First described in humans in the late 1980s and 1990s, Ehrlichia and Anaplasma have become among the most frequently reported tick-borne illnesses after Lyme disease. They are closely related enough that they were once classified in the same genus — in fact, Anaplasma was originally called Ehrlichia phagocytophilia before being reclassified. Their clinical presentations are nearly identical, their treatment is the same, and the key difference is which type of white blood cell each one targets.
Two bacteria — one clinical picture
Both Ehrlichia and Anaplasma are gram-negative, obligate intracellular bacteria. They cannot grow in standard blood culture media, which is why routine hospital cultures will not detect them. They infect white blood cells and form characteristic clusters called morulae — visible under microscopy as dark mulberry-like inclusions inside the infected cells. The word morula comes from the Latin for mulberry, which describes their appearance.
Morulae — the diagnostic signature inside white blood cells
When Ehrlichia or Anaplasma infect a white blood cell, they multiply inside membrane-bound vacuoles within the cell's cytoplasm. As their numbers increase, these vacuoles become visible under a light microscope as dark, mulberry-like clusters — the morulae. Their presence inside white blood cells on a Giemsa-stained peripheral blood smear is a strong indicator of infection.
However, morulae are not always visible. They are found in only 20–80% of confirmed cases, with lower detection rates in immunocompetent patients with milder infection. A negative blood smear does not rule out Ehrlichia or Anaplasma — PCR testing is significantly more sensitive and is the preferred diagnostic tool in early illness.
How they spread — and the Lyme connection
Both Ehrlichia and Anaplasma are transmitted by tick bites. The critical point for Lyme disease patients is that Anaplasma phagocytophilum is transmitted by the exact same Ixodes ticks that carry Lyme disease — meaning a single tick bite in an endemic area can transmit Lyme, Anaplasma, and potentially Babesia simultaneously. Co-infection is not rare; it is a regular clinical reality.
Ehrlichia chaffeensis is primarily transmitted by the Lone Star tick (Amblyomma americanum), which has a distinctive white spot on its back and is found throughout the southeastern and south-central United States, with its range expanding northward. Unlike Ixodes ticks, the Lone Star tick does not transmit Lyme disease — but it does transmit Ehrlichia, as well as a condition called Southern Tick-Associated Rash Illness (STARI), which mimics early Lyme disease. Understanding which tick is involved helps interpret the clinical picture.
Like Babesia, both Ehrlichia and Anaplasma can be transmitted through blood transfusions, though this route is less common. The diseases are not transmitted person-to-person through casual contact.
An acute febrile illness — often mistaken for severe flu
Both HME and HGA present with a remarkably similar clinical picture: acute, sudden onset of fever, headache, muscle pain, and malaise beginning 1–2 weeks after a tick bite. This non-specific presentation is why Ehrlichia and Anaplasma are so frequently dismissed as influenza, particularly in summer — when flu is uncommon but tick activity is at its peak. The distinction matters: these infections can progress rapidly to life-threatening illness without appropriate antibiotic treatment.
- Sudden high fever — often 39–40°C
- Severe headache
- Profound myalgia — deep muscle aching
- Chills and rigors
- Malaise and profound fatigue
- Loss of appetite, nausea
- Vomiting, diarrhoea in some cases
- Joint pain (arthralgia)
- Confusion or altered mental status
- Stiff neck — meningism
- Encephalitis in severe cases
- Seizures (rare but documented)
- Peripheral neuropathy
- Conjunctival injection (red eyes)
- Sensitivity to light
- Leukopenia — abnormally low white blood cell count
- Thrombocytopenia — low platelet count
- Elevated liver enzymes — ALT, AST raised
- Anaemia — in about 50% of patients
- Elevated creatinine — kidney stress
- Hyponatremia — low sodium
- Sepsis-like picture
- Acute respiratory distress
- Renal failure
- Haemorrhage — bleeding complications
- Multi-organ failure
- Coma in extreme cases
- Death in less than 3% — higher without treatment
Leukopenia (low white blood cell count), thrombocytopenia (low platelets), and elevated liver enzymes forming a cluster on routine bloodwork — in a patient with fever and a history of outdoor exposure — should immediately raise suspicion of Ehrlichia or Anaplasma. These findings are relatively unusual for viral flu and uncommon in uncomplicated Lyme disease. When this triad appears on a summer blood test in someone who spends time outdoors, tick-borne illness should be at the top of the differential. In practice it frequently is not, which is why these infections go untreated for days while the patient deteriorates.
Why the rash is an unreliable marker
In Lyme disease, erythema migrans provides a visible diagnostic clue. Ehrlichia and Anaplasma are not so obliging. A rash occurs in a minority of adults with HME, and is rare in HGA. In children, a rash appears in up to 60% of Ehrlichia cases — but it is non-specific and can be mistaken for many other conditions including drug reactions and viral exanthems.
