Gnathostomiasis, also known as larva migrans profundus, is the

human Humans (''Homo sapiens'') or modern humans are the most common and widespread species of primate, and the last surviving species of the genus ''Homo''. They are Hominidae, great apes characterized by their Prehistory of nakedness and clothing ...

infection An infection is the invasion of tissue (biology), tissues by pathogens, their multiplication, and the reaction of host (biology), host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmis ...

caused by the

nematode The nematodes ( or ; ; ), roundworms or eelworms constitute the phylum Nematoda. Species in the phylum inhabit a broad range of environments. Most species are free-living, feeding on microorganisms, but many are parasitic. Parasitic worms (h ...

'' Gnathostoma spinigerum'' and/or '' Gnathostoma hispidum'', which infects

vertebrate Vertebrates () are animals with a vertebral column (backbone or spine), and a cranium, or skull. The vertebral column surrounds and protects the spinal cord, while the cranium protects the brain. The vertebrates make up the subphylum Vertebra ...

Signs and symptoms

A few days after ingestion epigastric pain,

fever Fever or pyrexia in humans is a symptom of an anti-infection defense mechanism that appears with Human body temperature, body temperature exceeding the normal range caused by an increase in the body's temperature Human body temperature#Fever, s ...

vomiting Vomiting (also known as emesis, puking and throwing up) is the forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose. Vomiting can be the result of ailments like food poisoning, gastroenteritis, pre ...

, and loss of appetite resulting from the migration of larvae through the intestinal wall to the

abdominal cavity The abdominal cavity is a large body cavity in humans and many other animals that contain Organ (anatomy), organs. It is a part of the abdominopelvic cavity. It is located below the thoracic cavity, and above the pelvic cavity. Its dome-shaped roo ...

will appear in the patient. Migration of parasites in the subcutaneous tissues causing intermittent, migratory, painful, pruritic swellings is known as ''cutaneous larva migrans''. Patches of edema appear after initial symptoms clear and are usually found on the

abdomen The abdomen (colloquially called the gut, belly, tummy, midriff, tucky, or stomach) is the front part of the torso between the thorax (chest) and pelvis in humans and in other vertebrates. The area occupied by the abdomen is called the abdominal ...

. These

lesions A lesion is any damage or abnormal change in the tissue of an organism, usually caused by injury or diseases. The term ''Lesion'' is derived from the Latin meaning "injury". Lesions may occur in both plants and animals. Types There is no de ...

vary in size and can be accompanied by pruritus,

rash A rash is a change of the skin that affects its color, appearance, or texture. A rash may be localized in one part of the body, or affect all the skin. Rashes may cause the skin to change color, itch, become warm, bumpy, chapped, dry, cracke ...

, and stabbing pain. Swellings may last 1 to 4 weeks in a given area and reappear in a different location. Migration to other tissues causes ''visceral larva migrans'' and can result in

cough A cough is a sudden expulsion of air through the large breathing passages which can help clear them of fluids, irritants, foreign particles and Microorganism, microbes. As a protective reflex, coughing can be repetitive with the cough reflex fol ...

hematuria Hematuria or haematuria is defined as the presence of blood or red blood cells in the urine. "Gross hematuria" occurs when urine appears red, brown, or tea-colored due to the presence of blood. Hematuria may also be subtle and only detectable with ...

, ocular involvement,

meningitis Meningitis is acute or chronic inflammation of the protective membranes covering the brain and spinal cord, collectively called the meninges. The most common symptoms are fever, intense headache, vomiting and neck stiffness and occasion ...

encephalitis Encephalitis is inflammation of the Human brain, brain. The severity can be variable with symptoms including reduction or alteration in consciousness, aphasia, headache, fever, confusion, a stiff neck, and vomiting. Complications may include se ...

and eosinophilia. Eosinophilic myeloencephalitis may also result from invasion of the

central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain, spinal cord and retina. The CNS is so named because the brain integrates the received information and coordinates and influences the activity o ...

by the larvae.

Causes

Human gnathostomiasis is an infection by the migrating third-stage larvae of any of five species of '' Gnathostoma''. The most common cause in Asia is ''G. spinigerum'', and the most common cause in the Americas is ''G. binucleatum''. ''G. hispidium'' and ''G. doloresi'' occur in East and Southeast Asia; the former has also been found in Eastern Europe''.'' ''G. nipponicum'' occurs only in Japan and China. There is one unconfirmed report of G. ''malaysiae'' causing disease in humans.

