Tick-borne Disease: Laboratory Support of Diagnosis and Management

This Topic Brief provides information about the laboratory testing that supports the diagnosis of various types of tick-borne diseases.

Tick-borne Diseases: Laboratory Support of Diagnosis and Management

Topic Brief

Tick-borne Diseases

Laboratory Support of Diagnosis and Management

Contents:

Introduction

All tick-borne diseases

Table 1. Incidence of Tick-borne Diseases, United States

Table 2. Tests Available for Diagnosis and Management of All Tick-borne Diseases

Figure. Serological Test Selection for the Differential Diagnosis of Tick-borne Diseases Based on Geographic Origin and Symptoms of Infection

Lyme disease

Table 3. Clinical Features of Lyme Disease and Recommended Laboratory Testing

Table 4. Tests Available for Diagnosis and Management of Lyme Disease

Non-Lyme bacterial tick-borne diseases

Table 5. Clinical Features of Tick-borne Rickettsial Diseases

Table 6. Clinical Consequences of Tularemia

Table 7. Tests Available for Diagnosis and Management of Non-Lyme Bacterial Tick-Borne Diseases

Table 8. Confirmatory Diagnostic Testing for Non-Lyme Bacterial Tick-borne Diseases

Parasitic and viral tick-borne diseases

Table 9. Tests Available for Diagnosis and Management of Parasitic and Viral Tick-Borne Disease

References

Introduction [return to contents]

This Topic Brief describes the various tick-borne diseases and their incidence, prevalence, and geographic distribution across the United States; it also describes disease symptoms as well as available tests and their interpretation. After describing availability of general tests for all tick-borne diseases, sections follow that include Lyme disease, non-Lyme bacterial tick-borne diseases, and parasitic and viral tick-borne diseases.

The information provided is not intended as medical advice. Test selection and interpretation, diagnosis, and patient management decisions should be based on the physician’s education, clinical expertise, and assessment of the patient. The treating healthcare professional should refer to the manufacturer’s approved labeling for prescribing, warnings, side effects, and other important information relating to treatment options.

All tick-borne diseases [return to contents]

Tick-borne diseases are caused by infections transmitted to humans via a tick vector, such as the deer tick, dog tick, wood tick, or lone star tick. Causative agents include bacteria, viruses, and parasites. The incidence varies by geographic location and causative agent (Table 1).^1-7 Clinical manifestations also vary depending on the causative agent but frequently include fever, chills, sweating, headaches, myalgia, arthralgia, nausea, and vomiting; because of similar symptomology, tick-borne diseases have substantial clinical overlap.^2,5,8,9 Some patients develop a rash or lesion at the site of the bite. More severe disease may lead to hematologic, respiratory, cardiac, and neurologic complications as well as kidney or liver failure and arthritis. Although tick-borne illnesses can be fatal, antimicrobial agents are usually effective for treating bacterial tick-borne diseases. Some ticks can harbor more than 1 infectious agent that can be transmitted to humans, and coinfection may complicate the diagnosis and affect treatment selection.¹⁰

Table 1. Incidence of Tick-borne Diseases, United States [return to contents]

Disorder (reported cases, 2022)	Disease geographic distribution^1,2,4,5,a	Causative organism	Primary vector tick(s)
Lyme disease (62,551)³	Upper Midwest, Northeast, Mid-Atlantic, Northern California, Oregon, Washington	Borrelia burgdorferi, Borrelia mayonii	Black-legged tick, also known as deer tick (Ixodes scapularis) Western black-legged tick (Ixodes pacificus)
Anaplasmosis (5,633)³	Upper Midwest, Northeast, Pacific Coast states, Eastern states	Anaplasma phagocytophilum	Black-legged tick, also known as deer tick (Ixodes scapularis), Western black-legged tick (Ixodes pacificus)
Ehrlichiosis (HME) (1,557)³	South-Central, Southeast, East Coast extending to Texas	Ehrlichia chaffeensis	Lone star tick (Amblyomma americanum)
Human ewingii ehrlichiosis (25)³	South-Central, Southeast, East Coast extending to Texas	Ehrlichia ewingii	Lone star tick (Amblyomma americanum)
Spotted fever rickettsioses (1,271)^3,b	Nationwide; Arkansas, North Carolina, Alabama, Missouri and Tennessee account for over 50% of cases	Rickettsia rickettsii	American dog tick (Dermacentor variabilis) Brown dog tick (Rhipicephalus sanguineus) Rocky Mountain wood tick (Dermacentor andersoni)
		Rickettsia parkeri	Gulf Coast tick (Amblyomma maculatum)
Babesiosis (1,915)^3,c	Most common in New York, Massachusetts, Connecticut; cases reported on the West Coast	Babesia microti and other Babesia species (eg, Babesia duncani)	Black-legged tick, also known as deer tick (Ixodes scapularis)
Tularemia (167)³	Nationwide; predominately Midwest	Francisella tularensis	Lone star tick (Amblyomma americanum) Rocky Mountain wood tick (Dermacentor andersoni) American dog tick (Dermacentor variabilis)
Colorado tick fever (11)^6,d	Rocky Mountain region	Colorado tick fever virus	Rocky Mountain wood tick (Dermacentor andersoni)
Hard tick relapsing fever (unknown)	Upper Midwest, Northeast, Mid-Atlantic, Northern California, Oregon, Washington	Borrelia miyamotoi	Black-legged tick, also known as deer tick (Ixodes scapularis) Western black-legged tick (Ixodes pacificus)

HME, human monocytic ehrlichiosis; RMSF, Rocky Mountain spotted fever.
a	See reference 1 for detailed geographic distribution maps.
b	As of 2010, cases of Rocky Mountain spotted fever (RMSF), Rickettsia parkeri rickettsiosis, Pacific Coast tick fever, and rickettsialpox are reported under a category called Spotted Fever Rickettsiosis (SFR). Categorization under SFR is due to the inability to differentiate between spotted fever group Rickettsia species using commonly available serologic tests.⁷
c	Reported cases in 2021.
d	Median number of cases per year, 2013-2022.6

All tick-borne diseases: test availability

Laboratory tests that can help confirm the clinical diagnosis include tick identification, microscopic visualization of the causative organism in blood or other clinical specimens, various serologic techniques, culture, and polymerase chain reaction (PCR)-based assays (Table 2). Panel components may be ordered individually.

Table 2. Tests Available for Diagnosis and Management of All Tick-borne Diseases [return to contents]

Test code	Assay^a	Method	Clinical use
3946(X)	Tick (and Other Arthropods) Identification	Microscopy	Identify tick to determine risk of tick-borne disease; assist with differential diagnosis
94322	Tick-borne Disease, Acute Molecular Panel^b Includes Anaplasma phagocytophilum, Babesia microti, Borrelia miyamotoi, Ehrlichia chaffeensis, and Lyme disease Borrelia spp.	Real-time PCR (qualitative for A phagocytophilum and Borrelia spp [blood])	Diagnose tick-borne diseases when selecting tests for individual pathogen is challenging due to overlapping geographic distributions and clinical presentations of illness; especially useful to diagnose mixed infections
32338	Tick-borne Disease, Acute Molecular Panel, Non-Lyme^b Includes A phagocytophilum, B microti, B miyamotoi, and E chaffeensis.
16220	Tick-borne Disease, Antibody Panel With Reflexes^b,c Includes Lyme disease Ab with reflex to immunoassay (IgG, IgM) and A phagocytophilum antibodies (IgG and IgM), B microti antibodies (IgG, IgM), and E chaffeensis (IgG, IgM) with reflexes to titers.	IFA, immunoassay	Diagnose tick-borne diseases when selecting tests for individual pathogens is challenging due to substantial clinical overlap and coinfection

IFA, immunofluorescence assay; PCR, polymerase chain reaction.
a	Panel components may be ordered individually.
b	This test was developed and its analytical performance characteristics have been determined by Quest Diagnostics. It has not been cleared or approved by the US Food and Drug Administration. This assay has been validated pursuant to the CLIA regulations and is used for clinical purposes.
c	Reflex tests are performed at an additional charge and are associated with an additional CPT^® code(s).

All tick-borne diseases: test selection and interpretation

In most cases, presumptive diagnosis of tick-borne illness is based on clinical grounds. Submitting the removed tick for species identification (test code 3946[X]) is recommended as it allows for the determination of tick characteristics (ie, species, life stage, degree of blood engorgement) that can inform additional testing and treatment.⁹ Identification of the tick is recommended by the Infectious Diseases Society of America (IDSA),⁹ as some disease pathogens are carried by specific tick species.

Because of rapid disease progression associated with some tick-borne infections (eg, Lyme disease, tick-borne rickettsial diseases), treatment should not be delayed in symptomatic patients pending the results of laboratory tests or the development of more serious symptoms.² For prophylaxis after a tick bite, antibiotic therapy for Lyme disease is only recommended by the IDSA if the bite is considered high risk by meeting 3 criteria: (a) being caused by an Ixodes vector species, (b) occurring in a highly endemic area, and (c) the tick being attached for ≥36 hours.⁹

The clinical symptoms and type of rash or lesion, if present, guide the initial differential diagnosis among patients exposed to a tick-endemic area (Figure).^{1-5,8,9,11-14} This, in turn, guides appropriate test selection, which can include test panels for multiple organisms (test codes 94322, 32338, 16220) or confirmatory tests for specific organisms. Absence of a rash should not rule out a disease from the differential diagnosis.

Figure. Serological Test Selection for the Differential Diagnosis of Tick-borne Diseases Based on Geographic Origin and Symptoms of Infection
[return to contents]

Lyme disease [return to contents]

Lyme disease or Lyme borreliosis is by far the most common tick-borne disease in the United States. It is caused by the bacterium Borrelia burgdorferi and transmitted from the deer tick (Ixodes scapularis or Ixodes pacificus). In 2023, approximately 90,000 cases of Lyme disease were reported to the CDC by healthcare providers¹⁵ but, based on insurance claims data, the annual number of patients diagnosed and treated could be as high as 476,000 per year.¹⁶

Ticks transmitting Lyme disease are generally distributed in the Eastern United States and the Pacific Coast states. Lyme disease cases are most frequently reported from the upper midwestern, northeastern, and mid-Atlantic states.² However, cases are also reported from Northern California, Oregon, and Washington. Lyme disease is most common among children and middle-aged adults.¹⁷

The clinical presentation of Lyme disease is categorized as 1 of 3 stages: early localized, early disseminated, and late (Table 3).^2,5,8,9 In 70% to 80% of infected persons, early localized disease is characterized by erythema migrans (EM), a round or oval skin lesion at least 4 cm to 5 cm in diameter that may appear in a “bulls-eye” pattern and expand up to 30 cm across.² In the absence of EM, the differential diagnosis may include other tick-borne diseases such as hard tick relapsing fever (HTRF), which is often misdiagnosed as Lyme disease owing to overlapping symptoms.¹⁸

Table 3. Clinical Features of Lyme Disease and Recommended Laboratory Testing [return to contents]

Stage of disease^2,5	Symptom onset²	Symptoms²	Laboratory testing^8,9
Early localized (acute phase)	3-30 days after tick bite	EM Fever, myalgia, headache, nausea, fatigue	If EM is identified in a patient where Lyme disease is endemic, serologic testing is not recommended (ie, clinical diagnosis of Lyme is recommended) STTT or MTTT may be considered (weakly recommended) for patients with 1 or more skin lesions suggestive of but atypical for EM; however, serologic testing during the acute phase of infection is less sensitive and specific than testing at later stages of infection
Early disseminated	3-12 weeks after tick bite	Dermatologic: multiple EM rashes that are distant from bite Neurologic: LNB – common symptoms include Bell’s palsy, lymphocytic meningitis, painful radiculoneuritis (1 or more dermatomes), and others such as painful peripheral motor and sensory neuropathy (mononeuritis multiplex) and intracranial hypertension (rare) Cardiac: Lyme carditis leading to conduction abnormalities such as AV node block; can be fatal (rare) Rheumatologic: transient and/or migratory arthritis; effusion in 1 or more joints, often large joints; Baker’s cysts; migratory pain in tendons, bursae, muscle, and bones	When assessing for possible LNB affecting either the PNS or CNS, STTT or MTTT, serum is recommended If LNB or 1 or more acute symptoms (eg, meningitis, painful radiculoneuritis) of LNB is suspected, guideline recommendations include obtaining simultaneous samples of CSF and serum for measuring CSF:serum antibody index STTT or MTTT is recommended when assessing for rheumatologic symptoms of Lyme disease; PCR is recommended in seropositive patients
Late-stage	Months to years after tick bite	Patients may not have a history of EM, however, may present with sensory axonal polyneuropathy, encephalomyelitis (rare), or mononeuropathy Cognitive deficits, personality changes, extreme irritability, and depression Lyme arthritis Bluish red rash (acrodermatitis chronica atrophicans) in women	STTT or MTTT is recommended with IgG only considered >30 days after symptom onset

AV, atrioventricular; CNS, central nervous system; CSF, cerebrospinal fluid; EM, erythema migrans; LNB, Lyme neuroborreliosis; MTTT, modified 2-tiered testing; PCR, polymerase chain reaction; PNS, peripheral nervous system; STTT, standard 2-tiered testing.

