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发帖数: 548 | 1 12月27日 为什么我要替中国辩护
我要替中国辩护，并不是因为我是一个中国人，而是因为我知道中国就和这世界上绝大
数的国家一样，虽然有很多丑陋的现象，但是他们是受害者。就
象这个犯罪集团里很多的人一样，他们来自各种种族，他们可能充当了工具，但他们不
是制造这一切，谋划这一切的人。虽然经常会暴露中国产品出现问题。但要知道中国是
世界工厂，他们只是打工者，他们只是按照各种雇主提供的配方来生产，他们并不知道
他们会产生怎样的后果。或者这些工人知道后果，但他们只是奴隶，他们又如何去改变
这一切？ 所以，当我的调查不断往前推进的时候，不可避免地会涉及各国的企业，但
这并不表明是针对这个国家或这个国家的人民，而是针对一种社会现实和丑陋现象。就
拿菲律宾来说，菲律宾是一个犯罪猖獗的国家，有很多犯罪分子，但是菲律宾人民却是
这个集团的受害者，他们／她们被绑架，沦为了牺牲品，人体实验对象。一个日本人，
强奸上千名菲律宾女孩，却没有受到惩罚。以前我也提到过，有20个国家的名单，这20
个国家的人民其实都是受害者。现在他们把矛头对准中国，或许仅仅是因为我揭示了他
们图害世界人民的内幕，而我是一个中国人的缘故。对于这样狭隘心态的集团，它值得
任何人追随吗？ 我看文章说，川普视中国为敌人，如果川普真有这样的论调，那么我
很遗憾，只能说明川普是一个种族分子，已经沦为利益集团的代言人，他将不代表美国
人民的利益。就连这些人24小时攻击我，谋害我。我从来也没有说过美国，日本是我的
敌人。因为我还没有把这些犯罪集团，军阀集团等同于这些国家和这些国家的人民。普
通的群众，种族，宗教分子很容易被煽动。对着他们，我总是有着错综复杂的感觉。他
们是受害者，他们是被屠杀者，但他们又缺乏认知，他们容易被操纵，沦为帮凶和工具
。我们的任务就是唤醒人类善良的一面，教育人民，引导他们走正确的道路。从这一点
来说，我是不赞成那种不分青红皂白的屠杀。是不是日本军阀，黑社会集团制造病毒，
伤害人类，我们就应该不分是非，以牙还牙地针对整个日本人民？ 或者一个巴西人，
西班牙人，意大利人犯了罪，我们就应该针对他们整个种族？ 也或者您曾经被一个华
人所伤害，您就要屠杀整体华人？ 这正是我从这个犯罪集团身上看到的现象，肆无忌
惮地屠杀无辜，没有善恶标准。完全被个人情感，个人仇恨所驱使。这不是我要宣扬的
理念，如果滥杀无辜，不分是非，我们就不能最大限度地团结世界人民，对抗邪恶，就
没有力量争取他们的集团内部分裂，争取那些被奴役的奴隶起义，摧毁这个罪恶的系统
。我刚才在网上还看到一则消息说，以色列和很多国家断绝外交联系，这是非常狭隘观
念的一种表现。我的调查显示，当日本或其他犯罪集团企图掠夺企业或财富的时候，经
常都会采取各种手段去搞垮目标企业，比如说，如果是食品企业，就会污染其产品。其
他的企业也是如此。我们经常也会看到报道，有人拉了上百吨垃圾故意倾倒在中国的水
源处，这显然是一种敌对势力作为，对于这种刻意污染环境，伤害人类的行为，判处死
刑也不为过。来源于中国的产品问题，指使者未必就是中国。除了犯罪分子在各国都会
出现外，是各国人民都需要面对的问题外。我没有看到中国人民是个记仇的国家，对某
一个国家特别仇恨，会产生象日本军阀集团或其他西方犯罪集团灭绝其他种族的刻意伤
害人类的行为。况且中国和以色列也没有什么特别的矛盾。当然被暂停外交关系有很多
国家，但我认为以色列这种行为是一种狭隘的表现，会孤立自己。中国不是世界的敌人
，美日的军事犯罪集团才是世界的敌人，这些跨国集团的大药厂才是世界的敌人，他们
为了掠夺财富，肆无忌惮地散播病毒，在食品里，生活用品里添加有害物资，他们对人
类的伤害，以亿万为单位。他们如此大面积地伤害人类，是不是推动了医学的进步？
至少从我的观察，不是如此，几十年来，我没有看到有任何的进步，只有伤害，他们用
的是同一种手段，唯一的战略目的就是掠夺财富，权利，杀害异己，伤害人类。多少个
家庭在他们的伤害下，妻离子散，痛苦一生。你们身上很多的病痛都有可能是他们制造
的。所以，中国，还有世界，已经到了拨乱反正的时候了。我们的敌人，是这些特定的
犯罪集团，而不是某一个特定的种族或者某一个国家。我们反对那种狭隘的种族观，我
们反对操纵仇恨的势力，我们要争取这个世界所有善良的人，良知未泯的人一起携手前
行。这里也包括所有的美国人，日本人，想一想，如果你是那个受害者，你是什么感觉
。己所不欲，勿施于人！ 这是我对你们的劝告。停止屠杀受害者！ 其实中国国企的
收购往往显示和这个犯罪集团相反的趋势，这个犯罪集团是用各种手段摧毁目标企业，
压低买价。而中国往往是高价收购，因为这不是他们的企业，他们往往为了区区的一点
个人利益，而浪费了国家的钱财，企业的利益，这就是腐败。所以，中国就应该设立特
别的监管机构，审查各种国企收购，让这种腐败更难实行。
说到言论自由，我特别痛恨美国日本的犯罪集团，他们控制我的计算机，抹掉，阻碍我
的发言。他们根本没有资格抨击中国，因为他们就是世界上最大的黑客。他们攻进各国
的金融系统，然后嫁祸于人。而且，我知道，日本或其他犯罪集团下一个目标就是控制
苹果计算机，日本已经收购了很多供应苹果零件的供应商，就差直接控制苹果企业了。
难道日本军阀企业在世界的作为和势力，你们不感到威胁？ 不仔细审查。到烘染中国
的威胁？ 显然你们的判断力有问题。
Filariasis
From Wikipedia, the free encyclopedia
Filariasis
Life cycle of Wuchereria bancrofti, a parasite that causes filariasis
Classification and external resources
Specialty Infectious disease
ICD-10 B74
ICD-9-CM 125.0-125.9
Patient UK Filariasis
MeSH D005368
[edit on Wikidata]
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:
Lymphatic filariasis is caused by the worms Wuchereria bancrofti, Brugia
malayi, and Brugia timori. These worms occupy the lymphatic system,
including the lymph nodes; in chronic cases, these worms lead to the
syndrome of elephantiasis.
Subcutaneous filariasis is caused by Loa loa (the eye worm), Mansonella
streptocerca, and Onchocerca volvulus. These worms occupy the subcutaneous
layer of the skin, in the fat layer. L. loa causes Loa loa filariasis, while
O. volvuluscauses river blindness.
Serous cavity filariasis is caused by the worms Mansonella perstans and
Mansonella ozzardi, which occupy the serous cavity of the abdomen.
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.
Contents
1Signs and symptoms
2Cause
3Diagnosis
3.1Concentration methods
4Treatment
5Society and culture
5.1Research teams
6Other animals
6.1Cattle
6.2Horses
6.3Dogs
7See also
8References
9Further reading
10External links
Signs 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]
This section needs additional citations for verification. Please help
improve this article by adding citations to reliable sources. Unsourced
material may be challenged and removed. (May 2010) (Learn how and when to
remove this template message)
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]
Verminous hemorrhagic dermatitis is a clinical disease in cattle due to
Parafilaria bovicola.
Intradermal onchocerciasis of cattle results in losses in leather due to
Onchocerca dermata, O. ochengi, and O. dukei. O. ochengi is closely related
to human O. volvulus(river blindness), sharing the same vector, and could be
useful in human medicine research.
Stenofilaria assamensis and others cause different diseases in Asia, in
cattle and zebu.
Horses[edit]
"Summer bleeding" is hemorrhagic subcutaneous nodules in the head and upper
forelimbs, caused by Parafilaria multipapillosa (North Africa, Southern and
Eastern Europe, Asia and South America).[14]
Dogs[edit]
Heart filariasis is caused by Dirofilaria immitis.
See also[edit]
Neglected diseases
Eradication of infectious diseases
Helminthiasis
List of parasites (human)
References[edit]
^ Center for Disease Control and Prevention. "Lymphatic Filariasis".
