cgp-56697 and Hemolysis

Intravenous (i.v.) artesunate is now the recommended first-line treatment of severe falciparum malaria in adults and children by WHO guidelines. Nevertheless, several cases of haemolytic anaemia due to i.v. artesunate treatment have been reported. This paper describes the case of an HIV-infected patient with severe falciparum malaria who was diagnosed with haemolytic anaemia after treatment with oral artemether-lumefantrine.The patient presented with fever, headache, and arthromyalgia after returning from Central African Republic where he had been working. The blood examination revealed acute renal failure, thrombocytopaenia and hypoxia. Blood for malaria parasites indicated hyperparasitaemia (6%) and Plasmodium falciparum infection was confirmed by nested-PCR. Severe malaria according to the laboratory WHO criteria was diagnosed. A treatment with quinine and doxycycline for the first 12 hours was initially administered, followed by arthemeter/lumefantrine (Riamet(®)) for a further three days. At day 10, a diagnosis of severe haemolytic anaemia was made (Hb 6.9 g/dl, LDH 2071 U/l). Hereditary and autoimmune disorders and other infections were excluded through bone marrow aspiration, total body TC scan and a wide panel of molecular and serologic assays. The patient was treated by transfusion of six units of packed blood red cell. He was discharged after complete remission at day 25. At present, the patient is in a good clinical condition and there is no evidence of haemolytic anaemia recurrence.This is the first report of haemolytic anaemia probably associated with oral artemether/lumefantrine. Further research is warranted to better define the adverse events occurring during combination therapy with artemisinin derivatives.

Topics: Administration, Oral; Adult; Anemia, Hemolytic; Antimalarials; Artemether, Lumefantrine Drug Combination; Artemisinins; Coinfection; Drug Combinations; Drug Therapy, Combination; Erythrocytes; Ethanolamines; Fluorenes; Hemolysis; HIV; HIV Infections; Humans; Malaria, Falciparum; Male; Plasmodium falciparum; Severity of Illness Index

G6PD is an X-linked gene enzyme that protects erythrocytes from hemolysis when they are exposed to antimalarial drugs because of the effects of the free radicals generated by these drugs. We investigated the effects of Fansidar ™ (Sulfatoxine/Pyrimethamine) and Coartem ™ (Artemether/Lumefantrine) on the hemolysis of malaria parasitized female erythrocytes. Twelve (12) malarious patients attending the University of Benin Teaching Hospital, Benin City, Nigeria, were used in this study. Ten (10) apparently healthy female students from the Medical School, University of Benin, acted as control. Low, normal (the recommended adult dose) and high doses of Fansidar ™ and Coartem ™ were used to determine the percentage hemolysis by checking the absorbance of the various samples. Data was analyzed by the Student's t-test and ANOVA with p<0.05 indicating the level of significance. At low doses of Fansidar ™ and Coartem ™, no hemolysis occurred, while at normal doses, Fansidar ™ showed no hemolysis but significant hemolysis (p<0.05) was observed in the Coartem ™ group. At high doses, both FansidarTM and CoartemTM caused significant (p<0.05) hemolysis. High doses of both drugs and normal dose of CoartemTM caused significant hemolysis. There was no hemolysis observed in the normal dose of FansidarTM and low doses for both drugs, similar to the trend reported for male subjects.

Topics: Adult; Analysis of Variance; Antimanic Agents; Artemether, Lumefantrine Drug Combination; Artemisinins; Case-Control Studies; Dose-Response Relationship, Drug; Drug Combinations; Erythrocytes; Ethanolamines; Female; Fluorenes; Hemolysis; Humans; Malaria; Middle Aged; Nigeria; Pyrimethamine; Sulfadoxine; Young Adult