Pitfalls in a Discovery: The Chronicle of Chloroquine *

Gr, Coatney

doi:10.4269/ajtmh.1963.12.121

Cited by 172 publications

(92 citation statements)

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“…Primaquine and quinacrine were produced after the First World War. CQ followed shortly thereafter in 1934 (203), around 1946 it was designated the drug of choice for treatment of malaria (43). The earliest anecdotal reports of resistance to an antimalarial agent are those for quinine in 1844 and 1910 (67,143,144).…”

Section: Development Of the First Antimalarial Agents And Anecdotal Rmentioning

confidence: 99%

History, Dynamics, and Public Health Importance of Malaria Parasite Resistance

2004

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Despite considerable efforts, malaria is still one of the most devastating infectious diseases in the tropics. The rapid spread of antimalarial drug resistance currently compounds this grim picture. In this paper, we review the history of antimalarial drug resistance and the methods for monitoring it and assess the current magnitude and burden of parasite resistance to two commonly used drugs: chloroquine and sulfadoxine-pyrimethamine. Furthermore, we review the factors involved in the emergence and spread of drug resistance and highlight its public health importance. Finally, we discuss ways of dealing with such a problem by using combination therapy and suggest some of the research themes needing urgent answers

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Section: Development Of the First Antimalarial Agents And Anecdotal Rmentioning

confidence: 99%

History, Dynamics, and Public Health Importance of Malaria Parasite Resistance

2004

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“…44 chloroquine After an analogue that had been developed in Germany was captured in 1943, during World War II, chloroquine quickly came into universal use as therapy for and prophylaxis against malaria. 45 Chloroquine was highly effective, easily administered, and inexpensive and had good safety and tolerability. However, resistance in P. falciparum appeared in the late 1950s in Thailand and Colombia and emerged in the 1970s in New Guinea and eastern sub-Saharan Africa.…”

Section: Safety and Tolerabilitymentioning

confidence: 99%

Effectiveness of Antimalarial Drugs

Baird¹

2005

N Engl J Med

308

206

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“…Developed as resochin in the 1930s, its German developers abandoned the drug in favor of a seemingly less toxic methylated analog called sontochin. The U.S. Army obtained experimental sontochin tablets in Algeria during late 1943 and almost immediately (50). The recommended adult treatment was 25 mg/kg body weight administered in 3 doses over 48 h (typically 10 plus 10 plus 5 mg/kg at 24-h intervals).…”

Section: Chloroquine Therapymentioning

confidence: 99%

Resistance to Therapies for Infection by Plasmodium vivax

2009

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SUMMARY The gravity of the threat posed by vivax malaria to public health has been poorly appreciated. The widely held misperception of Plasmodium vivax as being relatively infrequent, benign, and easily treated explains its nearly complete neglect across the range of biological and clinical research. Recent evidence suggests a far higher and more-severe disease burden imposed by increasingly drug-resistant parasites. The two frontline therapies against vivax malaria, chloroquine and primaquine, may be failing. Despite 60 years of nearly continuous use of these drugs, their respective mechanisms of activity, resistance, and toxicity remain unknown. Although standardized means of assessing therapeutic efficacy against blood and liver stages have not been developed, this review examines the provisional in vivo, ex vivo, and animal model systems for doing so. The rationale, design, and interpretation of clinical trials of therapies for vivax malaria are discussed in the context of the nuance and ambiguity imposed by the hypnozoite. Fielding new drug therapies against real-world vivax malaria may require a reworking of the strategic framework of drug development, namely, the conception, testing, and evaluation of sets of drugs designed for the cure of both blood and liver asexual stages as well as the sexual blood stages within a single therapeutic regimen.

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Pitfalls in a Discovery: The Chronicle of Chloroquine *

Cited by 172 publications

References 0 publications

History, Dynamics, and Public Health Importance of Malaria Parasite Resistance

History, Dynamics, and Public Health Importance of Malaria Parasite Resistance

Effectiveness of Antimalarial Drugs

Resistance to Therapies for Infection by Plasmodium vivax

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