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12 月26日， 美国，日本军事基地的相关人体实验传播研究 FilariasisFrom Wikipedia, the free encyclopedia
Filariasis is a parasitic disease caused by an infection with roundworms of the Filarioidea type.[1] These are spread by blood-feeding black flies and mosquitoes. This disease belongs to the group of diseases called helminthiases. Eight known filarial nematodes use humans as their definitive hosts. These are divided into three groups according to the niche they occupy in the body:
The adult worms, which usually stay in one tissue, release early larval forms known as microfilariae into the host's bloodstream. These circulating microfilariae can be taken up with a blood meal by the arthropod vector; in the vector, they develop into infective larvae that can be transmitted to a new host. Individuals infected by filarial worms may be described as either "microfilaraemic" or "amicrofilaraemic", depending on whether microfilariae can be found in their peripheral blood. Filariasis is diagnosed in microfilaraemic cases primarily through direct observation of microfilariae in the peripheral blood. Occult filariasis is diagnosed in amicrofilaraemic cases based on clinical observations and, in some cases, by finding a circulating antigen in the blood. ContentsSigns and symptoms[edit]The most spectacular symptom of lymphatic filariasis is elephantiasis—edema with thickening of the skin and underlying tissues—which was the first disease discovered to be transmitted by mosquito bites.[2] Elephantiasis results when the parasites lodge in the lymphatic system. Elephantiasis affects mainly the lower extremities, while the ears, mucous membranes, and amputation stumps are affected less frequently. However, different species of filarial worms tend to affect different parts of the body; Wuchereria bancrofti can affect the legs, arms, vulva, breasts, and scrotum (causing hydrocele formation), while Brugia timorirarely affects the genitals.[citation needed] Those who develop the chronic stages of elephantiasis are usually free from microfilariae (amicrofilaraemic), and often have adverse immunological reactions to the microfilariae, as well as the adult worms.[2] The subcutaneous worms present with rashes, urticarial papules, and arthritis, as well as hyper- and hypopigmentation macules. Onchocerca volvulus manifests itself in the eyes, causing "river blindness" (onchocerciasis), one of the leading causes of blindness in the world.[citation needed] Serous cavity filariasis presents with symptoms similar to subcutaneous filariasis, in addition to abdominal pain, because these worms are also deep-tissue dwellers. Cause[edit]Human filarial nematode worms have complicated life cycles, which primarily consists of five stages. After the male and female worms mate, the female gives birth to live microfilariae by the thousands. The microfilariae are taken up by the vector insect (intermediate host) during a blood meal. In the intermediate host, the microfilariae molt and develop into third-stage (infective) larvae. Upon taking another blood meal, the vector insect injects the infectious larvae into the dermis layer of the skin. After about one year, the larvae molt through two more stages, maturing into the adult worms. Diagnosis[edit]Filariasis is usually diagnosed by identifying microfilariae on Giemsa stained, thin and thick blood film smears, using the "gold standard" known as the finger prick test. The finger prick test draws blood from the capillaries of the finger tip; larger veins can be used for blood extraction, but strict windows of the time of day must be observed. Blood must be drawn at appropriate times, which reflect the feeding activities of the vector insects. Examples are W. bancrofti, whose vector is a mosquito; night is the preferred time for blood collection. Loa loa's vector is the deer fly; daytime collection is preferred. This method of diagnosis is only relevant to microfilariae that use the blood as transport from the lungs to the skin. Some filarial worms, such as M. streptocerca and O. volvulus, produce microfilarae that do not use the blood; they reside in the skin only. For these worms, diagnosis relies upon skin snips and can be carried out at any time. Concentration methods[edit]
Various concentration methods are applied: membrane filter, Knott's concentration method, and sedimentation technique. Polymerase chain reaction (PCR) and antigenic assays, which detect circulating filarial antigens, are also available for making the diagnosis. The latter are particularly useful in amicrofilaraemic cases. Spot tests for antigen[3] are far more sensitive, and allow the test to be done anytime, rather in the late hours. Lymph node aspirate and chylous fluid may also yield microfilariae. Medical imaging, such as CT or MRI, may reveal "filarial dance sign" in the chylous fluid; X-ray tests can show calcified adult worms in lymphatics. The DEC provocation test is performed to obtain satisfying numbers of parasites in daytime samples. Xenodiagnosis is now obsolete, and eosinophilia is a nonspecific primary sign. Treatment[edit]The recommended treatment for people outside the United States is albendazole combined with ivermectin.[4][5] A combination of diethylcarbamazine and albendazole is also effective.[4][6] Side effects of the drugs include nausea, vomiting, and headaches.[7] All of these treatments are microfilaricides; they have no effect on the adult worms. While the drugs are critical for treatment of the individual, proper hygiene is also required.[8] Different trials were made to use the known drug at its maximum capacity in absence of new drugs. In a study from India, it was shown that a formulation of albendazole had better anti-filarial efficacy than albendazole itself.[9] In 2003, the common antibiotic doxycycline was suggested for treating elephantiasis.[10] Filarial parasites have symbiotic bacteria in the genus Wolbachia, which live inside the worm and seem to play a major role in both its reproduction and the development of the disease. This drug has shown signs of inhibiting the reproduction of the bacteria, further inducing sterility.[11] Clinical trials in June 2005 by the Liverpool School of Tropical Medicine reported an eight-week course almost completely eliminated microfilaraemia.[12] Society and culture[edit]Research teams[edit]In 2015 William C. Campbell and Satoshi ōmura were Co-awarded half of that year's Nobel prize in Physiology or Medicine for the discovery of the drug avermectin, which in the further developed form ivermectin has come to decrease the occurrence of lymphatic filariasis.[13] Other animals[edit]Filariasis can also affect domesticated animals, such as cattle, sheep, and dogs. Cattle[edit]
Horses[edit]
Dogs[edit]
See also[edit]References[edit]
Further reading[edit]
External links[edit]
Satoshi ōmuraFrom Wikipedia, the free encyclopedia
