Ehrlichiosis / Anaplasmosis

Ehrlichiosis and anaplasmosis are tick-borne illnesses caused by obligate intracellular, gram-negative bacteria of the family Anaplasmataceae. Both infect white blood cells rather than living freely in plasma, forming microcolonies called morulae inside the cell's cytoplasm — Ehrlichia chaffeensis, the main cause of human monocytic ehrlichiosis, infects monocytes; Anaplasma phagocytophilum, the cause of human granulocytic anaplasmosis, infects granulocytes (mainly neutrophils).^[1][2]

The two organisms are transmitted by genuinely different ticks, and that difference matters clinically. E. chaffeensis is transmitted by the lone star tick (Amblyomma americanum), a species found primarily in the south-central, southeastern, and mid-Atlantic United States that is not established in Canada — so ehrlichiosis in a Canadian patient is, to date, a travel-associated diagnosis, not a locally acquired one.^[1][3] A. phagocytophilum, by contrast, is transmitted by the blacklegged tick (Ixodes scapularis) in eastern Canada and the western blacklegged tick (Ixodes pacificus) in British Columbia — the exact same ticks that transmit Lyme disease and babesiosis. This shared vector is the single most important epidemiologic fact in this chapter: a tick that transmits Borrelia burgdorferi can, in the same bite, transmit A. phagocytophilum and Babesia microti as well, making co-infection a real and clinically relevant possibility rather than a curiosity.^[2][4]

Both diseases present as a nonspecific febrile illness — fever, headache, myalgia, malaise — that is genuinely easy to miss, in large part because a rash is either absent or inconsistent, unlike the classic erythema migrans of Lyme disease.^[2][5] Anaplasmosis has become nationally notifiable in Canada as of 2024, with documented cases in Ontario, Quebec, New Brunswick, Nova Scotia, Manitoba, and Alberta and a tick population expanding roughly 46 km northward per year in Ontario alone; ehrlichiosis has no confirmed Canadian cases reported to date.^[4][2]

Incubation and seasonality

Symptoms of anaplasmosis typically begin 5 to 21 days after the bite of an infected tick.^[2] Ehrlichiosis has a shorter median incubation of about 9 days, with symptom onset typically reported within 5-14 days of a bite.^[1][5] Both illnesses follow tick activity: cases occur whenever ticks are active (any time the ground is unfrozen and temperature is consistently above freezing), with anaplasmosis showing a bimodal Canadian/North American pattern — a larger peak in June-July (nymphal tick activity) and a smaller peak in October-November (adult tick activity) — and ehrlichiosis peaking in June-July in its endemic U.S. range.^[2][4][1]

The pattern: nonspecific fever, usually without a rash

Both diseases present as an undifferentiated febrile illness. Common early symptoms (days 1-5) include fever, chills/rigors, severe headache, malaise, myalgia, and gastrointestinal symptoms (nausea, vomiting, diarrhea, anorexia) in roughly 20% of anaplasmosis cases.^[7][5] Common laboratory abnormalities in both — appearing as early as the first week of illness — are leukopenia (often with lymphopenia), thrombocytopenia, and mild-to-moderate elevation of hepatic transaminases; normal labs do not rule out infection.^[4][7][5]

Life stages of Ixodes scapularis, the blacklegged tick — the same species that transmits Lyme disease and babesiosis in eastern Canada. The nymph (second from left) is roughly the size of a poppy seed and is responsible for most human infections, which is why so many patients never recall a bite. (CDC Public Health Image Library, U.S. federal government work, public domain)

A female lone star tick (Amblyomma americanum), the vector for Ehrlichia chaffeensis — identifiable by the single white spot on the female's back. This species is established in the south-central, southeastern, and mid-Atlantic United States, not in Canada, which is why a Canadian case of ehrlichiosis should prompt a specific travel-history question. (James Gathany/CDC Public Health Image Library #4407, U.S. federal government work, public domain)

