Clonorchis sinensis

Clonorchis sinensis
An adult Clonorchis sinensis has these main body parts: oral sucker, pharynx, caecum, ventral sucker, vitellaria, uterus, ovary, Mehlis' gland, testes, excretory bladder. (H&E stain)
Scientific classification
Kingdom: Animalia
Phylum: Platyhelminthes
Class: Trematoda
Order: Opisthorchiida
Family: Opisthorchiidae
Genus: Clonorchis
Species: C. sinensis
Binomial name
Clonorchis sinensis
Looss, 1907

Clonorchis sinensis, the Chinese liver fluke, is a human liver fluke belonging to the class Trematoda, phylum Platyhelminthes. This parasite lives in the liver of humans, and is found mainly in the common bile duct and gall bladder, feeding on bile. These animals, which are believed to be the third most prevalent worm parasite in the world, are endemic to Japan, China, Taiwan, and Southeast Asia, currently infecting an estimated 30,000,000 humans.[1] 85% of cases are found in China. The infection called clonorchiasis generally appears as jaundice, indigestion, biliary inflammation, bile duct obstruction, even liver cirrhosis, cholangiocarcinoma (CCA), and hepatic carcinoma.[2]

It is the most prevalent human trematode in Asia, and is still transmitted in Korea, China, Vietnam and also Russia, with 200 million people at constant risk. Recent studies have proved that it is definite cancer-causing agent in the liver (carcinoma) and bile duct (CCA). For this reason the International Agency for Research on Cancer has classed it as a group 1 biological carcinogen in 2009.[3][4][5]

Discovery

The symptoms of C. sinensis infection (clonorchiasis) have been known from ancient times in China. The earliest record is from corpses buried in 278 BCE at Jiangling County of Hubei Province and the Warring States tomb of the western Han Dynasty. But the parasite was discovered only in 1874 by James McConnell, a professor of pathology and resident physician at the Medical College Hospital in Calcutta. He recovered the fluke from a twenty-year-old Chinese carpenter who died on 8 September 1874. On autopsy, he observed that the corpse had swollen liver (hepatomegaly) and distended bile ducts, which he noted were blocked by "small, dark, vermicular-looking bodies." He recovered the vermicules (worms) and compared them with known flukes Fasciola hepatica and Distoma lanceolatum. He concluded that the new fluke was significantly different. He published his observations in the 21 August 1875 issue of The Lancet.[6] The formal scientific description was published by Thomas Spencer Cobbold in 1875. Cobbold named it Distoma sinense. But in 1876, Rudolf Leuckart named it as Distomum spithulatum. Kenso Ishisaka recorded the first case of clonorchiasis in Japan in 1877. McConnell identified another infection in a Chinese cook from Hong Kong in 1878. Erwin von Baelz reported the presence of similar flukes from an autopsy of a Japanese patient at Tokyo University in 1883. He recorded two different forms, naming the smaller, more pathogenic form as Distoma hepatis endemicum sive perniciosum, and the larger, less pathogenic form as D.h.e.s. innocuum. Isao Ijima correctly redescribed them as the same species, but still wrongly renamed it Distoma endemicum in 1886. When a new genus Opisthorchis was created by Émile Blanchard in 1895, Cobbold's species name D. sinense was moved to the new genus because of close similarities with the other members. But further analyses by Arthur Looss showed significant differences from the general features of Opisthorchis, particularly on the highly branched testes. He created a new genus Clonorchis (from Greek Klon meaning "twig/branch", orkhis meaning "testis") in 1907. But similar to Baelz, he differentiated the larger species as Clonorchis sinensis, which are mostly found in China, and the smaller species as C. endemicum, found mostly in Japan. In 1912, Harujiro Kobayashi corrected the classification that the differences in sizes were due to the nature of the host and intensity of infection, and had nothing to do with the biology.[7] Hence, he supported only C. sinensis. Kobayashi was also the first to discover fish as the second intermediate host in 1911. Masatomo Muto discovered snails as the first intermediate host in 1918.[8][9]