Retrieved 18 July2010.
^ a b "Lymphatic filariasis". Health Topics A to Z. Source: The World Health
Organization. Retrieved 2013-03-24.
^ "Seva Fila" (PDF). JB Tropical Disease Research Centre & Department of
Biochemistry, Mahatma Gandhi Institute of Medical Sciences.
^ a b The Carter Center, Lymphatic Filariasis Elimination Program,
retrieved2008-07-17
^ U.S. Centers for Disease Control, Lymphatic Filariasis Treatment,
retrieved2008-07-17
^ Bockarie, Moses; Hoerauf, Achim; Taylor, Mark J. (08 October 2010). "
Lymphatic filariasis and onchocerciasis". The Lancet. 376 (9747): 1175-1185.
Check date values in: |date= (help);
^ Turkington, Carol A. "Filariasis". The Gale Encyclopedia of Public Health.
1: 351-353.
^ Hewitt, Kirsten; Whitworth, James AG (1 August 2005). "Filariasis".
Medicine. 33 (8): 61–64.
^ Gaur RL, Dixit S, Sahoo MK, Khanna M, Singh S, Murthy PK (2007). "Anti-
filarial activity of novel formulations of albendazole against experimental
brugian filariasis".Parasitology. 134: 537–44. doi:10.1017/
S0031182006001612. PMID 17078904.
This article relies too much on references to primary sources. Please
improve this by adding secondary or tertiary sources. (October 2015) (Learn
how and when to remove this template message)
^ Hoerauf A, Mand S, Fischer K, Kruppa T, Marfo-Debrekyei Y, Debrah AY,
Pfarr KM, Adjei O, Buttner DW (2003), "Doxycycline as a novel strategy
against bancroftian filariasis-depletion of Wolbachia endosymbionts from
Wuchereria bancrofti and stop of microfilaria production", Med Microbiol
Immunol (Berl), 192 (4): 211–6,doi:10.1007/s00430-002-0174-6, PMID 12684759
^ Bockarie, Moses; Hoerauf, Achim; Taylor, Mark J. (8 October 2010). "
Lymphatic filariasis and onchocerciasis". The Lancet. 376 (9747): 1178.
^ Taylor MJ, Makunde WH, McGarry HF, Turner JD, Mand S, Hoerauf A (2005), "
Macrofilaricidal activity after doxycycline treatment of Wuchereria
bancrofti: a double-blind, randomised placebo-controlled trial", Lancet, 365
(9477): 2116–21,doi:10.1016/S0140-6736(05)66591-9, PMID 15964448
This article relies too much on references to primary sources. Please
improve this by adding secondary or tertiary sources. (October 2015) (Learn
how and when to remove this template message)
^ Jan Andersson; Hans Forssberg; Juleen R. Zierath; The Nobel Assembly at
Karolinska Institutet (5 October 2015), Avermectin and Artemisinin -
Revolutionary Therapies against Parasitic Diseases (PDF), retrieved 5
October 2015
^ Pringle, Heather (3 March 2011), The Emperor and the Parasite, retrieved 9
March2011
Further reading[edit]
"Special issue", Indian Journal of Urology, 21 (1), 2005
"Filariasis". Therapeutics in Dermatology. June 2012. Retrieved 24 July 2012.
External links[edit]
Wikimedia Commons has media related to Filariasis.
Filariasis Research at the University of Tuebingen
The Carter Center Lymphatic Filariasis Elimination Program
UK Health Charity working to cure and prevent Lymphatic filariasis
Brugia malayi Filarial worms. Video by R. Rao. Washington University in St.
Louis
Page from the "Merck Veterinary Manual" on "Parafilaria multipapillosa" in
horses
v
t
e
Infectious diseases
Parasitic disease: helminthiases
B65–B83
120–129
$$$$$$$$$$$$$$$$$$$$$
Satoshi ōmura
From Wikipedia, the free encyclopedia
Satoshi ōmura
Satoshi ōmura, Nobel Laureate in medicine in Stockholm December 2015
Native name 大村 智
Born 12 July 1935 (age 81)
Nirasaki, Yamanashi, Japan
Nationality Japanese
Fields Biochemistry
Institutions Kitasato University
Wesleyan University
Alma mater University of Yamanashi
Tokyo University of Science(M.S., Sc. D.)
University of Tokyo (Ph.D.)
Academic advisors Koji Nakanishi
Max Tishler
Known for Avermectin and Ivermectin
Notable awards Japan Academy Prize (1990)
Koch Gold Medal (1997)
Gairdner Global Health Award(2014)
Nobel Prize in Physiology or Medicine (2015)
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.
Contents
1Education
2Career
3Honors and awards
3.1Scientific and academic
3.2National
3.3Membership in learned societies
3.4Other
4See also
5References
6External links
Education[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 avermitilis
From Wikipedia, the free encyclopedia
Streptomyces avermitilis
Scientific classification
Kingdom: Bacteria
Phylum: Actinobacteria
Class: Actinobacteria
Order: Actinomycetales
Family: Streptomycetaceae
Genus: Streptomyces
Species: S. avermitilis
Binomial name
Streptomyces avermitilis
(ex Burg[1] et al. 1979) Kim andGoodfellow 2002[2]
Strains
Streptomyces avermitilis MA-4680
Synonyms
Streptomyces avermectiniusTakahashi et al. 2002[3]
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]
List of Streptomyces species
References[edit]
^ a b Burg, R. W.; Miller, B. M.; Baker, E. E.; Birnbaum, J.; Currie, S. A.;
Hartman, R.; Kong, Y. L.; Monaghan, R. L.; Olson, G.; Putter, I.; Tunac, J.
B.; Wallick, H.; Stapley, E. O.; Oiwa, R.; Omura, S. (1979). "Avermectins,
new family of potent anthelmintic agents: Producing organism and
fermentation". Antimicrobial Agents and Chemotherapy. 15 (3): 361–367. doi:
10.1128/AAC.15.3.361. PMC 352666. PMID 464561.
^ Kim, S. B.; Goodfellow, M. (2002). "Streptomyces avermitilis sp. nov., nom
. Rev., a taxonomic home for the avermectin-producing streptomycetes".
International Journal of Systematic and Evolutionary Microbiology. 52 (Pt 6)
^ Takahashi, Y.; Matsumoto, A.; Seino, A.; Ueno, J.; Iwai, Y.; Omura, S. (
2002). "Streptomyces avermectinius sp. nov., an avermectin-producing strain"
. International Journal of Systematic and Evolutionary Microbiology. 52 (Pt
6): 2163–2168. doi:10.1099/ijs.0.02237-0. PMID 12508884.
^ Ikeda H, Ishikawa J, Hanamoto A, Shinose M, Kikuchi H, Shiba T, Sakaki Y,
Hattori M, Omura S (2003). "Complete genome sequence and comparative
analysis of the industrial microorganism Streptomyces avermitilis". Nat.
Biotechnol. 21 (5): 526–531. doi:10.1038/nbt820.PMID 12692562.
^ Paul Dyson (1 January 2011). Streptomyces: Molecular Biology and
Biotechnology. Horizon Scientific Press. p. 5. ISBN 978-1-904455-77-6.
Retrieved 16 January 2012.
External links[edit]
Wikispecies has information related to: Streptomyces avermitilis
"Streptomyces avermitilis". National Center for Biotechnology Information (
NCBI).
Honors and awards[edit]
Scientific and academic[edit]
1985 – Hoechst-Roussel Award[4]
1986 – The Pharmaceutical Society of Japan Award[4]
1988 – Uehara Prize[4]
1990 – Japan Academy Prize (academics)[4]
1995 – Fujiwara Prize[4]
1997 – Robert Koch Gold Medal[5]
1998 – Prince Mahidol Award[4]
2000 – Nakanishi Prize (American Chemical Society and Chemical Society of
Japan)[4]
2005 – Ernest Guenther Award in the Chemistry of Natural Products (American
Chemical Society)[4]
2007 – Hamao Umezawa Memorial Award[4]
2010 – Tetrahedron Prize for Creativity in Organic Chemistry[4]
2011 – Arima Award[4]
2014 – Canada Gairdner Global Health Award[6]
2015 – Nobel Prize in Physiology or Medicine
National[edit]
1992 – Medal with Purple Ribbon[4]
2011 – Order of the Sacred Treasure, Gold and Silver Star[7]
2012 – Person of Cultural Merit[4]
Membership in learned societies[edit]
1992 – Academy of Sciences Leopoldina[8]
1999 – National Academy of Sciences[9]
2001 – Japan Academy[10]
2002 – Académie des sciences[11]
Other[edit]
2008 – Knight of the Legion of Honour of France
See also[edit]
List of Japanese Nobel laureates
Merck & Co.
