Artemisinin Resistance inPlasmodium falciparumMalaria

Dondorp, Arjen M.; Nosten, François; Yi, Poravuth; Das, Debashish; Phyo, Aung Phae; Tärning, Joel; Lwin, Khin Maung; Ariey, Frédéric; Hanpithakpong, Warunee; Lee, Sue J.; Ringwald, Pascal; Silamut, Kamolrat; Imwong, Mallika; Chotivanich, Kesinee; Lim, Pharath; Herdman, Trent; An, Sen Sam; Yeung, Shunmay; Singhasivanon, Pratap; Day, Nicholas P. J.; Lindegårdh, Niklas; Socheat, Duong; White, Nicholas J.

doi:10.1056/nejmoa0808859

Cited by 2,935 publications

(2,451 citation statements)

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“…Cameroon with 71% of the total population living in hightransmission areas and 4500 deaths recorded annually is one of the most affected countries in Africa (WHO, 2014). The currently prescribed treatments particularly the Artemisinin-based Combination Therapies (ACTs) are threatened by emerging resistance of P. falciparum strains (Dondorp et al, 2009). Given these limitations, there is a motivated search for new drugs against Plasmodium parasites.…”

Section: Introductionmentioning

confidence: 99%

In vitro and in vivo antiplasmodial activity of extracts from Polyalthia suaveolens, Uvaria angolensis and Monodora tenuifolia (Annonaceae)

Mfopa¹,

Mbouna²,

Tchokouaha³

et al. 2017

Int. J. Bio. Chem. Sci

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The present study aimed at investigating the in vitro and in vivo susceptibility of malaria parasites to crude extracts and fractions from Polyalthia suaveolens, Uvaria angolensis, and Monodora tenuifolia. The ethanolic extracts were partitioned using water, dichloromethane, hexane, and methanol. The most promising fraction was subjected to column chromatography. The antiplasmodial effect of extracts, fractions and subfractions against P. falciparum Chloroquine resistant (PfK1) strain was determined using SYBR green florescence assay. The promising fraction was assessed for cytotoxicity against Human Foreskin Fibroblast (HFF) cells and further for safety in Swiss albino mice and suppressive effect against P. berghei. The methanol sub-fraction of P. suaveolens [PStw(Ace)] showed the highest potency with IC 50 of 3.24 µg/mL. Sub-fraction PS8 from PStw(Ace) was the most active with IC 50 of 4.42 µg/mL. Oral administration of PStw(Ace) at 5000 mg/kg b.w in mice showed no signs of toxicity. Also, it exerted the highest suppressive effect against P. berghei at 400 mg/kg b.w throughout the 4 days experiment. Overall, the results achieved supported the use of the three plants in the traditional treatment of malaria in Cameroon. More interestingly, the PStw(Ace) fraction might be of interest in future development of an antimalarial phytodrug.

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Section: Introductionmentioning

confidence: 99%

In vitro and in vivo antiplasmodial activity of extracts from Polyalthia suaveolens, Uvaria angolensis and Monodora tenuifolia (Annonaceae)

Mfopa¹,

Mbouna²,

Tchokouaha³

et al. 2017

Int. J. Bio. Chem. Sci

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“…artesunate is activated for the rest of intra-erythrocytic development, and thus, K13 variant parasites are fully susceptible to prolonged exposure to artemisinin, as clearly seen in vitro [2,4,5] and in vivo [3,22,23].…”

Section: Variants Of Pfk13 and The Parasite Cell Cycle In Vitromentioning

confidence: 95%

“…This was soon followed by more extensive observations from the randomised study of Dondorp et al [2]. Importantly, the latter study demonstrated that slow parasite clearance was observed in malaria patients from western Cambodia irrespective of whether they had been treated with monotherapy, or with artemisinin-based combination therapy (ACT), but this was not observed in patients from the Thailand-Myanmar border to the northwest.…”