Satoshi ōmura [satoɕi oːmu͍ɽa] (大村 智 ōmura Satoshi?, born 12 July 1935) is a Japanese biochemist. He is known for the discovery and development of various pharmaceuticals originally occurring in microorganisms. In 2015, he was awarded the Nobel Prize in Physiology or Medicine jointly with William C. Campbell and Tu Youyou. ContentsEducation[edit]Omura graduated from the University of Yamanashi, he received his M.S. degree from Tokyo University of Science and his Ph.D. in Pharmaceutical Sciences from the University of Tokyo and a Ph.D. in Chemistry at the Tokyo University of Science.[1] Career[edit]Satoshi ōmura is professor emeritus at Kitasato University and Max Tishler Professor of Chemistry at Wesleyan University. He is known for the discovery and development of various pharmaceuticals originally occurring in microorganisms. He was awarded the 2015 Nobel Prize in Physiology or Medicine jointly with William C. Campbell and Tu Youyou for discoveries concerning a novel therapy against infections caused by roundworm parasites. More precisely, his research group isolated a strain of Streptomyces avermitilis that produce the anti-parasitical compound avermectin. Campbell later acquired these bacteria and developed the derived drug ivermectin that is today used against river blindness, lymphatic filariasis and other parasitic infections.[1][2][3] Atkinson, H.J. (1973). "The respiratory physiology of the marine nematodes Enoplus brevis(Bastian) and E. communis (Bastian): I. The influence of oxygen tension and body size"(PDF). J. Exp. Biol. 59 (1): 255–266. Streptomyces avermitilisFrom Wikipedia, the free encyclopedia
Streptomyces avermitilis is a bacterium species in the genus Streptomyces. The first complete genome sequence of S. avermitilis was completed in 2003.[4] This genome forms a chromosome with a linear structure, unlike most bacterial genomes, which exist in the form of circular chromosomes.[5] Avermectins are produced from S. avermitilis.[1] One of the most widely employed drugs against nematode and arthropod infestations is the avermectin derivative ivermectin, as well as abamectin, a widely used insecticide and antihelmintic. See also[edit]References[edit]
External links[edit]
"Streptomyces avermitilis". National Center for Biotechnology Information (NCBI). Honors and awards[edit]Scientific and academic[edit]
National[edit]
Membership in learned societies[edit]
Other[edit]
See also[edit]References[edit]
Astellas PharmaFrom Wikipedia, the free encyclopedia
Astellas Pharma Inc. (アステラス製薬株式会社 Asuterasu Seiyaku Kabushiki-gaisha?) is a Japanese pharmaceutical company, formed on 1 April 2005 from the merger of Yamanouchi Pharmaceutical Co., Ltd. (山之内製薬株式会社 Yamanouchi Seiyaku Kabushiki-gaisha?) and Fujisawa Pharmaceutical Co., Ltd. (藤沢薬品工業株式会社 Fujisawa Yakuhin Kōgyō Kabushiki-gaisha?). Astellas is a member of the Mitsubishi UFJ Financial Group (MUFJ) keiretsu. ContentsCompanies in the NBI must meet eligibility requirements, including minimum market capitalization, average daily trading volume, and seasoning as a public company, among other criteria. The index is evaluated semi-annually in May and November and serves as the basis for the iShares About History[edit]Early foundations[edit]Fujisawa Shoten was started in 1894 by Tomokichi Fujisawa in Osaka, and was renamed Fujisawa Pharmaceutical Co. in 1943. Yamanouchi Yakuhin Shokai was started in 1923 by Kenji Yamanouchi in Osaka. The company was renamed Yamanouchi Pharmaceutical Co. in 1940 and moved to Tokyo in 1942. Both companies started their overseas expansion at about the same time, opening offices in Taiwan in 1962 and 1963, respectively, and in the United States and Europe from 1977 onwards. Recent times & mergers[edit]Fujisawa acquired Lyphomed in 1990 and thereafter established its US R&D center in Deerfield, Illinois. Yamanouchi's R&D center in Leiderdorp was established with the acquisition of the pharmaceutical division of Royal Gist Brocades in 1991. Fujisawa and Yamanouchi combined in a "merger of equals," forming Astellas Pharma on 1 April 2005. At least some of its older products continue to be distributed under the original brand, ostensibly due to high brand-name recognition.[5] Astellas had a collaboration agreement with CoMentis from 2008 to 2014 focused on development of beta-secretase inhibitor therapeutics forAlzheimer's disease.[6] On June 9, 2010, Astellas acquired OSI Pharmaceuticals for $4.0 billion. In December 2014, Astellas expanded its 18-month-old collaboration with Cytokinetics, focussing on the R&D and commercialisation of skeletal muscle activators. The companies announced they will advance the development of CK-2127107 (a fast skeletal troponin activator) into Phase II clinical trials for the treatment of spinal muscular atrophy and possibly other neuromuscular conditions. The companies have extended their R&D program focussing on the discovery of additional skeletal sarcomere activators through into 2016. The collaboration is expected to generate more than $600 million for Cytokinetics as well as $75 million in milestone payments.[7] In November 2015 the company announced its move to acquire Ocata Therapeutics (formerly Advanced Cell Technology) for $379 million.[8] As of January 14, 2016, Astellas has not been able to acquire a majority of Ocata's common stock, which is necessary to complete the acquisition. The first deadline in the acquisition was November 17, 2015, and due to Astellas' failure to acquire a majority of Ocata's common stock, the deadline was extended to January 21, 2016. Many long-term stockholders have vowed to fight this acquisition by every legal means available to them, because they claim that the Astellas offer represents a huge discount - not a premium - to what they say is Ocata's true value. The deal was finally completed in February 2016.[9] [10] Later in November 2015 the company announce it would sell its dermatology business to LEO Pharma for $725 million.[11] In October 2016 Astellas announced it would acquire Ganymed Pharmaceuticals for $1.4 billion[12] Leo PharmaFrom Wikipedia, the free encyclopedia
Leo Pharma A/S is a multinational Danish pharmaceutical company, founded in 1908, with a presence in about 100 countries. Its headquarters are in Ballerup, near Copenhagen[2] The company is 100% integrated into a private foundation owned by the LEO Foundation.[3] Leo Pharma develops and markets products for dermatology, bone remodeling thrombosis and coagulation.[4] In 1945 it was the first producer of penicillin outside the USA and UK. ContentsHistory[edit]Formation & the 20th Century[edit]In 1908, pharmacists August Kongsted and Anton Antons bought the LEO Pharmacy in Copenhagen, Denmark. With the purchase, they established 'Københavns Løveapoteks kemiske Fabrik', today known as LEO Pharma. LEO Pharma celebrated its centennial in 2008. Flags bearing the LEO logo were flying in every country where LEO products are available, more than a hundred flags in total. Today, LEO Pharma has an ever growing pipeline with over 4,800 specialists focussing on dermatology and thrombosis.
