A summer vacation came to a sudden, dramatic end when a 52-year-old woman had a witnessed seizure at a social event. The patient, who had spent the previous 4 days visiting Martha’s Vineyard, an island off the coast of Massachusetts, was brought by ambulance to a community hospital. Over the course of the previous week, she had complained of worsening malaise, headaches, anorexia, and intermittent fevers. She had no significant medical history, and she did not take any medications. She was a regular smoker and drank alcohol socially, but she did not use recreational drugs.
The patient’s usual place of residence was a large urban center in Western Europe. Yet, for the past 18 months, she had been working for an international development organization in South Sudan. She left that country approximately 1 month before her presentation. While in South Sudan, she had not taken malaria prophylaxis. She reported having regular access to prepared food and clean water. Since arriving in the United States, she had spent time outdoors but had not noticed any insect bites.
Assessment
At the community hospital, the patient was disoriented and appeared ill. Her clothing was soaked with urine. She was febrile to 101.1°F (38.4°C) and tachycardic. Initial laboratory values were significant for thrombocytopenia, profound hyponatremia, acute kidney injury, elevated transaminase levels, hyperbilirubinemia, and anemia. Computed tomography of her head and a plain film of her chest produced unremarkable results. A thick smear of her peripheral blood was notable for intraerythrocytic parasites. She was treated empirically with atovaquone, doxycycline, and clindamycin for tick-borne infections endemic to Eastern Massachusetts, while a quinidine gluconate infusion was initiated for malaria. Hypertonic saline was also administered to correct her hyponatremia.
On arrival to this hospital, the patient was afebrile but had developed hypotension with a blood pressure of 80/48 mm Hg. She was diaphoretic, photophobic, somnolent, and ill-appearing. Her skin was diffusely jaundiced, and conjunctival icterus was present. Thin and thick blood smears showed Plasmodium falciparum parasites with an estimated parasite density of 50%.
Diagnosis
Although endemic malaria was eliminated from the United States more than 50 years ago, the annual number of imported cases continues to climb. In 2011, the Centers for Disease Control and Prevention (CDC) reported 1920 imported cases of malaria among people in the United States—the most since 1971. The parasites P. falciparum(64%) and Plasmodium vivax (28%) accounted for the majority of these infections, with the largest proportion occurring among travelers to Africa (69%); travelers to Asia (22%) and the Americas (8%) accounted for almost all remaining cases.
To avoid unnecessary treatment delays, clinicians must maintain a high index of suspicion when evaluating a febrile patient with a history of travel to an area endemic for malaria. The risk for infection varies according to the region visited. Our patient spent 18 months working for an international development organization in South Sudan, a country with one of the highest malaria burdens in Sub-Saharan Africa.
A large, retrospective review of more than 30,000 returning travelers found that fever or a history of fever significantly increased the likelihood of a malaria diagnosis (likelihood ratio [LR] 5.1; 95% confidence interval [CI] 4.9-5.3), whereas an absence of fever made malaria less likely (LR 0.12; 95% CI 0.10-0.15). Some physical examination findings, such as the presence of splenomegaly, jaundice, or pallor, increased the probability of malaria, but the absence of these findings only marginally decreased the odds of malaria. The most predictive laboratory results seem to be hyperbilirubinemia (LR 7.3; 95% CI 5.5-9.6) and thrombocytopenia (LR 5.6; 95% CI 4.1-7.5).
At presentation, our patient was postictal, febrile, and jaundiced. Her initial laboratory results were remarkable for hyponatremia, acute kidney injury, hyperbilirubinemia, and severe thrombocytopenia. Together with her travel history and lack of chemoprophylaxis, her symptoms, examination findings, and laboratory results placed malaria high on the differential diagnosis.
The clinical picture and travel history, however, were also concerning for human babesiosis. Our patient had vacationed in a highly endemic area of Massachusetts, with potential exposures to the primary vector, Ixodes scapularis, also known as the deer tick. In the New England states, parts of New York, and the upper Midwestern states, Babesia microti is an increasingly recognized pathogen, causing a broad range of syndromes, from subclinical infection with nonspecific symptoms to severe and even fatal illness with features such as acute respiratory distress syndrome, disseminated intravascular coagulation, and acute kidney injury. Risk factors for severe disease include asplenia, immunosuppression, cancer, and hemoglobinopathy. Lower on the differential diagnosis, but still possible, was co-infection with another endemic tick-borne infection, such as anaplasmosis or Lyme disease.
In this case, our patient was assumed to be immunocompetent. Thus, her high burden of parasitemia would argue against a B. microti mono-infection. We did consider that our patient could be co-infected with both malaria andB. microti, so careful examination of her smears was required. Differentiating between malaria and Babesiainfection on a thin smear, however, can be challenging. B. microti trophozoites are pleomorphic round, oval, or pear-shaped ring forms that can be found in both intra- or extra-erythrocytic forms. Immediately before the lysis of erythrocytes, merozoite tetrads may be visible under the microscope, though they are rarely seen. When these cross-shaped arrangements resembling the Maltese cross are found, they are a pathognomonic finding. By comparison, the P. falciparum species have no extracellular forms, and pathognomonic findings for P. falciparum include banana-shaped gametocytes.
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-Ross Boyce, MD, MSc, Julian Mitton, MD, Jacqueline Chu, MD, Kathleen Finn, MD, MPhil
This article originally appeared in the February 2016 issue of The American Journal of Medicine.