The first sign of early disseminated disease is often additional smaller skin lesions that may develop if Lyme disease is untreated; however, a recognized skin lesion does not always occur. Extracutaneous involvement in early disseminated disease can include cardiac, rheumatologic, and/or neurologic manifestations (Table 3).^2,5,8,9 About 10% to 15% of patients with untreated Lyme disease will develop Lyme neuroborreliosis (LNB).¹⁹ Lyme arthritis may also occur during late-stage disease and is the most common manifestation of Lyme disease months after initial tick exposure.²⁰ Left untreated, Lyme arthritis usually affects the knees over a period of several years.²⁰

If initiated in the early stages of Lyme disease, treatment with appropriate antibiotics is usually effective.^9,21 Prophylaxis or serologic testing after a tick bite is usually not indicated in areas where less than 20% of ticks are infected; however, in areas where infected ticks are endemic, laboratory testing, including tick identification, is recommended.^9,21

Lyme disease: test availability

Laboratory tests that can help confirm the clinical diagnosis of Lyme disease include tick identification, various serologic techniques and PCR-based assays (Table 4).

Table 4. Tests Available for Diagnosis and Management of Lyme Disease [return to contents]

Test code	Assay^a	Method	Clinical use
Lyme disease
39209	Borrelia burgdorferi DNA, Qualitative Real-Time PCR, Miscellaneous^b,c	Real-time PCR	Diagnose Lyme disease using whole blood, synovial fluid, or CSF
15777	Borrelia Species DNA, Qualitative Real-Time PCR, Miscellaneous^b		Detect Borrelia spp DNA in whole blood, synovial fluid, or CSF
15510	Borrelia Species DNA, Qualitative Real-Time PCR, Tick^b		Detect Borrelia spp DNA in ticks
39219	Borrelia Species DNA, Real-Time PCR, With Reflexes, Blood^b,c,d		Detect Borrelia spp DNA in whole blood
39218	Borrelia Species DNA, Real-Time PCR, With Reflexes, Synovial Fluid/CSF^b,c,d		Detect Borrelia spp DNA in synovial fluid or CSF
6646	Lyme Disease Ab With Reflex to Blot (IgG, IgM)^d	Immunoassay	Diagnose Lyme disease by standard 2-tiered test
39733	Lyme Disease Antibody With Reflex to Immunoassay (IgG, IgM) (MTTT)^d Includes reflex to Lyme disease supplemental antibodies (IgG, IgM) if Lyme disease total antibody is positive or equivocal.	Immunoassay	Diagnose Lyme disease by modified 2-tiered test
34194	Lyme Disease Antibody Index for CNS Infection	ELISA; nephelometry	Diagnose Lyme neuroborreliosis
29477	Lyme Disease Antibody (IgG), Immunoblot	Immunoblot	Diagnose Lyme disease when ELISA results are positive or equivocal
8593	Lyme Disease Antibodies (IgG, IgM), Immunoblot	Immunoblot
90558	Tick ID With Reflex to Lyme Disease DNA, Real-Time PCR, Tick^d	Microscopy; reflex to PCR	Identify tick and B burgdorferi to assess risk of tick-borne disease and assist with differential diagnosis

CSF, cerebrospinal fluid; ELISA, enzyme-linked immunosorbent assay; IFA, immunofluorescence assay; PCR, polymerase chain reaction.
a	Panel components may be ordered individually.
b	This test was developed and its analytical performance characteristics have been determined by Quest Diagnostics. It has not been cleared or approved by the US Food and Drug Administration. This assay has been validated pursuant to the CLIA regulations and is used for clinical purposes.
c	Please refer to the Quest Test Directory for your service area for test availability.
d	Reflex tests are performed at an additional charge and are associated with an additional CPT code(s).

Lyme disease: test selection and interpretation

A timeline of tick exposure in a tick-endemic area and symptoms of Lyme disease guide appropriate test selection (Table 3).^2,5,8,9 Guideline recommendations include testing for IgM and/or IgG antibodies using either standard 2-tiered testing (STTT, test code 6646) or modified 2-tiered testing (MTTT, test code 39733)^8,9,22; in MTTT, the second tier of testing is performed by a second enzyme immunoassay instead of a Western blot. MTTT detects up to 30% more cases compared to STTT in patients with early Lyme disease.^23,24 The following sections outline appropriate test selection based on the stage of disease along with characteristic test results.

Early localized Lyme disease

Diagnosis of early localized Lyme disease can sometimes be made on the basis of EM alone without laboratory testing.² Importantly, serologic testing during the acute phase of Lyme disease is less sensitive than at later stages of disease.⁸ When testing is done too soon (≤14 days) following infection, negative or equivocal results may occur due to the time needed for the immune system to develop a serologic response.⁸ Positive or repeat testing (test codes 29477, 8593) on another sample collected in 7 to 14 days is recommended.⁸ Serologic testing (MTTT or STTT) may also be considered in patients with 1 or more skin lesions suggestive of, but atypical for, EM.⁹

If first-tier testing performed 14 days after suspected infection is negative, then second-tier testing is not required.⁸ If first-tier testing is positive or equivocal, then second-tier testing is required.⁸ For samples collected from patients with symptoms lasting ≤30 days, positive IgM is consistent with infection regardless of IgG seropositivity.⁸

Early disseminated Lyme disease

Two-tiered testing is recommended when clinical findings are suggestive of early disseminated Lyme disease (Table 3).^2,5,8,9 For specimens collected at 2 to 4 weeks after onset of symptoms, 2-tiered testing that is positive for IgM and negative for IgG indicates early infection, unless obtained on a specimen collected more than 1 month after onset of symptoms.⁸ If the specimen was collected more than 1 month after onset of symptoms, a positive IgM finding is more likely to represent a false-positive result unless IgG is also positive; vaccination or other diseases may also cause false-positive results.⁸ A positive IgG result by 2-tiered testing is required to confirm the diagnosis of early disseminated Lyme disease, but it does not differentiate between active and past B burgdorferi infection.^9,25

A diagnosis of LNB involving either the peripheral nervous system or central nervous system (CNS) can be supported if Borrelia antibody or DNA are detected in serum or cerebrospinal fluid (CSF); however, serum antibody testing is recommended over PCR due to low clinical sensitivity (38%).^9,26 If LNB involving the CNS is suspected and CSF testing is performed, a validated laboratory method for the determination of the CSF:serum antibody index using simultaneously obtained CSF and serum samples is recommended.⁹ The antibody levels in the CSF that are compared to control levels (ie, serum antibody or albumin) in the CSF:serum antibody index can be measured by enzyme-linked immunosorbent assay (ELISA) or nephelometry (test code 34194); an elevated antibody index strongly supports a diagnosis of LNB.²⁷

Negative serology results may indicate lack of infection or lack of seroconversion, which may occur if samples are collected too early after disease onset or when early antibiotic therapy blunts the antibody response.⁸ PCR-based assays (test codes 94322, 39209, 15777, 39219, 39218, 15510, 90558) can be useful in the workup of B burgdorferi infection if seroconversion has not yet occurred; these assays, however, are limited by low clinical sensitivity (18%).²⁸ Untreated patients who continue to be symptomatic but are seronegative for 6 to 8 weeks are unlikely to have Lyme disease, and a differential diagnosis should be considered.⁹

Late-stage Lyme disease

In patients with suspected Lyme disease that has been left untreated for months to years after a tick bite, symptoms that are characteristic of late-stage disease such as Lyme arthritis or LNB can help guide diagnostic test selection. Detection of Borrelia DNA in synovial fluid, commonly from the knees, supports the diagnosis of Lyme arthritis (sensitivity, 78%; specificity, 100%).^20,28

Non-Lyme bacterial tick-borne diseases [return to contents]

Tick-borne diseases caused by bacterial agents other than Lyme disease include tick-borne rickettsial diseases (TBRDs), tick-borne relapsing fevers, and tularemia. Each disease is discussed in the following sections.

Tick-borne rickettsial diseases

TBRDs include Rocky Mountain spotted fever (RMSF), Rickettsia parkeri rickettsiosis, anaplasmosis, and ehrlichiosis. TBRDs commonly manifest with an acute onset of nonspecific symptoms that mimic benign viral infections, making diagnosis difficult (Table 5).² The presence or absence of a rash can be a useful diagnostic aid.

Table 5. Clinical Features of Tick-borne Rickettsial Diseases [return to contents]

Disease	Incubation period, days²	Signs and symptoms²	Rash²
Anaplasmosis	5-14	Fever, chills, rigors, severe headache, malaise, myalgia, gastrointestinal symptoms	Rare (<10%)
Human monocytic ehrlichiosis (HME)	5-14	Fever, chills, headache, malaise, muscle pain, gastrointestinal symptoms, altered mental status	More commonly reported in children
Human ewingii ehrlichiosis	5-14	Fever, chills, headache, malaise, muscle pain, gastrointestinal symptoms, altered mental status	Rare
Mediterranean spotted fever (boutonneuse fever)	5-7	Fever, headache, muscle pain	Eschar (usually single)
Rickettsia parkeri rickettsiosis	2-10	Fever, headache, muscle aches	Sparse maculopapular or papulovesicular eruptions on the trunk and extremities
Rocky Mountain spotted fever	3-12	Early signs/symptoms (1-4 days) include fever, headache, malaise, myalgia, edema around eyes and back of hands, nausea/vomiting Late signs/symptoms (5 days or later) include altered mental state, coma, cerebral edema, respiratory compromise, necrosis, multiorgan system damage	Early (2-5 days after symptom onset) maculopapular rash initially appearing on the wrists, forearms, and ankles Late (after day 6 of symptom onset) petechial rash that indicates progression to severe disease

Because antibiotic treatment is most effective when given early, therapy for symptomatic patients with clinically suspected TBRDs should not be delayed pending confirmatory laboratory results.^2,29,30 Once the presumptive diagnosis of TBRD is made based on endemic exposure and clinical signs and symptoms, doxycycline is generally the drug of choice for both children and adults.^29,31,32

Anaplasmosis

Anaplasmosis is caused by infection with Anaplasma phagocytophilum. In 2021, 6,729 anaplasmosis cases were reported, the most since being a nationally notifiable disease in 1999.³³ Anaplasmosis is most frequently reported in the upper Midwest and Northeast³³; however, ticks that transmit anaplasmosis can also be found in the Pacific Coast states in addition to the Eastern United States.² Anaplasmosis has substantial overlap of features with early Lyme disease but tends to be a more severe illness.³⁴ The incidence (per million population) is highest in adults 70 to 84 years (more than 50 per million population) and in those with compromised immune systems.³³

