Plasmodium berghei: parasite clearance after treatment with dihydroartemisinin in an asplenic murine malaria model.
Clinical reports indicate that malaria-infected asplenic patients have a reduced capacity for parasite clearance despite intensive antimalarial therapy. The aim of this study was to evaluate the efficacy of dihydroartemisinin in an asplenic murine malaria model. Mice were inoculated with Plasmodium berghei parasitised erythrocytes and received a single dose of dihydroartemisinin 56 h later, at 2-5% parasitaemia. Haematology, liver biochemistry and histopathology of key organs were performed to evaluate organ response to malaria infection. The nadir parasitaemia occurred 20 h after dihydroartemisinin administration, falling 2.8- to 6.0-fold and 2.7- to 6.9-fold in asplenic and intact mice, respectively, (10-100 mg/kg). Histopathology indicated increased stimulation of liver function/activity during malaria infection of asplenic mice (as compared to intact mice). Overall efficacy of single-dose dihydroartemisinin treatment in asplenic mice was similar to intact mice although the rate of recrudescence in asplenic mice was significantly greater than intact mice at 30 and 100 mg/kg. The asplenic murine malaria model could be used in pre-clinical studies of splenic function and clearance of malaria parasites, pathophysiological studies or antimalarial drug efficacy in asplenia.
Moore
Brioni R
BR
School of Pharmacy, Curtin University of Technology, P.O. Box U1987, Perth, WA 6845, Australia.
Jago
Jeffrey D
JD
Batty
Kevin T
KT
D000818:Animals; D000962:Antimalarials / Q000627:therapeutic use*; D037621:Artemisinins / Q000627:therapeutic use*; D001219:Aspartate Aminotransferases / Q000097:blood; D004195:Disease Models, Animal; D004912:Erythrocytes / Q000469:parasitology; D006420:Hemeproteins / Q000032:analysis; D006454:Hemoglobins / Q000032:analysis; D007958:Leukocyte Count; D008099:Liver / Q000737:chemistry / Q000469:parasitology / Q000473:pathology; D008168:Lung / Q000469:parasitology / Q000473:pathology; D008288:Malaria / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018512:Parasitemia / Q000188:drug therapy / Q000276:immunology / Q000469:parasitology; D010962:Plasmodium berghei / Q000187:drug effects*; D010976:Platelet Count; D012717:Sesquiterpenes / Q000627:therapeutic use*; D013154:Spleen / Q000737:chemistry / Q000473:pathology; D013156:Splenectomy
D000962:Antimalarials; D037621:Artemisinins; D006420:Hemeproteins; D006454:Hemoglobins; D012717:Sesquiterpenes; C020753:hemozoin; C039060:artenimol; D001219:Aspartate Aminotransferases