Description

Clonorchis sinensis under a light microscope. Notice the uterus. This species is monoecious

An adult C. sinensis is a flattened (dorso-ventrally flat) and leaf-shaped fluke. The body is slightly elongated and slender, measuring 15–20 mm in length and 3–4 mm in width.[10] It narrows down at the anterior region into a small opening called oral sucker, which act as the mouth. From the mouth run two tubes called caeca throughout the length of body. They are the digestive and excretory tracts. The posterior end is broad and blunt. A poorly developed ventral sucker lies behind the oral sucker, at about one-fourth of the body length form the anterior end. A common genital pore opens just in front of it. As a hermaphrodite, it has both male and female reproductive organs. A single rounded ovary is at the centre of the body, and two testes are towards the posterior end. The uterus from the ovary, and seminal ducts from the testes meet and opens at the genital pore. The testes are highly branched. Another highly branched organs called vitellaria (or vitelline glands) are distributed on either side of the body.[11][12]

The eggs are similar to those of other related flukes such as Opisthorchis viverrini and O. felineus, and are often confused during diagnosis. They small and oval in shape, measuring about 30x15 μm in diameter. They are sharply curved and with a clear convex operculum towards the narrower end. At the broader end is a stem-shaped knob. The larva called miracidium can be seen inside the fertilised egg.[13]

Life cycle

Life cycle of Clonorchis sinensis

Production of eggs

The eggs of a C. sinensis are released through the biliary tract, and excreted out along with the faeces. The eggs are embryonated and contain the larvae called miracidia. Unlike most other flukes in which the miracidia undergo development and swim in water to infect suitable host, the eggs of C. sinensis are simply deposited in water. The eggs are then eaten up by snails.[12]

First intermediate host

Freshwater snail Parafossarulus manchouricus often serves as a first intermediate host for C. sinensis in China, Japan, Korea and Russia.[14][15] Other snail hosts include Alocinma longicornis Bithynia longicornis, Bithynia fuchsiana, Bithynia misella, Parafossarulus anomalospiralis, Melanoides tuberculata, Semisulcospira cancellata, Koreoleptoxis amurensis, Semisulcospira libertina, and Assiminea lutea in China;[15] and Melanoides tuberculata in Vietnam.[16][17]

Once inside of the snail body, the embryonic membrane is dissolved by the snail's digestive enzymes so that the miracidium hatches from the egg. The ciliated miracidium can move about, penetrating the intestine, enters the haemocoel and digestive gland. Here it undergoes metamorphosis into a sporocyst. The sporocyst gives rise to small larvae called rediae. The rediae burst out from the sporocyst to become the next-stage larvae called cercaria. This system of asexual reproduction allows for an exponential multiplication of cercaria individuals from one miracidium. This aids the Clonorchis in reproduction, because it enables the miracidium to capitalize on one chance occasion of passively being eaten by a snail before the egg dies. The mature cercariae bore out of the snail body into the freshwater environment. However, they are non-feeding and must find a fish host within 2–3 days, otherwise they die.[12]

The ceraciae of C. sinensis are different from those of other flukes in that they do not swim. Instead, they initially hang upside-down in the water, and then sink to the bottom. They rise to the water surface to resume their initial position, and the movement is repeated again. They attack fish when they feel any disturbance in their life-style.[11]

Second intermediate host

When they detect fish, they attached themselves on the scales using their suckers. Boring their way into the fish's body, they penetrate into the fish muscle within 6 to 13 minutes. Within an hour of penetration they develop hard coverings called cysts, and become metacercariae. This protective cyst is useful when the fish muscle is consumed. The metacercariae gradually develop and become infective to their next hosts after 3 to 4 weeks.[11]

The common second intermediate hosts are freshwater fish: common carp (Cyprinus carpio), grass carp (Ctenopharyngodon idellus), crucian carp (Carassius carassius), goldfish (Carassius auratus), Pseudorasbora parva, Abbottina rivularis, Hemiculter spp., Opsariichthys spp., Rhodeus spp., Sarcocheilichthys spp., Zacco platypus, Nipponocypris temminckii , and pond smelt (Hypomesus olidus).[18] In China, 102 species of fish and four species of shrimp are known to be the intermediate hosts.[17] In Korea, 40 species of freshwater fish are recorded as hosts.[19] Seven species of fish are known as hosts in Russia.[20]

