April 25, 2007
Cerebral malaria: towards a prognostic test?
Researchers from the Institut Pasteur and the CNRS, in collaboration with clinicians in Gabon, recently conducted a study on cerebral malaria in Plasmodium falciparum infected children. Results from this research, published today in 'PLoS ONE', should allow a better understanding of this severe form of malaria affecting 20-40% of P. falciparum infected individuals developing a severe disease and which is fatal in 30-50% of cases. They may also allow the development of a test that should help in the prediction of outcome of patients with severe P. falciparum malaria.
Cerebral malaria is characterized by a high fever and convulsions, followed by a coma. Despite the availability of effective treatment, the high mortality rate associated to this complicated malaria form is due to a delayed diagnosis, the patients often arrive too late at the hospital. Therefore, a predictive test could be useful to improve the management of severe malaria cases.
This is one of the purposes of studies conducted by the team of Sylviane Pied, a researcher at the CNRS and supervisor of the Immunophysiology of Malaria group* at the Institut Pasteur, in collaboration with Maryvonne Kombila’s group at the Health Sciences University of Libreville, with the Central Hospital of Libreville, and the Owendo Paediatric Hospital (Gabon).
* Research performed in the Infectious Immunophysiopathology Unit (CNRS URA 1961) directed by Pierre-André Cazenave
This study concentrated on particular immune responses occurring in Plasmodium falciparum infected patients. B lymphocytes, the main antibody-producing cells, highly secrete a wide range of antibodies, in particular antibodies able to recognize different self-components (DNA, red blood cells, etc.). To date, it is not known if these "autoantibodies" are the result of pathological mechanisms due to the parasite infection or if they contribute to events leading to cerebral malaria.
French and Gabonese analysed if some of these autoantibodies were directed against brain molecules.
To do so, they studied blood samples from around 350 children aged from 6 months to 5 years monitored in the Gabonese hospitals. The cohort was divided into five groups: control individuals (without parasites in the blood), asymptomatic patients, patients developing acute malaria, severe non-cerebral malaria (most were suffering from severe anaemia), and finally cerebral malaria.
They found antibodies that recognise a protein of the brain, the brain alpha-spectrin in 90% of cerebral malaria children.
"Our hope today is that this discovery allows the development of a prognostic test for cerebral malaria, explained Pied. Our hypothesis is that the ability to produce a large amount of autoantibodies that recognize the brain alpha-spectrin would predispose to cerebral malaria, and our current research aims to verify this point."
"In the field, a test allowing to predict that a patient is susceptible to develop cerebral malaria, would considerably improve the patients care on admission", added Pied.
This study also opens a new area of research in malaria since the role plays by autoantibodies recognizing brain antigens in the development of cerebral malaria remains to be elucidated.
This work received support from the PAL+ programme of the French Ministry of Research and the Institut Pasteur’s Genopole.
"Self-reactivities to the non-erythroid alpha spectrin correlate with cerebral malaria in Gabonese children" : PLoS ONE, 25 April 2007
Guiyedi Vincent (1-2), Chanseaud Youri (1-3), Fesel Constantin (3), Snounou Georges (4), Rousselle Jean-Claude (5), Lim Pharat (1), Koko Jean (6), Namane Abdelkader (5), Cazenave Pierre-André (1), Kombila Maryvonne (2), et Pied Sylviane (1-3
1. Infectious Immunophysiopathology Unit, Institut Pasteur - URA CNRS 1961, Université Pierre et Marie Curie, Paris.
2. Parasitology-Mycology-Tropical Medicine Department, School of Medicine, Health Sciences University of Libreville, Gabon.
3. Instituto Gulbenkian de Ciëncia, Oeiras, Portugal
4. Comparative Parasitology and Experimental Models, Ecology and Biodiversity Management Department, Natural History Museum, Paris.
5. Proteomics Platform, Pasteur Genopole, Institut Pasteur, Paris.
6. Owendo Paediatric Hospital, Libreville, Gabon.