Head bulb of Gnathostoma spinigerum female worm using a scanning electron microscope[i]
Gnathostomiasis is a member of the phylum nematode and is considered to be blood- and tissue-dwelling nematodes[ii]. The most common form of gnathostomiasis affecting humans is Gnathostoma spinigerum[iii]. There have also been reported human cases resulting from infection with g. hispidium, G. doloresi, and G. malaysiae[iv]. The species G. spinigerum, G. hispidium, G. doloresi, and G. malaysiae are found in Asia, while G. binucleation is found in Central and South America[v].
Species: Gnathostoma spinigerum
Larva migrans profundus
Nodular migratory eosinophilic panniculitis
Spiruroid larva migrans
The first case of Gnathostoma was identified by Sir Richard Owen of London when inspecting the stomach of a young tiger that had died at the London Zoo from a ruptured aorta[viii]. However it was not until 1889 that the first human case was described by Levison when he found gnathostoma larva in an infested Thai woman[ix]. This delay in identification of the parasite in humans is due to the fact that humans are not a definitive host for this parasite making infection from this parasite rare. Gnathostomiasis infection is rare because the parasite must be digested when it has reached its third larvae stage, providing only a short time frame in which the parasite is capable of infecting humans. It is uncommon for the larvae to penetrate the skin of individuals exposed to contaminated food or water without ingestion[x]. Despite its difficulty in infecting humans, it is considered an emerging infection for travelers in Central and South America as well as in Southeast Asia[xi].
Clinical Presentation in Humans
Symptoms of Gnathostomiasis spinigerum
A few days after ingestion epigastric pain, fever, vomiting and anorexia resulting from migration of larvae through intestinal wall to the abdominal cavity will appear in the patient[xii]. These symptoms are characteristic of the first syndrome associated with infection by G. spinigerum[xiii]. The second syndrome associated with infection by this specie of gnathostomiasis is characterized by severe pain in the trunk or limbs and can lead to paralysis of extremities[xiv].
Symptoms associated with the New World
Infection seen in South and Central America is characterized by swelling generated by larvae migrans and the inflammatory response generated by the presence of the foreign pathogen[xv]. Distribution of skin lesion sis more commonly found in the trunk and extremities[xvi]. These lesions result from larvae migrans and are usually short and wide in length when examined[xvii].
Symptoms associated with Southeast Asia
The infective species found in the other endemic areas produce larger lesions which help in identifying the species responsible for the lesions[xviii]. The larvae migrans responsible for these lesions are often limited to the stomach area and to the back of the body[xix].
Regardless of the species of gnathostomiasis responsible for the infection, the larvae can be spontaneously expelled from an indurated red papule found on the patient[xx]. This papule appears in the form of a nodule.
Larva migrans on patient with gnathostomiasis (image on left) and specimen retrieved from skin scrapings of the patient with the larva migrans (image on right)[xxii]
Gnathostomiasis is primarily transmitted by ingestion of raw, insufficiently cooked intermediate hosts such as fresh water fish, birds or amphibians[xxiii]. There have also been reports of transmission by direct penetration of the skin on the palm resulting from the handling of infected meat[xxiv]. Mother to fetus transmission has also been identified as a result of larva migration to the fetus through the placenta[xxv].
The primary intermediate host for gnathostomiasis is the minute crustacean of the genus Cyclops[xxvi]. These crustaceans are then ingested by a second intermediate host such as fish, birds, and frogs.
The definitive host for gnathostomiasis includes cats, dogs, tigers, leopards, lions, minks, opossums, and raccoons[xxvii]. However the primary reservoirs for this parasite are cats and dogs.
There is no vector for the parasite gnathostomiasis[xxviii]
The incubation period for gnathostomiasis is 3-4 weeks which is when the larvae begin to migrate through the subcutaneous tissue of the body[xxix].
