Metagonimiasis is a disease caused by an intestinal

trematode Trematoda is a class of flatworms known as flukes. They are obligate internal parasites with a complex life cycle requiring at least two hosts. The intermediate host, in which asexual reproduction occurs, is usually a snail. The definitive h ...

, most commonly ''Metagonimus yokagawai'', but sometimes by ''M. takashii'' or ''M. miyatai''. The metagonimiasis-causing flukes are one of two minute flukes called the heterophyids. Metagonimiasis was described by Katsurasa in 1911–1913 when he first observed eggs of ''M. yokagawai'' in feces (date is disputed in various studies). ''M. takahashii'' was described later first by Suzuki in 1930 and then ''M. miyatai'' was described in 1984 by Saito.

Signs and symptoms

The main symptoms are

diarrhea Diarrhea, also spelled diarrhoea, is the condition of having at least three loose, liquid, or watery bowel movements each day. It often lasts for a few days and can result in dehydration due to fluid loss. Signs of dehydration often begin w ...

and colicky

abdominal pain Abdominal pain, also known as a stomach ache, is a symptom associated with both non-serious and serious medical issues. Common causes of pain in the abdomen include gastroenteritis and irritable bowel syndrome. About 15% of people have a m ...

. Because symptoms are often mild, infections can often be easily overlooked but diagnosis is important. Flukes attach to the wall of the small intestine, but are often asymptomatic unless in large numbers. Infection can occur from eating a single infected fish source. Peripheral eosinophilia is associated especially in early phase. When present in large numbers, can cause chronic intermittent

nausea Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. While not painful, it can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the ...

, and vague abdominal pains. Clinical complaints can also include

lethargy Lethargy is a state of tiredness, sleepiness, weariness, fatigue, sluggishness or lack of energy. It can be accompanied by depression, decreased motivation, or apathy. Lethargy can be a normal response to inadequate sleep, overexertion, overwo ...

and

anorexia Anorexia nervosa, often referred to simply as anorexia, is an eating disorder characterized by low weight, food restriction, body image disturbance, fear of gaining weight, and an overpowering desire to be thin. ''Anorexia'' is a term of Gre ...

. In acute metagonimiasis, clinical manifestations are developed only 5–7 days after infection. Heavy infection has also been associated with epigastric distress, fatigue, and malaise. Occasionally, flukes invade the mucosa and eggs deposited in tissue may gain access to circulation. This can then lead to eggs embolizing in the

brain A brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It is located in the head, usually close to the sensory organs for senses such as vision. It is the most complex organ in a ve ...

spinal cord The spinal cord is a long, thin, tubular structure made up of nervous tissue, which extends from the medulla oblongata in the brainstem to the lumbar region of the vertebral column (backbone). The backbone encloses the central canal of the sp ...

, or

heart The heart is a muscular organ in most animals. This organ pumps blood through the blood vessels of the circulatory system. The pumped blood carries oxygen and nutrients to the body, while carrying metabolic waste such as carbon dioxide to t ...

. Granulomas may form around eggs and can cause

seizures An epileptic seizure, informally known as a seizure, is a period of symptoms due to abnormally excessive or synchronous neuronal activity in the brain. Outward effects vary from uncontrolled shaking movements involving much of the body with l ...

, neurologic deficits, or cardiac insufficiency. An interesting case in Japan found

diabetes mellitus Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level ( hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ...

(DM) to be a sign of chronic infection with intracerebral hemorrhages as the acute sign of aggravation<. Two months after administering praziquantel, the hemorrhages were gone, as was the diabetes. This unique case shows the potential of additional symptoms associated with metagonimiasis that are still unknown.

