Lyme Disease Co-Infections: Babesia, Bartonella, Ehrlichia, and More

Babesia and Bartonella coinfections are treated with different drugs from Lyme disease itself, because the doxycycline or amoxicillin used for Lyme does not treat Babesia at all. Babesia, a malaria-like parasite, is treated for at least 7 to 10 days with atovaquone plus azithromycin (clindamycin plus quinine is the alternative), according to the 2020 IDSA babesiosis guideline, while Bartonella has no standard regimen in the tick-borne setting and clinicians usually combine a macrolide such as azithromycin or clarithromycin with rifampin for weeks to months.

If you have been treated for Lyme disease and you are not getting better, there is a good chance the problem is not just Borrelia. Ticks are dirty needles of the animal world. A single tick can carry multiple pathogens, and a single bite can transmit several of them simultaneously. These additional infections, called co-infections, require their own specific treatments. Miss them, and Lyme treatment alone will not get you well.

The main co-infections are Babesia, Bartonella, Ehrlichia, Anaplasma and Mycoplasma, with Borrelia miyamotoi and Powassan virus as rarer tick-borne companions. Each has its own symptom pattern, tests and drugs. For the underlying infection, see the overview of Lyme disease as a condition.

Why Co-Infections Matter So Much

Co-infections are not a footnote to Lyme disease. They fundamentally change the clinical picture. Research from Columbia University found that patients with Lyme plus co-infections had significantly more severe and prolonged symptoms than those with Lyme alone. The interactions between these organisms create a synergistic effect: each pathogen suppresses the immune system in its own way, making it harder for your body to fight any of them.

The standard Lyme treatment of doxycycline or amoxicillin will do nothing against Babesia (a parasite, not a bacterium) and may be insufficient for Bartonella. If your doctor treats only the Borrelia and ignores co-infections, you are likely to plateau or relapse once antibiotics stop.

Babesia: The Malaria-Like Parasite

Babesia is not a bacterium. It is a protozoan parasite, closely related to the organism that causes malaria. It invades and destroys red blood cells, which explains many of its distinctive symptoms. The most common species in the United States are Babesia microti (Northeast and upper Midwest) and Babesia duncani (West Coast).

Babesia Symptoms

Babesia has a symptom profile that differs from Lyme in characteristic ways:

• Drenching night sweats. This is the hallmark symptom. Patients describe waking up with sheets soaked through, needing to change clothes in the middle of the night.
• Air hunger. A feeling of not being able to get a full breath, sometimes described as a sigh that never satisfies. This is one of the most specific Babesia symptoms.
• Cyclical fevers and chills. Temperature fluctuations that can be dramatic, sometimes spiking and dropping within hours.
• Severe fatigue. Often more profound than Lyme fatigue alone, sometimes described as a bone-deep exhaustion.
• Headaches. Typically global (whole-head) rather than the neck-based headaches more common in Lyme.
• Hemolytic anemia. In severe cases, destruction of red blood cells causes anemia, dark urine, and jaundice.

Babesia Testing

Standard testing for Babesia includes antibody testing (IgM and IgG for B. microti) and blood smear examination (looking for parasites inside red blood cells under a microscope). PCR testing can detect Babesia DNA and is more sensitive than a smear when parasite levels are low. FISH (fluorescent in-situ hybridization) testing, offered by some specialty labs, is another option that some clinicians use.

A significant problem: most standard labs only test for B. microti. If you are infected with B. duncani or another species, the test may come back negative. Specialty labs that test for multiple Babesia species are often necessary.

Babesia Treatment

Because Babesia is a parasite, standard Lyme antibiotics are ineffective. The typical treatment combinations include:

• Atovaquone (Mepron) plus azithromycin: The most common first-line combination. Atovaquone is the yellow paint-like liquid that targets the parasite directly.
• Clindamycin plus quinine: Works about as well but causes more side effects. Often reserved for pregnancy, intolerance, or when atovaquone fails.
• Artemisinin: An herbal antimalarial derived from sweet wormwood. Used as an adjunct in many integrative protocols. Pulse dosing (taking it for a period, then cycling off) is typically recommended because Babesia can develop resistance.
• Cryptolepis: An herbal option with in vitro activity against Babesia that some practitioners use as part of combination protocols.

Treatment duration is where guidelines and Lyme-literate practice differ most. The CDC and the IDSA 2020 babesiosis guideline (Krause and colleagues) recommend at least 7 to 10 days of atovaquone plus azithromycin for ill patients with a normal immune system, while many Lyme-literate clinicians treat for weeks to months, particularly in immunocompromised patients or those with chronic infection.

