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ACT

A randomized controlled trial of dihydroartemisinin-piperaquine, artesunate-mefloquine and extended artemether-lumefantrine treatments for malaria in pregnancy on the Thailand-Myanmar border

June 16, 2021 - 10:01 -- Open Access
Author(s): 
Saito M, Carrara VI, McGready R, et al.
Reference: 
BMC Med. 2021 Jun 10;19(1):132

Artemisinin and artemisinin-based combination therapy (ACT) partner drug resistance in Plasmodium falciparum have spread across the Greater Mekong Subregion compromising antimalarial treatment. The current 3-day artemether-lumefantrine regimen has been associated with high treatment failure rates in pregnant women. Although ACTs are recommended for treating Plasmodium vivax malaria, no clinical trials in pregnancy have been reported.

Artemisinin combination therapy fails even in the absence of Plasmodium falciparum kelch13 gene polymorphism in Central India

May 13, 2021 - 12:39 -- Open Access
Author(s): 
Das S, Kar A, Manna S, Mandal S, Mandal S, Das S, Saha B, Hati AK
Reference: 
Sci Rep. 2021 May 11;11(1):9946

Artemisinin is the frontline fast-acting anti-malarial against P. falciparum. Emergence and spread of resistant parasite in eastern-India poses a threat to national malaria control programs. Therefore, the objective of our study is to evaluate the artesunate-sulfadoxine-pyrimethamine efficacy in Central India. 180 monoclonal P. falciparum-infected patients received standard ASSP therapy during August 2015-January 2017, soon after diagnosis and monitored over next 42-days. Artemisinin-resistance was assessed through in-vivo parasite clearance half-life (PC1/2), ex-vivo ring-stage survivability (RSA), and genome analysis of kelch13 and other candidate gene (pfcrt, pfmdr1, pfatpase 6, pfdhfr and pfdhps).

NOT Open Access | A Proteasome Mutation Sensitizes P. falciparum Cam3.II K13(C580Y) Parasites to DHA and OZ439

May 12, 2021 - 09:25 -- NOT Open Access
Author(s): 
Rosenthal MR, Ng CL
Reference: 
ACS Infect Dis. 2021 May 10

Artemisinin-based combination therapies (ACTs), the World Health Organization-recommended first-line therapy for uncomplicated falciparum malaria, has led to significant decreases in malaria-associated morbidity and mortality in the past two decades. Decreased therapeutic efficacy of artemisinins, the cornerstone of ACTs, is threatening the gains made against this disease.

NOT Open Access | Repurposing Anticancer Drugs To Tackle Malaria

May 5, 2021 - 11:36 -- NOT Open Access
Author(s): 
Le Govic Y, Houzé S, Papon N
Reference: 
ChemMedChem. 2021 May 1

Despite considerable efforts, malaria remains one of the most devastating infectious disease worldwide. In the absence of an effective vaccine, the prophylaxis and management of Plasmodium infections still rely on the therapeutic use of antimalarial agents. However, the emergence of resistant parasites has jeopardized the efficiency of virtually all antimalarial drugs, including artemisinin combination therapies (ACTs).

NOT Open Access | Design and synthesis of quinoline-pyrimidine inspired hybrids as potential plasmodial inhibitors

May 5, 2021 - 10:59 -- NOT Open Access
Author(s): 
Kayamba F, Malimabe T, Karpoormath R, et al.
Reference: 
Eur J Med Chem. 2021 May 5;217:113330

Presently, artemisinin-based combination therapy (ACT) is the first-line therapy of Plasmodium falciparum malaria. With the emergence of malaria parasites that are resistant to ACT, alternative antimalarial therapies are urgently needed. In line with this, we designed and synthesised a series of novel N-(7-chloroquinolin-4-yl)-N'-(4,6-diphenylpyrimidin-2-yl)alkanediamine hybrids (6a-7c) and evaluated their inhibitory activity against the NF54 chloroquine-susceptible strain as a promising class of antimalarial compounds.

