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Evolution of multidrug resistance in Plasmodium falciparum: a longitudinal study of genetic resistance markers in the Greater Mekong Subregion

September 15, 2021 - 11:46 -- Open Access
Imwong M, Suwannasin K, Dondorp AM, et al.
Antimicrob Agents Chemother. 2021 Sep 13:AAC0112121

Increasing drug resistance in Plasmodium falciparum to artemisinins and their ACT partner drugs jeopardises effective antimalarial treatment. Resistance is worst in the Greater Mekong Subregion. Monitoring genetic markers of resistance can help to guide antimalarial therapy. Markers of resistance to artemisinins (PfKelch mutations), mefloquine (amplification of P. falciparum multidrug resistance-1, PfMDR1,), and piperaquine (PfPlasmepsin2/3 amplification and specific P. falciparum chloroquine resistance transporter, PfCRT, mutations) were assessed in 6,722 P. falciparum samples from Vietnam, Lao PDR, Cambodia, Thailand, Myanmar between 2007 and 2019.

Are Artemisinin-Based Combination Therapies For Malaria Beginning To Fail in Africa

September 8, 2021 - 17:17 -- Open Access
Rosenthal PJ
Am J Trop Med Hyg. 2021 Sep 7:tpmd210797

Despite advances in many countries, notably the recent declaration that China is now malaria free, malaria remains entrenched in Africa, where over 90% of malaria morbidity and mortality is seen. 1. In the past, Africa suffered greatly from the effects for resistance to chloroquine, the mainstay of malaria treatment of decades, with increasing mortality from Plasmodium falciparum over the last decades of the 20th century.

NOT Open Access | Therapeutic Efficacy of Artemisinin-Based Combination Therapies in Democratic Republic of the Congo and Investigation of Molecular Markers of Antimalarial Resistance

September 8, 2021 - 17:15 -- NOT Open Access
Moriarty LF, Nkoli PM, Kahunu GM, et al.
Am J Trop Med Hyg. 2021 Sep 7:tpmd210214

Routine assessment of the efficacy of artemisinin-based combination therapies (ACTs) is critical for the early detection of antimalarial resistance. We evaluated the efficacy of ACTs recommended for treatment of uncomplicated malaria in five sites in Democratic Republic of the Congo (DRC): artemether-lumefantrine (AL), artesunate-amodiaquine (ASAQ), and dihydroartemisinin-piperaquine (DP). Children aged 6-59 months with confirmed Plasmodium falciparum malaria were treated with one of the three ACTs and monitored.

To what extent are the antimalarial markets in African countries ready for a transition to triple artemisinin-based combination therapies

September 1, 2021 - 17:12 -- Open Access
de Haan F, Bolarinwa OA, Amaratunga C, et al.
PLoS One. 2021 Aug 31;16(8):e0256567

Triple artemisinin-based combination therapies (TACTs) are being developed as a response to artemisinin and partner drug resistance in the treatment of falciparum malaria in Southeast Asia. In African countries, where current artemisinin-based combination therapies (ACTs) are still effective, TACTs have the potential to benefit the larger community and future patients by mitigating the risk of drug resistance. This study explores the extent to which the antimalarial drug markets in African countries are ready for a transition to TACTs.

Artemisinin-based combination therapy for uncomplicated Plasmodium falciparum malaria in Mali: a systematic review and meta-analysis

September 1, 2021 - 16:38 -- Open Access
Fatoumata O. Maiga, Mamadou Wele, Jeffrey G. Shaffer, et al.
Malaria Journal 2021 20:356, 30 August 2021

Artemisinin-based combination therapy (ACT) was deployed in 2005 as an alternative to chloroquine and is considered the most efficacious treatment currently available for uncomplicated falciparum malaria. While widespread artemisinin resistance has not been reported to date in Africa, recent studies have reported partial resistance in Rwanda. The purpose of this study is to provide a current systematic review and meta-analysis on ACT at Mali study sites, where falciparum malaria is highly endemic.

Not Open Access | Artemisinin inspired synthetic endoperoxide drug candidates: Design, synthesis, and mechanism of action studies

August 10, 2021 - 17:46 -- NOT Open Access
Woodley CM, Amado PSM, Cristiano MLS, O'Neill PM
Med Res Rev. 2021 Aug 6

Artemisinin combination therapies (ACTs) have been used as the first-line treatments against Plasmodium falciparum malaria for decades. Recent advances in chemical proteomics have shed light on the complex mechanism of action of semi-synthetic artemisinin (ARTs), particularly their promiscuous alkylation of parasite proteins via previous heme-mediated bioactivation of the endoperoxide bond. Alarmingly, the rise of resistance to ART in South East Asia and the synthetic limitations of the ART scaffold have pushed the course for the necessity of fully synthetic endoperoxide-based antimalarials.

NOT Open Access | Pharmacotherapy for artemisinin-resistant malaria

July 28, 2021 - 14:58 -- NOT Open Access
Koehne E, Adegnika AA, Held J, Kreidenweiss A
Expert Opin Pharmacother. 2021 Jul 27

Malaria, the most devastating parasitic disease, is currently treated with artemisinin-based combination therapies (ACTs). Unfortunately, some ACTs are unable to rapidly clear Plasmodium falciparum parasites from the blood stream and are failing to cure malaria patients; a problem, so far, largely confined to Southeast Asia. There is a fear of resistant Plasmodium falciparum emerging in other parts of the world including Sub-Sahara Africa. Strategies for alternative treatments, ideally non-artemisinin based, are needed.

The newly discovered role of endocytosis in artemisinin resistance

July 28, 2021 - 14:37 -- Open Access
Behrens HM, Schmidt S, Spielmann T
Med Res Rev. 2021 Jul 26

Artemisinin and its derivatives (ART) are the cornerstone of malaria treatment as part of artemisinin combination therapy (ACT). However, reduced susceptibility to artemisinin as well as its partner drugs threatens the usefulness of ACTs. Single point mutations in the parasite protein Kelch13 (K13) are necessary and sufficient for the reduced sensitivity of malaria parasites to ART but several alternative mechanisms for this resistance have been proposed.

Does subsidizing the private for-profit sector benefit the poor? Evidence from national antimalarial subsidies in Nigeria and Uganda

July 28, 2021 - 12:49 -- Open Access
Tougher S, Hanson K, Goodman CA
Health Econ. 2021 Jul 22

Subsidising quality-assured artemisinin combination therapies (QAACTs) for distribution in the for-profit sector is a controversial strategy for improving access. The Affordable Medicines Facility-malaria (AMFm) was the largest initiative of this kind. We assessed the equity of AMFm in two ways using nationally representative household survey data on care seeking for children from Nigeria and Uganda.

Is there evidence of anti-malarial multidrug resistance in Burkina Faso?

July 21, 2021 - 17:57 -- Open Access
Charlotte Rasmussen and Pascal Ringwald
Malaria Journal 2021 20:320, 19 July 2021

Recently, Gansané and colleagues published an article on inadequate efficacy of two different forms of artemisinin-based combination therapy (ACT) in Burkina Faso. The development of Plasmodium falciparum resistance to different ACT partner drugs at levels that could affect the efficacy of two ACT would both be startling and a cause for great concern. In reviewing the available data collected since 2008 on ACT efficacy in Burkina Faso, the analysis shows that the reported efficacy of the tested ACT varies greatly.


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