Severe disease

Most patients with either illness have mild-to-moderate disease, and some recover even without treatment — but a meaningful minority develop severe, life-threatening complications, particularly when treatment is delayed.^[4] Reported severe manifestations include renal or respiratory failure, disseminated intravascular coagulation-like coagulopathy, hemorrhage, rhabdomyolysis, peripheral neuropathies, toxic or septic shock-like syndrome, and neurologic involvement (confusion, meningitis, meningoencephalitis — reported in roughly 20% of severe ehrlichiosis cases); anaplasmosis can additionally cause cardiac complications such as heart failure, pericardial effusion, and cardiac tamponade.^[2][7][5] Risk factors for severe disease include age under 5 or over 60-70 years, immunocompromising conditions (advanced HIV, chemotherapy, other immunosuppression, splenectomy, organ transplantation), pre-existing comorbidities, and — critically — delayed antibiotic treatment.^[7][5][8] Case-fatality rates are low overall (anaplasmosis under 1% in Canadian/PHAC data; a 2024 global systematic review reported 3%, concentrated in patients over 50 with comorbidities) but a genuinely striking finding from that review is that half of the fatal anaplasmosis cases had not received appropriate antibiotic therapy — underscoring that most deaths from these diseases are preventable with timely doxycycline.^[2][4]

• Outdoor activity in wooded, brushy, or tall-grass habitat — hiking, camping, gardening, yard work — in an area with an established blacklegged or western blacklegged tick population (documented human anaplasmosis cases in Ontario, Quebec, New Brunswick, Nova Scotia, Manitoba, and Alberta).^[4][2]
• Travel to the south-central, southeastern, or mid-Atlantic United States (lone star tick range) — the key risk factor for ehrlichiosis specifically, since E. chaffeensis has no established Canadian vector.^[1][3]
• Prolonged tick attachment — in most cases, an infected blacklegged or western blacklegged tick needs to be attached for at least 24-48 hours to transmit A. phagocytophilum, though transmission can occur sooner; prompt tick removal genuinely reduces risk.^[2][9]
• Outdoor pets, which can carry ticks into the yard or home and increase household exposure.^[9]
• Age under 5 years or over 60-70 years, and immunocompromising conditions (advanced HIV, chemotherapy or other immunosuppression, splenectomy, organ transplantation) — risk factors for a severe course rather than for acquisition itself.^[7][5]
• Recent sulfonamide antimicrobial therapy has been associated with more severe ehrlichial illness in some reports — a detail relevant when reviewing a febrile patient's recent medication history.^[8]
• Very rarely, blood transfusion or solid organ transplantation — both organisms can survive more than a week in refrigerated blood, and blood products are not routinely screened for either pathogen, though no case of transfusion- or transplant-transmitted disease has been reported in Canada to date.^[2][3]

Treat first — confirm in parallel, not before

Both PHAC and CDC guidance are explicit: never delay or withhold empiric doxycycline while awaiting laboratory results, and do not withhold it because of an initial negative result. Early recognition and prompt treatment are what prevent progression to severe disease.^[2][6][12] This is especially important in Canada, where PCR testing for anaplasmosis is centralized at the National Microbiology Laboratory with a turnaround time of roughly 21 days — far too slow to guide an initial treatment decision.^[4]

History

Ask specifically about: a recent tick bite (many patients will not recall one — bites are painless and the responsible nymphal stage is roughly poppy-seed sized); outdoor exposure to wooded, brushy, or tall-grass habitat, including routine activities like gardening or yard work; and travel history to a region where the lone star tick is established, which is the key clue for ehrlichiosis in a Canadian patient. Absence of a recognized tick bite or outdoor exposure should never be used to exclude the diagnosis.^[12][6]

Laboratory testing

^[6][12][4]

Differential diagnosis — the shared-vector problem

Because the same Ixodes tick can carry multiple pathogens in one bite, always consider co-infection or an alternative tick-borne diagnosis when anaplasmosis is suspected.^[2][4]

^[4]

The presence of an erythema migrans rash points to Lyme disease or a Borrelia co-infection, not anaplasmosis or ehrlichiosis themselves. Hemolytic anemia in a febrile, tick-exposed patient should specifically raise babesiosis, which needs an entirely different antiparasitic regimen (see Choose Initial Treatment). Neurologic manifestations out of proportion to the rest of the picture should raise Powassan virus infection.^[4]

• Start empiric doxycycline as soon as either diagnosis is clinically suspected — do not wait for PCR or serology, which are too slow in Canada to guide an initial decision and are often negative early in illness regardless.
• Prevent progression to severe, potentially fatal disease (organ failure, hemorrhage, shock, neurologic involvement) through early antibiotic therapy — this is the single biggest driver of outcome in both diseases.
• Treat anaplasmosis for a duration long enough to also cover a possible, common concurrent Lyme disease infection, given the shared tick vector.
• Recognize and separately treat babesiosis co-infection, since doxycycline and rifampin have no activity against Babesia.
• Confirm defervescence within 24-48 hours of starting doxycycline as an early marker of response, and reconsider the diagnosis if it does not occur.
• Counsel on tick bite prevention and prompt, correct tick removal to reduce the risk of this — and co-transmitted — infections going forward.
• Report confirmed and probable anaplasmosis cases to public health, since it is now a nationally notifiable disease in Canada.

