Lyme Disease Co-Infections: Types, Symptoms, Diagnosis, and Treatment
One tick can transmit more than one pathogen
Symptoms may overlap with or differ from Lyme disease
Diagnosis and treatment depend on the specific infection
Blacklegged ticks can carry more than one infectious organism. A person exposed to Lyme disease may therefore also be exposed to another tick-borne pathogen through the same tick bite or through separate bites.
These additional infections are commonly called Lyme disease co-infections. The most established pathogens transmitted by blacklegged ticks in the United States include Babesia microti, Anaplasma phagocytophilum, Borrelia miyamotoi, and Powassan virus.
The presence of multiple organisms in a tick does not prove that every organism was transmitted. Likewise, overlapping symptoms do not establish a co-infection. Exposure history, geographic location, physical findings, laboratory abnormalities, and appropriately timed testing must be considered together.
What Are Lyme Disease Co-Infections?
A co-infection occurs when a patient has Lyme disease and another infection at the same time. A single blacklegged tick can potentially carry more than one pathogen, although the frequency varies considerably by tick species, geographic area, life stage, and study population.
In a Suffolk County, New York study, Tokarz and colleagues detected Borrelia burgdorferi, Babesia microti, Anaplasma phagocytophilum, Borrelia miyamotoi, and Powassan virus in collected blacklegged ticks. Coinfections were found in 11% of nymphal ticks and 45% of adult ticks collected at the study sites. These findings describe the sampled ticks and should not be interpreted as the risk from every tick bite.1
A separate review by Sanchez-Vicente and colleagues found substantial geographic variation in the prevalence and combinations of pathogens detected in ticks.2
Common Lyme Disease Co-Infections and Their Symptoms
Symptoms often overlap, but certain clinical findings may raise suspicion for a specific co-infection.
| Infection | Common symptoms and findings | Important diagnostic clues |
|---|---|---|
| Babesia microti | Fever, chills, sweats, fatigue, headache, body aches, nausea, or shortness of breath | Hemolytic anemia, low platelets, elevated bilirubin, or parasites detected by blood smear or PCR |
| Anaplasma phagocytophilum | Acute fever, headache, chills, malaise, and muscle aches | Low white blood cells, low platelets, elevated liver enzymes, or positive PCR early in illness |
| Borrelia miyamotoi | Fever, chills, severe headache, fatigue, muscle aches, and joint pain | Often no erythema migrans rash; specialized PCR or antibody testing may be needed |
| Powassan virus | Fever, headache, vomiting, weakness, confusion, seizures, or other neurologic symptoms | Encephalitis or meningitis; testing generally requires public-health or specialized laboratories |
This chart is not diagnostic. Patients with uncomplicated Lyme disease can have fever, fatigue, headache, and muscle aches, while some patients with a co-infection may have mild or initially nonspecific symptoms.
When Should a Co-Infection Be Considered?
A co-infection may warrant consideration when a patient with suspected or confirmed Lyme disease has:
- Unusually high or persistent fever
- Prominent chills or drenching sweats
- Shortness of breath
- Evidence of anemia or hemolysis
- Low platelets or low white blood cells
- Elevated liver enzymes
- Severe headache or new neurologic findings
- Symptoms that are not adequately explained by Lyme disease alone
- An incomplete response when the identified co-infection would not be treated by the medication prescribed for Lyme disease
These findings can also occur with other infections and medical conditions. Persistent symptoms alone do not prove that a co-infection is present.
Babesia and Lyme Disease
Babesia is a parasite that infects red blood cells. In the northeastern and upper midwestern United States, most reported cases are caused by Babesia microti. Other species, including Babesia duncani, have been reported in the United States.
Babesiosis is usually acquired through an infected tick bite, but it can also be transmitted through contaminated blood products. Rare cases of congenital transmission have been reported.3,4
Symptoms may include irregular fever, chills, sweats, profound fatigue, headache, nausea, body aches, and shortness of breath. Some infections are asymptomatic, while severe cases can produce hemolytic anemia, low platelets, kidney injury, respiratory complications, or other organ dysfunction.