The ticks that carry A phagocytophilum can also harbor B burgdorferi, B miyamotoi, or B microti,and detection of coinfection is recommended as it may affect treatment choices.³¹

Ehrlichiosis

Ehrlichiosis is mostly caused by Ehrlichia chaffeensis (human monocytic ehrlichiosis [HME]) and Ehrlichia ewingii (human ewingii ehrlichiosis) to a lesser extent.² These ehrlichioses are most identified in South-Central and Southeastern states, and from the East Coast extending to Texas.³⁵ In recent decades, cases of HME have increased 10-fold, from 200 reported cases in 2000 to 2,093 cases in 2019.³⁵ In comparison, only 353 cases of ehrlichiosis caused by E ewingii were reported to the CDC from 2008 to 2023.³⁵

Mediterranean spotted fever

Mediterranean spotted fever (boutonneuse fever) is an emerging TBRD of the spotted fever group, and the causative agent is Rickettsia conorii.³⁶ It has been reported in US patients who recently travelled to Europe (Mediterranean basin), the Middle East, the Indian subcontinent, or Africa.² Symptoms of boutonneuse fever are moderately severe (Table 5) and can include a single eschar rash.² The illness, which can be fatal, is transmitted from several species of Ixodes ticks.²

Rickettsia parkeri rickettsiosis

The first case of human R parkeri infection was documented in 2014; as of 2015, at least 40 cases have been identified.¹² It is carried by the Gulf Coast tick (Amblyomma maculatum), and its geographic distribution extends from the Southern and Mid-Atlantic regions. The first established population of the Gulf Coast tick was reported in Connecticut in 2021, and other populations were reported in New York in 2022 and in New Jersey in 2024; over 30% of these populations of Gulf Coast ticks were infected with R parkeri.³⁷

Rocky Mountain spotted fever

RMSF is a TBRD of the spotted fever group and is the most severe of the rickettsial diseases in the United States.¹¹ The disease is caused by the bacterium Rickettsia rickettsii, which infects endothelial cells and causes small-vessel vasculitis resulting in maculopapular or petechial rash.² Symptoms tend to appear 3 to 12 days after a bite.² Vasculitis in organs such as the brain or lungs can lead to life-threatening complications.²

Since 2010, RMSF has been reported as spotted fever rickettsiosis, which also includes other spotted fever rickettsioses (SFR) such as Rickettsia parkeri rickettsiosis. SFR have been reported throughout the United States, including Arizona where RMSF had not been previously seen.⁷ Five states (Arkansas, North Carolina, Alabama, Tennessee, and Missouri) accounted for more than 50% of cases during 2019 to 2023.⁷ The peak season for infection coincides with tick activity level for the region, but infection has been reported throughout the year.⁷ The reported incidence has increased in recent decades to about 19 cases per million population in 2017⁷; however, the increase in incidence has been accompanied by a decrease in case fatality rate to <0.5% in 2017.⁷ Although infection is most common in people over the age of 40 years, children younger than 10 years have the highest case-fatality rate.⁷

Hard tick relapsing fever

Borrelia miyamotoi is the causative agent of HTRF (also known as Borrelia miyamotoi disease [BMD]) and has been detected in both Ixodes species ticks (I scapularis and I pacificus) that transmit B burdorferi in Lyme disease. Hard tick relapsing fever may share the same geographic distribution as Lyme disease; however, unlike Lyme disease, which most commonly occurs in June and July, HTRF occurs mostly in July and August.²

The clinical presentation of HTRF is variable but shares a similar spectrum with other tick-borne diseases such as Lyme disease, anaplasmosis, and babesiosis.³⁸ A constellation of nonspecific symptoms includes fever, severe headache, myalgia, fatigue, and arthralgia. These symptoms are also characteristic of Lyme disease, babesiosis, and anaplasmosis, which may be included in a differential diagnosis.³⁸ A “toxic” appearance suggestive of sepsis is common on presentation in patients hospitalized for suspected infection and is often accompanied by elevated liver enzyme levels, neutropenia, and thrombocytopenia.³⁹

Tularemia

Ticks that transmit tularemia are widely distributed east of the Rocky Mountains; however, cases have been reported from nearly all US states and are most commonly found in parts of Massachusetts, including Martha’s Vineyard, the South Central United States, the Great Plains regions, and the Pacific Northwest.² It is caused by the bacterium Francisella tularensis and transmitted through varying portals of entry, including tick bites, deer fly bites, skin contact with infected animals, ingestion of contaminated food or water, and inhalation of contaminated aerosols or agricultural dust (Table 6).^2,40

Table 6. Clinical Consequences of Tularemia [return to contents]

Manifestation (portal of entry)^2,40,41	Signs and symptoms²
Oculoglandular (eyes)	Photophobia, vision impairment/loss, conjunctivitis, regional lymphadenopathy
Oropharyngeal (ingestion)	Severe throat pain, exudative pharyngitis or tonsilitis, regional lymphadenopathy
Pneumonic (inhalation)	Non-productive cough, substernal tightness, pleuritic chest pain; hilar adenopathy, infiltrate, or pleural effusion may be present on chest X-ray; most serious form of tularemia
Typhoidal (any)	Combination of general symptoms without the localized symptoms of other tularemia syndromes; infiltrates may be seen in chest X-ray even in the absence of respiratory symptoms
Ulceroglandular (skin)	Localized lymphadenopathy, cutaneous ulcer with a black base at site of infection (not always present)

General symptoms of tularemia include fever, chills, malaise, anorexia, myalgia, chest discomfort, cough, sore throat, vomiting diarrhea, and abdominal pain. Ulceroglandular tularemia is the most common form of tularemia and usually occurs following a tick bite or after handling an infected animal.⁴⁰ Infection via tick bites is characterized by an ulcerative lesion at the site of the tick bite and lymphadenopathy. An erythematous, tender, or pruritic papule typically appears within 3 to 5 days and subsequently enlarges to form an ulcer with a black base. Pneumonic tularemia, a pulmonary form that may be contracted by inhalation, is the most serious form of tularemia and may spread through the bloodstream to the lungs if left untreated.

Non-Lyme bacterial tick-borne diseases: test availability

Laboratory tests that can help diagnose non-Lyme bacterial disease include culture, immunoassays and PCR-based assays (Table 7).

Table 7. Tests Available for Diagnosis and Management of Non-Lyme Bacterial Tick-Borne Diseases [return to contents]

Test code		Assay^a	Method		Clinical use
Spotted fever rickettsiosis
91121	Febrile Antibodies Panel^b,c Includes Brucella IgG and IgM with reflex to agglutination (test code 91068), Rickettsia (RMSF) IgG and IgM with reflex to titer, Rickettsia typhi IgG and IgM with reflex to titer, and Salmonellatotal antibody (Salmonella H types A, B, D; Salmonella O types D, Vi; test code 10582).			See individual tests		Differential diagnosis of RMSF or Rickettsia typhi as a cause of febrile disease vs other infectious causes
37507	Rickettsia Antibody Panel With Reflex to Titers^b Includes IgG and IgM to causative organisms of RMSF and typhus fever.			IFA		Differential diagnosis of rickettsial disease
15332	Rickettsia conorii Antibody Panel, IFA^c Includes IgG and IgM.					Diagnose Rickettsia conorii infection
37478	Rickettsial Disease Panel Includes Rickettsia (RMSF) IgG and IgM with reflex to titer; Rickettsia (typhus fever) IgG and IgM with reflex to titer; and Q fever (Coxiella burnetii) IgG and IgM phase I and phase II with reflex to titers.					Differential diagnosis of rickettsial disease
70191	Rickettsia Species DNA, Real-Time PCR^c			Real-time PCR		Diagnose RMSF
6419	Rickettsia (RMSF) Antibodies (IgG, IgM) With Reflex to Titers^b			IFA
37503	Rickettsia (Typhus Fever) Antibodies (IgG, IgM) With Reflex to Titers^b Includes Rickettsia (RMSF) IgG and IgM with reflex to titer and Rickettsia (typhus fever) IgG and IgM with reflex to titer.			IFA		Differential diagnosis of rickettsial disease (tick-borne vs other organisms)
Anaplasmosis
16212	Anaplasma phagocytophilum and E.chaffeensis Antibody Panel Reflex to Titers^b,c Includes IgG and IgM for both organisms with reflex to titers.			IFA		Diagnose anaplasmosis and ehrlichiosis
16189	Anaplasma phagocytophilum Antibodies (IgG, IgM) With Reflex to Titers^b,c			IFA		Diagnose anaplasmosis
17320	Anaplasma phagocytophilum DNA, Qualitative, Real-Time PCR^d			Real-time PCR
Ehrlichiosis
16197	Ehrlichia chaffeensis Antibodies(IgG, IgM) With Reflex to Titers^b,c			IFA		Diagnose ehrlichiosis
11353	Ehrlichia chaffeensis DNA, Real-Time PCR^d			Real-time PCR
70194(X)	Ehrlichia ewingii DNA, Real-Time PCR^d			Real-time PCR
Tularemia
11873	Culture, Select Agent^d			Culture		Screen for tularemia
12707	Francisella tularensis Antibody, Antibody, IgM and IgG, ELISA, Serum^d			ELISA		Diagnose tularemia
*Hard tick relapsing fever (Borrelia* miyamotoi disease)**
39684	Borrelia miyamotoi Antibodies (IgG, IgM), Immunoassay^d			Immunoassay		Diagnose B miyamatoi infection
93795	Borrelia miyamotoi DNA, Real-Time PCR, Miscellaneous^d			Real-time PCR		Confirm diagnosis of B miyamotoi infection
93794	Borrelia miyamotoi DNA, Real-Time PCR, Tickd					Detect B miyamotoi in tick to assess risk of human infection
39219	Borrelia Species DNA, Real-Time PCR, With Reflexes, Blood^b,c,d			Real-time PCR		Detect Borrelia spp DNA; diagnose Lyme disease or B miyamotoi disease
39218	Borrelia Species DNA, Real-Time PCR, With Reflexes, Synovial Fluid/CSF^b,c,d

ELISA, enzyme-linked immunosorbent assay; IFA, immunofluorescence assay; PCR, polymerase chain reaction; RMSF, Rocky Mountain spotted fever.
a	Panel components may be ordered individually.
b	Reflex tests are performed at an additional charge and are associated with an additional CPT code(s).
c	This test was developed and its analytical performance characteristics have been determined by Quest Diagnostics. It has not been cleared or approved by the US Food and Drug Administration. This assay has been validated pursuant to the CLIA regulations and is used for clinical purposes.
d	Please refer to the Quest Test Directory for your service area for test availability.