What the IDSA 2020 guideline says about Babesia treatment

• Preferred regimen: atovaquone plus azithromycin, for both mild and severe illness. Clindamycin plus quinine is the alternative, and it causes more side effects such as ringing in the ears and stomach upset.
• Pregnancy: clindamycin plus quinine is generally preferred because there is more safety data for that combination in pregnancy, according to the CDC clinical care guidance for babesiosis.
• Immunocompromised patients: treatment for at least 6 consecutive weeks, continuing until no parasites are seen on blood smears for 2 consecutive weeks.
• Severe disease: red blood cell exchange transfusion is used for high-grade parasitemia (above 10%) or for severe hemolysis with organ involvement.
• Relapse: resistance to atovaquone plus azithromycin has emerged in some immunocompromised patients, as described by Wormser and colleagues in Clinical Infectious Diseases (2010).

Fatigue and a positive PCR can persist for several weeks after a standard course, and the CDC notes that relapse is unusual in people with a healthy immune system. Herbal options such as artemisinin and cryptolepis have not been tested in human trials for babesiosis, so they sit outside the guideline and are usually used alongside prescription drugs rather than instead of them.

Bartonella: The Stealth Infection

Bartonella is arguably the most underdiagnosed of all tick-borne co-infections. There are over 30 known Bartonella species, and at least a dozen infect humans. Bartonella henselae, the cause of cat scratch disease, gets the most attention. Bartonella quintana, the cause of trench fever, spreads through human body lice.

Whether ticks pass Bartonella to people is unsettled. According to the CDC page on Bartonella, the bacteria reach people through fleas, body lice, sand flies and scratches from flea-infested cats, and there is no evidence yet of spread through tick bites. Many Lyme-literate physicians still test for and treat Bartonella in people with tick-borne illness, and cats and fleas are a well documented route of exposure worth mentioning to your clinician.

Bartonella Symptoms

Bartonella has a distinctive set of symptoms that, once you know them, can be surprisingly recognizable:

• Shin and sole-of-foot pain. Pain in the shins, especially upon waking, is considered quite specific to Bartonella. Pain in the soles of the feet (plantar fascia area) is another clue.
• Ice-pick headaches. Sharp, stabbing headaches that feel like something is being driven into the skull. They often last seconds but recur frequently.
• Stretch-mark-like rashes (striae). Red or purple streaks on the skin that resemble stretch marks but appear in unusual locations (back, chest, arms) and in people who have not had rapid weight changes.
• Psychiatric symptoms. Bartonella has a particular affinity for the central nervous system. Anxiety, rage, irritability, depression, and in some cases psychotic symptoms can be driven by Bartonella infection.
• Swollen lymph nodes. Particularly in the neck and axillary (armpit) regions.
• Eye problems. Blurred vision, floaters, and light sensitivity. Bartonella can cause neuroretinitis, which an ophthalmologist may identify.
• Subcutaneous nodules. Small, tender lumps under the skin.

Bartonella Testing

Testing for Bartonella is notoriously unreliable. Standard antibody tests detect only B. henselae and sometimes B. quintana, missing many other species. Enrichment culture combined with PCR, offered by a few specialty labs, is more sensitive than antibody testing alone, but even it can miss the infection.

Many Lyme-literate physicians diagnose Bartonella clinically based on the symptom pattern, particularly when the characteristic triad of shin pain, ice-pick headaches, and psychiatric symptoms is present.

Bartonella Treatment

Bartonella is one of the more stubborn co-infections to eradicate. Treatment often requires months of therapy:

• Azithromycin or clarithromycin: Often used in combination with another agent.
• Rifampin: Frequently combined with a macrolide antibiotic. Rifampin penetrates intracellular spaces where Bartonella hides.
• Fluoroquinolones (levofloxacin): Sometimes used for resistant cases, though these carry side effect risks that need careful consideration.
• Methylene blue: An emerging option that some practitioners report effectiveness with, particularly for neuropsychiatric Bartonella symptoms. The support so far comes from laboratory studies and clinician reports rather than controlled human trials, and the methylene blue treatment guide explains how clinicians use it.
• Herbal approaches: Japanese knotweed, houttuynia, and cryptolepis are used in herbal protocols like the Buhner protocol for Bartonella.

