Comparative studies on the pathological findings and mortality in Schistosoma mansoni infected mice after treatment with artesunate and the current antischistosomal drugs.

The effect of artesunate (ART) on the pathology and mortality rate of in Schistosoma mansoni infected mice was comparatively studied with the current drugs of choice for the treatment of schistosomiasis mansoni: praziquantel (PZQ) and oxamniquine (OX). S. mansoni experimentally infected mice were treated at 9th week of infection with ART, PZQ or OX at an oral dosage of 300 mg kg(-1), 600 mg kg(-1) and 100 mg kg(-1), respectively. Untreated, infected mice and non-infected mice were added as controls. Samples of mice were sacrificed and examined for the pathological findings at 1 week, 1 month, and 3 months after treatment. At 1 week after treatment, both gross and microscopic lesions were observed. No significant differences were noted among the infected groups. Differences were observed at 1 month after treatment. The lesions decreased more rapidly in groups treated with PZQ and OX. At 3 months after treatment, there were significant differences in the pathological findings among groups. In the groups treated with PZQ and OX, the lesions were markedly reduced and rarely found, but they were clearly observed in the group treated with ART and in the untreated, infected group. High mortality was also recorded in the group treated with ART and in the untreated, infected group. Therefore, the treatment of S. mansoni infected mice at 9 weeks of infection with ART did not reduce the pathological findings or the mortality rate compared to treatment with the current recommended schistosomicides, PZQ and OX.

Therapeutic effect of subcurative dose praziquantel on Schistosoma mansoni infected mice and resistance to challenge infection after treatment.

The therapeutic effect of a subcurative dosage of praziquantel (PZQ) on Schistosoma mansoni infected mice and resistance to challenged worm infection after treatment were assessed and compared with conventional treatment using a curative dosage of PZQ. S. mansoni infected mice were treated with PZQ at a curative dosage (600 mg kg(-1)) or a subcurative dosage (300 mg kg(-1)) at 9 weeks after infection. Untreated mice and non-infected mice were added as controls. The therapeutic effect of the drug was evaluated in terms of the mortality of mice after treatment, and the parasitological and pathological findings in mice sacrificed at 1 week, 1 month, or 3 months after treatment. Another sample of mice was not killed but challenged with S. mansoni cercariae at 1 week, 1 month, or 3 months after treatment. Resistance to re-infection was evaluated by the extent of challenged worm reduction. In conclusion, there was no significant difference in mortality, or parasitological and pathological findings between mice treated with PZQ at the two dosages. However, resistance to challenged worm infection was more sustained in the group treated with subcurative dose PZQ, especially at 3 months after treatment.

Hematopoietic features and apoptosis in the bone marrow of severe Plasmodium falciparum-infected patients: preliminary study.

The mechanism of anemia in severe falciparum malaria is still not completely understood. The purpose of this study was to determine whether apoptosis in the erythroid lineage causes anemia in falciparum malaria. Bone marrow aspirated from 8 severe falciparum malaria patients, 3 normal volunteers and 5 retrospective normal bone marrow smears were investigated. By light microscopic study, 5 of 8 hyperparasitemic patients had hypocellular bone marrows and erythroid hypoplasia, whereas the other 3 patients had normal cellularity. The mean myeloid : erythroid ratio of these 5 patients was significantly (p < or = 0.05) higher than normal. Apoptosis of bone marrow nucleated cells (BMNC) could be determined from the exposure of phosphatidylserine (PS) on the cell membrane but not DNA fragmentation (180-250 bp) or ultrastructural morphology. The percentages of apoptotic BMNC and apoptotic erythroid cells in bone marrow from each patient and controls varied from low to high, and were not associated with parasitemia. This study suggests that destruction of erythroid lineage, particularly through apoptosis regulation, cannot solely account for anemia in falciparum malaria.