Koji Nakanishi
Tohru Fukuyama
Kitasato Shibasaburō
References[edit]
^ a b "Satoshi Omura PhD". Retrieved 5 October 2015.
^ http://www.nobelprize.org/nobel_prizes/medicine/laureates/2015/press.pdf
^ "Japanese microbiologist Satoshi Omura shares Nobel Prize for medicine".
The Japan Times. 5 October 2015. Retrieved 5 October 2015.
^ a b c d e f g h i j k l m Satoshi ōmura. "Satoshi ōmura Curriculum Vitae
" (PDF).
^ "Robert Koch Gold Medal". Robert-Koch-Stiftung e.V. Retrieved 2015-10-05.
^ http://www.gairdner.org/content/satoshi-omura
^ 【政府】11年「春の叙勲」┥锸悉诵裰亍⒋蟠迨悉鹬薬事日報 2011年6月20日
^ List of Members | Prof. Dr. Dr. Satoshi ōmura
^ Member Directory | Satoshi Omura
^ Japan Academy membership profile
^ Académie des sciences membership profile
Astellas Pharma
From Wikipedia, the free encyclopedia
Astellas Pharma Inc.
Type Public KK
Traded as
TYO: 4503
TOPIX 100 Component
Nikkei 225 Component
Industry Pharmaceutical
Predecessors Yamanouchi Pharmaceutical
Fujisawa Pharmaceutical
(Merged in 2005)
Founded 2005; 11 years ago
Headquarters 2-5-1, Nihonbashi-Honcho, Chūō-ku, Tokyo 103-8411, Japan
Key people Yoshihiko Hatanaka
(President and CEO)
Products
Prograf
Harnal
Vesicare
Funguard/Mycamine
Protopic
and other pharmaceuticals
Revenue US$11,060,000,000 (FY 2013)
Profit US$1,280,000,000 (￥1,139,000,000,000) (FY 2013)
Total assets $14.86 billion (2016)[1]
Number of employees 17,649 (consolidated as of March 2014)
Subsidiaries Astellas US
Website Official website
Footnotes / references
[2][3][4]
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.
Contents
1History
1.1Early foundations
1.2Recent times & mergers
1.3Acquisition history
2Business
2.1Products
3Operations
4References
5External links
SOUTH SAN FRANCISCO, Calif., Dec. 16, 2016 (GLOBE NEWSWIRE) -- Cytokinetics
(Nasdaq:CYTK) today announced it has been selected for addition to the
Nasdaq Biotechnology Index (Nasdaq:NBI). The addition will take effect as
part of the annual re-ranking of the NBI upon market open on Monday,
December 19, 2016.
Companies 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 NASDAQ
Biotechnology Index Fund. The Index is designed to track the performance of
a set of securities listed on the NASDAQ Stock Market that are classified as
either biotechnology or pharmaceutical according to the Industry
Classification Benchmark (ICB). For more information about the NASDAQ
Biotechnology Index, including eligibility criteria, visithttps://indexes.
nasdaqomx.com.
About Cytokinetics
Cytokinetics is a late-stage biopharmaceutical company focused on
discovering, developing and commercializing first-in-class muscle activators
as potential treatments for debilitating diseases in which muscle
performance is compromised and/or declining. As a leader in muscle biology
and the mechanics of muscle performance, the company is developing small
molecule drug candidates specifically engineered to increase muscle function
and contractility. Cytokinetics’ lead drug candidate is tirasemtiv, a fast
skeletal muscle troponin activator, for the potential treatment of ALS.
Tirasemtiv has been granted orphan drug designation and fast track status by
the U.S. Food and Drug Administration and orphan medicinal product
designation by the European Medicines Agency for the potential treatment of
ALS. Cytokinetics retains the right to develop and commercialize tirasemtiv,
subject to an option held by Astellas Pharma Inc. Cytokinetics is also
collaborating with Astellas to develop CK-2127107, a fast skeletal muscle
activator, for the potential treatment of spinal muscular atrophy, chronic
obstructive pulmonary disease and ALS.Cytokinetics is collaborating with
Amgen Inc. to develop omecamtiv mecarbil, a novel cardiac muscle activator,
for the potential treatment of heart failure. Amgen holds an exclusive
license worldwide to develop and commercialize omecamtiv mecarbil and
Astellas holds an exclusive license worldwide to develop and commercialize
CK-2127107. Both licenses are subject toCytokinetics' specified development
and commercialization participation rights. For additional information about
Cytokinetics, visit http://www.cytokinetics.com/.
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 Pharma
From Wikipedia, the free encyclopedia
Leo Pharma A/S
Type Aktieselskab A/S Danish Public Limited stock based corporation
Industry Pharmaceutical industry
Founded 1908
Founder August Kongsted and Anton Antons
Headquarters Ballerup, Copenhagen,Denmark
Area served Worldwide
Key people Gitte Aabo (CEO)
Products Prescription drugs fordermatology, bone remodelingthrombosis and
coagulation
Revenue 7.973 billion DKK (2014)[1]
Total assets 31.627 billion DKK (2014)[1]
Number of employees 4,712 (2014)[1]
Website Home Page
Footnotes / references
Wholly owned by a foundation (nonprofit)
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.
Contents
1History
1.1Formation & the 20th Century
1.221st Century & onwards
2References
History[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 'Kø
;benhavns 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.
1912 – The company launched its own Aspirin headache tablet
1917 – The company exported Denmarks first drug, Digisolvin
1940 – The company launched its own Heparin product.
1958-08-13 - Patent filed for Bendrofluazide.[5]
1962 – The company launched Fucidin to be used to treat staphylococcus
infections
21st Century & onwards[edit]
In 2015, the company announced it would acquire Astellas Pharmas dermatology
business for $725 million.[6]
References[edit]
^ a b c http://www.leo-pharma.com/Files/Filer/LEO_corporate_downloads/LEO_Pharma_Annual_Report_2014_FINAL_Web.pdf
^ Leo Pharma A/S published list of products
^ "About us - LEO Pharma". leo-pharma.com.
^ Highbeam news clipping service, UK
^ GB 863474
^ "LEO Pharma Buys Astellas' Dermatology Business for $725M". GEN.
OSI Pharmaceuticals
From Wikipedia, the free encyclopedia
This article relies too much on references to primary sources. Please
improve this by adding secondary or tertiary sources.(June 2014) (Learn how
and when to remove this template message)
OSI Pharmaceuticals, Inc.
Shaping Medicine, Changing Lives[1]
Type Subsidiary
Industry Pharmaceutical[2]
Founded 1983
Headquarters Melville, New York
Key people Colin Goddard, CEO
Michael G. Atieh, CFO
Robert A. Ingram, Chairman[2]
Products Biopharmaceuticals
Biotherapeutics
Revenue $375.7 MillionUSD(2006)[3]
Net income $-582.2 Million USD(2006)[3]
Number of employees 554 (2007-02)[4]
Parent Astellas Pharma (2010-present)
Website www.osip.com
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.
Contents
1Tarceva
2See also
3References
4External links
Tarceva[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]
Companies portal
Linsitinib (OSI-906), an inhibitor of IGF-1R in clinical trials for cancer
treatment
References[edit]
^ a b c "Who We Are". OSI Pharmaceuticals. Retrieved 2008-01-20.
^ a b c Kristi Park. "OSI Pharmaceuticals, Inc.". Hoover's. Retrieved 2008-
01-20.
^ a b "OSI Pharmaceuticals - Financials". Hoover's. EDGAROnline.
Retrieved2008-01-20.
^ "2006 Annual Report" (PDF). OSI Pharmaceuticals. 2007-02-28. pp. pg22.
Retrieved 2008-01-20. As of February 7, 2007, our number of employees
decreased to 554, of which 276 primarily are involved in research,
development and manufacturing activities and 140 primarily are involved in
the commercialization of our products.
^ a b c Querida Anderson (2007-06-15). "OSI Pharma Needs to Expand Pipeline"
.Genetic Engineering & Biotechnology News. Mary Ann Liebert, Inc. p. 14.
Retrieved2008-01-20. OSI has a single marketed product backed by a mostly
early-stage pipeline.
^ "2006 Annual Report" (PDF). OSI Pharmaceuticals. 2007-02-28. pp. pg5.
