Nanophyetiasis is caused by the digenetic intestinal trematode Nanophyetus salmincola, a fish-borne parasite belonging to the family Troglotrematidae. Human infection with this intestinal fluke has been mainly reported from the coastal region of the Pacific Northwest of the United States. It is usually acquired by ingesting raw or undercooked freshwater parasite-infested salmonid fish (Pacific salmon), steelhead trout, or steelhead eggs. Cases of human infection acquired after handling of infected Pacific salmon fish have been reported.

The life cycle of N. salmincola requires 3 hosts: 2 intermediate hosts and 1 definite host. The eggs of N. salmincola are passed in the stool and hatch into larvae called miracidia, which penetrate and infect snails (the first intermediate host) commonly found in the Northwest. Within these snails, larvae mature into cercariae that leave the snails and infect and encyst in the flesh of salmonid fishes or non-salmonid fishes (the second intermediate host). Those infected fishes are ingested in raw or partially cooked fish by the definitive hosts, which include dogs and humans. Once in the human host, there is an incubation period of 1-15 weeks before clinical symptoms appear.

Dogs are typically infected by feeding off the remains of fresh fish or eating dead salmon on riverbanks. This trematode worm is not known to cause clinical disease in dogs, but it carries a rickettsial bacteria known as Neorickettsia helminthoeca, which is mostly known for its association with "salmon poisoning disease" in canids, a fatal disease if left untreated. However, there are no known reported cases of human infection by this rickettsial organism.

Human nanophyetiasis usually manifests 1 week after ingestion of infected fish or 1 month after handling fresh fish. Clinical manifestations are usually nonspecific and include fatigue, abdominal discomfort, nausea, vomiting with diarrhea, and weight loss. Asymptomatic infections are common. The first human case of nanophyetiasis was reported in 1956 when a researcher experimentally infected himself; this was followed by the first report of human intestinal infection with N. salmincola from eating infected salmonid fish in Washington State in 1987. Two years later, a case series of an additional 10 patients with nanophyetiasis was reported from the same geographic region. Interestingly, a biological technician was infected with N. salmincola after he necropsied more than a thousand fresh-killed coho salmon without protective gloves in Washington State. Accidental hand-to-mouth transmission occurred during this handling, and symptoms typical of nanophyetiasis started after 1 month. Additional evidence of human nanophyetiasis reported in the literature is sparse and has been lacking since 1990. It is likely to be underreported given its nonspecific symptoms and because it does not result in long-term morbidity and mortality.

Of note, another subspecies of Nanophyetus, known as Nanophyetus schikhobalowi, has reportedly been endemic in Eastern Siberia since 1931 with similar clinical features as its counterpart N. salmincola.

Peripheral eosinophilia (>500/µL) is a significant laboratory finding seen in up to 50% of the patients. Stool examination typically shows light brown eggs with a characteristic operculum at one end and a small blunt point at the other. The eggs are usually first detected in stool approximately 1 week after ingestion of infected fish.

There are as of yet no reported cases of mortality from human nanophyetiasis. All patients treated with an anti-helminth responded well and were cured. Reportedly, one-third of patients with positive stool examination were asymptomatic, which suggests that a significant proportion of infected individuals may go undiagnosed.