21st Century & onwards[edit]In 2015, the company announced it would acquire Astellas Pharmas dermatology business for $725 million.[6] References[edit]
OSI PharmaceuticalsFrom Wikipedia, the free encyclopedia
OSI Pharmaceuticals, Inc. is an American pharmaceutical company based in Long Island, New York with facilities in Colorado, New Jersey and the United Kingdom. OSI specializes in the discovery and development of molecular targeted therapies. Thoughoncology is the top priority for OSI, research and development targeting type 2 diabetes and obesity is conducted through their U.K. subsidiary Prosidion Limited.[1][2] OSI has also made a foray into the ophthalmology market through a marketing agreement withPfizer over Macugen (Pegaptanib) for Age-related macular degeneration; however, acquisition of the firm Eyetech, meant to provide control over this product and diversify the company, has been unsuccessful, ending in divestiture.[5][6] In mid-2007, OSI's revenues were based primarily on proceeds from Tarceva sales (which are shared with Genentech andHoffmann–La Roche) and royalty payments related to dipeptidyl-peptidase IV inhibitor intellectual property.[5] On June 9, 2010, OSI was acquired by Japan-based, TSE-listed Astellas Pharma for $4.0 billion. ContentsTarceva[edit]See also: Erlotinib Tarceva (Erlotinib) was OSI's flagship and, as of 2007, only marketed product.[5][7] Tarceva is a small molecule inhibitor of theepidermal growth factor receptor (EGFR) and is the only EGFR inhibitor to have demonstrated the ability to improve overall survival in advanced non-small cell lung cancer and advanced pancreatic cancer.[1] Tarceva was discovered by Pfizer as CP-358774 (Moyer et al. Cancer Research, 1997, 57:4838), renamed OSI-774 when Pfizer was required to divest the compound in order to complete the buyout of Warner lambert/Parke-Davis and subsequently developed by OSI in conjunction with Genentech. See also[edit]
References[edit]
$$$$ Ocata TherapeuticsFrom Wikipedia, the free encyclopedia
Ocata Therapeutics (named Advanced Cell Technology, Incorporated (ACT) until November 2014)[4] is a biotechnologycompany located in Marlborough, Massachusetts, United States. The company specializes in the development and commercialization of cell therapies for the treatment of a variety of diseases. Ocata is primarily developing stem cell-based technologies, both adult and human embryonic, and other methods and treatments in the area of regenerative medicine.[5] In November 2015 the company announced it would be acquired by Astellas Pharma for $379 million,[6] which was finally completed in February 2016.[7] ContentsHistory[edit]Formed in 1994, the company was led from 2005 to late 2010 by William M. Caldwell IV, Chairman and Chief Executive Officer.[8]Upon Mr. Caldwell's death on December 13, 2010, Gary Rabin, a member of ACT's board of directors with experience in investment and capital raising, assumed the role of Chairman and CEO.[9] In 2007 the company's Chief Scientific Officer (CSO), Michael D. West, PhD, also founder of Geron (NASDAQ: GERN)[10] left Ocata to join a regenerative medicine firm, BioTime (NYSE MKT: BTX) as CEO. In 2008, for $250,000 plus royalties up to a total of $1 million, the company licensed its "ACTCellerate" technology to BioTime.[11] Robert Lanza was appointed CSO.[12] On November 22, 2010, the company announced that it had received approval from the U.S. Food and Drug Administration (FDA) to initiate the first human clinical trial usingembryonic stem cells to treat retinal diseases.[13] A preliminary report of the trial published in 2012,[14] and a follow-up article was published in February 2015.[15] In July 2014, Ocata announced that Paul K. Wotton, previously of Antares Pharma Inc (ATRS:NASDAQ CM), became President and Chief Executive Officer.[16] On August 27, 2014, Ocata announced a 1-100 reverse stock split of its common stock.[17] Ocata was listed on NASDAQ in February 2015.[18] Research[edit]Macular degeneration[edit]On November 30, 2010, Ocata filed an Investigational New Drug application with the U.S. FDA for the first clinical trial using embryonic stem cells to regenerate retinal pigment epithelium to treat Dry Age-Related Macular Degeneration (Dry AMD).[19] Dry AMD is the most common form of macular degeneration and represents a market size of $25–30 Billion in the U.S. and Europe.[20] Stargardt's disease[edit]In November 2010 the FDA allowed Ocata to begin a Phase I/II human clinical trial to use its retinal pigment epithelium cell therapy to treat Stargardt disease, a form of inherited juvenile macular degeneration.[21] See also[edit]References[edit]
External links[edit]Acquisition history[edit]The following is an illustration of the company's major mergers and acquisitions and historical predecessors (this is not a comprehensive list):
Business[edit]Astellas' franchise areas are urology, immunology (transplantation), dermatology, cardiology, and infectious disease. Priority areas for R&D are infectious diseases, diabetes,gastrointestinal diseases, oncology, and diseases of the central nervous system. Products[edit]Some of the key products produced by Astellas include:
Operations[edit]The company's headquarters are in Tokyo, with research centers in Tsukuba and Osaka. Clinical development is centered in Northbrook, Illinois and Leiden, Netherlands. Combined revenues of the two pre-merger companies were $7.9 billion in 2004. Worldwide the company employs about 17,000 people. The United States subsidiary of Astellas is Astellas US LLC.[13] The company's advertising slogans are: References[edit]
SuntoryFrom Wikipedia, the free encyclopedia
Suntory Holdings Limited (サントリーホールディングス株式会社 Santorī Hōrudingusu Kabushiki-Gaisha?) is a Japanese brewing and distilling company group. Established in 1899, it is one of the oldest companies in the distribution of alcoholic beverages in Japan, and makes Japanese whisky. Its business has expanded to other fields, and the company now also makes soft drinks and operates sandwich chains. With its 2014 acquisition of Beam, Inc., it has diversified internationally and become one of the largest makers of distilled beverages in the world. Suntory is headquartered in Dojimahama 2-chome, Kita-ku, Osaka, Osaka Prefecture. ContentsHistory[edit]
Suntory was started by Torii Shinjiro, who first opened his store Torii Shoten in Osaka on February 1, 1899, to sell imported wines. In 1907, the store began selling a sweet tasting red wine called Akadama Port Wine. The store became the Kotobukiya company in 1921 to further expand its business and in 1923, Torii Shinjiro built Japan's first malt whisky distillery Yamazaki Distillery. Production began in December 1924 and five years later Suntory Whisky Shirofuda (White Label), the first single malt whisky made in Japan, was sold. Due to shortages during World War II, Kotobukiya was forced to halt its development of new products, but in 1946 it re-released Torys Whisky, which sold well in post-war Japan. In 1961, Kotobukiya launched the "Drink Torys and Go to Hawaii" campaign. At the time, a trip abroad was considered a once-in-a-lifetime opportunity. In 1963, Kotobukiya changed its name to "Suntory", taken from the name of the whisky it produces. In the same year, Musashino Beer Factory began its production of the Suntory Beer. In 1997, the company becameJapan's sole bottler, distributor, and licensee of Pepsi products. On April 1, 2009, Suntory became a stockholding company named Suntory Holdings Limited (サントリーホールディングス株式会社?) and established Suntory Beverage and Food Limited (サントリー食品株式会社?), Suntory Products Limited (サントリープロダクツ株式会社?), Suntory Wellness Limited (サントリーウェルネス株式会社?), Suntory Liquors Limited (サントリー酒類株式会社?), Suntory Beer & Spirits Limited (サントリービア&スピリッツ株式会社?), Suntory Wine International Limited (サントリーワインインターナショナル株式会社?), and Suntory Business Expert Limited (サントリービジネスエキスパート株式会社?).[1] On July 14, 2009, Kirin announced that it was negotiating with Suntory on a merger.[2] On February 8, 2010, it was announced that negotiations between the two were terminated.[3] In 2009 they acquired Orangina, the orange soft drink for 300 billion yen, and Frucor energy drinks for 600 million euros.[4] On 2 July 2013 the company debuted on the Tokyo stock exchange and raised almost US$4 billion in the process.[5] In January 2014, Suntory announced an agreement to buy the largest U.S. bourbon producer, Beam Inc. for US$16 billion.[6] This deal would make Suntory the world's third largest spirits maker.[7] The acquisition was completed on April 30, 2014, when it was also announced that Beam would be renamed as Beam Suntory.[8][9] Also in January 2014, Suntory purchased the drinks division of British GlaxoSmithKline. This included the brands Lucozade and Ribena, however, the deal did not includeHorlicks.[10] Holdings[edit]
Joint ventures[edit]
From the early 1990s, Suntory has collaborated extensively with Melbourne biotechnology firm Florigene to genetically engineer the world's first true blue rose, a symbol often associated with the impossible or unattainable. In 1991, the team won the intense global race to isolate the gene responsible for blue flowers, and has since developed a range of genetically modified flowers expressing colors in the blue spectrum, as well as a number of other breakthroughs extending the vase life of cut flowers. In 2003, Suntory acquired a 98.5% equity holding in Florigene. Prior to this, Florigene had been a subsidiary of global agrochemicals giant Nufarm Limited since 1999. In July 2004, Suntory and Florigene scientists announced to the world the development of the first roses containing blue pigment, an important step toward the creation of a truly blue colored rose. In July 2011, Suntory Beverage and Food Limited together with PT GarudaFood from MNC Group in Indonesia have agreed to make a new firm to produce non-alcoholic drink with 51 percent and 49 percent shares respectively. It will produce Suntory Ooolong Tea, Boss and Orangina.[12] Media and advertising[edit]
Products[edit]
Alcoholic drinks[edit]
Soft drinks[edit]
Food for specified health uses[edit]The following drinks were approved as Food for Specified Health Uses (FOSHU).[13][14][15]
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Beam SuntoryFrom Wikipedia, the free encyclopedia (Redirected from Beam, Inc.)
