Anyone who drinks standing pond or well water contaminated by persons with Guinea worm infection is at risk. People who live in villages where the infection is common are at greatest risk.

Larvae of Guinea worm enter the human body when people drink water contaminated with the cyclops containing infective larvae in the stomach. Cyclops are digested and the larvae can move freely. They subsequently try to penetrate the thin intestinal wall. If successful they end up in the connective tissues of abdomen and thorax they develop in to adult worm, mating after 3 months. When mature, the female moves toward the surface, usually of the legs. About a year after the infection begins the female is ready to emerge from the body to reproduce by releasing up to 3 million larvae.

The female worm produces toxic substances that break down the overlying skin causing painful blisters and ulcers. The worm partly emerges and releases larvae over a period of 1–3 weeks frequently when the affected person enters water. For example to collect drinking water.

The released larvae are not directly infective to humans. They can remain active in water for about three days. Inside the cyclops, the guinea worm larvae develop over a period of about two weeks into larval stage that is infective to humans.