Babesiosis

Babesiosis

Jorge Cardenas-Alvarez, MD

Department of Medicine, Division of Infectious Diseases, Columbia University Irving Medical Center, New York, United States

Author: Jorge Cardenas-Alvarez

Luis A. Marcos, MD, MPH, FIDSA

Division of Infectious Diseases, Department of Medicine, Stony Brook University, Stony Brook, New York, USA

Editor: Luis A. Marcos

Section Contents

  1. Key Points
  2. Background & Epidemiology
  3. Life Cycle & Pathogenisis
  4. Clinical Presentation
  5. Diagnosis
  6. Treatment & Management
  7. Prevention
  8. References

Key Points

  • Babesia is a zoonotic protozoa that can be acquired through the bite of an Ixodes tick, blood transfusions, vertically-acquired, or through organ transplantation.
  • Human babesiosis is primarily seen in North America & Europe and less commonly in Asia.
  • Human infection can be either mild/moderate or severe, and it largely depends on the immune status of the host.
  • Patients without a spleen or with a non-functioning spleen are at higher risk for severe infection.
  • Diagnosis is often a combination of clinical suspicion and microscopy, antibodies, and/or PCR.
  • Most patients can be treated with azithromycin + atovaquone.

Background & Epidemiology

Babesiosis is a zoonotic disease caused by protozoa of the genus Babesia, which is primarily transmitted by the Ixodes ticks. The genus Babesia infects the erythrocytes in both humans and a wide array of animals, and ranges from asymptomatic parasitemia to severe multiorgan failure and death.

Figure 1. Ixodes spp

Human babesiosis is primarily seen in three regions of the world - summarized in Table 1.

  1. North America → Babesia is endemic in the Northeastern United States (i.e., Massachusetts, New York, Connecticut), and to a lower degree in the Midwest (i.e., Minnesota, Wisconsin). The dominant species is Babesia microti, which is transmitted by Ixodes scapularis (same vector as Lyme borreliosis and Anaplasma spp). Rodents are the main reservoir (i.e., meadow voles, white-footed mice).
  2. Europe → Babesia is seen throughout Europe, where is primarily caused by Babesia divergens and Babesia venatorum. These species tend to have a more severe presentation compared to their American counterparts (specially among immunocompromised patients). Cattle is the main resorvoir.
  3. Asia → much less common than in North America and in Europe. Biggest burden seen in mainland China and to a lesser extent in Japan and Russia. It is caused by the species Babesia microti and Babesia venatorum. Primary vectors are Ixodes persulcatus and Ixodes ovatus.
Main Distribution Primary genus/species Primary vector Main reservoir
North America United States (Northeast, MidWest) Babesia microti Ixodes scapularis Small mammals (i.e., rodents)
Note → rarely, Babesia duncani, seen in the Western United States
Europe Widely distributed throughout Europe Babesia divergens, Babesia venatorum Ixodes ricinus Cattle
Asia China, Japan, Russia Babesia microti, Babesia venatorum Ixodes persulcatus, Ixodes ovatus Deer (suspected)

Table 1. Babesia epidemiology

Life Cycle & Pathogenesis

Babesia spp. are closely related to Plasmodium spp. and life cycles share many similarities. Transmission is through an arthropod (i.e., Ixodes tick), but unlike malaria, occurs between animal reservoirs and humans (RARELY between humans). Because Babesia parasites infect erythrocytes, it can also be transmitted through blood transfusions, perinatally or through organ transplantation.

Note: In North America, endemic states will check for Babesia year-round among blood donors.

Life cycle: infection starts in humans when tick takes a blood meal and inadvertently introduces sporozoites in the saliva. Sporozoites invade erythrocytes and divide into daughter cells (merozoites) through asexual replication. Merozoites can create ring forms (trophozoites) or tetrad formations (“Maltese cross”), and after replication, they lyse the erythrocyte’s membrane (hemolysis), which releases further merozoites into the bloodstream that are able to parasitize other neighboring erythrocytes. In general, there is no sexual replication (production of gametocytes) in humans, and thus ticks do not continue the life cycle from infected humans.

