Malaria is a parasitic infection of red blood cells by Plasmodium species. The route of infection is via the bite of an infected female Anopheles mosquito. Less commonly, malaria may be transmitted via transfusion of blood products or by vertical transmission. In the United States, physicians encounter malaria as one of the most common causes of acute febrile illness in travelers returning from endemic areas, especially sub-Saharan Africa and South Asia. In addition, cases of malaria in the United States have increasingly been found in refugees relocating from sub-Saharan Africa to the United States.

Approximately 1500 cases of malaria are reported in the United States each year. Most are diagnosed in travelers returning from malaria-endemic regions (from high to low risk: West Africa, Oceania, other parts of Africa, South Asia, South America, Central America, and other parts of Asia).

Nine locally acquired cases of malaria were reported in the United States during summer 2023 in Florida (7 cases of Plasmodium vivax), Texas (1 case of Plasmodium vivax), and Maryland (1 case of Plasmodium falciparum in a resident of the National Capitol Region). These were the first locally acquired mosquito-borne cases in the United States in 20 years. The Florida cases lived within close geographic proximity, but there is no evidence to suggest that any of the cases are related.

Five Plasmodium species are responsible for human disease: P falciparum, P vivax, Plasmodium ovale, Plasmodium malariae, and Plasmodium knowlesi. Geographic distribution of each species is different. Plasmodium falciparum is more likely to be identified as a cause of malaria in travelers returning from Africa, and P vivax is more likely to be identified as a cause of malaria in travelers returning from Asia, Central America and the Caribbean, or South America. Plasmodium knowlesi is a simian malaria species that has increasingly been recognized as the cause of human infection in Malaysian Borneo and surrounding countries. Coinfection with more than one species of malaria can occur in regions where multiple Plasmodium species are present.

The typical incubation period is 7-30 days, with shorter periods commonly from P falciparum infection and longer periods from P malariae infection. Eighty percent of malaria cases present with symptoms within 30 days after return from travel (90% of cases with P falciparum but only 54% of cases with P vivax). Different antimalarial drugs taken prophylactically by travelers must be continued for variable durations after travel (7 days post travel for atovaquone / proguanil, 4 weeks post travel for chloroquine, 4 weeks post travel for doxycycline, and 4 weeks post travel for mefloquine) and can delay the appearance of symptoms but not avoid the development of infection if not taken appropriately.

Malaria disease can be categorized as uncomplicated or severe.

Symptoms of uncomplicated malaria are nonspecific and include fever, headache, back pain, chills, sweating, myalgia, nausea, vomiting, diarrhea, malaise, and cough. On physical examination, patients may have an enlarged spleen or liver, mild jaundice, and an increased respiratory rate. Differentiating malaria from other infectious and noninfectious diseases is difficult based on clinical symptoms alone.

The fever may become paroxysmal, preceded by rigors for 1-2 hours and followed by an intense diaphoresis. Periodic febrile episodes may be seen with P vivax or P ovale, with a febrile episode every 48 hours (tertian fever), or with P malariae, with a febrile episode every 72 hours (quartan fever).

Patients with severe or complicated malaria, which has very high mortality, may present with prostration, coma, respiratory distress (acidotic breathing), severe anemia, hemoglobinuria, renal failure, acute respiratory distress syndrome (ARDS), pulmonary edema, hypoglycemia, shock, disseminated intravascular coagulation (DIC), bleeding, low blood pressure, and/or convulsions. In cerebral malaria, abnormal behavior, altered states of consciousness, seizures, and/or cerebral edema are reported. Severe malaria is a medical emergency and should be treated urgently.

Relapsing malaria may occur with P vivax and P ovale, both of which have a dormant hypnozoite liver stage as part of the life cycle. Relapses can occur months or even years after infection.

Species identification is important because uncomplicated malaria with P falciparum can rapidly develop into severe infection, although any species can cause severe disease. Physicians cannot rely on symptoms and signs to diagnose malaria or to specify the infecting species.

Malaria, mainly due to P falciparum, has been associated with increased susceptibility and severity among pregnant individuals. This increases the risk of premature delivery. In congenital malaria, which is rare, infected mothers transmit parasites to their child before or during delivery.

Malaria should be included in the differential diagnosis of every patient with acute febrile illness and travel history to endemic areas.