Gnathostomiasis

Definitive hosts for Gnathostoma species include dogs, cats, pigs, wild boars, tigers, leopards, lions, minks, weasels, opossums, raccoons, and otters, in which adult worms live in a tumor-like mass within the host’s gastric wall. The definitive host is defined as the animal species in which the Gnathostoma species reproduce.  Adult worms range 13 to 55 mm in length. Adult females release eggs which are evacuated in the feces of the definitive host and later hatch as larvae in a freshwater environment (about 7 days later). Larvae in freshwater are eaten by tiny crustaceans (also known as copepods, tiny crustaceans of the genus Cyclops), which are in turn eaten by other animals, such as freshwater fish, eels, frogs, birds, and reptiles. Larvae penetrate the gastric wall of the copepods, migrate through the body cavity, and mature into second stage and early third stage larval forms. The copepods are then ingested by second-intermediate hosts (fish, frogs, snakes, eels, chicken, pigs), in which the larvae again penetrate the gastric wall, migrate into muscle tissue, and mature into advanced third-stage larvae before encysting there.

Definitive hosts that eat an infected animal, can become infected and the larvae can mature into the adult form and complete the nematode’s life cycle. When flesh from the second-intermediate hosts is eaten, the larvae excyst in the stomach, penetrate the gastric wall, migrate to the liver, and travel to connective tissues and muscles. After 4 weeks, they return to the gastric wall to form the tumor-like mass in the upper digestive system, where they mature into adults in 6-8 months. 8-12 months after initial ingestion, the worms mate, and eggs pass into the host’s feces.

Humans become infected when they ingest third-stage larvae in raw or undercooked flesh of freshwater fish or other definitive hosts or when they drink, work in, or bathe in freshwater contaminated with larvae or infected copepods. Humans are non-required hosts. Gnathostoma species survive in humans but cannot mature into adult worms capable of reproduction. In humans, the larvae do not return to the stomach wall, but rather, they can migrate throughout the body for as long as 10-12 years. For this reason, eggs are rarely, if ever, found in human feces.

Two alternate routes of human infection have been suggested: ingestion of freshwater containing infected copepods (thus taking the place of a second intermediate host) or penetration of food handlers’ skin by third-stage larvae from infected flesh. Symptoms in humans occur as the late third-stage larvae migrate through tissues, causing intermittent symptoms of cutaneous or visceral larva migrans. The larvae have been observed to move at 1 cm/hour.

Within 24-48 hours post-ingestion, larvae invade the gastric and/or intestinal wall, causing eosinophilia and local symptoms. Larvae migrate to and through the liver. Their migration throughout the body begins 3-4 weeks to several years post-ingestion. Typically, episodes last 1-2 weeks. Over time, episodes are often less frequent, less intense, and shorter.

The exact pathogenicity of gnathostomiasis is not known, but it is believed that the symptoms are due to several mechanisms: the combined effects of mechanical damage secondary to larval migration, larval excretions and secretions, and the host's immunological response. Studies in Japan, in the 1950s, defined the substances released contain various compounds, including one that resembles acetylcholine, a hyaluronidase, a proteolytic enzyme, and a hemolytic substance (hemolysin), Actions of these substances, in addition to the mechanical damage, cause the characteristic hemorrhagic tracks seen in the subcutaneous tissues in patients or in viscera or CNS postmortem studies. ^[3]

Causes include travel to or from the following endemic areas:

• Southeast Asia, especially Thailand

• Japan

• China

• Latin America, especially Mexico and Ecuador

• Western Australia

• South Central Africa

Causes include the following dietary/occupational exposures or ingestions:

• Raw or undercooked freshwater fish (ceviche in Mexico and South America, sashimi in Japan, sum-fak in Thailand). Nematode larvae not present in saltwater fish.

• Other raw or undercooked flesh

• Contaminated freshwater

United States statistics

An unconfirmed human case of gnathostomiasis acquired in the United States was reported, ^[4]  and another case was more recently reported in a patient with no travel history who had consumed raw freshwater fish from a local lake. ^[5] Gnathostomiasis remains rare in individuals who are exposed abroad.

International statistics

Gnathostomiasis is an uncommon disease, even in endemic areas of Japan, Korea, ^[6] Taiwan, Southeast Asia (Laos, ^[7] Malaysia, Thailand), and Latin America (mainly Mexico and Ecuador), although its incidence appears to be increasing, possibly due to changing diet. ^[8] It is most common in Thailand and Japan. About 5000 cases of gnathostomiasis have been reported throughout the world. ^[9]

In Thailand, it is the most common parasitic infection of the central nervous system (CNS), also called neurognathostomiasis. Neurognathostomiasis has only been reported in patients infected with G spinigerum. ^{[10, 11]}  Six percent of subarachnoid hemorrhages in adults and 18% of those in infants and children are due to gnathostomiasis in Thailand.

Pathogenicity in the CNS is from direct mechanical injury due to tearing, with or without destruction of the nerve tissue and its vascular structures. Additionally, inflammation and destruction of tissue due to toxin production occurs. Hallmark signs of neurognathostomiasis are hemorrhagic tracts, which have been documented postmortem throughout the spinal cord and cerebral tissue. Death occurs if vital structures in the brain stem are invaded, which may occur within 4 to 31 days following the onset of CNS symptoms, or if the larva burrows through a cerebral arteriole causing subarachnoid hemorrhage. ^[3]

Race-, sex-, and age-related demographics

Race

No racial predilection has been reported.

Sex

No predilection has been reported, except in cases in which occupation, diet and social habits are gender specific. Overall, females are more commonly affected than males, except in Vietnam where the opposite is true.

Age

Adults are infected more often than children, most likely related by factors such as occupation, diet and/or social behavior. However, all ages are affected. Infection in a newborn has been reported suggesting either prenatal or perinatal transmission.

Gnathostomiasis is seldom fatal, except in cases of CNS disease. Long-term morbidity is possible because of tissue injury during migration. With CNS disease, the mortality rate is 8-25%; one third of survivors have long-term sequelae.

Morbidity/mortality

Gnathostomiasis can persist 10-12 years and may cause significant morbidity because of its capability to involve any part of the body. Invasion of the CNS, which is the major cause of mortality, may cause death in 8-25% of patients or result in long-term sequelae in 30% of patients with neurognathostomiasis.

Complications

In Thailand, 6% of subarachnoid hemorrhages in adults and 18% of those in infants and children are due to gnathostomiasis.

Pneumonia, sepsis, paralysis, and/or long-term neurologic sequelae are possible.