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Blood schizontocidal activity of azithromycin and its combination with α/β arteether against multi-drug resistant Plasmodium yoelii nigeriensis, a novel MDR parasite model for antimalarial screening

Published online by Cambridge University Press:  08 June 2005

R. TRIPATHI ,
S. DHAWAN  and
G. P. DUTTA
R. TRIPATHI
Affiliation:
Division of Parasitology, P.O. Box No. 173, Central Drug Research Institute, Chattar Manzil Palace, Lucknow, 226001, India
S. DHAWAN
Affiliation:
C.I.M.A.P., Lucknow, India
G. P. DUTTA
Affiliation:
Emeritus Scientist, C.S.I.R., C.D.R.I., Lucknow, India
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Abstract

Many different drug-resistant lines of rodent malaria are available as screening models. It is obligatory to screen new compounds for antimalarial activity against a series of resistant lines in order to identify a compound with potential for the treatment of multi-drug resistant (MDR) malaria infections. Instead of using a battery of resistant lines, a single MDR Plasmodium yoelii nigeriensis strain that shows a wide spectrum of drug resistance to high doses of chloroquine, mepacrine, amodiaquine, mefloquine, quinine, quinidine, halofantrine as well as tetracyclines, fluoroquinolines and erythromycin, was used to assess the blood schizontocidal efficacy of a new macrolide azithromycin and other antibiotics. The present study shows that only azithromycin has the potential to control an MDR P. y. nigeriensis infection in Swiss mice, provided the treatment with a dose of 50–100 mg/kg/day by oral route is continued for a period of 7 days. Tetracycline, oxytetracycline, doxycyline, erythromycin, ciprofloxacin and norfloxacin, although active in vitro, failed to protect the mice. Tetracycline, ciprofloxacin and norfloxacin combinations with chloroquine did not control the infection. Additionally, the antimalarial efficacy of azithromycin can be potentiated with the addition of arteether, which is an ethyl ether derivative of artemisinin. A total (100%) curative effect has been obtained with a shorter regimen of 4 days only.

Keywords

Plasmodium yoelii nigeriensismulti-drug resistancemalariaantimalarialazithromycinantibioticsα/β arteether
Type
Research Article
Information
Parasitology , Volume 131 , Issue 3 , September 2005 , pp. 295 - 301
Copyright
© 2005 Cambridge University Press

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