Spotted Fever Group Rickettsiae

Spotted fever group (SFG) rickettsiae have been described from all continents. In North America, Rickettsia rickettsii is the most important SFG rickettsiae because this tick-transmitted organism can cause serious or fatal illness in dogs and people. The SFG group includes numerous closely related species including R. rickettsii (the type species), R. africae, R. akari, R. australis, R. conorii, R. felis, R. montana, R. parkeri, R. rhipicephali and R. sibirica, although many other SFG rickettsia have been described. The typhus group rickettsia, which includes Rickettsia typhi and Rickettsia prowazekii, have not been implicated as a cause of illness in domestic or wild animals. Experimental infection of dogs with typhus group rickettsiae in our laboratory did not result in illness. Throughout various regions of the world, spotted fever group rickettsiae are transmitted by Dermacentor, Rhipicephalus, Haemaphysalis and Amblyomma tick species. Regardless of the strain or species of SFG rickettsiae, these organisms generally induce an acute febrile illness secondary to endothelial cell damage, which results in vasculitis, altered vascular permeability, edema and necrosis.¹ To date, chronic infection with a SFG rickettsiae has not been confirmed in dogs or human beings in North America. Although it seems likely that other SFG rickettsiae could induce disease in dogs, to date only R. rickettsii in North America and R. conorii in southern Europe have been documented as canine pathogens.

Rocky Mountain Spotted Fever

Rocky Mountain spotted fever (RMSF) is a tick-transmitted rickettsial disease of dogs, people, and potentially other vertebrate species. The causative agent is Rickettsia rickettsii. In the context of morbidity, mortality, and severity of disease, RMSF is the most important tick-borne infection of dogs in the United States. Due to variation in the severity and location of vascular lesions among different patients, veterinarians should anticipate a spectrum of disease manifestations following naturally occurring infection with R. rickettsii. Much of the United States is considered endemic for the ticks (Dermacentor variabilis, Dermacentor andersoni, Rhipicephalus sanguineus) that transmit R. rickettsii. Rickettsia rickettsii infection ("Rocky Mountain spotted fever") also occurs in areas of Central and South America. Clinical abnormalities associated with RMSF include fever, anorexia, depression, mucopurulent ocular discharge, scleral injection, tachypnea, coughing, vomiting, diarrhea, muscle pain, neutrophilic polyarthritis, and a diverse group of neurologic signs including hyperesthesia, ataxia, vestibular signs, stupor, seizures, and coma. In some dogs weight loss is very severe, considering the short duration of illness. Poorly localizing joint, muscle and/or neurologic pain suggestive of polyarthritis, polymyositis, or meningitis may represent the only or most prominent clinical finding. Retinal hemorrhages are a consistent finding, but may be absent early in the course of the disease. Epistaxis, melena, hematuria, and petechial to ecchymotic hemorrhages occur in some dogs, but may not develop unless diagnosis and treatment are delayed for five or more days after the onset of clinical signs. Scrotal edema, hyperemia, hemorrhage, and epididymal pain are frequently observed in male dogs. Signs associated with cardiovascular collapse, oliguric renal failure or brain death can develop in the terminal stages of the disease. Gangrene affecting the distal extremities, scrotum, mammary glands, nose or lips is associated with severe vascular obstruction and can induce substantial tissue loss, necessitating reconstructive surgery. Clinical manifestations in dogs are identical in most instances to manifestations reported in human patients. From a public health perspective, it is important that veterinarians recognize and accurately diagnose RMSF.

