Carcinogenic parasite
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Carcinogenic parasites are parasitic organisms that depend on other organisms (called
hosts A host is a person responsible for guests at an event or for providing hospitality during it. Host may also refer to: Places *Host, Pennsylvania, a village in Berks County People *Jim Host (born 1937), American businessman *Michel Host ( ...
) for their survival, and cause cancer in such hosts. Three species of flukes (
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 ...
) are medically-proven carcinogenic parasites, namely the urinary blood fluke (''
Schistosoma haematobium ''Schistosoma haematobium'' (urinary blood fluke) is a species of digenetic trematode, belonging to a group (genus) of blood flukes (''Schistosoma''). It is found in Africa and the Middle East. It is the major agent of schistosomiasis, the most ...
''), the Southeast Asian liver fluke (''
Opisthorchis viverrini ''Opisthorchis viverrini'', common name Southeast Asian liver fluke, is a food-borne trematode parasite from the family Opisthorchiidae that infects the bile duct. People are infected after eating raw or undercooked fish. Infection with the par ...
'') and the Chinese liver fluke (''
Clonorchis sinensis ''Clonorchis sinensis'', the Chinese liver fluke, is a liver fluke belonging to the class Trematoda, phylum Platyhelminthes. It infects fish-eating mammals, including humans. In humans, it infects the common bile duct and gall bladder, feeding o ...
''). ''S. haematobium'' is prevalent in Africa and the Middle East, and is the leading cause of
bladder cancer Bladder cancer is any of several types of cancer arising from the tissues of the urinary bladder. Symptoms include blood in the urine, pain with urination, and low back pain. It is caused when epithelial cells that line the bladder become ma ...
(only next to tobacco smoking). ''O. viverrini'' and ''C. sinensis'' are both found in eastern and southeastern Asia, and are responsible for cholangiocarcinoma (cancer of the bile ducts). The
International Agency for Research on Cancer The International Agency for Research on Cancer (IARC; french: Centre International de Recherche sur le Cancer, CIRC) is an intergovernmental agency forming part of the World Health Organization of the United Nations. Its role is to conduct and ...
declared them in 2009 as a Group 1 biological carcinogens in humans. Other parasites are also linked to various cancers. Among protozoan parasites, ''
Toxoplasma gondii ''Toxoplasma gondii'' () is an obligate intracellular parasitic protozoan (specifically an apicomplexan) that causes toxoplasmosis. Found worldwide, ''T. gondii'' is capable of infecting virtually all warm-blooded animals, but felids, such as d ...
'', ''
Cryptosporidium parvum ''Cryptosporidium parvum'' is one of several species that cause cryptosporidiosis, a parasitic disease of the mammalian intestinal tract. Primary symptoms of ''C. parvum'' infection are acute, watery, and nonbloody diarrhea. ''C. parvum'' in ...
'', ''
Trichomonas vaginalis ''Trichomonas vaginalis'' is an anaerobic, flagellated protozoan parasite and the causative agent of a sexually transmitted disease called trichomoniasis. It is the most common pathogenic protozoan that infects humans in industrialized countri ...
'' and ''
Theileria ''Theileria'' is a genus of parasites that belongs to the phylum Apicomplexa, and is closely related to ''Plasmodium''. Two ''Theileria'' species, ''T. annulata'' and ''T. parva'', are important cattle parasites. ''T. annulata'' causes tropical ...
'' are associated with specific cancer cells. '' Plasmodium falciparum'' can also be an indirect cause of cancer. Tapeworms such as ''
Echinococcus granulosus ''Echinococcus granulosus,'' also called the hydatid worm, hyper tape-worm or dog tapeworm, is a cyclophyllid cestode that dwells in the small intestine of canids as an adult, but which has important intermediate hosts such as livestock and hu ...
'' and ''
Taenia solium ''Taenia solium'', the pork tapeworm, belongs to the cyclophyllid cestode family Taeniidae. It is found throughout the world and is most common in countries where pork is eaten. It is a tapeworm that uses humans as its definitive host and pigs ...
'' may directly or indirectly cause cancer. Liver flukes such as ''Opisthorchis viverrini'' and ''Platynosomum fastosum'' can cause cancer in domesticated animals. Roundworms such as ''
Strongyloides stercoralis ''Strongyloides stercoralis'' is a human pathogenic parasitism, parasitic nematode, roundworm causing the disease strongyloidiasis. Its common name in the US is threadworm. In the UK and Australia, however, the term ''threadworm'' can also refe ...
'', '' Heterakis gallinarum'', and ''
Trichuris muris ''Trichuris muris'' is a nematode parasite of mice. It is very similar to the human roundworm parasite '' Trichuris trichiura'' due to its immunological reactivity when crossed, and so is often used in related studies. Lifecycle Ingesting m ...
'' are known to cause cancer in animals.