Non-Lyme bacterial tick-borne diseases: test selection and interpretation

Tick-borne rickettsial diseases

Diagnosis of TBRDs is primarily clinical. However, laboratory testing can play an important role in distinguishing among closely related TBRDs and confirming infection. Confirmatory laboratory testing for TBRDs is primarily through serology and nucleic acid testing (Table 8).^2,31,42 Immunofluorescence antibody assays (test codes 37507, 15332, 37478, 6419, 37503) are considered the gold standard for TBRD serology testing.³¹ A 4-fold rise in titer of IgG or IgM in paired acute and convalescent samples is essential to confirm infection; the acute sample should be taken within the first 2 weeks of illness and the convalescent sample should be taken 2 to 4 weeks later.²

Table 8. Confirmatory Diagnostic Testing for Non-Lyme Bacterial Tick-borne Diseases [return to contents]

Disease	Confirmatory laboratory tests offered by Quest^a	Criteria for confirmation of diagnosis^a
Tick-borne rickettsial diseases^31,36,42
Anaplasmosis	Acute and convalescent serology (test codes 16212, 16189) or	4-fold increase in antibody titer^b,c
Anaplasmosis	A phagocytophilum DNA (test code 17320)	Detected
Human monocytic ehrlichiosis (HME)	Acute and convalescent serology (test code 16197, 16212) or	4-fold increase in antibody titer^b,c
Human monocytic ehrlichiosis (HME)	E chaffeensis DNA (11353)	Detected
Human ewingii ehrlichiosis	Acute and convalescent serology (test code 16197) or	4-fold increase in antibody titer^b,c
Human ewingii ehrlichiosis	E ewingii DNA (70194[X])	Detected
Mediterranean spotted fever (boutonneuse fever)	Acute and convalescent serology (test code 15332)	4-fold increase in antibody titer
Rickettsia parkeri rickettsiosis	Acute and convalescent serology (test codes 37507, 37478, 6419, 37503) or	4-fold increase in antibody titer^d
Rickettsia parkeri rickettsiosis	Rickettsia species DNA (test code 70191)	Detected
Rocky Mountain spotted fever (Rickettsia rickettsii)	Acute and convalescent serology (test codes 37507, 37478, 6419, 37503, 91121) or	4-fold increase in antibody titer^b,c
Rocky Mountain spotted fever (Rickettsia rickettsii)	R rickettsii DNA (test code 70191)	Detected
Non-rickettsial diseases
Hard tick relapsing fever²	Acute and convalescent serology (test code 39684)	Increase in antibody titer
	B miyamotoi DNA^e (test codes 93795, 93794, 39219, 39218, 15777, 15510)	Detected^e
	B hermsii DNA, B turicatae DNA^e (test codes 15777, 15510, 39218)	Detected^e
Tularemia	Serology (test code 12707)	Seroconversion from negative to positive IgM and/or IgG
Tularemia	Culture¹³ (test code 11873)	F tularensis detected in samples taken from ulcers, lymph node aspirates or biopsies, pharynx, pleural fluid (respiratory specimens)

a	Confirmation of the diagnosis is based on laboratory testing, but antibiotic therapy should not be delayed in a patient with suspected infection.²
b	Titers are often negative in the first 7 to 10 days of illness. Results from acute serology alone cannot be relied upon for confirmation of infection.²
c	IgM results alone should not be used for laboratory diagnosis.²
d	Results may not be specific to R parkeri; RMSF antibody tests often cross-react.²
e	Supportive of diagnosis.¹³

Note: although most patients have positive IgG or IgM antibody by the second week of illness, many people will be seronegative at the time of the first test, especially if done within the first week or so of illness. Therefore, negative results on serologic tests should not lead to discontinuation of therapy.³¹

Detection of DNA in whole blood is especially useful for confirming anaplasmosis and ehrlichioses because these organisms infect circulating leukocytes. In patients with suspected RMSF, detection of R rickettsii in blood is more likely in advanced disease or fulminant infection. Positive results confirm TBRD, but negative results do not exclude the diagnosis.

Hard tick relapsing fever

Laboratory diagnosis of HTRF is supported by molecular and serology testing and by visualization of spirochetes by microscopy of peripheral blood obtained during a febrile episode (Table 8).² PCR amplification of B miyamotoi DNA is part of an acute molecular panel of tests used to confirm a presumptive diagnosis of HTRF (BMD) based on clinical presentation. Cerebrospinal fluid, synovial fluid, whole blood, or urine are acceptable specimen types for analysis. Detection of B miyamotoi DNA in suspected tick specimens is supportive for the diagnosis of infection.² Guidelines also indicate serologic testing to confirm the diagnosis of HTRF.² Positive results on serology by ELISA or IgM and IgG immunoblot, however, may indicate coinfection by Borrelia species such as B burgdorferi and/or B hermsii.² Negative results do not rule out infection and may be due to testing prior to seroconversion during the acute phase of infection.⁴³

Tularemia

Various methods are available to assist in the diagnosis of tularemia. Culture (test code 11873) of F tularensis from appropriate sites provides definitive evidence of tularemia but can be challenging due to the slow-growing, fastidious nature of the organism.² Serology test results indicating seroconversion from negative to positive IgM and/or IgG antibodies in paired acute and convalescent specimens confirms a diagnosis of tularemia (Table 8, test codes 12707).^2,13 Tests that can support a diagnosis of tularemia include immunohistochemical staining, sequencing (eg, PCR), or single serologic tests performed on serum samples collected at least 14 days after the onset of symptoms.¹³

Parasitic and viral tick-borne diseases [return to contents]

Babesiosis

Babesiosis is a tick-borne disease caused by infection of erythrocytes by Babesia spp parasites. Most cases are caused by B microti, which is transmitted by Ixodes scapularis ticks.² During 2011 to 2019, more than half of the 16,456 cases of babesiosis reported to the CDC were reported from New York (4,738), Massachusetts (4,136), and Connecticut (2,200);⁴⁴ however, cases linked to B duncani have occurred on the West Coast.² Infection is primarily transmitted by ticks, although it can also be transmitted congenitally or through transfusion.²

Symptoms may appear 1 to 6 weeks after the tick bite but some infected persons remain asymptomatic.² Symptoms vary widely but may include a gradual onset of irregular fever, chills, sweating, myalgia, arthralgia, nausea/vomiting, fatigue, and dark urine.² Mild hepatosplenomegaly or jaundice may develop.² Less common symptoms include photophobia and conjunctival injection.² Treatment is not usually required for people without symptoms.²

Colorado tick fever

Colorado tick fever (CTF) is caused by an arbovirus (Colorado tick fever virus) that infects erythrocytes. It is found throughout the Rocky Mountain region, primarily in Colorado, Utah, Montana, and Wyoming (Table 1).² Although CTF is not a nationally notifiable condition, a total of 223 cases of CTF were reported to the CDC from 2003 through 2022.⁴⁵

Symptoms of CTF occur 1 to 14 days after a tick bite and include fever, chills, headache, body aches, and lethargy.² In about half of patients, a “biphasic” fever may occur in which a fever lasting 2 to 3 days disappears then reappears for another 2 to 3 days. In rare instances, severe complications may affect the central nervous system, resulting in symptoms that may include stiff neck and confusion.⁴⁶ Specific antiviral treatment is not available for CTF.⁴⁶

Parasitic and viral tick-borne diseases: test availability

Laboratory tests that can help diagnose parasitic and viral tick-borne diseases include microscopy, immunoassay, and PCR-based assays (Table 9).

Table 9. Tests Available for Diagnosis and Management of Parasitic and Viral Tick-Borne Diseases [return to contents]

Test code	Assay^a	Method	Clinical use
Babesiosis
16194	Babesia microti Antibodies (IgG, IgM) With Reflex to Titers^b,c	IFA	Diagnose babesiosis
37314	Babesia microti DNA, Real-Time PCR^b	Real-time PCR
17231	Babesia duncani (WA1) Antibody (IgG), IFA^b	IFA
831	Malaria/Babesia/Other Blood Parasites	Microscopy
Colorado tick fever
34986	Colorado Tick Fever Antibodies (IgG, IgM)^b	IFA	Diagnose Colorado tick fever

IFA, immunofluorescence assay; PCR, polymerase chain reaction; RMSF, Rocky Mountain spotted fever
a	Panel components may be ordered individually.
b	This test was developed and its analytical performance characteristics have been determined by Quest Diagnostics. It has not been cleared or approved by the US Food and Drug Administration. This assay has been validated pursuant to the CLIA regulations and is used for clinical purposes.
c	Reflex tests are performed at an additional charge and are associated with an additional CPT code(s).

Parasitic and viral tick-borne diseases: test selection and interpretation

Babesiosis

The diagnosis of babesiosis should be based on epidemiological risk factors and clinical evidence and confirmed by microscopic identification (test code 831) or detection of Babesia species (ie, B microti, B duncani) DNA by nucleic acid amplification (test code 37314).^2,47 Serologic testing may also confirm or support a diagnosis depending on antibody titers (test codes 16194, 17231).² A 4-fold increase in IgG levels seen in paired acute and convalescent specimens is confirmatory, while an IgG antibody titer of ≥1:1024 or the presence of IgM antibody are supportive of active or recent B microti infection.⁴⁷ Also supportive of infection are general laboratory findings that are consistent with hemolysis: hemolytic anemia with decreased haptoglobin, elevated lactate dehydrogenase, reticulocytosis, thrombocytopenia, elevated creatinine and blood urea nitrogen, elevated transaminase, and proteinuria.²

Colorado tick fever

Leukopenia is characteristically seen in a CBC, and moderate thrombocytopenia may be present.² Laboratory diagnosis by molecular testing (PCR) is preferred for serum (CSF if suspected CNS involvement) specimens collected at fewer than 14 days after symptom onset.² For specimens collected on or after day 14, acute and convalescent serology (test code 34986) is preferred but PCR should be considered for specimens collected up to 21 days after symptom onset.² A 4-fold rise of IgG or IgM titer in paired acute and convalescent specimens supports a diagnosis of CTF.² Paired specimens should be collected at least 2 weeks apart, with the convalescent specimen collected at least 3 weeks after symptom onset.²

References [return to contents]

