Editor’s note: This article summarizes key points from a Centers for Disease Control and Prevention (CDC) report published in Morbidity and Mortality Weekly Report (MMWR). To subscribe to MMWR, visit www.cdc.gov/MMWR.
Biggs HM, et al. “Diagnosis and Management of Tickborne Rickettsial Diseases: Rocky Mountain Spotted Fever and Other Spotted Fever Group Rickettsioses Ehrlichioses, and Anaplasmosis – United States.” MMWR Recomm Rep. 2016;65(No. RR-2):1-44, http://dx.doi.org/10.15585/mmwr.rr6502a1
Tickborne rickettsial infections are caused by the obligate intracellular bacteria of the order Rickettsiales. In the U.S., these infections include three major categories: spotted fever group rickettsioses, ehrlichioses and anaplasmosis, all of which are nationally notifiable.
Tickborne rickettsial infections peak during the spring and summer months along with tick exposures. Ticks inhabit a wide variety of environments, including urban and suburban yards, parks, golf courses and wooded areas. Clinical history should include questions about history of a recent tick bite, exposure to tick habitats, travel to endemic areas, similar illnesses in close contacts, and pet dogs. However, the absence of these factors, including a tick bite, does not exclude infections.
Tickborne rickettsial infections typically begin as a nonspecific febrile illness. Clinicians should maintain clinical vigilance since early treatment with doxycycline can prevent severe illness and death.
Tickborne rickettsial infections differ in etiology and epidemiology but share many clinical features, specifically initial symptoms of fever, headache, malaise and myalgias. Many infections will have an associated rash. Common laboratory features include abnormal white blood cell counts (either increased or decreased), thrombocytopenia and mildly elevated liver transaminases. The unique features of each infection are described below.
Spotted fever group rickettsioses The American dog tick, Dermacentor variabilis, is the primary vector of Rickettsia rickettsii, which causes Rocky Mountain spotted fever. It is found in Pacific coastal, eastern and central states. Photo courtesy of the Centers for Disease Control and Prevention.
Rocky Mountain spotted fever (RMSF) is caused by Rickettsia rickettsii. The primary vector is the American dog tick, Dermacentor variabilis, which is found in Pacific coastal, eastern and central states. The Rocky Mountain wood tick, Dermacentor andersoni, also transmits R. rickettsii in the western U.S.
The incubation period for RMSF is three to 12 days. In addition to symptoms common to all tickborne rickettsial infections, people with RMSF may have abdominal pain, anorexia and photophobia.
The rash begins two to four days after onset of fever as small, blanching, pink macules on the wrists, forearms and ankles with subsequent spread centrally and to the palms and soles. Over several days, the rash classically becomes maculopapular and sometimes petechial, a sign of severe disease. However, not all people with RMSF will have a rash or the classic rash.
R. rickettsii also causes a systemic vasculitis, hyponatremia, shock, acute respiratory distress syndrome (ARDS), renal failure, meningoencephalitis and neurologic sequelae. The overall case fatality rate is 5%-10%.
The Gulf Coast tick, Amblyomma maculatum, transmits R. parkeri rickettsiosis. Rickettsia species 364D has not yet been described fully, but all reported cases have occurred in California; the probable vector is the Pacific Coast tick, Dermacentor occidentalis. Unique clinical manifestations of both infections include an eschar at the tick bite site and regional lymphadenopathy.
Reported incidence rate of spotted fever group rickettsiosis by U.S. county from 2000-’13. In 2010, the name of the reporting category was changed from RMSF to spotted fever rickettsiosis. Courtesy of the CDC.
The lone star tick, Amblyomma americanum, is the vector for Ehrlichia chaffeensis and E. ewingii, and its geographic distribution is primarily in the Southeast with some extension to Midwest and Northeastern states. The blacklegged tick, Ixodes scapularis, is the vector for Ehrlichia muris-like (EML) agent, which has been identified in Wisconsin and Minnesota.
The incubation period for E. chaffeensis ehrlichiosis (human monocytic ehrlichiosis) is five to 14 days. Gastrointestinal tract symptoms (nausea, vomiting and diarrhea) may be prominent in addition to the other symptoms. Rash is present in approximately one-third of patients and most often involves the extremities and trunk.
E. chaffeensis also can cause meningoencephalitis, shock, ARDS, renal failure, liver failure and coagulopathy. Patients may have leukopenia and anemia. Morula (clusters of bacteria) may be seen in the cytoplasm of monocytes on a peripheral blood smear. The case fatality rate is approximately 3% for those who seek medical care. Many patients are asymptomatic or have mild infection.
Patients with EML agent ehrlichiosis can have rash, but this is rare among patients with E. ewingii. Unique laboratory abnormalities include leukopenia, lymphopenia and anemia (EML agent only) and morula in granulocytes (E. ewingii only).
Human granulocytic anaplasmosis
Human granulocytic anaplasmosis is caused by Anaplasma phagocytophilum. Both the blacklegged tick, Ixodes scapularis, which is found in the Northeast and Midwest, and the western blacklegged tick, I. pacificus, which is found along the West Coast, serve as vectors.
The typical incubation period for anaplasmosis is five to 14 days. Rash is relatively uncommon. Unique laboratory findings can include leukopenia, increased immature neutrophils, mild anemia and morula within granulocytes on a peripheral blood smear. Anaplasmosis most commonly is a self-limited illness. Severe manifestations are uncommon but include ARDS, coagulopathies, rhabdomyolysis, pancreatitis, renal failure and peripheral neuropathies.
Diagnostic tests and treatment
Paired serologic testing (via indirect immunofluorescent antibody assay) performed on serum early in the course of illness and two to four weeks later is diagnostic of an acute infection if the titers have increased at least four-fold. Many patients will be seronegative during the first week of infection, and therapy should not be discontinued in this case.
Polymerase chain reaction assays also can be performed on blood samples during the acute stage of infection. Immunostaining of skin biopsy specimens can be diagnostic for the spotted fever group rickettsioses.
The Academy and Centers for Disease Control and Prevention recommend doxycycline as the preferred treatment for tickborne rickettsial diseases in patients of all ages, including children younger than 8 years old. It should be started immediately when a tickborne rickettsial disease is suspected. The recommended dose is 2.2 mg/kg per dose (maximum 100 mg per dose) twice daily given either orally or intravenously depending on illness severity.
Treatment should continue until there is clinical improvement and for at least three days after fever resolution. Patients with anaplasmosis should be treated for 10 days to cover for possible co-infection with Borrelia burgdorferi. For patients who receive doxycycline during the first four to five days of illness, fever typically resolves within 24-48 hours. Patients with severe disease should be hospitalized, while immunocompetent patients with mild disease may be treated as an outpatient with close follow-up.
Which of the following is a tickborne rickettsial infection?
Dr. Collins is a member of the AAP Section on Infectious Diseases. She is a post-graduate training fellow in pediatric infectious diseases at Emory University School of Medicine in Atlanta. Dr. Pickering was editor of the AAP Red Book from 2000-’12. He is adjunct professor of pediatrics at Emory University School of Medicine.