Cerebral Malaria: Symptoms and Treatment

Cerebral malaria comprises the clinical reflections of plasmodium falciparum malaria which causes mutations in mental status and sometimes, coma. It is the infection caused by plasmodium falciparum, a protozoan parasite that causes malaria in humans. It is an intense disease of the brain, causing ring-like lesions in the brain, accompanied by fever. The histopathological trademark of this brain disorder is the segregation of cerebral capillaries and venules with parasitized red blood cells (PRBCs) and non-parasitized red blood cells (NPRBCs). The patient should be treated as early as possible, as cerebral malaria gets fatal within 24-72 hours. It is characterized with retinal whitening, which helps in distinguishing it from other causes of fever. Its risk factors primarily include children below 10 years of age; especially living in malaria-endemic areas.

Symptoms
Cerebral malaria is the most serious and life-threatening form of malaria, caused by plasmodium falciparum. This species causes chills, persistent high fever, headache, orthostatic hypotension, myalgia and red blood cell (RBC) sludging that leads to capillary blockage at several sites. The three initial stages are:

• Cold Stage: It ranges from chills to extreme shaking for 1-2 hours
• Hot Stage: It is characterized by a high fever up to 107°F (41.7°C) for 3-4 hours
• Wet Stage: It is characterized by profuse sweating for 2-4 hours

There are three primary symptoms of cerebral malaria which are common in both adults and children: impaired consciousness with non-specific fever, generalized convulsions and neurological abnormalities, and coma that lasts for 24-72 hours, initially rousable and then unrousable. If not treated on time, it can lead to complications like jaundice, hemoglobinuria, a tender and enlarged spleen, acute renal failure, and uremia, and is fatal in about 20% of patients. Further, it will manifest with signs of increased intracranial pressure, hemiplegia, encephalopathy, delirium, seizures and coma.

Treatment
Since cerebral malaria gets fatal within a few days of infection, immediate treatment is necessary. The natural immunity to this disease is not very clear but it can be artificially controlled by preventive strategies like antimalarial chemotherapy and adjunctive measures.

• Chemotherapy for cerebral malaria mainly involves the use of quinine (a bitter alkaloid extracted from chinchona bark), for a patient having chloroquine resistance. It is the only drug which has remained highly effective over a long period of time for treating this disease. Quinine functions similar to chloroquine and interferes with the parasite's enzymatic digestion.
• Artemisinin, a clinically proven drug, is known to cure fever and parasitemia faster than chloroquine or quinine. Commonly used by the Chinese as a traditional treatment for fever and malaria, it is a sesquiterpene lactone isolated from the plant Artemisia annua. It is commonly used as artesunate and artemether, and is an important factor in the treatment of multi-drug resistant falciparum malaria. It is cheap and effective, but not yet licensed for use in Europe, North America and Australia.

The use and efficacy of adjunctive measures are debatable. Some of the measures are as follows:

1. Antipyretics such as paracetamol helps in reducing fever. But, how this diminution in the core temperature benefits the cerebral consequences is not yet clear.
2. Microcirculatory flow such as pentoxifylline reduces the red cell deformation and blood viscosity. It impairs platelet aggregation and minimizes the systemic vascular resistance, and hence improves the microcirculatory flow.
3. Anticonvulsants such as phenobarbital sodium is used for seizures. It is necessary to control seizures, as they cause neuronal damage and are linked with fatal outcomes.
4. Desferrioxamine is an iron chelating adjuvant agent with antimalarial properties. It minimizes the formation of reactive oxygen species by decreasing the amount of free iron.

Cerebral malaria is a severe disease and fatal in many cases. According to the World Health Organization (WHO), it affects nearly 300-500 million people every year, causing over one million deaths, hence having a very high mortality ratio compared to other forms of malaria.