Geographic distribution of tickborne disease cases. Centers for Disease Control and Prevention. Updated August 6, 2025. Accessed December 15, 2025. https://www.cdc.gov/ticks/data-research/facts-stats/geographic-distribution-of-tickborne-disease-cases.html
Tickborne diseases of the United States. A Reference Manual for Health Care Providers, 6th ed. Centers for Disease Control and Prevention; 2022. Accessed December 23, 2025 https://www.cdc.gov/ticks/media/pdfs/2025/03/tickborne-diseases-manual-508.pdf?CDC_AAref_Val=https://www.cdc.gov/ticks/tickbornediseases/TickborneDiseases-P.pdf.
Tickborne disease surveillance data summary. Centers for Disease Control and Prevention. Updated July 15, 2024. Accessed December 15, 2025. https://www.cdc.gov/ticks/data-research/facts-stats/tickborne-disease-surveillance-data-summary.html#:~:text=During%202019%2D2022%2C%20state%20and,to%20CDC%20over%20the%20years.
Ehrlichiosis: Wisconsin Data. Updated June 30, 2025. Accessed December 15, 2025. https://www.dhs.wisconsin.gov/tick/ehrlichiosis-data.htm
Skar GL, Blum MA, Simonsen, KA Lyme Disease In: StatPearls [Internet]. StatPearls Publishing; 2024. Updated October 1, 2024. Accessed December 15, 2025 https://www.ncbi.nlm.nih.gov/books/NBK431066/.
Fagre A, Lehman J, Hills SL. Colorado tick fever in the United States, 2013-2022. Am J Trop Med Hyg. 2024;111(3):598-602. doi:10.4269/ajtmh.24-0044
Data and statistics on spotted fever rickettsiosis. Centers for Disease Control and Prevention. Updated May 15, 2024. Accessed December 15, 2025. https://www.cdc.gov/rocky-mountain-spotted-fever/data-research/facts-stats/?CDC_AAref_Val=https://www.cdc.gov/rmsf/stats/index.html
Suggested reporting language, interpretation and guidance for Lyme disease serologic test results (April 2024). Association of Public Health Laboratories. Updated April 2024. Accessed December 15, 2025. https://www.aphl.org/aboutAPHL/publications/Documents/ID-2024-Lyme-Disease-Serologic-Testing-Reporting.pdf
Lantos PM, Rumbaugh J, Bockenstedt LK, et al. 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;72(1):e1-e48. doi:10.1093/cid/ciaa1215
Cutler SJ, Vayssier-Taussat M, Estrada-Peña A, et al. Tick-borne diseases and co-infection: Current considerations. Ticks Tick Borne Dis. 2021;12(1):101607. doi:10.1016/j.ttbdis.2020.101607
Rocky Mountain Spotted Fever (RMSF). Clinical Signs and Symptoms. Centers for Disease Control and Prevention. Updated May 15, 2024. Accessed December 15, 2025. https://www.cdc.gov/rocky-mountain-spotted-fever/hcp/signs-symptoms/index.html.
Adams DA, Thomas KR, Jajosky RA, et al. Summary of notifiable infectious diseases and conditions - United States, 2014. MMWR Morb Mortal Wkly Rep. 2016;65(52). doi:10.15585/mmwr.mm6354a1
Clinical testing and diagnosis for tularemia. Centers for Disease Control and Prevention. Updated May 15, 2024. Accessed December 15, 2025. https://www.cdc.gov/tularemia/hcp/diagnosis-testing/index.html
Lyme disease rashes. Centers for Disease Control and Prevention. Updated May 15, 2024. Accessed December 15, 2025. https://www.cdc.gov/lyme/signs-symptoms/lyme-disease-rashes.html
Lyme disease surveillance data. Centers for Disease Control and Prevention. Updated February 11, 2025. Accessed December 15, 2025. https://www.cdc.gov/lyme/data-research/facts-stats/surveillance-data-1.html
Kugeler KJ, Schwartz AM, Delorey MJ, et al. Estimating the frequency of Lyme disease diagnoses, United States, 2010-2018. Emerg Infect Dis. 2021;27(2):616-619. doi:10.3201/eid2702.202731
Shapiro ED. Clinical practice: Lyme disease. N Engl J Med. 2014;370(18):1724-1731. doi:10.1056/NEJMcp1314325
Telford SR, Goethert HK, Molloy PJ, et al. Borrelia miyamotoi disease: neither Lyme disease nor relapsing fever. Clin Lab Med. 2015;35(4):867-882. doi:10.1016/j.cll.2015.08.002
Hildenbrand P, Craven DE, Jones R, et al. Lyme neuroborreliosis: manifestations of a rapidly emerging zoonosis. Am J Neuroradiol. 2009;30(6):1079-1087. doi:10.3174/ajnr.A1579
Steere AC. Treatment of Lyme arthritis. J Rheumatol. 2019;46(8):871-873. doi:10.3899/jrheum.190320
Wormser GP, Dattwyler RJ, Shapiro ED, et al. The clinical assessment, treatment, and prevention of Lyme disease, human granulocytic anaplasmosis, and babesiosis: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis. 2006;43(9):1089-1134. doi:10.1086/508667
Mead P, Petersen J, Hinckley A. Updated CDC recommendation for serologic diagnosis of Lyme disease. MMWR Morb Mortal Wkly Rep. 2019;68(32):703. doi:10.15585/mmwr.mm6832a4
Branda JA, Body BA, Boyle J, et al. Advances in serodiagnostic testing for Lyme disease are at hand. Clin Infect Dis. 2017;66(7):1133-1139. doi:10.1093/cid/cix943
B. burgdorferi IgG/IgM Test System. [Package insert]. ZEUS Scientific; 2020.
Kalish RA, McHugh G, Granquist J, et al. Persistence of immunoglobulin M or immunoglobulin G antibody responses to Borrelia burgdorferi 10–20 years after active Lyme disease. Clin Infect Dis. 2001;33(6):780-785. doi:10.1086/322669
Nocton JJ, Bloom BJ, Rutledge BJ, et al. Detection of Borrelia burgdorferi DNA by polymerase chain reaction in cerebrospinal fluid in Lyme neuroborreliosis. J Infect Dis. 1996;174(3):623-627. doi:10.1093/infdis/174.3.623
Blanc F, Jaulhac B, Fleury M, et al. Relevance of the antibody index to diagnose Lyme neuroborreliosis among seropositive patients. Neurology. 2007;69(10):953-958. doi:10.1212/01.wnl.0000269672.17807.e0
Aguero-Rosenfeld ME, Wang G, Schwartz I, et al. Diagnosis of Lyme borreliosis. Clin Microbiol Rev. 2005;18(3):484-509. doi:10.1128/CMR.18.3.484-509.2005
Snowden J, Simonsen KA. Rickettsia rickettsiae. In: StatPearls [Internet]. StatPearls Publishing; 2023. Updated July 17, 2023. Accessed December 15, 2025. https://www.ncbi.nlm.nih.gov/books/NBK430881/
Walker DH, Myers CTE, Blanton LS, et al. Rickettsiosis subcommittee report to the tick-borne disease working group. Ticks Tick Borne Dis. 2022;13(1):101855. doi:10.1016/j.ttbdis.2021.101855
Biggs HM, Behravesh CB, Bradley KK, et al. Diagnosis and management of tickborne rickettsial diseases: Rocky Mountain spotted fever and other spotted fever group rickettsioses, ehrlichioses, and anaplasmosis - United States. MMWR Recomm Rep. 2016;65(2):1-44. doi:10.15585/mmwr.rr6502a1
Rickettsiosis subcommittee report to the tick-borne disease working group. US Department of Health & Human Services. Updated January 24, 2020. Accessed December 15, 2025. https://www.hhs.gov/ash/advisory-committees/tickbornedisease/reports/rickettsiosis-subcomm-2020/index.html
Anaplasmosis. Epidemiology and statistics. Centers for Disease Control and Prevention. Updated March 3, 2025. Accessed December 15, 2025. https://www.cdc.gov/anaplasmosis/hcp/statistics/index.html
Wormser GP, Aguero-Rosenfeld ME, Cox ME, et al. Differences and similarities between culture-confirmed human granulocytic anaplasmosis and early Lyme disease. J Clin Microbiol. 2013;51(3):954-958. doi:10.1128/JCM.02929-12
Ehrlichiosis. Epidemiology and statistics. Centers for Disease Control and Prevention. Updated February 12, 2025. Accessed December 15, 2025. https://www.cdc.gov/ehrlichiosis/data-research/facts-stats/index.html
Spernovasilis N, Markaki I, Papadakis M, et al. Mediterranean spotted fever: current knowledge and recent advances. Trop Med Infect Dis. 2021;6(4)doi:10.3390/tropicalmed6040172
First human case of emerging tick-borne disease reported in Northeast. Yale School of Public Health. Updated September 30, 2024. Accessed December 15, 2025. https://ysph.yale.edu/news-article/first-human-case-of-emerging-tick-borne-disease-reported-in-northeast/
Krause PJ, Fish D, Narasimhan S, et al. Borrelia miyamotoi infection in nature and in humans. Clin Microbiol and Infect. 2015;21(7):631-639. doi:/10.1016/j.cmi.2015.02.006
Molloy PJ, Telford SR, Chowdri HR, et al. Borrelia miyamotoi disease in the Northeastern United States: a case series. Ann Intern Med. 2015;163(2):91-98. doi:10.7326/m15-0333
Tularemia. Signs and symptoms. Centers for Disease Control and Prevention. Updated May 15, 2024. Accessed 2025, December 15. https://www.cdc.gov/tularemia/signs-symptoms/index.html
Snowden J, Simonsen KA. Tularemia. In: StatPearls [Internet]. StatPearls Publishing; 2025. Updated July 17, 2023. Accessed January 5, 2026. https://www.ncbi.nlm.nih.gov/books/NBK430905/
MacConnachie K, Tishkowski K. Boutonneuse Fever. In: StatPearls [Internet]. StatPearls Publishing; 2021. Updated July 3, 2023. Accessed December 15, 2025 https://www.ncbi.nlm.nih.gov/books/NBK560914/
Sudhindra P, Wang G, Schriefer ME, et al. Insights into Borrelia miyamotoi infection from an untreated case demonstrating relapsing fever, monocytosis and a positive C6 Lyme serology. Diagn Microbiol Infect Dis. 2016;86(1):93-96. doi:10.1016/j.diagmicrobio.2016.06.015
Swanson M, Pickrel A, Williamson J, et al. Trends in Reported Babesiosis Cases - United States, 2011-2019. MMWR Morb Mortal Wkly Rep. 2023;72(11):273-277. doi:10.15585/mmwr.mm7211a1
Data and maps for Colorado tick fever. Centers for Disease Conrol and Prevention. Updated May 15, 2024. Accessed December 16, 2025. https://www.cdc.gov/colorado-tick-fever/data-maps/index.html
Colorado tick fever: symptoms, diagnosis, and treatment. Centers for Disease Control and Prevention. Updated November 19, 2025. Accessed December 16, 2025. https://www.cdc.gov/colorado-tick-fever/symptoms-diagnosis-treatment/index.html
Krause PJ, Auwaerter PG, Bannuru RR, et al. Clinical Practice Guidelines by the Infectious Diseases Society of America (IDSA): 2020 Guideline on Diagnosis and Management of Babesiosis. Clinical Infectious Diseases. 2021;72(2):e49-e64. doi:10.1093/cid/ciaa1216

Content reviewed 1/2026

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This Topic Brief provides information about the laboratory testing that supports the diagnosis of various types of tick-borne diseases.

Test Guide List

Tick-borne Diseases: Laboratory Support of Diagnosis and Management

Topic Brief

Tick-borne Diseases

Laboratory Support of Diagnosis and Management

Contents:

Introduction

All tick-borne diseases

Table 1. Incidence of Tick-borne Diseases, United States

Table 2. Tests Available for Diagnosis and Management of All Tick-borne Diseases

Figure. Serological Test Selection for the Differential Diagnosis of Tick-borne Diseases Based on Geographic Origin and Symptoms of Infection

Lyme disease

Table 3. Clinical Features of Lyme Disease and Recommended Laboratory Testing

Table 4. Tests Available for Diagnosis and Management of Lyme Disease

Non-Lyme bacterial tick-borne diseases

Table 5. Clinical Features of Tick-borne Rickettsial Diseases

Table 6. Clinical Consequences of Tularemia

Table 7. Tests Available for Diagnosis and Management of Non-Lyme Bacterial Tick-Borne Diseases

Table 8. Confirmatory Diagnostic Testing for Non-Lyme Bacterial Tick-borne Diseases

Parasitic and viral tick-borne diseases

Table 9. Tests Available for Diagnosis and Management of Parasitic and Viral Tick-Borne Disease

References

Introduction [return to contents]

All tick-borne diseases [return to contents]

Table 1. Incidence of Tick-borne Diseases, United States [return to contents]

Disorder (reported cases, 2022)	Disease geographic distribution^1,2,4,5,a	Causative organism	Primary vector tick(s)
Lyme disease (62,551)³	Upper Midwest, Northeast, Mid-Atlantic, Northern California, Oregon, Washington	Borrelia burgdorferi, Borrelia mayonii	Black-legged tick, also known as deer tick (Ixodes scapularis) Western black-legged tick (Ixodes pacificus)
Anaplasmosis (5,633)³	Upper Midwest, Northeast, Pacific Coast states, Eastern states	Anaplasma phagocytophilum	Black-legged tick, also known as deer tick (Ixodes scapularis), Western black-legged tick (Ixodes pacificus)
Ehrlichiosis (HME) (1,557)³	South-Central, Southeast, East Coast extending to Texas	Ehrlichia chaffeensis	Lone star tick (Amblyomma americanum)
Human ewingii ehrlichiosis (25)³	South-Central, Southeast, East Coast extending to Texas	Ehrlichia ewingii	Lone star tick (Amblyomma americanum)
Spotted fever rickettsioses (1,271)^3,b	Nationwide; Arkansas, North Carolina, Alabama, Missouri and Tennessee account for over 50% of cases	Rickettsia rickettsii	American dog tick (Dermacentor variabilis) Brown dog tick (Rhipicephalus sanguineus) Rocky Mountain wood tick (Dermacentor andersoni)
		Rickettsia parkeri	Gulf Coast tick (Amblyomma maculatum)
Babesiosis (1,915)^3,c	Most common in New York, Massachusetts, Connecticut; cases reported on the West Coast	Babesia microti and other Babesia species (eg, Babesia duncani)	Black-legged tick, also known as deer tick (Ixodes scapularis)
Tularemia (167)³	Nationwide; predominately Midwest	Francisella tularensis	Lone star tick (Amblyomma americanum) Rocky Mountain wood tick (Dermacentor andersoni) American dog tick (Dermacentor variabilis)
Colorado tick fever (11)^6,d	Rocky Mountain region	Colorado tick fever virus	Rocky Mountain wood tick (Dermacentor andersoni)
Hard tick relapsing fever (unknown)	Upper Midwest, Northeast, Mid-Atlantic, Northern California, Oregon, Washington	Borrelia miyamotoi	Black-legged tick, also known as deer tick (Ixodes scapularis) Western black-legged tick (Ixodes pacificus)

