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From methylene blue to chloroquine: A brief review of the development of an antimalarial therapy

Department of Pathology, University of Minnesota School of Medicine, Duluth, MN, USA.
Parasitology Research (Impact Factor: 2.33). 03/2012; 111(1):1-6. DOI: 10.1007/s00436-012-2886-x
Source: PubMed

ABSTRACT Malarial treatment is widely and readily available today. However, there was a time in the not-so-distant past when malaria was a deadly disease with no known cause or cure. In this article, we trace the origins of an antimalarial therapy from the discovery of the nature of the malarial parasite through the development of chloroquine. We dedicate this article to Johann "Hans" Andersag, the scientist who developed chloroquine, on the 110th anniversary of his birth, 16 February 1902.

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    • "Antimalarial medication, including chloroquine, has been the frontline choice in this battle. However, because of over-and inappropriate use, resistant strains of the malarial parasite started to evolve, diminishing the effects of the drug [6] [15]. Nevertheless, alternative uses of chloroquine include treatment of rheumatoid arthritis, discoid lupus erythematosus and amoebic hepatitis [5]. "
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    ABSTRACT: For many years chloroquine was used as a prophylactic agent against malaria, and more recently as a mild immunosuppressive. However, due to lengthy treatment periods, adverse effects have become apparent, which included retinopathy. The structurally related hydroxychloroquine is less toxic, thought to be owing to a lower tissue accumulation in melanin rich areas. This study primarily focused on quantifying melanin binding between chloroquine and hydroxychloroquine at physiological pH to investigate the potential link between binding and reported toxicity. In addition, for the first time this study quantified the actual extent of adsorption of chloroquine and hydroxychloroquine to melanin and examined the desorption profile of both drugs from melanin to demonstrate the affinity between the pigment and the solutes. The results suggest that there is a difference between the adsorption affinities of chloroquine and hydroxychloroquine, potentially explaining the differences in bioaccumulation in retinal tissue. In addition, both solutes displayed a strong physical attraction to the absorbent.
    Toxicology Reports 11/2014; 1. DOI:10.1016/j.toxrep.2014.10.019
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    • "For many years it was the first-line antimalarial drug. However, as for many antimicrobial drugs, eventually (two decades later) drugresistant strains developed (Krafts et al. 2012). In the second half of the twentieth century, another important antimalarial drug was also developed in a time of war: mefloquine was number 142,490 of a total of 250,000 antimalarial compounds screened during the US Army's antimalarial drug discovery program. "
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    ABSTRACT: Malaria is an ancient disease continuing to pose an enormous health, social, and economic burden. It is caused by infection with protozoan parasites belonging to the genus Plasmodium transmitted via the bite of female Anopheles species mosquitoes. Of more than 100 different species infecting a wide range of animals from rodents and birds to mammals, five species of malaria parasites are known to infect humans: Plasmodium falciparum, P. vivax, P. ovale (now being recognized as consisting of two subspecies), P. malariae and P. knowlesi. P. falciparum is most likely to cause severe disease and, if not promptly treated, may lead to death. References to the disease occur in the Chinese canon of medicine, clay tablets from Mesopotamia, Egyptian papyri and Indian medical works. Descriptions of malaria from classic Greece and the Roman Empire are abundant. It was commonly believed that malaria was caused by marsh water and foul vapors emanating from swamps, hence the word mal’aria, from the Italian for “bad air”. For thousands of years, no effective treatment was available. This changed with the discovery of Artemisia annua (sweet wormwood) in China and the use of quinine from Peruvian bark as potent and effective drugs against malaria. The current understanding of the malaria parasites and their lifecycle starts in the end of the nineteenth century with the discovery of the malaria parasites in the blood of malaria patients by Alphonse Laveran in 1880. Subsequently, Ronald Ross discovered in 1897 that a bird malaria parasite was transmitted by mosquitoes. In 1898 Giovanni Grassi, Camillo Golgi, Ettore Marchiafava, Amico Bignami, Angelo Celli and Giuseppe Bastianelli confirmed that malaria in humans was also a mosquito-borne disease, in this case Anopheles species. Grassi and Filetti introduced the names of P. vivax and P. malariae in 1890. The causative agent of what was dubbed ‘malignant malaria’ was baptized P. falciparum by William Welch in 1897 and P. ovale by John Stephens in 1922. The discovery of a liver stage before malaria enters the bloodstream was made by Henry Shortt and Cyril Garnham in 1948. The existence of dormant stages, in P. vivax and P. ovale was shown in 1982 by Wojciech Krotoski. This article describes the key discoveries and provides a short overview of the multifaceted history of malaria.
    Discoveries in Modern Science: Exploration, Invention, Technology, 1st Edition edited by James Trefil, Patricia Daniels, Donna McPhie, Craig Schiffries, 10/2014: chapter Malaria Is Transmitted by Mosquitoes: pages 640-647; Macmillan Reference USA., ISBN: 0028662482
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    • "After the key discoveries of the causative agents of malaria and its vectors at the end of the 19th century (Cox, 2010), more specific control tactics were developed through management of the environment (Konradsen et al., 2004). In addition, the discovery of the efficient and affordable curative drug chloroquine considerably reduced malarial morbidity and mortality for decades (Wellems, 2002; Krafts et al., 2012). The eradication of malaria from Brazil (Soper, 1965) and Italy (Romi et al., 1997) are some of the great historical examples of successful sanitation projects in the pre-DDT era (see de Zulueta, 2000; Killeen et al., 2002) where a quasi-military approach was used to rigorously remove Anopheles gambiae from their oviposition and resting sites, leading to an interruption of malaria transmission. "
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    ABSTRACT: The intolerable burden of malaria, when faced with high levels of drug resistance, increasing insecticide resistance and meagre resources at the national level, remains a great public health challenge to governments and the research/control community. Efficient control methods against the vectors of malaria are desperately needed. Control strategies for malaria that integrate the transfer of sterile sperm by released males to wild virgin females with other control tactics are currently being developed, and optimised mass-rearing, irradiation and release techniques are being validated in several field sites. However, the success of this strategy as part of wider pest control or health management programmes strongly depends on gaining public understanding and acceptance. Here we attempt to review what progress has been made and the remaining challenges surrounding the use of the sterile insect technique against malaria from technical and social perspectives.
    Acta tropica 11/2013; 132. DOI:10.1016/j.actatropica.2013.11.019
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