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Infectious Diseases - Tick-Borne Diseases - Fast Facts | NEJM Resident 360
According to the Centers for Disease Control (CDC), the number of cases of tick-borne diseases more than doubled in the last decade. In this section, we review the main causes of tick-borne diseases in the United States:
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Lyme Disease
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Human Granulocytic Anaplasmosis
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Human Monocytic Ehrlichiosis
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Babesiosis
Lyme Disease
Lyme disease was first described in 1977 in what was initially thought to be an outbreak of juvenile rheumatoid arthritis in children living in Lyme, Connecticut.
In the United States, Lyme disease is caused by the spirochete Borrelia burgdorferi, which is transmitted by the Ixodes tick (black-legged deer tick). While Lyme disease has been reported in all U.S. states, it is predominately found in the Northeast and Midwest.
Black-Legged Deer Tick
(Source: Lyme Disease. Centers for Disease Control 2018.)
Clinical Manifestations
Localized erythema migrans (EM) is the most common clinical manifestation of Lyme disease and is seen in 80% of patients. EM occurs 1 to 2 weeks after the tick bite, and in 75% of cases, the rash is uniformly erythematous or has raised central erythema. The classic bull’s-eye rash is only seen in 30% of cases and may be associated with multiple EM lesions (see photographs below).
Early disseminated disease can present within weeks to a few months after the tick bite. Symptoms include neurologic complications (facial palsy, meningitis, and radiculopathy) and cardiac complications (mainly heart block).
Arthritis is a late manifestation that can occur more than 6 months after a bite from an infected tick.
Diagnosis
Diagnosis of Lyme disease should be considered in someone from an endemic area with outdoor exposures who presents with a rash consistent with EM. Serologic testing in patients with EM is of limited utility given its poor sensitivity (25%–40%). Individuals with one or more atypical rashes for EM should undergo antibody testing on an acute phase serum sample, followed by a convalescent phase serum sample in 2 to 3 weeks if the initial result is negative.
Two-step serologic testing is recommended for disseminated forms of Lyme disease. Currently, this involves an enzyme immunoassay (EIA) to measure the concentration of antibodies to B. burgdoferi, and if positive or equivocal, a confirmatory Western blot. The two-step approach has a sensitivity of 80%–100% in early disseminated neurologic and cardiac disease and 100% in later manifestations.
Few nonserologic testing methods (e.g., nucleic amplification tests) have been studied. These tests are primarily thought to be beneficial when two-tiered serologic testing is positive (e.g., consideration of PCR of synovial fluid in seropositive patients for whom diagnosis of Lyme arthritis is being considered but treatment decisions require more definitive information).
Types of Erythema Migrans
(Source: Lyme Disease. N Engl J Med 2014.)
Treatment
Doxycycline, amoxicillin, or cefuroxime axetil are used for the treatment of Lyme disease. Intravenous ceftriaxone is used to treat Lyme meningitis. More treatment details are provided in the table below.
Note that both amoxicillin and cefuroxime are not used for the treatment of anaplasmosis and ehrlichiosis, which can be transmitted by the Ixodes tick. In 15% of patients, a self-limiting Jarisch–Herxheimer reaction (fevers, arthralgias, and myalgias) can occur within the first 24 hours of treatment of anaplasmosis or ehrlichiosis with amoxicillin or cefuroxime.
The following table summarizes the recommended treatment options:
(Source: Clinical Practice Guidelines by the Infectious Diseases Society of America (IDSA), American Academy of Neurology (AAN), and American College of Rheumatology (ACR): 2020 Guidelines for the Prevention, Diagnosis and Treatment of Lyme Disease. Clin Infect Dis 2021.)
Review the 2020 Guidelines for the Prevention, Diagnosis and Treatment of Lyme Disease.
Human Granulocytic Anaplasmosis
Anaplasmosis is caused by the obligate intracellular bacterium Anaplasma phagocytophilum. The vector is the same as for Lyme disease (the Ixodes tick). Cases of anaplasmosis are found in similar locations as cases of Lyme disease.
Clinical Manifestations
Symptoms of anaplasmosis occur 5 to 14 days after a bit from an infected tick. Patients have nonspecific symptoms including fever, myalgias, and arthralgias. Rash is seen in <10% of patients. Unlike patients with Lyme disease, patients with anaplasmosis often present with leukopenia, thrombocytopenia, and mild transaminitis.
