Spotted Fever Rickettsioses Information for Clinicians

In Illinois, starting in 2005, reported spotted fever rickettsioses (SFR) cases increased gradually until 2020 when the national SFR case definition change was implemented, eliminating the IgM titer, and tightening the IgG titer from 1:64 to 1:128, leading to a decrease in reported cases from 2020 onward. In 2005, there were 11 reported SFR cases in Illinois and by 2018 and 2019, there were 151 (peak) and 136 reported cases, respectively. From 2020-2022, the average reported SFR cases was 21, a more than 600% decrease from 2018 (151 cases), as reflected in IDPH reported tickborne cases 2012-2022.

In regard to national SFR epidemiology and statistics, between 3,000 and 7,000 SFR cases are reported in the United States each year, with an increase in the number of reported cases from 495 reported case in 2000 to a peak of 6,248 reported cases in 2017. There was a slight decrease in reported cases in 2018 and 2019.

In Illinois, Rocky Mountain spotted fever (RMSF) is spread through the bite of infected American dog ticks, and Rickettsia parkeri is spread through the bite of infected Gulf Coast ticks. Immature ticks called nymphs, which are the size of a poppy seed, infect most humans because they frequently go undetected.

SFR pathogens, including RMSF and Rickettsia parkeri, are transmitted to humans from the bite of an infected tick. In Illinois, ticks that can carry and transmit SFR pathogens to humans include American dog ticks and brown dog ticks.

When assessing a patient for SFR, health care providers should consider:

• The signs and symptoms of RMSF and Rickettsia parkeri
• The possibility that other illnesses may cause similar symptoms
  
• Results of laboratory tests, when indicated
  

Brain swelling, altered thought processes, difficulty breathing, coma, and risk of death if not treated prior to fifth day.

If a tick-borne disease is suspected, the clinician should collect complete exposure and travel history information from the patient to support their suspicion of Lyme disease or other tickborne illnesses. The clinician should ask the following:

1. Did the patient travel within Illinois, within the U.S., or outside the U.S. in the three months prior to symptom onset?
2. Did the patient enter a tick habitat (wooded or brushy areas with leaf litter or areas with tall grass)?
   
3. Does the patient have a recent history of a tick bite within the three months prior to symptom onset date?
   

If any of the above questions are answered “No,” the clinician should also document that in the medical record.

If providers suspect a tickborne illness, they should order a complete tickborne diagnostic panel that includes testing for the following pathogens:

• Anaplasmosis
• Babesiosis
  
• Bourbon virus
  
• Ehrlichiosis
  
• Heartland virus
  
• Lyme disease, including Borrelia burgdorferi and Borrelia mayonii
  
• Powassan virus
  
• Spotted fever rickettsioses, including Rocky Mountain spotted fever and Rickettsia parkeri
  
• Tularemia
  

Given there are various SFR species, including for example R. rickettsii, R. parkeri, R. akari, and R. 364D , testing for SFR should be done to identify and to confirm the specific rickettsial species the patient is infected with. The optimal diagnostic test depends on the timing relative to symptom onset and the type of specimen(s) available for testing. Below are various testing methodologies clinicians should consider in the diagnosis of SFR, including serology, molecular, culture, and IHC (immunohistochemical) assays.

• The standard serologic test for diagnosis of RMSF is the indirect immunofluorescence antibody (IFA) assay for immunoglobulin G (IgG) using R. rickettsii antigen.
• IgG IFA assays should be performed on paired acute and convalescent serum samples collected 2–4 weeks apart to demonstrate evidence of a fourfold seroconversion.
  
• Antibody titers are frequently negative in the first week of illness. RMSF cannot be confirmed using single acute antibody results.
  
• Immunoglobulin M (IgM) IFA assays are available through some reference laboratories; however, results might be less specific than IgG IFA assays for diagnosing a recent infection.
  
• R. rickettsii is closely related to other pathogenic spotted fever Rickettsia (SFR) species, including R. akari, R. parkeri, and Rickettsia 364D. Closely related species of SFR share similar antigens such that antibodies directed to one of these antigens can cross-react with other heterologous spotted fever antigens.
  
• Most commercial labs are unable to differentiate one spotted fever infection from another using these serologic methods.
  

When considering serologic testing, it is important for specimen collection to be appropriately timed, given rickettsial pathogens can persist for months to years after infection.

• Antibodies to R. rickettsii might remain elevated for many months after the disease has resolved.
• In certain people, high titers of antibodies against R. rickettsii have been observed up to four years after the acute illness.
  
• 10% or more of healthy people in some areas might have elevated antibody titers due to past exposure to R. rickettsii or other SFR.
  
• Comparison of paired, and appropriately timed, serologic assays provides the best evidence of recent infection.
  
• Single or inappropriately timed serologic tests, in relation to clinical illness, can lead to misinterpretation of results.
  

• Polymerase chain reaction (PCR) amplification is performed on DNA extracted from whole blood.
• R. rickettsii infect the endothelial cells that line blood vessels and may not circulate in large numbers in the blood until the disease has progressed to a severe phase of infection.
  
• Although a positive PCR result is helpful, a negative result does not rule out the diagnosis and treatment should not be withheld due to a negative result.
  
