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Research - The eye in cerebral malaria

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A research programme to improve our understanding of how cerebral malaria kills, how it can be better diagnosed and how treatments can be targeted to the most sick

Dr Nick Beare examining a child in a Malawi hospital. Malaria, in the severe forms of cerebral malaria and acute anaemia, still kills over a million young children in Africa each year.

Malaria parasites live in red blood cells and cause them to stick to the inside of small blood vessels, particularly in the brain and eyes. This produces a 'whitening' of the blood vessels.

The disease also harms light-sensitive tissue in the eye because the parasites feed on the supply of oxygen and nutrients it needs.

Even with the best treatment, 15% of children that reach hospital with cerebral malaria die, and 10% of survivors have long-term neurological damage.

St Paul’s has been involved with malaria research and how it affects the eye since 1995, mostly in Malawi and also in Kenya.

With our collaborators we have moved this field forward from interesting curiosity to vital diagnostic tool with unparalleled insight into how malaria becomes life-threatening when it infects the brain. In this disease the eye has truly been a “window on the brain”.

Ocular changes in severe malaria

In malaria, changes occur on the retina, the sensitive nerve tissue that detects light at the back of the eye. The retina develops white patches, multiple discreet haemorrhages and the retinal blood vessels, which are normally red, can become white. The optic nerve can become swollen, indicating increased pressure in the head. Remarkably the vision is rarely affected, but by investigating the nature of these changes we have shed light on disease mechanisms in the brain that lead to coma and death.

Recent Breakthroughs

Detecting blood flow abnormalities in the retina

The malaria parasite infects small blood vessels in the brain, but how this causes damage is unknown. The retina is closely related to the brain so findings can be relevant to both. Using ocular angiography techniques on children with cerebral malaria, we have shown blocked blood flow in the retina and leaky blood vessels. This has not been shown before and as similar processes occur in the brain this is a major breakthrough in the understanding of cerebral malaria. These findings suggest drugs to improve blood flow, or limit damage from lack of oxygen to the brain might be useful.

This work has been accepted for presentation at both the International Congress of Parasitology and American Society of Tropical Medicine meetings and is to be submitted to The Lancet.
Establishing malarial retinopathy as a diagnostic sign

In areas of Africa where malaria is rife, it is common for children to be infected by the malaria parasite. This means that when they come to the hospital unconscious, a malaria infection may or may not be the cause of their illness. Without sophisticated diagnostic equipment it is often difficult to rule out other causes of their coma. Recent studies suggest as many as a quarter of children dying of malaria may have another, more important cause of death.

However, because some of the abnormalities in the eye are unique to severe malaria, the fact that they are present can confirm the diagnosis. This will allow quicker identification of those children at most risk. The patient can then be given appropriate treatment before the disease kills them or leaves them with brain damage.

Beare et al, (2006): Malarial retinopathy: a newly established diagnostic sign in severe malaria. In press with the American Journal of Tropical Medicine and Hygiene.
Training African doctors to examine eyes for malarial retinopathy

Leading on from the work above, doctors from leading malaria centres in five African countries have been trained to detect malarial retinopathy. As well as improving the diagnosis of cerebral malaria in children in their care, it is hoped that studies of new treatments will be more accurate because only cerebral malaria cases will be included.
Photographic library

Use of a digital ocular camera has enabled the abnormalities caused by malaria in the eye to be extensively documented for the first time. These images are extremely useful for disseminating our results and teaching doctors to recognise malarial retinopathy.
Use of ultrasound to detect raised intracranial pressure in cerebral malaria

We have conducted a trial of using ultrasound to detect raised intracranial pressure by measuring the size of the optic nerve behind the eye.

The optic nerve is directly connected to the brain and can enlarge in size due to a rise in pressure in the brain. This swelling of the optic nerve can be detected by an ultrasound machine providing additional information for the attending clinician. One day this may lead to targeted treatment for those with high pressure.

Previous work

In previous studies we have demonstrated the value of malarial retinopathy for prognosis: the more severe the eye changes, the longer children take to recover consciousness and the more likely they are to die.
We have shown that the vision in children recovering from cerebral malaria does not appear to be affected by malarial retinopathy.
We have found a delay in the electrical brain waves which transmit vision in children deeply unconscious with cerebral malaria. This work is now being taken up in a new project to assess brain function in cerebral malaria by combining brain waves from different senses as well as vision.

Future Directions

It is planned to continue the study of retinal blood flow by angiography. Due to its importance and ground-breaking nature more patients are needed with findings analysed by in-depth image analysis. Additional photographic records of malarial retinopathy will also enable us to correlate them with histopathological findings for the first time.

Collaborating with vision scientists from the University of Liverpool we plan to investigate further the visual function of children after malarial retinopathy. This may also give us insights into the affect cerebral malaria has on brain processing and the social impact of the disease in affected populations.

Despite the amazing breakthroughs during the initial phases of the project, there is still much more work to be done if we are to help save the lives of more than a million children a year succumbing to cerebral malaria.

We are currently looking for funding to help employ a junior research ophthalmologist for 15 months in Africa, as well as an orthoptist and 2 nurses local to the region. We need all the support you can give us.

St Paul's investigators

Dr Nicholas Beare, MA, FRCOphth.

In Summer 2006, Nicholas returned from a second 18-month period in Malawi undertaking research and teaching in malarial retinopathy.
Professor Simon Harding, MD, FRCOphth.

Collaborating units:

Professor Malcolm Molyneux - Malawi-Liverpool-Wellcome Trust Clinical Research Programme, College of Medicine, Blantyre, Malawi and Liverpool School of Tropical Medicine.
Professor Terrie Taylor - Blantyre Malaria Project and Michigan State University, USA.
Dr Susan Lewallen - Kilimanjaro Centre for Community Ophthalmology, Tanzania.
Professor Charles Newton - Kenyan Medical Research Institute, Kilifi, Kenya.