Rossarin Suwanarusk1, Bruce Russell2, Alice Ong1, Kanlaya Sriprawat3, Cindy S Chu3, Aung PyaePhyo3, Benoit Malleret4, François Nosten5, Laurent Renia6. 1. Singapore Immunology Network (SIgN), Agency for Science Technology and Research, Biopolis, Singapore. 2. Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, National University Health System, Singapore. 3. Shoklo Malaria Research Unit, Mae Sot, Tak Province, Thailand. 4. Singapore Immunology Network (SIgN), Agency for Science Technology and Research, Biopolis, Singapore Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, National University Health System, Singapore. 5. Shoklo Malaria Research Unit, Mae Sot, Tak Province, Thailand Mahidol-Oxford University Research Unit, Bangkok, Thailand Centre for Tropical Medicine, University of Oxford, Churchill Hospital, Oxford, UK. 6. Singapore Immunology Network (SIgN), Agency for Science Technology and Research, Biopolis, Singapore renia_laurent@immunol.a-star.edu.sg.
Abstract
OBJECTIVES: Methylene blue, once discarded due to its unsettling yet mild side effects, has now found a renewed place in the pharmacopoeia of modern medicine. The continued spread of drug-resistant Plasmodium vivax and Plasmodium falciparum has also led to a recent re-examination of methylene blue's potent antimalarial properties. Here we examine the ex vivo susceptibility profile of Plasmodium spp. isolates to methylene blue; the isolates were from a region on the Thai-Myanmar border where there are increasing rates of failure when treating vivax malaria with chloroquine. METHODS: To do this we used a newly developed ex vivo susceptibility assay utilizing flow cytometry and a portable flow cytometer with a near-UV laser. RESULTS: P. vivax (median methylene blue IC50 3.1 nM, IQR 1.7-4.3 nM) and P. falciparum (median methylene blue IC50 1.8 nM, IQR 1.6-2.3 nM) are susceptible to methylene blue treatment at physiologically relevant levels. Unfortunately, the addition of chloroquine to combination treatments with methylene blue significantly reduces the ex vivo effectiveness of this molecule. CONCLUSIONS: Our data support further efforts to employ methylene blue as a safe, low-cost antimalarial to treat drug-resistant malaria.
OBJECTIVES:Methylene blue, once discarded due to its unsettling yet mild side effects, has now found a renewed place in the pharmacopoeia of modern medicine. The continued spread of drug-resistant Plasmodium vivax and Plasmodium falciparum has also led to a recent re-examination of methylene blue's potent antimalarial properties. Here we examine the ex vivo susceptibility profile of Plasmodium spp. isolates to methylene blue; the isolates were from a region on the Thai-Myanmar border where there are increasing rates of failure when treating vivax malaria with chloroquine. METHODS: To do this we used a newly developed ex vivo susceptibility assay utilizing flow cytometry and a portable flow cytometer with a near-UV laser. RESULTS:P. vivax (median methylene blue IC50 3.1 nM, IQR 1.7-4.3 nM) and P. falciparum (median methylene blue IC50 1.8 nM, IQR 1.6-2.3 nM) are susceptible to methylene blue treatment at physiologically relevant levels. Unfortunately, the addition of chloroquine to combination treatments with methylene blue significantly reduces the ex vivo effectiveness of this molecule. CONCLUSIONS: Our data support further efforts to employ methylene blue as a safe, low-cost antimalarial to treat drug-resistant malaria.
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Authors: Briegel De las Salas; Cesar Segura; Adriana Pabón; Stefanie C P Lopes; Fabio T M Costa; Silvia Blair Journal: Malar J Date: 2013-09-30 Impact factor: 2.979
Authors: B Russell; B Malleret; R Suwanarusk; C Anthony; S Kanlaya; Y L Lau; C J Woodrow; F Nosten; L Renia Journal: Antimicrob Agents Chemother Date: 2013-07-22 Impact factor: 5.191
Authors: Mathieu Gendrot; Océane Delandre; Marie Gladys Robert; Francis Tsombeng Foguim; Nicolas Benoit; Rémy Amalvict; Isabelle Fonta; Joel Mosnier; Marylin Madamet; Bruno Pradines; On Behalf Of The French National Reference Centre For Imported Malaria Study Group Journal: Pharmaceuticals (Basel) Date: 2021-04-09