Dose findings of dihydroartemisinin in treatment of falciparum malaria.

Forty patients with uncomplicated P. falciparum malaria were respectively treated in an open randomized comparative study of dihydroartemisinin tablets given at total doses of 480 mg over 5 days and 640 mg over 7 days in a drug-resistant malaria endemic area in Hainan, China. The result showed that all patients were clinically cured. In 5-day and 7-day groups, the mean fever clearance times (FCT) were 26.1+/-10.2 and 21.1+/-11.8 hours respectively; the mean parasite clearance times (PCT) were 58.7+/-20.9 and 59.4+/-20.9 hours respectively, which showed no significant difference. 28-day follow-ups were accomplished on 39 and 37 cases respectively in two groups, the recrudescence rates were 20.5% (8/39) in 5-day group, while 2.7% (1/37) in 7-day group with significant difference (chi2=4.19, p<0.05). No clinical drug-related side effect was found in two groups during treatment.

The infectivity of gametocytes of Plasmodium falciparum from patients treated with artemisinin.

Twenty-seven patients with gametocytes of Plasmodium falciparum (PF) were divided into groups A, B, and C. A daily dose of 1200 mg artemisinin was given for 5 days to group A, a state dose of 750 mg of mefloquine to group B and a single dose of 750 mg mefloquine combined with 45 mg primaquine to group C. After treatment, the gametocyte count was taken daily, and infectivity of the gametocytes to Anopheles dirus via membrane feeding was also studied. Results showed that in group A, the density of gametocyte and infectivity were significantly reduced on days 4, 7, 14 and 21 after treatment; In group B, the gametocytes were significantly reduced on days 7, 14 and 21 and infectivity was significantly cut down on days 14 and 21 after medication. In group C, gametocytes disappeared in 5 out of 9 patients with failure of infecting mosquitoes in all 9 patients on day 4 after treatment. These indicate that artemisinin can effectively influence the infectivity of gametocytes of PF. Artemisinin is much better in blocking the transmission of PF malaria than mefloquine.

Clinical trials of artemisinin and its derivatives in the treatment of malaria in China.

Since 1979 several derivatives of artemisinin have been synthesized and studied in China. Artemisinin suppositories, artesunate (oral or parenteral), intramuscular artemether and dihydroartemisinin tablets have all proved rapidly effective. In all, 2352 patients (2150 with Plasmodium falciparum and 202 with P. vivax) have been included in clinical trials from our centre. All preparations have been well tolerated. These drugs have now replaced chloroquine and quinine for the treatment of malaria in China.

[The infectivity of gametocytes of Plasmodium falciparum from patients treated with artemisinine].

27 patients with gametocytes of P. falciparum were divided into groups A, B and C. 1,200 mg of artemisinine was given as a daily dose for 5 days to group A, 750 mg of mefloquine plus 45 mg of primaquine as a single dose to group C. After medication, gametocyte count was observed daily in addition to the infectivity of gametocytes of P. falciparum to Anopheles dirus. In group A, the density of gametocytes and the infectivity were significantly reduced on days 4, 7, 14 and 21 during the study. In group B, the density of gametocytes was significantly reduced on days 7, 14 and 21 and the infectivity was obviously lowered on days 14 and 21 after medication. In group C, gametocytes disappeared in 5 out of 9 patients with the failure of infection to mosquitoes on day 4 after treatment. This indicates that artemisinine can effectively influence the infectivity of gametocytes of P. falciparum. Artemisinine is superior to mefloquine in blocking the transmission of P. falciparum malaria.

[Randomised comparison on the treatment of falciparum malaria with dihydroartemisinin and piperaquine].

In 1988, 50 cases each of falciparum malaria were treated by dihydroartemisin (360 mg in 5 days and 480 mg in 7 days respectively), and compared randomly with piperaquine phosphate group. The results showed that the plasmodium of falciparal malaria in Dong Fang County, Hainan province, is much more resistant to piperaquine phosphate, in the 51 cases treated by piperaquine, 33.3% were sensitive, 19.0% were RI, 21.6% were RII, and 25.5% were RIII. The effect of dihydroartemisinin (both 5 days and 7 days therapy) were obviously better than that of pipera quine, fever subsidence time and parasite clearance time were similar and parasite recrudescence rate showed no obvious difference in these two groups too.

[Comparative study of artemisinin suppositories and piperaquine phosphate in the treatment of falciparum malaria].

Artemisinin, developed by Chinese scientists, is a new type of anti-malarial drug with quick effect and low toxicity. Since its solubility in water or oil is very low, it cannot be made into a clear injection to be given intramuscularly or intravenously for emergency use. The artemisinin suppositories used in the study was provided by the institute of Chinese Materia Medica in 1982. Phase I and Phase II clinical trials of the drug were made by Guangzhou College of TCM. The results showed that the therapeutic effect of Artemisinin suppositories was satisfactory with no apparent side effects. The total dosage recommended was 2800-3200 mg. In 1986, fifty-six adults with falciparum malaria were treated with a total dose of 2800 mg Artemisinin suppositories for 3 days and randomly compared with a control group of Piperaquine phosphate in the Dongfang Town Hospital, Dongfang ( ) County of Hainan Island. The parasite clearance time in Artemisinin suppositories group (71.8 +/- 16.0 hrs) was significantly faster than that of Piperaquine phosphate group (100.3 +/- 20.3hrs), but recrudescence rate by 28 days (48.2%) was much higher than that of Piperaquine phosphate (17.0%). Artemisinin suppositories is simple to administrate and therefore it could be applied in endemic area of remote countryside and to the patients of incapable of oral dosing.