Transmission

Gnathostomiasis is transmitted by the ingestion of third-stage larvae from raw or insufficiently cooked second intermediate or paratenic hosts such as freshwater

fish A fish (: fish or fishes) is an aquatic animal, aquatic, Anamniotes, anamniotic, gill-bearing vertebrate animal with swimming fish fin, fins and craniate, a hard skull, but lacking limb (anatomy), limbs with digit (anatomy), digits. Fish can ...

snakes Snakes are elongated Limbless vertebrate, limbless reptiles of the suborder Serpentes (). Cladistically Squamata, squamates, snakes are ectothermic, amniote vertebrates covered in overlapping Scale (zoology), scales much like other members of ...

poultry Poultry () are domesticated birds kept by humans for the purpose of harvesting animal products such as meat, Eggs as food, eggs or feathers. The practice of animal husbandry, raising poultry is known as poultry farming. These birds are most typ ...

, or

frog A frog is any member of a diverse and largely semiaquatic group of short-bodied, tailless amphibian vertebrates composing the order (biology), order Anura (coming from the Ancient Greek , literally 'without tail'). Frog species with rough ski ...

s. In Thailand and Vietnam, the most common cause appears to be consumption of undercooked Asian swamp eels ('' Monopterus albus,'' also called ''Fluta alba'') which transmit ''G. spinigerum''. ''Monopterus albus'' is an invasive species in North America, but no ''Gnathostoma'' infections in humans have yet been conclusively identified in the US. It is unclear if humans can be infected from drinking water contaminated with infected copepods.

Hosts

Intermediate host

The primary

intermediate host In biology and medicine, a host is a larger organism that harbours a smaller organism; whether a parasitic, a mutualistic, or a commensalist ''guest'' (symbiont). The guest is typically provided with nourishment and shelter. Examples include ...

is the minute

crustacean Crustaceans (from Latin meaning: "those with shells" or "crusted ones") are invertebrate animals that constitute one group of arthropods that are traditionally a part of the subphylum Crustacea (), a large, diverse group of mainly aquatic arthrop ...

s of the genus ''

Cyclops In Greek mythology and later Roman mythology, the Cyclopes ( ; , ''Kýklōpes'', "Circle-eyes" or "Round-eyes"; singular Cyclops ; , ''Kýklōps'') are giant one-eyed creatures. Three groups of Cyclopes can be distinguished. In Hesiod's ''Th ...

''. These crustaceans are then ingested by a second intermediate host, such as frogs and freshwater fish. Paratenic hosts are usually animals that prey on second intermediate hosts, such as snakes and birds.

Definitive host

The definitive hosts for gnathostomiasis include

omnivorous An omnivore () is an animal that regularly consumes significant quantities of both plant and animal matter. Obtaining energy and nutrients from plant and animal matter, omnivores digest carbohydrates, protein, fat, and fiber, and metabolize ...

carnivorous A carnivore , or meat-eater (Latin, ''caro'', genitive ''carnis'', meaning meat or "flesh" and ''vorare'' meaning "to devour"), is an animal or plant whose nutrition and energy requirements are met by consumption of animal tissues (mainly mu ...

mammals A mammal () is a vertebrate animal of the class Mammalia (). Mammals are characterised by the presence of milk-producing mammary glands for feeding their young, a broad neocortex region of the brain, fur or hair, and three middle e ...

such as cats, dogs, tigers,

leopard The leopard (''Panthera pardus'') is one of the five extant cat species in the genus ''Panthera''. It has a pale yellowish to dark golden fur with dark spots grouped in rosettes. Its body is slender and muscular reaching a length of with a ...

lion The lion (''Panthera leo'') is a large Felidae, cat of the genus ''Panthera'', native to Sub-Saharan Africa and India. It has a muscular, broad-chested body (biology), body; a short, rounded head; round ears; and a dark, hairy tuft at the ...

mink Mink are dark-colored, semiaquatic, carnivorous mammals of the genera ''Neogale'' and '' Mustela'' and part of the family Mustelidae, which also includes weasels, otters, and ferrets. There are two extant species referred to as "mink": the A ...

opossum Opossums () are members of the marsupial order Didelphimorphia () endemic to the Americas. The largest order of marsupials in the Western Hemisphere, it comprises 126 species in 18 genera. Opossums originated in South America and entered North A ...

s or

raccoon The raccoon ( or , ''Procyon lotor''), sometimes called the North American, northern or common raccoon (also spelled racoon) to distinguish it from Procyonina, other species of raccoon, is a mammal native to North America. It is the largest ...

s. Humans are accidental hosts, not definitive hosts.

