Malaria and Methylene Blue

Methylene blue is both a dye and a medicine. Methylene blue is a thiazine dye and was first prepared in 1876 by Heinrich Caro, a German chemist. It is mainly used to treat methemoglobinemia, a condition caused by elevated levels of methemoglobin in the blood. Methemoglobin is a form of hemoglobin that contains the ferric [Fe3+] form of iron.

Methylene blue has a similar mode of action as chloroquine and has moreover been shown to selectively inhibit the Plasmodium falciparum glutathione reductase[1].

The mature gametocytes of Plasmodium are solely responsible for parasite transmission from the mammalian host to the mosquito. They are therefore a logical target for transmission-blocking antimalarial interventions, which aim to break the cycle of reinfection and reduce the prevalence of malaria cases[2].

Now, research had shown that methylene blue was found to target these gametocytes[3]. It is proposed to be used as a gametocytocidal adjunct with artemisinin-based combination therapy. Further exploration of methylene blue in clinical studies, including G6PD deficient patients, is recommended.

Common side effects of ingesting methylene blue include headache, vomiting, confusion, shortness of breath, and high blood pressure. Other side effects include serotonin syndrome, red blood cell breakdown and allergic reactions. Its use often turns the urine, sweat and stool blue to green in colour.

[1] Meissner et al: Methylene blue for malaria in Africa: results from a dose-finding study in combination with chloroquine in Malaria Journal – 2006. See here.
[2] Delves et al: Male and Female Plasmodium falciparum Mature Gametocytes Show Different Responses to Antimalarial Drugs in Antimicrobial Agents and Chemotherapy – 2013. See here.
[3] Wadi et al: Methylene blue induced morphological deformations in Plasmodium falciparum gametocytes: implications for transmission-blocking in Malaria Journal - 2018