Gnathostomiasis (also known as larva migrans profundus) is the

human Humans (''Homo sapiens'') are the most abundant and widespread species of primate, characterized by bipedalism and exceptional cognitive skills due to a large and complex brain. This has enabled the development of advanced tools, cultu ...

infection An infection is the invasion of tissues by pathogens, their multiplication, and the reaction of host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmissible disease or communicable di ...

caused by the

nematode The nematodes ( or grc-gre, Νηματώδη; la, Nematoda) or roundworms constitute the phylum Nematoda (also called Nemathelminthes), with plant- parasitic nematodes also known as eelworms. They are a diverse animal phylum inhabiting a bro ...

(roundworm) ''

Gnathostoma spinigerum ''Gnathostoma spinigerum'' is a parasitic nematode that causes gnathostomiasis in humans, also known as its clinical manifestations are '' creeping eruption'', ''larva migrans'', ''Yangtze edema'', ''Choko-Fuschu Tua chid'' and ''wandering swelli ...

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

vertebrate Vertebrates () comprise all animal taxa within the subphylum Vertebrata () ( chordates with backbones), including all mammals, birds, reptiles, amphibians, and fish. Vertebrates represent the overwhelming majority of the phylum Chordata, with ...

Symptoms and signs

A few days after ingestion epigastric pain,

fever Fever, also referred to as pyrexia, is defined as having a temperature above the normal range due to an increase in the body's temperature set point. There is not a single agreed-upon upper limit for normal temperature with sources using val ...

vomiting Vomiting (also known as emesis and throwing up) is the involuntary, 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, gastroenter ...

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

abdominal cavity The abdominal cavity is a large body cavity in humans and many other animals that contains many organs. It is a part of the abdominopelvic cavity. It is located below the thoracic cavity, and above the pelvic cavity. Its dome-shaped roof is th ...

will appear in the patient. Migration in the subcutaneous tissues (under the

skin Skin is the layer of usually soft, flexible outer tissue covering the body of a vertebrate animal, with three main functions: protection, regulation, and sensation. Other animal coverings, such as the arthropod exoskeleton, have different ...

) causes intermittent, migratory,

pain Pain is a distressing feeling often caused by intense or damaging stimuli. The International Association for the Study of Pain defines pain as "an unpleasant sensory and emotional experience associated with, or resembling that associated with, ...

ful, pruritic swellings (cutaneous larva migrans). Patches of edema appear after the above symptoms clear and are usually found on the

abdomen The abdomen (colloquially called the belly, tummy, midriff, tucky or stomach) is the part of the body between the thorax (chest) and pelvis, in humans and in other vertebrates. The abdomen is the front part of the abdominal segment of the to ...

. These

lesions A lesion is any damage or abnormal change in the tissue of an organism, usually caused by disease or trauma. ''Lesion'' is derived from the Latin "injury". Lesions may occur in plants as well as animals. Types There is no designated classifi ...

vary in size and can be accompanied by

pruritus Itch (also known as pruritus) is a sensation that causes the desire or reflex to scratch. Itch has resisted many attempts to be classified as any one type of sensory experience. Itch has many similarities to pain, and while both are unpleasant ...

(itchy anus),

rash A rash is a change of the human skin which 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, c ...

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

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

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 w ...

(blood in urine), ocular ( eye) 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, headache, and neck stiffness. Other symptoms include confusion or ...

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

and

eosinophilia Eosinophilia is a condition in which the eosinophil count in the peripheral blood exceeds . Hypereosinophilia is an elevation in an individual's circulating blood eosinophil count above 1.5 x 109/ L (i.e. 1,500/ μL). The hypereosinophilic sy ...

Eosinophilic myeloencephalitis Eosinophilic (Greek suffix -phil-, meaning ''loves eosin'') is the staining of tissues, cells, or organelles after they have been washed with eosin, a dye. Eosin is an acidic dye for staining cell cytoplasm, collagen, and muscle fibers. ''Eosi ...

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 and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all p ...

by the larvae.

Causes

Human gnathostomiasis is infection by the migrating third-stage larvae of any of five species of

Gnathostoma ''Gnathostoma'' is a genus of parasitic nematode The nematodes ( or grc-gre, Νηματώδη; la, Nematoda) or roundworms constitute the phylum Nematoda (also called Nemathelminthes), with plant- parasitic nematodes also known as eelw ...

, which is type of worm (more specifically a type of

). 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 raw or insufficiently cooked definitive hosts such as fresh water

fish Fish are Aquatic animal, aquatic, craniate, gill-bearing animals that lack Limb (anatomy), limbs with Digit (anatomy), digits. Included in this definition are the living hagfish, lampreys, and Chondrichthyes, cartilaginous and bony fish as we ...

poultry Poultry () are domesticated birds kept by humans for their eggs, their meat or their feathers. These birds are most typically members of the superorder Galloanserae (fowl), especially the order Galliformes (which includes chickens, qu ...

