Cerebral Malaria Caused by Immune Cells in the Brain

Highlights

• Study finds cerebral malaria like condition in mice caused due to aggregation of immune cells near blood vessels in the brain.
• This was found to lead to leakage of blood in the brain and consequent brain swelling.
• This study provides new insight into the pathogenesis in cerebral malaria and new targets for drug therapy.

Cerebral malaria is one of the most severe neurological manifestation associated with infection by Plasmodium falciparum. A new study has found that the swelling in the brain is due to cytotoxic T cells attacking blood vessels. Malaria is a disease of global significance

• 300 to 500 million people are affected annually
• 40% of the population of the world lives in an area that is endemic for malaria
• 1.5 to 2 million deaths occur every year due to malaria
• 2.4 million cases are reported from South Asia every year, out of which 75% are from India
• There have been an increase in P. falciparum infections in Central India in recent years

Cerebral malaria is one of the most severe complications of malaria. The infection leads to neurological complications as well as multi-organ failure. This condition is characterized by swelling in the brain and it leads to the death of 15 to 30% of people who contract it. The pathogenesis of this condition has never been fully understood, which led Dr. Phillip Swanson of the National Institute of Health to carry out a study on mice. In the study, the researchers examined the brain of mice that were infected by a parasite resulting in a similar condition.

To understand immune cell activity in the living mice and to determine the path of disease progression, the researchers used intravital microscopy. The study found that there was an aggregation of the cytotoxic T cells along the blood vessels in mice that were infected. These T-cells interacted with small parasite fragments that were presented by the blood vessels that led to leakage of blood from the blood vessels. The resultant swelling of the brain affected the neurons that were responsible for the functioning of the heart and the lungs.

Antibodies Against T Cells

The scientists injected antibodies against the T cells that were found to lead to the fatal swelling of the brain. The antibodies prevented the cytotoxic T cells from getting attached to the blood vessels. The antibody treatment proved that T-cells were responsible for mice with a condition similar to cerebral malaria.

Dr. Swanson, talking about the study said, "By watching immune cells function in the living brain during cerebral malaria, the investigators of this study revealed that parasite-specific CD8 T cells attack the wall of the cerebral blood vessels, causing excessive swelling and damage to a vital brain center. This fatal disorder can be prevented by therapeutically displacing the pathogenic T cells from the vessel wall."

Cerebral malaria is characterized by increased mortality and patients who survive are often neurologically impaired. The clinical condition of cerebral malaria is a state of coma and the presence of malarial cells in the peripheral blood. There is no other reason that can be ascertained to the coma including hypoglycemia (low blood glucose). The increase in drug resistance has resulted in increased mortality rates, which could be controlled by identifying new targets for therapy.

In a study in rural India, it was found that a large number of rural children were at high risk for cerebral malaria. The study recommends a focused approach to treating malarial fever in children, as early identification and treatment could save the children from potential harm. The study conducted by Kamble MB and colleagues and published in The Indian Journal of Pediatrics and titled “Cerebral Malaria in India” found that

• All patients presented with fever and an involvement of the central nervous system
• 66% of the patients had convulsions
• Out of 56 malaria patients, 7 went into coma
• 60% had anemia
• 20% required blood transfusion
• 53.3% had splenomegaly (enlargement of the spleen)
• 47% of the patients had hepatomegaly (enlarged liver)
• Cerebral malaria is a serious condition and it is identified in 32% of malaria patients who are infected by P.falciparum.

The current study by Dr. Swanson highlights the pathogenesis in mice with a condition similar to cerebral malaria in humans, further studies on humans will ascertain if the same pathogenesis exists. New drug targets will aid in ending the problems that arise due to drug resistance and will provide a better treatment method.

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References:

1. Burden of Cerebral Malaria in Central India (2004–2007) - (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2710578/)
2. Cerebral Malaria in Rural India - (https://www.ncbi.nlm.nih.gov/pubmed/12356215)

Source-Medindia