Emergence of Indigenous Artemisinin-Resistant <i>Plasmodium falciparum</i> in Africa

Lu, Feng; Culleton, Richard; Zhang, Meihua; Ramaprasad, Abhinay; Seidlein, Lorenz von; Zhou, Huayun; Zhu, Guoding; Tang, Jianxia; Liu, Yaobao; Wang, Weiming; Cao, Yuanyuan; Xu, Shutu; Gu, Yixuan; Li, Julin; Zhang, Chao; Gao, Qi; Ménard, Didier; Pain, Arnab; Huang, Yang; Zhang, Qingfeng; Cao, Jun

doi:10.1056/nejmc1612765

Cited by 240 publications

(217 citation statements)

References 5 publications

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“…There is currently no detectable impact of K13 mutations on ART efficacy in Africa, except for one recent report of a migrant worker with a P. falciparum K13-variant infection from western Africa who showed delayed parasite clearance following ACT treatment 20,21,25 . Explanations for the current lack of impact of K13 mutations in Africa could include the greater degree of acquired immunity there, resulting from repeated exposure to P. falciparum , which builds host immunity to help control drug-resistant infections.…”

Section: Artemisinin Resistancementioning

confidence: 99%

Antimalarial drug resistance: linking Plasmodium falciparum parasite biology to the clinic

Blasco

Leroy

Fidock

2017

Nat Med

440

419

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The global adoption of artemisinin-based combination therapies (ACTs) in the early 2000s heralded a new era in effectively treating drug-resistant Plasmodium falciparum malaria. However, several Southeast Asian countries have now reported the emergence of parasites that have decreased susceptibility to artemisinin (ART) derivatives and ACT partner drugs, resulting in increasing rates of treatment failures. Here we review recent advances in understanding how antimalarials act and how resistance develops, and discuss new strategies for effectively combatting resistance, optimizing treatment and advancing the global campaign to eliminate malaria.

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Section: Artemisinin Resistancementioning

confidence: 99%

Antimalarial drug resistance: linking Plasmodium falciparum parasite biology to the clinic

Blasco

Leroy

Fidock

2017

Nat Med

440

419

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“…The WHO recommends artemisinin-based combination therapy (ACT) for first-line treatment of non-complicated falciparum malaria. Alarmingly, resistance to artemisinin has arisen in geographic pockets in multiple countries in Southeast Asia [2–5], and one case of a Chinese migrant worker was recently reported in equatorial Guinea [6]. ART-resistant parasites are defined as parasites that clinically display delayed parasite clearance times in patients treated with an ART derivative or an ART-based combination therapy (ACT), and which in vitro can withstand short pulses of high ART concentrations (for recent reviews of artemisinin resistance, see [7] and [8]).…”

Section: Combating Drug-resistant Malaria: Upsetting the Proteostaticmentioning

confidence: 99%

Protein Degradation Systems as Antimalarial Therapeutic Targets

Fidock

Bogyo

2017

Trends in Parasitology

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Artemisinin (ART)-based combination therapies are the most efficacious treatment of non-complicated Plasmodium falciparum infection. Alarmingly, P. falciparum strains have acquired resistance to ART in Southeast Asia and Africa. ART creates widespread protein and lipid damage inside intra-erythrocytic parasites, necessitating macromolecule degradation. The proteasome is the main engine of Plasmodium protein degradation. Indeed, proteasome inhibition and ART synergized in ART-resistant parasites. Moreover, ubiquitin modification is associated with resistance to multiple antimalarials. Targeting the ubiquitin-proteasome system, therefore, is an attractive avenue to combat drug resistance. Here, we review recent advances leading to specific targeting of the Plasmodium proteasome. We also highlight the potential for targeting other non-proteasomal protein degradation systems as an additional strategy to disrupt protein homeostasis.

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“…Globally, artemisinin resistance in P. falciparum has emerged, especially in Southeast Asia, slowing therapeutic response and increased rates of treatment failures [10, 11]. Similarly, artemisinin resistance has been reported from Africa although there is no evidence that it has taken hold currently [12]. Many studies assessing the efficacy of anti-malarial agents against P. falciparum and P. vivax have been published.…”

Section: Introductionmentioning

confidence: 99%

Anti-malarial treatment outcomes in Ethiopia: a systematic review and meta-analysis

Gebreyohannes

Bhagavathula

Seid

et al. 2017

Malar J

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BackgroundEthiopia is among countries with a high malaria burden. There are several studies that assessed the efficacy of anti-malarial agents in the country and this systematic review and meta-analysis was performed to obtain stronger evidence on treatment outcomes of malaria from the existing literature in Ethiopia.MethodsA systematic literature search using the preferred reporting items for systematic review and meta-analysis (PRISMA) statement was conducted on studies from Pubmed, Google Scholar, and ScienceDirect databases to identify published and unpublished literature. Comprehensive meta-analysis software was used to perform all meta-analyses. The Cochrane Q and the I 2 were used to evaluate heterogeneity of studies. Random effects model was used to combine studies showing heterogeneity of Cochrane Q p < 0.10 and I 2 > 50.ResultsTwenty-one studies were included in the final analysis with a total number of 3123 study participants. Treatment outcomes were assessed clinically and parasitologically using World Health Organization guidelines. Adequate clinical and parasitological response was used to assess treatment success at the 28th day. Overall, a significant high treatment success of 92.9% (95% CI 89.1–96.6), p < 0.001, I 2 = 98.39% was noticed. However, treatment success was higher in falciparum malaria patients treated with artemether–lumefantrine than chloroquine for Plasmodium vivax patients [98.1% (97.0–99.2), p < 0.001, I 2 = 72.55 vs 94.7% (92.6–96.2), p < 0.001, I 2 = 53.62%]. Seven studies reported the adverse drug reactions to anti-malarial treatment; of 822 participants, 344 of them were exposed to adverse drug reactions with a pooled event rate of 39.8% (14.1–65.5), p = 0.002.ConclusionsOn the basis of this review, anti-malarial treatment success was high (92.9%) and standard regimens showed good efficacy against Plasmodium falciparum (98.1%) and P. vivax (94.7%) infections in Ethiopia, but associated with high rates of adverse drug reactions (ADRs). However, these ADRs were not serious enough to discontinue anti-malarial treatment. The results of this study suggest that the current anti-malarial medications are effective and safe; however, greater priority should be placed on the discovery of new anti-malarial drugs to achieve successful outcomes as resistance seems inevitable since cases of anti-malarial drug resistance have been reported from other areas of the world.Electronic supplementary materialThe online version of this article (doi:10.1186/s12936-017-1922-9) contains supplementary material, which is available to authorized users.

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Emergence of Indigenous Artemisinin-Resistant Plasmodium falciparum in Africa

Cited by 240 publications

References 5 publications

Antimalarial drug resistance: linking Plasmodium falciparum parasite biology to the clinic

Antimalarial drug resistance: linking Plasmodium falciparum parasite biology to the clinic

Protein Degradation Systems as Antimalarial Therapeutic Targets

Anti-malarial treatment outcomes in Ethiopia: a systematic review and meta-analysis

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