Older clinical research found that patients with concurrent Lyme disease and babesiosis experienced more symptoms and a longer duration of illness than patients with either infection alone.5 In that study, 50% of coinfected patients remained symptomatic for at least three months, compared with 4% of patients with Lyme disease alone. These historical findings should not be applied to every patient, but they illustrate how babesiosis can alter the clinical presentation.
Patients can learn more in the Babesia guide.
Testing for Babesia
Testing may include examination of a peripheral blood smear, PCR testing for Babesia DNA, and antibody testing. A single test may not identify every case, particularly when the level of parasites in the blood is low or testing occurs at an unfavorable time.
Blood counts, bilirubin, lactate dehydrogenase, haptoglobin, and liver tests can provide additional evidence of hemolysis or systemic illness. Test results must be interpreted in the context of symptoms, exposure risk, and treatment history.
Treatment of Babesiosis
Babesiosis requires different treatment from Lyme disease because Babesia is a parasite rather than a bacterium. Common regimens include atovaquone combined with azithromycin. Clindamycin combined with quinine may be used in selected situations. Severe babesiosis may require hospitalization, intravenous treatment, or exchange transfusion.
Management depends on illness severity, immune status, age, pregnancy, spleen function, laboratory findings, and the infecting species. Treatment should be individualized by a clinician familiar with tick-borne infections.
Anaplasmosis and Lyme Disease
Anaplasmosis is caused by Anaplasma phagocytophilum. It is transmitted by the blacklegged tick in the eastern United States and the western blacklegged tick along the Pacific Coast. These ticks can also transmit Lyme disease, making concurrent exposure possible.
Symptoms typically begin with fever, severe headache, chills, malaise, and muscle aches. Laboratory findings may include low white blood cells, low platelets, and elevated liver enzymes.
Most cases are mild or moderate, but severe illness can occur, particularly when diagnosis and treatment are delayed or a patient is older or immunocompromised.
Testing and Treatment for Anaplasmosis
PCR performed on whole blood is most useful during the first week of illness. Antibody testing may be negative early, and paired acute and convalescent samples may be needed to demonstrate a change in antibody levels.
Treatment should not be delayed when anaplasmosis is strongly suspected. Doxycycline is the recommended first-line treatment for adults and children of all ages.6
Hard Tick Relapsing Fever Caused by Borrelia miyamotoi
Borrelia miyamotoi is a spiral-shaped bacterium transmitted by the same blacklegged ticks that transmit Lyme disease. It causes hard tick relapsing fever and should not be confused with Lyme disease caused by Borrelia burgdorferi.
Patients commonly report fever, chills, headache, fatigue, muscle aches, and joint pain. Despite its name, a clearly relapsing fever pattern is not present in every documented case. Unlike early Lyme disease, an erythema migrans rash is usually absent.
Severe complications, including meningoencephalitis, have been reported, particularly in immunocompromised patients.
Testing and Treatment for Borrelia miyamotoi
Standard Lyme disease antibody tests are not designed to diagnose Borrelia miyamotoi infection. Diagnosis may involve PCR testing during acute illness or antibody testing directed against specific B. miyamotoi proteins. Blood smears have poor sensitivity and should not be relied upon to exclude the infection.7
There are no large randomized trials defining the optimal treatment regimen. Published case series describe successful treatment with antibiotics also used for Lyme disease. Current CDC guidance states that a two-week course of doxycycline or amoxicillin has been effective for most patients, while severe neurologic illness may require intravenous treatment such as ceftriaxone.8
Powassan Virus and Lyme Disease
Powassan virus is a rare but potentially serious infection transmitted by several tick species. The deer tick virus subtype can be transmitted by blacklegged ticks in areas where Lyme disease also occurs.
Many infections may be asymptomatic. Symptomatic patients can develop fever, headache, vomiting, weakness, confusion, loss of coordination, seizures, meningitis, or encephalitis.
