Safety of epoietin beta-quinine drug combination in children with cerebral malaria in Mali.
BACKGROUND
Cerebral malaria carries an unacceptable case fatality rate in children despite timely and adequate chemotherapy. To improve the survival rate, adjunctive therapies previously tested mainly focused on the modulation of the inflammatory response, without definitive effect in humans. In this context, a new adjunctive strategy using a neuroprotective drug: erythropoietin (epoietin-beta, Epo) was proposed.


METHODS
An open-labelled study including cerebral malaria children (Blantyre coma score below 3) was conducted in Mali. The objective was to assess the short-term safety (seven days) of erythropoietin at high doses (1,500 U/kg/day during three days) combined to quinine.


RESULTS
35 patients with unrousable coma were included in the study. None of expected side effects of erythropoietin were observed during the seven days follow-up. No significant increase in the case fatality rate (7/35 patients) was observed compared to other studies with mortality rates ranging from 16 to 22% in similar endemic areas.


CONCLUSIONS
These data provide the first evidence of the short-term safety of erythropoietin at high doses combined to quinine. A multicentre study is needed to assess the potential of Epo as an adjunctive therapy to increase the survival during cerebral malaria. CLINICAL REGISTRATION NUMBER: ClinicalTrials.gov ID: NCT00697164.
Picot
Stéphane
S
Malaria Research Unit, EA 4170, University Lyon 1, Faculty of Medicine, Lyon, France. picot@sante.univ-lyon1.fr
Bienvenu
Anne-Lise
AL
Konate
Salimata
S
Sissoko
Sibiri
S
Barry
Abdoulaye
A
Diarra
Elisabeth
E
Bamba
Karidiatou
K
Djimdé
Abdoulaye
A
Doumbo
Ogobara K
OK
D000962:Antimalarials / Q000009:adverse effects* / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D004338:Drug Combinations; D004921:Erythropoietin / Q000009:adverse effects* / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007223:Infant; D016779:Malaria, Cerebral / Q000188:drug therapy*; D008297:Male; D008302:Mali; D011803:Quinine / Q000009:adverse effects* / Q000627:therapeutic use*; D011994:Recombinant Proteins
D000962:Antimalarials; D004338:Drug Combinations; D011994:Recombinant Proteins; C103998:epoetin beta; D004921:Erythropoietin; D011803:Quinine