Cause

Metagonimiasis is most commonly caused by one of the two smallest flukes known to infect man, ''Metagonimus yokagawai'', also called the Japanese fluke. More rarely, metagonimiasis can arise from infection with ''M. takahashii'' or ''M. miyatai''. Recent studies analyzing the DNA of the three agents causing metagonimiasis found that DNA sequencing supports ''M. yokagawai'' and ''M. takahashii'' be placed in the same clade, and phylogenic tree analysis supports their genetic similarity. ''M. miyatai'', however, was found to be more genetically distinct, and the authors concluded it should be nominated as a separate species. An additional study examining karyotype data on the three disease-causing agents also supported the nomination of ''M. miyatai'' as a separate species. Trematodes are one class of phylum ''

Platyhelminthes The flatworms, flat worms, Platyhelminthes, or platyhelminths (from the Greek πλατύ, ''platy'', meaning "flat" and ἕλμινς (root: ἑλμινθ-), ''helminth-'', meaning "worm") are a phylum of relatively simple bilaterian, unsegme ...

'' from the order '' Digenia'' and are generally referred to as flukes. Metagonimiasis is of the family '' Herterophyidae''.

Transmission

Transmission requires two intermediate hosts, the first of which is

snails A snail is, in loose terms, a shelled gastropod. The name is most often applied to land snails, terrestrial pulmonate gastropod molluscs. However, the common name ''snail'' is also used for most of the members of the molluscan class Gastro ...

, most commonly of

species In biology, a species is the basic unit of classification and a taxonomic rank of an organism, as well as a unit of biodiversity. A species is often defined as the largest group of organisms in which any two individuals of the appropriate s ...

''Semisucospira libertina'', '' Semiculcospira coreana'', and ''

Thiara granifera ''Tarebia granifera'', common name (in the aquarium industry) the quilted melania, is a species of freshwater snail with an operculum, an aquatic gastropod mollusk in the family Thiaridae. MolluscaBase eds. (2020). MolluscaBase. Tarebia gr ...

''. Infection is acquired through the secondary intermediate host,

fish Fish are aquatic, craniate, gill-bearing animals that lack limbs with digits. Included in this definition are the living hagfish, lampreys, and cartilaginous and bony fish as well as various extinct related groups. Approximately 95% of ...

, that have not been thoroughly cooked. Metacercariae encyst under the scales or in the flesh of fish from fresh or brackish water. Sweetfish (''Pecoglossus altevelis'') is one of the most common fish species infected, but others include the golden carp (''Carassius auratus''), common carp (''Cyprinus carpio''), ''Zacco temminckii, Protimus steindachneri, Acheilognathus lancedata'', and ''Pseudorashora parva''. Definitive hosts include humans and various fish-eating mammals, primarily

dog The dog (''Canis familiaris'' or ''Canis lupus familiaris'') is a domesticated descendant of the wolf. Also called the domestic dog, it is derived from the extinct Pleistocene wolf, and the modern wolf is the dog's nearest living relative. Do ...

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, and

pig The pig (''Sus domesticus''), often called swine, hog, or domestic pig when distinguishing from other members of the genus '' Sus'', is an omnivorous, domesticated, even-toed, hoofed mammal. It is variously considered a subspecies of ''Sus ...

s. Fish-eating birds may also be infected with metagonimiasis.

Reservoirs

Reservoirs include fish-eating mammals such as dogs, cats and pigs as well as fish-eating birds. The presence of heterophyid infection in humans is generally caused by a lack of ''host specificity'' by the

parasites 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 ha ...

, as seen in the many non-human reservoirs for metagonimiasis. The many reservoirs also have negative implications on the efficacy of prevention and eradication efforts of the disease.

Incubation period

The incubation period is around 14 days and infestation may persist for more than one year.

Morphology

Eggs

The morphology of the eggs is very important for diagnosis, but is difficult as eggs are very small. Eggs have a smooth, hard shell that is

transparent Transparency, transparence or transparent most often refer to: * Transparency (optics), the physical property of allowing the transmission of light through a material They may also refer to: Literal uses * Transparency (photography), a still, ...

and yellow-brown with a more conventional, ovoid egg shape. They are about the same size as those of '' Heterophyes'' and '' Clonorchis'', usually measuring 26-28 μm length and 15-17μm width. The egg also has a very slight opercular shoulder, marking the line of cleavage between the shell and operculum, an "escape hatch" for the ''mircidium''. The ''Clonorchis'' has more distinctive tapering and a seated operculum that help distinguish it more readily from ''Metagonimus'' species.