No guideline sets a regimen for Bartonella in people with Lyme disease. The most cited review, Rolain and colleagues in Antimicrobial Agents and Chemotherapy (2004), matches drug choice to the illness: azithromycin for cat scratch lymph node disease, and combinations built on doxycycline, rifampin or gentamicin for eye, heart valve and other deep infections. Lyme-literate physicians adapt those combinations, so regimens and durations vary from one clinician to the next.

Ehrlichia and Anaplasma

These are closely related intracellular bacteria that infect white blood cells. Ehrlichia chaffeensis causes human monocytic ehrlichiosis (HME), while Anaplasma phagocytophilum causes human granulocytic anaplasmosis (HGA). Anaplasma is carried by the same blacklegged ticks that carry Lyme, while Ehrlichia chaffeensis is spread mainly by the lone star tick (Amblyomma americanum) in the South and East; a related species, Ehrlichia muris eauclairensis, is carried by blacklegged ticks in the upper Midwest.

Symptoms

Ehrlichia and Anaplasma infections tend to present more acutely than Lyme:

• High fever (often 102 F or higher)
• Severe headache
• Muscle pain (myalgia)
• Low white blood cell count (leukopenia), a distinctive lab finding
• Low platelet count (thrombocytopenia)
• Elevated liver enzymes

Treatment

The good news is that doxycycline, the same antibiotic used for early Lyme, is highly effective against both Ehrlichia and Anaplasma. Most patients respond rapidly, often within 24 to 48 hours. This is one reason many Lyme-literate physicians prefer doxycycline as a first-line Lyme treatment: it covers these co-infections simultaneously.

The CDC clinical guidance on anaplasmosis recommends doxycycline for patients of all ages, including children, and advises 10 to 14 days when Lyme co-infection is possible so the course also covers Borrelia. Rifampin is an alternative in pregnancy or doxycycline allergy, but it does not treat Lyme disease. The full recommendations are in the CDC rickettsial disease report by Biggs and colleagues in MMWR (2016). A lack of response to doxycycline suggests the illness is something other than ehrlichiosis or anaplasmosis.

Mycoplasma

Mycoplasma species, particularly Mycoplasma fermentans and Mycoplasma pneumoniae, are found in a significant percentage of chronic Lyme patients. Whether Mycoplasma is truly tick-transmitted or is an opportunistic infection that takes hold when the immune system is suppressed by Lyme is debated. Regardless, its presence complicates recovery.

Symptoms

Mycoplasma symptoms overlap heavily with Lyme, making clinical distinction difficult:

• Fatigue (often severe)
• Joint and muscle pain
• Cognitive dysfunction
• Respiratory symptoms (cough, shortness of breath)
• Skin rashes

Treatment

Mycoplasma lacks a cell wall, which means antibiotics that target cell wall synthesis (like amoxicillin and cephalosporins) are useless against it. Effective options include doxycycline, azithromycin, clarithromycin, and fluoroquinolones. Treatment courses are typically 3 to 6 months for chronic Mycoplasma infection.

Evidence for long courses comes mainly from clinician experience rather than randomized trials, and mainstream infectious disease guidelines do not list Mycoplasma among tick-borne co-infections.

Other Tick-Borne Infections That Travel With Lyme

Borrelia miyamotoi is a relapsing fever bacterium carried by the same blacklegged ticks as Lyme. It causes fever, chills, headache and muscle aches, usually without the bull's-eye rash, and it is treated with the same antibiotics as Lyme disease, most often doxycycline. Standard Lyme antibody tests are not designed to detect it, so PCR testing of blood is the usual way to confirm it.

Powassan virus is a rare tick-borne virus that can cause encephalitis and meningitis. No antiviral drug treats it, so care is supportive, sometimes in hospital. A sudden fever with confusion, weakness or a seizure after a tick bite needs urgent medical care rather than a co-infection protocol.

Co-Infection Comparison Table

Co-Infection	Organism Type	Key Distinguishing Symptoms	Primary Treatment
Babesia	Parasite (protozoan)	Night sweats, air hunger, cyclical fevers	Atovaquone + azithromycin
Bartonella	Bacterium (intracellular)	Shin pain, ice-pick headaches, striae, psychiatric symptoms	Azithromycin + rifampin
Ehrlichia	Bacterium (intracellular)	High fever, low WBC, low platelets	Doxycycline
Anaplasma	Bacterium (intracellular)	High fever, low WBC, low platelets	Doxycycline
Mycoplasma	Bacterium (no cell wall)	Fatigue, respiratory symptoms, overlapping Lyme symptoms	Doxycycline or azithromycin