Incubation period

The

incubation period Incubation period (also known as the latent period or latency period) is the time elapsed between exposure to a pathogenic organism, a chemical, or ionizing radiation, radiation, and when symptoms and signs are first apparent. In a typical infect ...

for gnathostomiasis is 3–4 weeks when the larvae begin to migrate through the subcutaneous tissue of the body.

Morphology

The adult parasite is reddish-brown and has a globular cephalic dome separated from the rest of the body by constriction. The posterior portion of the nematode is smooth. At the same time, the

anterior Standard anatomical terms of location are used to describe unambiguously the anatomy of humans and other animals. The terms, typically derived from Latin or Greek roots, describe something in its standard anatomical position. This position pro ...

half is covered with fine leaf-like spines. The head is round and contains 4 to 8 transverse rows of hooklets protected by a pair of fleshy lips. The

males Male (symbol: ♂) is the sex of an organism that produces the gamete (sex cell) known as sperm, which fuses with the larger female gamete, or ovum, in the process of fertilisation. A male organism cannot reproduce sexually without access to ...

are shorter than the females, compared to respectively. Eggs are oval and have a mucoid plug at one end.

Life cycle

Life cycle in definitive hosts

Adult worms are 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 Feces (also known as faeces American and British English spelling differences#ae and oe, or fæces; : faex) are the solid or semi-solid remains of food that was not digested in the small intestine, and has been broken down by bacteria in the ...

and in about a week hatch in water to develop into first stage larvae. Larvae are then ingested by minute copepods of the genus ''Cyclops''. Once entering the

copepod Copepods (; meaning 'oar-feet') are a group of small crustaceans found in nearly every freshwater and saltwater habitat (ecology), habitat. Some species are planktonic (living in the water column), some are benthos, benthic (living on the sedimen ...

, the larvae penetrate the gastric wall of their intermediate host and begin to develop into second-stage and even early third-stage larvae. The copepods are ingested by a second intermediate host such as fish, frogs, or snakes. Within this second intermediate or definitive host 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. These larvae then encyst within the musculature of the new host. If the

cyst A cyst is a closed sac, having a distinct envelope and division compared with the nearby tissue. Hence, it is a cluster of cells that have grouped together to form a sac (like the manner in which water molecules group together to form a bubb ...

containing flesh of these hosts is ingested by a definitive host, such as dogs, and cats, the cysts are ingested and the larvae escape the cysts and penetrate the gastric wall. These released larvae travel to the

connective tissue Connective tissue is one of the four primary types of animal tissue, a group of cells that are similar in structure, along with epithelial tissue, muscle tissue, and nervous tissue. It develops mostly from the mesenchyme, derived from the mesod ...

and muscle as observed before and after 4 weeks they return to the gastric wall as adults. Here they form a

tumor A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...

and continue to mature into adults for the next 6–8 months. Worms mate and females begin to excrete fertilized eggs with feces 8–12 months after ingestion of cysts. They are passed out in the feces and eaten by another fish.

Life cycle in humans

Infection of humans by gnathostomiasis is accidental because humans are not one of the definitive hosts of the parasite and do not allow the parasite to complete its life cycle. Infection in humans follows ingestion of raw or insufficiently cooked infected intermediate hosts. The ingested third-stage larva migrates from the gastric wall and its migration results in the symptoms associated with infection by gnathostomiasis. The third-stage larvae don't return to the gastric wall preventing it from maturing into adult worms, leaving the life cycle incomplete. Instead, the larvae continue to migrate unpredictably unable to develop into adults, so eggs are seldom found in diagnostic tests or human feces. This also means the number of worms present in humans is a reflection of the number of third-stage larvae ingested.

Diagnosis

Diagnosis Diagnosis (: diagnoses) is the identification of the nature and cause of a certain phenomenon. Diagnosis is used in a lot of different academic discipline, disciplines, with variations in the use of logic, analytics, and experience, to determine " ...

of gnathostomiasis is possible (with

microscopy Microscopy is the technical field of using microscopes to view subjects too small to be seen with the naked eye (objects that are not within the resolution range of the normal eye). There are three well-known branches of microscopy: optical mic ...

