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

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.

This article covers the major co-infections, what they look like clinically, how to test for them, and how they are treated.

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. The FISH (fluorescent in-situ hybridization) test offered by iGeneX is considered one of the more sensitive options.

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: More potent but also more side effects. Often reserved for severe cases 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 typically longer than standard recommendations suggest. While the CDC recommends 7 to 10 days, many experienced clinicians treat for weeks to months, particularly in immunocompromised patients or those with chronic infection.

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. While Bartonella henselae (the cause of cat scratch disease) gets the most attention, tick-transmitted species like B. quintana and others may be more clinically relevant in the Lyme context.

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. Galaxy Diagnostics offers an enrichment culture (ePCR) that is considered the gold standard, but even it has limited sensitivity.

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.
• Herbal approaches: Japanese knotweed, houttuynia, and cryptolepis are used in herbal protocols like the Buhner protocol for Bartonella.

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). Both are transmitted by the same ticks that carry Lyme.

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.

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.

Co-Infection Comparison Table

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. iGeneX, Galaxy Diagnostics, and Vibrant Wellness offer more sensitive panels.
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.

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.

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