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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.

Carboxymefloquine, the major metabolite of the antimalarial drug mefloquine, induces drug-metabolizing enzyme and transporter expression by activation of pregnane X receptor.

September 2, 2015 - 16:36 -- Open Access
Piedade R, Traub S, Bitter A, Nüssler AK, Gil JP, Schwab M, Burk O
Antimicrob Agents Chemother. 2015 Jan;59(1):96-104

Therefore, this study aimed to elucidate the potential of nonartemisinin antimalarial drugs and drug metabolites to activate PXR. We screened 16 clinically used antimalarial drugs and six major drug metabolites for binding to PXR using the two-hybrid PXR ligand binding domain assembly assay; this identified carboxymefloquine, the major and pharmacologically inactive metabolite of the antimalarial drug mefloquine, as a potential PXR ligand. 

Plasmodium falciparum susceptibility to standard and potential anti-malarial drugs in Dakar, Senegal, during the 2013–2014 malaria season

March 4, 2015 - 15:06 -- Open Access
Bécaye Fall, Cheikhou Camara, Mansour Fall, Aminata Nakoulima, Pierre Dionne, Bakary Diatta, Yaya Diemé, Boubacar Wade, Bruno Pradines
Malaria Journal 2015, 14:60 (6 February 2015)

The prevalence of isolates with a reduced susceptibility to MQ remains high and stable in Dakar. Since 2004, the prevalence of CQ resistance decreased, but rebounded in 2013 in Dakar. PND, PPQ and PVB showed high in vitro activity in P. falciparum parasites from Dakar

Intermittent Preventive Treatment of Malaria in Pregnancy with Mefloquine in HIV-Infected Women Receiving Cotrimoxazole Prophylaxis: A Multicenter Randomized Placebo-Controlled Trial

October 1, 2014 - 17:53 -- Open Access
Raquel González, Meghna Desai, Clara Menéndez, et al.
PLoS Med 11(9): e1001735.

We studied the safety and efficacy of mefloquine (MQ) in women receiving CTXp and long-lasting insecticide treated nets (LLITNs).

Intermittent Preventive Treatment of Malaria in Pregnancy with Mefloquine in HIV-Negative Women: A Multicentre Randomized Controlled Trial

September 29, 2014 - 16:39 -- Open Access
Raquel González , Ghyslain Mombo-Ngoma, Clara Menéndez, et al.
PLoS Med 11(9): e1001733

The study arms were: (1) SP, (2) single dose MQ (15 mg/kg), and (3) split-dose MQ in the context of long lasting insecticide treated nets. There was no difference on low birth weight prevalence (primary study outcome) between groups (360/2,778 [13.0%]) for MQ group and 177/1,398 (12.7%) for SP group; risk ratio [RR], 1.02 (95% CI 0.86–1.22; p = 0.80 in the ITT analysis).

Distribution of pfmdr1 polymorphisms in Plasmodium falciparum isolated from Southern Thailand

April 11, 2014 - 18:51 -- Open Access
Mungthin M, Intanakom S, Suwandittakul N, Suida P, Amsakul S, Sitthichot N, Thammapalo S, Leelayoova S
Malaria Journal 2014, 13 :117 (27 March 2014)

This study was conducted to compare the distribution pattern of the pfcrt and pfmdr1 polymorphisms in the parasites from the lower southern provinces, Thai-Malaysia border and the upper southern provinces, Thai-Myanmar border.

Not Open Access | Effects of the combined artesunate and mefloquine antimalarial drugs on rat embryos

August 14, 2013 - 04:46 -- NOT Open Access
A.C. Boareto, J.C. Müller, E.L.B. Lourenço, N. Lombardi, A.C. Lourenço, I. Rabitto, R.N. de Morais, F.S. Rios, P.R. Dalsenter
Hum Exp Toxicol September 2013 vol. 32 no. 9 930-941

To evaluate the effects of isolated and combined artesunate (AS)/mefloquine (MQ) on embryo rats, pregnant rats were treated orally with AS (15 and 40 mg/kg body weight (bwt)/day), MQ (30 and 80 mg/kg bwt/day) and AS/MQ (15/30 and 40/80 mg/kg bwt/day) on days 9–11 post coitum (pc).

NOT Open Access | Increased pfmdr1 copy number in Plasmodium falciparum isolates from Suriname

June 24, 2013 - 11:46 -- NOT Open Access
Mergiory Labadie-Bracho and Malti R. Adhin
Tropical Medicine & International Health, Volume 18, Issue 7, pages 796–799, July 2013

Amplification of the pfmdr1 gene is associated with clinical failures and reduced in vivo and in vitro sensitivity to both mefloquine and artemether–lumefantrine in South-East Asia.



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