Emerging Tickborne Illnesses: Beyond Lyme Disease


Patients who remain asymptomatic following a tick bite do not require evaluation as there is no prophylaxis for babesiosis, HME, or HGA, and treating asymptomatic individuals even if they test positive for these diseases is not recommended by the Infectious Diseases Society of America (IDSA). Antibiotic prophylaxis for Lyme disease is generally not recommended by IDSA, except under certain circumstances. 12

Due to limitations in diagnostic testing, clinical diagnosis that takes into consideration epidemiologic, geographic, and laboratory features is most practical. For example, exposure to ticks in an endemic area during spring or summer in a patient who develops febrile illness, leukopenia, or thrombocytopenia is strongly suggestive of HME and is sufficient justification for treatment.4 Testing for Lyme disease should be considered in patients diagnosed with babesiosisand HGA as coinfection with the Ixodes tick vector is common. In symptomatic individuals, the standard to diagnose babesiosis, HME,and HGA is light microscopy of Giemsa-stained peripheral blood smears. Babesia can be seen within erythrocytes in its ring-form trophozoite and tear drop-shaped merozoite stages, which classically but rarely appear as a “Maltese-cross” tetrad. The observation of extracellular ring forms is also suggestive of Babesia.10 The presence of characteristic intracytoplasmic morulae (membrane-bound vacuoles with irregular edges containing clustered purple or blue colonies of gram-negative bacteria) on buffy coat examination are highly suggestive of HME (if in monocytes) or HGA (in granulocytes). Absence of morulae does not rule out infection as they are present in 1% to 20% of patients with HME and in 20% to 80% of patients with HGA.4 If initial smears are negative but clinical suspicion is high, subsequent smears may be obtained over a period of days to increase yield.

Polymerase chain reaction (PCR) testing is available for Babesia, HME,andHGA. It is more sensitive than microscopy so is useful when parasitemia is very low; it can also distinguish between Babesia species.3The reported sensitivity of PCR for HGA varies from 60% to 70% and from 52% to 87% for HME.4 If symptoms persist but microscopy has been negative, repeat blood smear and PCR testing should be performed. Of note, parasite DNA may be detectable by PCR for several months following completion of antibiotic therapy and resolution of symptoms.3 The preferred and most widely available method of diagnosis of HME and HGA is the indirect fluorescent antibody (IFA) test that can be obtained through state health departments.4 The IFA test is 94% to 100% sensitive if the second sample is obtained 2 weeks after the onset of symptoms; a 4-fold rise is considered positive.4 An important limitation of the test is that antibodies first become detectable 2 to 3 weeks after the onset of the illness. Enzyme-linked immunosorbent assay (ELISA) testing is also available. Serology is of limited use in acute disease but provides retrospective evidence of infection; a 4-fold rise in titers confirms recent infection. Because serologic cross reactivity can occasionally occur between E chaffeensis and A phagocytophilum, it is not possible to reliably differentiate between these 2 infections with a single serologic assay.4


The preferred treatment of babesiosis for adults is azithromycin 500 mg orally on day 1, followed by 250 mg orally plus atovaquone 750 mg orally every 12 hours to complete 7 to 10 days of therapy. The therapy is weight-based for children. An alternative regimen includes clindamycin plus quinine, which has the same efficacy but with a higher side effect profile.  Symptoms usually begin to improve within 48 hours of initiating antimicrobial therapy and resolve within 1 to 2 weeks. Management of severe babesiosis consists of hospitalization, antimicrobial therapy, and, in some cases, red blood cell exchange transfusion for parasitemia >10%, severe hemolysis, or organ failure.4

Treatment should be initiated in all patients suspected of having HME or HGA. The medication of choice in all patients, including children and pregnant women, is doxycycline. This is also the preferred therapy for spotted fever rickettsiosis, the disorder most frequently confused with HME and Lyme disease.4Doxycycline can be given orally or intravenously at 100 mg twice daily for 10 days or for 3 to 5 days after fever abates.4 Patients who have intolerance or allergy to tetracyclines can be treated with rifampin 300 mg twice daily for 7 to 10 days.


Mild to moderate babesiosis in immunocompetent patients is usually associated with <4% parasitemia and does not require hospital admission.3 Severe babesiosis is often associated with parasitemia ≥4% and is more likely to lead to complications and/or persistent or relapsing disease. Of 34 cases of babesiosis on Long Island, acute respiratory failure and DIC proved to be the 2 most common complications, occurring in 7 out of 34 cases and 6 out of 34 cases, respectively.13 In HME and HGA, delay in treatment with doxycycline was associated with increase rates of mechanical ventilation and prolonged hospitalization.3Estimated mortality rates have been 2% to 5% for HME and as high as 7% to 10% for HGA.4 Life-threatening infection is more common in the immunocompromised population and secondary opportunistic infections were common in patients who died.4