Retrieved2008-01-20. As a result of our decision to divest the eye disease
business held by our wholly owned subsidiary, (OSI) Eyetech, Inc., the
operating results for (OSI) Eyetech are shown as discontinued operations...
^ "Products & Pipeline". OSI Pharmaceuticals. Retrieved 2008-01-20.
$$$$
Ocata Therapeutics
From Wikipedia, the free encyclopedia
Ocata Therapeutics, Inc.
Type Public
Traded as NASDAQ: OCAT
Industry Biotechnology
Founded 1994
Headquarters Marlborough, MA
Key people
Mr. Paul K. Wotton, Ph.D.: President and CEO[1]
Robert Lanza, MD: Chief Scientific Officer
Products Stem cell therapies for macular degeneration (human safety trial
started in 2010[2]), retinis pigmentosa, glaucoma and corneal blindness [3]
Website Ocata.com
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]
Contents
1History
2Research
2.1Macular degeneration
2.2Stargardt's disease
3See also
4References
5External links
History[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]
Key stem cell research events
Somatic cell nuclear transfer
Stem cells without embryonic destruction
Michael D. West
Geron Corporation
BioTime
References[edit]
^ http://www.advancedcell.com/about-act/leadership-team/senior-executive-officers/
^ "Company seeks to test stem cells for blindness". Reuters. 2009-11-25.
^ Ocata website: Pipeline Overview
^ "Advanced Cell Technology Changes Name to Ocata Therapeutics". Ocata
Therapeutics. 2014-11-14. Retrieved 2015-04-25.
^ "Race is on to use embryonic stem cells in humans". New Scientist.
November 19, 2009.
^ http://www.genengnews.com/gen-news-highlights/astellas-to-acquire-ocata-therapeutics-for-379m/81251957/
^ http://newsroom.astellas.us/news-releases?item=137160%29.
^ "Executive Profile". BusinessWeek.com. 23 March 2010.
^ "Advanced Cell Technology Senior Executive Officers". Advanced Cell
Technology. Retrieved 2014-08-13.
^ "Bloomberg Longevity Economy Conference 2013 Panelist Bio".
^ "Press Release: ACTCellerate Technology Licensed to BioTime, Inc by
Advanced Cell Technology".
^ "New Method for Controversy Free Embryonic Stem Cells". Wired Science. 9
July 2008.
^ "FDA approves second human embryonic stem cell trial". CNN.com. 22
November 2010.
^ http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(12)60028-2/abstract
^ http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2814%2961376-3/abstract
^ http://www.marketwatch.com/story/advanced-cell-technology-appoints-paul-k-wotton-phd-president-and-chief-executive-officer-2014-06-24
^ http://online.wsj.com/article/PR-CO-20140827-918716.html
^ Ocata Therapeutics Approved for Listing on NASDAQ February 26, 2015
^ Advanced Cell Technology Files IND with FDA for First Clinical Trial Using
Embryonic Stem Cells to Treat Dry AMD.
^ ACT Seeks FDA Approval For Stem Cell Study.
^ "Advanced Cell Technology Receives FDA Clearance to Initiate Clinical
Trials". Retina Today. Retrieved 5 April 2015.
External links[edit]
Official website
Dr. Lanza's webpage
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):
Astellas
Fujisawa Pharmaceutical Co
Fujisawa Pharmaceutical Co
(Est 1894)
Lyphomed
(Acq 1990)
Yamanouchi Pharmaceutical Co
(Est 1923)
OSI Pharmaceuticals
(Acq 2010)
Ocata Therapeutics
(Acq 2016)
Ganymed Pharmaceuticals
(Acq 2016)
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:
Prograf (tacrolimus) - Prevention of post-transplant organ rejection
Protopic (tacrolimus ointment) - Atopic dermatitis (eczema)
Amevive (alefacept) - Plaque psoriasis
VESIcare (solifenacin succinate) - Overactive bladder (OAB) marketed with
GlaxoSmithKline
Myrbetriq (mirabegron) - Overactive bladder (OAB) US only marketed by Pfizer
Outside of US
Flomax (tamsulosin hydrochloride) - Benign prostatic hyperplasia (BPH)
Adenocard (adenosine injection) - Pharmacologic stress agent for myocardial
perfusion scan
Adenoscan (adenosine injection) - Pharmacologic stress agent for myocardial
perfusion scan
Lexiscan (regadenoson injection) - Pharmacologic stress agent for myocardial
perfusion scan
Vaprisol (conivaptan) - Hyponatremia
AmBisome (amphotericin B) - Anti-fungal
Cresemba (isavuconazole) - Anti-fungal
Mycamine (micafungin sodium) - Anti-fungal
Symoron (methadone HCL) - narcotics misuse cessation
Tarceva (erlotinib) - Non-small cell lung cancer and pancreatic cancer
Xtandi (enzalutamide) - Prostate cancer
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:
English: Leading Light for Life
Japanese: Ashita wa kaerareru. (明日は変えられる。 Changing Tomorrow.?)[14]
References[edit]
^ http://www.forbes.com/companies/astellas-pharma/
^ "Corporate Profile". Astellas Pharma. Retrieved September 9, 2014.
^ "Annual Report 2014" (PDF). Astellas Pharma. Retrieved September 9, 2014.
^ "Astellas Pharma Snapshot". Bloomberg Businessweek. Retrieved January 25,
2015.
^ "Yamanouchi Pimafucin (natamycin) product line manufactured at least up to
11/2007"
^ Staff (November 15, 2014). "Astellas Ends Alzehimer's Collaboration with
CoMentis". Discovery & Development. Gen. Eng. Biotechnol. News (paper). 34 (
20). p. 14.
^ http://www.genengnews.com/gen-news-highlights/astellas-cytokinetics-expand-muscle-drug-collaboration/81250735/
^ http://www.genengnews.com/gen-news-highlights/astellas-to-acquire-ocata-therapeutics-for-379m/81251957/
^ http://www.genengnews.com/gen-news-highlights/astellas-to-acquire-ocata-therapeutics-for-379m/81251957/
^ http://newsroom.astellas.us/news-releases?item=137160%29.
^ http://www.genengnews.com/gen-news-highlights/leo-pharma-buys-astellas-dermatology-business-for-725m/81251969/
^ http://www.genengnews.com/gen-news-highlights/astellas-to-acquire-ganymed-pharmaceuticals-for-up-to-14b/81253378
^ Slatko, Joshua (December 2013). "BMS changes senior management team".
People on the Move: Pharma. Med Ad News. p. 27.
^ "Corporate Philosophy of Astellas Pharma". Astellas Pharma. Retrieved
September 9, 2014.
$$$$$$$$$$$$$$$$$$
Suntory
From Wikipedia, the free encyclopedia
Suntory Holdings Limited
サントリーホールディングス株式会社
Type Kabushiki gait
Industry Beverage
Founded Osaka, Japan
1899; 117 years ago
Founder Torii Shinjiro
Headquarters Osaka, Japan
Key people Nobutada Saji
Subsidiaries Beam, Inc.
Website suntory.com
Suntory Holdings Limited (サントリーホールディングス株式会社 Santorī Hō
rudingusu 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.
Contents
1History
2Holdings
3Joint ventures
4Media and advertising
5Products
5.1Alcoholic drinks
5.2Soft drinks
5.3Food for specified health uses
6See also
7References
8External links
History[edit]
Suntory headquarters, Osaka,Japan
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]
Suntory Malt's beer
Beam Suntory
Cerebos Pacific Ltd
Chateau Lagrange S.A.S
Florigene Pty Ltd
Frucor Beverages Limited
Gold Knoll Ltd
Grupo Restaurante Suntory Mexico
Louis Royer S.A.S
Morrison Bowmore Distillers, Limited
OranginaSchweppes Group[11]
Pepsi Bottling Ventures LLC
Subway Japan
Tipco F&B Co., Ltd
Joint ventures[edit]
A Suntory "Kaku-bin" Whisky bottle and glass display at a Yamaya Liquor
store in Iizaka, Japan
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]
Advertising poster of "AKADAMA Port Wine”, the first nude advertising
poster in Japan. Published in 1922 (Taisho 11). Directed by Toshiro Kataoka
featuring Emiko Matsushima
Suntory and its various products are featured in the Ryū ga Gotoku/Yakuza
series of games.
Suntory was one of the first Asian companies to specifically employ American
celebrities to market their product.[citation needed] One of the most
notable is Sammy Davis, Jr., who appeared in a series of Suntory commercials
in the early 1970s. In the late 1970s, Akira Kurosawa directed a series of
commercials featuring American celebrities on the set of his film Kagemusha.
