Using Evolution to Fight Malaria

Jun 13, 2017

For many in the developed world, life before vaccines and antibiotics is hard to imagine, let alone remember. In a mere matter of decades, we have rapidly reduced the risk of death from common infections and even eliminated some deadly diseases. But disease-causing organisms are fighting back, evolving ways to survive our biomedical weapons.

The U.N. calls such antimicrobial resistance one of the greatest human health threats in the world. And it’s not just bacteria. Malaria kills more than a million people each year. Most of those deaths are due to unavailability of treatment, or failure to seek it out, but drug resistance is a major concern.

“The original best antimalarial drug, chloroquine, is unusable for the malaria that causes the greatest number of cases, and the greatest morbidity and mortality,” said Dyann Wirth, a malaria researcher at Harvard’s School of Public Health and the Broad Institute. “The world has been forced to develop new drugs and resistance has developed to each of these drugs a they’ve been introduced.”

Today, the standard of care is a combination of anti-malarial drugs, but resistance to even these cocktails is already widespread in southeast Asia. And researchers worry that such resistance could also crop up in Africa and South America.

In general, each species has to evolve drug resistance independently. But Wirth says there are patterns – commonalities – and some strategies that can confer broad-spectrum drug resistance. In many cases, including malaria, drug resistance involves a molecule that moves drugs away from their target inside the cell.

It’s not entirely clear why such molecules exist in the first place, although it may be part of organisms’ defenses against the many chemicals that are found in nature.

What is clear is that the changes malaria makes to become drug resistant come at a cost. In a drug-free environment, drug-resistant malaria is less fit – less likely to survive – than non-resistant strains of the parasite.

“The balance between resistance and fitness is extremely important to how fast resistance spreads,” Wirth explained. “In the case of chloroquine, for example, resistant parasites don’t appear to be different when you grow them in the laboratory, but if chloroquine is removed from a population - as has been done in Malawi- you see the return of chloroquine-sensitive parasites into the population.”

Wirth says understanding the evolution of infectious diseases, like malaria, is critical to treating, and possibly eliminating, them.

“These organisms have adapted to humans and humans have adapted to humans,” said Wirth. “Understanding that gives us a sense of new ways to intervene.”

Wirth says the parts of the parasitic genome that vary the least may be essential to malaria survival, and thus, good drug targets. Still, Wirth says she’s looking forward to eventually having a vaccine for malaria, and the possibility of eradicating the disease, altogether.

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