Information for Health Care Providers

Transmission and Epidemiology

Rocky Mountain spotted fever (RMSF) is most often spread by the American dog tick (Dermacentor variabilis) [PDF – 1 page], found east of the Rocky Mountains, but may also be spread by the Rocky Mountain wood tick (D. andersoni) [PDF – 1 page] in the Rocky Mountain region. The brown dog tick (Rhipicephalus sanguineus sensu lato) [PDF – 1 page] has been shown to spread RMSF in parts of the southwestern United States and Mexico. This tick species is found throughout the world and spends the majority of its life on domestic dogs or in areas where dogs may be found (including kennels, yards, and even inside homes). RMSF cases in these areas occur year-round and tick exposure is often reported to occur in and around the home. Unlike cases reported elsewhere in the United States, cases in these areas are characterized by unusually high incidence and case fatality rates, particularly among children.

Signs and Symptoms

RMSF is the most severe rickettsiosis in the United States. The first manifestations of RMSF begin 3-12 days after the bite of an infected tick. The illness generally begins with sudden onset of fever and headache and most people visit a health care provider during the first few days of symptoms. Signs and symptoms may include:

• Fever
• Rash (typically occurs 2-4 days after the onset of fever, but in approximately 10% of cases, may be absent entirely)
• Headache
• Nausea
• Vomiting
• Abdominal pain (may mimic appendicitis or other causes of acute abdominal pain)
• Myalgia
• Anorexia

Progression of the disease varies greatly. Patients who are treated early may recover quickly with outpatient treatment, while those who experience a more severe course may require intravenous antibiotics, prolonged hospitalization, or intensive care.

Rash

While most (90%) people with RMSF have some type of rash during the course of illness, less than 50% of patients have a rash during the first 3 days of illness, the interval during which most people first seek medical care. For this reason, clinicians should consider RMSF if other signs and symptoms support a diagnosis, even if a rash is not present.

A classic case of RMSF involves a rash that appears 2-4 days after the onset of fever as small, flat, pink, macules on the wrists, forearms, and ankles and spreads to include the trunk and sometimes the palms and soles. Rash can be highly variable and people who fail to develop a rash, or develop an atypical rash, are at increased risk of being misdiagnosed. The petechial rash of RMSF is usually not seen until day 5-6 of illness. Petechiae are a sign of progression to severe disease and every attempt should be made to begin treatment before petechiae develop.

Infection in Children

Children with RMSF frequently report experiencing nausea, vomiting, loss of appetite, and rash, but are less likely to report a headache than adults. Other frequently observed signs and symptoms in children with RMSF include abdominal pain, altered mental status, and edema involving the dorsum of the hands or around the eyes.

Severe Illness and Long-term Effects

Untreated disease may lead to more severe manifestations that include encephalitis, shock, seizures, gangrene, and acute respiratory and renal failure. Clinical suspicion for RMSF should be maintained for cases of non-specific febrile illness and sepsis of unknown origin, particularly during spring and summer months when ticks are most active. Most deaths occur within the first 8 days of illness.

Patients who had severe RMSF requiring prolonged hospitalization may have long-term health problems caused by disease. R. rickettsii infects the endothelial cells that line the blood vessels causing vasculitis, and bleeding or clotting in the brain or other vital organs may occur. Loss of fluid from damaged vessels can result in loss of circulation to the extremities, fingers, toes or even limbs, injured irreversibly by ischemic damage may sometimes need to be amputated. Patients who suffer this kind of severe vasculitis in the first 2 weeks of illness may also be left with permanent life-altering health problems such as profound neurological deficits or damage to internal organs. Those who do not have this kind of vascular damage in the initial stages of the disease typically experience a full recovery. There is no evidence that R. rickettsii causes persistent or chronic disease.

For more in-depth information about signs and symptoms of RMSF, please read the updated MMWR Recommendations and Reports.

Diagnosis

RMSF can be difficult to diagnose due to the non-specific signs and symptoms in early stages of illness. Signs and symptoms can vary from patient to patient and can resemble other, more common diseases. Nonetheless, early consideration of rickettsial disease in the differential diagnosis and empiric treatment is crucial to prevent severe illness and death. Many diagnostic tests, especially tests based on the detection of antibodies, will frequently appear negative in the first 7-10 days of illness and cannot be relied upon for initiation of antibiotic therapy.

Patient History

Because RMSF can progress rapidly to severe illness, patients should be diagnosed and treated presumptively based on clinical suspicion. Information such as recent tick bites, exposure to tick habitats, contact with dogs, similar illnesses in family members or pets, or history of recent travel to areas of high incidence can be helpful in making the diagnosis. Tick bites are often painless and are only reported in about half of the people who develop RMSF.

Other Clinical Evidence

Clinical indicators such as thrombocytopenia, hyponatremia, or elevated levels of hepatic transaminases can be helpful predictors of spotted fever infection but may not be present in all patients, particularly those in early stages of illness. After a suspect diagnosis is made on clinical suspicion and treatment has begun, specialized laboratory testing should be used to confirm the diagnosis.