One of these featuredFrancis Ford Coppola (an executive producer of the
film), which later inspired his daughter Sofia Coppola in her writing of
Lost in Translation, a film which focuses on an American actor filming a
Suntory commercial in Tokyo.
A Reuters photo by Toshiyuki Aizawa from July 2003 showed Suntory's
marketing strategy of TV helmets. In this scheme, advertising company
employees clad in orange jumpsuits wear television cameras that broadcast
wide-screen digital feeds of the brewing company's commercial on top of
their helmets.
Suntory operates two museums, the Suntory Museum of Art in Tokyo and the
Suntory Museum Tempozan in Osaka, in addition to a number of cultural and
social programs across Japan.
Suntory produced several drinks under the name "Final Fantasy Potion", named
for the weakest and most common healing item in the game. Each was released
in Japan only for a limited time to promote the release of the Square Enix
game Final Fantasy XII, the 10th anniversary of Final Fantasy VII, and the
release of Dissidia Final Fantasy, which comes in two varieties. All the
drinks are different despite sharing the name. For the release of Final
Fantasy XIII, the Potion name was abandoned and replaced with Elixir, an
item which typically heals one party member fully and restores all MP.
Suntory owns a top Japanese rugby club called the Suntory Sungoliath.
In the 1970s, Suntory engaged the US pop group the Carpenters to advertise
its new line of soft drinks.
Suntory is a former sponsor of the professional match play golf tournament,
played annually at Wentworth Club, near London.
Suntory Kakubin is featured in an episode of the 2006 anime series Bartender
entitled "Menu of the Heart".
In the 2000s, to advertise its The Premium Malt beer, there were a series of
television ads featuring Eikichi Yazawa and various versions of the title
song of "Shall We Dance?".[disambiguation needed]
Products[edit]
Malt's beer served at Suntory's Kyoto brewery, Kyoto
Alcoholic drinks[edit]
Beers
Malt's
Suntory
Brandy (Centenario, Courvoisier, Fundador)
Gin (Gilbey's, Larios)
Rum (Cruzan, Ronrico)
Tequila (100 Años, El Tesoro, Hornitos, Sauza, Sauza Tres Generaciones)
Vodka (Effen, Kamchatka, Pinnacle, Vox)
Whisky
American whiskey
Blended whiskey (Beam's Eight Star, Kessler)
Kentucky Bourbon
Jim Beam (the top-selling brand of Kentucky bourbon)
Jim Beam small batch brands (Baker's, Basil Hayden's, Booker's, Knob Creek)
Maker's Mark
Old Crow
Old Grand-Dad
Rye whiskey (Jim Beam Rye, Knob Creek Rye, Old Overholt, (ri)1)
Canadian whisky (Alberta Premium, Canadian Club, Tangle Ridge, Windsor)
Irish whiskey (2 Gingers, Connemara, Grenore, Kilbeggan, Tyrconnell)
Japanese whisky (Hakushu, Hibiki, Torys, Suntory, Yamazaki)
Scotch whisky (Ardmore, Auchentoshan, Bowmore, Glen Garioch, Laphroaig,
McClelland's, Teacher's)
Spanish whisky (DYC)
Cocktails and liqueurs
Calico Jack flavored rum
Midori Melon liqueur
Rubis Strawberry liqueur
Lena Banana liqueur
Mohala Mango liqueur
Blue Curacao
Skinnygirl pre-mixed margarita
Aki (discontinued in 1988)
Pavan
Soft drinks[edit]
Bikkle
Boss Coffee
C.C. Lemon
Iced Oolong Tea
Iemon (伊右衛門), a brand of green tea drink
Mizone
Natchan
Orangina
Dakara
Lucozade
Ribena
Food for specified health uses[edit]
The following drinks were approved as Food for Specified Health Uses (FOSHU)
.[13][14][15]
Black Oolong Tea
Calcium and Iron Beverage
Sesame Barley Tea
See also[edit]
Osaka portal
Suntory Sungoliath rugby team – champions of the 2007-08 Top League (fifth
season)
Suntory Mermaid II – wave powered catamaran
References[edit]
^ Suntory News Release on January 19, 2009 (Global website), (Japan website)
- Suntory Limited
^ キリン：サントリーと経営統合へ交渉 - 毎日ｊｐ(毎日新聞) Mainichi Shimbun (
Retrieved on July 13, 2009)
^ Termination of Merger Negotiation with Kirin Suntory News Release (
Retrieved on February 8, 2010)
^ "Suntory buys Frucor from Groupe Danone October 2008". Danone. 23 October
2008. Retrieved 16 January 2009.
^ Suntory IPO
^ Suntory News Release on January 13th, 2014 (Global website)
^ MARTINNE GELLER AND OLIVIA ORAN (14 January 2014). "Japan's Suntory to buy
U.S. spirits maker Beam for $13.6 billion cash". Reuters.
^ Beam Suntory, Suntory press release, April 30, 2014.
^ Suntory Still has M&A Thirst, The Wall Street Journal, May 15, 2014.
^ Angela Monaghan "Ribena and Lucozade sold to Japanese drinks giant", The
Guardian, 9 September 2013
^ "Japan's Suntory snaps up Orangina". BBC News. BBC. 2009-11-13. Retrieved
2009-11-15.
^ "GarudaFood, Suntory form joint venture". The Jakarta Post. 2011-07-16.
Retrieved 2012-10-14.
^ "Food for Specified Health Uses (FOSHU)", Ministry of Health, Labour and
Welfare (Retrieved on May 1, 2010)
^ "Beverages, Health Beverages", Suntory (Retrieved on May 1, 2010)
^ "Soft drink product information" (Japanese), Suntory (Retrieved on May 1,
2010)
External links[edit]
Wikimedia Commons has media related to Suntory.
Official website
Florigene corporate site
Yahoo! - Suntory Group company profile
Yahoo! - Suntory Limited company profile
v
t
e
Suntory Holdings Limited
Subsidiaries
Chateau Lagrange S.A.S (1983)
Florigene Pty Ltd (2003)
Frucor Beverages Limited (2008)
Gold Knoll Ltd
Louis Royer S.A.S
Morrison Bowmore Distillers, Limited (1994)
First Kitchen
Pepper Lunch2
Beam Suntory (2014)
Spirits & wine
Hakushu
Hibiki
Yamazaki
Auchentoshan
Bowmore
Glen Garioch
McClelland's Single Malt
Midori
Akadama
Soft drinks
Bikkle
Boss Coffee
C.C. Lemon
Calcium and Iron Beverage
Dakara
Mizone
Natchan
Iced Oolong Tea
Orangina1
Lucozade
Ribena
V
Pepsi Special
Beam Suntory
Whiskey
Jim Beam
Maker's Mark
Old Grand-Dad
Old Crow
Basil Hayden's
Booker's
Knob Creek
Kessler
Beam's Eight Star
Laphroaig
Ardmore
Teacher's Highland Cream
The Tyrconnell
Connemara
Greenore
Kilbeggan
Alberta Premium
Canadian Club
DYC whisky
Other spirits
Sauza
Hornitos de Sauza
El Tesoro de Don Felipe
Courvoisier
VOX
Gilbey's
Pinnacle
Cruzan
Gilbey's
Kamora
After Shock
Leroux
Castellana
Sourz
Harvey's Bristol Cream
Other
Nobutada Saji
Yuka Saitō
Suntory Sungoliath
Suntory Sunbirds
Suntory Hall
Suntory Open
Suntory Ladies Open
Suntory Music Award
Suntory Mermaid II
Suntory Museum of Art
1 In North America the brand is owned by Dr Pepper Snapple Group. 2
International operations.
Category
Authority control
WorldCat Identities
VIAF: 257372483
NDL: 01156953
$$$$$$$$$$$$$$$$$$$$$$$$
Beam Suntory
From Wikipedia, the free encyclopedia
(Redirected from Beam, Inc.)
Beam Suntory
Type Subsidiary
Industry Distilled beverages
Founded October 4, 2011
Founder Remainder company created from Fortune Brands
Headquarters Deerfield, Illinois, United States
Area served Worldwide
Key people Matthew John Shattock (CEO& President), John Owen (CFO)
Products Spirits
Revenue US$ 2.46 billion (FY 2012)[1]
Operating income $ 5.75 million (FY 2012)[1]
Net income $ 3.82 million (FY 2012)[1]
Total assets $ 8.64 billion (FY 2012)[1]
Total equity $4.61 million (FY 2012)[1]
Number of employees 3400 [1]
Parent Suntory
Website www.beamsuntory.com
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]
Old logo.
