A species of malaria-causing parasite that is increasingly being transmitted from macaques to humans in South Asia has the potential to evolve into a more virulent form that is also capable of being efficiently transmitted from human to human. This is according to a paper published Monday morning in the journal Nature Communications by researchers at the Harvard TH Chan School of Public Health.
P. knowlesi, aka "monkey malaria," has been stalking the Earth already for some 257,000 years, but in that time the parasite has largely left humans out of its business. In some large part this has to do with a relative lack of overlap between human populations and macaque populations. As such, mosquitoes get to feast on the blood of one species or the other but rarely both.
Lately, however, monkey malaria has become a significant human threat in the countries of South Asia, particularly Borneo. In February, researchers were able to link massive deforestation in that country to the parasite's increasing spread—it turns out that one species of macaque known to carry P. knowlesi thrives on deforested land. Put this together with a general increase in human encroachment on macaque territory in the region and we have an ideal case for introducing the parasite to human populations in far greater numbers.
Fortunately, P. knowlesi isn't all that deadly to humans. Or at least that's been the case up until now.
"Most human blood-stage infections are mild and associated with low parasitaemias, but increasing numbers of severe infections accompanied by high parasitaemias are being reported," the study notes. "There is growing concern that this simian parasite is adapting to infect humans more efficiently."
"There is growing concern that this simian parasite is adapting to infect humans more efficiently."
There are five variations of malaria known to infect humans, but the parasites all share basically the same life cycle: infect host via mosquito, head for said host's liver, and then reproduce. The resulting parasite multitudes then spread throughout the body invading red blood cells, where they reproduce again, bursting the blood cells in the process. Malaria parasites make for some really shitty guests in the human body, even by parasite standards.
When it comes to human infection, P. knowlesi hasn't been much of a player because it's very poorly equipped for invading human red blood cells. Around 3.2 million years ago, early humans lost the ability to convert a certain kind of acidic sugar into another kind of acidic sugar often found on the outsides of red blood cells. Apes, however, did not. As it turns out this converted form of sugar is largely what P. knowlesi needs to breach blood cells.
And yet that natural defense seems to be losing its effectiveness, according to this week's study, in part because the parasite has figured out (genetically) that it can work its way into older red blood cells without the aforementioned pathway.
What the Harvard researchers wanted to know is what would happen if humans again started producing the parasite's preferred sugar. So, they basically just undid the ancient mutation that changed our red blood cells from those of our ape kin, with the result being, "enhancement of P. knowlesi invasion," according to the paper.
Of even more concern was that the parasites were eventually able to adapt to human red blood cells in such a way that they no longer needed the sugar pathway being studied. Currently, they need that sugar to make the molecule required to bind to the blood cells, but the researchers found the parasites were eventually able to duplicate it independently.
That doesn't mean this is currently happening in human cells not in a dish in a lab, but the potential is there. And as P. knowlesi spends more time around people, as is the trend, then that potential only increases. Add that to a potential if not likely increase in human-to-human transmission, and we have a bad scene.
"There is already evidence suggesting the clustering of P. knowlesi infections in households, where individuals had not been in proximity to macaques," the paper notes. "In the 1950s, the use of P. knowlesi as a treatment for tertiary neurosyphilis had to be stopped because of increased pathogenicity of the parasite, with continuous passaging in humans. This suggests that increased parasite adaptation to humans may be associated with severe disease."