Definitive host

The metacercariae are eaten along with raw or undercooked fish. The cysts of the metacercariae are gradually digested by the human gastric acids, and upon reaching the small intestines, the entire cyst is lost. The free metacercariae penetrate the intestinal mucosa and enters the bile ducts. It takes 1-2 day for migration into the bile ducts. They start feeding on the bile secreted from the liver, and gradually grow.[13] They become adult in about a month, and start laying eggs. The average lifespan of an adult fluke is 30 years.[11] An individual fluke can produce 4,000 eggs in a day.[21]

The definitive hosts are fish-eating mammals such as dogs, cats, rats, pigs, badgers, weasels, camels, and buffaloes.[18]

Effects on human health

Dwelling in the bile ducts, Clonorchis induces an inflammatory reaction, epithelial hyperplasia and sometimes even cholangiocarcinoma, the incidence of which is raised in fluke-infested areas.[22]

One adverse effect of Clonorchis is the possibility for the adult metacercaria to consume all bile created in the liver, which would inhibit the host human from digesting, especially fats. Another possibility is obstruction of the bile duct by the parasite or its eggs, leading to biliary obstruction and cholangitis (specifically oriental cholangitis).

Unusual cases of liver abscesses due to clonorchiasis have been reported. Liver abscesses may be seen even without dilatation of intrahepatic bile ducts.[23]

Symptoms

While normally asymptomatic most pathological manifestations result from inflammation and intermittent obstruction of the biliary ducts. The acute phase consists of abdominal pain with associated nausea and diarrhea. Long-standing infections consist of fatigue, abdominal discomfort, anorexia, weight loss, diarrhea, and jaundice. The pathology of long-standing infections consist of bile stasis, obstruction, bacterial infections, inflammation, periductal fibrosis, and hyperplasia. Development of cholangiocarcinoma is progressive.[24]

Diagnosis and treatment

Infection is detected mainly on identification of eggs by microscopic demonstration in faeces or in duodenal aspirate. But other sophisticated methods have been developed such as ELISA, which has become the most important clinical technique. Diagnosis by detecting DNAs from eggs in faeces are also developed using PCR, real-time PCR, and LAMP, which are highly sensitive and specific. Imaging diagnosis has been studied in depth and is now widely used.[3][25] Drugs used to treat infestation include triclabendazole, praziquantel, bithionol, albendazole, levamisole and mebendazole. However, benzimidazoles are very weak as vermicide. As with other trematodes, praziquantel is the drug of choice. Lately, tribendimidine has been acknowledged as an effective and safe drug.[3][26]

Genetics

The draft genome sequence of C. sinensis was published in 2011.[27] The total genome size is estimated to be 580 Mb, and the GC content was calculated as approximately 43.85%. About 16,000 genes are predicted, out of which 13,634 genes have been identified.[28]

