Research
Suppressive effect of azithromycin on Plasmodium berghei mosquito stage development and apicoplast replication
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* Corresponding author: Meiji Arai marai@med.kagawa-u.ac.jp
1 Department of Immunology and Parasitology, University of Occupational and Environmental Health, Japan, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu 807-8555, Japan
2 First Department of Internal Medicine, University of Occupational and Environmental Health, Japan, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu 807-8555, Japan
3 Department of International Medical Zoology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793, Japan
Malaria Journal 2010, 9:73 doi:10.1186/1475-2875-9-73
Published: 10 March 2010Abstract
Background
Azithromycin (AZM) is a macrolide antibiotic that displays an excellent safety profile even in children and pregnant women and has been shown to have anti-malarial activity against blood stage Plasmodium falciparum. This study evaluated the transmission-blocking effect of AZM using a rodent malaria model.
Methods
AZM-treated mice infected with Plasmodium berghei were exposed to Anopheles stephensi mosquitoes, followed by the observation of parasite development at different phases in the mosquito, i.e., ookinetes in the midgut, oocysts on the midgut, and sporozoites in the midgut and salivary glands. Furthermore, to evaluate the effect on organelle replication of each stage, quantitative real-time PCR analysis was performed.
Results
The inhibitory effect of AZM was noticeable in both gametocyte-ookinete transformation in the midgut and sporozoite production in the oocyst, while the latter was most remarkable among all the developmental phases examined. Real-time PCR analysis revealed that AZM suppressed apicoplast replication at the period of sporozoite production in oocysts.
Conclusions
AZM inhibits parasite development in the mosquito stage, probably through the same mechanism as in the liver and blood stages. Such a multi-targeting anti-malarial, along with its safety, would be ideal for mass drug administration in malaria control programmes.