Rocky Mountain Spotted Fever

Information for Healthcare Providers/Veterinarians

  • Signs & Symptoms
  • Rash
  • Long-term Health Problems
  • Physician Diagnosis
  • Laboratory Confirmation
  • Treatment
  • Prophylaxis (Preventive Treatment)

Signs and Symptoms

The first symptoms of RMSF typically begins about 7 days after the bite of an infected tick, however symptoms can begin anywhere from 2 to 14 days, and the disease often starts with the sudden onset of fever and headache.

The following is a list of symptoms commonly seen with RMSF; however, it is important to note that few people with the disease will develop all symptoms:

  • Fever
  • Rash (occurs 2-5 days after fever, may be absent in some cases)
  • Headache
  • Nausea
  • Vomiting
  • Abdominal pain
  • Muscle pain
  • Lack of appetite
  • Upper respiratory symptoms

*Children are less likely than adults to report a headache, but more likely to develop an early rash

Few people with the disease will develop all symptoms; therefore, it is important to remember:

  • The number and combination of symptoms varies greatly from person to person
  • Symptoms like cough, sore throat, and diarrhea can be seen, and may lead to misdiagnosis
  • Patients should be treated on clinical diagnosis before laboratory tests are ordered

Rash

About 60% of cases have some type of rash during the course of illness, but some do not develop the rash until late in the disease process. (The rash is uncommon in Arizona RMSF cases.)

 

A classic case of RMSF involves

  • A rash that first appears 2-5 days after the onset of fever
  • A rash that appears as small, flat, pink, non-itchy spots (macules) on the wrists, forearms, and ankles and spreads to include the trunk and sometimes the palms and soles
  • The rash is usually not seen until the sixth day or later after onset of symptoms
  • This petechial rash is a sign of organ damage

Long-term Health Problems

Rocky Mountain spotted fever (RMSF) can result in long-term health problems that differ from case to case.

Physician Diagnosis

The diagnosis of RMSF must be made based on clinical signs and symptoms, and can later be confirmed using specialized confirmatory laboratory tests. Treatment should never be delayed pending the receipt of laboratory test results, or be withheld on the basis of an initial negative finding for R. rickettsii.

Diagnostic tests for RMSF antibodies

  • Typically appears negative the first 7-10 days of illness
  • There is no test available that can provide a conclusive result in time to make treatment decisions

Information such as recent tick bites, exposure to tick-infested areas, contact with dogs, similar illnesses in family members or pets, or history of travel to areas of high incidence can be helpful in making a correct diagnosis.

Helpful predictors of RMSF infection that may appear on routine blood tests in some patients include:

  • Thrombocytopenia (low platelet count)
  • Hyponatremia (low sodium levels)
  • Elevated liver enzyme levels

After a suspect diagnosis is made on clinical suspicion and treatment has begun, specialized laboratory testing should be used to confirm the diagnosis of RMSF and two blood samples must be taken: one early in the patients’ illness and one 2-4 weeks later to confirm illness and positively diagnose RMSF.

Clinical Algorithm

Laboratory Confirmation

R. rickettsii infects the endothelial cells that line blood vessels, and does not circulate in large numbers in the blood unless the patient has progressed to a very serious phase of infection. For this reason, blood specimens (whole blood and serum) are not always useful for detection of the organism through polymerase chain reaction (PCR) or culture.

During RMSF infection, a patient’s immune system develops antibodies to R. rickettsii, with detectable antibody titers usually observed 7-10 days after illness onset. It is important to note that antibodies are not detectable in the first week of illness in 85% of patients, and a negative test during this time does not rule out RMSF as a cause of illness.

The gold standard serologic test for diagnosis of RMSF is the indirect immunofluorescence assay (IFA) with R. rickettsii antigen, performed on two paired serum samples to demonstrate a significant (four-fold) rise in antibody titers. The first sample (acute sample) should be taken as early in the disease as possible, preferably in the first week of symptoms, and the second sample (convalescent sample) should be taken 2 to 4 weeks later.

Interpretation of Acute vs. Convalescent IFA for IgG

To demonstrate a significant (four-fold) rise in antibody titers

  1. Acute - first sample taken as early in the disease as possible (preferably in the first week of symptoms)
  2. Convalescent - second sample taken 2 to 4 weeks later

*In most RMSF cases, the first IgG IFA titer is low or negative and the second shows a significant (fourfold) increase in IgG, so a negative acute test doesn’t mean the patient does not have the disease. Do not stop treatment with doxycycline if the first IgG IFA test is negative.