Efficacy and safety of artemisinin-based combination therapies for the treatment of uncomplicated malaria in pediatrics: a systematic review and meta-analysis

April 14, 2021 - 16:50 -- Open Access
Author(s): 
Shibeshi W, Alemkere G, Mulu A, Engidawork E
Reference: 
BMC Infect Dis. 2021 Apr 7;21(1):326

Malaria is a major cause of morbidity and mortality in pediatrics in malaria endemic areas. Artemisinin-based combination therapies (ACTs) are the drugs of choice for malaria management particularly across malaria-endemic countries. This systematic review and meta-analysis was performed to assess efficacy and safety of ACTs for uncomplicated malaria in pediatric populations.

Historical trends and new surveillance of Plasmodium falciparum drug resistance markers in Angola

April 14, 2021 - 07:47 -- Open Access
Author(s): 
Emily R. Ebel, Fátima Reis, Dmitri A. Petrov and Sandra Beleza
Reference: 
Malaria Journal 2021 20:175, 7 April 2021

Plasmodium falciparum resistance to chloroquine (CQ) and sulfadoxine-pyrimethamine (SP) has historically posed a major threat to malaria control throughout the world. The country of Angola officially replaced CQ with artemisinin-based combination therapy (ACT) as a first-line treatment in 2006, but malaria cases and deaths have recently been rising. Many classic resistance mutations are relevant for the efficacy of currently available drugs, making it important to continue monitoring their frequency in Angola.

Novel anti-malarial drug strategies to prevent artemisinin partner drug resistance: A model-based analysis

March 30, 2021 - 14:22 -- Open Access
Author(s): 
Kunkel A, White M, Piola P
Reference: 
PLoS Comput Biol. 2021 Mar 25;17(3):e1008850

Emergence of resistance to artemisinin and partner drugs in the Greater Mekong Subregion has made elimination of malaria from this region a global priority; it also complicates its achievement. Novel drug strategies such as triple artemisinin combination therapies (ACTs) and chemoprophylaxis have been proposed to help limit resistance and accelerate elimination. The objective of this study was to better understand the potential impacts of triple ACTs and chemoprophylaxis, using a mathematical model parameterized using data from Cambodia.

NOT Open Access | Structure-switching aptamer sensors for the specific detection of piperaquine and mefloquine

March 24, 2021 - 15:06 -- NOT Open Access
Author(s): 
Coonahan ES, Yang KA, Pecic S, De Vos M, Wellems TE, Fay MP, Andersen JF, Tarning J, Long CA
Reference: 
Sci Transl Med. 2021 Mar 17;13(585):eabe1535

Tracking antimalarial drug use and efficacy is essential for monitoring the current spread of antimalarial drug resistance. However, available methods for determining tablet quality and patient drug use are often inaccessible, requiring well-equipped laboratories capable of performing liquid chromatography-mass spectrometry (LC-MS). Here, we report the development of aptamer-based fluorescent sensors for the rapid, specific detection of the antimalarial compounds piperaquine and mefloquine-two slow-clearing partner drugs in current first-line artemisinin-based combination therapies (ACTs).

Assessment of Plasmodium falciparum anti-malarial drug resistance markers in pfk13-propeller, pfcrt and pfmdr1 genes in isolates from treatment failure patients in Democratic Republic of Congo, 2018–2019

March 18, 2021 - 09:09 -- Open Access
Author(s): 
Doudou M. Yobi, Nadine K. Kayiba, Marie-Pierre Hayette, et al.
Reference: 
Malaria Journal 2021 20:144, 11 March 2021

The national policy for malaria treatment of the Democratic Republic of Congo recommends two first-line artemisinin-based combinations for the treatment of uncomplicated malaria: artesunate-amodiaquine and artemether-lumefantrine. This study investigated the presence of markers associated with resistance to the current first-line artemisinin-based combination therapy (ACT) in isolates of Plasmodium falciparum from treatment failure patients in the Democratic Republic of Congo.

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