HME, human monocytic ehrlichiosis; RMSF, Rocky Mountain spotted fever.
a	See reference 1 for detailed geographic distribution maps.
b	As of 2010, cases of Rocky Mountain spotted fever (RMSF), Rickettsia parkeri rickettsiosis, Pacific Coast tick fever, and rickettsialpox are reported under a category called Spotted Fever Rickettsiosis (SFR). Categorization under SFR is due to the inability to differentiate between spotted fever group Rickettsia species using commonly available serologic tests.⁷
c	Reported cases in 2021.
d	Median number of cases per year, 2013-2022.6

All tick-borne diseases: test availability

Table 2. Tests Available for Diagnosis and Management of All Tick-borne Diseases [return to contents]

Test code	Assay^a	Method	Clinical use
3946(X)	Tick (and Other Arthropods) Identification	Microscopy	Identify tick to determine risk of tick-borne disease; assist with differential diagnosis
94322	Tick-borne Disease, Acute Molecular Panel^b Includes Anaplasma phagocytophilum, Babesia microti, Borrelia miyamotoi, Ehrlichia chaffeensis, and Lyme disease Borrelia spp.	Real-time PCR (qualitative for A phagocytophilum and Borrelia spp [blood])	Diagnose tick-borne diseases when selecting tests for individual pathogen is challenging due to overlapping geographic distributions and clinical presentations of illness; especially useful to diagnose mixed infections
32338	Tick-borne Disease, Acute Molecular Panel, Non-Lyme^b Includes A phagocytophilum, B microti, B miyamotoi, and E chaffeensis.
16220	Tick-borne Disease, Antibody Panel With Reflexes^b,c Includes Lyme disease Ab with reflex to immunoassay (IgG, IgM) and A phagocytophilum antibodies (IgG and IgM), B microti antibodies (IgG, IgM), and E chaffeensis (IgG, IgM) with reflexes to titers.	IFA, immunoassay	Diagnose tick-borne diseases when selecting tests for individual pathogens is challenging due to substantial clinical overlap and coinfection

IFA, immunofluorescence assay; PCR, polymerase chain reaction.
a	Panel components may be ordered individually.
b	This test was developed and its analytical performance characteristics have been determined by Quest Diagnostics. It has not been cleared or approved by the US Food and Drug Administration. This assay has been validated pursuant to the CLIA regulations and is used for clinical purposes.
c	Reflex tests are performed at an additional charge and are associated with an additional CPT^® code(s).

All tick-borne diseases: test selection and interpretation

Figure. Serological Test Selection for the Differential Diagnosis of Tick-borne Diseases Based on Geographic Origin and Symptoms of Infection
[return to contents]

Lyme disease [return to contents]

Table 3. Clinical Features of Lyme Disease and Recommended Laboratory Testing [return to contents]

Stage of disease^2,5	Symptom onset²	Symptoms²	Laboratory testing^8,9
Early localized (acute phase)	3-30 days after tick bite	EM Fever, myalgia, headache, nausea, fatigue	If EM is identified in a patient where Lyme disease is endemic, serologic testing is not recommended (ie, clinical diagnosis of Lyme is recommended) STTT or MTTT may be considered (weakly recommended) for patients with 1 or more skin lesions suggestive of but atypical for EM; however, serologic testing during the acute phase of infection is less sensitive and specific than testing at later stages of infection
Early disseminated	3-12 weeks after tick bite	Dermatologic: multiple EM rashes that are distant from bite Neurologic: LNB – common symptoms include Bell’s palsy, lymphocytic meningitis, painful radiculoneuritis (1 or more dermatomes), and others such as painful peripheral motor and sensory neuropathy (mononeuritis multiplex) and intracranial hypertension (rare) Cardiac: Lyme carditis leading to conduction abnormalities such as AV node block; can be fatal (rare) Rheumatologic: transient and/or migratory arthritis; effusion in 1 or more joints, often large joints; Baker’s cysts; migratory pain in tendons, bursae, muscle, and bones	When assessing for possible LNB affecting either the PNS or CNS, STTT or MTTT, serum is recommended If LNB or 1 or more acute symptoms (eg, meningitis, painful radiculoneuritis) of LNB is suspected, guideline recommendations include obtaining simultaneous samples of CSF and serum for measuring CSF:serum antibody index STTT or MTTT is recommended when assessing for rheumatologic symptoms of Lyme disease; PCR is recommended in seropositive patients
Late-stage	Months to years after tick bite	Patients may not have a history of EM, however, may present with sensory axonal polyneuropathy, encephalomyelitis (rare), or mononeuropathy Cognitive deficits, personality changes, extreme irritability, and depression Lyme arthritis Bluish red rash (acrodermatitis chronica atrophicans) in women	STTT or MTTT is recommended with IgG only considered >30 days after symptom onset

Lyme disease: test availability

Laboratory tests that can help confirm the clinical diagnosis of Lyme disease include tick identification, various serologic techniques and PCR-based assays (Table 4).

Table 4. Tests Available for Diagnosis and Management of Lyme Disease [return to contents]

Test code	Assay^a	Method	Clinical use
Lyme disease
39209	Borrelia burgdorferi DNA, Qualitative Real-Time PCR, Miscellaneous^b,c	Real-time PCR	Diagnose Lyme disease using whole blood, synovial fluid, or CSF
15777	Borrelia Species DNA, Qualitative Real-Time PCR, Miscellaneous^b		Detect Borrelia spp DNA in whole blood, synovial fluid, or CSF
15510	Borrelia Species DNA, Qualitative Real-Time PCR, Tick^b		Detect Borrelia spp DNA in ticks
39219	Borrelia Species DNA, Real-Time PCR, With Reflexes, Blood^b,c,d		Detect Borrelia spp DNA in whole blood
39218	Borrelia Species DNA, Real-Time PCR, With Reflexes, Synovial Fluid/CSF^b,c,d		Detect Borrelia spp DNA in synovial fluid or CSF
6646	Lyme Disease Ab With Reflex to Blot (IgG, IgM)^d	Immunoassay	Diagnose Lyme disease by standard 2-tiered test
39733	Lyme Disease Antibody With Reflex to Immunoassay (IgG, IgM) (MTTT)^d Includes reflex to Lyme disease supplemental antibodies (IgG, IgM) if Lyme disease total antibody is positive or equivocal.	Immunoassay	Diagnose Lyme disease by modified 2-tiered test
34194	Lyme Disease Antibody Index for CNS Infection	ELISA; nephelometry	Diagnose Lyme neuroborreliosis
29477	Lyme Disease Antibody (IgG), Immunoblot	Immunoblot	Diagnose Lyme disease when ELISA results are positive or equivocal
8593	Lyme Disease Antibodies (IgG, IgM), Immunoblot	Immunoblot
90558	Tick ID With Reflex to Lyme Disease DNA, Real-Time PCR, Tick^d	Microscopy; reflex to PCR	Identify tick and B burgdorferi to assess risk of tick-borne disease and assist with differential diagnosis

CSF, cerebrospinal fluid; ELISA, enzyme-linked immunosorbent assay; IFA, immunofluorescence assay; PCR, polymerase chain reaction.
a	Panel components may be ordered individually.
b	This test was developed and its analytical performance characteristics have been determined by Quest Diagnostics. It has not been cleared or approved by the US Food and Drug Administration. This assay has been validated pursuant to the CLIA regulations and is used for clinical purposes.
c	Please refer to the Quest Test Directory for your service area for test availability.
d	Reflex tests are performed at an additional charge and are associated with an additional CPT code(s).

Lyme disease: test selection and interpretation

Early localized Lyme disease

Early disseminated Lyme disease

Late-stage Lyme disease

Non-Lyme bacterial tick-borne diseases [return to contents]

Tick-borne rickettsial diseases

Table 5. Clinical Features of Tick-borne Rickettsial Diseases [return to contents]

Disease	Incubation period, days²	Signs and symptoms²	Rash²
Anaplasmosis	5-14	Fever, chills, rigors, severe headache, malaise, myalgia, gastrointestinal symptoms	Rare (<10%)
Human monocytic ehrlichiosis (HME)	5-14	Fever, chills, headache, malaise, muscle pain, gastrointestinal symptoms, altered mental status	More commonly reported in children
Human ewingii ehrlichiosis	5-14	Fever, chills, headache, malaise, muscle pain, gastrointestinal symptoms, altered mental status	Rare
Mediterranean spotted fever (boutonneuse fever)	5-7	Fever, headache, muscle pain	Eschar (usually single)
Rickettsia parkeri rickettsiosis	2-10	Fever, headache, muscle aches	Sparse maculopapular or papulovesicular eruptions on the trunk and extremities
Rocky Mountain spotted fever	3-12	Early signs/symptoms (1-4 days) include fever, headache, malaise, myalgia, edema around eyes and back of hands, nausea/vomiting Late signs/symptoms (5 days or later) include altered mental state, coma, cerebral edema, respiratory compromise, necrosis, multiorgan system damage	Early (2-5 days after symptom onset) maculopapular rash initially appearing on the wrists, forearms, and ankles Late (after day 6 of symptom onset) petechial rash that indicates progression to severe disease

Anaplasmosis

The ticks that carry A phagocytophilum can also harbor B burgdorferi, B miyamotoi, or B microti,and detection of coinfection is recommended as it may affect treatment choices.³¹

Ehrlichiosis

Mediterranean spotted fever

Rickettsia parkeri rickettsiosis

Rocky Mountain spotted fever

Hard tick relapsing fever

Tularemia

Table 6. Clinical Consequences of Tularemia [return to contents]

Manifestation (portal of entry)^2,40,41	Signs and symptoms²
Oculoglandular (eyes)	Photophobia, vision impairment/loss, conjunctivitis, regional lymphadenopathy
Oropharyngeal (ingestion)	Severe throat pain, exudative pharyngitis or tonsilitis, regional lymphadenopathy
Pneumonic (inhalation)	Non-productive cough, substernal tightness, pleuritic chest pain; hilar adenopathy, infiltrate, or pleural effusion may be present on chest X-ray; most serious form of tularemia
Typhoidal (any)	Combination of general symptoms without the localized symptoms of other tularemia syndromes; infiltrates may be seen in chest X-ray even in the absence of respiratory symptoms
Ulceroglandular (skin)	Localized lymphadenopathy, cutaneous ulcer with a black base at site of infection (not always present)

Non-Lyme bacterial tick-borne diseases: test availability

Laboratory tests that can help diagnose non-Lyme bacterial disease include culture, immunoassays and PCR-based assays (Table 7).