  • IgM and IgG Antibody Levels
    IgM antibodies usually rise at the same time as IgG near the end of the first week of illness and remain elevated for months or even years. Also, IgM antibodies are less specific than IgG antibodies and more likely to result in a false positive. For these reasons, physicians requesting IgM serologic titers should also request a concurrent IgG titer.

    Both IgM and IgG levels may remain elevated for months or longer after the disease has resolved, or may be detected in persons who were previously exposed to antigenically related organisms. Up to 10% of healthy people in some areas can have elevated antibody titers due to past exposure to R. rickettsii or similar organisms. Therefore, if only one sample is tested it can be difficult to interpret, whereas two paired samples taken weeks apart demonstrating a significant (four-fold) rise in antibody titer provide the best evidence for a correct diagnosis of RMSF.
  • Skin Biopsy
    If the patient has a rash, PCR or immunohistochemical (ICH) staining can be performed on a skin biopsy taken from the rash site. This can often deliver a rapid result. These tests have good sensitivity (70%) when applied to tissue specimens collected during the acute phase of illness and before antibiotic treatment has been started, but a negative result should not be used to guide treatment decisions.
  • Autopsy Specimens
    PCR, culture, and IHC can also be applied to autopsy specimens (live, spleen, kidney, etc.) collected after a patient dies. Culture of R. rickettsii is only available at specialized laboratories; routine hospital blood cultures cannot detect R. rickettsii.

Treatment

Doxycycline is the first line treatment for adults and children of all ages and should be initiated immediately whenever RMSF is suspected.

Treatment for RMSF is

  • Most effective at preventing death if doxycycline is started in the first 5 days of symptoms
  • Based on clinical suspicion alone
  • Recommended before laboratory results return or symptoms of severe disease develop.

If the patient is treated within the first 5 days of the disease, fever generally subsides within 24-72 hours (failure to respond to doxycycline suggests that the patient's illness might not be caused by RMSF). Severely ill patients may require longer periods before their fever resolves, especially if they have experienced damage to multiple organ systems.

  • Treating Children
    Both the CDC and the AAP (American Academy of Pediatrics) Committee on Infectious Diseases recommend that children with RMSF are treated using doxycycline. Use of antibiotics other than doxycycline increases the risk of patient death.

    Unlike older tetracyclines used as antibiotics to treat RMSF, the recommended dose and duration of doxycycline needed to treat RMSF has not been shown to cause staining of permanent teeth in children (even when five courses are given before the age of eight).

    More information on doxycycline use in children can be found in the American Academy of Pediatrics 2012 Red Book pages 632-325.
  • Recommended Dosage
    Doxycycline is the first line treatment for adults and children of all ages:
    • Adults – 100 mg every 12 hours
    • Children under 45kg (100 lbs) - 2.2 mg/kg body weight given twice a day
    Patients should be treated for at least 3 days after the fever subsides and until there is evidence of clinical improvement. Standard duration of treatment is 5-14 days.
  • Other Treatments
    Other antibiotics, such as broad spectrum antibiotics, are not effective in the treatment of RMSF and the use of sulfa drugs may even worsen the infection.

    Chloramphenicol may be considered as an alternative antibiotic in patients who may have a life threatening allergies to doxycycline or some pregnant women with a mild RMSF case; however patients treated with chloramphenicol are at a greater risk for fatal outcomes when compared to patients treated with doxycycline.

Prophylaxis (Preventive Treatment)

According to the CDC, antibiotic treatment following a tick bite is not recommended to prevent RMSF as it may simply delay onset of disease. There is also no vaccine or prophylaxis available to prevent RMSF.

Veterinarians

Rocky Mountain spotted fever (RMSF) is an important zoonotic disease that causes clinical illness in both dogs and humans. It is caused by the organism Rickettsia rickettsii, a small gram-negative obligate intracellular parasite from the family Rickettsiaceae. Although RMSF been long identified as a human pathogen, RMSF was not recognized in dogs until the 1970's¹²

The primary vector of RMSF is hard-bodied ticks. Rhipicephalus sanguineous (The Brown Dog Tick) is the most common vector in Arizona.

R. rickettsii is transmitted to the dog through the bite of an infected tick. Once inside the body:

  • the organism undergoes a 2-14 day incubation period
  • The organism then invades endothelial cells of the venules and capillaries and begins replicating, causing a vasculitis

The replication of R. rickettsii and subsequent vasculitis may lead to edema, hemorrhage, shock, and vascular collapse. Endarterial organs (brain, skin, heart and kidneys) are affected most often. Vascular leakage also triggers activation of the animal's platelets and coagulation system.

