Combinations Drug Effect Of Chlorochine And Azithromycin On Plasmodium Berghei In Mice

Objective:To investigate activity of single chlorochine or azithromycin and combination against P. berghei. This study is to provide more reference for all work on prevention and treatment of malaria in science research and clinical practice in the future.Methods:There are 70 health mice with 25-30mg weight to attend this test. All were randomed to 7 groups, that is 10 doses and 5 doses chlorochine -group , 10 doses and 5 doses azithromycin-group, low-dose combination group and ultra low-dose combination group, and control group. Parasites by blood stored in liquefied nitrogen were resuscitated and then transferred into mice by intraperitoneal injection. And blood transmission was repeated once. When parasite densities were higher, all 70 mice were infected parasites by blood from keeping P. berghei mice by intraperitoneal injection. Check the plasmodium with microscope every day. When parasites were found in all mice and average parasite density have 15141.2/μl, the mice received oral different doses chlorochine and azithromycin which is similar to the quintupling and decuple dose of people recommended dosage and compatibility therapy of respective half-value dose. All thick and thin blood smears were stainned by 3% Giemsa stain after mehanol fixation. Thick and thin blood smears of microscopic examination by oil immersion lens was used to check parasites and classify,then calculate densities. To evaluate the effects, the dates on parasite density were statistically dealed with by Microsoft Excel, and also cure rates and survival rates were observed.Results:The parasites of 7 mice of 10 times azithromycin- group were all cleared in the 8th day. Till the 9th day the parasites of all 10 mice were all cleared and have 100% cure rate and 100% survival rate. Cure rate and survival rate of 5 times azithromycin- group were 20% and 50% respectively in 9 days. And cure rates of 10 times chlorochine– group and 5 times chlorochine– group were both 20% and survival rates were 80% and 70% respectively after 8 days. The parasites were cleared in a mouse in the second day and gradually all mice were cured in 5 days in the low-dose combined group and healing rate and survival rate were both 100%. There were simultaneous cure and recrudescence in the ultra low-dose combination group, and cure rate and survival rate were 50% and 80% respectively in 8 days. As control group, the parasites were not cleared in all 10 mice and survival rate were 70%.Conclusion:According to the first study using azithromycin to treat malaria in China showed single azithromycin can cure P. berghei malaria. But the time of therapy was longer. When combined with chlorochine ,synergistic effect occured. Which has not only lesser dose but also high and rapid effect on P. berghei. Azithromycin has widely used in clinical practice and has many advantages as the second generation macrolide antibiotics. We expect azithromycin in combination with other antimalarial drugs can treat and prevent all sensitive strain and resistant strain malaria and reduce relapse and recrudescence. Meanwhile, azithromycin may be primaquine replacement in malaria patients with glucose-6-phosphate dehydrogenase deficiency. And azithromycin also can be used in pregnant women and children with malaria.