Testing for Co-Infections: A Practical Approach

Given the limitations of co-infection testing, here is a pragmatic approach:

1. Test broadly at diagnosis. When Lyme is suspected or confirmed, order co-infection panels at the same time. Do not wait for Lyme treatment to fail before looking for co-infections.
2. Use specialty labs when indicated. Standard lab panels miss many co-infections. Specialty tick-borne disease labs offer broader panels covering more species, though their results are not always validated to the same standard as hospital labs, so interpret them with a clinician who knows their limits. The Lyme disease testing guide compares the main test types.
3. Pay attention to symptoms. Night sweats suggest Babesia. Shin pain and psychiatric symptoms suggest Bartonella. Low blood counts suggest Ehrlichia/Anaplasma. Symptoms are often more reliable than tests.
4. Check a CBC. A complete blood count is inexpensive and widely available. Low white blood cells and low platelets are red flags for Ehrlichia/Anaplasma. Low red blood cells (anemia) can point to Babesia.
5. Consider empirical treatment. When clinical suspicion is high but tests are negative, many Lyme-literate physicians will treat based on the symptom pattern. If the patient improves on co-infection treatment, that response itself is diagnostic.

How Are Babesia and Bartonella Co-Infections Treated?

Babesia and Bartonella co-infections are treated with separate drug combinations, because Babesia is a parasite and Bartonella is a bacterium that hides inside cells. Babesia is treated with atovaquone plus azithromycin for at least 7 to 10 days under the IDSA 2020 guideline, while Bartonella is usually treated with azithromycin or clarithromycin plus rifampin, often for one to several months. When both are present, many clinicians treat Babesia first and add Bartonella treatment once night sweats and air hunger settle.

Attribute	Babesia	Bartonella
Organism	Protozoan parasite in red blood cells	Intracellular bacterium
Main US species	B. microti (Northeast, upper Midwest), B. duncani (West Coast)	B. henselae, B. quintana
Preferred drugs	Atovaquone plus azithromycin	Azithromycin or clarithromycin plus rifampin
Alternatives	Clindamycin plus quinine	Doxycycline plus rifampin, levofloxacin, gentamicin for deep infection
Standard duration	At least 7 to 10 days; at least 6 weeks if immunocompromised	No standard for the Lyme setting; weeks to months in practice
Guideline basis	IDSA 2020 babesiosis guideline, CDC	Rolain and colleagues (2004) review; no Lyme co-infection guideline
Integrative adjuncts	Artemisinin, cryptolepis	Japanese knotweed, houttuynia, methylene blue

Why Babesia usually comes first

Babesia drives fevers, sweats and anemia, and those symptoms make it hard to judge whether anything else is working. Bartonella treatment often triggers Herxheimer reactions, a temporary flare of symptoms as bacteria die off, which patients tolerate better once Babesia is under control.

Can Babesia and Bartonella be treated at the same time?

Azithromycin appears in both regimens, which is why some clinicians overlap the two: atovaquone plus azithromycin for Babesia, with rifampin added later for Bartonella. Rifampin interacts with many drugs and can lower atovaquone blood levels, so combined plans need a prescriber who checks interactions, liver tests and blood counts during treatment. Neither combination has been tested in trials of people with both infections, so these plans rest on clinical judgment.

Treatment Sequencing: Which Infection to Address First

When multiple infections are present, the order of treatment matters. Most experienced practitioners follow this general framework:

1. Babesia first (or concurrently with Lyme). Babesia suppresses the immune system in ways that make it harder to clear Borrelia. Treating Babesia early often improves the patient’s ability to respond to Lyme treatment.
2. Lyme (Borrelia) next. Once Babesia is under control (or if it is not present), focus on the primary Lyme infection.
3. Bartonella last. Bartonella treatment can cause significant Herxheimer reactions. Patients tolerate this better when they are not simultaneously fighting Babesia and acute Borrelia infection.

This is a general guideline, not a rigid rule. Treatment plans should be individualized based on which infection is causing the most symptoms and the patient’s overall clinical status.

When to Suspect Co-Infections

Consider co-infections in any of these scenarios:

• You have been treated for Lyme but are not improving as expected
• Your symptoms do not fit the typical Lyme pattern (especially psychiatric symptoms, air hunger, or night sweats)
• You relapse quickly after completing Lyme treatment
• Your illness began with a tick bite in an area where co-infections are endemic
• Standard Lyme testing is negative but your clinical picture strongly suggests a tick-borne illness

The takeaway is straightforward: if you are dealing with Lyme disease, do not assume Lyme is all you are dealing with. A thorough evaluation for co-infections can make the difference between a treatment plan that works and one that falls short.