Beam Suntory, Inc. is an American manufacturer of spirits headquartered in Deerfield, Illinois. It is a subsidiary of Suntory Beverage & Food Ltd, which itself is a subsidiary of Suntory Holdings of Osaka, Japan. The company'’s principal products include bourbon whiskey, tequila, Scotch whisky, Irish whiskey, Canadian whisky, vodka, cognac,rum, cordials, and ready-to-drink pre-mixed cocktails. As a distinct entity, the company was established as Beam Inc. on October 3, 2011, from the remainder of the Fortune Brandsholding company after it sold and divested various other product lines to form a business focused exclusively on spirits and directly related products.[2] On January 13, 2014, Suntory announced a deal to buy Beam Inc. for about $13.6 billion.[3] The acquisition was completed on April 30, 2014, for a final cost of about $16 billion – when it was also announced that Beam would become a subsidiary named "Beam Suntory".[4][5] Suntory Beverage & Food Ltd trades on the Tokyo Stock Exchange (2587). In March 2016, the company announced it would move its headquarters to the Merchandise Mart building on Chicago's Near North Side.[6] ContentsProducts[edit]The company's self-produced brands include the following:
The company sells its products to wholesale distributors, state governments, third party distributors, global or regional duty-free customers, other spirits producers, and joint ventures. In addition to brands produced directly by the company and its subsidiaries, it imports and markets some brands produced by others, such as the DeKuyper cordial. Additionally, Beam facilities produce spirits for brands owned by other companies, such as Calvert Extra blended whiskey, now owned by Luxco. The company also previously sold Harvey's Bristol Cream sherry, as well as brandys Fundador, Terry Centenario, Tres Cepas before selling these brands to Grupo Emperador Spain S.A., part of the Alliance Global Group.[7] Prior acquisitions[edit]On December 16, 2011, Beam Inc., agreed to buy the only independent Irish whiskey distiller that existed at the time, the Cooley Distillery, for $95 million.[8] On April 23, 2012, Beam announced it would acquire the Pinnacle vodka and Calico Jack rum brands for $600 million.[9] References[edit]
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InteractionToolsPrint/exportLanguages$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$ Lymphatic filariasisFrom Wikipedia, the free encyclopedia
Lymphatic filariasis, also known as elephantiasis,[2] is a human disease caused by parasitic worms known as filarial worms.[3]Most cases of the disease have no symptoms.[3] Some people, however, develop a syndrome called elephantiasis, which is marked by severe swelling in the arms, legs, or genitals.[3][4] The skin may also become thicker, and pain may occur. The changes to the body can cause social and economic problems for the affected person.[3] The worms are spread by the bites of infected mosquitoes. Three types of worms are known to cause the disease: Wuchereria bancrofti, Brugia malayi, and Brugia timori, with Wuchereria bancrofti being the most common. These worms damage thelymphatic system.[3] The disease is diagnosed by microscopic examination of blood collected during the night. The blood is typically examined as a smear after being stained with Giemsa stain. Testing the blood for antibodies against the disease may also permit diagnosis.[5] Other roundworms from the same family are responsible for river blindness.[6] Prevention can be achieved by treating entire groups in which the disease exists, known as mass deworming. This is done every year for about six years, in an effort to rid a population of the disease entirely. Medications used include antiparasitics such asalbendazole with ivermectin, or albendazole with diethylcarbamazine. The medications do not kill the adult worms but prevent further spread of the disease until the worms die on their own. Efforts to prevent mosquito bites are also recommended, including reducing the number of mosquitoes and promoting the use of bed nets.[3] Lymphatic filariasis is one of the main neglected tropical diseases and one of the four main worm infections.[6] More than 120 million people are infected with lymphatic filariasis and about 1.4 billion people are at risk of the disease in 73 countries. It is most common in tropical Africa and Asia. The disease results in economic losses of many billions of dollars a year.[3] ContentsSigns and symptoms[edit]The most spectacular symptom of lymphatic filariasis is elephantiasis, a stage 3 lymphedema with thickening of the skin and underlying tissues. This was the first mosquito-borne disease to be discovered.[7] Elephantiasis results when the parasites lodge in the lymphatic system and cause blockages to the flow of lymph. Infections usually begin inchildhood.[3] The skin condition the disease causes is called "elephantiasis tropica" (also known as "elephantiasis arabum").[8]:438 Elephantiasis mainly affects the lower extremities; the ears, mucous membranes, and amputation stumps are affected less frequently. However, various species of filarial worms tend to affect different parts of the body: Wuchereria bancrofti can affect the arms, breasts, legs, scrotum, and vulva (causing hydrocele formation), while Brugia timori rarely affects the genitals.[citation needed] Those who develop the chronic stages of elephantiasis are usually amicrofilaraemic and often have adverse immunological reactions to the microfilariaeas well as the adult worms.[citation needed] The subcutaneous worms present with skin rashes, urticarial papules, and arthritis, as well as hyper- and hypopigmentation macules. Onchocerca volvulus manifests itself in the eyes, causing "river blindness" (onchocerciasis), one of the leading causes of blindness in the world.[9] [10] Serous cavity filariasis presents with symptoms similar to subcutaneous filariasis, in addition to abdominal pain, because these worms are also deep-tissue dwellers.[citation needed] Elephantiasis leads to marked swelling of the lower half of the body.
