Babesia vs Malaria: How Babesiosis Can Be Mistaken for Malaria

Babesiosis can closely resemble malaria
A Maltese cross on a blood smear may suggest Babesia
Early recognition is important because treatment differs

Babesia vs malaria can be difficult to distinguish because both infections can cause fever, chills, anemia, low platelet counts, and parasites within red blood cells. Two women developed babesiosis after traveling from South Korea to the United States. In both cases, the organisms initially resembled Plasmodium on a peripheral blood smear, leading clinicians to suspect malaria.

Kwon and colleagues described two women who contracted Babesia microti while visiting the United States. One woman also had positive testing for Lyme disease. The cases were published in the Korean Journal of Parasitology in 2018.¹

Babesia vs malaria

Babesiosis and malaria are caused by different parasites, but they can produce similar symptoms and may look alike on a peripheral blood smear. Both organisms infect red blood cells and can lead to fever, chills, fatigue, anemia, and thrombocytopenia.

Malaria is caused by Plasmodium parasites transmitted through the bite of an infected mosquito. Babesiosis is most often caused in the United States by Babesia microti, a parasite transmitted by the same Ixodes ticks that can transmit Lyme disease and other tick-borne coinfections.

A Maltese cross formation within red blood cells is strongly suggestive of Babesia. However, this finding is not always present, and early Babesia ring forms may resemble Plasmodium species on a peripheral blood smear. Travel history, possible tick exposure, malaria testing, polymerase chain reaction testing, and careful examination of the blood smear can all help distinguish babesiosis from malaria.

Babesia treatment of the first woman

The first patient was a 50-year-old woman who was admitted to a hospital in South Korea with fever, abdominal pain, and nausea.

Four weeks earlier, she had visited a forest in New Jersey. She noticed a reddish skin lesion on her right upper calf that was suspicious for a tick bite. Two days later, she developed headache, muscle soreness, fever, and chills.

If she had remained in the United States, clinicians familiar with tick-borne diseases might have considered Lyme disease and its coinfections. After she returned to South Korea, however, malaria was an important diagnostic consideration because malaria occurs in the northern provinces of the country.

Her blood smear appeared suspicious for Plasmodium, and imaging revealed an infarction of the spleen. Because Plasmodium causes malaria, she was initially treated with hydroxychloroquine for suspected malaria.

Subsequent blood tests did not confirm malaria.

The clinicians examined the blood smear again. Four organisms that initially resembled Plasmodium appeared to form a Maltese cross, a tetrad formation within a red blood cell that can be seen with Babesia.

Polymerase chain reaction testing was also positive for Babesia microti.

Babesia microti is a parasite transmitted primarily by the same blacklegged tick that transmits Lyme disease. The patient was started on treatment for babesiosis. Her fever and abdominal pain improved, and her abnormal laboratory findings began to resolve within one day of treatment.

[bctt tweet=”Two women developed babesiosis after traveling to the United States. Their infections were initially mistaken for malaria.” username=”DrDanielCameron”]

Babesia treatment of the second woman

The second patient was 72 years old. She was evaluated at the same hospital in South Korea with a low-grade fever.

She was moderately anemic, with a hemoglobin level of 10.8 g/dL, and had a low platelet count. Her C-reactive protein level and sedimentation rate were elevated, indicating inflammation.

Malaria-like organisms were identified on her blood smear, but her malaria antigen test was negative.

When the clinicians reviewed the blood smear again, they identified Maltese cross forms within the red blood cells similar to those seen in the first patient.

The patient was initially treated with atovaquone/proguanil and azithromycin.

Her medical condition continued to worsen. She developed a higher fever and pulmonary congestion.

Her treatment was changed to quinine and clindamycin, a combination historically used for severe babesiosis. Quinine and clindamycin can cause more adverse effects than atovaquone-based regimens and may be difficult for some patients to tolerate.

She also underwent a red blood cell exchange transfusion. During this procedure, infected red blood cells are removed and replaced with healthy donor red blood cells. Exchange transfusion may be considered in selected patients with severe babesiosis, particularly in those with a high parasite burden or serious organ dysfunction.

Despite these interventions, her condition worsened, and she required intubation because of respiratory failure.

Doctors added doxycycline because they were concerned about possible coinfection with Lyme disease or anaplasmosis.

Serologic testing later supported concurrent Lyme disease, with both IgM and IgG Western blot results reported as positive.

