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Cells associated with inflammation and coagulation accumulate in the brains of children with cerebral malaria (CM), according to research published in mBio.
The researchers studied autopsied brain tissue from more than 100 African children and found that children with CM had a more than 9-fold greater number of intravascular monocytes and platelets than children who did not have malaria.
In addition, HIV-positive children had more than twice the amount of intravascular monocytes and platelets than was observed in children who were not HIV-positive.
“Our study clearly shows that HIV exacerbates the disease process in cerebral malaria and also leads to some really interesting insights into what may be going on with children who are dying of cerebral malaria, which has been very controversial,” said study author Kami Kim, MD, of the Albert Einstein College of Medicine in the Bronx, New York.
“Children who are HIV-positive and at risk for malaria may benefit from targeted antimalaria drugs, and adjunctive therapies that target inflammation or blood clotting may improve outcomes from CM.”
CM is one of the most severe complications of malaria and can lead to behavioral problems, seizures, coma, or death. It is mainly seen in children younger than 5 living in sub-Saharan Africa.
CM is fairly rare, affecting about 2% of children with malaria, but CM is also thought to be responsible for half of malaria deaths.
“So it’s a big deal,” Dr Kim said. “The more we know about CM, the more that we can theoretically do something either to better treat or prevent it.”
With this goal in mind, Dr Kim and her colleagues analyzed children in an ongoing study of pediatric CM in Blantyre, Malawi. The researchers enrolled more than 3000 participants and completed 103 autopsies in those who died from either CM or other causes of coma.
HIV prevalence was higher than expected and led to higher mortality in CM patients. The prevalence of HIV was 14.5% in children enrolled in the study, compared to 2% in the general Malawi pediatric population.
Twenty-three percent of HIV-positive children died, while 17% of those without HIV died. Twenty percent of autopsy cases were HIV-positive.
The researchers noted that HIV-infected children with CM were older than children without HIV (an average of 99 months vs 32 months) and were not severely immunocompromised.
In addition, monocytes and platelets were significantly more prevalent in HIV-positive children with CM than neutrophils.
“We identified a unique and pervasive pathology pattern in pediatric CM, marked by monocytes and platelets, which is more severe in HIV-positive children,” Dr Kim said.
“It doesn’t prove that these cells cause clinical disease, but the fact that they’re there in huge abundance when there’s a lot of parasites is pretty strongly suggestive evidence that they’re doing something. We never see that in healthy brain tissue.”
Additional studies of children with varying severities of malaria are necessary in order to design better treatment algorithms, Dr Kim added. 
Image by Bruce Blaus
Cells associated with inflammation and coagulation accumulate in the brains of children with cerebral malaria (CM), according to research published in mBio.
The researchers studied autopsied brain tissue from more than 100 African children and found that children with CM had a more than 9-fold greater number of intravascular monocytes and platelets than children who did not have malaria.
In addition, HIV-positive children had more than twice the amount of intravascular monocytes and platelets than was observed in children who were not HIV-positive.
“Our study clearly shows that HIV exacerbates the disease process in cerebral malaria and also leads to some really interesting insights into what may be going on with children who are dying of cerebral malaria, which has been very controversial,” said study author Kami Kim, MD, of the Albert Einstein College of Medicine in the Bronx, New York.
“Children who are HIV-positive and at risk for malaria may benefit from targeted antimalaria drugs, and adjunctive therapies that target inflammation or blood clotting may improve outcomes from CM.”
CM is one of the most severe complications of malaria and can lead to behavioral problems, seizures, coma, or death. It is mainly seen in children younger than 5 living in sub-Saharan Africa.
CM is fairly rare, affecting about 2% of children with malaria, but CM is also thought to be responsible for half of malaria deaths.
“So it’s a big deal,” Dr Kim said. “The more we know about CM, the more that we can theoretically do something either to better treat or prevent it.”
With this goal in mind, Dr Kim and her colleagues analyzed children in an ongoing study of pediatric CM in Blantyre, Malawi. The researchers enrolled more than 3000 participants and completed 103 autopsies in those who died from either CM or other causes of coma.
HIV prevalence was higher than expected and led to higher mortality in CM patients. The prevalence of HIV was 14.5% in children enrolled in the study, compared to 2% in the general Malawi pediatric population.
Twenty-three percent of HIV-positive children died, while 17% of those without HIV died. Twenty percent of autopsy cases were HIV-positive.
The researchers noted that HIV-infected children with CM were older than children without HIV (an average of 99 months vs 32 months) and were not severely immunocompromised.
In addition, monocytes and platelets were significantly more prevalent in HIV-positive children with CM than neutrophils.
“We identified a unique and pervasive pathology pattern in pediatric CM, marked by monocytes and platelets, which is more severe in HIV-positive children,” Dr Kim said.
“It doesn’t prove that these cells cause clinical disease, but the fact that they’re there in huge abundance when there’s a lot of parasites is pretty strongly suggestive evidence that they’re doing something. We never see that in healthy brain tissue.”
Additional studies of children with varying severities of malaria are necessary in order to design better treatment algorithms, Dr Kim added.
Image by Bruce Blaus
Cells associated with inflammation and coagulation accumulate in the brains of children with cerebral malaria (CM), according to research published in mBio.
The researchers studied autopsied brain tissue from more than 100 African children and found that children with CM had a more than 9-fold greater number of intravascular monocytes and platelets than children who did not have malaria.
In addition, HIV-positive children had more than twice the amount of intravascular monocytes and platelets than was observed in children who were not HIV-positive.
“Our study clearly shows that HIV exacerbates the disease process in cerebral malaria and also leads to some really interesting insights into what may be going on with children who are dying of cerebral malaria, which has been very controversial,” said study author Kami Kim, MD, of the Albert Einstein College of Medicine in the Bronx, New York.
“Children who are HIV-positive and at risk for malaria may benefit from targeted antimalaria drugs, and adjunctive therapies that target inflammation or blood clotting may improve outcomes from CM.”
CM is one of the most severe complications of malaria and can lead to behavioral problems, seizures, coma, or death. It is mainly seen in children younger than 5 living in sub-Saharan Africa.
CM is fairly rare, affecting about 2% of children with malaria, but CM is also thought to be responsible for half of malaria deaths.
“So it’s a big deal,” Dr Kim said. “The more we know about CM, the more that we can theoretically do something either to better treat or prevent it.”
With this goal in mind, Dr Kim and her colleagues analyzed children in an ongoing study of pediatric CM in Blantyre, Malawi. The researchers enrolled more than 3000 participants and completed 103 autopsies in those who died from either CM or other causes of coma.
HIV prevalence was higher than expected and led to higher mortality in CM patients. The prevalence of HIV was 14.5% in children enrolled in the study, compared to 2% in the general Malawi pediatric population.
Twenty-three percent of HIV-positive children died, while 17% of those without HIV died. Twenty percent of autopsy cases were HIV-positive.
The researchers noted that HIV-infected children with CM were older than children without HIV (an average of 99 months vs 32 months) and were not severely immunocompromised.
In addition, monocytes and platelets were significantly more prevalent in HIV-positive children with CM than neutrophils.
“We identified a unique and pervasive pathology pattern in pediatric CM, marked by monocytes and platelets, which is more severe in HIV-positive children,” Dr Kim said.
“It doesn’t prove that these cells cause clinical disease, but the fact that they’re there in huge abundance when there’s a lot of parasites is pretty strongly suggestive evidence that they’re doing something. We never see that in healthy brain tissue.”
Additional studies of children with varying severities of malaria are necessary in order to design better treatment algorithms, Dr Kim added.