Adult flukes

The body of the adult disease-causing agent of metagonimiasis is often described as leaf-shaped, similar to most

trematodes Trematoda is a class of flatworms known as flukes. They are obligate internal parasites with a complex life cycle requiring at least two hosts. The intermediate host, in which asexual reproduction occurs, is usually a snail. The definitive host ...

. It is one of the smallest intestinal flukes, and is only slightly larger than '' Heteropheres''. The most prominent feature is that its ventral sucker is deflected to the right of its midline and is closely associated with the opening of the genital pore. The

testes A testicle or testis (plural testes) is the male reproductive gland or gonad in all bilaterians, including humans. It is homologous to the female ovary. The functions of the testes are to produce both sperm and androgens, primarily testoste ...

are large and diagonal to each other while the smaller ovary is anterior to the testes and the

uterus The uterus (from Latin ''uterus'', plural ''uteri'') or womb () is the organ in the reproductive system of most female mammals, including humans that accommodates the embryonic and fetal development of one or more embryos until birth. The ...

is filled with eggs. The uterus winds forward to the genital pore and is the largest organ in the body. The size of the adult fluke does not exceed 2.5 mm length by .75 mm width.

Diagnosis

Metagonimiasis is diagnosed by eggs seen in feces. Only after antihelminthic treatment will adult worms be seen in the feces, and then can be used as part of a diagnostic procedure. A 1993 analysis of the efficacy of

ELISA 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 presen ...

tests to diagnose metagonimiasis implied that simultaneous screening of specific antibodies to several parasite agents are important in serological diagnosis of acute parasitic disease and more research should be done on the efficacy of these methods of diagnosis. Diagnosis may be difficult because the egg-laying capacity of heterophyids is limited, and therefore sedimentation concentration procedures may be needed to demonstrate eggs in lighter infections. Accurate species identification is also difficult because eggs of most flukes are similar in size and morphology, especially those of '' Heterophyes heterophyes'', '' Clonorchis'' and '' Opisthorchis''. It is important to ask where the person may have contracted the disease, find out if they have been to en endemic area, and check for signs and symptoms that would lead to metagonimiasis.

Prevention

Several public health prevention strategies could help lower the rates of metagonimiasis. One is to control the intermediate host (snails). This can be done through use of molluscidals. Another is to use education to ensure all people, especially in areas were the disease regularly occurs, fully cook all fish. This could potentially be problematic and not as effective as hoped as many of the people affected by metagonimiasis eat raw or pickled fish as part of a traditional, long-seated dietary practice. Additionally, implementing more sanitary water conditions would reduce the continual reintroduction of eggs to water sources, thus restarting the lifecycle. Complete control of metagonimiasis presents several potential problems because it does have several reservoir hosts, thus eradication is unlikely.

Treatment

Praziquantel Praziquantel (PZQ), sold under the brandname Biltricide among others, is a medication used to treat a number of types of parasitic worm infections in mammals, birds, amphibians, reptiles, and fish. In humans specifically, it is used to treat sc ...

is recommended in both adult and pediatric cases with dosages of 75 mg/kg/d in 3 doses for 1 day. Praziquantel is a Praziniozoquinoline derivative that alters the calcium flux through the parasite

tectum The midbrain or mesencephalon is the forward-most portion of the brainstem and is associated with vision, hearing, motor control, sleep and wakefulness, arousal ( alertness), and temperature regulation. The name comes from the Greek ''mesos'', " ...

and causes muscular paralysis and detachment of the fluke. Prizaquantel should be taken with liquids during a meal and as provided commercially as Biltricide. Praziquantel is not approved by the

U.S. Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...

(FDA) for treatment of metagonimiasis, but is approved for use on other parasitic infections. Praziquantel has some side effects but they are generally relatively mild and transient and a review of evidence shows it overall a well-tolerated drug. Possible side effects include

allergy Allergies, also known as allergic diseases, refer a number of conditions caused by the hypersensitivity of the immune system to typically harmless substances in the environment. These diseases include hay fever, food allergies, atopic derm ...

, headache,

liver problems Liver disease, or hepatic disease, is any of many diseases of the liver. If long-lasting it is termed chronic liver disease. Although the diseases differ in detail, liver diseases often have features in common. Signs and symptoms Some of the s ...