Tickborne diseases in the United States will continue to be a significant public health problem, and ongoing expansion of these vectors emphasizes the need for effective prevention methods. Surveillance of expansion of vectors over the past 20 years has shown an overall 277% increase from 69 to 260 counties in high-incidence areas for Lyme disease.1 This is likely a surrogate marker for the expansion of other tick populations. Avoidance of tick bites remains the mainstay of prevention, and patients should be educated to use insect repellents as directed. Products with higher percentages of DEET [N,N-diethyl-meta-toluamide] are preferred and are directly applied to exposed skin and clothing. The product label includes details about how and where to apply the repellent, how often to reapply, and how to use it safely on children. For those patients wary of DEET, a newer odorless, nongreasy repellant known as picaridin has been available in the United States since 2005. Created by Bayer from plant extract, picaridin is the best-selling insect repellant in Europe and Australia, is equal in efficacy to DEET, and does not dissolve plastics or other synthetics. The United States Environmental Protection Agency has a website tool 14 that provides guidance on which insect repellant is most appropriate based on duration of exposure and which insects it repels, season, and region. Additionally, permethrin products can be applied to clothing and shoes, but not to skin, to kill ticks on contact. It is usually effective through several washings. Patients should be educated to avoid high-risk areas if possible, especially wooded and brushy areas, overgrown grasses, and leaf litter. Hikers and those who enjoy recreational outdoor activities should walk in the center of cleared trails, cover exposed skin (ie, tuck pant legs into socks), and perform thorough tick checks immediately after engaging in outdoor activities to increase likelihood of prompt removal. Clinicians should be comfortable identifying specific tick vectors and be familiar with endemic geographic regions for disease exposure. Prompt recognition and treatment of isolated infection or coinfection with babesiosis, HME, and HGA improves outcomes. Information on other tick-borne infections in the United States, including spotted fever rickettsioses, southern tick-associated rash illness and tickborne viruses (ie, Colorado tick fever, Powassan) is available from the CDC.15

Kimberly Damato, PA-C, is a physician assistant in neurosurgery at Brookdale University Hospital and Medical Center, in Brooklyn, New York. Danielle Kruger PA-C, MS Ed, is an associate professor in the physician assistant program at St. John’s University, in New York City.


  1. Lyme Disease. Data and Surveillance. Centers for Disease Control and Prevention. https://www.cdc.gov/lyme/stats/index.html. Published November 13, 2017. Accessed April 9, 2019.
  2. Parasites: Babesiosis. Centers for Disease Control and Prevention. https://www.cdc.gov/parasites/babesiosis/. Published May 24, 2016. Accessed April 9, 2019.
  3. Krause PJ, Vannier EG. Babesiosis: Microbiology, epidemiology, and pathogenesis. UpToDate website. https://www.uptodate.com/contents/babesiosis-microbiology-epidemiology-and-pathogenesis?search=babesiosis&source=search_result&selectedTitle=3~69&usage_type=default&display_rank=3. Published May 7, 2018. Accessed April 9, 2019.
  4. Sexton DJ, McClain MT. Human ehrlichiosis and anaplasmosis. UpToDate website. https://www.uptodate.com/contents/human-ehrlichiosis-and-anaplasmosis?search=human ehrlichiosis&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1. Published August 15, 2016. Accessed April 9, 2019.
  5. Snowden J, Simonsen KA. Ehrlichiosis. In: StatPearls [Internet]. Treasure Island, FL: StatPearls Publishing; 2018 Jan-.
  6. Ehrlichiosis: Signs and symptoms. Centers for Disease Control and Prevention. https://www.cdc.gov/ehrlichiosis/symptoms/index.html. Updated January 17, 2019. Accessed April 9, 2019.
  7. Anaplasmosis: Signs and symptoms. Centers for Disease Control and Prevention. https://www.cdc.gov/anaplasmosis/symptoms/index.html.  Updated January 11, 2019. Accessed April 9, 2019.
  8. Dunn JM, Krause PJ, Davis S, et al. Borrelia burgdorferi promotes the establishment of Babesia microti in the northeastern United States. PLoS ONE. 2014;9(12):e115494.
  9. Knapp KL, Rice NA. Human coinfection with Borrelia burgdorferi and Babesia microti in the United States.J Parasitol Res. 2015;2015:587131.
  10. Brennan-Krohn T. Nothing new under the sun: detecting Babesia as it reemerges. American Society for Microbiology website. https://www.asm.org/index.php/clinmicro-blog/item/6790-nothing-new-under-the-sun-detecting-babesia-as-it-reemerges. Published September 5, 2017. Accessed April 9, 2019.
  11. Dumler JS, Choi KS, Garcia-Garcia JC, et al.  Human granulocytic anaplasmosis and Anaplasma phagocytophilum. Emerg Infect Dis. 2005;11(12):1828-1834.
  12. Tickborne diseases of the United States: Tick Bites/Prevention. Centers for Disease Control and Prevention. https://www.cdc.gov/ticks/tickbornediseases/tick-bites-prevention.html. Updated January 10, 2019. Accessed February 9, 2019.
  13. Akel T, Mobarakai N.  Hematologic manifestations of babesiosis. Ann Clin Microbiol Antimicrob. 2017;16(1):6.
  14. Find the repellent that is right for you. United States Environmental Protection Agency. https://www.epa.gov/insect-repellents/find-repellent-right-you. Updated June 14, 2017. Accessed April 9, 2019.

15. Tickborne diseases of the United States. Centers for Disease Control and Prevention. https://www.cdc.gov/ticks/diseases/index.html. Updated January 10, 2019. Accessed April 9, 2019.

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