Rocky Mountain Spotted Fever

CAPC Recommends

• Diagnosing Rickettsia rickettsii infection in dogs can be challenging and relies upon compatible clinical signs, serology, and PCR testing.
• Doxycycline is the treatment of choice (see Treatment guidelines) and should be started if R. rickettsii is suspected. Do not withhold treatment while waiting for confirmatory test results.
• Reduce the risk of infection through effective year-round tick control and avoiding areas with ticks. Remove ticks promptly when found.
• Dogs can serve as sentinels for the risk of Rocky Mountain spotted fever in people.

Species

Rickettsia rickettsii

Overview of Life Cycle

• Dogs and people become infected with Rickettsia rickettsii when feeding ticks transmit rickettsial organisms. Cats may be seropositive but are not known to develop clinically apparent disease.
• Transmission is generally thought to occur 5 to 20 hours after tick attachment.
• The primary tick vectors in North America are Dermacentor spp.; other tick species have also been implicated in this region (e.g., Rhipicephalus sanguineus, Amblyomma americanum).

Stages

• Intracellular organisms are found predominantly in endothelial cells of small vessels.
• The microscopic bacteria, which vary in size from 0.2-0.5 X 0.3-2.0 µm, are disseminated via the circulatory system.
• Rickettsia rickettsii is difficult to identify in tissue sections without special stains or through molecular methods.

Disease

• Disease caused by infection with Rickettsia rickettsii is known as Rocky Mountain Spotted Fever (RMSF).
• The organisms invade and replicate in endothelial cells of small vessels (arterioles and venules), causing vasculitis.
• Damage to vessel walls results in leakage of blood and subsequent macular skin rash. Petechial and ecchymotic hemorrhages may develop in skin and other affected organs, particularly those with pronounced microcirculation (end-arterioles) such as kidney, brain, and heart. Petechiae are often easily observed on the gums, buccal mucosa, or conjunctiva.
• Thrombocytopenia and decreased circulation can result in multi-organ involvement.
• Lymphocytopenia followed by lymphocytosis may develop.
• The incubation period varies from a few days to 2 weeks.

Dogs

• Early clinical signs are often vague and do not identify R. rickettsii specifically as the causative agent.
• Some of the earliest signs of infection are fever, lethargy, depression, and anorexia.
• Additional signs can include lymph node enlargement, edema, hyperemia, joint pain and muscle pain, petechial hemorrhage, ecchymoses, and macular to maculopapular skin rash.
• Many cases also present with ocular signs which are often bilateral which include signs of hemorrhage, anterior uveitis, and retinal vasculitis.
• In late-stage disease, tissue necrosis can be seen particularly in the extremities.
• Neurologic abnormalities may be present and can include signs of vestibular disease, tremors, paraparesis, tetraparesis, altered mentation, and seizures.
• Dogs with neurologic dysfunction carry a worse prognosis.

People

• The classic triad of RMSF in people includes fever, rash, and severe headache.
• Initially patients report fever, nausea, vomiting, severe headache, muscle pain, and lack of appetite.
• The skin rash (which may be difficult to see) usually occurs between 2 and 5 days after fever develops. The rash first appears as small, red to pink, non-pruritic spots on the wrists, forearms, and ankles.
• Late-stage illness is similar to that in dogs and includes neurologic dysfunction, respiratory disease, tissue necrosis, and multi-organ system damage.
• Humans can also be infected with other rickettsial diseases that present with similar signs and symptoms, however they are generally less severe than RMSF.

Incidence and Prevalence

• RMSF is a reportable disease in people and falls under the spotted fever rickettsiosis. Recently, there have been approximately 40-200 confirmed cases of spotted fever rickettsiosis diagnosed each year with around 1,000 – 6,000 additional suspected cases.
• Most cases occur from April to September, which corresponds to the highest seasonal activity of adult and nymphal Dermacentor spp. ticks.
• A history of exposure to ticks or visits to tick infested habitats is documented in about two-thirds of the reported human cases.
• Most cases occur in the South and Midwest regions of the US. North Carolina, Oklahoma, Arkansas, Tennessee, and Missouri account for over 60% of reported cases.
  • Although the first cases of RMSF were described from the Rocky Mountain region, fewer than 5% of human cases are currently reported from that region.
  • In recent years, increased numbers of cases have been reported in Arizona where it has been associated with a newly recognized vector (Rhipicephalus sanguineus).
• Free roaming dogs and people in rural areas are generally at greater risk of disease due to their increased likelihood of exposure to ticks.
• In people, the preponderance of cases of RMSF occurs in children, with males overrepresented in reported cases.