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]
Contents
1Products
2Prior acquisitions
3References
4External links
Products[edit]
The company's self-produced brands include the following:
American whiskey:
Bourbon whiskey – Jim Beam, Maker's Mark, Old Grand-Dad, Old Crow, Baker's,
Basil Hayden's, Booker's, Knob Creek
Rye whiskey – Jim Beam Rye, Knob Creek Rye, Old Overholt, (rī)1
Blended American whiskey – Kessler, Beam's Eight Star
Scotch whisky:
Single malt Scotch – Laphroaig, Bowmore, Ardmore
Blended Scotch whisky – Teacher's Highland Cream
Irish whiskey:
Single malt Irish whiskey – The Tyrconnell, Connemara
Single grain Irish whiskey – Greenore
Blended Irish whiskey – Kilbeggan
Canadian whisky
Alberta Premium, Canadian Club, Tangle Ridge, Windsor Canadian
Spanish whisky:
DYC whisky
Japanese whisky
Yamazaki, Hakushu, Hibiki
Tequila
Sauza, Hornitos de Sauza, El Tesoro de Don Felipe, Tres Generaciones
Cognac
Courvoisier, Salignac
Vodka
VOX, Wolfschmidt, Gilbey's, Effen, Kamchatka, Pinnacle,
Rum
Cruzan, Calico Jack, Ronrico
Gin
Larios, Gilbey's, Calvert, Sipsmith
Liqueur
Starbucks Liqueurs, Kamora, After Shock, Leroux, Castellana, Sourz
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]
^ a b c d e f "Beam, Inc. (BEAM)-Key Statistics". Yahoo! Finance.[dead link]
^ "Beam Inc. Begins Life as a Pure-Play Spirits Industry Leader". TheStreet.
com. October 4, 2011. Retrieved March 1, 2016.
^ Horovitz, Bruce (January 13, 2014). "Suntory buys spirits maker Beam for $
13.6B". USA Today.
^ Beam Suntory, Suntory press release, April 30, 2014.
^ Pfanner, Eric (May 15, 2014). "Suntory Still has M&A Thirst". The Wall
Street Journal. Retrieved March 1, 2016. (subscription required (help)).
^ Frost, Peter (February 29, 2016). "Beam Suntory moving HQ to Merchandise
Mart". Crain's Chicago Business.
^ Arceo-Dumlao, Tina (December 1, 2015). "Andrew Tan's Emperador buys Spain'
s Fundador". Philippine Daily Inquirer.
^ (December 16, 2011). "Cooley Distillery Sold for $95M". Irish Examiner.
Retrieved January 11, 2012.
^ "Beam buys Pinnacle Vodka and Calico Jack rum from White Rock". USA Today.
Associated Press. April 23, 2012. Retrieved November 24, 2012.
External links[edit]
Liquor portal
Drink portal
Beam Suntory – official company website
v
t
e
Suntory Holdings Limited
Subsidiaries
Chateau Lagrange S.A.S (1983)
Florigene Pty Ltd (2003)
Frucor Beverages Limited (2008)
Gold Knoll Ltd
Louis Royer S.A.S
Morrison Bowmore Distillers, Limited (1994)
First Kitchen
Pepper Lunch2
Beam Suntory (2014)
Spirits & wine
Hakushu
Hibiki
Yamazaki
Auchentoshan
Bowmore
Glen Garioch
McClelland's Single Malt
Midori
Akadama
Soft drinks
Bikkle
Boss Coffee
C.C. Lemon
Calcium and Iron Beverage
Dakara
Mizone
Natchan
Iced Oolong Tea
Orangina1
Lucozade
Ribena
V
Pepsi Special
Beam Suntory
Whiskey
Jim Beam
Maker's Mark
Old Grand-Dad
Old Crow
Basil Hayden's
Booker's
Knob Creek
Kessler
Beam's Eight Star
Laphroaig
Ardmore
Teacher's Highland Cream
The Tyrconnell
Connemara
Greenore
Kilbeggan
Alberta Premium
Canadian Club
DYC whisky
Other spirits
Sauza
Hornitos de Sauza
El Tesoro de Don Felipe
Courvoisier
VOX
Gilbey's
Pinnacle
Cruzan
Gilbey's
Kamora
After Shock
Leroux
Castellana
Sourz
Harvey's Bristol Cream
Other
Nobutada Saji
Yuka Saitō
Suntory Sungoliath
Suntory Sunbirds
Suntory Hall
Suntory Open
Suntory Ladies Open
Suntory Music Award
Suntory Mermaid II
Suntory Museum of Art
1 In North America the brand is owned by Dr Pepper Snapple Group. 2
International operations.
Category
Categories:
Beam Suntory
2011 establishments in Illinois
Drink companies of the United States
Companies based in Deerfield, Illinois
Companies established in 2011
Suntory
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Lymphatic filariasis
From Wikipedia, the free encyclopedia
Lymphatic filariasis
Synonyms elephantiasis tropica, elephantiasis arabum[1]
"Bellevue Venus" Oscar G. Mason's portrait of a woman with elephantiasis.
Classification and external resources
Specialty infectious disease
ICD-10 B74
ICD-9-CM 125.0-125.9
eMedicine derm/888
MeSH D005368
[edit on Wikidata]
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]
Contents
1Signs and symptoms
2Causes
3Diagnosis
4Prevention
5Treatment
5.1Antibiotics
6Prognosis
7Epidemiology
8History
9Research directions
10References
Signs 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
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.
Drawn from the collection at the National Museum of Health and Medicineand
shows the effect of elephantiasis in an historic context. Anatomical items:
Left Leg, Scrotum.
Elephantiasis of the legs due to filariasis. Luzon, Philippines.
Man with massive scrotal elephantiasis, Tanzania, early 20th century
Causes[edit]
Life cycle of Wuchereria bancrofti, a parasite that causes lymphatic
filariasis
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]
Disability-adjusted life year for lymphatic filariasis per 100,000
inhabitants
no data
less than 10
10-50
50-70
70-80
80-90
90-100
100-150
150-200
200-300
300-400
400-500
more than 500
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 the Americas, it is present in Brazil, Costa Rica, the Dominican Republic
, Guyana, Haiti, Suriname, and Trinidad and Tobago.
In Asia, it is present in
Bangladesh,
Cambodia,
India,
Indonesia,
Laos,
Malaysia,
Maldives,
the Philippines,
Sri Lanka,
Thailand,
Timor-Leste, and
Vietnam.
In the Middle East, it is present only in Yemen.
In the Pacific region, it is endemic in American Samoa, the Cook Islands,
Fiji, French Polynesia, Micronesia, Niue, Papua New Guinea, Samoa, Tonga,
Tuvalu, and Vanuatu.
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]
“ Many people in Malabar, Nayars as well as Brahmans and their wives —
in fact about a quarter or a fifth of the total population, including the
people of the lowest castes — have very large legs, swollen to a great size
; and they die of this, and it is an ugly thing to see. They say that this
is due to the water through which they go, because the country is marshy.
This is called pericaes in the native language, and all the swelling is the
same from the knees downward, and they have no pain, nor do they take any
notice of this infirmity. ”
— -Portuguese diplomat Tomé Pires, Suma Oriental, 1512–1515.[33]
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]
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Onchocerciasis
From Wikipedia, the free encyclopedia
(Redirected from River blindness)
Onchocerciasis
Synonyms river blindness, Robles disease
An adult black fly with the parasite Onchocerca volvulus coming out of the
insect's antenna, magnified 100x
Pronunciation /ˌɒŋkoʊsɜːrˈsaɪ&#
601;sᵻs, -ˈkaɪ-/
Classification and external resources
Specialty infectious disease
ICD-10 B73
ICD-9-CM 125.3
DiseasesDB 9218
eMedicine med/1667 oph/709
MeSH D009855
[edit on Wikidata]
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]
Contents
1Signs and symptoms
1.1Mazzotti reaction
1.2Nodding disease
1.3Classification
2Cause
2.1Life cycle
3Prevention
4Treatment
4.1Antibiotics
4.2Ivermectin
5Epidemiology
6History
7Society and culture
8Research
9See also
10References
11External links
Signs 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]
Acute papular onchodermatitis – scattered pruritic papules
Chronic papular onchodermatitis – larger papules, resulting in
hyperpigmentation
Lichenified onchodermatitis – hyperpigmented papules and plaques, with
edema, lymphadenopathy, pruritus and common secondary bacterial infections
Skin atrophy – loss of elasticity, the skin resembles tissue paper, 'lizard
skin' appearance
Depigmentation – 'leopard skin' appearance, usually on anterior lower leg
Glaucoma effect – eyes malfunction, begin to see shadows or nothing
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.
