Abstract
BackgroundAzithromycin (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.MethodsAZM-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.ResultsThe 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.ConclusionsAZM 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.
Highlights
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
Determination of appropriate timing for blood feeding It has already been reported that AZM exerts schizontocidal effects against P. berghei blood stage four days after drug administration [19]
Effect of AZM on replication of P. berghei apicoplast In the case of blood stages, inhibition of apicoplast replication by chemicals has been usually evaluated by the ratio of apicoplast DNA to nuclear DNA [31,32]
Summary
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. The strategy of blocking malarial transmission has been claimed to limit the spread of malaria and to reduce the spread of drug-resistant parasites [5,6,7,8]. Considering that very high coverage is essential for a significant impact on malaria transmission, mass drug administration (MDA) for people including children and pregnant women in endemic area is required [6]. A limited number of drugs or compounds has been confirmed to possess transmission-blocking activity [5,11,12,13]. If licensed antibiotics are proven to have transmission-blocking activity, practical evaluation should be greatly accelerated and their impact should be fully exploited [14]
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