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, gastroenteri ...

, exacerbation of porphyries,

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 ...

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 ...

somnolence Somnolence (alternatively sleepiness or drowsiness) is a state of strong desire for sleep, or sleeping for unusually long periods (compare hypersomnia). It has distinct meanings and causes. It can refer to the usual state preceding falling asleep ...

vertigo Vertigo is a condition where a person has the sensation of movement or of surrounding objects moving when they are not. Often it feels like a spinning or swaying movement. This may be associated with nausea, vomiting, sweating, or difficulties w ...

, or

dizziness Dizziness is an imprecise term that can refer to a sense of disorientation in space, vertigo, or lightheadedness. It can also refer to disequilibrium or a non-specific feeling, such as giddiness or foolishness. Dizziness is a common medical c ...

. In fact, in 2002, the

World Health Organization The World Health Organization (WHO) is a specialized agency of the United Nations responsible for international public health. The WHO Constitution states its main objective as "the attainment by all peoples of the highest possible level of ...

recommended the use of Praziquantel in pregnant and lactating women, though controlled trials are still needed to verify this. Another possible drug option is

Tetrachloroethylene Tetrachloroethylene, also known under the systematic name tetrachloroethene, or perchloroethylene, and many other names (and abbreviations such as "perc" or "PERC", and "PCE"), is a chlorocarbon with the formula Cl2C=CCl2 . It is a colorless li ...

, a chlorinated hydrocarbon, but its use has been superseded by new antihelminthic drugs (like Praziquantel). A 1978 study also looked at the efficacy of several drugs on metagonimiasis infection, including bithionol, niclosamide, nicoflan, and Praziquantel. All drugs showed lower prevalence of eggs in feces, however only Praziquantel showed complete radical cure. Therefore, the authors concluded Praziquantel was the most highly effective, was very well tolerated, and was the most promising drug against metagonimiasis.

Epidemiology

Metagonimiasis infections are endemic or potentially endemic in 19 countries including Japan, Korea, China, Taiwan, the Balkans, Spain, Indonesia, the Philippines and Russia. Human infections outside endemic areas may result from ingesting pickled fish or sushi made from fish imported from endemic areas.

Korea

Food-borne trematodes are currently the most important parasitic infections in Korea and approximately 240,000 Koreans are believed to be currently infected. Of the 240,000 estimated to be infected, 120,000 are caused by M. yokagawai, 20,000 by M. takahashii, and 100,000 by M. miyatai. The national rate of infections among randomly selected people was 1.2% in 1981, 1.0% in 1986, and down to 0.5% in 2004. M. yokagawai infections are found mostly around the large and small streams where sweetfish live and have been identified as endemic foci. M. miyatai and M. takahashii are prevalent along the upper reaches of the big rivers where minnows and carps are caught for eating raw.

Japan

Metagonimiasis is also common in Japan, with 10-15% prevalence rates in populations bordering major rivers and 150,000 estimated infected. Food-borne trematodes are most common in rural areas where traditional food habits are more preserved and raw freshwater fishes are incorporated into the diet. Both clonorchiasis and metagonimiasis have become infections of higher social classes in Hong Kong and Japan, owing to their frequent consumption of raw fish.

India

There have also recently been two reported cases in India, a location in which occurrence of infection is almost unknown. The second case, in 2005, was in a 6-year-old female patient presenting with loose watery stools for four days (however more details were not obtained as the patient was both deaf and dumb since birth). Upon examination, M. yokagawai eggs were found in stool, but the patient left and further analysis and treatment could not be completed.