Section: A New Artemisinin Susceptibility Phenotype Arises In Asiamentioning

confidence: 99%

“…Curiously, the in vivo slow-clearance phenotype of P. falciparum, spreading through the GMS, was not consistently reflected in estimates of the 50% effective concentration (EC 50 ) of dihydroartemisinin (DHA, the dominant parasiticidal artemisinin metabolite in vivo) against parasites cultured in vitro [2,4]. Only after the Pasteur Institute teams in Phnom Penh and Paris had devised an in vitro DHA susceptibility test specific for the earliest blood-stage parasites, the ring-stage survival assay (RSA) [5], Ariey et al [6] were then able to demonstrate that certain mutations in the pfk13 locus correlated with the ex vivo parasite phenotype in the RSA.…”

Section: A New Artemisinin Susceptibility Phenotype Arises In Asiamentioning

confidence: 99%

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Genetic markers of artemisinin resistance in Plasmodium spp. parasites

Sutherland

2017

Emerging Topics in Life Sciences

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The vast majority of malaria patients worldwide are currently treated with combination therapy comprising one of the artemisinin family of drugs, characterised by rapid action and short plasma half-life, co-formulated with a longer-lasting drug from the amino arylalcohol or quinoline families. There is now a widely perceived threat to treatment efficacy, as reduced susceptibility to rapid artemisinin clearance in vivo has become prevalent among populations of Plasmodium falciparum in the Greater Mekong subregion since 2008. In vitro and in vivo drug selection studies, heterologous cell expression experiments and genetic epidemiology have identified many candidate markers of reduced ring-stage susceptibility to artemisinin. Certain variants of the P. falciparum pfk13 gene, which encodes a kelch domain protein implicated in the unfolded protein response, are strongly associated with slow parasite clearance by artemisinin in the Mekong subregion. However, anomalies in the epidemiological association of pfk13 variants with true treatment failure in vivo and the curious cell-cycle stage specificity of this phenotype in vitro warrant exploration in some depth. Taken together, available data suggest that the emergence of P. falciparum expressing K13 variants has not yet precipitated a public health emergency. Alternative candidate markers of artemisinin susceptibility are also described, as K13-independent treatment failure has been observed in African P. falciparum and in the rodent malaria parasite Plasmodium chabaudi.

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“…As the movement of both the malaria vector and parasite is not restricted by national boundaries regional drug pressure can influence drug efficacy within countries, as seen in KZN Province, SA [20] and Maputo Province, Mozambique. [37] Given the first-line antimalarial in all southern African countries is AL and that artemisinin resistance has been confirmed in Southeast Asia, [38] routine monitoring of AL efficacy is recommended, particularly in Limpopo Province, which currently experiences the highest incidence of African immigrant visitors.…”

Section: Regional Drug Pressurementioning

confidence: 99%

Case management of malaria: Treatment and chemoprophylaxis

et al. 2013

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Corresponding author: D Moonasar (moonad@health.gov.za)Malaria case management is a vital component of programmatic strategies for malaria control and elimination. Malaria case management encompasses prompt and effective treatment to minimise morbidity and mortality, reduce transmission and prevent the emergence and spread of antimalarial drug resistance. Malaria is an acute illness that may progress rapidly to severe disease and death, especially in non-immune populations, if not diagnosed early and promptly treated with effective drugs. In this article, the focus is on malaria case management, addressing treatment, monitoring for parasite drug resistance, and the impact of drug resistance on treatment policies; it concludes with chemoprophylaxis and treatment strategies for malaria elimination in South Africa.

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Artemisinin Resistance inPlasmodium falciparumMalaria

Abstract: Please refer to usage guidelines at http://researchonline.lshtm.ac.uk/policies.html or alternatively contact researchonline@lshtm.ac.uk. Available under license: Copyright the publishersT h e ne w e ngl a nd jou r na l o f m e dic i ne n engl j med 361;5 nejm

Cited by 2,935 publications

References 28 publications

<i>In vitro</i> and <i>in vivo</i> antiplasmodial activity of extracts from <i>Polyalthia suaveolens, Uvaria angolensis and Monodora tenuifolia</i> (Annonaceae)

<i>In vitro</i> and <i>in vivo</i> antiplasmodial activity of extracts from <i>Polyalthia suaveolens, Uvaria angolensis and Monodora tenuifolia</i> (Annonaceae)

Genetic markers of artemisinin resistance in Plasmodium spp. parasites

Case management of malaria: Treatment and chemoprophylaxis

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