Table of Contents: Malaria: targets and drugs for all stages


Image Credit: Delves M, Plouffe D, Scheurer C, Meister S, et al.
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April 25th is World Malaria Day. Malaria remains one of the largest Global Health Challenges, with over 40% of the world population at risk for infection, and ~0.7 million deaths per year still occurring, mostly among children and pregnant woman. Drugs are essential tools for treatment, control and eventual elimination and eradication of malaria. Insecticides have been a main stay in prior eradication campaigns but treatment and prevention with drugs has played a critical role in reducing malaria burdens at many endemic sites. Some diseases (like small pox) have been successfully eradicated through vaccines. Although the first antimalarial vaccine will soon be marketed, control and eradication will require drugs. This is because protective immunity against malaria is partial at best. It is also temporary and does not develop to latent stages. The parasite has a complex life cycle, and different stages of management and eradication, need different and multiple drugs. Thus it is unlikely that a single 'super' drug will eliminate the vast reservoirs of infection and disease.

The burden of malaria has decreased in many endemic sites, but increased in others. Drugs are essential for the treatment of blood stage infection, which is responsible for the symptoms and pathologies of malaria as well as development of transmission stage parasites. Drugs are also required to break the cycle of infection and to target latent stages in multiple parasite species that cause human malaria. Moreover resistance has emerged to every known antimalarial, including artemisinin, which is critical to the current frontline combination therapy against blood stage infection. If drug resistance to artemisinin becomes wide-spread any gains that have been made to control malaria will be erased.

To successfully overcome these hurdles, we need multiple combination therapies to provide first, second and third line chemotherapeutic options. Thus ACTs need to be followed by additional combinations against each of the four different stage (blood, transmission, vector and liver) parasites. Private public partnerships such as the Medicine for Malaria Venture have developed successful strategies to progress new drugs against malaria. Key to the success has been bridging basic discovery research in academia and drug development by pharma (including virtual pharma)

Editor-in-Chief Kasturi Haldar and Dr. Margaret A. Phillips (UT Southwestern) elaborate on this in their Speaking of Medicine editorial, titled "More drugs for malaria: time to expand the antimalarial portfolio" through mining screens and identifying novel targets to develop multiple, front line combination therapies. To highlight the existing literature PLOS (Pathogens, NTDs and Medicine) authors have contributed to basic drug discovery research, Drs. Haldar and Phillips combed the archives to find those articles on novel targets, drug screens and best practices. They further discuss activities of the world malaria community to successfully integrate basic drug discovery research with translation into a pipeline of treatments that needs expansion and support to control and ultimately eradicate malaria.

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