References

Ahn, Yung-Kyum. "Intestinal flukes of genus Metagonimus and their second intermediate hosts in Kangwon-do." Korean Journal of Parasitology. Vol. 31: 331–340. 1993. Ash, Lawrence; Orihel, Thomas. Atlas of Human Parasitology. Fourth Edition. American Society of Clinical Pathologists. 1997. Chai, Jong-Yil et al. "An epidemiological study of metagonimiasis along the upper reaches of the Namham River." Korean Journal of Parasitology. Vol. 31: 99–108. 1993. Chi, Je G. et al. "Intestinal Pathology in Human Metagonimiasis with Ultrastructural Observation of Parasites." Journal of Korean Medical Science. Vol. 3: 171–177. 1998. Despommier D.; Gwadz R.; Hotez P.; Knirsch C. Parasitic Diseases. Fifth Edition. New York: Apple Trees Productions. 2006. Doenhoff, M. J., D. Cioli, and J. Utzinger. "Praziquantel: mechanisms for action, resistance, and new derivatives for schistosomiasis." Current Opinion in Infectious Diseases. Vol 21:659-667. 2008. FAO/NACA/WHO. "Food Safety Issues Associated with Products from Aquaculture." WHO Technical Report Series. Geneva, 1999. Han, In-Soo et al. "An Epidemiologic Study on Clonorchiasis and Metagonimiasis in Riverside Areas in Korea." Korean Journal of Parasitology. Vol. 19: 137–150. 1981. Lee, Jin-Ju, et al. "Decrease of Metagonimus yokogawai Endemicity along the Tamjin River Basin." Korean Journal of Parasitology. Vol. 46: 269–291. 2008. Lee, Gye-Sung et al. "Epidemiological study of clonorchiasis and metagonimiasis along the Geum-gang in Okcheon-gun, Korea." Korean Journal of Parasitology. Vol. 40: 9–16. 2002. Lee, Seoung Cheol et al. "Antigenti c protein fractions of Metagonimus yokogawai reacting with patient sera." Korean Journal of Parasitology. Vol. 31: 43–48. 1993. Lee, Soo-ung et al. "Sequence comparisons of 28S ribosomal DNA and mitochondrial cytochrome c oxidase subunit I of Metgonimus yokogawai, M. takahashii, and M. miyatai." Korean Journal of Parasitology. Vol. 24: 129–135. 2004. Lee, Soo-ung et al. "A cytogenetic study on human intestinal trematodes of the genus Metagonimus in Korea." Korean Journal of Parasitology. Vol. 37: 237–241. 1999. Markell, EK; John, DT; Krotoski, WA. Markell and Voge's Medical Parasitology. Ninth Edition. Philadelphia: W.B. Saunders Company. 2006. Mehlhorn, Heinz. Encyclopedic Reference of Parasitology. Second Edition. Germany: Springer. 2001. Pawlowski, Zbigniew S. "Intestinal Helminthiases and Human Health: Recent Advances and Future Needs." Parasitic Disease Programme, WHO. 1987. Rim, Han-Jong et al. "Antihelminthic Effects of Various Drugs against Metagonimiasis." Korean Journal of Parasitology. Vol. 16: 117–122. 1978. Rim, Han-Jong. "Classification and host specificity of Metagonimus spp. from Korean freshwater fish." Korean Journal of Parasitology. Vol. 34: 7-14. 1996. Shin, Eun-Hee et al. "Trends in parasitic diseases in the Republic of Korea." Trends in Parasitology. Vol. 24: 143–150. 2008. "The Medical Letter." Drugs for Parasitic Infections. 2005. www.medicalletter.org/parasitic_cdc. Uppal, B. and V. Wadhwal. "Rare Case of Metagonimus Yokogawai." Indian Journal of Medical Microbiology. Vol. 23: 61–62. 2005. WHO/FAO. "Food-Borne Trematode Infections in Asia." Ha Noi, Vietnam, 2002. WHO. "Integrated Guide to Sanitary Parasitology." Jordan, 2004. WHO. "Review on the Epidemiological Profile of Helminthes and their Control in the Western Pacific region, 1997-2008." 2006. Yamada, Shoko Merrit et al. "A Case of Metagonimiasis Complicated with Multiple Intracerbral Hemorrhages and Diabetes Mellitus." Journal of Nippon Medical School. 2008.

External links

{{Medical resources , DiseasesDB = , ICD10 = {{ICD10, B, 66, 8 , ICD9 = {{ICD9, 121.5 , ICDO = , OMIM = , MedlinePlus = , eMedicineSubj = , eMedicineTopic = , MeshID =
Metagonimiasis
Helminthiases