Rocky Mountain Spotted Fever in Dogs

William L. Otis, DVM; Heather L. Tarpley, DVM; Perry J. Bain, DVM, PhD; Kenneth S. Latimer, DVM, PhD; Bruce E. LeRoy, DVM, PhD

Class of 2004 (Otis) and Department of Pathology (Tarpley, Bain, Latimer, LeRoy), College of Veterinary Medicine, The University of Georgia, Athens, GA 30602-7388

Introduction

Rocky Mountain Spotted Fever (RMSF) is an important zoonotic disease that may cause clinical signs in both dogs and humans. It is caused by the organism Rickettsia rickettsii, a small gram-negative obligate intracellular parasite from the family Rickettsiaceae. RMSF was first recognized in humans in the western United States during the 1930’s but, despite its name, RMSF is prevalent throughout the contiguous United States with the exception of the state of Maine. Although it has been long identified as a human pathogen, RMSF was not recognized in dogs until the 1970’s. ^1,2

Transmission

Hard-bodied ticks are the vectors of RMSF, and there are several species that have been known to be involved in its transmission. The most common vector in the eastern United States is Dermacentor variabilis (the American dog tick, Fig. 1) while Dermacentor andersoni (the wood tick, Fig. 2) is responsible for infections in the western part of the country. Amblyomma americanum and Rhipicephalus sanguineous also have been reported to carry the disease, although the vast majority of infections are due to the Dermacentor species.²

Figure 1. American dog tick (Dermacentor variabilis) is involved with transmission of Rocky Mountain Spotted Fever in the eastern United States.	Figure 2. The wood tick (Dermacentor andersoni) is involved with transmission of Rocky Mountain Spotted Fever in the western United States.

There are two ways in which ticks may become infected with R. rickettsii. Ticks may acquire the organism by feeding on parasitemic small mammals such as chipmunks and squirrels. Larger mammals rarely achieve the degree of parasitemia necessary to transmit the disease to a feeding tick. These small mammals function as reservoirs for the organism. Dogs and humans also function as reservoirs for the RMSF; however, they are incidental hosts and are the only reservoirs that display clinical signs of disease.¹ The larvae and nymphs of the Dermacentor species typically feed on small mammals, while the adult ticks prefer larger mammalian hosts. Therefore, it is the larval and nymphal stages that are most often infected with R. rickettsii during feeding.

Figure 3. Life cycle of Rickettsia rickettsii, the etiological agent of Rocky Mountain Spotted Fever.

Once infected, ticks may transstadially spread RMSF among their own population through the transfer of bodily fluids during mating, or transovarially spread the organism from the pregnant female to her offspring. Transovarial infection is the primary means by which R. rickettsii propagates in nature. Once infected, ticks then transmit RMSF to vertebrates (including dogs and humans) through their saliva when taking blood meals. Generally, an infected tick must be attached to its host from 5 to 20 hours for transmission of R. rickettsii to occur.⁵ This organism may also be transmitted through contact with infected tick hemolymph or excrement (Fig. 4), especially when engorged ticks are crushed.²

Figure 4. Tick hemolymph cells infected with R. rickettsii. Rickettsia appear as red particles in the cytoplasm of the cells (Gimenez stain).

Pathogenesis

R. rickettsii is transmitted to the dog through the bite of an infected tick. Once inside the body, the organism undergoes a 2-14 day incubation period, which is followed by its entrance into the animal’s circulatory system. The organism then invades endothelial cells of the venules and capillaries and begins replicating, causing a vasculitis (Fig. 5). Recent evidence has shown that the organism prevents apoptosis (programmed death) of the vascular endothelial cell, allowing adequate time for the organism to effectively replicate and spread.⁶ The replication of R. rickettsii and subsequent vasculitis may lead to edema, hemorrhage, shock, and vascular collapse. Endarterial organs (brain, skin, heart and kidneys) are affected most often. Vascular leakage also triggers activation of the animal’s platelets and coagulation system.²

Figure 5. R. rickettsii (red staining) infecting endothelial cells of a human blood vessel (immunoperoxidase stain).