Diagnosis
Diagnosis can be made by identification of morulae in a buffy-coat smear, polymerase chain reaction (PCR) of blood, or serologies drawn 2 to 3 weeks after infectious symptoms.
Peripheral-Blood Smear of Anaplasma phagocytophilum Morulae
(Source: Case 16-2018: A 45-Year-Old Man with Fever, Thrombocytopenia, and Elevated Aminotransferase Levels. N Engl J Med 2018.)
Treatment
Most cases of anaplasmosis are self-limiting, but severe illness can occur. The reported case fatality rate is <1%. Treatment is with doxycycline for 10 days. Reponses are typically prompt (within 48 hours). Lack of improvement during this time frame should raise concern for another coinfected tick-borne illness or alternative diagnosis.
Human Monocytic Ehrlichiosis
Ehrlichiosis is caused by infection of monocytes and tissue macrophages with the intracellular bacteria Ehrlichia chaffeensis, E. ewingii, or E. muris eauclairensis. Most cases are caused by E. chaffeensis, which is carried by the Lone Star tick (Amblyomma americanum). This tick is found predominantly in the Southeastern states and extends into the Midwest and New England states. Symptoms of E. chaffeensis are similar to those of anaplasmosis (nonspecific symptoms including fever, myalgias, and arthralgias), with the addition of gastrointestinal symptoms and a higher rate of rash (33%). The mortality rate associated with ehrlichiosis is also higher, with a case fatality rate of 3% in patients presenting with severe disease. Treatment is with doxycycline, and a prompt response is expected.
Adult Female Amblyomma americanum (Lone Star Tick)
(Source: Lyme and Other Tickborne Diseases. Centers for Disease Control 2018.)
Babesiosis
Babesiosis is caused by intraerythrocytic protozoa. It was first discovered by microbiologist Victor Babes in 1888 as a cause of hemolytic disease in cattle. As with Lyme disease and anaplasmosis, the Ixodes tick is the vector of transmission. The predominating species is Babesia microti in the U.S. and Babesia divergens in Europe. The natural reservoir is the white-footed mouse. During a blood feed of a tick, sporozoites within the salivary gland enter human blood. The sporozoites attach to red blood cells, replicate, and eventually rupture the red cells to infect other cells.
Clinical Manifestations
The presentation of babesiosis can range from asymptomatic disease to death. The time to onset after a bite from an infected Ixodes tick is 1 to 4 weeks. Symptoms include fevers/chills, headache, and arthralgias. Lab findings show mild-to-moderate hemolytic anemia, supported by elevated lactate dehydrogenase and low haptoglobin levels. Thrombocytopenia is common. Severe babesiosis can develop in immunosuppressed patients, particularly those who are asplenic, transplant recipients, or undergoing treatment with rituximab.
Diagnosis
The definitive diagnosis of babesiosis is made with a Giemsa- or Wright-stained blood smear that shows trophozoites in the shape of rings within red blood cells (see figure below). Although rare, tetrads of merozoites resembling a Maltese cross can be seen. If no forms are visible, smears can be repeated every 12 to 24 hours. If blood smears remain negative despite high pretest probability, PCR blood tests can be ordered.
Peripheral-Blood Smear of a Patient with Babesiosis
(Source: Babesiosis. N Engl J Med 2008.)
The following algorithm can be used to guide diagnostic laboratory testing for babesiosis:
Algorithm for Diagnosis of Babesiosis Caused by Babesia microti
(Source: Human Babesiosis. N Engl J Med 2012.)
Treatment
The preferred treatment choice is a combination of atovaquone and azithromycin for 7 to 10 days for immunocompetent hosts; treatment duration is often extended for immunocompromised patients. Removal of parasites by red-cell–exchange transfusion should be considered in patients with high levels of parasitemia (>10%); significant anemia; or renal, hepatic, or pulmonary compromise.The duration of antiparasitic therapy is 6 weeks, with potentially longer therapy required if the parasitemia has not resolved. For immunocompetent patients, the recommendation is to monitor Babesia parasitemia during treatment of acute illness with peripheral blood smears, but experts recommend against testing for parasitemia once symptoms have resolved. For immunocompromised patients, the recommendation is to monitor parasitemia using blood smears, even after patients are asymptomatic, until the blood cultures are negative.
The following table summarizes the recommended treatment for patients with Babesiosis:
(Source: Clinical Practice Guidelines by the Infectious Diseases Society of America (IDSA): 2020 Guideline on Diagnosis and Management of Babesiosis. Clin Infect Dis 2021.)