Case Presentation: A 58-year-old Nigerian American man with a history of pancreatic neuroendocrine tumor with metastases to the liver and spleen, developed large volume hematemesis while traveling in Nigeria, requiring stabilization at a local hospital. He received 13 units of blood and an upper endoscopy revealed gastric varices. Two weeks later, he presented to our academic medical center for further management. Imaging showed a pancreatic mass invading the spleen resulting in splenomegaly and splenic varices. He underwent particle embolization of splenic masses by Interventional Radiology (IR) in efforts to relieve the pressure in the varices. Despite this initial approach, splenic embolization was ultimately required, followed by coiling and gluing of the gastric varices via upper endoscopy. Following the first IR procedure, he developed fevers. Considering his recent travel, a broad workup was sent including testing for malaria, chikungunya, dengue fever and Zika virus, and was unrevealing. Fevers were thought to be related to post-embolization syndrome and eventually resolved, but then returned with associated myalgias after receiving post-splenectomy vaccines. Repeat infectious workup was unremarkable and it was suspected that post-embolization syndrome and recent vaccines were the sources of his ongoing fevers. However, he continued to have sporadic high-grade fevers and was started on empiric antibiotics. Due to continued intermittent fevers, rapid malaria antigen and blood parasites were repeated and returned positive for Plasmodium falciparum. Parasitemia percentage was less than one. He had no evidence of any systemic manifestations. He was treated with artemether-lumefantrine (coartem) with resolution of his fevers.
Discussion: Malaria should be suspected in the setting of fever and related epidemiologic exposure. The incubation period for P. falciparum infection can range from 7 to 30 days but is typically 12 to 14 days. The clinical features of malaria are nonspecific and overlap with those of other febrile illnesses. Malaria is characterized by paroxysms of fever, as seen in our case report. The fever is due to the release of inflammatory cytokines and the pattern of intermittent, short bursts, corresponds to the rupture of infected red blood cells, which is unique to each species of Plasmodium. The time between fever paroxysms for other Plasmodium species are 24, 48, or 72 hours, whereas for P. falciparum, the time between can be variable. The CDC recommends blood smears in nonimmune individuals be repeated every 12 to 24 hours for three evaluations before ruling out malaria. In our case report, initial malaria rapid antigen and blood smear were negative and may be explained by early infection and low parasitemia at the time of testing. Cognitive limitations and biases played a role in our case. Our case highlights the importance of re-visiting diagnoses that were once thought to be ruled out and identifying when repeat testing is appropriate. Lastly, it is critical to continuously re-frame clinical information. Our patient had a long, complex hospital stay complicated by many factors, and by simplifying the clinical case back to reflecting on the differential for fever in a returning traveler, helped our team achieve the correct diagnosis.
Conclusions: When caring for a patient who continues to fever after traveling to an endemic region, it is essential to keep the differential broad, as some diagnoses such as malaria may require re-testing to reveal the correct diagnosis.