Seasonal occurrence, history of tick infestation, fever, and combinations of the previously described clinical findings should suggest the possibility of RMSF. Due to marked variation in clinical presentation, confirmation of the diagnosis of RMSF is also important for the clinician to gain familiarity with the disease. In addition, confirmation of RMSF in household pets warrants owner education as to the enhanced risk associated with tick exposure in the local environment, as transovarial transmission of R. rickettsii from female ticks to progeny results in focal geographic locations in which a high percentage of ticks are capable of R. rickettsii transmission. Thrombocytopenia, generally mild in degree, is the most consistent hematologic finding associated with RMSF in dogs and people. Leukopenia generally occurs during the early stages of infection (first 24 to 48 hours), followed by progressive leukocytosis, which increases in proportion to the severity of vascular injury. Toxic granulation of neutrophils, metamyelocytes, eosinopenia, lymphopenia, and monocytosis may accompany the more typical changes in platelet and neutrophil number. A mild anemia may occur. Severe anemia, leukopenia, and thrombocytopenia can accompany severe or fatal cases of canine Rocky Mountain spotted fever. In severe cases, co-infection with other tick-borne organisms should be pursued diagnostically. Biochemical abnormalities reflect the effects of generalized vascular damage and vary with the severity and duration of infection. Hypoproteinemia, hypoalbuminemia, azotemia, hyponatremia, hypocalcemia, bilirubinuria and bilirubinemia and increased liver enzymes (serum alkaline phosphatase, alanine aminotransferase) may occur in dogs with RMSF. Synovial or cerebrospinal fluid analysis will generally reflect a mild increase in protein and cells, which, in the early disease process, are composed of a high percentage of neutrophils and later, mononuclear cells.

Diagnostic conformation of RMSF requires either direct immunofluorescent testing for R. rickettsii antigen in tissue biopsy or necropsy specimens, documentation of seroconversion, or PCR amplification of rickettsial DNA from blood, CSF, or tissue samples. Utilizing the indirect fluorescent antibody test, documentation of a fourfold or greater increase in antibody titer between acute and convalescent sera confirms a diagnosis of RMSF. To facilitate the accurate interpretation of serologic results, it is important to obtain the acute phase sample as early in the disease course as possible and the convalescent sample two to three weeks thereafter. If acute phase serum is obtained several (i.e., 5–7 days or longer) days after the onset of clinical signs, a high R. rickettsii antibody titer may be found. Although early initiation of anti-rickettsial antibiotic therapy will slightly decrease the intensity of the humoral immune response to R. rickettsii antigen, experimental studies indicate that collection of appropriately timed serum samples should reflect seroconversion and thereby facilitate an accurate diagnosis of RMSF in dogs. Direct immunofluorescent testing or PCR amplification of Rickettsia DNA provides the opportunity for rapid diagnosis by demonstrating R. rickettsii in skin biopsies or by detecting DNA in blood or tissue samples. Unfortunately, direct IFA testing is not readily available; however, PCR testing is becoming widely available for use by practicing veterinarians. Prior initiation of antibiotic therapy can cause a false-negative test result when using direct immunofluorescent testing or PCR amplification of R. rickettsii DNA.

Tetracycline (22 mg/kg TID for 14 days) or doxycycline (5 mg/kg BID for 14 days) is effective for treatment of SFG rickettsiae infection. Fluoroquinolones, such as enrofloxacin, appear to be equally effective for treating RMSF, but are not effective for treatment of ehrlichiosis. Following initiation of treatment, a rapid clinical response occurs in dogs without severe vascular damage or neurologic sequela. Defervescence should be anticipated within 24 hours after the initiation of antibiotics. Delay in diagnosis, or the use of antibiotics that lack anti-rickettsial spectrum, such as penicillin, cephalosporin derivatives, or aminoglycosides, may result in increased morbidity or mortality. Due to severe vascular damage, fluid therapy should be utilized with extreme caution to avoid iatrogenic induction of cerebral edema. Prednisolone administered at anti-inflammatory or immunosuppressive dosages in conjunction with doxycycline does not potentiate the severity of R. rickettsii infection in experimentally infected dogs.

Prevention

Immunity following natural infection is probably life-long. It is possible that undiagnosed mild or asymptomatic R. rickettsii infections, or repeated exposure to nonpathogenic spotted fever group rickettsiae (such as Rickettsia montanensis, Rickettsia bellii, or Rickettsia rhipicephali) can also contribute to naturally induced immunity and therefore the prevention of severe RMSF in dogs with prior tick exposure in endemic regions. Minimizing tick exposure, the use of acaricidal preparations, and routine, rapid removal of ticks from dogs represent the most effective means of prevention for RMSF. There is a broad spectrum of acaricides currently available in the markets of the United States. There is a large number of topically applied products in many formulations and newly developed long-lasting tick collars that prevent tick attachment and feeding. Also, now becoming available are orally administered acaricides of the isoxazoline class that kill ticks soon after they begin to feed on a dog. Restating the text above: "In the context of morbidity, mortality, and severity of disease, RMSF is the most important tick-borne infection of dogs in the United States." Dogs that go outside, especially in the eastern United States where RMSF is most common, need to be protected against tick attack. They should be protected against ticks year round.

