Are Various Babesia Species a Missed Cause for Hypereosinophilia? A Follow-up on the First Reported Case of Imatinib Mesylate for Idiopathic Hypereosinophilia

James L. Schaller, MD, MAR; Glenn A. Burkland, DMD; PJ Langhoff


February 27, 2007



After 6 years we decided to follow up on this patient's treatment. We interviewed the patient, his son, aunt, and 2 consulting physicians and also reviewed relevant sample laboratory results to determine whether his HES had returned and whether his residual morbidity while on imatinib had changed.


After the patient was weaned off imatinib approximately 5 years ago, he had serial complete blood counts (CBCs), every 2-4 weeks for a year, due to a serious concern over a relapse. Eosinophils remained in the low-normal range, and ECP never surpassed the high-normal range.

Off imatinib, the patient was able to work a 50-hour week successfully, but did have ongoing medical and neuropsychiatric symptoms that began with the onset of his HES. The most significant was an intractable headache, paresthesia of the calves and feet, mild fatigue (requiring 9 hours of sleep per night), mild irritability, mild cognitive rigidity, a mild decrease in interpersonal relational skills, mild depression, and middle-age onset of an obsessive personality disorder, according to a board-certified psychiatrist and neuropsychologist.

Although imatinib caused some transient relief from his severe headache, the benefit was lost and 2-week trials of 150 mg, 200 mg, 250 mg, and 300 mg did not regain any relief. The patient failed to receive headache relief despite full and complete trials with all major prophylactic and abortive medications over 12 years by 8 different neurologists. In 2006, a research-oriented, board-certified neurologist felt that the patient had failed all available headache medications. Other treatments for his remaining morbidities (eg, antidepressants from 5 medication classes and many mood stabilizers) had no clear benefit.

In late 2006, the patient's son was slowly unable to function in school due to profound fatigue. Evaluations by specialists in endocrinology, infectious disease, oncology, and pediatric psychiatry yielded no clear diagnosis. Then the child was tested for Babesia by the family pediatrician after she read that Ixodes ticks can carry these protozoa. The family requested broad laboratory testing, and the results included a positive PCR for B microti. The pediatrician chose to ignore the negative IgG and IgM B microti titers and began an unspecified treatment for 3 weeks for presumed babesiosis infection; there was no clear benefit. The child is pursuing other medical consultations and is receiving home instruction due to ongoing profound fatigue and occasional sweats.

Also in late 2006, an aunt living in the same household began experiencing "signs of menopause" which she described as "waves of warmth, chills, and sweats." Her gynecologist, however, was not convinced on the basis of a menses history and laboratory results, and referred her back to her internist who thought her symptoms could just as easily be fever, chills, and sweats related to an infection. Her temperature was 99.0-99.8 °F during 2 weeks of daily afternoon checks. The aunt's internist heard about the patient's son and ordered B microti IgG, IgM, PCR, and sedimentation rate tests as well as manual CBC. After all returned negative, a relative who worked in pathology asked for the manual differential to be repeated. He called and discussed his limited experience and recent reading on Babesia with the pathologist, including the need for red blood cell (RBC) examination to be done at a power 1000x with oil, with instructions to look for specific Babesia intracellular RBC inclusions. The full recommendations to increase the capacity of the manual RBC examination are unavailable. Surprisingly, the repeat manual yielded a positive finding of a Babesia-like infectious agent in the woman's RBCs.

In this context, the same testing was run on our recovered HES patient, but no Babesia was found.

Over the following weeks, this academically advanced and motivated family began to discuss their experience with neighbors and others in their small community, an area characterized as having a very high deer population and also a presumed high Ixodes tick concentration. Some individuals reported having various Ixodes infections, including babesiosis. At this time, the aunt found an article on the WA-1 strain of Babesia on PubMed; it described 5 patients in a West Coast neighborhood as infected with a form never tested for in our HES recovered patient.[17]

The patient with HES in remission was then also tested for WA-1, newly named Babesia duncani,[3] which yielded negative results on IgM, IgG, and PCR.

Our HES patient decided that Babesia should still be considered in his case. He did gardening and nature walking as hobbies, and believed that he was at higher risk than anyone in his household for Ixodes tick attachments. He reasoned with his doctors that his son had a positive PCR, had less outdoor contact than him, and that a repeated manual CBC only caught the aunt's Babesia after special communication with the pathologist.

Two consultants agreed on a 4-week babesiosis treatment trial to determine whether the patient's headache and other morbidity improved. He was placed on atovaquone (Mepron) 750 mg twice daily with fatty food to enhance absorption, and azithromycin (Zithromax) 250 mg 3 times daily. Babesiosis treatments may also be used to treat malaria; this makes some sense because Babesia and malaria are partially similar-appearing intracellular RBC parasites. The patient also treated himself with a derivative of Artemisia annua, a Chinese herb considered by the World Health Organization and the United Nations Children's Fund to be the first-line treatment for malaria if combined with a standard synthetic antimalarial agent.[18,19,20,21,22,23,24,25]

The patient has begun to improve with these treatments and therefore they are being extended a month. Specifically, the paresthesias of the calves and feet have markedly decreased and his fatigue has improved. His sleep has decreased from 9 hours a night to 7.5-8 hours a night. His mood has significantly improved and his cognitive rigidity, relational skills, and obsessive personality problems have improved approximately 75%. His ECP has gone from high-normal to low-normal levels. He has experienced a 50% overall improvement in his headache pain. He is not at baseline, but his mu agonist/antagonist pain treatment, a buprenorphine/naloxone combination (Suboxone) which was the only treatment besides oxycodone to relieve his pain, was able to be reduced from 2 mg every 8 hours to a mere 1 mg per day. (Buprenorphine for pain is typically dosed at 3-4 times daily and rarely relieves pain at this low dose.)[26]

Currently, his physicians believe that his HES might have been due to an undiagnosed infectious agent, ie, Babesia. They feel that his residual morbidity is responding to babesiosis and malaria medications. Because the patient had been a gardener and nature walker for years before his HES, they believe that it is possible that he had Ixodes exposures via his brush- and woods-lined home and while hiking. Various family members, pets, and neighbors have had clear Ixodes tick attachments with rare highly variable rashes. The patient is not sure whether a few scalp "bumps" when grooming his hair were tick attachments.


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