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Even when severe malaria is not itself fatal, the legacy of an infection may be felt well after recovery. Attention to date has tended to focus on acute illness, but it is becoming clear that episodes of malaria can have a long-term neurological impact that significantly affects a child's development and later life.
A major programme of work at the KEMRI-Wellcome Trust Research Programme in Kilifi, Kenya, is assessing neurological impairment in local children following infectious diseases. Led by Wellcome Trust Senior Research Fellow Dr Charles Newton, together with Dr Norbert Peshu and Dr Penny Holding, the research has found that severe malaria predisposes to epilepsy and congnitive impairment.
Roughly one in ten children will suffer from neurological impairment after cerebral malaria, be it epilepsy, learning disability, changes in behaviour, loss of coordination or impairments to speech. As well as being discomforting physically, these problems can also lead to stigmatisation in the community and can reduce individuals' capacity for work, imposing an additional economic burden.
The full extent of these long-term problems is not clear, however, and an aim of Dr Newton's research is to gain a clearer picture of the type and extent of neurological damage in the community. The approach is twofold: in one strand, patients who recover from an episode of severe malaria are being followed up to see how many go on to suffer epilepsy or show signs of cognitive impairment. With Victor Odera and colleagues, the team is carrying out a large community study to identify neurological impairment and disability in the general population, and to determine the possible causes of impairment. An initial questionnaire is used to screen for potential cases, and this subset is subject to more detailed analysis.
The Programme is aiming to pick up subtle disturbances as well as more obvious medical problems such as epilepsy. Even mild mental or physical disability can create real difficulties for families and impair schooling, and although there is at present little infrastructure to support affected individuals, an awareness of the scale of the problem could mobilise greater support.
Allied to the follow-up work, Dr Newton and colleagues such as Dr Bernhards Ogutu are investigating the mechanisms responsible for brain damage. The factors associated with brain damage in children – seizures, coma and hypoglycaemia – are common to several diseases, including malaria, meningitis and tetanus. Studies have therefore concentrated on the causes of seizures and coma, monitoring children closely and examining possible interventions. In cerebral malaria, for example, abnormalities of blood flow within the brain may be a major cause of oxygen deprivation, causing neuronal damage, an area also being studied further.
The clinical work encompasses the effects of drugs on young children. In the past, drug treatments and doses tended to be extrapolated from adult measures as testing on children raised difficult ethical issues. Now, with the realisation that extrapolation is possibly misleading and potentially deadly, more trials and pharmacokinetic studies are carried out on children to determine effective doses and treatments. For example, a study in Kilifi discovered a serious drawback to the use of phenobarbitone to reduce seizures, a treatment that had many advocates: the incidence of seizures did drop, but overall mortality significantly increased. Several projects are assessing similar questions, including the possible benefits of other anticonvulsants such as fosphenytoin as a convenient treatment for seizures in severe malaria.