Guidelines for the Diagnosis and Treatment of Tick-Borne Illness
Antimicrobial Stewardship Subcommittee · Pharmacy and Therapeutics Committee · University of Kentucky Health Care
| Authors | Katie Olney, PharmD, BCIDP; Thein Myint, MBBS; Sarah Jeter, PharmD, BCIDP, AAHIVP; Laura Stadler, MD; Joel Howard, MD; Morgan McCoy, MD |
|---|---|
| Target Population | Adult patients undergoing workup for tick-borne illness |
| Overview | Evidence-based guidelines for the diagnosis and treatment of tick-borne illnesses. |
| Effective Date | 09/2020 |
| Revised | 10/2022; 10/2024 |
| Expiration | 10/2027 · Reviewed every 3 years |
| Primary Outcome | Selection of antimicrobial therapy and duration of therapy. |
Purpose & Goals
To provide evidence-based information for the treatment of tick-borne infections in pediatric and adult patients admitted to the University of Kentucky Health Care System. The goals are to expedite collection of appropriate diagnostic studies, assist with early and appropriate diagnosis, and facilitate early initiation of appropriate antibiotics.
Background
Annual confirmed cases of Ehrlichiosis and Rocky Mountain Spotted Fever (RMSF) increased approximately eight-fold from 2000 to 2018 within the United States. Diagnosis of tick-borne illnesses is challenging because microbiologic testing is often not performed and clinical improvement frequently occurs before laboratory diagnosis. Ticks can harbor multiple pathogens, leading to simultaneous infections.
Kentucky has a significantly higher incidence of RMSF and ehrlichiosis than other common tick-borne illnesses (Babesia, Borrelia, Anaplasma, etc.). Both RMSF and ehrlichiosis are well known to cause severe morbidity including meningoencephalitis, cardiovascular failure, hepatic injury, acute respiratory distress syndrome, and renal failure.
Diagnosis & Initial Workup
Tick-borne illnesses can be difficult to diagnose and often present with non-specific symptoms. The classic triad is fever, headache, and rash. The most common presentation is an initial prodrome of flu-like illness including fever, myalgia, headache, malaise, nausea, vomiting, and diarrhea. Although most tick-borne illnesses occur between April and October, transmission can occur year-round in warmer climates.
Obtain a complete exposure history including: (1) history of tick bite, (2) exposure to environments with ticks, (3) identification of clusters of illness among contacts, and (4) travel history to endemic areas. Although tick exposure history is important, lack of a tick bite cannot serve as a diagnostic rule-out.
The decision to initiate treatment is commonly based on a clinical presumptive diagnosis from clinical findings and epidemiological risk factors. Treatment should not be withheld pending diagnostic test results — therapy should be initiated promptly and should not be discontinued until appropriate diagnostics return negative.
Infectious Diseases (ID) Consultation
An ID consultation is recommended in the following patients and/or clinical scenarios:
- Pregnant patients
- Pediatric patients
- Immunocompromised patients
- Patients with a life-threatening allergy to doxycycline
- Lack of defervescence or improvement after >48 hours on doxycycline
- Suspicion for Babesiosis
- Suspicion for disseminated (neurological, cardiac, arthritic) Lyme disease
- Equivocal diagnostic testing
Pediatric Concerns
Although tetracycline has historically been associated with teeth discoloration, doxycycline has not demonstrated the same affinity for calcium binding. Recent comparative data suggest doxycycline is not likely to cause visible teeth staining or enamel hypoplasia in young children (<8 years). Per the American Academy of Pediatrics (2018 Red Book), doxycycline may be administered for durations ≤21 days without regard to the patient's age. Doxycycline is the drug of choice for human ehrlichiosis and anaplasmosis and should be used regardless of patient age.