Host Associations and Transmission Between Hosts

• Dogs and people become infected with Rickettsia rickettsii when feeding ticks inoculate rickettsial organisms via tick salivary secretions.
• Transmission can also occur via tick fluids, crushed tick tissues, or tick feces.
• Ticks are infected by transstadial (stage to stage), transovarial (female tick to ovum), and sexual (during tick mating) transmission of rickettsial organisms.
• In endemic areas during outbreaks, very few (approximately 1-3%) of ticks are reported to be infected with R. rickettsii.

Prepatent Period and Environmental Factors

• Transmission generally occurs 5 to 20 hours after tick attachment.
• The incubation period varies from a few days to 2 weeks. In people, the incubation period ranges from 3-12 days after exposure to infected ticks.

Diagnosis

• Clinical signs, geographic region, time of year, and/or a history of tick exposure or recovery of potential vector ticks should raise the index of suspicion for RMSF. The lack of history of recent tick exposure and/or ticks at presentation does not exclude RMSF. A retrospective study found that only a small percentage of dogs with RMSF had a history of recent tick exposure and/or ticks at the time of presentation to a veterinarian.
• Complete blood count may reveal anemia, thrombocytopenia, leukopenia, and/or leukocytosis.
• Serum chemistry profile often shows hypoproteinemia, hypoalbuminemia, hyperbilirubinemia, azotemia, hyponatremia, hypocalcemia, and/or increased liver enzymes.
• A four-fold increase in IgG titer on an immunofluorescent antibody test (IFA) confirms infection, although cross reactions with other rickettsial organisms are common. Additionally, a single high IgG titer > 1024 on IFA is suggestive of active infection when paired with appropriate clinical signs and findings.
• Because dogs are often seronegative during initial clinical disease, serology should not be used to eliminate RMSF as a diagnosis in an acutely ill dog; treatment must be instituted based on clinical impression to avoid fatalities associated with delay of antibiotic administration.
• Serologic tests for antibodies to R. rickettsia have been shown to cross-react with other Rickettsia spp. that are not known to cause disease in dogs. Therefore, due to the potential cross-reactivity, IFA testing is most appropriate for dogs that are exhibiting clinical signs.
• The presence of R. rickettsii in biopsy or necropsy samples of tissues can be confirmed via direct detection of antigen with a FA or by polymerase chain reaction (PCR); PCR may also be useful to test whole blood during acute infection although organisms are not consistently present in circulation or detected.
• Culture of organisms is not usually attempted and requires specialized (BSL3) biosafety procedures and facilities.

Treatment

• Do not delay antibiotic treatment in suspect RMSF cases. If RMSF is suspected, treatment should be instituted while waiting for diagnostic results.
• The antibiotic treatment of choice for RMSF is doxycycline (10 mg/kg orally or intravenously q 24 hours for 14 -28 days). Generally, clinical improvement is noted within the first few days of treatment.
  • A split-dose protocol of doxycycline (5 mg/kg orally or intravenously q 12 hours) can also be used.
  • Shorter courses of therapy (7 – 14 days) may be adequate for uncomplicated cases, however prolonged treatment is recommended especially in cases with the potential for co-infections with other tick-borne diseases.
• Due to the high cross-reactive nature of IFA tests for Rickettsia spp., veterinarians are encouraged to consider other causes of bleeding disorders if the patient is not responding to doxycycline within the first few days, although continuing the doxycycline for the full course or until another disease is diagnosed is still most appropriate.
• Relapses following 14 days of treatment have been reported.
• Other alternative treatments include tetracycline (22 mg/kg orally q 8 hours for 14-21 days) and enrofloxacin (5 mg/kg orally or intravenously q 12 hours for 7-14 days). Enrofloxacin should be avoided in young animals.
• A short course of corticosteroids may help in cases with severe inflammatory or immune-mediated complications, however their use is controversial. One study found no detrimental effects when prednisolone was administered in combination with doxycycline to dogs with experimentally induced mild to moderate RMSF.
• Supportive care, such as fluid therapy or extended hospitalization, may be needed especially in more severely affected animals.
• Immunity to reinfection occurs if the disease is successfully treated; dogs that recover from RMSF appear to be protected from future infections with R. rickettsii.

