to search for exposure to other agents transmitted by similar vectors.

Emerging vector-borne zoonotic infectious agents of importance in dogs, cats, and humans include:

Borrelia burgdorferi

Borrelia burgdorferi is the cause of Lyme disease, the most common vector-borne disease in humans. The seroprevalence of Lyme in dogs in the western states is currently poorly understood, and we are currently recruiting canine serum samples in order to determine this more accurately. Although Lyme disease is being increasingly recognized in humans, PCR evidence of Borrelia infection in archival rodent specimens dates back to 1894. Ecological changes, primarily farmland reforestation and residential development in wooded areas, an associated explosion in deer populations, together with close proximity of reservoirs, ticks, humans and dogs, have probably contributed to emergence of Lyme disease.

The vector in the upper Midwest and north-eastern United States is Ixodes scapularis, and in the west it is Ixodes pacificus. The primary reservoir in the upper Midwest and the northeast is Peromyscus leucopus, the white-footed mouse. In the west, recently evidence was published that Western gray squirrels may be an important reservoir in California.

Following inoculation of spirochetes into the host by the tick, the organisms migrate through connective tissue from the bite site, causing fever, inappetence, thrombocytopenia and lameness due to neutrophilic polyarthritis in some dogs approximately 2-5 months after infection. As a result, seronegative Lyme disease is rare in dogs. A small percentage of dogs may develop more severe complications, including chronic, treatment-resistant arthritis or protein-losing nephropathy, especially in Golden and Labrador Retrievers. The vast majority of dogs show no signs of illness.

Specific diagnosis is generally performed using serology for antibodies, and is often difficult because of the widespread subclinical exposure in endemic areas. In dogs, diagnosis usually involves detection of antibodies to the C6 peptide, which can be performed using the SNAP 4Dx test kit, or the quantitative C6 ELISA available through IDEXX. Vaccination with Borrelia burgdorferi vaccines should not interfere with diagnosis using the C6 ELISA assay. Detection of antibodies in conjunction with suggestive clinical signs should prompt quantification of C6 antibody titers using acute and convalescent serology, such that recent infection may be documented. Asymptomatic, seropositive dogs should probably be evaluated for proteinuria and coinfections with other tick-borne pathogens, tick control should be recommended. Treatment of sick dogs is with doxycycline for 4 weeks, but although clinical signs may resolve, complete elimination of the spirochete may not occur. Vaccination is still controversial, but there is evidence from the human literature that use of the recombinant ospA vaccine is safe and relatively efficacious. It should be reserved for dogs in endemic areas that frequent tick-infected areas.

Anaplasma phagocytophilum

Anaplasma phagocytophilum is the cause of granulocytic anaplasmosis. This disease was first recognized in humans and dogs in the upper Midwest in 1990. The emergence of this disease has been postulated to be due to repopulation of habitats previously devoid of ticks by deer, small rodents, and humans, together with improved diagnostic capabilities. The vectors appear to be the same as those for Borrelia burgdorferi. A variety of species may be infected including horses, ruminants, dogs, cats and wildlife. The largest number of cases has been seen in the upper Midwest and northeastern United States, and the disease is increasingly reported from other states including northern California, the northwest coast and Vancouver.

Clinical signs include fever, lethargy, inappetence, peripheral lymphadenopathy, and lameness due to neutrophilic polyarthritis. Neurologic signs have been reported anecdotally but are rare. Laboratory abnormalities may include leukopenia, thrombocytopenia, and elevated ALP activity and sometimes ALT activity.

Morulae may occasionally be seen on blood smears within granulocytes, most commonly neutrophils. Diagnosis is otherwise based on acute and convalescent phase serology using IFA; acute titers may be low or negative. The SNAP 4Dx test kit includes a spot for antibodies to Anaplasma species. A positive result should prompt the clinician to perform IFA serology that is specific for Anaplasma phagocytophilum. PCR assays are also available. Treatment is with doxycycline for 2 weeks, which usually results in cure.

Bartonella species

Bartonella species include Bartonella henselae and Bartonella vinsonii subspecies berkhoffii. These bacteria are curved, Gram-negative bacteria that reside within erythrocytes and endothelial cells, and are transmitted by a variety of arthropod vectors, including fleas and ticks. Infection of cats by Bartonella henselae in endemic areas may be as high as 30%, and is generally considered to be subclinical. In dogs, infection with Bartonella has been associated most commonly with endocarditis. In northern California, most dogs with evidence of exposure to Bartonella have concurrent evidence of exposure to Anaplasma phagocytophilum. The prognosis for Bartonella endocarditis is poor when compared with that due to other bacterial pathogens. Diagnosis is generally using serology. Infections with Bartonella may be difficult to eliminate using antimicrobial therapy. Doxycycline and azithromycin have been the most common antibiotics used.

Rickettsia rickettsii

Rickettsia rickettsii is the cause of Rocky Mountain Spotted Fever. This is an acute disease transmitted by Dermacentor ticks, and is emerging in the southeastern US. Infection of endothelial cells results in a systemic vasculitis, which can be associated with severe edema and tissue necrosis. Diagnosis is based on the result of acute and convalescent phase serology, and/or direct fluorescence antibody on affected tissues. Cross-reactions can occur to non-pathogenic Spotted Fever Group rickettsiae, and this must be kept in mind when interpreting the results of serology. Treatment is with doxycycline for at least 7 days. The mortality in humans may be as high as 10%, and dogs are important sentinels for human exposure.

West Nile virus

West Nile virus is a mosquito-borne flavivirus. This virus is now distributed across the US and has spread into Canada and the Carribean. Ingestion of infected birds or rodents may also lead to infection. There has been several case reports published of canine infection with West Nile virus. Dogs typically show fever, lethargy, myocarditis and progressive neurologic signs. Diagnosis relies on acute and convalescent phase serology, polymerase chain reaction testing, and immunohistochemistry on tissues collected at necropsy. Treatment is supportive.

Although less common in the US, other arthropod-borne infections of considerable importance to humans, dogs and cats include plague (Yersinia pestis), tularemia (Francisella tularensis), Q fever (Coxiella burnetii) and leishmaniasis (Leishmania infantum).