Who Treats Lyme Co-Infections?

Lyme co-infections are treated by infectious disease specialists, primary care physicians, and Lyme-literate physicians (often called LLMDs), many of whom follow the treatment approach of the International Lyme and Associated Diseases Society (ILADS). Infectious disease specialists tend to follow the IDSA guidelines and shorter courses, while LLMDs more often treat on clinical grounds and for longer.

Many integrative and functional medicine clinics offer co-infection care alongside prescription drugs, sometimes with adjunct therapies such as hyperbaric oxygen therapy or ozone therapy. These adjuncts are cash pay in most cases, are not FDA approved for Lyme disease or its co-infections, and rest on small studies and clinical reports. The Lyme disease treatment guide sets out the main options and the evidence behind each, and chronic Lyme disease treatment covers longer protocols for persistent symptoms.

To compare practices that treat tick-borne illness, browse the directory of Lyme disease treatment clinics. Listing order there is not paid ranking, Featured slots are clearly labeled and capped, and Verified means the clinic has completed credential checks, not that it paid. Regenerated.com is free for patients, and inclusion in the directory is not an endorsement, so ask any clinic which co-infections it tests for. The guide to Featured, Verified and organic listings explains each label.

Frequently asked questions

How are Bartonella and Babesia coinfections treated?

Babesia is treated with atovaquone plus azithromycin for at least 7 to 10 days, according to the IDSA 2020 guideline, with clindamycin plus quinine as the alternative. Bartonella has no guideline regimen in the Lyme setting, so clinicians usually combine azithromycin or clarithromycin with rifampin for weeks to months. Many treat Babesia first, then add Bartonella treatment once fevers and night sweats settle, and they check drug interactions because rifampin lowers atovaquone levels.

Does doxycycline treat Babesia or Bartonella?

Doxycycline does not treat Babesia, because Babesia is a parasite rather than a bacterium, and it needs antiparasitic drugs such as atovaquone. Doxycycline has some activity against Bartonella and is part of several combination regimens, usually with rifampin, but on its own it is rarely enough. It does treat Lyme disease, Ehrlichia, Anaplasma and Borrelia miyamotoi, which is why it is the usual first drug after a tick bite illness.

How long does Babesia treatment take?

Standard Babesia treatment lasts at least 7 to 10 days for ill patients with a healthy immune system, according to the CDC and the IDSA 2020 guideline. Highly immunocompromised patients may need at least 6 consecutive weeks, continuing until blood smears show no parasites for 2 weeks in a row. Fatigue can linger for weeks after treatment. Many Lyme-literate physicians treat chronic cases for longer, which is a clinical choice rather than a guideline recommendation.

What are the signs of Bartonella in Lyme patients?

The signs most often linked to Bartonella are shin pain on waking, sole-of-foot pain, sudden ice-pick headaches, red or purple stretch-mark-like streaks, swollen lymph nodes, and mood changes such as anxiety, rage or irritability. Eye problems, including floaters and neuroretinitis, can also occur. Because Bartonella tests miss many infections, Lyme-literate physicians often diagnose it from this symptom pattern together with a history of cat or flea exposure.

Can you have Lyme, Babesia and Bartonella at the same time?

Yes, a person can have Lyme disease, Babesia and Bartonella at the same time. The blacklegged tick can carry Borrelia, Babesia and Anaplasma together, and Bartonella can come from fleas or cats in the same person. Triple infection makes symptoms harder to read and treatment longer, so clinicians usually treat in stages: Babesia first or alongside Lyme, then Borrelia, then Bartonella once the patient can tolerate stronger reactions.

Which doctor treats Lyme co-infections?

Infectious disease specialists, primary care physicians and Lyme-literate physicians all treat Lyme co-infections. Infectious disease specialists usually follow IDSA and CDC guidance with defined courses, while Lyme-literate physicians, many trained through ILADS, more often use longer, symptom-guided plans. Integrative and functional medicine clinics may add adjunct therapies. Whoever you choose, ask which co-infections they test for, which labs they use and how they will judge progress.

Related Reading

• Lyme Disease: The Complete Guide to Diagnosis, Treatment, and Recovery
• Chronic Lyme Disease Treatment Options
• Lyme Disease Testing: Types, Accuracy, and When to Get Tested
• Lyme Disease Diet: What to Eat and Avoid During Treatment