Patch test
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]
Erisipela de la costa
An acute phase, it is characterized by swelling of the face, with erythema
and itching.[17]:440 This skin change, erisípela de la costa, of acute
onchocerciasis is most commonly seen among victims in Central and South
America.[18]
Mal morando
This cutaneous condition is characterized by inflammation accompanied by
hyperpigmentation.[17]:440
Sowda
A cutaneous condition, it is a localized type of onchocerciasis.[17]:440
Additionally, the various skin changes associated with onchocerciasis may be
described as follows:[17]:440
Leopard skin
The spotted depigmentation of the skin that may occur with onchocerciasis[17
]:440
Elephant skin
The thickening of human skin that may be associated with onchocerciasis[17]:
440
Lizard skin
The thickened, wrinkled skin changes that may result with onchocerciasis[17]
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]
A Simulium female black fly takes a blood meal on an infected human host,
and ingests microfilaria.
The microfilaria enter the gut and thoracic flight muscles of the black fly,
progressing into the first larval stage (J1.).
The larvae mature into the second larval stage (J2.), and move to the
proboscis and into the saliva in its third larval stage (J3.). Maturation
takes about seven days.
The black fly takes another blood meal, passing the larvae into the next
human host’s blood.
The larvae migrate to the subcutaneous tissue and undergo two more molts.
They form nodules as they mature into adult worms over six to 12 months.
After maturing, adult male worms mate with female worms in the subcutaneous
tissue to produce between 700 and 1,500 microfilaria per day.
The microfilaria migrate to the skin during the day, and the black flies
only feed in the day, so the parasite is in a prime position for the female
fly to ingest it. Black flies take blood meals to ingest these microfilaria
to restart the cycle.
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]
The burden of onchocerciasis: children leading blind adults in Africa
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]
Disability-adjusted life year for onchocerciasis per 100,000 inhabitants
no data
less than 10
10–50
50–60
60–70
70–80
80–90
90–100
100–150
150–200
200–300
300–400
more than 400
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]
Medicine portal
Carter Center River Blindness Program
List of parasites (human)
Neglected tropical diseases
Rodolfo Robles
United Front Against Riverblindness
Harold Ridley (ophthalmologist)
References[edit]
^ a b c d e f g h i j "Onchocerciasis Fact sheet N°374". World Health
Organization. March 2014. Retrieved 20 March 2014.
^ a b "Onchocerciasis (also known as River Blindness)". Parasites. CDC. May
21, 2013. Retrieved 20 March 2014.
^ a b "Parasites – Onchocerciasis (also known as River Blindness)
Epidemiology & Risk Factors". CDC. May 21, 2013. Retrieved 20 March 2014.
^ "Onchocerciasis (also known as River Blindness) Diagnosis". Parasites. CDC
. May 21, 2013. Retrieved 20 March 2014.
^ a b "Onchocerciasis (also known as River Blindness) Prevention & Control".
Parasites. CDC. May 21, 2013. Retrieved 20 March 2014.
^ a b Murray, Patrick (2013). Medical microbiology (7th ed.). Philadelphia:
Elsevier Saunders. p. 792. ISBN 9780323086929.
^ a b c Brunette, Gary W. (2011). CDC Health Information for International
Travel 2012 : The Yellow Book. Oxford University Press. p. 258. ISBN
9780199830367.
^ Lok, James B.; Walker, Edward D.; Scoles, Glen A. (2004). "9. Filariasis".
In Eldridge, Bruce F.; Edman, John D.; Edman, J. Medical entomology (
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^ Reddy M, Gill SS, Kalkar SR, Wu W, Anderson PJ, Rochon PA (October 2007).
"Oral drug therapy for multiple neglected tropical diseases: a systematic
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^ Baldo L, Desjardins CA, Russell JA, Stahlhut JK, Werren JH (2010-02-17). "
Accelerated microevolution in an outer membrane protein (OMP) of the
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1471-2148-10-48. PMC 2843615. PMID 20163713.
^ a b Francesca Tamarozzi; Alice Halliday; Katrin Gentil; Achim Hoerauf;
Eric Pearlman; Mark J. Taylor (2011-07-24). "Onchocerciasis: the Role of
Wolbachia Bacterial Endosymbionts in Parasite Biology, Disease Pathogenesis,
and Treatment". Clinical Microbiology Reviews. 24: 459:468. doi:10.1128/CMR
.00057-10. PMC 3131055.PMID 21734243.
^ a b Wani, MG (February 2008). "Onchocerciasis". Southern Sudan Medical
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^ Ali MM, Baraka OZ, AbdelRahman SI, Sulaiman SM, Williams JF, Homeida MM,
Mackenzie CD (15 February 2003). "Immune responses directed against
microfilariae correlate with severity of clinical onchodermatitis and
treatment history". Journal of Infectious Diseases. 187 (4): 714–7. doi:10.
1086/367709. JSTOR 30085595.PMID 12599094.
^ Murdoch ME, Hay RJ, Mackenzie CD, Williams JF, Ghalib HW, Cousens S,
Abiose A, Jones BR (September 1993). "A clinical classification and grading
system of the cutaneous changes in onchocerciasis". Br J Dermatol. 129 (3):
260–9. doi:10.1111/j.1365-2133.1993.tb11844.x. PMID 8286222.
^ http://microblog.me.uk/420
^ Dowell SF, Sejvar JJ, Riek L, Vandemaele KA, Lamunu M, Kuesel AC,
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^ a b c d e f g h James, William D.; Berger, Timothy G.; Elston, Dirk M;
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^ Marty AM. "Filariasis". eMedicine. Retrieved 2009-10-22.
^ "Onchocerciasis Control Programme (OCP)". Programmes and Projects. World
Health Organization. Retrieved 2010-06-15.
^ "African Programme for Onchocerciasis Control (APOC)". Programmes and
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^ "Onchocerciasis Elimination Program for the Americas (OEPA)". Programmes
and Projects. World Health Organization. Retrieved 2010-06-15.
^ "NEWS SCAN: Columbia ousts river blindness; Vaccine-derived polio in India
; Danish Salmonella trends". CIDRAP News. July 30, 2013.
^ "Brazil and Venezuela border is the last place in the Americas with river
blindness". Outbreak News Today. Retrieved 3 October 2015.
^ "Onchocerciasis Elimination Program for the Americas (OEPA)". World Health
Organization. Retrieved 3 October 2015.
^ "Onchocerciasis". World Health Organization. Retrieved 3 October 2015.
^ Sauerbrey, M (September 2008). "The Onchocerciasis Elimination Program for
the Americas (OEPA).". Annals of tropical medicine and parasitology. 102
Suppl 1: 25–9.doi:10.1179/136485908x337454. PMID 18718151.
^ a b c d e Rea PA, Zhang V, Baras YS (2010). "Ivermectin and River
Blindness".American Scientist. 98 (4): 294–303.
^ Trattler, Bill; Gladwin, Mark (2007). Clinical Microbiology Made
Ridiculously Simple. Miami: MedMaster. ISBN 0-940780-81-X. OCLC 156907378.
^ Taylor MJ, Bandi C, Hoerauf A (2005). "Wolbachia bacterial endosymbionts
of filarial nematodes". Advances in Parasitology. 60: 245–84. doi:10.1016/
S0065-308X(05)60004-8. PMID 16230105.
^ a b Hoerauf A (2008). "Filariasis: new drugs and new opportunities for
lymphatic filariasis and onchocerciasis". Current Opinion in Infectious
Diseases. 21 (6): 673–81.doi:10.1097/QCO.0b013e328315cde7. PMID 18978537.
^ Yates DM, Wolstenholme AJ (August 2004). "An ivermectin-sensitive
glutamate-gated chloride channel subunit from Dirofilaria immitis".
International Journal for Parasitology. 34(9): 1075–81. doi:10.1016/j.
ijpara.2004.04.010. PMID 15313134.
^ Harder A (2002). "Chemotherapeutic approaches to nematodes: current
knowledge and outlook". Parasitology Research. 88 (3): 272–7. doi:10.1007/
s00436-001-0535-x.PMID 11954915.