History

A rat roundworm ''Gongylonema neoplasticum'' was the first parasite discovered—allegedly—to cause cancer. A Danish physician
Johannes Fibiger Johannes Andreas Grib Fibiger (23 April 1867 – 30 January 1928) was a Danish physician and professor of anatomical pathology at the University of Copenhagen. He was the recipient of the 1926 Nobel Prize in Physiology or Medicine "for his disco ...
discovered it in 1907, and experimentally showed that he could induce stomach cancer in rats using the roundworm infection in 1913. In 1914, he gave the name ''Spiroptera'' (''Gongylonema'') ''neoplastica'', but later changed it to ''Spiroptera carcinoma''. Fibiger won the 1926 Nobel Prize in Physiology or Medicine "for his discovery of the Spiroptera carcinoma". However, his interpretation was later found to be false, and that the roundworm was not carcinogenic on its own. Fibiger's Nobel Prize was described as "one of the biggest blunders made by the Karolinska Institute." The first true carcinogenic parasite discovered was ''Schistosoma haematobium''. Theodor Maximillian Bilharz, a German physician at the Kasr el-Aini Hospital in Cairo recovered the adult fluke from a dead soldier in 1851. He named it ''Distomum haematobium''. The disease is often called bilharzia in honour of the discoverer. The infectivity and life cycle was discovered by Scottish physician
Robert Thomson Leiper Robert Thomson Leiper (17 April 1881 – 21 May 1969) FRS CMG was a British parasitologist and helminthologist. Early life and education Leiper was born on 17 April 1881 in Witch Road, Kilmarnock, Scotland; the eldest of three children of John ...
in 1915. A British Surgeon
Reginald Harrison Reginald Harrison FRCS (24 August 1837 – 28 February 1908) was a British surgeon, sometime vice-president and Member of the Council of the Royal College of Surgeons and Consulting Surgeon to St Peter's Hospital. Life Harrison was educated at ...
, at the Liverpool Royal Infirmary, was the first to note its role in cancer. In 1889, he found that four people out of five cancer victims had bilharzia. A German physician Carl Goebel confirmed in 1903 that bladder tumour occurred in most bilharzia patients. By 1905, he was convinced that carcinoma of bladder was due to bilharzia.


Group 1 carcinogens in human

Three flukes, urinary blood fluke (''Schistosoma haematobium''), Southeast Asian liver fluke (''Opisthorchis viverrini'') and Chinese liver fluke (''Clonorchis sinensis'') are classified as Group 1 carcinogens, i.e. they are substantiated and directly cancer-causing agents.


''Schistosoma haematobium''

''S. haematobium'' is a digenetic
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 ...
found in Africa and the Middle East. It is the major agent of schistosomiasis, the most prevalent parasitic infection in humans. It is the only blood fluke that infects the urinary tract, causing urinary schistosomiasis, and is the leading cause of
bladder cancer Bladder cancer is any of several types of cancer arising from the tissues of the urinary bladder. Symptoms include blood in the urine, pain with urination, and low back pain. It is caused when epithelial cells that line the bladder become ma ...
(only next to tobacco smoking). Its life cycle is transmission between humans and freshwater snail, species of ''Bulinus''. The larvae live in water bodies from where they infect the hosts by penetrating the skin. Adults are found in the
venous plexus In vertebrates, a venous plexus is a normal congregation anywhere in the body of multiple veins. A list of venous plexuses: * Basilar plexus * Batson venous plexus * Internal vertebral venous plexuses * Pterygoid plexus * Submucosal venous ...
es around the
urinary bladder The urinary bladder, or simply bladder, is a hollow organ in humans and other vertebrates that stores urine from the kidneys before disposal by urination. In humans the bladder is a distensible organ that sits on the pelvic floor. Urine ente ...
and the released eggs travels to the wall of the urine bladder causing
haematuria 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 ...
and fibrosis of the bladder. The bladder becomes
calcified Calcification is the accumulation of calcium salts in a body tissue. It normally occurs in the formation of bone, but calcium can be deposited abnormally in soft tissue,Miller, J. D. Cardiovascular calcification: Orbicular origins. ''Nature Ma ...
, and there is increased pressure on ureters and kidneys (
hydronephrosis Hydronephrosis describes hydrostatic dilation of the renal pelvis and calyces as a result of obstruction to urine flow downstream. Alternatively, hydroureter describes the dilation of the ureter, and hydronephroureter describes the dilation of t ...
). Inflammation of the genitals due to ''S. haematobium'' may contribute to the propagation of HIV. Antigens produced by the eggs induce granuloma formation. Granulomata in turn coalesce to form tubercles, nodules or masses that often
ulcerate Ulcerate is a New Zealand-based extreme metal band formed by guitarist Michael Hoggard and drummer Jamie Saint Merat in 2000. The band have released six studio albums to date. The band have been featured in numerous articles as one of New Zea ...
. This creates the pathological lesions found in the bladder wall, ureter and renal; and also tumour, both
benign Malignancy () is the tendency of a medical condition to become progressively worse. Malignancy is most familiar as a characterization of cancer. A ''malignant'' tumor contrasts with a non-cancerous ''benign'' tumor in that a malignancy is not s ...
and
malignant Malignancy () is the tendency of a medical condition to become progressively worse. Malignancy is most familiar as a characterization of cancer. A ''malignant'' tumor contrasts with a non-cancerous ''benign'' tumor in that a malignancy is not s ...
.


