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

Abstract

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.

Figure 1.. Ixodes and Amblyomma americanum ticks.

In the upper panel are shown I. scapularis nymphal and adult ticks that can potentially transmit B. burgdorferi, A. phagocytophilum and B. microti. In the lower panel are depicted A. americanum nymphal and adult ticks that are linked to Southern Tick Associated Rash Illness (STARI). Their geographic distributions in the USA (shown on the right) overlap, with the exception of the upper Midwest. B. burgdorferi is also transmitted by I. pacificus ticks that are found along the Pacific Coast. Reprinted with permission from Tibbles et al.

Figure 2.. Examples of erythema migrans (EM)

(A) An EM skin lesion that developed at the site of a tick bite on the abdomen of a patient. The lesion is circular and homogeneous, a pattern which is more common than the well-recognized “bull’s eye” appearance of the skin lesion. The primary EM lesion typically is at least 5 cm in diameter. (B) Multiple EM lesions on the back of a patient during disseminated Lyme disease. Secondary EM lesions may be smaller than the primary lesion. The photograph in panel A is courtesy of Dr. Roger Clark, Faulkner Hospital, Boston, MA.

Figure 3.. Anaplasma phagocytophilum bacteria in human neutrophils.

A. phagocytophilum microcolonies (often called morulae) are observed within a neutrophil on a Giemsa stained buffy coat smear. Arrows point to the morulae. The micrograph is courtesy of Dr. Maria Aguero-Rosenfeld, New York University, NY.

Figure 4.. Babesia microti parasites in human red blood cells.

(A) B. microti trophozoites often appear as rings with one chromatin dot. Arrow points to a classic ring form of babesia. (B) Asexual division of the parasite yields up to four merozoites which can arrange in a tetrad, also known as Maltese cross (see arrow). Maltese crosses can be formed by B. microti, B. duncani, and B. divergens in human red blood cells. (C) Following rupture of an infected red blood cell, free merozoites (see arrow) quickly seek to adhere and invade an intact red blood cell. Micrographs are courtesy of Rouette Hunter and Stephen Johnson from the Hematology Laboratory at Tufts Medical Center, Boston, MA.