Following infection with R. rickettsii, the duration of rickettsemia in dogs is brief, approximately 5–14 days. Therefore, infected dogs do not play an important reservoir role, and pose a minimal zoonotic threat to humans. In contrast, if RMSF is diagnosed in a household pet, the dog serves as a valuable environmental sentinel for potential human exposure to infected ticks. Care should be exercised in removing ticks, so as not to contaminate one's hands with infective hemolymph from ticks. Although the risk of inadvertent transmission is small, contact with rickettsemic blood during intravenous catheter placement, blood collection procedures, or laboratory sample analysis should be avoided. Zoonotic warning labels are recommended for blood samples obtained from dogs in which a differential diagnosis of RMSF is being considered.

References

1.  Davidson MG, Breitschwerdt EB, Walker DH, et al. Vascular permeability and hemostatic mechanisms during Rickettsia rickettsii infection in dogs. Am J Vet Res. 1990;51:165–170.

2.  Greene CE, Burgdorter W, Cavagnolo R, et al. Rocky Mountain spotted fever in dogs and its differentiation from canine ehrlichiosis. J Am Vet Med Assoc. 1985;186:465–472.

3.  Breitschwerdt EB, Meuten DM, Walker DH, et al. Rocky Mountain spotted fever: a kennel epizootic. Am J Vet Res. 1985;46:2124–2128.

4.  Breitschwerdt EB, Levy M, Davidson MG, et al. Kinetics of IgM and IgG responses to experimental and naturally occurring Rickettsia rickettsii infection in dogs. Am J Vet Res. 1990;51:1312–1316.

5.  Davidson M, Breitschwerdt EB, Nasisse M, et al. Ocular manifestations of Rocky Mountain spotted fever in dogs. J Am Vet Med Assoc. 1989;194:777–781.

6.  Weiser IB, Greene CE. Dermal necrosis associated with Rocky Mountain spotted fever in four dogs. J Am Vet Med Assoc. 1989;195:1756–1758.

7.  Breitschwerdt EB, Davidson MG, Aucoin DP, et al. Efficacy of chloramphenicol, enrofloxacin and tetracycline for treatment of experimental Rocky Mountain spotted fever in dogs. Antimicrob Agents Chemother. 1991;35:2375–2381.

8.  Davidson MG, Breitschwerdt EB, Walker DH, et al. Identification of rickettsiae in cutaneous biopsies from dogs with experimental Rocky Mountain spotted fever. J Vet Intern Med. 1989;3:8–11.

9.  Breitschwerdt EB, Davidson MG, Hegarty BC, et al. Prednisolone at anti-inflammatory or immunosuppressive dosages in conjunction with doxycycline does not potentiate the severity of Rickettsia rickettsii infection in dogs. Antimicrob Agents Chemother. 1997;48:141–147.

10. Breitschwerdt EB, Hegarty BC, Davidson MG, et al. Evaluation of the pathogenic potential of Rickettsia canada and Rickettsia prowazekii organisms in dogs. J Am Vet Med Assoc. 1995;207:58–63.

11. Drost WT, Berry CR, Breitschwerdt EB, et al. Thoracic radiographic findings in dogs infected with Rickettsia rickettsii. Vet Radiol Ultrasound. 1997;38:260–266.

12. Grindem CB, Breitschwerdt EB, Perkins PC, Cullins LD, Thomas TJ, Hegarty BC. Platelet-associated immunoglobulin (antiplatelet antibody) in canine Rocky Mountain spotted fever and ehrlichiosis. J Am Anim Hosp Assoc. 1999;35:55–61.

13. Gasser AM, Birkenheuer AJ, Breitschwerdt EB. Canine Rocky Mountain spotted fever: a retrospective study of 30 cases. J Am Anim Hosp Assoc. 2001;37:41–47.