Rocky Mountain Spotted Fever

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., Amblyomma americanum, Rhipicephalus sanguineus).

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 µm, are disseminated via the circulatory system.
• Rickettsia rickettsii is difficult to identify in tissue sections without special stains or through molecular methods.

Disease

• 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. Petecchae 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

• Clinical signs are often vague and do not identify R. rickettsii specifically as the causative agent.

• Fever, joint, and muscle pain are often observed within 3 days of exposure to infected ticks.

• Additional signs include lethargy, anorexia, depression, tremors and emesis.

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.

Incidence and Prevalence

• RMSF is a reportable disease in people, with 250-1200 cases reported annually.
• 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 southern Atlantic states (Delaware, Maryland, Washington D.C., Virginia, West Virginia, North Carolina, South Carolina, Georgia, and Florida) and the southcentral states (Arkansas, Oklahoma, Louisiana, Texas). North Carolina and Oklahoma account for approximately 35% of the total reported human cases each year. Infections also occur in the Pacific Northwest (Oregon, Washington, California). 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 is usually 5-10 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.
• Complete blood count may reveal anemia, thrombocytopenia, leukopenia, and/or leukocytosis.
• Serum chemistry profile often shows hypoproteinemia, hypoalbumineamia, azotemia, hyponatremia, hypocalcemia, and/or increased liver enzymes.
• A four-fold increase in IgG titer or a single IgG titer > 1024 on an immunofluorescent antibody test (IFA) confirms infection, although cross reactions with other rickettsial organisms are common.
• 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.
• The presence of R. rickettsia in biopsy or necropsy samples of tissues can be confirmed via direct detection of antigen with an 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 (BL3) biosafety procedures and facilities.

Treatment

• The antibiotic treatment of choice for RMSF is doxycycline (10-20 mg/kg orally or intravenously q 12-24 hours for 14 -21 days) or tetracycline (22 mg/kg orally q 8 hours for 14-21 days). Generally defervescence and improvement in energy and appetite occur within days after the first dose.
• Relapses following 14 days of treatment have been reported.
• Prednisone may help with immune-mediated complications (1-4 mg/kg orally q 24 hours), and supportive fluid therapy may be needed.
• Immunity to reinfection occurs if the disease is successfully treated; dogs that recover from RMSF appear to be protected from future infections with R. rickettsia.

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.
• Less than 5% of the ticks in a given area are infected; prophylactic antibiotic use is not recommended following a single tick bite.
• Vaccines are not available to protect pets or people from infection with R. rickettsia.

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

• Warner RD, Marsh WW. 2002. Rocky Mountain spotted fever. JAVMA 221:1413-1417.
• 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.
• 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.
• 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
• 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