, or

frog A frog is any member of a diverse and largely Carnivore, carnivorous group of short-bodied, tailless amphibians composing the order (biology), order Anura (ανοὐρά, literally ''without tail'' in Ancient Greek). The oldest fossil "proto-f ...

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.

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 (Crustacea, ) form a large, diverse arthropod taxon which includes such animals as decapoda, decapods, ostracoda, seed shrimp, branchiopoda, branchiopods, argulidae, fish lice, krill, remipedes, isopoda, isopods, barnacles, copepods, ...

s of the genus ''

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

''. These crustaceans are then ingested by a second intermediate host, such as frogs.

Definitive host

The definitive hosts for gnathostomiasis include

cat The cat (''Felis catus'') is a domestic species of small carnivorous mammal. It is the only domesticated species in the family Felidae and is commonly referred to as the domestic cat or house cat to distinguish it from the wild members of ...

s, dogs, tigers,

leopard The leopard (''Panthera pardus'') is one of the five extant species in the genus '' Panthera'', a member of the cat family, Felidae. It occurs in a wide range in sub-Saharan Africa, in some parts of Western and Central Asia, Southern Russia, ...

lion The lion (''Panthera leo'') is a large cat of the genus '' Panthera'' native to Africa and India. It has a muscular, broad-chested body; short, rounded head; round ears; and a hairy tuft at the end of its tail. It is sexually dimorphic; adu ...

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": ...

opossum Opossums () are members of the marsupial order Didelphimorphia () endemic to the Americas. The largest order of marsupials in the Western Hemisphere, it comprises 93 species in 18 genera. Opossums originated in South America and entered No ...

raccoon The raccoon ( or , ''Procyon lotor''), sometimes called the common raccoon to distinguish it from other species, is a mammal native to North America. It is the largest of the procyonid family, having a body length of , and a body weight of ...

s, poultry, frogs, freshwater fish,

snake Snakes are elongated, limbless, carnivorous reptiles of the suborder Serpentes . Like all other squamates, snakes are ectothermic, amniote vertebrates covered in overlapping scales. Many species of snakes have skulls with several more ...

s or

bird Birds are a group of warm-blooded vertebrates constituting the class Aves (), characterised by feathers, toothless beaked jaws, the laying of hard-shelled eggs, a high metabolic rate, a four-chambered heart, and a strong yet lightweig ...

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 radiation, and when symptoms and signs are first apparent. In a typical infectious disease, the in ...

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 in color and has a globular cephalic dome that is separated from the rest of the body by constriction. The posterior portion of the nematode is smooth while the

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

half is covered with fine leaf-like spines. The head is round and contains 4 to 8 transverse rows of hooklets that are 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 fertilization. A male organism cannot reproduce sexually without access to ...

are shorter than the

females Female (symbol: ♀) is the sex of an organism that produces the large non-motile ova (egg cells), the type of gamete (sex cell) that fuses with the male gamete during sexual reproduction. A female has larger gametes than a male. Females ...

, compared to respectively.

Eggs Humans and human ancestors have scavenged and eaten animal eggs for millions of years. Humans in Southeast Asia had domesticated chickens and harvested their eggs for food by 1,500 BCE. The most widely consumed eggs are those of fowl, especial ...

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 ( or faeces), known colloquially and in slang as poo and poop, 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 large intestine. Feces contain a rela ...

and in about a week hatch in water to develop into first stage larva. 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. Some species are planktonic (inhabiting sea waters), some are benthic (living on the ocean floor), a number of species have ...

, 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 then 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 Muscle tissue (or muscular tissue) is soft tissue that makes up the different types of muscles in most animals, and give the ability of muscles to contract. Muscle tissue is formed during embryonic development, in a process known as myogenesis. M ...

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 bubble) ...

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, along with epithelial tissue, muscle tissue, and nervous tissue. It develops from the mesenchyme derived from the mesoderm the middle embryonic germ layer. Connective tiss ...

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 Fertilisation or fertilization (see spelling differences), also known as generative fertilisation, syngamy and impregnation, is the fusion of gametes to give rise to a new individual organism or offspring and initiate its development. Proc ...

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. This also means the number of worms present in humans is a reflection of the number of third stage larvae ingested.

Diagnosis

Diagnosis Diagnosis is the identification of the nature and cause of a certain phenomenon. Diagnosis is used in many different disciplines, with variations in the use of logic, analytics, and experience, to determine "cause and effect". In systems engin ...

of gnathostomiasis is possible (with

microscopy Microscopy is the technical field of using microscopes to view objects and areas of objects that cannot 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 micr ...

) after removal of the worm. The primary form of diagnosis of gnathostomiasis is the identification of larva in the tissue. Serological testing such as

enzyme-linked immunosorbent assay The enzyme-linked immunosorbent assay (ELISA) (, ) is a commonly used analytical biochemistry assay, first described by Eva Engvall and Peter Perlmann in 1971. The assay uses a solid-phase type of enzyme immunoassay (EIA) to detect the presence ...