Figure 1: Acute Tick-Borne Illness Testing & Treatment Algorithm
Table 1: Clinical Presentation of Selected Tick-Borne Illnesses
| Disease | Vector | Endemic Region(s) | Incubation | Laboratory Indices | Initial Presentation | Cutaneous Features |
|---|---|---|---|---|---|---|
| Rocky Mountain Spotted Fever | Wood tick (D. variabilis, D. andersoni) | Five states (NC, OK, AR, TN, MO) account for 60% of cases | 3–12 days | Normal or ↑WBC; ↑ANC; ↑transaminases; thrombocytopenia; hyponatremia | Fever, chills, severe headache, myalgia, nausea, vomiting, diarrhea, anorexia | Maculopapular rash ~2–4 days after fever onset in most; may become petechial and involve palms and soles |
| Human Monocytic Ehrlichiosis | Lone star tick (A. americanum); Blacklegged tick (I. scapularis) | Southeast, Northeast, East of the Rocky Mountains, Pacific Coast | 5–14 days | ↓WBC; ↑transaminases; hyponatremia; thrombocytopenia | Fever, headache, myalgia, nausea, diarrhea, vomiting, confusion, rash | Variable pattern ~5 days after onset; may involve palms and soles. Rash in ~30% of adults, ~60% of children |
| Anaplasmosis | Blacklegged tick (Ixodes scapularis) | Upper Midwest, Northeast | 5–14 days | ↓WBC; ↑transaminases; thrombocytopenia | Fever, headache, myalgia, nausea, diarrhea, vomiting | Rare (<10%) |
| Babesiosis | Blacklegged tick (Ixodes scapularis) | Upper Midwest, Northeast | ≥1–9 weeks | ↑transaminases; ↓hematocrit; ↓reticulocytes; thrombocytopenia | Chills, headache, myalgia, arthralgia | None |
| Lyme Disease — Early Stage | Blacklegged tick (Ixodes scapularis) | Northeast, Mid-Atlantic, Upper Midwest | 3–30 days | None | Fever, myalgia, headache, nausea, fatigue | Erythema migrans |
| Lyme Disease — Early Disseminated | Blacklegged tick (Ixodes scapularis) | Northeast, Mid-Atlantic, Upper Midwest | ≥2 weeks | None | Cardiac or musculoskeletal manifestations (see Table 2) | None |
| Lyme Disease — Disseminated | Blacklegged tick (Ixodes scapularis) | Northeast, Mid-Atlantic, Upper Midwest | ≥2 weeks | None | Neurologic or musculoskeletal manifestations (see Table 2) | None |
Source: CDC — cdc.gov/ticks/tickbornediseases
Lyme Disease
Per the CDC, Kentucky is a low Lyme incidence state with <10 confirmed cases/100,000 over the last three reporting years. Per the Kentucky Department of Public Health, there were only six confirmed Lyme cases in Kentucky in 2017, the majority in southern and western Kentucky.
- Accurate history is crucial. Over-diagnosis of disseminated Lyme disease can lead to inappropriate use of health services and avoidable treatment-related illness.
- For patients with neurological symptoms, the American Academy of Neurology and IDSA recommend parenteral regimens for the treatment of neuroborreliosis.
- European studies suggest oral doxycycline and parenteral ceftriaxone may be equally effective for neuroborreliosis with facial palsy, though this remains untested in the US.
Given the complexities of diagnosing disseminated Lyme disease, ID consultation is advised.
Table 2: CDC Surveillance Definitions of Lyme Disease
| Organ System | Definition | Caveats |
|---|---|---|
| Skin | Erythema Migrans (EM): expanding skin lesion, often with partial central clearing (bullseye) around tick bite. Primary lesion must be ≥5 cm across largest diameter and diagnosis must be made by a physician. | Annular erythematous lesions occurring within hours of tick bite represent hypersensitivity reactions and do NOT qualify as EM. |
| Musculoskeletal | Recurrent, brief attacks (weeks or months) of objective joint swelling, sometimes followed by chronic arthritis. | Chronic progressive arthritis not preceded by brief attacks, chronic symmetrical polyarthritis, or arthralgia/myalgia/fibromyalgia syndromes alone are NOT criteria. |
| Central Nervous System | Any of the following alone or in combination: lymphocytic meningitis; cranial neuritis, particularly facial palsy (may be bilateral); radiculoneuropathy; encephalomyelitis. | Headache, fatigue, paresthesia, or mildly stiff neck alone is NOT criteria. Encephalomyelitis must be confirmed by antibody production against Borrelia burgdorferi in CSF (higher titer in CSF than serum). |
| Cardiovascular | Acute onset of high-grade (2nd or 3rd degree) atrioventricular (AV) conduction defect that resolves in days to weeks. | Palpitations, bradycardia, bundle branch block, or myocarditis alone is NOT criteria. |
Table 3: Selected Laboratory & Treatment Regimens
| Disease | Diagnostic Test(s) | Confirmation & Timing | Treatment | Other Considerations |
|---|---|---|---|---|
| Rocky Mountain Spotted Fever Rickettsia rickettsii |
Acute and convalescent serology | 4-fold increase in antibody titer. IgM present day 3–8, peaks at 1 month; IgG present within 3 weeks, peaks 1–3 months. | Doxycycline 100 mg IV/PO q12h. Duration: 7–14 days; treat at least 3 days after clinical improvement and fever resolution. | Serology preferred. PCR may be positive in advanced disease. Cannot confirm with a single antibody test. |
| Human Monocytic Ehrlichiosis Ehrlichia chaffeensis |
E. chaffeensis PCR | Chaffeensis DNA detected; or 4-fold titer increase; or morulae detected with positive antibody titer. | Doxycycline 100 mg IV/PO q12h. Duration: 7–14 days; treat at least 3 days after improvement and fever resolution. | CSF findings include pleocytosis and protein elevation. Negative PCR does not rule out disease. |
| Human Granulocytic Anaplasmosis Anaplasma phagocytophilum |
A. phagocytophilum PCR | A. phagocytophilum DNA detected; or 4-fold titer increase; or morulae detected with positive antibody titer. | Doxycycline 100 mg IV/PO q12h. Duration: 10–14 days. | CSF usually normal. Negative PCR does not rule out disease. Cannot confirm with a single antibody test. |
| Babesiosis Babesia microti |
Peripheral blood smear of intraerythrocytic parasites (stat); Babesia PCR; antibody titer by IFA (supportive) | Identification of Babesia in RBC; or Babesia DNA detected. Antibodies present within 4 weeks of onset of parasitemia. | Atovaquone 750 mg q12h PLUS Azithromycin 1000 mg q24h. Duration: Consult ID. | ID consult strongly recommended. Treat symptomatic patients with positive PCR or microscopic identification. |
| Lyme Disease Borrelia burgdorferi |
ELISA with Western Blot | Acute/convalescent IgG serology in serum; or B. burgdorferi DNA in CSF or synovial fluid. Antibodies develop 2–4 weeks after bite. | Erythema Migrans: Doxycycline 100 mg IV/PO q12h × 10 days. Lyme Arthritis: × 28 days. Lyme Carditis: × 14 days. Neurological Lyme: × 14 days. |
ID consult strongly recommended. EM at presentation = presumptive diagnosis. CSF/synovial testing not diagnostic without concurrent serum testing. Consider cardiology consult for cardiac involvement. |
Note: Delay in treatment may result in severe illness or death. Antibodies may not be present in the first week of disease. Patients receiving doxycycline should avoid extended sun exposure (phototoxicity risk) and take doses with food to decrease GI toxicity.
