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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
Saito M, Carrara VI, McGready R, et al.
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.

NOT Open Access | Novel molecule combinations and corresponding hybrids targeting artemisinin-resistant Plasmodium falciparum parasites

May 5, 2021 - 11:03 -- NOT Open Access
Ouji M, Nguyen M, Mustière R, Jimenez T, Augereau JM, Benoit-Vical F, Deraeve C
Bioorg Med Chem Lett. 2021 May 1;39:127884

Malaria is still considered as the major parasitic disease and the development of artemisinin resistance does not improve this alarming situation. Based on the recent identification of relevant malaria targets in the artemisinin resistance context, novel drug combinations were evaluated against artemisinin-sensitive and artemisinin-resistant Plasmodium falciparum parasites.

NOT Open Access | Association between ABCB1 Polymorphisms and Artesunate-Mefloquine Treatment Responses of Patients with Falciparum Malaria on the Thailand-Myanmar Border

May 5, 2021 - 08:45 -- NOT Open Access
Boonprasert K, Kosa N, Muhamad P, Cheoymang A, Na-Bangchang K
Am J Trop Med Hyg. 2021 May 3:tpmd210047

A decrease in the clinical efficacy of a 3-day artesunate-mefloquine combination treatment was reported in the areas of multidrug-resistant Plasmodium falciparum along the Thailand-Myanmar border. The current study investigated the possible contribution of genetic polymorphisms of the three major genes encoding drug efflux transporters, ABCB1, ABCG2, and ABCC1, to responses to the aforementioned treatment in 91 patients with acute uncomplicated falciparum malaria residing along the Thailand-Myanmar border. Patients carrying homozygous mutant genotype ABCB1 c.1236C>T (TT) were found to have a three-times higher chance of successful treatment with this combination compared with other genotypes (CC and CT).

NOT Open Access | Review of the mechanism underlying mefloquine-induced neurotoxicity

April 29, 2021 - 07:14 -- NOT Open Access
Martins AC, Paoliello MMB, Docea AO, Santamaria A, Tinkov AA, Skalny AV, Aschner M
Crit Rev Toxicol. 2021 Apr 27:1-8

Mefloquine, a potent blood schizontocide, is effective against drug-resistant Plasmodium falciparum. This property, along with its unique pharmacokinetic profile, makes mefloquine a widely prescribed antimalarial drug. However, several epidemiological studies have raised concerns on the safety of mefloquine as prophylaxis for malaria. Well-documented side-effects of mefloquine include abnormal dreams, insomnia, anxiety, and depressed mood, as well as nausea and dizziness (the last two most frequent effects).

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

March 24, 2021 - 15:06 -- NOT Open Access
Coonahan ES, Yang KA, Pecic S, De Vos M, Wellems TE, Fay MP, Andersen JF, Tarning J, Long CA
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).

NOT Open Access | Efficacy and safety of malarial prophylaxis with mefloquine during pregnancy in Kisangani, Democratic Republic of Congo: a randomized clinical trial

January 6, 2021 - 12:37 -- NOT Open Access
Labama Otuli N, Marini Djang'eing'a R, Manga Okenge JP, et al.
Br J Clin Pharmacol. 2021 Jan 4

Kisangani is an area with intense malaria transmission and sulfadoxine‐pyrimethamine resistance. Alternative anti‐malaria prophylaxis medication and protocols are needed, particularly with pregnant individuals. In this study, we compare the tolerance and effectiveness of mefloquine regimen as a split dose with meal versus sulfadoxine‐pyrimethamine for the intermittent preventive treatment in pregnant individuals in Kisangani.

Genetic analysis of the orthologous crt and mdr1 genes in Plasmodium malariae from Thailand and Myanmar

September 1, 2020 - 10:28 -- Open Access
Yupawadee Pimpat, Naowarat Saralamba, Usa Boonyuen, Sasithon Pukrittayakamee, Francois Nosten, Frank Smithuis, Nicholas P. J. Day, Arjen M. Dondorp and Mallika Imwong
Malaria Journal 2020 19:315, 31 August 2020

Plasmodium malariae is a widely spread but neglected human malaria parasite, which causes chronic infections. Studies on genetic polymorphisms of anti-malarial drug target genes in P. malariae are limited. Previous reports have shown polymorphisms in the P. malariae dihydrofolate reductase gene associated with pyrimethamine resistance and linked to pyrimethamine drug pressure. This study investigated polymorphisms of the P. malariae homologous genes, chloroquine resistant transporter and multidrug resistant 1, associated with chloroquine and mefloquine resistance in Plasmodium falciparum.

NOT Open Access | Mefloquine for malaria prophylaxis in military personnel

March 2, 2020 - 14:05 -- NOT Open Access
Williamson V, Blamey H, Sharpley J, David A, Greenberg N
BMJ Mil Health. 2020 Feb 20. pii: jramc-2019-001295

The British Army adopted mefloquine (Lariam) as its preferred drug for chemoprophylaxis against malaria in 1993. Treatment doses of mefloquine had already been reported to cause an acute brain syndrome. In 1996, army doctors reported a private soldier who, after six doses of mefloquine prophylaxis, saw the Grim Reaper standing behind the chaplain, heard incoherent voices, and was admitted to a psychiatric hospital; more reports followed.

NOT Open Access | Association of lipid levels with mefloquine and carboxy-mefloquine concentrations in patients with uncomplicated falciparum malaria

December 23, 2019 - 15:12 -- NOT Open Access
Vieira JLF, Rivera JGB, de Sena LWP, Ferreira MVD
Antimicrob Agents Chemother. 2019 Dec 16. pii: AAC.01731-19

Mefloquine shows a high capacity to bind plasma proteins, which influences the amount of drug in erythrocytes. The study investigated the association of lipids levels with plasma concentrations of mefloquine and carboxy-mefloquine in 85 Brazilian patients with uncomplicated falciparum malaria.


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