Causes[edit]
Elephantiasis occurs in the presence of microscopic, thread-like parasitic worms such as Wuchereria bancrofti (the most common[3]), Brugia malayi, and Brugia timori (also known as B. timori), all of which are transmitted by bites from infected mosquitoes.[11] It is a type of helminth infection. Three types of worm cause the disease and damage the lymphatic system: The disease itself is a result of a complex interplay between several factors: the worm, the endosymbiotic Wolbachia bacteria within the worm, the host’s immune response, and the numerous opportunistic infections and disorders that arise. The adult worms only live in the human lymphatic system.[12] The parasite infects the lymph nodes and blocks the flow of lymph throughout the body; this results in chroniclymphedema, most often noted in the lower torso (typically in the legs and genitals).[13] Diagnosis[edit]The standard method for diagnosing active infection is by finding the microfilariae via microscopic examination.[14] This may be difficult, as in most parts of the world, microfilariae only circulate in the blood at night.[5][14] For this reason, the blood has to be collected nocturnally.[14]The blood sample is typically in the form of a thick smear and stained with Giemsa stain. Testing the blood serum for antibodies against the disease may also be used.[5] Prevention[edit]The World Health Organization recommends mass deworming—treating entire groups of people who are at risk with a single annual dose of two medicines, namely albendazole in combination with either ivermectin or diethylcarbamazine citrate.[15]With consistent treatment, since the disease needs a human host, the reduction of microfilariae means the disease will not be transmitted, the adult worms will die out, and the cycle will be broken.[16] In sub-Saharan Africa, albendazole (donated by GlaxoSmithKline) is being used withivermectin (donated by Merck & Co.) to treat the disease, whereas elsewhere in the world, albendazole is used with diethylcarbamazine.[17]Transmission of the infection can be broken when a single dose of these combined oral medicines is consistently maintained annually for a duration of four to six years.[15] Using a combination of treatments better reduces the number of microfilariae in blood. Avoiding mosquito bites, such as by using insecticide-treated mosquito bed nets, also reduces the transmission of lymphatic filariasis.[16][18] The Carter Center's International Task Force for Disease Eradication declared lymphatic filariaisis one of six potentially eradicable diseases.[16] According to medical experts, the worldwide effort to eliminate lymphatic filariasis is on track to potentially succeed by 2020.[19] For similar-looking but causally unrelated podoconiosis, international awareness of the disease will have to increase before elimination is possible. In 2011, podoconiosis was added to the World Health Organization's Neglected Tropical Diseases list, which was an important milestone in raising global awareness of the condition.[20] The efforts of the Global Programme to Eliminate LF are estimated to have prevented 6.6 million new filariasis cases from developing in children between 2000 and 2007, and to have stopped the progression of the disease in another 9.5 million people who had already contracted it.[21] Dr. Mwele Malecela, who chairs the programme, said: "We are on track to accomplish our goal of elimination by 2020."[19] In 2010, the WHO published a detailed progress report on the elimination campaign in which they assert that of the 81 countries with endemic LF, 53 have implemented mass drug administration, and 37 have completed five or more rounds in some areas, though urban areas remain problematic.[22] Treatment[edit]Treatments for lymphatic filariasis differ depending on the geographic location of the endemic area.[17] In sub-Saharan Africa, albendazole is being used with ivermectin to treat the disease, whereas elsewhere in the world, albendazole is used with diethylcarbamazine.[17] Geo-targeting treatments is part of a larger strategy to eventually eliminate lymphatic filariasis by 2020.[17] Additionally, surgical treatment may be helpful for issues related to scrotal elephantiasis and hydrocele. However, surgery is generally ineffective at correcting elephantiasis of the limbs.[citation needed] A vaccine is not yet available but in 2013 the University of Illinois was reporting 95% efficacity in testing against B. malayi in mice.[23] Treatment for podoconiosis consists of consistent shoe-wearing (to avoid contact with the irritant soil) and hygiene - daily soaking in water with an antiseptic (such as bleach) added, washing the feet and legs with soap and water, application of ointment, and in some cases, wearing elastic bandages.[24] Antibiotics are used in cases of infection.[25] Antibiotics[edit]The antibiotic doxycycline is effective in treating lymphatic filariasis.[26] Its drawbacks are that it requires a 4 to 6 weeks treatment and should not be used in young children and pregnant women, which prevent its use for mass prophyllaxis.[26] The parasites responsible for elephantiasis have a population of endosymbiotic bacteria, Wolbachia, that live inside the worm. When the symbiotic bacteria of the adult worms are killed by the antibiotic, they no longer provide chemicals which the nematode larvae need to develop, which either kill the larvae or prevent their normal development. This permanently sterilizes the adult worms, which additionally die within 1 or 2 years instead of after their normal 10 to 14 years lifespan.[27] Prognosis[edit]About 40 million people were disfigured or incapacitated by the disease in 2015.[28] Elephantiasis caused by lymphatic filariasis is one of the most common causes of disability in the world.[17] In endemic communities, approximately 10 percent of women can be affected with swollen limbs, and 50 percent of men can have mutilating genital disease.[17] In areas endemic for podoconiosis, prevalence can be 5% or higher.[29] Epidemiology[edit]
A 2012 report noted that lymphatic filariasis affected 120 million people[30] and one billion people at risk for infection.[31] It is consideredendemic in tropical and subtropical regions of Africa, Asia, Central and South America, and Pacific Island nations. In communities where lymphatic filariasis is endemic, as many as 10% of women can be afflicted with swollen limbs, and 50% of men can suffer from mutilating genital symptoms.[17] Filariasis is considered endemic in 73 countries; 37 of these are in Africa.
In many of these countries, considerable progress has been made towards elimination of filariasis. Elimination of the disease may have been achieved in several countries, but awaits official confirmation by the WHO.[when?] History[edit]Lymphatic filariasis is thought to have affected humans for about 4000 years.[32] Artifacts from ancient Egypt (2000 BC) and the Nok civilization in West Africa (500 BC) show possible elephantiasis symptoms. The first clear reference to the disease occurs in ancient Greek literature, wherein scholars differentiated the often similar symptoms of lymphatic filariasis from those of leprosy.[citation needed] The first documentation of symptoms occurred in the 16th century, when Jan Huyghen van Linschoten wrote about the disease during the exploration of Goa. Similar symptoms were reported by subsequent explorers in areas of Asia and Africa, though an understanding of the disease did not begin to develop until centuries later. In 1866, Timothy Lewis, building on the work of Jean Nicolas Demarquay (de) and Otto Henry Wucherer, made the connection between microfilariae and elephantiasis, establishing the course of research that would ultimately explain the disease. In 1876, Joseph Bancroft discovered the adult form of the worm. In 1877, the lifecycle involving an arthropod vector was theorized by Patrick Manson, who proceeded to demonstrate the presence of the worms in mosquitoes. Manson incorrectly hypothesized that the disease was transmitted through skin contact with water in which the mosquitoes had laid eggs. In 1900, George Carmichael Low determined the actual transmission method by discovering the presence of the worm in the proboscis of the mosquito vector.[32]
Research directions[edit]Researchers at the University of Illinois at Chicago (UIC) have developed a novel vaccine for the prevention of lymphatic filariasis. This vaccine has been shown to elicit strong, protective immune responses in mouse models of lymphatic filariasis infection. The immune response elicited by this vaccine has been demonstrated to be protective against bothW. bancrofti and B. malayi infection in the mouse model and may prove useful in the human.[34] On September 20, 2007, geneticists published the first draft of the complete genome (genetic content) of Brugia malayi, one of the roundworms which causes lymphatic filariasis.[35]This project had been started in 1994 and by 2000, 80% of the genome had been determined. Determining the content of the genes might lead to the development of new drugs and vaccines.[36] References[edit]
