Published On: Fri, Mar 9th, 2012

Why cerebral malaria is dangerous for children – By Olufemi Omotayo

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What is your impression of malaria? As a mother, do you see it as a deadly disease or one to be handled with levity? Do you belong to that group of mothers that do not bother to treat malaria in your child when you notice its symptoms?

Well, even if you do not bother that malaria could make your child miss some days at school, experts warn that it should concern you that it might turn out to be cerebral malaria, a severe form of the disease, whose aftermath, when not treated promptly, may be epilepsy. Cerebral malaria, one of the deadliest forms of malaria, is a medical emergency demanding immediate diagnosis and treatment. Experts warn that malaria is best prevented, especially since its severe form is a potential cause of epilepsy in children. This is the crux of our research in this edition.

Looking at the retina in the eyes of patients with cerebral malaria has provided scientists with a vital insight into why malaria infection in the brain is so deadly. In a study funded by the Wellcome Trust and Fight for Sight and published in the Journal of Infectious Diseases, researchers in Malawi have shown for the first time in patients that the build-up of infected blood cells in the narrow blood vessels of the brain leads to a potentially lethal lack of oxygen to the brain.

Malaria is one of the world’s biggest killers, killing over a million people every year, mainly children and pregnant women in Africa, and adults in South-east Asia. Malaria parasites enter the bloodstream from bites by infected mosquitoes and live in red blood cells, making them stick to the inside of narrow blood vessels and causing blockages. Most deaths occur as a result of cerebral malaria, where red blood cells infected by malaria parasites build up into the brain, leading to coma and convulsions and, if not treated swiftly, death.

Scientists have known for some time that cerebral malaria is accompanied by changes in the retina, known as malarial retinopathy which can be seen by examining the eye. Because the retina can be considered as an extension of the central nervous system, it has been used previously as a “window into the brain”, allowing for swifter diagnosis of cerebral malaria. However, until now it was not clearly understood why the disease should be so deadly.

Cerebral malaria is a severe or complicated form of malaria affecting the brain, occurring predominantly in children, with a mortality rate of 15-25 per cent. It affects about one million children every year, primarily in sub-Saharan Africa. Coma, headaches, seizures, and impaired consciousness are frequent manifestations of this infection.

Children less than five years of age are particularly susceptible because of low levels of immunity. It only takes one bite from an infected mosquito to contract the disease that directly affects the brain, causing fever, vomiting, chills, and coma.

In addition, children with cerebral malaria are at risk of developing several adverse neurological outcomes, including epilepsy, disruptive behaviour disorders and disabilities characterised by motor, sensory or language deficits. Since most of the neurological effects did not present themselves immediately, they were not evident at the time of the child’s discharge from the hospital after the initial malaria illness.

A new study on cerebral malaria in African children reported that almost a third of cerebral malaria survivors developed epilepsy or other behavioural disorders.

The research, which appeared in the journal, The Lancet Neurology, looked at several hundred children during a nearly five-year period in Blantyre, Malawi. The children were evaluated for cognitive function in three major areas: attention, working memory, and tactile learning. Evaluation was done at hospitalisation, six months after the initial malaria episode, and two years after the episode.

They found that at six months, 21 per cent of children with cerebral malaria had cognitive impairment compared with six per cent of their healthy Ugandan peers. At two years, cognitive impairment was present in 26 per cent of the patients, compared with 8 per cent of the community children.

The researchers involved in this first-ever prospective study of cerebral malaria survivors that included a control group suggested that cognitive impairment may begin to manifest itself months after the initial episode. In fact, cognitive function was most dramatically impaired in the area of attention.

The impact of the findings on African society is no doubt immeasurable. By extrapolation, they stated that about 135,000 African children younger than five years might have developed epilepsy due to cerebral malaria-induced brain injury each year, and cerebral malaria may be one of the more common causes of epilepsy in malaria-endemic regions.

Since these are children that had survived the malaria, their quality of life and what they contribute to society is severely hampered, the experts declared the need to be more aggressive in treating the two major risk factors: seizures and high fever before better treatment for seizure and fever are identified in hopes of minimising the risk of epilepsy in years to come.

Previous studies had linked epilepsy to disruption of brain development during early childhood – roughly between the ages of one and five -because of the fragility of the brain during this period.

Nonetheless, Dr. Ikeoluwa Lagunju, a consultant paediatric neurologist, University College Hospital (UCH), Ibadan, Oyo State, declaring the importance of preventing malaria, stated that cerebral malaria was a severe form of malaria in which you have malaria parasite invading the brain.

