Malaria remains one of the biggest public health problems worldwide. Nearly half the world’s population, or over 3 billion people are at risk of malaria infection, which can cause fever, fatigue, bleeding, seizure, and even death. Although the World Health Organization reports death rates from malaria are dropping, the disease still claimed nearly 438,000 deaths in 2015.
Drugs developed to combat malaria have been thwarted by resistance, which renders the drug unusable as can’t kill the parasite as intended. This was the case for the drug Atovaquone, which showed evidence of resistance soon after it was introduced. Consequently, the drug was phased out of use.
But a team of dedicated researchers at the University of Melbourne, Australia, did not give up hope for atovaquone. As they studied this drug to find out the mechanism behind drug resistance, the team stumbled upon a highly desired outcome: a genetic mutation enabled the parasite to have resistance early in the life, but then later cripples a later part of its life cycle. In essence, the drug doesn’t do much to the parasite in the beginning, but acts to prevent the spread of drug resistance later on.
"We now understand the particular genetic mutation that gave rise to drug resistance in some malaria parasite populations and how it eventually kills them in the mosquito, providing new targets for the development of drugs," said Geoff McFadden, lead study author. They are calling atovaquone’s actions a “gene trap,” which represents a huge leap in the fight against malaria.
"So the development of drug resistance may not be a major problem if the resistance cannot spread, meaning the drug atovaquone could be more widely used in malaria control," McFadden added. Indeed, mouse experiments with the resistant parasites showed drug resistance did not spread by mosquitos.
"We are the first group to follow the drug resistant malaria parasite through its entire life cycle to understand what happens after drug resistance initially develops and whether they pass on resistance," said McFadden, proudly. "It is very rewarding that our fascination with basic biology has produced such significant results."
“The big picture is that Atovaquone, once thought of as a second rate drug because parasites can easily become resistant to it, might be extremely effective at stopping malaria transmission and could therefore be important for disease eradication,” commented Paul Gilson, Senior research officer from the Burnett Institute.
Their next goal is to test the drug in the field, including regions such as Kenya and Zambia, countries with very high risks of malaria transmission. We are hopeful that with the development of cheaper generic forms of the drug atovaquone, that there is a new hope in the treatment of malaria," said McFadden.
Additional source: Science Daily, BBC