Ri Quinine-Fansidar Resistant Falciparum Malaria From Malawi

Warhurst, David C.; Hall, Andy; Tjokrosonto, Soesanto

doi:10.1016/s0140-6736(85)90376-9

Cited by 13 publications

(4 citation statements)

References 2 publications

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“…Parasite resistance to CQ resulted in a switch to the antifolate combination sulfadoxine-pyrimethamine (SP), which encountered resistance within a few years. Later, multidrug resistance (defined as resistance to three or more drugs) appeared in Southeast Asia and South America in response to the switch to either mefloquine (MFQ) or quinine (QUIN) and then in Africa in the late 1970s (6,8,53). Recently, the majority of countries have switched to highly efficient artemisinin derivative combinations (ACTs); nevertheless, there is new evidence for clinical resistance to these drugs (11).…”

mentioning

confidence: 99%

Novel 4-Aminoquinoline Analogs Highly Active against the Blood and Sexual Stages of Plasmodium In Vivo and In Vitro

Saénz

Mutka

Udenze

et al. 2012

Antimicrob Agents Chemother

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New drugs to treat malaria must act rapidly and be highly potent against asexual blood stages, well tolerated, and affordable to residents of regions of endemicity. This was the case with chloroquine (CQ), a 4-aminoquinoline drug used for the prevention and treatment of malaria. However, since the 1960s, Plasmodium falciparum resistance to this drug has spread globally, and more recently, emerging resistance to CQ by Plasmodium vivax threatens the health of 70 to 320 million people annually. Despite the emergence of CQ resistance, synthetic quinoline derivatives remain validated leads for new drug discovery, especially if they are effective against CQ-resistant strains of malaria. In this study, we investigated the activities of two novel 4-aminoquinoline derivatives, TDR 58845, N 1 -(7-chloro-quinolin-4-yl)-2-methyl-propane-1,2-diamine, and TDR 58846, N 1 -(7-chloro-quinolin-4-yl)-2,N 2 ,N 2 -trimethylpropane-1,2-diamine and found them to be active against P. falciparum in vitro and Plasmodium berghei in vivo. The P. falciparum clones and isolates tested were susceptible to TDR 58845 and TDR 58846 (50% inhibitory concentrations [IC 50 s] ranging from 5.52 to 89.8 nM), including the CQ-resistant reference clone W2 and two multidrug-resistant parasites recently isolated from Thailand and Cambodia. Moreover, these 4-aminoquinolines were active against early and late P. falciparum gametocyte stages and cured BALB/c mice infected with P. berghei. TDR 58845 and TDR 58846 at 40 mg/kg were sufficient to cure mice, and total doses of 480 mg/kg of body weight were well tolerated. Our findings suggest these novel 4-aminoquinolines should be considered for development as potent antimalarials that can be used in combination to treat multidrug-resistant P. falciparum and P. vivax.

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mentioning

confidence: 99%

Novel 4-Aminoquinoline Analogs Highly Active against the Blood and Sexual Stages of Plasmodium In Vivo and In Vitro

Saénz

Mutka

Udenze

et al. 2012

Antimicrob Agents Chemother

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“…Chloroquine-resistant parasites in Africa were thought by some to share the same origin as the Indo-China strains, but by others to have developed locally as a result of mass drug administration plus intrinsic entomological, epidemiological and parasitological factors that promoted local resistance selection (Diribe and Warhurst, 1985). Current molecular studies suggest the Asian origin of African isolates, but at least four different foci of chloroquine resistance have so far been identified (Warhurst et al, 1995). Resistance to chloroquine spread to almost all the countries thus limiting the effective use of this low cost antimalarial.…”

Section: Status Of Resistancementioning

confidence: 99%

Is chloroquine making a comeback?

Saifi

Beg²,

Harrath³

et al. 2012

Afr. J. Pharm. Pharmacol.

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Malaria remains one of the leading causes of disease and death in the tropics, mainly of children under 5 years of age. Chloroquine began as a first-line antimalarial in 1946; it became the corner stone of antimalarial chemotherapy for the next 40 years. It is one of the least expensive antimalarials available and is still in widespread use. Chloroquine can be taken both as prophylactic and as a treatment. For decades, chloroquine was a remarkably effective, safe, and inexpensive antimalarial. Optimism about effectiveness of chloroquine led public health professionals to predict the eradication of malaria by 2000. Despite much research during the last 40 years, the exact mechanism by which the chloroquine kills the malaria parasite remains controversial. Biochemical analyses suggest that this class of compounds enter acidic vacuoles of host cells, where they inhibit the growth of parasites by forming a complex with haematin. Unfortunately, Plasmodium falciparum gradually became resistant to chloroquine. After first appearing in Southeast Asia and South America in the late 1950s, resistance spread throughout Africa by the 1980s. Resistance to chloroquine was slow to develop, taking almost 20 years, despite extensive use of the drug, suggesting that mutations in several genes were required to produce the resistance phenotype. The mechanism of chloroquine resistance also is uncertain. Similar to the artemisinin derivatives, prospects for long-term chloroquine efficacy will be enhanced if it can be used in combination, such as chloroquine-azithromycin. With the right dosage and combination, the prospects for a chloroquine comeback are good.

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“…It also lowers malaria incidence and the rate at which resistance emerges and spreads. Artemisinin (qinghaosu) is the antimalarial principle isolated by Chinese scientists from Artemisia annua L [20,21]. It is a sesquiterpene lactone with a peroxide bridge link- Fig.…”

Section: Treatmentmentioning

confidence: 99%

“…In 1983, Malawi was the first country in East Africa to change from CQ to the SP combination as standard treatment, and other Africans countries followed this example in the late 1990s [21]. Due to the extensive use of this combination, resistance also spread in East Africa [29].…”

Section: Antimalarial Drug Resistancementioning

confidence: 99%

Molecular and Biological Aspects of Antimalarial Resistance in Plasmodium falciparum and Plasmodium vivax

Bustamante

Batista²,

Zalis³

2009

CDT

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The development of antimalarial drugs involving novel mechanisms of action is of imminent importance. Several potential drug candidates of synthetic and natural origin as well as their combination therapies are currently being evaluated for their efficacy against drug-resistant strains of the parasite. Various plasmodial targets/pathways, such as the Purine salvage pathway, Pyrimidine biosynthesis pathway and also the processes in the apicoplast, have been identified and are being utilized for the discovery and development of novel antimalarial therapies. This article provides an overview of the latest developments in terms of cell and molecular biology that will improve the knowledge related to drug-resistant malaria and to new molecular targets.

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Ri Quinine-Fansidar Resistant Falciparum Malaria From Malawi

Cited by 13 publications

References 2 publications

Novel 4-Aminoquinoline Analogs Highly Active against the Blood and Sexual Stages of Plasmodium In Vivo and In Vitro

Novel 4-Aminoquinoline Analogs Highly Active against the Blood and Sexual Stages of Plasmodium In Vivo and In Vitro

Is chloroquine making a comeback?

Molecular and Biological Aspects of Antimalarial Resistance in Plasmodium falciparum and Plasmodium vivax

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