Immunity to Babesia: is complex, and we will not go through it in detail. The most important concept is that the spleen plays a key role in eliminating Babesia-infected erythrocytes. Thus, individuals with immunosuppressive conditions or who have no spleen or a non-functioning spleen may have trouble controlling the infection.

Note: sexual replication occurs mainly in ticks. Ticks acquire gametocytes from animal reservoirs, and NOT from humans.

Clinical Presentation

After an incubation period of 1-4 weeks (up to 9 weeks in non-vectorial transmission), babesiosis can present in many different ways. The presentation can vary from uncomplicated to severe, and largely depends on the immune status of the patient. Note that B. divergens & B. venatorum (European forms) are more commonly seen among immunocompromised individuals (therefore, tend to have a more severe course). Click below to see the clinical spectrum of Babesia.

Uncomplicated babesiosis
Severe babesiosis
When should you suspect Babesia?

Answer

  1. FUO or unexplained intermittent fever
  2. Signs of hemolytic anemia & thrombocytopenia
  3. Recent exposures → Residence or travel to endemic area (North America, Europe, China), previous blood transfusions, tick bites
  4. Summer months, less commonly seen in other seasons

Diagnosis

As with all diseases, diagnosis starts with a clinical suspicion in the right epidemiological context (What is the presentation? Who is the host?). Definitive diagnosis can be supported through the following modalities:

  1. Thick/thin blood-smears (Wright, Giemsa-stained) → microscopy may reveal merozoites and/or ring forms (trophozoites). The pathognomonic sign of “Maltese Cross” (tetrad formation of the merozoites) is rarely seen. Microscopy might be falsely negative with <1% parasitemia. However, when patients end up in the emergency room (the sickest), they usually have positive blood smears.
    1. NOTE - just like in malaria, multiple set of blood films should be examined to evaluate for babesiosis.
    2. If you’re looking for more information about the morphology of the parasites, go to this amazing blog.
  2. Antibodies (IgM/IgG IFA) → IgM takes ~2 weeks to seroconvert and false positives are common. IgG levels >1:256 are typically considered positive (lower titers may apply for blood donors). A four-fold increase in titers after 2 weeks is considered more consistent with recent infection, but rarely useful in clinical practice. IgG levels do not distinguish between present and past infection.
  3. PCR → highly sensitive, detection limit is approximately 1-3 parasites/uL of blood. It's the best when the parasitemia is low (usually mildly symptomatic cases, or seen in the outpatient clinics).

FIGURE 2. Legend: Blood smear showing Babesia spp

Figure 3. Blood smear showing Babesia spp.

Treatment & Management

Treatment depends on the immune status of the patient and the severity of the presentation. For a more in-depth explanation, please reference the following treatment guidelines:

Here is a quick summary so you can remember the most high-yield concepts!

Immunocompetent Immunocompromised
Uncomplicated (mild/moderate) PO Azithromycin + PO Atovaquone
(Alternative: PO Clindamycin + Quinine)
Severe IV Azithromycin + PO Atovaquone
(Alternative: IV Clindamycin + Quinine/Quinidine)
Duration 7 - 10 days Minimum of 6 weeks if: highly immunocompromised, severe cases, or relapsed cases
Relapse Rare Can occur
Monitoring Treatment until most symptoms resolve and blood smears become negative Obtain daily blood smears until parasitemia <4%, and then weekly. Can finish treatment once parasites are no longer detected on smears for 2 consecutive weeks
Management pearls * Fatigue may persist for months and is not an indication for re-tx
* Parasitemia >10% OR severe organ dysfunction → consider exchange transfusion!
* Splenic infarcts can happen. Management is conservative since these are due to congestion from dead parasites.

Table 2. Treatment of babesiosis

Prevention

  1. Vector avoidance & control
    1. Avoid tick habitats during peak-season (spring-summer-fall)
    2. Wear protective clothing
    3. Use DEET insect repellents
    4. Tick removal - watch this video to learn how to remove a tick!
    5. Control of tick-infested regions
  2. Non-vectorial prevention
    1. Blood transfusion screening in endemic areas
    2. Avoid blood transfusions after Babesia infection

References

This lesson was last updated May 23 2025


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