Saturday, November 26, 2016

Future of the Guinea Worm

Guinea worm (Dracunculus medinensis) is one of those parasites that nightmares are made of. Juvenile worms infect freshwater copepods, which invariably end up getting ingested [by humans] when drinking contaminated water. The adult female grows up to a few feet long. It migrates to the skin (usually in the lower leg) and induces an extremely painful blister about a year after infection. The blister is described like being set on fire. The pain is alleviated best by standing in water, which is exactly what the worm wants. When the blister is in water, the female worm releases hundreds or thousands of babies into the water.

Former US President Jimmy Carter has been leading an organization working to make the worm go extinct. As a disease organism, few people are going to lament its extinction. When I first learned about this organism, it was invariably described as infecting humans only. This would make the process of wiping it out so much simpler. Unfortunately, the story isn't quite so simple. The worm has other plans.

Figure 1 from paper.
Increasingly, dogs in Chad are being found with lower-leg lesions that have worms hanging out of them. Genetic analysis has shown it is the same species as the Guinea worm which infects people. Even if we prevent all human infections for long enough to interrupt the parasite's life cycle, it can still persist in other animals. It looks like it would take continuing diligence to keep it from erupting into an active human disease again.

Adapted from page.
Over the last several years, the number of infections observed in dogs has been going up and up, while human infections have been minimal. This pattern of yearly increases suggests the worms have been adapting to their new hosts.

The researchers did find evidence for human behavior that helped give the parasite the opportunity to make this transition. At the end of the dry season, the locals do a mass harvest of fish. The fish are processed and dried/smoked for later use. The guts and other undesirable bits are discarded for the dogs, chickens, etc. to deal with. The dogs are then getting infected by eating the fish guts. It also appears that uncooked/undercooked fish are responsible for the human cases of infection.

Adapted from Figure 9 of paper.
Historically, most human infections by this parasite were due to ingestion of water contaminated by infected copepods (an host to an earlier stage of the worm). With increasing knowledge about this mode of transmission, it became dramatically less useful of a pathway for the parasite. At the same time, any alternate pathway for the parasite to get into its main host would have been positively selected. Essentially, we've just seen a parasite go from a life-cycle with one intermediate host to a life-cycle with two intermediate hosts.

Many parasites are known to have complicated life-cycles passing through several intermediate hosts, but this is the first case I've come across that helps to illustrate how those complex life-cycles could have evolved.

Better control of the fish discards will help minimize the infection pathway through dogs, but it won't necessarily get rid of the problem. While adapting to their new hosts, the worms have had to evolve to better escape notice by the canine immune system. A consequence of this is that they will be better prepared to infect dogs later by other pathways, even if fish discards aren't available. Maybe dogs will start getting infected by ingesting infected copepods like humans used to. Maybe dogs will start getting infected by eating scavenged fish that died in the dry season. I can't predict what will happen exactly, but I understand the power of natural selection and very much believe the worm will find another way to survive even if we completely prevent transmission to humans in the near future.