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INTRODUCTION

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Malaria, a protozoan disease transmitted by the bite of the Anopheles mosquito, is caused by the genus Plasmodium. Five species of the protozoan Plasmodium infect humans: P. falciparum, P. vivax, P. ovale, P. malariae, and P. knowlesi. Consider malaria in patients who have recently traveled to endemic areas and present with an unexplained febrile illness.

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Malaria transmission occurs in large areas of Central and South America, the Caribbean, sub-Saharan Africa, the Indian subcontinent, Southeast Asia, the Middle East, and Oceania (e.g., New Guinea, Solomon Islands). More than 50% of malaria cases in the United States, including most cases due to P. falciparum, arise from travel to sub-Saharan Africa. Resistance of P. falciparum to chloroquine and other drugs continues to spread and strains of P. vivax with chloroquine resistance have also been identified.

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CLINICAL FEATURES

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Plasmodial sporozoites first infect the liver, where asexual reproduction occurs in the exoerythrocytic stage. During this initial incubation stage, which usually lasts 1 to 4 weeks, patients are often asymptomatic. Partial chemoprophylaxis or incomplete immunity can prolong the incubation period to months or even years. The clinical signs of malaria first appear during the erythrocytic stage, which occurs when hepatocyte rupture releases merozoites to invade erythrocytes. In P. vivax and P. ovale infection, a portion of the intrahepatic forms are not released, but remain dormant as hypnozoites, which can reactivate a malaria infection after months or years.

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Early symptoms of malaria are nonspecific, including fever, chills, malaise, myalgias, and headache. Chest pain, cough, abdominal pain, or arthralgias may also be seen. Patients then develop a high fever, followed by diaphoresis and exhaustion when fever abates. Classically, cycles of fever and chills followed by profuse diaphoresis and exhaustion occur at regular intervals, reflecting the ongoing and intermittent hemolysis of infected erythrocytes.

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Physical examination findings are nonspecific. During a febrile paroxysm, most patients appear acutely ill, with high fever, tachycardia, and tachypnea. Splenomegaly and abdominal tenderness are common. In P. falciparum infections, hepatomegaly, edema, and scleral icterus often occur.

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Infections caused by any species of Plasmodium can result in hemolysis with anemia, splenic enlargement, and potential splenic rupture. Severe or complicated malaria infections may also occur, and are usually due to P. falciparum. Prostration, severe anemia, acidosis, hypoglycemia, acute renal failure, acute respiratory distress syndrome, pulmonary edema, jaundice, shock, and disseminated intravascular coagulation may occur in severe infections. Cerebral malaria is characterized by somnolence, coma, delirium, and seizures. In 2011, 22% of malaria cases imported to the United States were classified as severe. Blackwater fever is a severe complication seen almost exclusively in P. falciparum infections, with massive intravascular hemolysis, jaundice, hemoglobinuria, and acute renal failure.

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DIAGNOSIS AND DIFFERENTIAL

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The diagnosis of malaria relies on a history of potential exposure in an endemic area, along ...

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