Gnathostomiasis

Gnathostomiasis

Gnathostomiasis is a kind of parasitic diseases caused by Gnathostoma spp. The diseases is a zoonotic food borne diseases which is normally caused by the consumption of fresh fishes containing advance third stage larva of Gnathostoma spp. water copepod or cyclops. The disease is mainly characterizing by the migratory pain and skin piercing pain.

There are many different species of Gnathostoma spp however only five species have been reported as the medically important one cause infections to human beings. These are

G. binucleatum, G. doloresi, G. hispidum, G. nipponicum and G. spinigerum. G. malaysiae ia a potential pathogen which has not been reported in Thailand.

The disease is highly prevalent in South east Asia including Thailand, China, Japan and also been reported from India. The diseases is also been reported from Latin America and many parts of Mexico.

Life cycle:

Gnathostoma spp has two intermediate hosts to complete their life cycle. Human is only accidental hosts in which they can’t complete their sexual life cycles. The definitive hosts for the parasite are the fresh water fish eating animals such as dogs, cats, leopards and etc. The advance stage larva they harvest from the fish can be developed into an adult worm in their intestine. They lay the eggs and pass through the feces. The Unembryonated eggs are changed into embryonated eggs and are hatched to release first stage larva in the fresh water. These larvae are nutrient for many cyclopes including copepods. Once they are eaten by copepods of the fresh water, the first stage of larva (L1) is changed in to the second stage (L2) of larva in their intestine. The cyclops are then consumed by the fresh water fishes, where the larva developed into the advance third stage larva (L3), an infective form of Gnathostoma spp. Some animals eat those fresh water fishes and where the parasite complete their life cycles. Initially the parasite move through the skin to tissue and then to liver and abdominal cavity. They remained 4 weeks there and returned back to stomach where the parasite changed into adult worms. These adults worm then lay eggs and complete their life cycles within the 6 months. However, when human consume undercooked or raw fresh water foods, they acquire the infective form of larva. These larvae move to intestine and from where they migrate to skin via the tissue. They start migrating aimlessly in different parts if body such as lungs, eye, GI tract, genitourinary tract and cause migratory swellings. Rarely but very fatal, they can also migrate to central nervous system and spinal cord to cause CNS Gnathostomiasis.

Figure 1: Life cycle of Gnathostoma spinigerum. (Adapted from an image from the CDC-DPDx [www.dpd.cdc.gov/dpdx/HTML/gnathostomiasis.htm].)

Pathogenesis:

The mechanism of pathogenesis of Gnathostomiasis are due to combined action of mechanical trauma, ES products of parasites and host inflammatory response. The mechanical trauma is caused due to aimless migration of larva through the skin and many other body parts. This causes migratory swellings and moving piercing pain. During the migration of larva, due to spines throughout their body, there is itchy, irritation and urticaria in the body. Another important factor in pathogenesis of Gnathostomiasis is by the ES biproducts from the adult worms. The ES biproduct contain the proteases, toxic substances, anti-inflammatory molecules and anticoagulants. The biproducts initially degrade the tissues and deteriorate the protein of the hosts for their nutrients. They also act as anticoagulant and inhibit the activation of platelets. Most importantly these products also disturb the immune response of host. The host inflammatory response specially in parasitic infections may have role in cytotoxicity of its own cells. During the infection, they inhibit the cytotoxic effects of NK cell by decreasing NKG2D expression. They also interfere with functions of monocytes or macrophages related to phagocytosis by reducing the FCrR-1 (CD64) expression and finally damage the immune cells by apoptosis.

Clinical manifestations:

General clinical signs and symptoms

Fever, malaise, nausea, anorexia, vomiting, urticaria, epigastric pain or upper right quadrant pain and diarrhea.

Normally the incubation period is 24 to 48 hrs.

