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Malaria Treatment with Methylene Blue

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What is Malaria?

Malaria is an illness in which the person suffers from high fever and chills. Malaria is caused by a parasite that is spread to humans by the bite of infected female Anopheles mosquitos. Malaria is triggered by five parasitic species, two of which – P. falciparum and P. vivax are the deadliest. This disease often causes severe disease, including high fevers, shivering chills, and flu-like symptoms.

Because the malaria parasite is found in the infected person’s red blood cells, it can be transmitted through blood transfusions or the common use of blood-contaminated needles or syringes. It can also be passed from a woman to her unborn child before or after birth (this is known as “congenital” malaria).

Symptoms of Malaria:-  Most people get a fever, sweating, shivering, headaches, muscular pains, nausea, and vomiting during the start of the disease. Malaria can quickly deteriorate into a severe and perhaps fatal condition. Timely diagnosis of malaria and treatment decreases sickness, avoids fatalities, and helps to minimise transmission. Malaria should be confirmed in all possible cases using parasite-based diagnostic assays.

Malaria can be treated and prevented with drugs that destroy the parasite that induces the sickness. These medications are known as antimalarials. Various medications target various aspects of the parasite’s development and life cycle. Chloroquine, for instance, attacks the blood phases, whereas primaquine eliminates the dormant liver stages. As a result, medications are frequently used in combination to ensure that the malaria parasite is eradicated from all parts of the body. To treat Plasmodium vivax, for instance, primaquine is used with chloroquine. World Health Organisation is suggesting RTS, S/AS01, also known as Mosquirix malaria vaccine, for the prevention of P. falciparum malaria.

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How Methylene Blue treats Malaria

Methylene blue was the first synthesised antimalarial drug to be developed and was used to treat all forms of malaria in the nineteenth and early twentieth century. 

Methylene blue was identified by Paul Ehrlich and Paul Guttmann in 1891 for the treatment of Malaria. Prior to World War I, researchers such as Ehrlich believed that drugs and dyes functioned in the same manner, preferring staining pathogens and possibly damaging them. It was rejected by soldiers during the Pacific War in the tropics because of its two features of changing urine blue or green and turning Scalera (the white portion of the eyes) blue.

MB functioned synergistically with artemisinin derivates in preliminary experiments and had a substantial effect on gametocyte decrease in P. falciparum. As a result, Methylene Blue has been identified as a potentially helpful companion medicine for artemisinin-based combination treatment (ACT), especially when eradication is the ultimate target. Following that, it was widely used in many epidemic regions and against all subtypes of malaria, particularly malaria sickness that did not respond well to quinine therapy.

Methylene blue is approved by the FDA and is one of the safest drugs. Because of its low cost, interest in its use as an antimalarial drug has recently resurfaced. Many clinical trials are in progress to find a suitable combination for this drug.

Mechanism of methylene blue against Malaria

The antimalarial effect of Methylene Blue has been related to antioxidant responses that selectively target glutathione reductase, a key enzyme in the life cycle of P. falciparum. Methylene Blue reduces parasite multiplication in the late trophozoite stages when haemoglobin digestion is intensive; this reduction of parasite multiplication coincides with plasmodial GR peak activity during the 24th hour of the intraerythrocytic cycle. Methylene Blue achieves peak plasma levels in humans 1-2 hours after oral ingestion of 100 mg. It has a plasmatic half-life of around 5-6.5 hours and a modest renal excretion rate of about 20-30%.

Summary of all the research so far on methylene blue and malaria

In an article published on on 25th June 2019, it was mentioned that the study of malaria therapy with Methylene Blue was restarted at three biochemical laboratories near the late 1990s; at that time, multi-drug resistance had become a severe threat to worldwide malaria control programs. The discovery of P. falciparum glutathione reductase as a pharmacological target cleared the path for more study on the function of Methylene Blue in the treatment of malaria, with significant investigations being undertaken at the Heidelberg University Biochemistry Centre and led by the late Heiner Schirmer.

A comprehensive assessment of the effectiveness and safety of Methylene Blue in the treatment of malaria was undertaken, which included all trials published up to early 2017. It convincingly confirmed Methylene Blue’s effectiveness and safety in the treatment of malaria. While additional clinical research on the effects of Methylene Blue in P. vivax malaria is needed, there is currently solid evidence for the drug’s powerful effects against P. falciparum, particularly gametocytes.

Another article published on on 5th February 2018 stated that Radboud University Medical Center academics and foreign collaborators made the discovery during a study effort in Mali, which showed Methylene blue was revealed to be a non-toxic antimalarial dye with an unrivalled ability to destroy malaria parasites. Patients recover in two days and are no longer contagious if bitten by another mosquito.

According to a research paper published in “The Lancet Infectious Diseases,” the use of Methylene Blue to treat malaria was not as strange as it seemed. Methylene Blue was proved to be helpful in treating malaria if used in the early stages of the parasitic attack.

