Case Presentation: A 44-year-old woman presented with five days of intermittent fevers and headaches. Her medical history included hypothyroidism, uterine fibroids, and migraines. The patient lives in East Africa and had traveled to Europe for work within the past month. Three days after flying to NYC, she began to experience subjective daily fevers in the early morning and evening accompanied by frontal, throbbing headaches more severe than past migraines but without photophobia or aura. Upon arrival to the ED, the patient was tachycardic to the 130s, tachypneic, and febrile to 39.4°C. Blood testing was notable for normocytic anemia with Hgb 12, LDH 500, haptoglobin 3, direct bilirubin 4, indirect bilirubin 2.5, and lactate 4.2. Bilateral pleural effusions were noted on her chest X-ray.The patient’s blood parasite panel was positive for malarial antigen; she was initiated on oral artemether-lumefantrine as well as vancomycin and piperacillin-tazobactam for bacterial coverage. Initial blood smear revealed a parasite level of 0.3% (Figure 1) and P. falciparum was identified as the causative organism. Given the low level parasitemia, strong consideration was given towards bacterial co-infection or pulmonary embolism. CTPE was negative for pulmonary embolism. Her symptoms worsened and she became dyspneic, requiring oxygen via nasal cannula for O2 saturations in the low 90s. A second blood smear performed 12 hours after the first revealed a parasite level of 35% (Figure 2). IV artesunate therapy (3 doses each separated by 12 hours) was initiated given the severity of her infection. Subsequently, laboratory markers of hemolysis resolved, and her symptoms improved. Peripheral smear obtained after the final dose of artesunate revealed a parasitemia level of less than 0.1%. She was discharged on oral artemether-lumefantrine with follow-up with infectious disease clinic.
Discussion: P. falciparum malaria is a life-threatening disease with 1500-2000 cases per year in the US. In countries where malaria is not endemic, cases are commonly misdiagnosed as intracranial or systemic viral or bacterial infections (1). Parasitemia level is a measure of peripheral circulating ring-form-infected erythrocytes and can fluctuate widely (2). There may be significant differences between the number of infected cells in circulation and the number of erythrocytes sequestered, depending on the stage of development of the parasite as well as its multiplication rate (3). Patients are commonly infected by multiple mosquitos and therefore have asynchronous subpopulations of parasites (4). The patient’s initially low parasite level of 0.3% led to higher suspicion for bacterial co-infection; in reality, her cyclic fevers, noncardiogenic pulmonary edema, transaminitis, and hemolytic anemia were sequelae of severe parasitemia and wide-spread inflammation. Per the CDC, malaria can only be ruled out if three sets of blood smears repeated 12-24 hours apart reveal an undetectable parasitemia level, guidance driven by fluctuating levels of active parasites in the bloodstream throughout the lifecycle of P. falciparum (5).
Conclusions: Severe plasmodium falciparum malaria infection is a rare clinical entity in the United States. Clinicians need to be aware of the presentation, severity, and treatment of the disease. Three negative blood smears must be obtained before malaria can be ruled out, which is important given the fluctuating levels of parasitemia due to the lifecycle of P. falciparum.