See also

References

  1. ↑ Wu W, Qian X, Huang Y, Hong Q (2012). "A review of the control of Clonorchiasis sinensis and Taenia solium taeniasis/cysticercosis in China". Parasitology Research. 111 (5): 1879–1884. PMID 23052782. doi:10.1007/s00436-012-3152-y.
  2. ↑ Hong, Sung-Tae; Fang, Yueyi (2012). "Clonorchis sinensis and clonorchiasis, an update". Parasitology International. 61 (1): 17–24. PMID 21741496. doi:10.1016/j.parint.2011.06.007.
  3. 1 2 3 Hong ST, Fang Y (2012). "Clonorchis sinensis and clonorchiasis, an update". Parasitology International. 61 (1): 17–24. PMID 21741496. doi:10.1016/j.parint.2011.06.007.
  4. ↑ Sripa B, Brindley PJ, Mulvenna J, Laha T, Smout MJ, Mairiang E, Bethony JM, Loukas A (2012). "The tumorigenic liver fluke Opisthorchis viverrini--multiple pathways to cancer". Trends in Parasitology. 28 (10): 395–407. PMC 3682777 Freely accessible. PMID 22947297. doi:10.1016/j.pt.2012.07.006.
  5. ↑ American Cancer Society (2013). "Known and Probable Human Carcinogens". cancer.org. American Cancer Society, Inc. Retrieved 2013-06-02.
  6. ↑ Qian, Men-Bao; Utzinger, Jürg; Keiser, Jennifer; Zhou, Xiao-Nong (2016). "Clonorchiasis". The Lancet. 387 (10020): 800–810. doi:10.1016/S0140-6736(15)60313-0.
  7. ↑ Yoshitaka, Komiya (1967). "Clonorchis and clonorchiasis". In Dawes, Ben. Advances in Parasitology Volume 4. Burlington: Elsevier. pp. 53–101. ISBN 978-0-08-058050-0.
  8. ↑ Yoshida, Yukio (2012). "Clonorchiasis—A historical review of contributions of Japanese parasitologists". Parasitology International. 61 (1): 5–9. PMID 21749930. doi:10.1016/j.parint.2011.06.003.
  9. ↑ Sripa, Banchob; Tesana, Smarn; Yurlova, Natalia; Nawa, Yukifumi (2017). "A historical review of small liver fluke infections in humans". Parasitology International. Online. PMID 28069407. doi:10.1016/j.parint.2017.01.004.
  10. ↑ Kim, TS; Pak, JH; Kim, JB; Bahk, YY (2016). "Clonorchis sinensis, an oriental liver fluke, as a human biological agent of cholangiocarcinoma: a brief review". BMB reports. 49 (11): 590–597. PMID 27418285. doi:10.5483/BMBRep.2016.49.11.109.
  11. 1 2 3 4 Adams, Ann M. (2006). "Foodborne trematodes". In Ortega, Ynes R. Foodborne Parasites. New York: Springer Science+Business Media. pp. 168–173. ISBN 978-0-387-31197-5.
  12. 1 2 3 Bogitsh, Burton Jerome; Carter, Clint Earl; Oeltmann, Thomas N. (2005). Human Parasitology (3 ed.). Amsterdam: Elsevier Academic Press. pp. 207–210. ISBN 978-0-12-088468-1.
  13. 1 2 Ridley, John W. (2012). Parasitology for Medical and Clinical Laboratory Professionals. Clifton Park, N.Y.: Delmar. pp. 187–188. ISBN 978-1-4-3544816-2.
  14. ↑ Clonorchis sinensis. Web Atlas of Medical Pathology, accessed 1 April 2009
  15. 1 2 World Health Organization (1995). Control of Foodborne Trematode Infection. WHO Technical Report Series. 849. PDF part 1, PDF part 2. page 125-126.
  16. ↑ Hung, Nguyen; Dung, Do; Lan Anh, Nguyen; Van, Phan; Thanh, Bui; Van Ha, Nguyen; Van Hien, Hoang; Canh, Le (2015). "Current status of fish-borne zoonotic trematode infections in Gia Vien district, Ninh Binh province, Vietnam". Parasites & Vectors. 8 (1): 21. PMC 4299372 Freely accessible. PMID 25586313. doi:10.1186/s13071-015-0643-6.