OnchocerciasisFrom Wikipedia, the free encyclopedia (Redirected from River blindness)
Onchocerciasis, also known as river blindness, is a disease caused by infection with the parasitic worm Onchocerca volvulus.[1] Symptoms include severe itching, bumps under the skin, and blindness.[1] It is the second most common cause of blindness due to infection, after trachoma.[2] The parasite worm is spread by the bites of a black fly of the Simulium type.[1] Usually, many bites are required before infection occurs.[3] These flies live near rivers, hence the name of the disease.[2] Once inside a person, the worms create larvae that make their way out to the skin.[1] Here, they can infect the next black fly that bites the person.[1] There are a number of ways to make the diagnosis including: placing a biopsy of the skin in normal saline and watching for the larva to come out, looking in the eye for larvae, and looking within the bumps under the skin for adult worms.[4] A vaccine against the disease does not exist.[1] Prevention is by avoiding being bitten by flies.[5] This may include the use ofinsect repellent and proper clothing.[5] Other efforts include those to decrease the fly population by spraying insecticides.[1]Efforts to eradicate the disease by treating entire groups of people twice a year is ongoing in a number of areas of the world.[1]Treatment of those infected is with the medication ivermectin every six to twelve months.[1][6] This treatment kills the larva but not the adult worms.[7] The antibiotic doxycycline weakens the worms by killing an associated bacterium called Wolbachia, and is recommended by some as well.[7] The lumps under the skin may also be removed by surgery.[6] About 17 to 25 million people are infected with river blindness, with approximately 0.8 million having some amount of loss of vision.[3][7] Most infections occur in sub-Saharan Africa, although cases have also been reported in Yemen and isolated areas ofCentral and South America.[1] In 1915, the physician Rodolfo Robles first linked the worm to eye disease.[8] It is listed by theWorld Health Organization as a neglected tropical disease.[9] ContentsSigns and symptoms[edit]Adult worms remain in subcutaneous nodules, limiting access to the host's immune system.[citation needed] Microfilariae, in contrast, are able to induce intense inflammatory responses, especially upon their death. Wolbachia species have been found to be endosymbionts of O. volvulus adults and microfilariae, and are thought to be the driving force behind most of O. volvulus morbidity. Dying microfilariae have been recently discovered to release Wolbachia surface protein that activates TLR2 and TLR4, triggering innate immune responses and producing the inflammation and its associated morbidity.[10] The severity of illness is directly proportional to the number of infected microfilariae and the power of the resultant inflammatory response.[11] Skin involvement typically consists of intense itching, swelling, and inflammation.[12] A grading system has been developed to categorize the degree of skin involvement:[13][14][verification needed]
Ocular involvement provides the common name associated with onchocerciasis, river blindness, and may involve any part of the eye from conjunctiva and cornea to uvea and posterior segment, including the retina and optic nerve.[12] The microfilariae migrate to the surface of the cornea. Punctate keratitis occurs in the infected area. This clears up as the inflammation subsides. However, if the infection is chronic, sclerosing keratitis can occur, making the affected area become opaque. Over time, the entire cornea may become opaque, thus leading to blindness. Some evidence suggests the effect on the cornea is caused by an immune response to bacteria present in the worms.[11] The skin is itchy, with severe rashes permanently damaging patches of skin. Mazzotti reaction[edit]Main article: Mazzotti Reaction The Mazzotti reaction, first described in 1948, is a symptom complex seen in patients after undergoing treatment of onchocerciasis with the medication diethylcarbamazine(DEC). Mazzotti reactions can be life-threatening, and are characterized by fever, urticaria, swollen and tender lymph nodes, tachycardia, hypotension, arthralgias, oedema, and abdominal pain that occur within seven days of treatment of microfilariasis. The phenomenon is so common when DEC is used that this drug is the basis of a skin patch test used to confirm that diagnosis. The drug patch is placed on the skin, and if the patient is infected with O. volvulus microfilaria, localized pruritus and urticaria are seen at the application site.[15] Nodding disease[edit]Main article: Nodding disease This is an unusual form of epidemic epilepsy associated with onchocerciasis.[16] This syndrome was first described in Tanzania by Louise Jilek-Aall, a Norwegian psychiatric doctor in Tanzanian practice, during the 1960s. It occurs most commonly in Uganda and South Sudan. It manifests itself in previously healthy 5–15-year-old children, is often triggered by eating or low temperatures and is accompanied by cognitive impairment. Seizures occur frequently and may be difficult to control. The electroencephalogram is abnormal but cerebrospinal fluid (CSF) and magnetic resonance imaging (MRI) are normal or show non-specific changes. If there are abnormalities on the MRI they are usually present in the hippocampus. Polymerase chain reaction testing of the CSF does not show the presence of the parasite. Classification[edit]Onchocerciasis causes different kinds of skin changes, which vary in different geographic regions; it may be divided into the following phases or types:[17]:440–441[verification needed]
Additionally, the various skin changes associated with onchocerciasis may be described as follows:[17]:440
Cause[edit]The cause is Onchocerca volvulus Life cycle[edit]The life of the parasite can be traced through the black fly and the human hosts in the following steps:[citation needed]
Prevention[edit]Various control programs aim to stop onchocerciasis from being a public health problem. The first was the Onchocerciasis Control Programme (OCP), which was launched in 1974, and at its peak, covered 30 million people in 11 countries. Through the use of larvicide spraying of fast-flowing rivers to control black fly populations, and from 1988 onwards, the use of ivermectin to treat infected people, the OCP eliminated onchocerciasis as a public health problem. The OCP, a joint effort of the World Health Organisation, the World Bank, the United Nations Development Programme, and the UN Food and Agriculture Organization, was considered to be a success, and came to an end in 2002. Continued monitoring ensures onchocerciasis cannot reinvade the area of the OCP.[19] In 1995, the African Programme for Onchocerciasis Control began covering another 19 countries, mainly relying upon the use of ivermectin. Its goal is to set up a community-directed supply of ivermectin for those who are infected. In these ways, transmission has declined.[20] In 2015, WHO was facilitating launch of an elimination program in Yemen. In 1992, the Onchocerciasis Elimination Programme for the Americas, which also relies on ivermectin, was launched.[21] On July 29, 2013, the Pan American Health Organization(PAHO) announced that after 16 years of efforts, Colombia had become the first country in the world to eliminate the parasitic disease onchocerciasis.[22] In September 2015, the Onchocerciasis Elimination Program for the Americas announced that onchocerciasis only remained in a remote region on the border of Brazil and Venezuela.[23][24] The area is home to the Yanomami indigenous people. The first countries to receive verification of elimination were Colombia in 2013, Ecuador in 2014, and Mexico in 2015.[25] Guatemala has submitted a request for verification. The key factor in elimination is mass administration of the antiparasitic drug ivermectin. The initial projection was that the disease would be eliminated from remaining foci in the Americas by 2012.[26] No vaccine to prevent onchocerciasis infection in humans is available. A vaccine to prevent onchocerciasis infection for cattle is in phase three trials. Cattle injected with a modified and weakened form of O. ochengi larvae have developed very high levels of protection against infection. The findings suggest that it could be possible to develop a vaccine that protects people against river blindness using a similar approach. Unfortunately, a vaccine to protect humans is still many years off.[citation needed] Treatment[edit]