Table 4: Diagnostic Order Identification in Epic
| Diagnostic | Epic Order |
|---|---|
| Identification of Tick Species | "Arthropod Identification" |
| RMSF Acute & Convalescent Serology | "Rickettsia (RMSF) Ab IgG and IgM w/ Reflex Titer" |
| Anaplasma phagocytophilum & Ehrlichia chaffeensis PCR | "EHRLICHIA AND ANAPLASMA SPECIES BY REAL TIME PCR (SO)" |
| Serum Ehrlichia Antibodies | "EHRL Chaffeensis AB" |
| Anaplasma & Ehrlichia Peripheral Blood Smear | "Peripheral Blood Smear" → Click "Add Comments" → specify Anaplasma and Ehrlichia |
| Lyme ELISA with Western Blot | "Borrelia burgdorferi VlsE1/pepC10 antibodies, total by ELISA with reflex to IgG and IgM (modified Two-Tier Testing) SO" |
| Lyme Disease CSF Antibodies | "Borrelia species by PCR (Lyme Disease) (SO)" |
Tick Bite Prevention & Prophylaxis
Prevention
Ticks live in grassy, wooded, or bushy areas — but many bites happen in people's own yards. Ticks can be carried indoors on pets, clothing, and gear. Clothing that doesn't need washing should be tumbled in a dryer on high for ten or more minutes to kill ticks; if washing is needed first, use hot water. After potential exposure, check the entire body and shower as soon as possible. Ticks prefer skin folds and hair-covered areas (in/around the ears, in the hair, between the thighs, under the armpit).
Prophylaxis
Before going outdoors, the CDC recommends treating clothing and gear with products containing 0.5% permethrin, and using insect repellents containing DEET, picaridin, IR3535, Oil of Lemon Eucalyptus (OLE), para-menthane-diol (PMD), or 2-undecanone. Avoid tall grasses and brushy areas, and stick to hiking trails. Talk to a veterinarian about prophylactic products for dogs; the CDC generally recommends against applying tick-prevention products to cats, which are extremely sensitive to many chemicals.
For prevention of Lyme disease after a recognized tick bite, routine antimicrobial prophylaxis or serologic testing is not recommended. In areas with high endemic rates of Lyme disease, a single 200 mg dose of doxycycline can be considered for high-risk bites where the tick has been attached for ≥36 hours.
References
- Wormser GP, et al. The Clinical Assessment, Treatment, and Prevention of Lyme Disease, Human Granulocytic Anaplasmosis, and Babesiosis: Clinical Practice Guidelines by the IDSA. Clin Infect Dis. 2006;43(9):1089–1134.
- CDC. Diagnosis and management of tickborne rickettsial diseases. MMWR. 2016;65(RR-2).
- Kimberlin DW, et al. Red Book: 2018–2021 Report of the Committee on Infectious Diseases. 31st ed. 2018.
- Bakken JS, et al. Human granulocytic anaplasmosis. Infect Dis Clin North Am. 2015:341–355.
- CDC. Updated CDC Recommendation for Serologic Diagnosis of Lyme Disease. MMWR. 2019;68(32):703.
- Ismail N, et al. Human Ehrlichiosis and Anaplasmosis. Clin Lab Med. 2010;30(1):261–292.
- CDC. Ehrlichiosis & RMSF Epidemiology and Statistics. 2020.
- Reid MC, et al. The consequences of overdiagnosis and overtreatment of Lyme disease. Ann Intern Med. 1998;128(5):354–362.
- Halperin JJ, et al. Practice Parameter: Treatment of nervous system Lyme disease. Neurology. 2007;69(1):91–102.
- Miller JM, et al. Guide to Utilization of the Microbiology Laboratory for Diagnosis of Infectious Diseases: 2018 Update. Clin Infect Dis. 2018;67(6):e1–e94.
- Kentucky Cabinet for Health and Family Services. Story-Map of Tickborne Disease in Kentucky.
Abbreviated reference list. See the original guideline document for the complete citations.
For more information: CDC Tick-Borne Diseases