The patient died 31 days after being admitted to the hospital despite treatment for babesiosis and possible tick-borne coinfections.

At the time of the report, only eight cases of babesiosis had been reported in South Korea, seven of which were imported from other countries, according to Kwon and colleagues.¹

Why Babesia is mistaken for malaria

These cases illustrate why clinicians should ask patients with fever, anemia, low platelet counts, or parasites seen on a blood smear about recent travel and possible tick exposure. A patient who becomes ill after returning from an area where babesiosis is endemic may be evaluated initially for infections that are more familiar in the patient’s home country.

That approach is understandable, but it can delay recognition of an imported tick-borne illness. Babesiosis should remain in the differential diagnosis when an apparent malaria infection is not confirmed or does not respond as expected to malaria treatment.

Kwon and colleagues cautioned that as international travel increases, physicians and travelers should become familiar not only with diseases endemic to their own regions but also with infections found at their travel destinations.¹

What can we learn from these cases?

1. Babesiosis can resemble malaria clinically and on a peripheral blood smear.
2. Early Babesia ring forms may be mistaken for Plasmodium.
3. A Maltese cross formation favors Babesia, although it is not always present.
4. Babesiosis symptoms may begin days or weeks after a tick exposure.
5. A negative malaria evaluation should prompt consideration of other infections when parasites are seen in red blood cells.
6. Travel history and possible tick exposure can provide essential diagnostic clues.
7. Patients with babesiosis may also have Lyme disease or another tick-borne coinfection.

What questions do these cases raise?

1. How can clinicians promptly distinguish Babesia from malaria in regions where malaria is more familiar?
2. Could earlier recognition of babesiosis and Lyme disease have changed the outcome for the second patient?
3. When should severe babesiosis prompt consideration of exchange transfusion or intensive care?

Frequently Asked Questions

What is the difference between Babesia and malaria?

Babesiosis is caused by Babesia parasites and is usually transmitted by ticks. Malaria is caused by Plasmodium parasites and is transmitted by mosquitoes. Both can infect red blood cells and cause fever, anemia, and other similar symptoms, but their treatments differ.

Can Babesia be mistaken for malaria?

Yes. Babesia and Plasmodium can both appear as ring-like organisms inside red blood cells. Clinical history, malaria antigen testing, polymerase chain reaction testing, and careful review of the blood smear can help distinguish them.

Can Babesia and malaria look the same on a blood smear?

Yes. Early Babesia ring forms can closely resemble Plasmodium species on a peripheral blood smear. Identifying a Maltese cross formation, reviewing the patient’s travel and tick exposure history, and using confirmatory laboratory testing can help establish the correct diagnosis.

What is a Maltese cross on a blood smear?

A Maltese cross is a formation of four Babesia organisms arranged as a tetrad within a red blood cell. It is considered a characteristic finding of babesiosis, although it is not seen in every case.

Is Babesia transmitted by mosquitoes?

Babesia is usually transmitted through the bite of an infected Ixodes tick. It can also rarely be transmitted through contaminated blood products, organ transplantation, or from a pregnant mother to her baby. Malaria, in contrast, is generally transmitted by infected mosquitoes.

Can someone have Babesia and Lyme disease at the same time?

Yes. The same blacklegged tick can transmit Babesia microti and Borrelia burgdorferi, the bacterium responsible for Lyme disease. Coinfection may complicate the clinical presentation and should be considered when symptoms are severe, persistent, or atypical.

Clinical Takeaway

Babesiosis should be considered when a patient has fever, anemia, low platelet counts, and parasites within red blood cells—particularly after travel to a region where Babesia-infected ticks are present.

Distinguishing Babesia from malaria may require more than an initial blood-smear interpretation. Exposure history, repeated smear examination, malaria testing, and Babesia PCR testing can all contribute to the diagnosis.

Early recognition matters because babesiosis and malaria require different treatment approaches, and severe babesiosis can progress rapidly.

Related Articles

Learn more about Babesia, Lyme disease coinfections, and related diagnostic challenges:

Babesia treatment
Lyme disease misdiagnosis
Persistent Lyme disease

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Dr. Daniel Cameron, MD, MPH
Lyme disease clinician with over 30 years of experience and past president of ILADS.

Symptoms • Testing • Coinfections • Recovery • Pediatric • Prevention