Pediatric Cerebral Malaria: A Scourge of Africa

Abstract

Cerebral malaria, defined as an otherwise unexplained coma in a patient with Plasmodium falciparum parasitemia, affects up to 1 million people per year, the vast majority of them being children living in sub-Saharan Africa. Despite optimal treatment, this condition kills 15% of those affected and leaves 30% of survivors with neurologic sequelae. The clinical diagnosis is hampered by its poor specificity, but the presence or absence of a malarial retinopathy in cerebral malaria has proven to be important in the differentiation of underlying coma etiology. Both antimalarials and intense supportive care are necessary for optimal treatment. As of yet, clinical trials of adjunctive therapies have not improved the high rates of mortality and morbidity. Survivors are at high risk of neurologic sequelae including epilepsy, neurodisabilities and cognitive–behavioral problems. The neuroanatomic and functional bases of these sequelae are being elucidated. Although adjunctive therapy trials continue, the best hope for African children may lie in disease prevention. Strategies include bednets, chemoprophylaxis and vaccine development.

Cerebral Malaria Retinopathy Predictors of Persisting Neurocognitive Outcomes in Malawian Children

“…8 This type of brain injury from CM may also disrupt neuropsychological functions of the sort observed in the present study, including working memory, visual-spatial processing and problem solving, and learning. 20, 21 With the availability of MRI braining imaging technology now at the Blantyre Malaria Project site in Malawi, there is now the capability to relate the four principal types of retinopathy severity (hemorrhage, retinal whitening, papilledema, vascular abnormalities) to brain MRI structural abnormalities and corresponding persisting neuropsychological deficits. This is planned in future studies.…”

Immunobiology of Plasmodium in liver and brain

“…In contrast, according to the cytokine hypothesis, factors pertaining to changes such as oedema and reversible coma led to the proposal that CM was akin to an encephalopathy suggesting an inflammatory basis for the syndrome (85,(96)(97)(98)(99). Only recently have the obstruction and inflammation hypotheses started to converge (Figure 2c), based on findings supporting both, leading to a third model that links the two original hypotheses (34). The central questions remain.…”

“…Hypoxia is unlikely the primary cause of coma as it more often than not dissipates after several days with no ill effects, compared with a large body of literature documenting that even a brief loss of consciousness during a stroke predicts striking permanent functional deficiencies (194). Therefore, extensive microvascular and parenchymal injury is at variance with the relative reversibility of coma and frequent lack of neurological sequelae (34,35,85). Further, iRBC sequestration does not always correlate with disease severity (85,100), and we would argue that the presence of parasites in the brain neither predicts nor causes CM.…”

“…Repeated exposure to the parasite generally results in partial adaptive immunity. However, a considerable number of people, principally infants and children up to 5 years of age, develop potentially fatal complications such as severe anaemia or malarial encephalopathy, commonly known as CM, resulting in 15–20% mortality despite optimum care and antimalarial treatment . Approximately 30% of the CM survivors are left with neurological sequelae .…”

“…However, a considerable number of people, principally infants and children up to 5 years of age, develop potentially fatal complications such as severe anaemia or malarial encephalopathy, commonly known as CM, resulting in 15–20% mortality despite optimum care and antimalarial treatment . Approximately 30% of the CM survivors are left with neurological sequelae . Another severe complication of P. falciparum malaria, caused by trophozoite harbouring iRBC binding to placental chondroitin‐4‐sulphate, is a leading cause of perinatal and maternal morbidity in primigravid women .…”