There is no specific antiviral treatment for Powassan virus disease. Patients with severe neurologic symptoms may require hospitalization and supportive care. Antibiotics prescribed for Lyme disease do not treat viral infections.
Other Tick-Borne Illnesses in the Differential Diagnosis
Not every infection associated with ticks should be classified as a Lyme disease co-infection transmitted by the same tick. Geography, tick species, animal exposure, and the strength of evidence for transmission matter.
Ehrlichiosis
Ehrlichiosis is most commonly caused by Ehrlichia chaffeensis or Ehrlichia ewingii. In the United States, these organisms are primarily transmitted by the lone star tick rather than the blacklegged tick.
Symptoms may include fever, headache, muscle aches, fatigue, nausea, vomiting, diarrhea, or rash. Low white blood cells, low platelets, and elevated liver enzymes may provide additional clues.
Doxycycline is the recommended first-line treatment for suspected ehrlichiosis in adults and children of all ages. Treatment should begin promptly when the illness is strongly suspected rather than waiting for confirmatory results.9
Bartonella
Bartonella henselae is best known for causing cat-scratch disease after exposure to an infected cat or cat flea. Other Bartonella species can cause different human illnesses.
Bartonella DNA has been detected in some ticks, but detecting an organism in a tick does not establish that the tick can transmit it to a person. Human transmission of Bartonella through tick bites has not been established, and this uncertainty should be discussed clearly.10
Symptoms and treatment depend on the particular Bartonella species and clinical syndrome. A diagnosis should not be made from nonspecific symptoms alone.
Southern Tick-Associated Rash Illness
Southern tick-associated rash illness, or STARI, is associated with bites from the lone star tick. It can cause an expanding rash resembling the erythema migrans rash of early Lyme disease, accompanied by fatigue, headache, fever, and muscle pain.
The cause of STARI has not been established. STARI is better regarded as a separate tick-associated illness that can resemble Lyme disease rather than as a proven Lyme disease co-infection.
Why Co-Infections Can Be Difficult to Diagnose
Lyme disease and other tick-borne infections share many nonspecific symptoms, including fever, fatigue, headache, muscle aches, and joint pain. A patient may not remember a tick bite, and different tests perform best at different stages of illness.
Testing must be selected for the suspected organism. A Lyme disease antibody test does not diagnose babesiosis, anaplasmosis, hard tick relapsing fever, ehrlichiosis, or Powassan virus disease.
Likewise, a negative early test may not always exclude an infection. Clinicians must consider the timing of testing, previous treatment, immune response, laboratory abnormalities, and the limitations of the particular assay. More information is available in the Lyme disease testing guide.
Why Correct Identification Matters for Treatment
Treatment effective for one tick-borne infection may not treat another:
- Lyme disease is treated with antibacterial medications.
- Babesiosis requires antiparasitic combination treatment.
- Anaplasmosis and ehrlichiosis are treated first-line with doxycycline.
- Hard tick relapsing fever is treated with antibiotics, although the evidence base remains limited.
- Powassan virus disease does not respond to antibiotics and is managed with supportive care.
This is why persistent fever, sweats, blood-count abnormalities, elevated liver enzymes, hemolysis, respiratory symptoms, or neurologic deterioration should prompt a broader evaluation rather than an automatic assumption that every symptom is caused by Lyme disease.
Frequently Asked Questions
What are the most common co-infections with Lyme disease?
The most established infections transmitted by blacklegged ticks in Lyme-endemic areas include babesiosis, anaplasmosis, hard tick relapsing fever caused by Borrelia miyamotoi, and Powassan virus disease. Their prevalence varies by geographic region.
What symptoms suggest a Lyme disease co-infection?
High or persistent fever, chills, sweats, shortness of breath, anemia, low platelets, low white blood cells, elevated liver enzymes, hemolysis, or severe neurologic symptoms may raise concern. None of these findings proves a co-infection without further evaluation.
Can one tick transmit more than one infection?
Yes. Blacklegged ticks can carry more than one pathogen, and simultaneous transmission is possible. However, finding multiple organisms in a tick does not prove that each organism was transmitted during a particular bite.