Table 7. Tests Available for Diagnosis and Management of Non-Lyme Bacterial Tick-Borne Diseases [return to contents]

Test code		Assay^a	Method		Clinical use
Spotted fever rickettsiosis
91121	Febrile Antibodies Panel^b,c Includes Brucella IgG and IgM with reflex to agglutination (test code 91068), Rickettsia (RMSF) IgG and IgM with reflex to titer, Rickettsia typhi IgG and IgM with reflex to titer, and Salmonellatotal antibody (Salmonella H types A, B, D; Salmonella O types D, Vi; test code 10582).			See individual tests		Differential diagnosis of RMSF or Rickettsia typhi as a cause of febrile disease vs other infectious causes
37507	Rickettsia Antibody Panel With Reflex to Titers^b Includes IgG and IgM to causative organisms of RMSF and typhus fever.			IFA		Differential diagnosis of rickettsial disease
15332	Rickettsia conorii Antibody Panel, IFA^c Includes IgG and IgM.					Diagnose Rickettsia conorii infection
37478	Rickettsial Disease Panel Includes Rickettsia (RMSF) IgG and IgM with reflex to titer; Rickettsia (typhus fever) IgG and IgM with reflex to titer; and Q fever (Coxiella burnetii) IgG and IgM phase I and phase II with reflex to titers.					Differential diagnosis of rickettsial disease
70191	Rickettsia Species DNA, Real-Time PCR^c			Real-time PCR		Diagnose RMSF
6419	Rickettsia (RMSF) Antibodies (IgG, IgM) With Reflex to Titers^b			IFA
37503	Rickettsia (Typhus Fever) Antibodies (IgG, IgM) With Reflex to Titers^b Includes Rickettsia (RMSF) IgG and IgM with reflex to titer and Rickettsia (typhus fever) IgG and IgM with reflex to titer.			IFA		Differential diagnosis of rickettsial disease (tick-borne vs other organisms)
Anaplasmosis
16212	Anaplasma phagocytophilum and E.chaffeensis Antibody Panel Reflex to Titers^b,c Includes IgG and IgM for both organisms with reflex to titers.			IFA		Diagnose anaplasmosis and ehrlichiosis
16189	Anaplasma phagocytophilum Antibodies (IgG, IgM) With Reflex to Titers^b,c			IFA		Diagnose anaplasmosis
17320	Anaplasma phagocytophilum DNA, Qualitative, Real-Time PCR^d			Real-time PCR
Ehrlichiosis
16197	Ehrlichia chaffeensis Antibodies(IgG, IgM) With Reflex to Titers^b,c			IFA		Diagnose ehrlichiosis
11353	Ehrlichia chaffeensis DNA, Real-Time PCR^d			Real-time PCR
70194(X)	Ehrlichia ewingii DNA, Real-Time PCR^d			Real-time PCR
Tularemia
11873	Culture, Select Agent^d			Culture		Screen for tularemia
12707	Francisella tularensis Antibody, Antibody, IgM and IgG, ELISA, Serum^d			ELISA		Diagnose tularemia
*Hard tick relapsing fever (Borrelia* miyamotoi disease)**
39684	Borrelia miyamotoi Antibodies (IgG, IgM), Immunoassay^d			Immunoassay		Diagnose B miyamatoi infection
93795	Borrelia miyamotoi DNA, Real-Time PCR, Miscellaneous^d			Real-time PCR		Confirm diagnosis of B miyamotoi infection
93794	Borrelia miyamotoi DNA, Real-Time PCR, Tickd					Detect B miyamotoi in tick to assess risk of human infection
39219	Borrelia Species DNA, Real-Time PCR, With Reflexes, Blood^b,c,d			Real-time PCR		Detect Borrelia spp DNA; diagnose Lyme disease or B miyamotoi disease
39218	Borrelia Species DNA, Real-Time PCR, With Reflexes, Synovial Fluid/CSF^b,c,d

ELISA, enzyme-linked immunosorbent assay; IFA, immunofluorescence assay; PCR, polymerase chain reaction; RMSF, Rocky Mountain spotted fever.
a	Panel components may be ordered individually.
b	Reflex tests are performed at an additional charge and are associated with an additional CPT code(s).
c	This test was developed and its analytical performance characteristics have been determined by Quest Diagnostics. It has not been cleared or approved by the US Food and Drug Administration. This assay has been validated pursuant to the CLIA regulations and is used for clinical purposes.
d	Please refer to the Quest Test Directory for your service area for test availability.

Non-Lyme bacterial tick-borne diseases: test selection and interpretation

Tick-borne rickettsial diseases

Table 8. Confirmatory Diagnostic Testing for Non-Lyme Bacterial Tick-borne Diseases [return to contents]

Disease	Confirmatory laboratory tests offered by Quest^a	Criteria for confirmation of diagnosis^a
Tick-borne rickettsial diseases^31,36,42
Anaplasmosis	Acute and convalescent serology (test codes 16212, 16189) or	4-fold increase in antibody titer^b,c
Anaplasmosis	A phagocytophilum DNA (test code 17320)	Detected
Human monocytic ehrlichiosis (HME)	Acute and convalescent serology (test code 16197, 16212) or	4-fold increase in antibody titer^b,c
Human monocytic ehrlichiosis (HME)	E chaffeensis DNA (11353)	Detected
Human ewingii ehrlichiosis	Acute and convalescent serology (test code 16197) or	4-fold increase in antibody titer^b,c
Human ewingii ehrlichiosis	E ewingii DNA (70194[X])	Detected
Mediterranean spotted fever (boutonneuse fever)	Acute and convalescent serology (test code 15332)	4-fold increase in antibody titer
Rickettsia parkeri rickettsiosis	Acute and convalescent serology (test codes 37507, 37478, 6419, 37503) or	4-fold increase in antibody titer^d
Rickettsia parkeri rickettsiosis	Rickettsia species DNA (test code 70191)	Detected
Rocky Mountain spotted fever (Rickettsia rickettsii)	Acute and convalescent serology (test codes 37507, 37478, 6419, 37503, 91121) or	4-fold increase in antibody titer^b,c
Rocky Mountain spotted fever (Rickettsia rickettsii)	R rickettsii DNA (test code 70191)	Detected
Non-rickettsial diseases
Hard tick relapsing fever²	Acute and convalescent serology (test code 39684)	Increase in antibody titer
	B miyamotoi DNA^e (test codes 93795, 93794, 39219, 39218, 15777, 15510)	Detected^e
	B hermsii DNA, B turicatae DNA^e (test codes 15777, 15510, 39218)	Detected^e
Tularemia	Serology (test code 12707)	Seroconversion from negative to positive IgM and/or IgG
Tularemia	Culture¹³ (test code 11873)	F tularensis detected in samples taken from ulcers, lymph node aspirates or biopsies, pharynx, pleural fluid (respiratory specimens)

a	Confirmation of the diagnosis is based on laboratory testing, but antibiotic therapy should not be delayed in a patient with suspected infection.²
b	Titers are often negative in the first 7 to 10 days of illness. Results from acute serology alone cannot be relied upon for confirmation of infection.²
c	IgM results alone should not be used for laboratory diagnosis.²
d	Results may not be specific to R parkeri; RMSF antibody tests often cross-react.²
e	Supportive of diagnosis.¹³

Hard tick relapsing fever

Tularemia

Parasitic and viral tick-borne diseases [return to contents]

Babesiosis

Colorado tick fever

Parasitic and viral tick-borne diseases: test availability

Laboratory tests that can help diagnose parasitic and viral tick-borne diseases include microscopy, immunoassay, and PCR-based assays (Table 9).

Table 9. Tests Available for Diagnosis and Management of Parasitic and Viral Tick-Borne Diseases [return to contents]

Test code	Assay^a	Method	Clinical use
Babesiosis
16194	Babesia microti Antibodies (IgG, IgM) With Reflex to Titers^b,c	IFA	Diagnose babesiosis
37314	Babesia microti DNA, Real-Time PCR^b	Real-time PCR
17231	Babesia duncani (WA1) Antibody (IgG), IFA^b	IFA
831	Malaria/Babesia/Other Blood Parasites	Microscopy
Colorado tick fever
34986	Colorado Tick Fever Antibodies (IgG, IgM)^b	IFA	Diagnose Colorado tick fever

IFA, immunofluorescence assay; PCR, polymerase chain reaction; RMSF, Rocky Mountain spotted fever
a	Panel components may be ordered individually.
b	This test was developed and its analytical performance characteristics have been determined by Quest Diagnostics. It has not been cleared or approved by the US Food and Drug Administration. This assay has been validated pursuant to the CLIA regulations and is used for clinical purposes.
c	Reflex tests are performed at an additional charge and are associated with an additional CPT code(s).

Parasitic and viral tick-borne diseases: test selection and interpretation

Babesiosis

Colorado tick fever

References [return to contents]

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Content reviewed 1/2026

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Test Code 90558

Tick ID with Reflex to Borrelia species DNA, Real-Time PCR, Tick

Identification of the Ixodes tick species will result in reflex to Real-Time PCR for detection of Borrelia species in the tick. The diagnosis of Borreliosis is most often made by clinical examination combined with evidence of a tick bite and/or exposure in endemic areas. Amplification of Borrelia genomic DNA from a tick can help support the diagnosis.

Test Code 16194

Babesia microti Antibodies (IgG, IgM) with Reflex to Titers

This test is for the detection of IgG and IgM antibodies against Babesia microti to aid in the diagnosis of Babesiosis. Babesiosis is a tickborne disease caused by transmission of the protozoa via the bite of an infected tick. B. microti is most common in the northern and upper Midwestern United States.

Testing for B. microti is based on a clinical evaluation and risk of tick exposure with consideration to the geographic region. Symptoms may be nonspecific, including headach

Test Code 93795

Borrelia miyamotoi DNA, Real-Time PCR, Miscellaneous

Persons infected with Borrelia miyamotoi most likely have fever, joint pains, fatigue, and headache, though unlike Lyme disease, rash is uncommon.
The diagnosis of Borrelia miyamotoi is most often made by history and clinical examination combined with exposure in endemic areas. Amplification of B. miyamotoi genomic DNA from blood, fluids or tissues confirms the diagnosis.

Test Code 39218

Borrelia Species DNA, Real-Time PCR, with Reflexes, Synovial Fluid/CSF

This test is intended for the qualitative detection of Borrelia DNA in CSF or synovial fluid. Borrelia are spirochetes and are commonly classified into two categories: those that cause Lyme disease (Lyme borreliosis) and those that cause relapsing fever. This test detects species in both categories.

Borrelia are typically transmitted to humans via the bite of an infected tick, including hard-bodied ticks of the genera Amblyomma and Ixodes and soft

Test Code 91121

Febrile Antibodies Panel

This panel comprises antibody testing for infections caused by Ricketssia rickettsii, Richetssia typhi, Salmonella, and Brucella in patients with fever. A 4-fold change in titers of antibodies between acute and convalescent sera confirms the infection. This panel provides targeted identification of antibodies, which supports differential diagnosis and can provide evidence of exposure.

R rickettsii causes Rocky Mountain spotted fever (RMSF), the

Test Code 11353

Ehrlichia chaffeensis DNA, Real-Time PCR

Ehrlichia chaffeensis DNA PCR is a highly sensitive method to detect the presence of ehrlichia chaffeensis DNA in clinical specimens.
The diagnosis of ehrlichia chaffeensis infection should not rely solely upon the result of PCR assay. A positive result should be considered in conjunction with clinical presentation and additional established clinical tests. Moreover, this assay cannot differentiate between viable and nonviable organisms. A negative PCR result in

Test Code 16212

Anaplasma phagocytophilum and E.chaffeensis Antibody Panel Reflex to Titers

This panel is for the detection of IgG and IgM antibodies against Anaplasma phagocytophilum and Ehrlichia chaffeensis. Anaplasmosis (human granulocytic anaplasmosis) and Ehrlichiosis (human monocytic ehrlichiosis) are tickborne diseases caused by transmission of the bacteria via the bite of an infected tick. Anaplasmosis is most common in the Northeastern and upper Midwestern United States. Ehrlichiosis is most common in the eastern, southeastern and south-central United States.