  17. 1 2 Tang, Ze-Li; Huang, Yan; Yu, Xin-Bing (6 July 2016). "Current status and perspectives of Clonorchis sinensis and clonorchiasis: epidemiology, pathogenesis, omics, prevention and control". Infectious Diseases of Poverty. 5 (1): 71. PMC 4933995 Freely accessible. PMID 27384714. doi:10.1186/s40249-016-0166-1.
  18. 1 2 Chai JY, Darwin Murrell K, Lymbery AJ (2005). "Fish-borne parasitic zoonoses: Status and issues". International Journal for Parasitology. 35 (11-12): 1233–1254. PMID 16143336. doi:10.1016/j.ijpara.2005.07.013.
  19. ↑ Sohn, Woon-Mok (2009). "Fish-borne zoonotic trematode metacercariae in the Republic of Korea". The Korean Journal of Parasitology. 47 (Suppl): S103–113. PMC 2769214 Freely accessible. PMID 19885326. doi:10.3347/kjp.2009.47.S.S103.
  20. ↑ Fattakhov, RG; Ushakov, AV; Stepanova, TF; Ianovich, VA; Kopylov, PV (2012). "[Epizootiological characteristics of clonorchiasis foci in the Amur River ecosystem in the Jewish autonomic region]". Meditsinskaia Parazitologiia i Parazitarnye Bolezni (4): 15–18. PMID 23437716.
  21. ↑ Kim, Jae-Hwan; Choi, Min-Ho; Bae, Young Mee; Oh, Jin-Kyoung; Lim, Min Kyung; Hong, Sung-Tae; Ito, Akira (2011). "Correlation between Discharged Worms and Fecal Egg Counts in Human Clonorchiasis". PLoS Neglected Tropical Diseases. 5 (10): e1339. PMC 3186755 Freely accessible. PMID 21991401. doi:10.1371/journal.pntd.0001339.
  22. ↑ Kumar et al.: Robbins & Cotran Pathologic Basis of Disease 7E
  23. ↑ Jang, Yun-Jin; Byun, Jae Ho; Yoon, Seong Eon; Yu, EunSil (2007-01-01). "Hepatic Parasitic Abscess Caused by Clonorchiasis: Unusual CT Findings of Clonorchiasis". Korean Journal of Radiology. 8 (1): 70–73. ISSN 1229-6929. PMC 2626702 Freely accessible. PMID 17277566. doi:10.3348/kjr.2007.8.1.70.
  24. ↑ Dr. Kuo, O. Sinensis Lecture, ATSU School of Osteopathic Medicine Arizona, June 2012
  25. ↑ Huang SY, Zhao GH, Fu BQ, Xu MJ, Wang CR, Wu SM, Zou FC, Zhu XQ (2012). "Genomics and molecular genetics of Clonorchis sinensis: current status and perspectives". Parasitology International. 61 (1): 71–76. PMID 21704726. doi:10.1016/j.parint.2011.06.008.
  26. ↑ Xu LL, Xue J, Zhang YN, Qiang HQ, Xiao SH (2011). "In vitro effect of seven anthelmintic agents against adult Clonorchis sinensis". Zhongguo Ji Sheng Chong Xue Yu Ji Sheng Chong Bing Za Zhi. 29 (1): 10–15. PMID 21823316.
  27. ↑ Wang, Xiaoyun; Chen, Wenjun; Huang, Yan; Sun, Jiufeng; Men, Jingtao; Liu, Hailiang; Luo, Fang; Guo, Lei; et al. (2011). "The draft genome of the carcinogenic human liver fluke Clonorchis sinensis". Genome Biology. 12 (10): R107. PMC 3333777 Freely accessible. PMID 22023798. doi:10.1186/gb-2011-12-10-r107.
  28. ↑ Huang, Yan; Chen, Wenjun; Wang, Xiaoyun; Liu, Hailiang; Chen, Yangyi; Guo, Lei; Luo, Fang; Sun, Jiufeng; Mao, Qiang; Liang, Pei; Xie, Zhizhi; Zhou, Chenhui; Tian, Yanli; Lv, Xiaoli; Huang, Lisi; Zhou, Juanjuan; Hu, Yue; Li, Ran; Zhang, Fan; Lei, Huali; Li, Wenfang; Hu, Xuchu; Liang, Chi; Xu, Jin; Li, Xuerong; Yu, Xinbing; Ralph, Stuart Alexander (30 January 2013). "The Carcinogenic Liver Fluke, Clonorchis sinensis: New Assembly, Reannotation and Analysis of the Genome and Characterization of Tissue Transcriptomes". PLoS ONE. 8 (1): e54732. PMC 3559784 Freely accessible. PMID 23382950. doi:10.1371/journal.pone.0054732.

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