• PCR detection of R. rickettsii in whole blood of an acute blood specimen is possible but less sensitive because low numbers of rickettsiae typically circulate in the blood in the absence of advanced disease.
  
• Tissue specimens are a more useful source of SFG rickettsial DNA than acute blood samples (e.g., a skin biopsy of a rash lesion or in post-mortem tissue specimens). See instructions for the collection of a skin biopsy.
  

• Culture and immunohistochemistry (IHC) assays can also be performed on skin biopsies of a rash lesion or post-mortem tissue specimens.
• Culture isolation and IHC assays of R. rickettsii are only available at specialized laboratories. Routine hospital blood cultures cannot detect the organism.
  

For more in-depth information about diagnostic testing, see Diagnosis and Management of Tickborne Rickettsial Diseases: Rocky Mountain Spotted Fever and Other Spotted Fever Group Rickettsioses, Ehrlichiosis, and Anaplasmosis - United States: A Practical Guide for Health Care and Public Health Professionals (2016).

• The decision to initiate antibiotic therapy for RMSF should be made based on clinical signs and symptoms and a careful patient history, including a recent tick bite or exposure to areas with ticks. A confirmatory diagnosis can be established later using specialized laboratory tests. Never delay or withhold treatment pending the receipt of laboratory test results or on the basis of an initially negative result.
• Doxycycline is the treatment of choice for RMSF and all other tickborne rickettsial diseases. Use of antibiotics other than doxycycline is associated with a higher risk of a fatal outcome from RMSF.
  
• Presumptive treatment with doxycycline is recommended in patients of all ages, including children <8 years of age.
  
• Doxycycline is most effective at preventing severe complications from developing if started within the first five days of illness.
  

• When treated with doxycycline, fever generally subsides within 24–48 hours.
• Severely ill patients may require longer periods of treatment before fever will resolve, especially if they have experienced damage to organ systems.
  
• Resistance to doxycycline or relapses in symptoms after the completion of the recommended course has not been documented.
  

Doxycycline is the first-line treatment for adults and children of all ages.

• Adults: 100 mg every 12 hours
• Children under 45 kg (100 pounds): 2.2 mg/kg body weight given twice a day.
  

Patients with suspected RMSF should be treated with doxycycline for at least three days after the fever subsides and there is evidence of clinical improvement. Minimum course of treatment is 5-7 days.

• Doxycycline is the drug of choice recommended by both CDC and the American Academy of Pediatrics Committee on Infectious Diseases to treat suspected rickettsial disease in children. A recent study found that short courses of doxycycline (5–10 days) did 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.
• Use of antibiotics other than doxycycline increases the risk of severe illness and death.
  

• Doxycycline should be used whenever possible.
• In cases of severe doxycycline allergy, rapid desensitization procedures in an inpatient setting may be considered. Physicians should carefully weigh the benefits of doxycycline use and the risks of adverse effects on a case-by-case basis with an infectious disease or other specialist.
  
• Chloramphenicol is the only alternative drug used to treat RMSF; however, epidemiologic studies suggest that RMSF patients treated with chloramphenicol are at higher risk for death than people 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.
    
• The use of sulfa-containing drugs may worsen clinical course and increase the likelihood of death from RMSF.
  
• Other antibiotics, including almost all other classes of broad-spectrum antibiotics, are not effective in treating RMSF.
  
• The most current evidence-based information indicates 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.
  
• Health care providers should be cautious when exploring treatments other than doxycycline, which is highly effective in treating multiple tickborne diseases, including anaplasmosis, ehrlichiosis, Lyme disease, and other SFR.
  

• Post-tick bite antibiotic prophylaxis is not recommended to prevent RMSF.
• People who were bitten by a tick should be advised to watch for signs and symptoms and see their health care provider if fever, rash, or other symptoms develop within two weeks of tick bite.
  
• Treatment for asymptomatic individuals is not currently recommended.
  

For more in-depth information about the recommended treatment for Rocky Mountain spotted fever see Diagnosis and Management of Tickborne Rickettsial Diseases: Rocky Mountain Spotted Fever and Other Spotted Fever Group Rickettsioses, Ehrlichiosis, and Anaplasmosis - United States: A Practical Guide for Health Care and Public Health Professionals (2016).

Spotted fever rickettsioses (spotted fevers) occur worldwide and result in a broad range of illnesses, from relatively mild to life-threatening.

This table includes the disease, geographic distribution of human cases, etiologic pathogen, and signs and symptoms of each disease.

This eLearning course for providers is designed to increase knowledge and change competency of Rocky Mountain spotted fever practices and strategies.

Course Objectives: At the conclusion of the session, the participant will be able to:

1. Describe Rocky Mountain spotted fever epidemiology, vectors, and risk factors.
2. Identify clinical characteristics of Rocky Mountain spotted fever.
   
3. Explain the importance of early clinical diagnosis and recommended Rocky Mountain spotted fever treatment.
   
4. Describe available laboratory tests for Rocky Mountain spotted fever diagnosis.
   
5. Explain how to prevent and to respond to tick bites.
   
6. Describe the importance of collaboration between clinicians and public health personnel in responding to outbreaks of Rocky Mountain Spotted Fever.