Dr. Lagunju stated: “We see cases of cerebral malaria quite often, particularly during the rainy season. Transmission of malaria parasite is quite high during the rainy season and so you tend to have many cases of malaria and its severe forms during this season.”

According to her, “malaria parasite is usually found circulating in the blood stream and that is why you have fever, vomiting, chills and rigours. But in severe cases, these parasites would go through the blood to the brain and when you have a heavy load of malaria parasite in the brain, it is believed that it could block some blood vessels, cause swelling of the brain and some other abnormalities.

“When this happens, the child becomes unconscious, but afterwards, a number of them recover consciousness. But cerebral malaria is highly fatal and can kill rapidly, with poor management, when it is not recognised or involves someone who has not been in a malaria-endemic area.

However, Dr Lagunju remarked that in those who survived cerebral malaria, the brain had been affected. “It is a form of injury to the brain. The brain is peculiar in the sense that it does not regenerate. You can injure your finger nail and then it grows back. You can have a wound and then you lose the skin and the skin grows back, but the brain is not like that,” she stated.

According to her, ‘If you have a child who has had cerebral malaria, he may recover from the illness, but then he may have problems with vision and hearing and few of them may later continue to have seizures and have what we call epilepsy.

“So, these are the things that we worry about with cerebral malaria and that is why prevention of malaria remains the best option.”

Certainly, nobody can tell which malaria will be severe enough to involve the brain. According to Dr Lagunju, the best option is to prevent malaria through the use of insecticide-treated nets, ensure clean surroundings, maintain low lawns and clean drains, prevent stagnant waters and ensure a clean environment.

She reiterated the need for mothers to know how to treat malaria. “Gone are the days of: are you a doctor? Why did you then give anti-malarial medicines? We actually expected that mothers should have a pack of rapidly acting anti-malarial drug that they can readily administer as soon as they notice that the child is unwell. This will help to quickly clear the malaria parasite and reduce the risk of the child going on to develop severe forms of malaria.”

Professor Surajudeen Arigbabu, a consultant neurosurgeon at the Lagos University Teaching Hospital, reiterated that once the brain is injured, it cannot recover. According to him,” for any loss of a part of the brain or an injury, the effect is permanent and for that reason, if a person is diagnosed with cerebral malaria and there is a damage to any part of the brains later in life, that part of the brain that is damaged may become an epileptogenic focus and with resultant convulsions from time to time.”

In new research, Dr Nick Beare of the Royal Liverpool University Hospital, together with colleagues at the Queen Elizabeth Central Hospital in Blantyre, Malawi, examined the retinas of 34 children admitted to the hospital with cerebral malaria. They used a technique known as fluorescein angiography, which involves injecting a special dye into the arm intravenously and photographing its passage through the blood vessels of the retina. It is used to identify fluid leakage or blockages in the small blood vessels at the back of the eye.

More than four in five of the children examined by Dr Beare and colleagues were found to have impaired blood flow in the blood vessels of their eyes. Three-quarters had whitening to areas of the retina where blood did not appear to reach, implying that the parasites were disrupting the supply of oxygen and nutrients.

“We have previously used the retina to accurately diagnose severe malaria, but now this window into the brain has opened up our knowledge of what makes cerebral malaria so deadly,” says Dr Beare. “This is the first study to clearly show impaired blood flow in the eyes of patients with cerebral malaria. It has provided strong evidence to support what, until now, had been merely hypothesised: that cerebral malaria causes inadequate blood flow to the brain, depriving it of oxygen and causing potentially life-threatening damage.”

If caught in time, the effects of cerebral malaria can be reversed with no lasting damage to the patient’s cognitive functions or vision. Dr Beare believes these new findings point to new therapeutic measures for treating cerebral malaria more effectively, particularly in comatose children.

“Many children are dying across Africa with cerebral malaria because we don’t understand how to help them whilst the anti-malarial drugs have an effect,” he says. “Drugs that improve circulation and limit the damage caused by the lack of oxygen could help prevent many deaths.”

The research has been welcomed by Michele Acton, chief executive of Fight for Sight, who comments: “The findings of Dr Beare’s work on malaria are incredibly important. Fight for Sight is delighted to have helped to fund such progress towards better therapies to prevent children dying from cerebral malaria.”

  • With additional reports from internet sources

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Why cerebral malaria is dangerous for children – By Olufemi Omotayo