Quinine-resistant Severe Falciparum Malaria Effectively Treated with Atovaquone and Proguanil Hydrochloride Combination Therapy

Uchiyama, Hitoji; Okamoto, Akio; Sato, Katsuaki; Yamada, Tomohiro; Murakami, Sadatsugu; Yoneda, Seiichi; Kajita, Yoshihiro; Tegoshi, Tatsuya; Arizono, Naoki

doi:10.2169/internalmedicine.43.624

Cited by 12 publications

(13 citation statements)

References 9 publications

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“…[349] Tetracycline (96) has been administered in combination with quinine (1), and minocycline (98) is sporadically used in the clinic. [350] Doxycycline (97) is used in combination with quinine against severe malaria. For both drugs, intravenous formulations are available.…”

Section: Tetracyclinesmentioning

confidence: 99%

Malaria Chemotherapeutics Part I: History of Antimalarial Drug Development, Currently Used Therapeutics, and Drugs in Clinical Development

2007

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Since ancient times, humankind has had to struggle against the persistent onslaught of pathogenic microorganisms. Nowadays, malaria is still the most important infectious disease worldwide. Considerable success in gaining control over malaria was achieved in the 1950s and 60s through landscaping measures, vector control with the insecticide DDT, and the widespread administration of chloroquine, the most important antimalarial agent ever. In the late 1960s, the final victory over malaria was believed to be within reach. However, the parasites could not be eradicated because they developed resistance against the most widely used and affordable drugs of that time. Today, cases of malaria infections are on the rise and have reached record numbers. This review gives a short description of the malaria disease, briefly addresses the history of antimalarial drug development, and focuses on drugs currently available for malaria therapy. The present knowledge regarding their mode of action and the mechanisms of resistance are explained, as are the attempts made by numerous research groups to overcome the resistance problem within classes of existing drugs and in some novel classes. Finally, this review covers all classes of antimalarials for which at least one drug candidate is in clinical development. Antimalarial agents that are solely in early development stages will be addressed in a separate review.

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Section: Tetracyclinesmentioning

confidence: 99%

Malaria Chemotherapeutics Part I: History of Antimalarial Drug Development, Currently Used Therapeutics, and Drugs in Clinical Development

2007

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“…Tetracycline had previously been used in combination with quinine, but is nowadays replaced with doxycycline. Minocycline is sporadically used as a doxycycline replacement [119]. It has the unique property to down-regulate transcript expression of the chemokine CXCR 3, which in mice is of critical importance for the development of cerebral malaria [120].…”

Section: Tetracyclinesmentioning

confidence: 99%

Antibiotics in Malaria Therapy and their Effect on the Parasite Apicoplast

Pradel¹,

Schlitzer

2010

CMM

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The impact of selected antibiotics on combating malaria infections was discovered in the mid of last century. Only recently, studies on their modes of action in malaria parasites have been initiated, prompted by the discovery of a prokaryotic organelle, the apicoplast. This plastid-derived structure, which originates from a secondary endosymbiotic event, possesses important metabolic as well as housekeeping functions, including fatty acid and heme biosynthesis. Due to its indispensability for parasite survival it represents a promising target for the use of antibiotics in malaria therapy. Most antibiotics cause a delayed death phenotype, which manifests in the late onset of antimalarial activity during the second replication cycle of the pathogen. This review will describe the effect of classical antibacterial agents against malaria parasites and the use of some of these compounds in clinical settings. Firstly we discuss the current knowledge about the physiological and morphological effects of antibiotics on the parasite and the apicoplast in particular, with special focus on the delayed death effect. Secondly antimalarial antibiotics are specified and their effects in vitro are compared with available in vivo data and clinical studies. Major precautions and side effects are described.

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“…Atovaquone-proguanil has reported cure rates of 94% to 100% for P falciparum infections acquired in Southeast Asia, Africa, and South America. 52,[94][95][96][97][98][99][100][101][102][103][104][105][106][107][108][109] To date, there have been 12 published cases of atovaquone-proguanil failure for the treatment of P falciparum malaria (from East, West, and Central Africa), 7 of which have had isolates with genetically confirmed markers of resistance (ie, mutations in the cytochrome b gene), [110][111][112][113][114][115][116][117] and thus, clinicians should remain aware of the rare possibility of atovaquone-proguanil treatment failures.…”

Section: Uncomplicated Falciparum Malariamentioning

confidence: 99%