Ravindra Kumar Garg MD (Dr. Garg of King George's Medical University in Lucknow, India, has no relevant financial relationships to disclose.)
John E Greenlee MD, editor. (

Dr. Greenlee of the University of Utah School of Medicine has no relevant financial relationships to disclose.

Originally released December 29, 1994; last updated April 17, 2019; expires April 17, 2022

This article includes discussion of malaria, paludism, symmetric encephalopathy, algid malaria, cerebral malaria, congenital malaria, malaria in pregnancy, malarial retinopathy, postmalarial neurologic syndrome, severe malaria, and uncomplicated malaria. The foregoing terms may include synonyms, similar disorders, variations in usage, and abbreviations.


Malaria is among the leading causes of morbidity and mortality in a large part of the world. Severe and complicated malaria is caused by Plasmodium falciparum. Severe malaria is characterized by a set of clinical and laboratory parameters that are associated with an increased risk of death. Severe malaria is particularly common in travelers from nonendemic areas. Pregnant women are also prone to severe malaria because of decreased immunity. Age is an independent risk factor for a fatal outcome of malaria; older patients may have a bad prognosis. The influence of host genetics on susceptibility to Plasmodium falciparum malaria has been suggested. According to World Health Organization recommendations, universal diagnostic testing of malaria should be a mandatory step in the management of malaria. Artemisinin-based combination therapies are the recommended treatments for uncomplicated Plasmodium falciparum malaria. Cerebral malaria is one of the most life-threatening complications of malaria. Sequestration of Plasmodium falciparum-infected red blood cells into the cerebral capillaries and venules is central to the pathogenesis of cerebral malaria. Most patients with cerebral malaria are already in deep coma by the time they reach the hospital. Several other factors such as seizures, acidosis, or hypoglycemia also contribute to unconsciousness. Malarial retinopathy consists of a set of retinal abnormalities that are unique to severe malaria and common in children with cerebral malaria. Histopathologically, retinal hemorrhages in cerebral malaria are similar to ring hemorrhages seen in the brain parenchyma. Diagnosis of cerebral malaria must be confirmed rapidly. An investigation noted that lumbar puncture is safe, even in children with signs of raised intracranial pressure. Lumbar puncture is needed to detect other CNS infections. The treatment of choice for severe or complicated malaria in adults and children is intravenous artesunate. Intravenous quinine should be started if artesunate is not available. Patients treated with intravenous quinine should be monitored for hypoglycemia. The usefulness of adjunct therapy, like mannitol and corticosteroids, is controversial. Half of pediatric survivors of cerebral malaria remain neurodevelopmentally impaired. Prompt treatment with artemisinin-based therapies, use of insecticide-treated mosquito nets, and indoor residual spraying with insecticide help in reducing the malaria burden in many countries. Primaquine is a potent gametocidal agent – a single dose can reduce the transmissibility of Plasmodium falciparum infection. The author provides information on epidemiology, clinical features, differential diagnosis, and management of malaria and its most dreaded complication, cerebral malaria.

Key points


• Severe and complicated malaria is caused by Plasmodium falciparum.


• Cerebral malaria is the most severe neurologic complication of Plasmodium falciparum malaria.


• Severe malaria is a medical emergency, so patients should be immediately started with readily available full doses of parenteral antimalarial treatment.


• Prompt parasitological confirmation is recommended in all patients suspected of malaria before treatment is started.


• The best available treatment, particularly for P falciparum malaria, is artemisinin-based combination therapy.


• Supportive treatment in patients with severe falciparum malaria is also equally important.


• Mortality in untreated severe falciparum malaria is almost 100%.

Historical note and terminology

Malaria or a disease resembling malaria has been noted for more than 4000 years. In China and the Indian subcontinent, malaria was known long before the beginning of the Christian era. The word "malaria" is derived from “mal aria,” which means "bad air" in Italian. On the route to India, Alexander the Great is said to have died of malaria. The disease is also called "paludism" (“palus” in Latin means "marsh"). Both names suggest that malaria is associated with air and marsh waters. In 1880, Alphonse Laveran was the first to notice parasites in the blood of a patient suffering from malaria in Algeria (Guillemin 2002). In 1897, Ronald Ross, a British officer in the Indian Medical Service, was the first to demonstrate that malaria parasites could be transmitted from infected patients to mosquitoes. He demonstrated the oocyst of malarial parasite in the gut wall of a mosquito (Guillemin 2002; Capanna 2006). Italian scientist Giovanni Batista Grassi, in 1898, proved that malaria was transmitted by Anopheles to a human (Guillemin 2002; Capanna 2006). In 1820, 2 French scientists, Joseph B Caventou and Pierre J Pelletier, isolated quinine from the bark of the cinchona tree (Paidhungat 2001). In 1892, the Italian scientists Marchiafava and Bignami proposed that the fundamental pathological process underlying lethal falciparum malaria was microvascular obstruction (White et al 2013). Artemisinin, or qinghaosu, was extracted from the traditional Chinese medical drug qinghao (the blue-green herb) in the early 1970s (Hsu 2006). Paul Hermann Müller was given the Nobel Prize in 1948 for his discovery of insecticidal properties of dichlorodiphenyltrichloroethane (DDT) as a contact poison against several arthropods (Rieckmann 2006). In 2002, the complete genome sequences of the parasite, Plasmodium falciparum, and the main insect vector, Anopheles gambiae, have been determined (Anonymous 2002).

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