Dosing and duration

^[10][11]

Ehrlichiosis continue for at least 5-7 days, and until 72 hours after fever resolves with clinical improvement.^[11] Anaplasmosis continue for 10-14 days total — a longer course than ehrlichiosis alone would require, specifically chosen to also treat a possible, common concurrent Lyme disease infection given the shared Ixodes vector, not because A. phagocytophilum itself needs a longer course.^[10][4] With appropriate treatment, fever typically resolves within 24-48 hours; no doxycycline resistance or relapse after a completed course has been documented for either disease, so lack of improvement by 48 hours should prompt reconsidering the diagnosis rather than simply extending the same regimen.^[10][11]

Alternative agents — specialist-directed only

Rifampin has been used successfully in several pregnant women with mild anaplasmosis, and studies suggest it is effective against A. phagocytophilum; small numbers of children under 8 have also been treated successfully for anaplasmosis with a 7-10 day rifampin course. Its evidence base for ehrlichiosis is weaker — rifampin appears effective against E. chaffeensis only in laboratory studies, and clinical effectiveness has not been established.^[10][13] Important limitations rifampin is not effective for Rocky Mountain spotted fever, a disease that can be confused with anaplasmosis/ehrlichiosis, and it is not effective against a concurrent Borrelia (Lyme) infection.^[10][13] Reserve rifampin strictly for a life-threatening doxycycline allergy, severe doxycycline intolerance, or select pregnant patients with an apparently mild course, and only after consultation with an infectious diseases specialist.^[13][10]

Chloramphenicol is explicitly not an acceptable alternative for either disease, despite older literature suggesting otherwise — do not substitute it.^[10] In vitro data also show beta-lactams, cephalosporins, macrolides, and aminoglycosides are ineffective against E. chaffeensis — none of these drug classes should be reached for as ehrlichiosis/anaplasmosis therapy, even though some of them (e.g., azithromycin) have an entirely separate, legitimate role in treating a co-infecting organism (see below).^[1]

Babesiosis co-infection — doxycycline and rifampin do not treat this

If hemolytic anemia is present, or babesiosis is confirmed or strongly suspected as a co-infection, treat it concurrently with a separate regimen — neither doxycycline nor rifampin has any anti-babesial activity.^[4][14] Preferred, mild-to-moderate disease Combo: atovaquone 750 mg PO every 12 hours + azithromycin 500 mg PO on day 1, then 250 mg PO daily for a total of 7-10 days.^[14] Alternative, or preferred for severe disease/pregnancy Combo: clindamycin 600 mg PO every 8 hours (or 600 mg IV every 6 hours if hospitalized) + quinine 650 mg PO every 8 hours for 7-10 days; because safety data on atovaquone in pregnancy are limited, clindamycin plus quinine is generally the preferred regimen specifically in pregnancy for babesiosis, unless the preferred agents are unavailable or not tolerated.^[14]

• Supportive care — hydration, antipyretics, and close monitoring for evolving organ dysfunction — alongside antibiotic therapy; hospitalize any patient with severe features or significant risk factors for a severe course.^[7][5]
• Tick bite prevention is the only real primary prevention available — there is no vaccine for either disease. Counsel on an EPA/Health Canada-registered insect repellent (e.g., DEET or icaridin), permethrin-treated clothing, long sleeves/pants tucked into socks in wooded or brushy areas, staying on cleared trails where possible, and a full-body tick check (plus a prompt shower) after any outdoor exposure.^[9]
• Prompt, correct tick removal matters — in most cases a tick needs to be attached at least 24-48 hours to transmit A. phagocytophilum, so early removal genuinely reduces transmission risk. Use fine-tipped tweezers, grasp the tick as close to the skin surface as possible, and pull upward with steady, even pressure — do not twist, jerk, or crush the body. Clean the bite site afterward.^[2][9]
• Outdoor pets can carry ticks into the home and yard — advise pet owners to discuss tick prevention with a veterinarian.^[9]
• Report confirmed and probable anaplasmosis cases to public health — it has been a nationally notifiable disease in Canada since 2024, and both confirmed and probable cases are reportable under the national case definition.^[2]
• No special isolation precautions are needed — neither disease is transmitted person-to-person through casual contact; standard precautions are sufficient. The rare exception is blood transfusion or organ/tissue transplantation (see Special Populations).^[2][3]