In a patient with an erythema migrans rash who also has a co-infection with Ehrlichia or Anaplasma, the rash can lead clinicians to focus on Lyme disease alone — and miss the co-infection. The clues that suggest co-infection alongside Lyme disease include: high fever (uncommon in uncomplicated early Lyme), leukopenia and thrombocytopenia on bloodwork, and unusually rapid or severe progression of illness. These findings alongside an EM rash should prompt testing for co-infections, not reassurance.
How to confirm it — and why speed matters
Unlike most tick-borne illnesses, Ehrlichia and Anaplasma present acutely and can progress rapidly. The window for diagnosis and treatment is short — delaying by even a few days in a severe case can make the difference between full recovery and organ failure. This makes accurate and timely diagnosis especially important.
A Giemsa-stained peripheral blood smear can sometimes show morulae inside white blood cells within the first week of illness. When visible, morulae are essentially diagnostic. However, sensitivity is limited — morulae are seen in only 20–80% of cases, with higher rates in immunocompromised patients where bacterial burden is greater. Never rely on a negative smear to rule out infection in a symptomatic patient.
Polymerase chain reaction testing on blood detects Ehrlichia or Anaplasma DNA directly. Most sensitive during the first week of illness before antibody response develops. PCR is the preferred test for acute diagnosis. Note that Ehrlichia and Anaplasma require different PCR assays — testing for one does not detect the other. In co-infection-endemic areas, testing for both simultaneously is appropriate.
Serological tests (immunofluorescence assay, IFA) detect the immune response to Ehrlichia or Anaplasma. Antibodies typically take 2–4 weeks to rise to detectable levels — meaning serology is negative in the first week when diagnosis is most urgent. Serology is used for confirmatory purposes retrospectively, not for acute diagnosis. Some cross-reactivity between Ehrlichia and Anaplasma antibodies can cause diagnostic confusion.
In clinical practice, when the presentation is consistent — high fever, leukopenia, thrombocytopenia, elevated liver enzymes, tick exposure history in summer — treatment with doxycycline should not wait for laboratory confirmation. The illness can progress to multi-organ failure within days. A rapid response to doxycycline within 24–48 hours is itself diagnostically informative.
Doxycycline — effective but time-critical
Both Ehrlichia and Anaplasma respond well to doxycycline — the same antibiotic used for Lyme disease. Unlike many tick-borne illnesses where the evidence base is contested, here the evidence for doxycycline is clear and consistent. Improvement typically begins within 24–48 hours of starting treatment; failure to improve rapidly should prompt reconsideration of the diagnosis or the possibility of co-infection with another agent.
Doxycycline 100 mg twice daily for 7–14 days. Treatment should be initiated empirically in clinically suspected cases without waiting for laboratory confirmation. In children under 8 or pregnant women (for whom doxycycline is generally avoided), rifampin is an alternative — though evidence is more limited. These infections are fatal in less than 3% of treated cases; the fatality rate without treatment is substantially higher.
Patients without a functioning immune system, those on immunosuppressive medications, and the elderly are at substantially higher risk of severe and prolonged illness. In these patients, treatment should be started even earlier and continued for the full course regardless of clinical improvement. The risk of relapse and complications is greater in this group.
When Ehrlichia or Anaplasma accompanies Lyme
Because Anaplasma phagocytophilum shares the same Ixodes tick vector as Lyme disease in both North America and Europe, the two infections co-occur regularly. For patients already navigating a Lyme diagnosis, an unrecognised Anaplasma co-infection can complicate the picture significantly.
When a patient has an EM rash and tests positive for Lyme disease, both physician and patient tend to attribute all symptoms to Lyme. A co-infecting Anaplasma may produce additional symptoms — high fever, leukopenia, rapid onset — that are more acute than typical Lyme. These are sometimes attributed to a "severe Lyme reaction" when in fact they signal a second organism requiring separate attention. The clue is in the bloodwork: low white blood cells and low platelets are not typical features of early Lyme disease alone.
Unlike the Lyme-Babesia combination — where entirely different drug classes are needed — doxycycline is effective against both Lyme disease and Anaplasma/Ehrlichia simultaneously. A patient being treated with doxycycline for Lyme disease is also receiving appropriate treatment for any Ehrlichia or Anaplasma co-infection. This is one area where the standard Lyme treatment framework happens to provide adequate coverage for a co-infection without modification.
Sources & further reading
- Dumler JS et al. — Human Ehrlichiosis and Anaplasmosis. Clinical Microbiology Reviews, PMC2882064
- Paddock CD, Childs JE — Current management of HGA, HME and Ehrlichia ewingii ehrlichiosis. PMC2739015
- New York State Department of Health — Anaplasmosis and Ehrlichiosis fact sheet
- WikiTropica — Ehrlichia and Anaplasma clinical overview
- Maryland Department of Health — Ehrlichiosis and Anaplasmosis fact sheet
- Mayo Clinic Laboratories — Ehrlichia/Anaplasma molecular detection
- Statpearls — Anaplasma phagocytophilum, NBK513341
Last updated: April 2026