Clinical Signs

Most cases of RMSF in dogs are reported between the months of March and October, coinciding with the prevalence of ticks in the environment. Most infected dogs are less than 3 yrs old and have had a recent history of exposure to tick habitat.¹ While the disease is generally thought to be self-limiting and of approximately 2 weeks duration in dogs, recent evidence has shown that untreated RMSF may lead to death of the affected animal.⁵

Rocky Mountain Spotted Fever is most closely associated with development of a red rash ~ 12 days after the initial tick bite (Fig. 6). However, this is rash is an inconsistent finding in dogs and is only seen in ~ 85% of infected humans. The onset of fever, ranging from 102.6-104.9º F approximately 5 days after the tick bite, is a more consistent clinical finding. Petechiae and ecchymotic hemorrhages associated with destruction of platelets in response to vasculitis are often seen on exposed mucosal surfaces in the dog. Vasculitis also may cause edema in the extremities including the scrotum, prepuce, and ears of affected dogs.¹

Figure 6. Appearance of an early macular rash on the sole of a human foot.

Other signs that may be evident include joint swelling, myalgia, dyspnea, and neurological abnormalities due to meningoencephalitis. Vestibular ataxia is the most common neurologic affliction. The presence of these signs generally indicates a more disseminated lesion and a poorer clinical prognosis.¹

Ocular lesions often are associated with RMSF and result from vasculitis and hemorrhage. Conjunctival hyperemia, hyphema, retinal hemorrhage, and anterior uveitis also have been associated with RMSF. These ophthalmic lesions tend to be mild and usually occur bilaterally. A fundic examination often is required to diagnose RMSF-associated ocular disease and retinal hemorrhages are the most common lesion (Fig. 7).³

Figure 7. Appearance of intraretinal hemorrhage (dark gray, round spots), the most common ocular manifestation of Rocky Mountain Spotted Fever.

Laboratory Diagnosis

The most consistent laboratory finding with RMSF is thrombocytopenia, with platelet counts ranging from 23,000 to 220,000 /µl. The resolution of thrombocytopenia also may be used to gauge the animal’s response to treatment.² Other laboratory findings with RMSF include a moderate leukocytosis that may have a mild left shift. A normocytic, normochromic anemia also may be present. Biochemical abnormalities may include elevated glucose and cholesterol concentrations as well as increased activity of alkaline phosphatase (ALP) and alanine aminotransferase (ALT). Hypoalbuminemia from vasculitis is often present. If the kidneys are involved in the disease, the BUN may be elevated corresponding to the degree of renal failure. This is normally observed only in the terminal stages of the RMSF. Proteinuria may also be present, but is an inconsistent finding.²

Serologic testing is the most useful means to detect infection of animals with R. rickettsii. The presence of a four-fold increase or decrease in IgG antibody titers to R. rickettsii along with appropriate clinical signs of RMSF is considered diagnostic for the disease. Antibody titers may not be clinically useful, as IgG concentration does not increase until 2-3 weeks post infection. Alternatively, a single high IgG titer (>1024) is suggestive of exposure within the last tick season. A single positive IgM titer (>8) indicates a more recent exposure to the organism. Positive IgG titers may persist for 3-10 months post infection but positive IgM titers normally decrease after 4 weeks. Cross reactivity to other spotted fever rickettsia exists and may confound test interpretation in certain instances.^1,3,5

Several human serologic tests have been developed to detect anti- R. rickettsii antibodies in humans. ELISA, complement fixation microscopic immunofluorescence assay (IFA), and latex agglutination are the most useful tests for evaluation of canine sera.^1,2 Paired serum samples should be submitted simultaneously to the laboratory to ensure consistency of laboratory analysis and allow interpretation of rising or falling IgG titers. These samples also should be evaluated for the concentration of IgM antibody in order to determine the time course of the disease.²

Other less practical tests used to detect RMSF include PCR of a biopsy or skin lesion sample. This test detects rickettsial DNA through the amplification of the 16S rRNA gene sequence of R. rickettsii; however, this test is relatively insensitive. Another more useful test is direct fluorescent antibody (FA) staining, which detects organisms frozen sections of tissues or ticks. Unfortunately, this test has a high incidence of false negative test results (30-40%), particularly in animals where antibiotic therapy has been initiated.² As many of these tests are difficult or cumbersome to run, a retrospective diagnosis often is made by simply evaluating the patient’s response to antibiotic treatment.¹