) after removal of the worm. The primary form of diagnosis of gnathostomiasis is the identification of a larva in the tissue. Serological testing such as enzyme-linked immunosorbent assay (ELISA) or the

Western blot The western blot (sometimes called the protein immunoblot), or western blotting, is a widely used analytical technique in molecular biology and immunogenetics to detect specific proteins in a sample of tissue homogenate or extract. Besides detect ...

are also reliable but may not be easily accessible in

endemic Endemism is the state of a species being found only in a single defined geographic location, such as an island, state, nation, country or other defined zone; organisms that are indigenous to a place are not endemic to it if they are also foun ...

areas.

CT scan A computed tomography scan (CT scan), formerly called computed axial tomography scan (CAT scan), is a medical imaging technique used to obtain detailed internal images of the body. The personnel that perform CT scans are called radiographers or ...

ning or

MRI Magnetic resonance imaging (MRI) is a medical imaging technique used in radiology to generate pictures of the anatomy and the physiological processes inside the body. MRI scanners use strong magnetic fields, magnetic field gradients, and rad ...

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. The presence of haemorrhagic tracks on gradient-echo T2-weighted MRI is characteristic and possibly diagnostic.

Prevention

The best strategy for preventing accidental infection of humans is to educate those living in endemic areas to only consume fully cooked meat. 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 of gnathostomiasis. So instead, individuals in endemic areas should avoid eating raw and undercooked meat in endemic areas, but this may be difficult in these areas. The dish ceviche is native to

Peru Peru, officially the Republic of Peru, is a country in western South America. It is bordered in the north by Ecuador and Colombia, in the east by Brazil, in the southeast by Bolivia, in the south by Chile, and in the south and west by the Pac ...

and a favorite of Mexico. It consists of

onion An onion (''Allium cepa'' , from Latin ), also known as the bulb onion or common onion, is a vegetable that is the most widely cultivated species of the genus '' Allium''. The shallot is a botanical variety of the onion which was classifie ...

, cubed fish, lime or

lemon The lemon (''Citrus'' × ''limon'') is a species of small evergreen tree in the ''Citrus'' genus of the flowering plant family Rutaceae. A true lemon is a hybrid of the citron and the bitter orange. Its origins are uncertain, but some ...

juice and Andean spices including

salt In common usage, salt is a mineral composed primarily of sodium chloride (NaCl). When used in food, especially in granulated form, it is more formally called table salt. In the form of a natural crystalline mineral, salt is also known as r ...

and chili. The ingredients are mixed and marinated for several hours before being served at room temperature. Then in endemic areas in Southeast Asia, there are traditional dishes associated with these areas that also include raw uncooked fish, such as koipla in Thailand, goi ca song in Vietnam,

sashimi is a Japanese cuisine, Japanese delicacy consisting of fresh raw fish or Raw meat, meat sliced into thin pieces and often eaten with soy sauce. Origin The word ''sashimi'' means 'pierced body', i.e., "wikt:刺身, 刺身" = ''sashimi'', whe ...

and

sushi is a traditional Japanese dish made with , typically seasoned with sugar and salt, and combined with a variety of , such as seafood, vegetables, or meat: raw seafood is the most common, although some may be cooked. While sushi comes in n ...

in Japan. Acknowledging these cultural traditions, individuals in these cultures can be educated on adapting their food preparation activities to remove the larvae without greatly altering these traditional dishes. For instance, meat should be marinated in

vinegar Vinegar () is an aqueous solution of diluted acetic acid and trace compounds that may include flavorings. Vinegar typically contains from 5% to 18% acetic acid by volume. Usually, the acetic acid is produced by a double fermentation, converting ...

for six hours or in

soy sauce Soy sauce (sometimes called soya sauce in British English) is a liquid condiment of China, Chinese origin, traditionally made from a fermentation (food), fermented paste of soybeans, roasted cereal, grain, brine, and ''Aspergillus oryzae'' or ''A ...

for 12 hours to kill the larvae successfully. In areas with reliable electricity, meat can be frozen at -20 degrees Celsius for 3–5 days to achieve the same results of killing the larvae present.