Does doxycycline treat every Lyme disease co-infection?
No. Doxycycline treats Lyme disease, anaplasmosis, ehrlichiosis, and some cases of hard tick relapsing fever. It does not adequately treat babesiosis and has no effect on Powassan virus.
How are Lyme disease co-infections diagnosed?
Diagnosis may involve exposure history, symptoms, examination findings, blood counts, liver tests, blood smears, PCR, antibody testing, and specialized testing. The appropriate test and its timing depend on the suspected infection.
Can persistent symptoms after Lyme treatment prove a co-infection?
No. Persistent symptoms can have multiple explanations. A co-infection should be evaluated using the clinical presentation, exposure history, objective findings, and testing appropriate for the suspected pathogen.
Clinical Takeaway
A person exposed to Lyme disease may also be exposed to another tick-borne pathogen. Babesiosis, anaplasmosis, hard tick relapsing fever, and Powassan virus disease can overlap with Lyme disease but may require different diagnostic tests and treatments.
Clinicians should consider a broader tick-borne evaluation when symptoms are unusually severe, include persistent fever or sweats, produce characteristic laboratory abnormalities, or are not adequately explained by Lyme disease alone.
Recognizing the specific infection matters because a treatment effective for Lyme disease may not treat a parasitic or viral co-infection.
Related Articles
Persistent Lyme disease overview
Recovery from Lyme disease
Autonomic dysfunction and Lyme disease
Pediatric Lyme disease
References
- Tokarz R, Tagliafierro T, Sameroff S, et al. Detection of Anaplasma phagocytophilum, Babesia microti, Borrelia burgdorferi, Borrelia miyamotoi, and Powassan virus in ticks by a multiplex real-time reverse transcription-PCR assay. mSphere. 2017;2(2):e00151-17.
- Sanchez-Vicente S, Tagliafierro T, Coleman JL, Benach JL, Tokarz R. Polymicrobial nature of tick-borne diseases. mBio. 2019;10(5):e02055-19.
- Mohan KVK, Leiby DA. Emerging tick-borne diseases and blood safety: Summary of a public workshop. Transfusion. 2020;60(7):1624-1632.
- Saetre K, Godhwani N, Maria M, et al. Congenital babesiosis after maternal infection with Borrelia burgdorferi and Babesia microti. Journal of the Pediatric Infectious Diseases Society. 2018;7(1):e1-e5.
- Krause PJ, Telford SR III, Spielman A, et al. Concurrent Lyme disease and babesiosis: Evidence for increased severity and duration of illness. JAMA. 1996;275(21):1657-1660.
- Centers for Disease Control and Prevention. Clinical care of anaplasmosis. CDC. 2024.
- Telford SR III, Goethert HK, Molloy PJ, Berardi V. Blood smears have poor sensitivity for confirming Borrelia miyamotoi disease. Journal of Clinical Microbiology. 2019;57(3):e01468-18.
- Centers for Disease Control and Prevention. Clinical guidance for hard tick relapsing fever. CDC. 2026.
- Centers for Disease Control and Prevention. Clinical care of ehrlichiosis. CDC. 2024.
- Telford SR III, Wormser GP. Bartonella species transmission by ticks not established. Emerging Infectious Diseases. 2010;16(3):379-384.
This article is for educational purposes and is not a substitute for individualized medical evaluation, diagnosis, or treatment.
Dr. Daniel Cameron, MD, MPH
Lyme disease clinician with over 30 years of experience and past president of ILADS.
Symptoms • Testing • Coinfections • Recovery • Pediatric • Prevention
Thank you! My daughter just tested positive for Babesia Duncani and Bartonella Bacilliformis. I am thankful to find your blog! There is one Lyme specialist in our state and I understand he sometimes has a 6-month waiting list. So the info you share is very helpful to us!
What are the tests for lymes disease co- infections? How does one find a doctor that specializes in lymes disease? I’m in Arizona, and was diagnosed 20 years ago.