The latest clinical trials conducted

Pharmacokinetic interaction of chloroquine phosphate and methylene blue  combination against malaria (2004)

This study was conducted at the Department of Internal Medicine VI, Clinical Pharmacology and Pharmacoepidemiology and it was approved by the ethics committee of the Medical Faculty of the University of Heidelberg. The objective of using a combination of chloroquine with methylene blue was to find effective treatment against malaria caused by Plasmodium falciparum.

Test– The combined oral dose of Chloroquine (2.5g for males & 1.88 g for females) and desethylchloroquine with 185 mg Methylene Blue was administered to 24 healthy persons, twice daily for 3 days.

 Result– The combination of Chloroquine and Methylene Blue is not effective in low doses of methylene blue against Malaria.

Safety and Efficacy of Methylene Blue Combined with Artesunate or Amodiaquine for Uncomplicated Falciparum Malaria: A Randomized Controlled Trial from Burkina Faso (2006)

After an unsuccessful trial of methylene blue and Chloroquine, a phase 2 trial of the controlled study was conducted on 180 children aged 6-10 years with uncomplicated falciparum malaria at Nouna district hospital outpatient clinic, north-western Burkina Faso. The main objective of this study was to find out the safety and efficiency of Methylene blue-Artesunate (AS) and Methylene blue- Amodiaquine (AQ).

Test– Dosage of these compounds were Methylene blue (10 mg per kilogram of body weight twice daily over three days.) Artesunate (4 mg per kilogram of body weight once daily over three days.) Amodiaquine (10 mg per kilogram of body weight once daily over three days.) If vomiting occurred within the first 30 minutes, the medication was repeated. If vomiting happened again, the patient was excluded and referred to the hospital’s paediatrics department. Children with a temperature of 38.5°C were given a routine dose of 10 mg per kilogram paracetamol tablets every 6 hours (Essential Drug Store, Ministry of Health, Burkina Faso) until the symptoms went away.

 Result- The efficiency of Methylene blue-amodiaquine was higher than expected.

Efficacy and Safety of Triple Combination Therapy With Artesunate-Amodiaquine–Methylene Blue for Falciparum Malaria in Children: A Randomized Controlled Trial in Burkina Faso (August to October 2011)

Test– In Burkina Faso, A phase 2B study was conducted for 3 days of treatment with a triple combination of Artesunate, Amodiaquine and Methylene Blue combined on 221 children aged 6 to 59 months weight ≥6 kg with uncomplicated falciparum malaria in the urban research zone of the Centre de Recherche en Santé de Nouna (CRSN). Dosage determined by weight group (6.0–8.9 kg, 25 mg of AS plus 67.5 mg of AQ; 9.0–17.9 kg, 50 mg of AS plus 135 mg of AQ; >17.9 kg, 100 mg AS plus 270 mg of AQ), combined with once-daily MB (15 mg/kg) minitablets in prepackaged sachets according to weight group (6.0–8.9 kg, 100 mg MB; 9.0–12.9 kg, 150 mg MB; 13.0–16.9 kg, 200 mg MB; >16.9 kg, 250 mg MB).

Result- This combination has been confirmed against Plasmodium falciparum.

The discovery of malaria medication combinations that are safe, effective, and economical has been a top focus for the medical community. The outcomes of the studies done to investigate the efficacy of methylene Blue against malaria provided some indirect evidence that Methylene Blue, a low-cost drug licensed in most countries, may be effective against malaria.


Which dye is used for malaria?

Methylene Blue is the first and most widely known synthetic dye used for treating malaria.  

Is methylene blue good for health?

If consumed in the appropriate quantity and dosage limits, methylene blue has no adverse side effects. Its use has also been approved for treating methemoglobinemia and cyanide poisoning. Methylene blue injections for approved treatments are available in the market against prescriptions. We do not recommend the use of methylene blue without the guidance of a medical professional. 

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The information provided here is based on general knowledge, articles, research publications etc. We do not claim the authenticity of any of the information provided above. We do not claim or suggest/advise any medical, therapeutic, health or nutritional benefits of methylene blue. We do not supply or promote our methylene blue product for the applications which are covered by valid patents and which are not approved by the FDA.

Macsen Labs is a manufacturer and supplier of several grades of Methylene Blue such as:-

Macsen Labs group’s Methylene Blue Synthesis Process granted a patent from the Indian patent office

The Indian Patent Office granted a patent to Mr Achal Agrawal, CEO of Macsen Labs, Udaipur. The title of the patent is Novel Improved Method for Synthesis of Diaminophenothiazine Compounds and it concerns a novel process for synthesising the compound Methylthioninium Chloride or Methylene Blue. Macsen Labs has now achieved a unique position by this patent and from now nobody will be able to copy this process. Read more

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