Treatment

Doxycycline is the treatment of choice for RMSF, and other spotted fevers including R. parkeri rickettsiosis, Pacific Coast tick fever, and rickettsialpox.

Empiric treatment with doxycycline is recommended in patients of all ages with suspected RMSF. Treatment is most effective at preventing death and severe RMSF when doxycycline is started within the first 5 days of symptoms. Use of antibiotics other than doxycycline is associated with a higher risk of fatal outcome from RMSF.

Treatment Duration

When a patient is treated within the first 5 days of illness, fever generally subsides within 24-48 hours. In fact, failure to respond to doxycycline suggests that the patient’s condition might not be caused by rickettsial infection. Severely ill patients may require longer periods before their fever resolves, especially if they have experienced damage to organ systems. Resistance to doxycycline or relapses in symptoms after the completion of the recommended course of treatment have not been documented.

Treating Children

The use of doxycycline to treat suspected rickettsial disease in children is standard practice recommended by both CDC and the American Academy of Pediatrics Committee on Infectious Diseases. Use of antibiotics other than doxycycline increases the risk of severe illness and patient death. In a recent study, experts at the CDC and the Indian Health Service found that short courses of doxycycline do not result in staining of permanent teeth or enamel hypoplasia. Use doxycycline as the first-line treatment for suspected RMSF in patients of all ages.

Other Treatments

Chloramphenicol is the only alternative drug that has been used to treat RMSF; however, epidemiologic studies suggest that RMSF patients treated with chloramphenicol are at higher risk for death than persons who received a tetracycline-class antibiotic. Oral formulations of chloramphenicol are not available in the United States, and use of this drug carries the potential for other adverse risks, such as aplastic anemia and Grey baby syndrome. Other antibiotics, including almost all other classes of broad- spectrum antibiotics, are not effective in the treatment of RMSF. The use of sulfa-containing drugs may worsen clinical course and increase the likelihood of death from RMSF.

The most current evidence-based information indicate that the use of doxycycline during pregnancy is unlikely to pose substantial teratogenic effects; nonetheless, it is still not possible to conclude that no risk exists. Pregnant patients should be counseled on the potential risks versus benefits when making a treatment decision.

Antibiotics as Prophylaxis

Post-tick bite antibiotic prophylaxis is not recommended to prevent RMSF. Persons who experience a tick bite should watch for symptoms of RMSF and consult a health care provider if fever, rash, or other symptoms develop within 2 weeks of tick bite.

For more information on the recommended treatment of RMSF, please read the updated MMWR Recommendations and Reports.

Laboratory Confirmation

Serology

Serologic assays are the most frequently used methods for confirming cases of RMSF. The reference standard for serologic diagnosis is the indirect immunofluorescence antibody (IFA) assay. Diagnosis is typically confirmed by documenting a four-fold or greater rise in antibody titer between acute- and convalescent-phase serum samples. Acute-phase specimens are taken during the first week of illness and convalescent-phase samples are generally obtained 2–4 weeks after the resolution of illness. Eighty-five percent of patients will not have detectable antibody titers during the first week of illness, and a negative test during this time does not rule out RMSF. In most patients with RMSF, the first immunoglobulin G (IgG) IFA titer is often negative, and the second typically shows a four-fold or greater increase in IgG antibody levels.

Immunoglobulin M (IgM) antibodies are less specific than IgG antibodies and more likely to produce a falsely positive result. R. rickettsii is closely related to other SFGR species, including R. akari, R. parkeri, and R. philipii.  Closely related species of SFGR share similar antigens such that antibodies directed to one of these antigens can cross-react with other heterologous spotted fever group antigens. Most commercial labs are unable to differentiate one spotted fever infection from another using these serologic methods.

Persistent Antibodies

Antibody titers can remain elevated for months or longer after the disease has resolved, or can be detected in persons who were exposed previously to antigenically related organisms. For these reasons, as many as 10% of persons in some areas of the United States can have elevated levels of antibodies that react with R. rickettsii or similar organisms. Therefore, a single antibody titer should not be used to document or exclude a diagnosis of RMSF. The most conclusive method is the evaluation of paired serum samples, collected 2-4 weeks apart, which reveal a four-fold or greater rise in antibody titer.

PCR, IHC, and Culture

Rickettsia rickettsii infect the endothelial cells that line blood vessels and do not circulate in large numbers in the blood until the disease has progressed to a severe phase of infection. For this reason, whole blood specimens obtained during the first several days of illness are often negative when tested by polymerase chain reaction (PCR) assays or culture. If the patient has a rash, PCR or immunohistochemical (IHC) assays can be performed on a skin biopsy specimen. See instructions for the collection of skin biopsy [PDF – 1 page]. PCR, culture, and IHC assays can also be applied to autopsy tissue specimens. Rickettsia rickettsii are obligate intracellular pathogens and cannot be propagated using routine blood culture methods. Culture of R. rickettsii is generally available only at specialized laboratories that perform cell culture and are equipped with the appropriate biosafety facilities.

For more in-depth information about testing, please read the updated MMWR Recommendations and Reports.