Treatment

As with other rickettsial infections, the treatment of choice for RMSF is tetracycline (22-30 mg/kg body weight given three times daily) or doxycycline (10-20 mg /kg body weight given twice a day). Chloramphenicol (15-30 mg /kg body weight given three times a day) may be used in young puppies (<6 months old) to avoid dental staining by tetracycline. Chloramphenicol also may be used in pregnant bitches. Fluoroquinolones (enrofloxacin at 3 mg /kg body weight given twice a day) also have shown efficacy in treating RMSF, although their use should be restricted to older animals to prevent damage of cartilage.

Since a definitive diagnosis of RMSF may take days to weeks to acquire, treatment should be initiated immediately after samples are taken for laboratory testing. Response to antibiotics usually is seen within 24-48 hours, although advanced cases with signs of necrosis or thrombosis may not respond at all to treatment. Supportive care should be instituted concomitantly with antibiotic administration; however, fluid therapy should be administered conservatively due to the vasculitis and subsequent potential for pulmonary and cerebral edema.^2,3

Mild ocular lesions should resolve with systemic antibiotic therapy. Anterior uveitis or hyphema that does not respond to antibiotics generally can be cleared with topical corticosteroids. More serious lesions, such as retinal hemorrhage or chorioretinitis, may be treated with systemic corticosteroid administration. Anti-inflammatory doses of prednisolone have been shown to have no negative effects on the treatment of RMSF, although antibody titers may be decreased.³ Dogs that have recovered from RMSF have demonstrated effective protective immunity to further reinfection.²

Prevention

Due to the lack of a vaccine against Rickettsia rickettsii, the best way to prevent dogs from contracting RMSF is to limit their exposure to ticks. This includes limiting their access to tick infested areas, particularly between the months of March through October. Dogs also should be inspected closely for ticks on a regular basis; any ticks that are found should be removed quickly and safely with a gloved hand.² The application of topical agents for tick control (such as fiprinol or permethrin) have been shown to be effective. Tick collars containing amitraz also have proved to be beneficial.¹

References

1. Warner RD, Marsh WW: Rocky Mountain Spotted Fever. J Vet Intern Med, 10:1413-1417, 2002.

2. Greene CE: Infectious Diseases of the Dog and Cat, 2nd ed. WB Saunders and Co., Philadelphia, 1998, pp. 155-162.

3. Stiles J: Rocky Mountain Spotted Fever. Vet Clin N Am Small Animal Pract 30: 1144-1148, 2000.

4. Hinrichsen VL, Whitworth UG, Breitschwerdt EB, Hegarty BC, Mather TN: Assessing the association between the geographic distribution of deer ticks and seropositivity rates to various tick-transmitted disease organisms in dogs. J Vet Intern Med 7:1092-1096, 2001.

5. Breitschwerdt EB: Rocky Mountain Spotted Fever. www.petshealth.com/library/rsms.html, accessed August 1, 2003.

6. Clifton DA, Goss RA, Sahni SK, van Antwerp D: NF-kappa B-dependent inhibition of apoptosis is essential for host cell survival during Rickettsia rickettsii infection. Proc Natl Academy Sci USA 95: 4646, 1998.

Acknowledgements

Picture of Great Dane and ticks from the "Tick Fever" DaDane feature at Ginnie.Com

Figure 1 from http//southernlyme.healingwell.com/catalog.htm

Figure 2 from http//www.hsc.wvu.edu/som/micro/317PRINT/lecture10/sld046.htm

Figure 3 from J Am Vet Med Assoc 10:1413, 2002.

Figure 4 courtesy of the Centers for Disease Control and Prevention http://www.cdc.gov/ncidod/dvrd/rmsf/Organism.htm

Figure 5 courtesy of the Centers for Disease Control and Prevention http://www.cdc.gov/ncidod/dvrd/rmsf/Laboratory.htm

Figure 6 courtesy of the Centers for Disease Control and Prevention htpp://www.cdc.gov/ncidod/dvrd/rmsf/Signs.htm

Figure 7 from Stiles J: Veterinary Clinics of North America Small Animal Practice, 30: 1146, 2000.

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