Click on a link below to view the veterinarian information.

  • Signs & Symptoms
  • Laboratory Confirmation
  • Treatment
  • Prevention

Signs and Symptoms

Symptoms usually appear 4 or 5 days following a tick bite and almost always include:

  • Fever (39.2°C [102.6°F] to 40.5°C [104.9°F]) and
  • Severe lethargy

Other symptoms that may occur are:

  • Petechiae and ecchymoses on oral, nasal, ocular, and genital mucous membranes
  • Focal retinal hemorrhages
  • Edema of the extremities and/or lips, pinna of ears, penile sheath, and scrotum.

In late-stage disease or during recovery, symptoms may include:

  • Necrosis (acryl gangrene) of the extremities
  • Abdominal pain, vomiting, and/or anorexia
  • Altered mental status (signs of depression, stupor)
  • Myalgia and/or polyarthritis
  • Vestibular deficits (circling, head tilt, or nystagmus)
  • Dyspnea or cough

Such signs indicate more disseminated lesions, substantial organ edema, and a worse prognosis.

The most likely abnormal clinical laboratory findings are:

  • Hypoalbuminemia,
  • Moderate leukocytosis (minimal left shift)
  • Thrombocytopenia

Platelet counts usually range from 25,000 to 250,000/µL. If hypoalbuminemia develops, it probably results from widespread damage to the vascular endothelium and subsequent intercellular leakage. In dogs that are examined primarily because of cough or dyspnea, thoracic radiography typically reveals diffuse interstitial densities (pneumonitis). Clinical RMSF may also resemble infection with Ehrlichia canis, which is also transmitted by the brown dog tick, although RMSF tends to be more severe.

Laboratory Confirmation

The gold standard serologic test for diagnosis of RMSF is the indirect immunofluorescence assay (IFA) with R. rickettsii antigen, performed on two paired serum samples to demonstrate a significant (four-fold) rise in antibody titers.

  • The first sample should be taken as early in the disease as possible, preferably in the first week of symptoms
  • The second sample should be taken 2 to 4 weeks later

Veterinarians should request IgM serologic titers and a concurrent IgG titer because:

  • The first IgG IFA titer is typically low or negative
  • The second typically shows a significant (fourfold) increase in IgG antibody levels
  • IgM antibodies usually rise at the same time as IgG near the end of the first week of illness and remain elevated for months or even years
  • IgM antibodies are less specific than IgG antibodies and more likely to result in a false positive

IgM and IgG levels may remain elevated for months or longer after the disease has resolved, or may be detected in dogs that were previously exposed to antigenically related organisms. Because there is no widely available rapid laboratory assay to provide early confirmation of RMSF, specific antibiotic treatment decisions should be made on the basis of epidemiologic and clinical clues rather than awaiting laboratory confirmation.

Treatment

  • The antibiotic of choice for treating RMSF in dogs is doxycycline (10 to 20 mg/kg [4.5 to 9.1 mg/lb]).
  • Mortality from RMSF is directly related to incorrect treatment, delayed diagnosis, or both.
  • The prompt use of antibiotic treatment reduces the severity of illness when it is given before tissue necrosis (thrombotic lesions) or coagulation disorders develop.

Naturally acquired immunity most likely plays a role in limiting or protecting against clinical illness. Healthy dogs from endemic areas often possess anti-Spotted Fever Group (SFG) antibodies, possibly a result of prior R. rickettsii infection or exposure to nonpathogenic SFG rickettsiae.

Prevention

To prevent RMSF in Dogs:

  • Prevent tick attachment (promptly and carefully removed using forceps or gloved hands)
  • Use a topical or systemic tick-control treatment such as permethrin, fipronil
  • Use a seasonal tick and flea dips
  • Use of impregnated collars containing amitraz or propoxur

In areas with a high tick population and/or human cases of RMSF, regular applications of an acaricidal treatment to kennels and yards can reduce the number of ticks in a dog's environment. Brown dog ticks have also been found inside homes when dogs are permitted to come inside, and inside treatments from experienced pesticide technicians may be required to control infestations. There are no anti-rickettsial vaccines available for use in either dogs or humans.

References
  1. Warner RD, Marsh WW: Rocky Mountain Spotted Fever. J Vet Intern Med, 10:1413-1417, 2002.
  2. Greene CE: Infectious Diseases of the Dog and Cat, 2nd ed. WB Saunders and Co., Philadelphia, 1998, pp. 155-162.