In mass drug administration (MDA) programmes, the treatment for onchocerciasis is ivermectin (trade name: Mectizan); infected people can be treated with two doses of ivermectin, six months apart, repeated every three years. The drug paralyses and kills the microfilariae causing fever, itching, and possibly oedema, arthritis and lymphadenopathy. Intense skin itching is eventually relieved, and the progression towards blindness is halted. In addition, while the drug does not kill the adult worms, it does prevent them for a limited time from producing additional offspring. The drug therefore prevents both morbidity and transmission for up to several months. Ivermectin treatment is particularly effective because it only needs to be taken once or twice a year, needs no refrigeration, and has a wide margin of safety, with the result that it has been widely given by minimally trained community health workers.[27] Antibiotics[edit]For the treatment of individuals, doxycycline is used to kill the Wolbachia bacteria that live in adult worms. This adjunct therapy has been shown to significantly lower microfilarial loads in the host, and may have activity against the adult worms, due to the symbiotic relationship between Wolbachia and the worm.[28][29] In four separate trials over 10 years with various dosing regimens of doxycycline for individualized treatment, doxycycline was found to be effective in sterilizing the female worms and reducing their numbers over a period of four to six weeks. Research on other antibiotics, such as rifampicin, has shown it to be effective in animal models at reducing Wolbachia both as an alternative and as an adjunct to doxycycline.[30] However, doxycycline treatment requires daily dosing for at least four to six weeks, making it more difficult to administer in the affected areas.[27] Ivermectin[edit]Ivermectin kills the parasite by interfering with the nervous system and muscle function, in particular, by enhancing inhibitory neurotransmission. The drug binds to and activatesglutamate-gated chloride channels.[27] These channels, present in neurons and myocytes, are not invertebrate-specific, but are protected in vertebrates from the action of ivermectin by the blood–brain barrier.[27] Ivermectin is thought to irreversibly activate these channel receptors in the worm, eventually causing an inhibitory postsynaptic potential. The chance of a future action potential occurring in synapses between neurons decreases and the nematodes experience flaccid paralysis followed by death.[31][32][33] Ivermectin is directly effective against the larval stage microfilariae of O. volvulus; they are paralyzed and can be killed by eosinophils and macrophages. It does not kill adult females (macrofilariae), but does cause them to cease releasing microfilariae, perhaps by paralyzing the reproductive tract.[27] Ivermectin is very effective in reducing microfilarial load and reducing number of punctate opacities in individuals with onchocerciasis.[34] Epidemiology[edit]
About 37 million people are infected with this parasite;[35] about 300,000 of those had been permanently blinded.[36] As of 2008, about 99% of onchocerciasis cases occurred in Africa.[37] Onchocerciasis is currently endemic in 30 African countries, Yemen, and isolated regions of South America.[38] Over 85 million people live in endemic areas, and half of these reside in Nigeria. Another 120 million people are at risk for contracting the disease. Due to the vector’s breeding habitat, the disease is more severe along the major rivers in the northern and central areas of the continent, and severity declines in villages farther from rivers.[citation needed] Onchocerciasis was eliminated in the northern focus in Chiapas, Mexico,[39] and the focus in Oaxaca, Mexico, where Onchocerca volvulus existed, was determined, after several years of treatment with ivermectin, as free of the transmission of the parasite.[40] According to a 2002 WHO report, onchocerciasis has not caused a single death, but its global burden is 987,000 disability adjusted life years (DALYs). The severe pruritus alone accounts for 60% of the DALYs. Infection reduces the host’s immunity and resistance to other diseases, which results in an estimated reduction in life expectancy of 13 years.[38] History[edit]Onchocerca originated in Africa and was probably exported to the Americas by the slave trade, as part of the Columbian exchange that introduced other old world diseases such as yellow fever into the New World. Findings of a phylogenetic study in the mid-90s are consistent with an introduction to the New World in this manner. DNA sequences of savannah and rainforest strains in Africa differ, while American strains are identical to savannah strains in western Africa.[41] The microfilarial parasite that causes the disease was first identified in 1874 by an Irish naval surgeon, John O’Neill, who was seeking to identify the cause of a common skin disease along the west coast of Africa, known as “craw-craw”.[42] Rudolf Leuckart, a German zoologist, later examined specimens of the same filarial worm sent from Africa by a German missionary doctor in 1890 and named the organism Filaria volvulus.[43] Rodolfo Robles and Rafael Pacheco in Guatemala first mentioned the ocular form of the disease in the Americas about 1915. They described a tropical worm infection with adult Onchocerca that included inflammation of the skin, especially the face (‘erisipela de la costa’), and eyes.[44] The disease, commonly called the “filarial blinding disease”, and later referred to as “Robles disease”, was common among coffee plantation workers. Manifestations included subcutaneous nodules, anterior eye lesions, and dermatitis. Robles sent specimens to émile Brumpt, a French parasitologist, who named it O. caecutiens in 1919, indicating the parasite caused blindness (Latin “caecus” meaning blind).[45] The disease was also reported as being common in Mexico.[46] By the early 1920s, it was generally agreed that the filaria in Africa and Central America were morphologically indistinguishable and the same as that described by O’Neill 50 years earlier. Robles hypothesized that the vector of the disease was the day-biting black fly, Simulium. Scottish physician Donald Blacklock of the Liverpool School of Tropical Medicineconfirmed this mode of transmission in studies in Sierra Leone. Blacklock’s experiments included the re-infection of Simulium flies exposed to portions of the skin of infected subjects on which nodules were present, which led to elucidation of the life cycle of the Onchocerca parasite.[47] Blacklock and others could find no evidence of eye disease in Africa. Jean Hissette, a Belgian ophthalmologist, discovered in 1930 that the organism was the cause of a “river blindness” in the Belgian Congo.[48] Some of the patients reported seeing tangled threads or worms in their vision, which were microfilariae moving freely in the aqueous humor of the anterior chamber of the eye.[49] Blacklock and Strong had thought the African worm did not affect the eyes, but Hissette reported that 50% of patients with onchocerciasis near the Sankuru river in the Belgian Congo had eye disease and 20% were blind. Hisette Isolated the microfilariae from an enucleated eye and described the typical chorioretinal scarring, later called the “Hissette-Ridley fundus” after another ophthalmologist, Harold Ridley, who also made extensive observations on onchocerciasis patients in north west Ghana, publishing his findings in 1945.[50] Ridley first postulated that the disease was brought by the slave trade. The international scientific community was initially skeptical of Hisette’s findings, but they were confirmed by the Harvard African Expedition of 1934, led by Richard P. Strong, an American physician of tropical medicine.[51] Society and culture[edit]Since 1988, ivermectin has been provided free of charge for use in humans by Merck through the Mectizan donation program (MDP). The MDP works together with ministries of health and nongovernmental development organisations, such as the World Health Organization, to provide free ivermectin to those who need it in endemic areas.[52] In 2015 William C. Campbell and Satoshi ōmura were co-awarded half of that year's Nobel prize in Physiology or Medicine for the discovery of the avermectin family of compounds, the forerunner of ivermectin. The latter has come to decrease the occurrence of lymphatic filariasis and onchoceriasis.[53] Uganda's government, working with the Carter Center river blindness program since 1996, switched strategies for distribution of Mectizan. The male-dominated volunteer distribution system had "failed to take advantage of traditional kinship structures and roles." The program switched in 2014 from village health teams to community distributors, primarily selecting women with the goal of assuring that everyone in the circle of their family and friends received river blindness information and Mectizan.[54] Research[edit]Animal models for the disease are somewhat limited, as the parasite only lives in primates, but there are close parallels. Litomosoides sigmodontis , which will naturally infect cotton rats, has been found to fully develop in BALB/c mice. Onchocerca ochengi, the closest relative of O. volvulus, lives in intradermal cavities in cattle, and is also spread by black flies. Both systems are useful, but not exact, animal models.[55] A study of 2501 people in Ghana showed the prevalence rate doubled between 2000 and 2005 despite treatment, suggesting the parasite is developing resistance to the drug.[30][56][57] A clinical trial of another antiparasitic agent, moxidectin (manufactured by Wyeth), began on July 1, 2009 (NCT00790998).[58] A Cochrane review compared outcomes of people treated with ivermectin alone versus doxycycline plus ivermectin. While there were no differences in most vision-related outcomes between the two treatments, there was low quality evidence suggesting treated with doxycycline plus ivermectine showed improvement in iridocyclitis and punctate keratitis, over those treated with ivermectine alone.[59] See also[edit]