Test Code 831

Malaria/Babesia/Other Blood Parasites

The identification of malarial parasites, Babesia, and other blood parasites is used to determine treatment and prognosis. Calculating percent parasitemia is helpful in monitoring the therapeutic response. Microfilaria can be detected from a Giemsa stain, but this test in not recommended for microfilaria detection. One negative result cannot rule out infection.

Resources:
The CDC Malaria Hotline at 770-488-7788
Centers for Disease Control and Preventio

Test Code 6646

Lyme Disease Ab with Reflex to Blot (IgG, IgM)

Lyme disease is caused by a bacterium borrelia burgdorferi and is transmitted by ticks. A screening test with high sensitivity is used as the first step in the CDC recommended algorithm. Immunoblot testing qualitatively examines, with high specificity, antibodies in a patient's specimen. Immunoblot testing is appropriate for confirming a detected screening result.

Test Code 39733

Lyme Disease Antibody with Reflex to Immunoassay (IgG, IgM) (MTTT)

This test is for the qualitative detection of antibodies against Borrelia burgdorferi, the causative agent of Lyme disease, using the modified two-tier testing (MTTT) algorithm. Initial testing is performed using a Lyme total (IgG and IgM) antibody assay and if positive or equivocal, the sample is then tested using separate IgG and IgM immunoassays. This algorithm differs from the STTT algorithm in that the second-tier assays are chemiluminescent immunoassays, not immunoblots. MTTT may be

Test Code 15510

Borrelia species DNA, Qualitative Real-Time PCR, Tick

This test is intended for the qualitative detection of Borrelia DNA in ticks. Borrelia are spirochetes and are commonly classified into two categories: those that cause Lyme disease (Lyme borreliosis) and those that cause relapsing fever. This test detects species in both categories.

Borrelia are typically transmitted to humans via the bite of an infected tick, including hard-bodied ticks of the genera Amblyomma and Ixodes and soft-bodied ticks of the ge

Test Code 37478

Rickettsial Disease Panel

Rickettsiae are gram negative coccobacilli and short bacilli for which humans are incidental hosts except for human louse-borne typhus. Infections include Q Fever, Rocky Mountain Spotted Fever, and many types of typhus.

Test Code 34194

Lyme Disease Antibody Index for CNS Infection

The Lyme disease antibody index is used as an aid for diagnosing neuroborreliosis. The assay requires paired serum and CSF. A result set of lyme disease antibody index >1.2, control antibody index <1.0, and albumin ratio <0.0078 provides strong evidence of intrathecal synthesis of b. Burgdorferi antibodies and supports the diagnosis of neuroborreliosis.

Test Code 29477

Lyme Disease Antibody (IgG), Immunoblot

Lyme disease is caused by a tick vector carrying borrelia burgdorferi. Immunoblot testing qualitatively examines with high specificity antibodies in a patient's specimen. Immunoblot testing is appropriate for confirming a detected EIA or IFA test result.

Test Code 15777

Borrelia Species DNA, Qualitative Real-Time PCR, Miscellaneous

This test is intended for the qualitative detection of Borrelia DNA in whole blood, CSF, or synovial fluid. Borrelia are spirochetes and are commonly classified into two categories: those that cause Lyme disease (Lyme borreliosis) and those that cause relapsing fever. This test detects species in both categories.

Borrelia are typically transmitted to humans via the bite of an infected tick, including hard-bodied ticks of the genera Amblyomma and Ixode

Test Code 70191

Rickettsia Species DNA, Real-Time PCR

According to the CDC, Rocky Mountain Spotted Fever is the most severe and most frequently reported rickettsial illness in the United States. Infection is transmitted by ixodid (hard) ticks carried by dogs and other mammal species. Initial signs and symptoms of the disease include sudden onset of fever, headache, and muscle pain, followed by development of rash. The disease can be fatal without prompt treatment.

Test Code 37314

Babesia microti DNA, Real-Time PCR

This test is intended for the qualitative detection of Babesia microti DNA in whole blood or ticks. Babesia microti is a protozoan parasite that infects red blood cells and causes Babesiosis. Transmission to humans occurs primarily through the bite of an infected Ixodes scapularis or Ixodes pacificus tick, occasionally through transfusion of contaminated blood products, and rarely through organ transplantation or from an infected mother to her baby during pregnancy or

Test Code 16220

Tick-Borne Disease Antibodies Panel with Reflexes

This panel contains components for the detection of antibodies against Borrelia burgdorferi (Lyme disease) using the modified two-tier algorithm, Anaplasma phagocytophilum, Ehrlichia chaffeensis, and Babesia microti. Infection with these organisms can occur from the bite of a tick found in endemic regions, including the upper Northeast and Midwestern United States. Appropriate reflex testing of individual components is performed for initial screen results.

The

Test Code 70194

Ehrlichia ewingii DNA, Real-Time PCR

The Ehrlichia ewingii DNA PCR test is highly sensitive and specific, and can be used to confirm the diagnosis of human ehrlichiosis especially during the acute phase of the disease.

Test Code 16197

Ehrlichia chaffeensis Antibodies (IgG, IgM) with Reflex to Titers

This test is for the detection of IgG and IgM antibodies against Ehrlichia chaffeensis to aid in the diagnosis of Ehrlichiosis (human monocytic ehrlichiosis). Ehrlichiosis is a tickborne disease caused by transmission of the bacteria via the bite of an infected tick. It is most common in the eastern to southeastern and south-central United States.

Testing for E. chaffeensis is based on a clinical evaluation and risk of tick exposure with consideration to the geographic regio

Test Code 12707

Francisella tularensis Antibody, IgM and IgG, ELISA, Serum

Aiding in the diagnosis of tularemia caused by Francisella tularensis.

This test should not be used as a test of cure as it is not quantitative. Patients may remain seropositive for months to years following resolution of disease.

Test Code 8593

Lyme Disease Antibodies (IgG, IgM), Immunoblot

Lyme disease is transmitted by a tick vector carrying Borrelia burgdorferi. Immunoblot testing qualitatively examines, with high specificity, antibodies in a patient's specimen. Immunoblot testing is appropriate for confirming a detected EIA or IFA test result.

Test Code 37503

Rickettsia (Typhus Fever) Antibodies (IgG, IgM) with Reflex to Titers

Antigen specific IgG and IgM titers allow rapid diagnosis of infection by one or more of the typhus fever group of rickettsial agents. This group includes Rickettsia typhi (endemic or murine typhus) R. prowazeki (epidemic typhus), and Brill-Zinsser disease caused by reactivation of latent R. prowazeki.

Test Code 16189

Anaplasma phagocytophilum Antibodies (IgG, IgM) with Reflex to Titers

This test is for the detection of IgG and IgM antibodies against Anaplasma phagocytophilum to aid in the diagnosis of Anaplasmosis (human granulocytic anaplasmosis). Anaplasmosis is a tickborne disease caused by transmission of the bacteria via the bite of an infected tick. It is most common in the Northeastern and upper Midwestern United States during warmer months.

Testing for Anaplasmosis is based on a clinical evaluation and risk of tick exposure with consideration to the geog

Test Code 39219

Borrelia Species DNA, Real-Time PCR, with Reflexes, Blood

The diagnosis of Borreliosis is most often made by clinical examination combined with exposure in endemic areas. Amplification of Borrelia genomic DNA from blood can support the diagnosis. This test detects Borrelia species which are associated with either Lyme disease (Borrelia burgdorferi), or relapsing fever (Borrelia miyamotoi). A positive result for Borrelia species but negative result for Borrelia burgdorferi and Borrelia miyamotoi, may indi

Test Code 6419

Rickettsia (RMSF) Antibodies (IgG, IgM) with Reflex to Titers

Antigen specific IgG and IgM titers allow rapid diagnosis of infection by any of the spotted fever group of rickettsial agents. This group of agents include R. rickettsii (Rocky Mountain Spotted Fever) and R. akari (rickettsial pox), both seen in the continental United States.

Test Code 37507

Rickettsia Antibody Panel with Reflex to Titers

Antigen-specific IgG and IgM titers allow rapid diagnosis of infection by organisms within either of the two major groups of Rickettsia. The spotted fever group includes R. rickettsia (Rocky Mountain Spotted Fever) and R. akari (Rickettsial pox). The typhus group includes R. typhi (endemic/murine typhus) and R. prowazeki (epidemic typhus).

Test Code 93794

Borrelia miyamotoi DNA, Real-Time PCR, Tick

Detection of Borrelia miyamotoi DNA in black-legged ticks supports the potential for transmission of this organism to humans; human infection must be confirmed independently through patient testing.

Test Code 3946

Tick (and Other Arthropods) ID

Arthropods/insects may be vectors of disease and may cause infestations of skin, hair, and mucous membranes. Diagnosis of a disease or infestation may be achieved by recovery and identification of the intact arthropod/insect.

Test Code 39684

Borrelia miyamotoi Antibodies (IgG, IgM), Immunoassay

Borrelia miyamotoi is a tick-borne bacterial organism that causes a nonspecific febrile illness that may be misdiagnosed as Lyme disease or other tick-borne infections. Positive antibody results suggest B. miyamotoi infection; however, other tick-borne organisms may induce cross-reactive antibodies. Negative IgG and IgM results do not exclude the possibility of B. miyamotoi infection.

Test Code 32338

Tick-borne Disease, Acute Molecular Panel, Non-Lyme

Persons infected with Borrelia miyamotoi most likely have fever, joint pains, fatigue, and headache, though unlike Lyme disease, rash is uncommon.
The diagnosis of Borrelia miyamotoi is most often made by history and clinical examination combined with exposure in endemic areas. Amplification of B. miyamotoi genomic DNA from blood, fluids or tissues confirms the diagnosis.

Test Code 34986

Colorado Tick Fever Antibody Panel, IFA

Recent or current Colorado Tick Fever is indicated by a four-fold or greater rise in IgG titer between acute and convalescent sera and/or an IgM level of 1:20 or greater.

Test Code 17231

Babesia duncani (WA1) Antibody (IgG), IFA

⁠⁠⁠⁠⁠⁠⁠Babesia duncani, also known as WA1, causes symptoms similar to those seen in cases of babesiosis caused by Babesia microti. Most of the documented cases have occurred in the Pacific Northwest.

Test Code 39209

Borrelia burgdorferi DNA, Qualitative Real-Time PCR, Miscellaneous

The diagnosis of Lyme disease is most often made by history and clinical examination combined with exposure in endemic areas. Amplification of Borrelia genomic DNA from blood, fluids or tissues can support the diagnosis. A negative result does not rule out Borrelia infection and appropriate serology testing may be clinically warranted.

Test Code 94322

Tick-borne Disease, Acute Molecular Panel

Test Code 17320

Anaplasma phagocytophilum DNA, Qualitative Real-Time PCR

Human granulocytic ehrlichiosis (HGE) DNA PCR is a highly sensitive and specific method to detect the agent responsible for HGE, Ehrlichia equi and Ehrlichia phagocytophilia. This assay does not recognize sequences for the human ehrlichial pathogen Ehrlichia chaffeensis. The diagnosis of HGE infection should be considered in conjunction with clinical presentation and additional established clinical tests. A negative PCR result indicates the absence of HGE at detectable level

Test Code 11873

Culture, Select Agent

Pathogens recovered with this culture fit the categorical description of a Select Agent defined by the CDC and NIH. These pathogens include but are not limited to Bacillus anthracis, Brucella, Francisella tularensis, Yersinia pestis, Burkholderia mallei, Burkholderia pseudomallei. These select agents may cause anthrax, plague, mellioidosis and glanders, tularemia, and brucellosis. Each of these can cause septicemia, pneumonia, and tissue involvement.

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Tick-borne Disease: Laboratory Support of Diagnosis and Management

Tick-borne Disease: Laboratory Support of Diagnosis and Management

Topic Brief

Anaplasmosis

Topic Brief

Anaplasmosis

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