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Diagnosis, Treatment, and Prevention of Lyme Disease, Human Granulocytic Anaplasmosis, and Babesiosis A Review

Edgar Sanchez, MD1; Edouard Vannier, PhD1; Gary P. Wormser, MD2; Linden T. Hu, MD3
[+] Author Affiliations
1Division of Geographic Medicine and Infectious Diseases, Tufts Medical Center, Boston, Massachusetts
2Division of Infectious Diseases, New York Medical College, Valhalla, New York
3Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, Massachusetts
JAMA. 2016;315(16):1767-1777. doi:10.1001/jama.2016.2884.
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Published online

Importance  Lyme disease, human granulocytic anaplasmosis (HGA), and babesiosis are emerging tick-borne infections.

Objective  To provide an update on diagnosis, treatment, and prevention of tick-borne infections.

Evidence Review  Search of PubMed and Scopus for articles on diagnosis, treatment, and prevention of tick-borne infections published in English from January 2005 through December 2015.

Findings  The search yielded 3550 articles for diagnosis and treatment and 752 articles for prevention. Of these articles, 361 were reviewed in depth. Evidence supports the use of US Food and Drug Administration–approved serologic tests, such as an enzyme immunoassay (EIA), followed by Western blot testing, to diagnose extracutaneous manifestations of Lyme disease. Microscopy and polymerase chain reaction assay of blood specimens are used to diagnose active HGA and babesiosis. The efficacy of oral doxycycline, amoxicillin, and cefuroxime axetil for treating Lyme disease has been established in multiple trials. Ceftriaxone is recommended when parenteral antibiotic therapy is recommended. Multiple trials have shown efficacy for a 10-day course of oral doxycycline for treatment of erythema migrans and for a 14-day course for treatment of early neurologic Lyme disease in ambulatory patients. Evidence indicates that a 10-day course of oral doxycycline is effective for HGA and that a 7- to 10-day course of azithromycin plus atovaquone is effective for mild babesiosis. Based on multiple case reports, a 7- to 10-day course of clindamycin plus quinine is often used to treat severe babesiosis. A recent study supports a minimum of 6 weeks of antibiotics for highly immunocompromised patients with babesiosis, with no parasites detected on blood smear for at least the final 2 weeks of treatment.

Conclusions and Relevance  Evidence is evolving regarding the diagnosis, treatment, and prevention of Lyme disease, HGA, and babesiosis. Recent evidence supports treating patients with erythema migrans for no longer than 10 days when doxycycline is used and prescription of a 14-day course of oral doxycycline for early neurologic Lyme disease in ambulatory patients. The duration of antimicrobial therapy for babesiosis in severely immunocompromised patients should be extended to 6 weeks or longer.

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Figure 1.
Ixodes and Amblyomma americanum Ticks and Their Geographic Distributions in the United States

Top, Ixodes scapularis nymphal and adult ticks (ticks in black circles are shown at actual size). The nymphs and adult females can transmit Borrelia burgdorferi, Anaplasma phagocytophilum, and Babesia microti; adult males may attach but do not feed and thus do not transmit these pathogens. Bottom, Amblyomma americanum nymphal and adult ticks linked to southern tick-associated rash illness (STARI) (ticks in black circles are shown at actual size). As shown on the right, the geographic distributions of I scapularis and A americanum in the United States overlap, with the exception of the upper Midwest. Borrelia burgdorferi is also transmitted by Ixodes pacificus ticks found along the Pacific Coast. Adapted from Tibbles et al.1

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Figure 2.
Erythema Migrans Skin Lesion at the Site of a Tick Bite on the Abdomen of a Patient

The lesion is circular and homogeneous, a pattern more common than the well-recognized “bull’s-eye” appearance. The primary erythema migrans lesion typically is at least 5 cm in diameter. Photograph courtesy of Roger Clark, DO, Faulkner Hospital, Boston, Massachusetts.

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Figure 3.
Anaplasma phagocytophilum Bacteria in Human Neutrophils

Anaplasma phagocytophilum microcolonies (often called morulae) are observed within a neutrophil on a Giemsa-stained buffy coat smear (original magnification ×1000). Arrowheads indicate the morulae. Micrograph courtesy of Maria Aguero-Rosenfeld, MD, New York University, New York, New York.

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Figure 4.
Babesia microti Parasites in Human Red Blood Cells

A, Babesia microti trophozoites often appear as rings with 1 chromatin dot. Arrowhead indicates a classic ring form of babesia. B, Asexual division of the parasite yields up to 4 merozoites that can arrange in a tetrad, also known as a Maltese cross (arrowhead). Maltese crosses can be formed by B microti, B duncani, and B divergens in human red blood cells. C, After rupture of an infected red blood cell, free merozoites (arrowhead) quickly seek to adhere and invade an intact red blood cell. Original magnification ×1000; Giemsa stain. Micrographs courtesy of Rouette Hunter, BS, MT(ASCP), and Stephen Johnson, BS, from the Hematology Laboratory, Tufts Medical Center, Boston, Massachusetts.

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