It's hard to imagine that a blue dye sold in pet food stores in the U.S. to fight fungal infections in tropical fish could be a potent weapon against malaria.
A study published this week in The Lancet Infectious Diseases showed that might be possible. Researchers added doses of the dye to dihydroartemisinin-piperaquine, a go-to malaria drug, and found that the dye killed the parasites that spread malaria within two days. So if a mosquito were to bite a person recovering from malaria, the mosquito couldn't pick up live parasites and spread them to its next human target.
By contrast, after a week, people who got that malaria drug without methylene blue continued to pass the parasite to mosquitoes.
Actually, the use of the dye to fight malaria is not quite as odd as it sounds. The blue dye in question, called methylene blue, is the oldest synthetic anti-malarial drug. A paper published in 1891 tells how two scientists successfully used it to treat a malaria patient.
But there was a catch.
"The treatment being followed by an intense blue coloring of the urine, and the faeces becoming blue on exposure to light, it is not very likely that methylene blue will be much used outside of hospitals," reads an 1892 publication of the Proceedings of the American Pharmaceutical Association.
"Because of the color, it never really took off," agrees Ingrid Chen, one of the study's lead authors and an assistant professor of epidemiology and biostatistics at the University of California, San Francisco's School of Medicine. UCSF's Institute of Global Health Sciences collaborated on the study with the Malaria Research and Training Center in Mali, the Radboud Institute for Health Sciences and the London School of Hygiene & Tropical Medicine.
The dye contains carbon, hydrogen, chlorine, nitrogen and sulfur. It's often added to a liquid and used as a lab stain, making it easier to see some cell parts and types of bacteria through a microscope
Chen and her colleagues designed a study based at the University of Bamako in Mali to test the safety and impact of methylene blue in stopping transmission of malaria parasites to mosquitoes.
All of the 80 participants, men and boys ages 5 to 50, were carrying gametocytes, a stage of the malaria parasite that can be passed from humans to mosquitoes. But they weren't experiencing any malaria symptoms and had not taken any anti-malarials within seven days of screening for the study.
Participants were split into four groups and given four different types of treatment, ranging from anti-malarial pills containing methylene blue to malaria medication with no added dye.
"As the [malaria] infection is dying, it releases a wave of these different forms of parasites — the male and female gametocyte. It tries to catch the next mosquito out of there to a more healthy environment," says Chris Plowe, director of the Global Health Institute at Duke University, who was not involved in the study. "You do cure the infection, but at a cost of sending out these waves of gametocytes to other people via mosquito."
Plowe sees the blue-dye approach as potentially helpful in countries like Mali, where malaria rates remain high despite efforts to lower transmission, such as distributing bed nets and rapid diagnostic testing.
William Moss, a professor at the Johns Hopkins Malaria Research Institute who also wasn't involved in the study, adds that primaquine and methylene blue could be particularly helpful in places that already have low malaria transmission and are trying to eliminate it.
But there are still some unknowns: Will methylene blue actually be able to reduce transmission rates in the field?
Moss sees some potential challenges.
One concern is that you'd have to give this treatment to a "high enough proportion of individuals within the community who are infectious," Moss says.
And then there's the problem cited back in the 19th century: the blue urine.
"The knee-jerk reaction is, 'My body's full of this chemical,' " Chen says, adding that the color change doesn't cause any health problems. "It looks worse than it is." And it only lasts about a week.
So people would have to be educated about this side effect, she notes.
Moss agrees: If "people don't like the blue urine, they refuse to take the meds."
Courtney Columbus, a multimedia journalist, covers science, global health and consumer health. Her work has appeared in the Arizona Republic and on Arizona PBS. Contact her @cmcolumbus11.