Azithromycin for Malaria?

Malaria continues to be one of the greatest infectious disease problems in the world.Antimalarial drugs play an essential role in the treatment and control of malaria.For treatment, older drugs are limited by resistance, but artemisinin-based combination therapy remains highly effective in most areas.However, artemisinin resistance has emerged in southeast Asia, 1 and resistance to artemisinin partner drugs is already common in many areas.2 In Cambodia, where resistance to both artemisinins and piperaquine is prevalent, frequent failures after treatment with dihydroartemisinin-piperaquine have been seen.3 We can anticipate that artemisinin resistance will spread to other areas, and that resistance to artemisinins and partner drugs will seriously threaten our ability to treat malaria.Chemoprevention is an important strategy for malaria control.Nonimmune travelers to malaria-endemic countries are typically prescribed atovaquone-proguanil (Malarone), mefloquine, or doxycycline to prevent malaria.This practice is highly effective, but impractical for endemic populations due to cost and toxicity concerns.In Africa, intermittent preventive therapy is advocated in high-risk populations, with intermittent administration of sulfadoxine-pyrimethamine (SP) to pregnant women, and seasonal administration of SP-amodiaquine to children in the Sahel subregion, where there is a relatively low level of resistance to these drugs.However, the utility of drugs to prevent malaria in endemic populations is limited by resistance to available agents.Monthly dihydroartemisinin-piperaquine has shown strong protective efficacy in African children in some trials, 4 but is not standard practice yet.For both treatment and chemoprevention, antimalarial drugs are increasingly limited by resistance.New drugs are greatly needed, and a quite robust pipeline of drugs is under development.5 However, development is challenging, typically with slow progress even after promising agents show excellent efficacy, and with the potential for lead compounds to fail in later stages of development.Indeed, no new classes of antimalarial drugs have been broadly approved in a few decades, and it remains unclear if the pipeline will satisfy upcoming needs.With this background, it behooves us to consider repurposing of available antimicrobial drugs to treat malaria.One such drug is azithromycin, a macrolide antibiotic with broad-spectrum activity against gram-positive and atypical bacteria.As is the case with some other antibacterial protein synthesis inhibitors, including doxycycline, azithromycin exerts antimalarial activity by inhibiting function of the apicoplast.6,7 This action is necessarily slow.