Children under 8 years

Doxycycline remains first-line despite the usual tetracycline-class avoidance in young children — a genuine, well-established exception. A study specifically evaluating short courses (5-10 days, matching the duration used here) found no staining of permanent teeth and no enamel hypoplasia, and this recommendation is jointly endorsed by CDC and the American Academy of Pediatrics Committee on Infectious Diseases.^[13][8] Dose at 2.2 mg/kg PO/IV every 12 hours (maximum 100 mg per dose) for children under 45 kg. Case-fatality rates for both diseases are, notably, highest among children under 10 — reinforcing why prompt empiric treatment matters even more in this group, not less.^[8]

Pregnancy

Doxycycline is likewise preferred in pregnancy. Current evidence indicates that doxycycline use during pregnancy is unlikely to pose substantial teratogenic risk, though it is not possible to state that no risk exists — counsel patients on this risk/benefit balance directly, weighed against the real risk of untreated tickborne rickettsial disease.^[8] Rifampin has been used successfully in several pregnant women specifically with mild anaplasmosis and may be considered by the treating physician in that narrow situation; its evidence base for ehrlichiosis in pregnancy is far weaker (laboratory data only).^[10][13] If babesiosis co-infection is also present, clindamycin plus quinine is generally preferred over atovaquone plus azithromycin in pregnancy, given limited safety data on atovaquone in this population.^[14]

Breastfeeding

Confirm the specific regimen against a current lactation-safety reference and the infant's own risk factors (e.g., age, feeding pattern) before dispensing; this was not addressed in the primary sources used for this chapter and warrants individualized pharmacist input rather than a blanket statement.

Older adults and immunocompromised patients

Both groups are at meaningfully higher risk for a severe or fatal course — maintain a lower threshold for hospitalization and closer monitoring even when the initial presentation looks mild, and do not let a reassuring early exam delay treatment.^[7][5][4]

Blood and organ/tissue donation

Both A. phagocytophilum and E. chaffeensis can survive more than a week in refrigerated blood, and transfusion- or transplant-transmitted cases have been reported internationally, though none has been documented in Canada to date. Blood products are not routinely screened for either organism, and leukoreduction may reduce but does not eliminate the risk. A patient who develops compatible symptoms within about 30 days of receiving a transfusion or solid organ transplant should be reported to public health/the relevant blood service (Canadian Blood Services or Héma-Québec) for investigation.^[2][3]

Renal and hepatic impairment

Doxycycline generally requires no dose adjustment in renal impairment. Use rifampin cautiously in significant hepatic impairment given its hepatotoxicity potential, and review it for interactions with any other hepatically metabolized medication before starting it.

• Expect defervescence within 24-48 hours of starting doxycycline — this is a genuinely useful early marker of a correct diagnosis and adequate treatment. No documented case of doxycycline resistance or relapse after a completed course exists for either disease.^[10][11]
• If fever or symptoms have not clearly improved by 48 hours, reconsider the diagnosis — including an unrecognized babesiosis co-infection, since doxycycline will not treat that organism — rather than simply extending the same regimen.^[10][11]
• Recheck baseline abnormal labs (CBC, transaminases) to confirm they are trending toward normal as clinical improvement occurs.
• Complete the full prescribed course even after symptoms resolve — 10-14 days for anaplasmosis (to also cover a possible Lyme co-infection), at least 5-7 days and 72 hours afebrile for ehrlichiosis.^[10][11]
• Report confirmed or probable anaplasmosis to public health under the national case definition, since it has been nationally notifiable in Canada since 2024.^[2]
• Do not retreat based solely on a persistently elevated IgG serology titre found months later in an asymptomatic patient — antibodies can remain elevated for months to years after resolved infection, and a new treatment decision should be driven by new symptoms, not by an old titre.^[6][12]
• If babesiosis co-infection was treated concurrently, follow parasitemia with peripheral blood smears (daily until parasitemia is under 4% in immunocompromised patients, then at least weekly) and continue therapy until parasites are no longer detected on two consecutive weekly smears in that population.^[14]