Control and Prevention

• The key to prevention in both dogs and people is to limit exposure to potentially infected ticks.
  • The CAPC recommends that all dogs be maintained year-round on tick control products to prevent attachment and feeding of ticks.
  • Year-round tick control is particularly important to prevent establishment of home infestations with R. sanguineus, a confirmed vector of RMSF.
• Tick control efforts can be aided by removing tick habitat around the home (e.g. trimming brush, clipping grass, removing leaf litter), excluding wildlife by installing fencing and removing debris, and limiting contact with infested areas by preventing roaming in dogs. 
• Care should be taken in the removal of ticks from pets to prevent human contact with infectious organisms.
• Vaccines are not available to protect pets or people from infection with R. rickettsii.

Public Health Considerations

• RMSF is a potentially fatal zoonosis acquired from ticks.
• The vector ticks, clinical signs of disease, and treatment and preventive strategies are similar for dogs and people.
• RMSF infection in dogs should alert the owner of their potential exposure to infected ticks. However, direct transmission of organisms from dogs to people is not known to occur.

Selected References

• Breitschwerdt EB, Davidson MG, Aucoin DP, Levy MG, Szabados NS, Hegarty BC, Kuehne AL, James RL. 1991. Efficacy of chloramphenicol, enrofloxacin, and tetracycline for treatment of experimental Rocky Mountain spotted fever in dogs. Antimicrob Agents Chemother 35(11):2375-2381.
• Breitschwerdt EB, Davidson MG, Hegarty BC, Papich MG, Grindem CB. 1997. 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 41(1):141-147.
• Centers for Disease Control and Prevention. CDC WONDER. https://wonder.cdc.gov/
• Centers for Disease Control and Prevention. (2024, May 15). Rocky Mountain Spotted Fever (RMSF): Clinical Overview of Transmission and Epidemiology. 15 May 2024. https://www.cdc.gov/rocky-mountain-spotted-fever/hcp/clinical-overview/index.html
• Dahlgren FS, Holman RC, Paddock CD, Callinan LS, McQuiston JH. 2012. Fatal Rocky Mountain spotted fever in the United States, 1999-2007. Am J Trop Med Hyg. 86(4):713-719.
• Davidson MG, Breitschwerdt EB, Nasisse MP, Roberts SM. 1989. Ocular manifestions of Rocky Mountain spotted fever in dogs. JAVMA 194(6):777-781.
• Drexler N, Miller M, Gerding J, Todd S, Adams L, Dahlgren FS, Bryant N, Weis E, Herrick K, Francies J, Komatsu K, Piontkowski S, Velascosoltero J, Shelhamer T, Hamilton B, Eribes C, Brock A, Sneezy P, Goseyun C, Bendle H, Hovet R, Williams V, Massung R, McQuiston JH. Community-based control of the brown dog tick in a region with high rates of Rocky Mountain spotted fever, 2012-2013. PLoS One. 2014 Dec 5;9(12):e112368. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4257530
• Gasser AM, Birkenheuer AJ, Breitschwerdt EB. 2001. Canine Rocky Mountain spotted fever: a retrospective study of 30 cases. JAAHA 37:41-48.
• Levin ML, Killmaster LF, Zemtsova GE, Ritter JM, Langham G. Clinical presentation, convalescence, and relapse of rocky mountain spotted fever in dogs experimentally infected via tick bite. PLoS One. 2014 Dec 26;9(12):e115105. http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0115105
• McQuiston JH, Guerra MA, Watts MR, Lawaczeck E. Levy C, Nicholson WL, Adjemian J, Swerdlow DL. 2011. Evidence of exposure to spotted fever group rickettsiae among Arizona dogs outside a previously documented outbreak area. Zoonoses Public Health 58(2):85-92.
• Mikszewski JS, Vite CH. 2005. Central nervous system dysfunction associated with Rocky Mountain spotted fever infection in five dogs. JAAHA 41(4):259-266.
• Warner RD, Marsh WW. 2002. Rocky Mountain spotted fever. JAVMA 221:1413-1417.