Rocky Mountain Spotted Fever ROCKY MOUNTAIN SPOTTED FEVER Edward B. Breitschwerdt, DVM, Diplomate, ACVIM Professor Veterinary Medicine North Carolina State Veterinary School http://www.cvm.ncsu.edu/ Objectives 1.Describe the clinicopathologic abnormalities associated with Rickettsia rickettsii infection in dogs. 2.Discuss factors which influence the prognosis for ehrlichiosis and Rocky Mountain spotted fever. 3.Describe how you would confirm a diagnosis of Rocky Mountain spotted fever. 4.Describe the zoonotic considerations associated with the diagnosis of Rocky Mountain spotted fever in a dog. Rocky Mountain spotted fever (RMSF) is an infectious rickettsial disease of dogs, that is characterized by severe vascular damage. Canine susceptibility to Rickettsia rickettsii was demonstrated in 1933. Recent reports emphasize that, contrary to previous literature, untreated naturally-occurring RMSF can result in death. Clinical reports suggest that RMSF is a much more common cause of disease in dogs than was previously recognized. Geographic Distribution Despite its name and original description as a disease of humans in the western United States, the majority of human cases of RMSF occur in the southeastern United States. Human cases of RMSF have been reported from nearly every state in the United States, western Canada, Mexico, and South America. Distribution of the disease is related to the distribution of the vector ticks Dermacentor variabilis, the American dog tick found in the eastern United States, and Dermacentor andersoni, the wood tick, which is the principal vector in the western United States. Canine RMSF has been recognized in most southeastern states, New York, Massachusetts, and Ohio. Etiologic Agent R. rickettsii is a small intracellular parasite in the family Rickettsiaceae. The organism is a member of the spotted fever group rickettsiae, which includes both pathogenic and nonpathogenic rickettsiae. Dogs and rodents comprise the mammalian reservoir for R. rickettsii. Following tick bite, infection may occur in humans, dogs, and cats. Within the general tick population, few ticks contain infective R. rickettsii. However, there are geographic centers which contain large numbers of infective ticks. Attachment of a tick to a host for 5 to 20 hours is required before infection can take place. Pathogenesis R. rickettsii is transmitted to the dog by a tick bite. The rickettsiae enter the circulatory system and replicate. Rickettsiae cause direct damage to cells lining the vascular system, resulting in vascular inflammation and death of the cells sewelling of the skin, hemorrhage, which if severe can cause low blood pressure, shock and death. Central nervous system swelling may contribute to the development of neurologic signs, rapid clinical deterioration, and death. Fliud accumulation in the lungs may occur,and may be detected with an x-ray. Clinical signs include rapid breathing, difficult breathing or coughing in some dogs. In severe cases, acute renal failure may occur. Due to increased vascular permeability, fluid therapy should be used with caution, when treating dogs with Rocky Mountain spotted fever. Clinical Findings Some dogs develop mild illness following experimental and naturally_occurring infection with R. rickettsii. In addition to the infective dose or strain variation in rickettsiae, breed predisposition may play a role in determining the severity of illness. For example, we have observed severe disease in Siberian husky dogs, whereas deerhounds sustain high antibody titers without prior evidence of associated illness. Clinical signs in canine infection are identical to human cases of RMSF. Unlike ehrlichiosis in which chronic infection can persist, the total duration of illness following R. rickettsii infection is generally short (2 weeks or less). For this reason, canine RMSF is a disease that presents in the spring and summer (April to September). Fever, loss of appetite, depression, vomiting, diarrhea, and neurologic abnormalities are typically associated with the clinical presentation of the animal. Redness of the eyes and a pussy discharge may be seen and nasal discharge, coughing are frequent findings. In some dogs, weight loss is very severe, considering the short duration of illness. Joint pain and/or muscle pain suggestive of polyarthritis or muscular pain may represent the only or most prominent clinical finding. One dog with serologically confirmed RMSF was presented for depression, and massive liver enlargement was the sole clinical finding. Bloody