1. No defervescence or clinical improvement within 48 hours of starting doxycycline: reconsider the diagnosis rather than extending the same regimen — consider an alternative diagnosis entirely, an unrecognized babesiosis co-infection (doxycycline has no anti-babesial activity), or, in a patient started on rifampin, whether Rocky Mountain spotted fever is actually present (rifampin does not treat RMSF).^[10][11][10]
2. Persistent or new hemolytic anemia despite adequate doxycycline therapy: strongly suspect babesiosis co-infection and start atovaquone plus azithromycin (or clindamycin plus quinine) concurrently rather than waiting for confirmatory testing.^[4][14]
3. High-grade babesiosis parasitemia (≥10%) or severe hemolysis with pulmonary, renal, or hepatic decline: escalate to clindamycin plus quinine if not already on it, involve infectious diseases and hematology, and consider red blood cell exchange transfusion.^[14]
4. Any patient developing severe features (organ dysfunction, hemodynamic instability, significant neurologic involvement) at any point: hospitalize, involve infectious diseases, and consider IV doxycycline.^[2][7]
5. True inability to tolerate doxycycline (life-threatening allergy or severe intolerance): obtain infectious diseases consultation before substituting rifampin, and be explicit with the treating team about its narrower evidence base for ehrlichiosis and its lack of activity against RMSF and Borrelia.^[13][10]

• Withholding empiric doxycycline while awaiting PCR or serology — in Canada, PCR turnaround is roughly 21 days, far too slow to guide an initial treatment decision, and early serology is frequently negative regardless.^[4][6]
• Avoiding doxycycline in a child under 8 or a pregnant patient out of reflexive tetracycline-class caution — this is a genuine, deliberate exception grounded in real evidence (no tooth staining with the short courses used here), and the risk of untreated disease is far greater.^[13][8]
• Substituting chloramphenicol as an alternative — it is explicitly not an acceptable choice for either disease.^[10]
• Treating rifampin as an equivalent substitute for doxycycline in ehrlichiosis — its evidence for E. chaffeensis is laboratory-only, materially weaker than its evidence for anaplasmosis.^[13]
• Using rifampin when Rocky Mountain spotted fever remains a realistic differential diagnosis, or when a Borrelia (Lyme) co-infection is likely — rifampin treats neither.^[10][13]
• Assuming a fever that responds to doxycycline rules out a babesiosis co-infection — it does not; doxycycline has no anti-babesial activity, and a persisting hemolytic-anemia pattern needs its own regimen.^[4][14]
• Dismissing the diagnosis because there is no rash — a rash is absent in the majority of anaplasmosis cases and a meaningful share of ehrlichiosis cases; its absence is the expected pattern, not a reason to look elsewhere.^[2][5]
• Ruling out either diagnosis because the patient does not recall a tick bite — most patients with a confirmed infection do not recall one, since the responsible tick stages are tiny and bites are painless.^[12][6]
• Prescribing prophylactic doxycycline after a tick bite specifically to prevent anaplasmosis or ehrlichiosis — this is not recommended, unlike the distinct, narrower Lyme disease post-exposure prophylaxis practice.^[11]
• Treating a single positive acute-phase IgG serology result as diagnostic confirmation, or retreating a patient based solely on a persistently elevated titre found later without new symptoms — a single titre is only presumptive, and elevated antibodies can persist for months to years after resolved infection.^[6][12]
• Excluding ehrlichiosis from the differential in a febrile Canadian patient simply because it is not locally endemic — always ask about travel to the lone star tick's range in the southeastern/south-central/mid-Atlantic United States.^[3]

How to use this table: Doses are adult doses and require patient-specific confirmation (renal/hepatic function, weight, allergy history). Pediatric dosing is weight-based per the current product monograph unless stated. Drug pricing is intentionally omitted. Select any drug name to open its complete Pharmasist Drug Database page.

First-Line Therapy — All Ages, Including Children and Pregnancy

Start as soon as anaplasmosis or ehrlichiosis is clinically suspected. Do not withhold pending PCR or serology results.

Alternative Therapy — Infectious Diseases Consultation Required

Reserve for a life-threatening doxycycline allergy, severe intolerance, or select pregnant patients with an apparently mild course.

Not Recommended

Included specifically because these might otherwise be reached for empirically — each has a documented reason not to use it for anaplasmosis or ehrlichiosis.

Babesiosis Co-Infection Therapy — Not a Substitute for Doxycycline

Doxycycline and rifampin have no anti-babesial activity. If babesiosis is confirmed or strongly suspected (e.g., hemolytic anemia in a tick-exposed febrile patient), treat with one of these regimens concurrently, alongside — not instead of — the anaplasmosis/ehrlichiosis regimen above.