Scientists at CNRS and the Pasteur Institute, collaborating with physicians in Gabon, have just undertaken a study on cerebral malaria in children living in an endemic region. This study, which was published in PLoS ONE, should allow us to better understand this severe form of malaria which affects 20 to 40 percent of people infected by the Plasmodium falciparum parasite, and is fatal in 30 to 50 percent of cases. The study also provides a lead on how to perfect a diagnostic test, which should allow for better patient care.
Cerebral malaria presents with a high fever and convulsions followed by coma. The high mortality rate from this form of malaria is also linked to a problem of patient care because, despite the availability of effective treatment, patients often arrive at hospital too late. The availability of predictive tests would therefore be useful in improving patient care. It is this hope that has been raised by the study undertaken by Sylviane Pied and her team. Pied, a scientist at CNRS, leads the malaria immunophysiology group* at the Pasteur Institute, which collaborated on the study with Maryvonne Kombila of the Science and Health University of Libreville, the Libreville Hospital Center, and with the Owendo Pediatric Hospital (Gabon).
The study concentrated on the particular immunological phenomenon observed in people infected by Plasmodium falciparum. The B-lymphocytes, the main antibody - producing cells, increase their secretion of a range of antibodies, notably those directed against various components of the organism (DNA, red blood cells, etc.). Today we still don't know if these "auto-antibodies" are the result of pathological mechanisms associated with the infection or if they contribute to the events leading to the severe forms of the illness.
The French and Gabonese teams sought to understand if some of these auto-antibodies were directed against the molecules in the brain. In order to do this, they worked on the blood samples of some 350 children aged between 6 months and 5 years who had been treated in Gabonese hospitals. The cohort was divided into 5 groups: control patients (without parasites in the blood), asymptomatic patients, patients developing simple malaria, patients suffering from serious, non-cerebral malaria (notably severe anaemia), and finally patients suffering from neurological infection. The results of the study show that, in 90% of children suffering from cerebral malaria, the antibodies specifically recognize a protein in the brain, cerebral alpha-spectrin.
"Our hope today is that this discovery will allow for the development of a diagnostic test for cerebral malaria," explains Pied. "Our hypothesis is that the production of auto-antibodies against alpha-spectrin is a predisposition to the development of cerebral malaria, and our current research aims to verify this. If, in the field, we had a test which allowed us to tell whether or not a person is susceptible to developing cerebral malaria it would enable us to considerably improve their treatment".
This study also opens a new sector of malaria research; understanding the role of auto-antibodies directed against cerebral antigens in the development of the illness.
* Study undertaken in the Infectious Immunophysiopathology Unit (CNRS URA 1961) directed by Pierre-André Cazenave
This project received the support of the PAL+ program of the French Ministry of Research and the Genopole of the Pasteur Institute.
Self-reactivities to the non-erythroid alpha spectrin correlate with cerebral
malaria in Gabonese children: PLoS ONE, 25 avril 2007
Guiyedi Vincent1-2, Chanseaud Youri1-3, Fesel Constantin3, Snounou Georges4, Rousselle Jean- Claude5, Lim Pharat1, Koko Jean6, Namane Abdelkader5, Cazenave Pierre-André1, Kombila Maryvonne2, et Pied Sylviane1-3
1. Infectious Immunopathology Unit, Pasteur Institute - URA CNRS 1961, Pierre et Marie Curie University, Paris
2. Department of Tropical Parasitology-Mycology-Medecine, Department of Medicine, Science and Health University, Libreville, Gabon
3. Gulbenkian de Ciëncia Institute, Oeiras, Portugal
4. Comparative Parasitology and Experimental Models, Department of Ecology et Biodiversity Management, Natural History Museum, Paris
5. Proteomics Platform, Pasteur Génopole, Pasteur Institute, Paris
6. Owendo Pediatric Hospital, Libreville, Gabon
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