The activity of methylene blue against asexual and sexual stages of Plasmodium vivax

Fabbri, C.; Ramos, Glenda Quaresma; Baía-da-Silva, Djane Clarys; Trindade, Alexandre Oliveira; Salazar-Alvarez, Luis Carlos; Neves, Juliana Costa Ferreira; Bastos, Ivanildes dos Santos; Costa, Allyson Guimarães; Lacerda, Marcus Vinícius Guimarães; Monteiro, Wuelton Marcelo; Costa, Fábio Trindade Maranhão; Lopes, Stefanie Costa Pinto

doi:10.3389/fcimb.2023.1108366

“…This supports earlier observations that artemisinin derivatives had greater activity than chloroquine in reducing gametocyte carriage in vivax malaria (17,18). High concentrations of methylene blue, which has a potent gametocytocidal activity in P. falciparum (19,20), were shown recently to block transmission of P. vivax gametocytes in membrane feeding experiments but the sample size was very small (only five patients were recruited in this study) (21).…”

Section: Introductionmentioning

confidence: 99%

Transmission-blocking activity of artesunate, chloroquine and methylene blue onPlasmodium vivaxgametocytes

Chaumeau,

Wasisakun,

Watson

et al. 2024

Preprint

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Plasmodium vivax is now the main cause of malaria outside Africa. The gametocytocidal effects of antimalarial drugs are important to reduce malaria transmissibility, particularly in low transmission settings, but they are not well characterized for P. vivax. The transmission-blocking effects of chloroquine, artesunate and methylene blue on P. vivax gametocytes were assessed. Blood specimens were collected from patients presenting with vivax malaria, incubated with or without the tested drugs, and then fed to mosquitos from a laboratory-adapted colony of Anopheles dirus (a major malaria vector in Southeast Asia). The effects on oocyst and sporozoite development were analyzed under a multi-level Bayesian model accounting for assay variability and the heterogeneity of mosquito Plasmodium-infection. Artesunate and methylene blue, but not chloroquine, exhibited potent transmission-blocking effects. This suggests that patients with vivax malaria often remain infectious to anopheline mosquitos after treatment with chloroquine. Immediate initiation of primaquine radical cure or use of artemisinin combination therapies would reduce the transmissibility of P. vivax infections.

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Transmission-blocking activities of artesunate, chloroquine, and methylene blue on Plasmodium vivax gametocytes

Chaumeau,

Wasisakun,

Watson

et al. 2024

Antimicrob Agents Chemother

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Plasmodium vivax is now the main cause of malaria outside Africa. The gametocytocidal effects of antimalarial drugs are important to reduce malaria transmissibility, particularly in low-transmission settings, but they are not well characterized for P. vivax . The transmission-blocking effects of chloroquine, artesunate, and methylene blue on P. vivax gametocytes were assessed. Blood specimens were collected from patients presenting with vivax malaria, incubated with or without the tested drugs, and then fed to mosquitos from a laboratory-adapted colony of Anopheles dirus (a major malaria vector in Southeast Asia). The effects on oocyst and sporozoite development were analyzed under a multi-level Bayesian model accounting for assay variability and the heterogeneity of mosquito Plasmodium infection. Artesunate and methylene blue, but not chloroquine, exhibited potent transmission-blocking effects. Gametocyte exposures to artesunate and methylene blue reduced the mean oocyst count 469-fold (95% CI: 345 to 650) and 1,438-fold (95% CI: 970 to 2,064), respectively. The corresponding estimates for the sporozoite stage were a 148-fold reduction (95% CI: 61 to 470) and a 536-fold reduction (95% CI: 246 to 1,311) in the mean counts, respectively. In contrast, high chloroquine exposures reduced the mean oocyst count only 1.40-fold (95% CI: 1.20 to 1.64) and the mean sporozoite count 1.34-fold (95% CI: 1.12 to 1.66). This suggests that patients with vivax malaria often remain infectious to anopheline mosquitos after treatment with chloroquine. Use of artemisinin combination therapies or immediate initiation of primaquine radical cure should reduce the transmissibility of P. vivax infections.

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Pyronaridine – the Current Antimalarial Standing Up to Parasite Resistance

Auparakkitanon

2024

Rama Med J

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Pyronaridine, an aza-9-anilinoacridine schizonticide, was synthesized in China 54 years ago and since 2012 has been prescribed globally in combination with artesunate, marketed under the name Pyramax. Artesunate is an analog of artemisinin, a sesquiterpene lactone with an endoperoxide moiety, extracted from Artemisia annua L., and used as an herbal remedy in Chinese traditional medicine to treat jungle fever, also discovered in China at nearly the same time. Pyramax is one of the safest and most efficacious forms of artemisinin combination therapy (ACT) for treating uncomplicated Plasmodium falciparum malaria in adults and children. This narrative review explains the mechanism of action of pyronaridine, why it remains effective against P. falciparum even though the parasite has evolved resistance or tolerance to all other antimalarial drugs used in clinical practice, and suggests possible antiplasmodial deaza-pyronaridine (acridine) analogs that could be used should pyronaridine becomes ineffective.

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The activity of methylene blue against asexual and sexual stages of Plasmodium vivax

Cited by 3 publications

References 38 publications

Transmission-blocking activity of artesunate, chloroquine and methylene blue onPlasmodium vivaxgametocytes

Transmission-blocking activity of artesunate, chloroquine and methylene blue onPlasmodium vivaxgametocytes

Transmission-blocking activities of artesunate, chloroquine, and methylene blue on Plasmodium vivax gametocytes

Pyronaridine – the Current Antimalarial Standing Up to Parasite Resistance

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