The adult parasite is reddish-brown in color and has a globular cephalic dome that is separated from the rest of the body by constriction[xxx]. The posterior portion of the nematode is smooth while the anterior half is covered with fine leaf-like spines[xxxi]. The head is round and contains 4 to 8 transverse rows of hooklets that are protected by a pair of fleshy lips[xxxii]. The males are shorter than the females, 11 to 25 mm compared to 25 to 54 mm respectively[xxxiii]. Eggs are usually yellow or brown, oval, and have a mucoid plug at one end[xxxiv]. The third stave larva is the infective form of this parasite and can be identified by its round extremes and cylindrical body as well as the rows of cuticular spines that decrease towards the posterior end[xxxv]. The number of hooklets present on the advanced third stage larvae is used in the identification of the parasite when removed from a patient[xxxvi]
Image of third stage larval of Gnathostoma spinigerum. A) Complete larva B) Close up of head[xxxvii]
Life Cycle of Gnathostomiasis
Life Cycle of Gnathostomiasis[xxxviii]
Life Cycle in Definitive Hosts of Gnathostomiasis
Adult worms found in a tumor located in the gastric wall of the definitive hosts and release eggs into the host’s digestive tract. The eggs are then released with feces and in about a week hatch in water to develop into the first larva stage[xxxix]. Larvae are then ingested by minute copepods of the genus Cyclops[xl]. Once entering the copepod, the larva penetrate the gastric wall of their intermediate host and begin to develop into second-stage and even early third-stage larval[xli]. The copepods are then ingested by a second intermediate host such as fish, frogs, or snakes[xlii]. Within this second intermediate the larva repeat a similar pattern of penetrating the gastric wall, but then continue to migrate to muscular tissue and develop into advanced third-stage larvae[xliii]. These larvae then encyst within the musculature of the new host[xliv]. If the cyst containing flesh of these hosts is ingested by a definitive host, such as tigers, the cysts are ingested and the larvae escape the cysts and penetrate the gastric wall[xlv]. These released larvae travel to the connective tissue and muscle as observed before and after 4 weeks they return to the gastric wall as adults[xlvi]. Here they form a tumor and continue to mature into adults for the next 6-8 months. Worms mate and begin to excrete eggs with feces 8-12 months after ingestion of cysts[xlvii].
Life Cycle in Humans
Infection in humans follows ingestion of raw, insufficiently cooked infected intermediate hosts[xlviii]. The ingested third stage larvae migrate from the gastric wall and its migration through subcutaneous tissues results in the symptoms associated with gnathostomiasis infection[xlix]. The third stage larvae do not return to the gastric wall, which prevents the larvae from maturing into adult worms, leaving the parasite unable to complete its life cycle. Instead the larvae continue to migrate unpredictably in the patient, and are unable to develop into adults, so eggs are seldom found in diagnostic tests[l]. This also means the number of larvae present in humans is a reflection of the number of third stage larvae ingested.
The primary form of diagnosis of gnathostomiasis is the identification of larva in the tissue[li]. Serological testing such as enzyme-linked immunosorbent assay (ELISA) or the Western blot are also reliable but may not be easily accessible in endemic areas[lii]. CT scan can be used to help identify a soft tissue worm and when looking at CNS disease it can be used to reveal the presence of the worm[liii]. Urinalysis can also be used to identify the presence of hematuria or the worm, but it is not a very reliable diagnostic tool.
Management and Therapy
The most prescribed treatment for gnathostomiasis is surgical removal of the larvae but this is only effective when the worms are located in an accessible location[liv]. In addition to surgical excision, albendazole and ivermectin have been noted in their ability to eliminate the parasite[lv]. Albendazole is recommended to be administered at 400mg daily for 21 days as an adjunct to surgical excision, while ivermectin is better tolerated as a single dose[lvi]. Ivermectin can also serve as a replacement for those that can’t handle albendazole 200 ug/kg p.o. as a single dose[lvii]. However, ivermectin has been shown to be less effective then albendazole.
Endemic areas include Asia, Mexico, India and parts of South Africa[lx]. However it is Mexico, Japan, Thailand, and Vietnam that have high levels of gnathostomiasis prevalence[lxi]. Originally believed to be confided to Asia, in the 1970’s gnathostomiasis was discovered in Mexico[lxii]. In Mexico, the primary reservoir for this parasite is Eleotris picta which is not a commercial fish, meaning that its potential for being a cause to disease burden is slight[lxiii]. Even though it is endemic in areas of Southeast Asia and Latin America, it is an uncommon disease. However, researchers have noticed recently an increase in incidence. This disease is most common in both Thailand and Japan, but in Thailand it is responsible for most of the observed CNS parasitic infection[lxiv]. As of 2005, the number of people infected in these endemic areas was 3,107 in Mexico, 39 in Japan, 3,173 in Thailand, and 600 in Vietnam[lxv].