nasal discharge, blood in stools,and blood in the urine and areas of bruizing occur in some dogs, but may not develop unless diagnosis and treatment are delayed for 5 or more days after the onset of clinical signs. Ocular hemorrhage are a consistent finding, even early in the course of the disease. Scrotal swelling, hemorrhage, and testicular pain are frequently observed in male dogs. This finding correlates with the disease in man and experimental infections in rodents. Neurologic signs including pain, loss of balance, tilting of the head, stupor, seizures, and coma may occur in dogs with RMSF. Similar to ehrlichiosis, this presentation can mimic canine distemper in the young dog. Diagnosis The marked variation in clinical presentation allows RMSF to mimic numerous other infectious and noninfectious diseases. Seasonal occurrence, history of tick infestation, fever, or the previously described clinical findings would suggest the possibility of RMSF. Decreased platelets, generally mild in degree, is the most consistent finding in blood counts. Bochemical abnormalities reflect the effects of generalized vascular damage and vary with the severity and duration of infection. Low protien levels,elevated kidney function tests,and increased liver enzymes (serum alkaline phosphatase, alanine aminotransferase) may occur in dogs with RMSF. In general biochemical abnormalities are mild. If joint swelling is present-inflammatory cells may be present. Confirmation of a diagnosis requires either direct immunofluorescent testing for R. rickettsii antigen in tissue biopsies, or serologic testing utilizing an indirect fluorescent antibody test. Evaluation of acute and convalescent sera with greater than or equal to a four_fold increase in antibody titers confirms a diagnosis of RMSF. Timing of sample collection for acute and convalescent sera will greatly influence the serologic results. Cross reaction with other spotted fever group rickettsiae and persistent tick exposure to R. rickettsii complicates the interpretation of serologic results from clinical patients with suspected RMSF. Direct immunofluorescent testing of tissue biopsies provides the opportunity for rapid diagnosis of RMSF. R. rickettsii are generally more readily demonstrated in human patients in areas of hemorrhage prior to initiation of treatment. This also appears applicable to canine patients, although organisms may be more readily identifiable in clinically unaffected skin from dogs. If acute phase sera is obtained several days after the onset of clinical signs, antibody titer to R. rickettsii antigens will be high. Treatment Tetracycline (22 mg/kg TID for 14 days) or doxycycline (5 mg/kg every 12 hours) is the treatment of choice. Based upon studies from our laboratory, chloramphenicol and enrofloxacin are equally effective. A rapid clinical response occurs in dogs without neurologic signs following the initiation of treatment. If fever persists, another diagnosis should be considered likely. Delay in diagnosis and initiation of tetracycline or the use of antibiotics lacking efficacy for treating rickettsial diseases may result in a fatal outcome. Due to severe vascular damage, fluid therapy should be utilized with caution. We have demonstrated that prednisolone, when used at anti-inflammatory or immunosuppressive dosages in conjunction with doxycycline does not potentiate the severity of Rickettsia rickettsii infection in experimentally-infected dogs. However, the results of this study should not be construed as providing definitive support for the use of corticosteroids for treatment of severe RMSF. Prevention Asymptomatic infection possibly contributes to the prevention of severe RMSF in certain groups of dogs with heavy tick exposure in endemic regions. This is evidenced by the high seroprevalence of antibodies to R. rickettsii in serosurveys performed in endemic regions. Minimizing tick exposure and routine removal of ticks from dogs represent the most effective means of prevention. Several new products, available to the veterinarian, appear to provide enhanced efficacy for killing ticks. Care should be exercised in removing ticks, so as not to contaminate one's hands with infective hemolymph from ticks. Infected dogs should be handled carefully, so as to avoid contact with rickettsemic blood during intravenous catheter placement and blood collection. To avoid inadvertent exposure to laboratory personnel, biosafety labels should be placed on blood samples derived from febrile, thrombocytopenic dogs during the tick season.