References[edit]
IvermectinFrom Wikipedia, the free encyclopedia
Ivermectin is a medication that is effective against many types of parasites.[1] It is used to treat head lice,[2] scabies,[3] river blindness,[4] strongyloidiasis,[5] and lymphatic filariasis, among others.[6] It can be either applied to the skin or taken by mouth. The eyes should be avoided.[2] Common side effects include red eyes, dry skin, and burning skin.[2] It is unclear if it is safe for use during pregnancy, but is likely acceptable for use during breastfeeding.[7] It is in the avermectin family of medications and works by causing an increase in permeability of cell membrane resulting in paralysis and death of the parasite.[2] Ivermectin was discovered in 1975 and came into medical use in 1981.[6][8] It is on the World Health Organization's List of Essential Medicines, the most important medications needed in a basic health system.[9] The wholesale cost in the developing world is about US$0.12 for a course of treatment.[10] In the United States it costs $25–50.[5] In other animals it is used to prevent and treat heartworm among other diseases.[1] ContentsMedical uses[edit]Ivermectin is a broad-spectrum antiparasitic agent, traditionally against parasitic worms. It is mainly used in humans in the treatment of onchocerciasis (river blindness), but is also effective against other worm infestations (such as strongyloidiasis,ascariasis, trichuriasis, filariasis and enterobiasis), and some epidermal parasitic skin diseases, including scabies. Ivermectin is currently being used to help eliminate river blindness (onchocerciasis) in the Americas, and to stop transmission oflymphatic filariasis and onchocerciasis around the world in programs sponsored by the Carter Center using ivermectin donated by Merck.[11][12][13] The disease is common in 30 African countries, six Latin American countries, and Yemen.[14] The drug rapidly kills microfilariae, but not the adult worms. A single oral dose of ivermectin, taken annually for the 10–15-year lifespan of the adult worms, is all that is needed to protect the individual from onchocerciasis.[15] Arthropod[edit]More recent evidence supports its use against parasitic arthropods and insects:
Rosacea[edit]An ivermectin cream has been approved by the FDA, as well as in Europe, for the treatment of inflammatory lesions of rosacea. The treatment is based upon the hypothesis that parasitic mites of the genus Demodex play a role in rosacea. In a clinical study, ivermectin reduced lesions by 83% over 4 months, as compared to 74% under a metronidazole standard therapy.[25][26][27] Contraindications[edit]Ivermectin is contraindicated in children under the age of five, or those who weigh less than 15 kilograms (33 pounds)[28] and those who are breastfeeding, and have a hepatic or renal disease.[29] Side effects[edit]The main concern is neurotoxicity, which in most mammalian species may manifest as central nervous system depression, and consequent ataxia, as might be expected from potentiation of inhibitory GABA-ergic synapses. Dogs with defects in the P-glycoprotein gene (MDR1), often collie-like herding dogs, can be severely poisoned by ivermectin. Since drugs that inhibit CYP3A4 enzymes often also inhibit P-glycoprotein transport, the risk of increased absorption past the blood-brain barrier exists when ivermectin is administered along with other CYP3A4 inhibitors. These drugs include statins, HIV protease inhibitors, many calcium channel blockers, and glucocorticoids such as dexamethasone, lidocaine, and the benzodiazepines.[30] For dogs, the insecticide spinosad may have the effect of increasing the potency of ivermectin.[31] Pharmacology[edit]Pharmacodynamics[edit]Ivermectin and other avermectins (insecticides most frequently used in home-use ant baits) are macrocyclic lactones derived from the bacterium Streptomyces avermitilis. Ivermectin kills by interfering with nervous system and muscle function, in particular by enhancing inhibitory neurotransmission. The drug binds to glutamate-gated chloride channels (GluCls) in the membranes of invertebrate nerve and muscle cells, causing increased permeability to chloride ions, resulting in cellular hyper-polarization, followed by paralysis and death.[2][32] GluCls are invertebrate-specific members of the Cys-loop family of ligand-gated ion channels present in neuronsand myocytes. Pharmacokinetics[edit]Ivermectin can be given either by mouth or injection. It does not readily cross the blood–brain barrier of mammals due to the presence of P-glycoprotein,[33] (the MDR1 gene mutation affects function of this protein). Crossing may still become significant if ivermectin is given at high doses (in which case, brain levels peak 2–5 hr after administration). In contrast to mammals, ivermectin can cross the blood–brain barrier in tortoises, often with fatal consequences. Ecotoxicity[edit]Field studies have demonstrated the dung of animals treated with ivermectin supports a significantly reduced diversity of invertebrates, and the dung persists longer.[34] History[edit]The discovery of the avermectin family of compounds, from which ivermectin is chemically derived, was made by Satoshi ōmura of Kitasato University, Tokyo and William C. Campbell of the Merck Institute for Therapeutic research. ōmura identified avermectin from the bacterium Streptomyces avermitilis. Campbell purified avermectin from cultures obtained from ōmura and led efforts leading to the discovery of ivermectin, a derivative of greater potency and lower toxicity.[35] Ivermectin was introduced in 1981.[36] Half of the 2015 Nobel Prize in Physiology or Medicine was awarded jointly to Campbell and ōmura for discovering avermectin, "the derivatives of which have radically lowered the incidence of river blindness and lymphatic filariasis, as well as showing efficacy against an expanding number of other parasitic diseases".[37] Brand names[edit]It is sold under brand names Heartgard, Sklice[38] and Stromectol[39] in the United States, Ivomec worldwide by Merial Animal Health, Mectizan in Canada by Merck, Iver-DT[40] in Nepal by Alive Pharmaceutical and Ivexterm in Mexico by Valeant Pharmaceuticals International. In Southeast Asian countries, it is marketed by Delta Pharma Ltd. under the trade name Scabo 6. While in development, it was assigned the code MK-933 by Merck.[41] Veterinary use[edit]In veterinary medicine ivermectin is used against many intestinal worms (but not tapeworms), most mites, and some lice. Despite this, it is not effective for eliminating ticks, flies, flukes, or fleas. Eggs and larvae mature and come back to the host. It is effective against larval heartworms, but not against adult heartworms, though it may shorten their lives. The dose of the medicine must be very accurately measured as it is very toxic in over-dosage. It is sometimes administered in combination with other medications to treat a broad spectrum of animal parasites. Some dog breeds (especially the Rough Collie, the Smooth Collie, the Shetland Sheepdog, and the Australian Shepherd), though, have a high incidence of a certain mutation within the MDR1 gene (coding for P-glycoprotein); affected animals are particularly sensitive to the toxic effects of ivermectin.[42][43] Clinical evidence suggests kittens are susceptible to ivermectin toxicity.[44] A 0.01% ivermectin topical preparation for treating ear mites in cats (Acarexx) is available. Ivermectin is sometimes used as an acaricide in reptiles, both by injection and as a diluted spray. While this works well in some cases, care must be taken, as several species of reptiles are very sensitive to ivermectin. Use in turtles is particularly contraindicated. Research[edit]Ivermectin is also being studied as a potential antiviral agent against the viruses chikungunya and yellow fever.[45] A 2012 Cochrane review found weak evidence suggesting that ivermectin could result in the reduction of chorioretinal lesions and prevent loss of vision in people withonchocerciasis.[46] See also[edit]Notes and references[edit]
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