Map of endemic areas in the New World (right) as compared to Southeast Asia (left)[lxvi]
Public Health and Prevention Strategies/Vaccines
The best strategies for preventing accidental infection of humans education of those living in endemic areas is to educate those living in endemic areas about the risk associated with eating raw seafood. The inability of the parasite to complete its life cycle within humans means that transmission can easily be contained by adequate preparation of meat from intermediate hosts. This is especially useful because of the difficulty and lack of feasibility inherent in eliminating all intermediate hosts. So instead, individuals in endemic areas should avoid eating raw and undercooked meat in endemic areas, but this may be difficult in these areas. This is due to the preference for dishes containing raw fish in these endemic areas. The dish ceviche is native to Peru and is a favorite of Mexico. It consists of onion, cubed fish, lime or lemon juice, and Andean spices including salt and chili[lxvii]. These ingredients are mixed together and are allowed to marinate for several hours before being served at room temperature[lxviii]. Then in endemic areas in Southeast Asia there are traditional dishes that contain raw seafood that are also associated with these endemic areas, such as koipla in Thailand, koi ga in Vietnam, and sushi in Japan[lxix]. By acknowledging these cultural traditions, education can be tailored to these cultures and individuals can be educated on methods of adapting their food preparation activities in order to remove the larvae without greatly altering these traditional dishes. For instance, meat should be marinated in vinegar for six hours or in soy sauce for 12 hours in order to successfully kill the larvae. In areas with reliable electricity, meat can be frozen at -20 degrees centigrade for 3-5 days to achieve the same results of killing the larvae present[lxx].
Useful Web Links
Map of Endemic Areas
Animal Diversity Web
[ii] John D and Petri W. Markell and Voge’s Medical Parasitology. 2006 Elsevier Inc.
[iii] John D and Petri W. 2006
[iv] Seal GN, Gupta AK, Das MK. Intra-ocular Gnathostomiasis. Indian J Ophthalmol 1969;17:109-13
[v] Murrell K and Fried B. Food-Borne Parasitic Zoonoses, Fish and Plant-Borne Parasites. 2007 Springer Science + Business Media, LLC
[vi] Tseng, J. 2003. "Gnathostoma spinigerum" (On-line), Animal Diversity Web. Accessed February 26, 2009 at http://animaldiversity.ummz.umich.edu/site/accounts/information/Gnathostoma_spinigerum.html.
[vii] Gideon; Gnathostomiasis. http://web.gideononline.com/web/epidemiology/index.php?disease=10990&country=&view=General
[ix] Bussaratid V, et al. Tolerability of Ivermectin in Gnathostomiasis. Southeast Asian J Trop Med Public Health. 36(3) 2005
[x] Tolan, R. Gnathostomiasis. ; Jan 2009. http://emedicine.medscape.com/article/998278-overview
[xi] Murrell K and Fried B, 2007
[xii] John D and Petri W, 2006
[xiii] Murrell K and Fried B, 2007
[xiv][xiv] Murrell K and Fried B, 2007
[xv] Murrell K and Fried B, 2007
[xvi] Murrell K and Fried B, 2007
[xvii] Murrell K and Fried B, 2007
[xviii] Murrell K and Fried B, 2007
[xix] Murrell K and Fried B, 2007
[xx] Murrell K and Fried B, 2007
[xxiii] John D and Petri W, 2006
[xxiv] Murrell K and Fried B, 2007
[xxv] Murrell K and Fried B, 2007
[xxvi] Tolan R, 2009
[xxix]Seal GN, Gupta AK, Das MK. Intra-ocular Gnathostomiasis. Indian J Ophthalmol 1969;17:109-13
[xxx] Seal GN, et al., 1969
[xxxi] Seal GN, et al. 1969
[xxxii] Seal GN, 1969
[xxxiii] Seal GN, 1969
[xxxiv] Seal GN, 1969
[xxxv] Murrell K and Fried B, 2007
[xxxvi] Murrell K and Fried B, 2007
[xxxix] Murrell K and Fried B. 2007
[xl] http://www.dpd.cdc.gov/DPDx/HTML/gnathostomiasis.htm CDC Life Cycle of Gnathostomiasis
[xli] Murrell K and Fried B, 2007
[xlii] John D and Petri W, 2006
[xliii] Murrell K and Fried B, 2007
[xlv] Murrell K and Fried B, 2007
[xlvi] Murrell K and Fried B, 2007
[xlvii]Tolan R, 2009
[xlviii] Tolan R, 2009
[xlix] John D and Petri W, 2006
[l] John D John D John D John D
[liii] John D and Petri W, 2006
[liv] Tolan R, 2009
[lv] John D and Petri W, 2006
[lx] John D and Petri W, 2006
[lxi] Murrell K and Fried B, 2007
[lxii] Ogata K, et al. Short Report: Gnathostomiasis in Mexico. Am. J. Trop. Med. Hyg., 58(3), 1998 p.316-318
[lxiii] Murrell K and Fried B, 2007
[lxiv] Tolan R, 2009
[lxv] Murrell K and Fried B, 2007
[lxvi] Murrell K and Fried B, 2007
[lxix] Murrell K and Fried B, 2007
[lxx] Tolan R, 2009