(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 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 found else ...

areas. CT scanning or

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

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 strategies 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 , image_flag = Flag of Peru.svg , image_coat = Escudo nacional del Perú.svg , other_symbol = Great Seal of the State , other_symbol_type = National seal , national_motto = "Firm and Happy f ...

and a favorite of Mexico. It consists of

onion An onion (''Allium cepa'' L., from Latin ''cepa'' meaning "onion"), 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 on ...

, cubed fish, lime or

lemon The lemon (''Citrus limon'') is a species of small evergreen trees in the flowering plant family Rutaceae, native to Asia, primarily Northeast India (Assam), Northern Myanmar or China. The tree's ellipsoidal yellow fruit is used for culin ...

juice and Andean spices including

salt Salt is a mineral composed primarily of sodium chloride (NaCl), a chemical compound belonging to the larger class of salts; salt in the form of a natural crystalline mineral is known as rock salt or halite. Salt is present in vast quant ...

and chili. The ingredients are mixed together and they are allowed to marinate 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 and sushi in Japan. Acknowledging these cultural traditions, individuals in these cultural 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 Vinegar is an aqueous solution of acetic acid and trace compounds that may include flavorings. Vinegar typically contains 5–8% acetic acid by volume. Usually, the acetic acid is produced by a double fermentation, converting simple sugars to eth ...

for six hours or in

soy sauce Soy sauce (also called simply soy in American English and soya sauce in British English) is a liquid condiment of Chinese origin, traditionally made from a fermented paste of soybeans, roasted grain, brine, and ''Aspergillus oryzae'' or '' As ...

for 12 hours in order to successfully kill the larvae. 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 (also known as albendazolum) is a broad-spectrum anthelmintic and antiprotozoal agent of the benzimidazole type. It is used for the treatment of a variety of intestinal parasite infections, including ascariasis, pinworm infection, ho ...

ivermectin Ivermectin (, '' EYE-vər-MEK-tin'') 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, today it is used to treat i ...

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 recommended to be 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. However, ivermectin has been shown to be less effective than albendazole.

Epidemiology

Endemic areas include

Asia Asia (, ) is one of the world's most notable geographical regions, which is either considered a continent in its own right or a subcontinent of Eurasia, which shares the continental landmass of Afro-Eurasia with Africa. Asia covers an are ...

Mexico Mexico (Spanish language, Spanish: México), officially the United Mexican States, is a List of sovereign states, country in the southern portion of North America. It is borders of Mexico, bordered to the north by the United States; to the so ...

India India, officially the Republic of India (Hindi: ), 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 and dependencies by population, second-most populous ...

and parts of

South Africa South Africa, officially the Republic of South Africa (RSA), is the southernmost country in Africa. It is bounded to the south by of coastline that stretch along the South Atlantic and Indian Oceans; to the north by the neighbouring coun ...

. 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, also spelled South East Asia and South-East Asia, and also known as Southeastern Asia, South-eastern Asia or SEA, is the geographical south-eastern region of Asia, consisting of the regions that are situated south of mainland ...

and

Latin America Latin America or * french: Amérique Latine, link=no * ht, Amerik Latin, link=no * pt, América Latina, link=no, name=a, sometimes referred to as LatAm is a large cultural region in the Americas where Romance languages — languages derived ...

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

Thailand Thailand ( ), historically known as Siam () and officially the Kingdom of Thailand, is a country in Southeast Asia, located at the centre of the Indochinese Peninsula, spanning , with a population of almost 70 million. The country is b ...

and

Japan Japan ( ja, 日本, or , and formally , ''Nihonkoku'') is an island country in East Asia. It is situated in the northwest Pacific Ocean, and is bordered on the west by the Sea of Japan, while extending from the Sea of Okhotsk in the n ...

, but in Thailand it is responsible for most of the observed parasitic CNS infection. It has long been recognised in China, but reports have only recently appeared in the English literature.

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 anatomist and paleontologist. Owen is generally considered to have been an outstanding naturalist with a remarkable gift for interpreting fossils. Ow ...

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

London Zoo London Zoo, also known as ZSL London Zoo or London Zoological Gardens 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 collection for scientific study. In 1831 or 1832, ...

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 Chalerm Prommas ( th, เฉลิม พรมมาส, 19 August 1896 – 26 May 1975), also known by his former noble title as Luang Chaloem Khamphirawet (), was a Thai medical doctor. He was a pioneering figure at Thailand's two oldest medical ...

from Thailand in 1933 and 1936. This delay in identification of the parasite in humans is due to the fact that humans are not a definitive host for this

parasite Parasitism is a close relationship between species, where one organism, the parasite, lives on or inside another organism, the host, causing it some harm, and is adapted structurally to this way of life. The entomologist E. O. Wilson h ...

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.

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, and is headquartered in Atlanta, Georg ...