Treatment

Surgical removal or treatment with

albendazole Albendazole is a broad-spectrum antihelmintic and antiprotozoal agent of the benzimidazole type. It is used for the treatment of a variety of intestinal parasite infections, including ascariasis, pinworm infection, hookworm infection, trichuri ...

ivermectin Ivermectin is an antiparasitic drug. After its discovery in 1975, its first uses were in veterinary medicine to prevent and treat heartworm and acariasis. Approved for human use in 1987, it is used to treat infestations including head lice ...

is recommended. 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. In addition to surgical excision, albendazole and ivermectin have been noted in their ability to eliminate the parasite. Albendazole is administered at 400 mg daily for 21 days as an adjunct to surgical excision, while ivermectin is better tolerated as a single dose. Ivermectin can also serve as a replacement for those that can't handle albendazole 200 ug/kg p.o. as a single dose. Ivermectin is less effective than albendazole.

Epidemiology

Endemic areas include

Asia Asia ( , ) is the largest continent in the world by both land area and population. It covers an area of more than 44 million square kilometres, about 30% of Earth's total land area and 8% of Earth's total surface area. The continent, which ...

Mexico Mexico, officially the United Mexican States, is a country in North America. It is the northernmost country in Latin America, and borders the United States to the north, and Guatemala and Belize to the southeast; while having maritime boundar ...

India India, officially the Republic of India, is a country in South Asia. It is the List of countries and dependencies by area, seventh-largest country by area; the List of countries by population (United Nations), most populous country since ...

and parts of

South Africa South Africa, officially the Republic of South Africa (RSA), is the Southern Africa, southernmost country in Africa. Its Provinces of South Africa, nine provinces are bounded to the south by of coastline that stretches along the Atlantic O ...

. Originally believed to be confined to Asia, in the 1970s gnathostomiasis was discovered in Mexico, and found in Australia in 2011. Even though it is endemic in areas of

Southeast Asia Southeast Asia is the geographical United Nations geoscheme for Asia#South-eastern Asia, southeastern region of Asia, consisting of the regions that are situated south of China, east of the Indian subcontinent, and northwest of the Mainland Au ...

and

Latin America Latin America is the cultural region of the Americas where Romance languages are predominantly spoken, primarily Spanish language, Spanish and Portuguese language, Portuguese. Latin America is defined according to cultural identity, not geogr ...

, it is an uncommon disease. However, researchers have noticed recently an increase in incidence. This disease is most common in both

Thailand Thailand, officially the Kingdom of Thailand and historically known as Siam (the official name until 1939), is a country in Southeast Asia on the Mainland Southeast Asia, Indochinese Peninsula. With a population of almost 66 million, it spa ...

and

Japan Japan is an island country in East Asia. Located in the Pacific Ocean off the northeast coast of the Asia, Asian mainland, it is bordered on the west by the Sea of Japan and extends from the Sea of Okhotsk in the north to the East China Sea ...

. In Thailand, it is the most common cause of central nervous system parasitic infections. As of 2009, 23 cases in China were reported in Chinese literature. As of 2020, about 5,000 cases of Gnathostomiasis have been reported globally.

History

The first case of ''Gnathostoma'' infection was identified by Sir

Richard Owen Sir Richard Owen (20 July 1804 – 18 December 1892) was an English biologist, comparative anatomy, comparative anatomist and paleontology, palaeontologist. Owen is generally considered to have been an outstanding naturalist with a remarkabl ...

in 1836, when inspecting the stomach of a young tiger that had died at

London Zoo London Zoo, previously known as ZSL London Zoo or London Zoological Gardens and sometimes called Regent's Park Zoo, is the world's oldest scientific zoo. It was opened in London on 27 April 1828 and was originally intended to be used as a colle ...

from a ruptured aorta. However it was not until 1889 that the first human case was described by Levinson when he found the ''Gnathostoma'' larva in an infested Thai woman. The lifecycle of ''G. spinigerum'' was described by Svasti Daengsvang and Chalerm Prommas from Thailand in 1933 and 1936. This delay in identification of the parasite in humans is because humans are not a definitive host for this

parasite Parasitism is a Symbiosis, close relationship between species, where one organism, the parasite, lives (at least some of the time) on or inside another organism, the Host (biology), host, causing it some harm, and is Adaptation, adapted str ...

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 in which the parasite can infect humans. It is uncommon for the larvae to penetrate the skin of individuals exposed to contaminated food or water without ingestion.

References

External links

Gnathostomiasis
at

CDC The Centers for Disease Control and Prevention (CDC) is the national public health agency of the United States. It is a United States federal agency under the Department of Health and Human Services (HHS), and is headquartered in Atlanta, ...