Rickettsial Infection Guidelines

Updated: Nov 22, 2021
  • Author: Mobeen H Rathore, MD, CPE, FAAP, FIDSA; Chief Editor: Russell W Steele, MD  more...
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Guidelines Summary

In 2016, the Centers for Disease Control and Prevention updated their recommendations on the diagnosis and management of tickborne rickettsial diseases in the United States.

Recommendations include the following [39] :

Summary of epidemiologic clues from the clinical history

  • The absence of known tick attachment should never dissuade a health care provider from considering the diagnosis of tickborne rickettsial disease.
  • Clustering of certain tickborne rickettsial diseases is well recognized and has been reported among family members, pet dogs, coworkers, military personnel, and other groups.
  • Dogs and humans are susceptible to infection with many of the same tickborne rickettsial pathogens, including Rickettsia rickettsii, Ehrlichia chaffeensis, Ehrlichia ewingii, and Anaplasma phagocytophilum; in some instances, pet dogs might serve as sentinels for tickborne rickettsial disease in humans.

Summary of clinical features of Rocky Mountain spotted fever and other spotted fever group rickettsioses

  • Rocky Mountain Spotted Fever (RMSF) is the most severe rickettsial illness in the United States. Delay in recognition and treatment is the most important factor associated with risk of death from RMSF.
  • The classic triad of fever, rash, and reported tick bite is rarely present when patients with RMSF first seek care.
  • Rash is present in most patients during the course of RMSF, although it can appear late or be atypical, localized, faint, evanescent, and difficult to recognize in persons with darker pigmented skin.
  • Rickettsia parkeri rickettsiosis is typically milder than RMSF, and the first manifestation in nearly all patients is an inoculation eschar.

Summary of clinical features of ehrlichioses

  • Symptoms of Ehrlichia chaffeensis ehrlichiosis typically include fever, headache, malaise, myalgia, and gastrointestinal symptoms. With E chaffeensis ehrlichiosis, rash is present in approximately one third of patients but is more common among children than among adults.
  • Neurologic manifestations are reported for approximately 20% of patients with E chaffeensis ehrlichiosis.
  • Increased severity of E chaffeensis ehrlichiosis has been associated with increased age (≥60 yr) and immunosuppression.
  • Leukopenia, thrombocytopenia, and elevated hepatic transaminase levels are characteristic laboratory findings in the first week of E chaffeensis ehrlichiosis.
  • E chaffeensis has a predilection for mononuclear phagocytic cells, and morulae might be observed in monocytes of the blood, CSF, or bone marrow phagocytes.
  • Ehrlichia ewingii ehrlichiosis has similar clinical features as E chaffeensis ehrlichiosis; however, rash and gastrointestinal symptoms are less common. E ewingii has a predilection for granulocytes, and morulae might be observed in granulocytes of the blood, CSF, or bone marrow.
  • The case-fatality rate for E chaffeensis ehrlichiosis is approximately 3%; no deaths from E ewingii or E muris-like (EML) agent ehrlichiosis have been reported.

Summary of clinical features of anaplasmosis

  • Anaplasma phagocytophilum has a predilection for granulocytes, and blood smear or bone marrow examination might reveal morulae within these cells.
  • The tick vector that transmits A phagocytophilum also transmits other pathogens, and coinfections with Borrelia burgdorferi or Babesia microti have been described.

Recommended treatment for tickborne rickettsial diseases

  • Doxycycline is the drug of choice for treatment of all tickborne rickettsial diseases in children and adults; empiric therapy should be initiated promptly in patients with a clinical presentation suggestive of a rickettsial disease.
  • Tickborne rickettsial diseases respond rapidly to doxycycline, and fever persisting for >48 hr after initiation of therapy should prompt consideration of an alternative or additional diagnosis, including the possibility of coinfection.
  • Doxycycline is recommended by the American Academy of Pediatrics and CDC as the treatment of choice for patients of all ages, including children aged < 8 yr, with a suspected tickborne rickettsial disease.
  • Delay in treatment of tickborne rickettsial diseases can lead to severe disease and death.
  • In persons with severe doxycycline allergy or who are pregnant, chloramphenicol may be an alternative treatment for RMSF; however, persons treated with chloramphenicol have a greater risk of death compared with those treated with doxycycline.
  • Chloramphenicol is not an acceptable alternative for the treatment of ehrlichiosis or anaplasmosis.
  • For mild cases of anaplasmosis, rifampin might be an alternative to doxycycline for patients with a severe drug allergy or who are pregnant.
  • Data on the risks of doxycycline use during pregnancy suggest that treatment at the recommended dose and duration for tickborne rickettsial diseases is unlikely to pose a substantial teratogenic risk; however, data are insufficient to state that no risk exists.
  • Prophylactic use of doxycycline after a tick bite is not recommended for the prevention of tickborne rickettsial diseases.
  • Treatment of asymptomatic persons seropositive for tickborne rickettsial disease is not recommended, regardless of past treatment status, because antibodies can persist for months to years after infection.

Summary of confirmatory diagnostic tests

  • Antibacterial treatment should never be delayed while awaiting laboratory confirmation of rickettsial illness, nor should treatment be discontinued solely on the basis of a negative test result with an acute phase specimen.
  • The reference standard for diagnosis of tickborne rickettsial diseases is the indirect immunofluorescence antibody (IFA) assay using paired serum samples obtained soon after illness onset and 2-4 wk later. Demonstration of at least a 4-fold rise in antibody titer is considered confirmatory evidence of acute infection.
  • Patients usually do not have diagnostic serum antibody titers during the first week of illness, and a negative result by IFA assay or enzyme-linked immunosorbent assay (ELISA) during this period does not exclude the diagnosis of tickborne rickettsial diseases.
  • For ehrlichioses and anaplasmosis, diagnosis during the acute stage can be made using polymerase chain reaction (PCR) amplification of DNA extracted from whole blood.
  • PCR assay of whole blood is less sensitive for diagnosis of RMSF than it is for ehrlichiosis or anaplasmosis; however, sensitivity increases in patients with severe disease.
  • For spotted fever group (SFG) rickettsioses, immunostaining of skin rash or eschar biopsy specimens or a PCR assay using DNA extracted from these specimens can help provide a pathogen-specific diagnosis.
  • Immunostaining of autopsy specimens can be particularly useful for diagnosing fatal tickborne rickettsial infections.
  • Blood-smear or buffy-coat preparation microscopy might reveal the presence of morulae in infected leukocytes, which is highly suggestive of anaplasmosis or ehrlichiosis. Blood-smear microscopy is not useful for RMSF, other SFG rickettsioses, or EML agent ehrlichiosis.
  • Rickettsiae cannot be isolated with standard blood culture techniques because they are obligate intracellular pathogens; specialized cell culture methods are required. Because of limitations in availability and facilities, culture is not often used as a routine confirmatory diagnostic method for tickborne rickettsial diseases.

Summary of prevention of tickborne rickettsial diseases

  • Use tick repellents containing DEET, IR3535, picaridin (1-piperidinecaboxylic acid, 2-[2-hydroxyethyl], 1-methlypropyl ester), or other EPA-registered products when outdoors. Follow package label instructions for application.
  • Wear protective clothing, including long-sleeved shirts, pants, socks, and closed-toe shoes.
  • Permethrin-treated or impregnated clothing can significantly reduce the number of tick bites when working outdoors.
  • Protect pets from tick bites by regularly applying veterinarian-approved ectoparasite control products, such as monthly topical acaricide products, acaricidal tick collars, oral acaricidal products, and acaricidal shampoos.