''Opisthorchis viverrini''

''O. viverrini'' is a food-borne liver fluke that mainly attacks the area of the
bile duct A bile duct is any of a number of long tube-like structures that carry bile, and is present in most vertebrates. Bile is required for the digestion of food and is secreted by the liver into passages that carry bile toward the hepatic duct. It ...
. Infection with the parasite, called
opisthorchiasis Opisthorchiasis is a parasitic disease caused by certain species of genus '' Opisthorchis'' (specifically, '' Opisthorchis viverrini'' and '' Opisthorchis felineus''). Chronic infection may lead to cholangiocarcinoma, a cancer of the bile ducts. ...
is the major cause of cholangiocarcinoma, a cancer of the
bile duct A bile duct is any of a number of long tube-like structures that carry bile, and is present in most vertebrates. Bile is required for the digestion of food and is secreted by the liver into passages that carry bile toward the hepatic duct. It ...
s, in northern Thailand, the Lao People's Democratic Republic, Vietnam and Cambodia. ''O. viverrini'' has three successive host for its life cycle – the first intermediate hosts are freshwater snails of the genus ''Bithynia'', the second intermediate hosts are different cyprinid fish, and humans are the definitive hosts. Generally opisthorchiasis due to ''O. viverrini'' is harmless without any clinical symptoms, but in rare cases, cholangitis,
cholecystitis Cholecystitis is inflammation of the gallbladder. Symptoms include right upper abdominal pain, pain in the right shoulder, nausea, vomiting, and occasionally fever. Often gallbladder attacks (biliary colic) precede acute cholecystitis. The pai ...
, and cholangiocarcinoma can develop. ''O. viverrini'' invades the bile ducts and, rarely, the gall bladder and pancreatic duct. Heavy infection can produce problems such as fibrosis in the liver, gall bladder and bile ducts. Pathological effects on the bile ducts including inflammation, epithelial desquamation, goblet cell metaplasia, epithelial and adenomatous hyperplasia and periductal fibrosis collectively promote cholangiocarcinoma. Though it is not immediately life-threatening, cancer develops after 30–40 years, and the ensuing death is rapid—within 3–6 months of diagnosis.


''Clonorchis sinensis''

''C. sinensis'' is also a food-borne liver fluke. It is the most prevalent human trematode in Asia, and is found in Korea, China, Vietnam and also Russia. 85% of the cases are found in China. It is transmitted similarly to ''O. viverrini'', but the species of snails are varied, of which '' Parafossarulus manchouricus'' is the most common. The cyprinid fish hosts are also different. General clonorchiasis is indicated with fatigue, abdominal discomfort, anorexia, weight loss, diarrhea,
liver cirrhosis Cirrhosis, also known as liver cirrhosis or hepatic cirrhosis, and end-stage liver disease, is the impaired liver function caused by the formation of scar tissue known as fibrosis due to damage caused by liver disease. Damage causes tissue repai ...
and jaundice. The most severe infections cause cholangiocarcinoma and hepatic carcinoma.


Indirect or putative carcinogens

Infection with malarial parasite ''Plasmodium falciparum'' is classified by IARC as probable (Group 2A) carcinogen. ''Schistosoma japonicum'' is a possible (Group 2B) carcinogen. There is a close association between the cat liver fluke ''Opisthorchis felineus'' and bile duct cancer among people in Russia. ''Toxoplasma gondii'' and eye cancer (intraocular lymphoma) was detected by PCR from two human cases. ''Strongyloides stercoralis'' eggs and adult worms may be linked with gastric adenocarcinoma and colon adenocarcinoma in Korea. ''Cryptosporidium parvum'' infection is associated with colorectal carcinoma.


Carcinogens in animals

The roundworm ''Trichuris muris'' infection can increase the number of tumours in mice. Heavy infection with the trematode ''Platynosomum fastosum'' is associated with cholangiocarcinoma in cats. ''Cryptosporidium parvum'' infection can be the cause of carcinoma in the gut of mice.


References

{{Reflist, 30em Parasitic diseases Infectious causes of cancer Helminthiases Helminthology