Once they start to migrate in the skin (cutaneous infections), one may feel the migratory swellings, moving piercing pain, eosinophilia,

Further the larva can spread to many other organs randomly causing visceral infections to lungs, GI tract, Genitourinary tract, eyes and rarely to CNS causing

Increased pressure on intracranial

Fever, neck stiffness photophobia, migratory neurological findings, paralysis, cranial nerve involvement and urinary retention,

Finally, death

Cutaneous Gnathostomiasis

Cutaneous gnathostomiasis is the most common manifestation of infection and is known by several local names, e.g., Yangtze River’s edema and Shanghai’s rheumatism in China, tuao chid in Japan, and paniculitis nodular migratoria eosinofilica in Latin America. It typically presents with intermittent migratory swellings, (nodular migratory panniculitis), usually affecting the trunk or upper limbs. These nonpitting edematous swellings vary in size and may be pruritic, painful, or erythematous. They usually occur within 3 to 4 weeks of ingestion of the larvae, typically last 1 to 2 weeks, and are commonly due to only one larva, but on occasion infection with two or more has been found. The swellings are due to both mechanical damage from the larva and the host’s

immunological response to the parasite and its secretions. As the larva migrates, subcutaneous hemorrhages may be seen along its tracks, which are pathognomonic of gnathostomiasis and can help differentiate it from other causes of larva migrans, e.g., sparganosis or strongyloidiasis. Episodes of swelling slowly become less intense and shorter in duration, but in untreated patients’ symptoms may recur intermittently for up to 10 to 12 years.

Visceral Disease

The Gnathostoma larva is highly invasive and motile and therefore can produce an extremely wide range of symptoms affecting virtually any part of the body. In noncerebral disease the larvae may continue to cause intermittent symptoms until they die after about 12 years, if left untreated.

Pulmonary manifestations. Pulmonary symptoms that have been attributed to infection with Gnathostoma spp. include cough, pleuritic chest pain, heamoptysis, lobar consolidation or collapse, pleural effusions, and pneumo- or hydropneumothorax.

Gastrointestinal manifestations. Gastrointestinal manifestations are less common in humans but may present as sharp abdominal pains as the larva migrates through the liver and spleen or as a chronic mass in the right lower quadrant. Less commonly, there may be acute right iliac fossa pain with fever mimicking acute appendicitis or intestinal obstruction. Infection has also been found as an incidental (and asymptomatic) finding at surgery for a different problem.

Genitourinary manifestations. Involvement of the genitourinary tract is uncommon, but hematuria and the passage of the larva in the urine have been reported. Other symptoms attributed to Gnathostoma spp. include profuse vaginal bleeding, cervicitis, balanitis, an adnexal mass, and hematospermia.

Ocular. The eye is the only organ in which the larva may be visualized, and therefore there are many more literature reports of ocular involvement than of involvement of other organs. Eye involvement has led to symptoms of uveitis (usually anterior), iritis, intraocular hemorrhage, glaucoma, retinal scarring, and detachment.

Auricular manifestations. Various reports have described a wide variety of manifestations, which include mastoiditis, sensorineural hearing loss, and extrusion of the larva from the external auditory canal, the soft palate, the cheek, the tip of tongue, and the tympanic membrane.

CNS manifestations. In the subsequent year the parasite was found on the surface of the cerebral

hemisphere and attached to the choroid plexus of the lateral ventricle in two patients with fatal meningoencephalitis. There have been several case series of CNS diseases, which has increased understanding of the pathophysiology. Compared to other forms of disease, the CNS form of the infection carries the highest mortality, with reported rates of 8 to 25%, and 30% of survivors having long-term sequelae.

Treatments

Albendazole (200 mg)

400-800 mg/kg/day for 21 days

Ivermectin (6 mg)

200 microgram/KG/single dose for 14 days.

Diagnosis:

Diagnosis of Gnathostomiasis can be done with Microscopy, Immunodiagnosis and by Molecular techniques

The larva is removed by surgery and identified under the microscope by the numbers of hooks present, different rows od hooks and also by spines arrangements. Very difficult to identify.

Immunodiagnosis:

Mainly ELISA and Immunoblot are used.

Using CsAg, crude somatic antigen IgG1 is analyzed with high sensitivity and specificity.

In immunoblot, same antigens is used to detect IgG4 antibody.