Networks Untangle Malaria’s Deadly Shuffle

The world’s most dangerous malaria parasite shuffles its genes in a clever attempt to avoid the immune system. A new approach has begun to reveal how the process works.

Veronique Greenwood in Quanta:

Think of a deck of cards,” said Dan Larremore. Now, take a pair of scissors and chop the 52 cards into chunks. Throw them in the air. Card confetti rains down, so the pieces are nowhere near where they started. Now tape them into 52 new cards, each one a mosaic of the original cards. After 48 hours, repeat.

You have just reenacted the process that Plasmodium falciparum uses to avoid the immune system. P. falciparum is the world’s most dangerous malaria parasite, causing 600,000 deaths every year and killing more children under the age of 5 than any other infectious disease on the planet. Larremore, an applied mathematician, was introduced to its promiscuous habits while doing postdoctoral research at what is now the Harvard T.H. Chan School of Public Health.

Each card represents a gene for a protein that attaches to the walls of the host’s blood vessels, anchoring the parasite so that it cannot be dragged into the spleen, where it would be detected and destroyed. Each falciparum parasite has 50 to 60 of these vargenes, as they are called, and as time passes the parasite uses first one, then another, presenting a constantly morphing face to immune cells that might spot it clinging to the blood vessel. The crowning glory of this tactic, though, is that when the parasite divides, which it does every couple of days, chunks and snippets of the genes swap places up and down the chromosomes. In one out of every 500 parasites, this process will generate an entirely new gene. With the number of parasites out there, that adds up quickly. “It’s crazy. It means the total number of var gene sequences in the world is millions and millions — virtually infinite,” said Antoine Claessens, a malaria researcher with the Medical Research Council, The Gambia Unit, in Fajara.

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