^ Wolstenholme AJ, Rogers AT (2005). "Glutamate-gated chloride channels and
the mode of action of the avermectin/milbemycin anthelmintics". Parasitology
. 131 (Suppl:S85–95): S85–95. doi:10.1017/S0031182005008218. PMID 16569295.
^ Ejere HO, Schwartz E, Wormald R, Evans JR (2012). "Ivermectin for
onchocercal eye disease (river blindness)". Cochrane Database Syst Rev. 8:
CD002219.doi:10.1002/14651858.CD002219.pub2. PMC 4425412. PMID 22895928.
^ Fenwick, A (Mar 2012). "The global burden of neglected tropical diseases."
. Public health. 126 (3): 233–6. doi:10.1016/j.puhe.2011.11.015. PMID
22325616.
^ "What is river blindness?". Sightsavers International. Archived from the
original on 2007-12-15. Retrieved 2008-01-28.
^ "Status of onchocerciasis in APOC countries". World Health Organization.
2008. Retrieved 2010-04-26.
^ a b "Epidemiology". Stanford University. 2006.
^ Peña Flores G.; Richards F.; et al. (2010). "Lack of Onchocerca
volvulus transmission in the northern focus in Chiapas". Am. J. Trop. Med.
Hyg. 83 (1): 15–20.doi:10.4269/ajtmh.2010.09-0626.
^ Peña Flores G.; Richards F.; Domínguez A. (2010). "Interruption of
transmission ofOnchocerca volvulus in the Oaxaca focus". Am. J. Trop. Med.
Hyg. 83 (1): 21–27.doi:10.4269/ajtmh.2010.09-0544.
^ Zimmerman, PA; Katholi, CR; Wooten, MC; Lang-Unnasch, N; Unnasch, TR (May
1994). "Recent evolutionary history of American Onchocerca volvulus, based
on analysis of a tandemly repeated DNA sequence family.". Molecular Biology
and Evolution. 11 (3): 384–92. PMID 7516998.
^ O’Neill, John (1875). "O'Neill J. On the presence of a filaria in " craw-
craw" (PDF).The Lancet. 105: 265–266. doi:10.1016/s0140-6736(02)30941-3.
^ "A Short History of Onchocerciasis". Retrieved 18 October 2015.
^ Robles, Roberto (1917). "Enfermedad nueva en Guatemala". La Juventud Mé
dica.
^ Strong, Richard (1942). Stitt’s Diagnosis, prevention and treatment of
tropical diseases. The Blakiston.
^ Manson-Bahr, Philip H (1943). Tropical diseases; a manual of the diseases
of warm climates [Internet] (11th ed.). Williams & Wilkins Co.
^ Blacklock, DB (22 January 1927). "THE INSECT TRANSMISSION OF ONCHOCERCA
VOLVULUS (LEUCKART, 1893): THE CAUSE OF WORM NODULES IN MAN IN AFRICA.".
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20772951.
^ Kluxen, G; Hoerauf, A (2008). "The significance of some observations on
African ocular onchocerciasis described by Jean Hissette (1888-1965)". Bull
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^ Hisette, Jean (1932). Mémoire sur l’Onchocerca volvulus "Leuckart" et
ses manifestations oculaires au Congo belge. pp. 433–529.
^ Ridley, Harold (1945). "OCULAR ONCHOCERCIASIS Including an Investigation
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suppl.3.
^ Kluxen, G. "Harvard African Expedition [Internet]". Retrieved 18 October
2015.
^ Thylefors B, Alleman MM, Twum-Danso NA (May 2008). "Operational lessons
from 20 years of the Mectizan Donation Program for the control of
onchocerciasis". Trop Med Int Health. 13 (5): 689–96. doi:10.1111/j.1365-
3156.2008.02049.x. PMID 18419585.
^ Jan Andersson; Hans Forssberg; Juleen R. Zierath (5 October 2015),
Avermectin and Artemisinin - Revolutionary Therapies against Parasitic
Diseases (PDF), The Nobel Assembly at Karolinska Institutet, retrieved 5
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^ "Kinship Powerful in River Blindness Fight." Carter Center Update, The
Carter Center, Atlanta, Georgia. Summer, 2016. pp. 4-5.
^ Allen JE, Adjei O, Bain O, Hoerauf A, Hoffmann WH, Makepeace BL, Schulz-
Key H, Tanya VN, Trees AJ, Wanji S, Taylor DW (April 2008). Lustigman S, ed.
"Of Mice, Cattle, and Humans: The Immunology and Treatment of River
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. PMC 2323618. PMID 18446236.
^ "River blindness resistance fears". BBC News. 2007-06-14. Retrieved 2007-
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^ Osei-Atweneboana MY, Eng JK, Boakye DA, Gyapong JO, Prichard RK (June 2007
)."Prevalence and intensity of Onchocerca volvulus infection and efficacy of
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17574093.
^ [No author listed] (11 July 2009). "Fighting river blindness and other
ills". Lancet. 374(9684): 91. doi:10.1016/S0140-6736(09)61262-9. PMID
19595328. (editorial)
^ Abegunde AT, Ahuja RM, Okafor NJ (2016). "Doxycycline plus ivermectin
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PMID 26771164.
Ivermectin
From Wikipedia, the free encyclopedia
Ivermectin
Clinical data
Trade names Stromectol, Soolantra cream
AHFS/Drugs.com Monograph (antiparasitic)
FDA Professional Drug Information (rosacea)
MedlinePlus a607069
Pregnancy
category
AU: B3
US: C (Risk not ruled out)
Routes of
administration Oral, topical
ATC code D11AX22 (WHO) P02CF01(WHO) QP54AA01 (WHO)QS02QA03 (WHO)
Legal status
Legal status
US: ℞-only
Pharmacokinetic data
Protein binding 93%
Metabolism Liver (CYP450)
Biological half-life 18 hours
Excretion Feces; <1% urine
Identifiers
IUPAC name
22,23-dihydroavermectin B1a + 22,23-dihydroavermectin B1b
CAS Number 70288-86-7 71827-03-7
PubChem (CID) 9812710
DrugBank DB00602
ChemSpider 7988461
UNII 8883YP2R6D
KEGG D00804
ChEMBL CHEMBL341047
PDB ligand ID IVM (PDBe, RCSB PDB)
ECHA InfoCard 100.067.738
Chemical and physical data
Formula C
48H
74O
14(22,23-dihydroavermectin B1a)
C
47H
72O
14(22,23-dihydroavermectin B1b)
Molar mass 875.10 g/mol
3D model (Jmol) Interactive image
SMILES
CC[[email protected]/* */](C)[C@@H]1[[email protected]/* */](CC[C@@]2(O1)C[C@@H]3C[[email protected]/* */](O2)C/C=C(/[[email protected]/* */]([[email protected]/* */](/C=C
/C=C/4CO[[email protected]/* */]5[C@@]4([C@@H](C=C([[email protected]/* */]5O)C)C(=O)O3)O)C)O[[email protected]/* */]6C[C@@H]([[email protected]/* */]([
C@@H](O6)C)O[[email protected]/* */]7C[C@@H]([[email protected]/* */]([C@@H](O7)C)O)OC)OC)C)C.C[[email protected]/* */]1CC[C@]2(C[C@@
H]3C[[email protected]/* */](O2)C/C=C(/[[email protected]/* */]([[email protected]/* */](/C=C/C=C/4CO[[email protected]/* */]5[C@@]4([C@@H](C=C([[email protected]/* */]5O)
C)C(=O)O3)O)C)O[[email protected]/* */]6C[C@@H]([[email protected]/* */]([C@@H](O6)C)O[[email protected]/* */]7C[C@@H]([[email protected]/* */]([C@@H](
O7)C)O)OC)OC)C)O[C@@H]1C(C)C
InChI
InChI=1S/C48H74O14.C47H72O14/c1-11-25(2)43-28(5)17-18-47(62-43)23-34-20-33(
61-47)16-15-27(4)42(26(3)13-12-14-32-24-55-45-40(49)29(6)19-35(46(51)58-34)
48(32,45)52)59-39-22-37(54-10)44(31(8)57-39)60-38-21-36(53-9)41(50)30(7)56-
38;1-24(2)41-27(5)16-17-46(61-41)22-33-19-32(60-46)15-14-26(4)42(25(3)12-11-
13-31-23-54-44-39(48)28(6)18-34(45(50)57-33)47(31,44)51)58-38-21-36(53-10)43
(30(8)56-38)59-37-20-35(52-9)40(49)29(7)55-37/h12-15,19,25-26,28,30-31,33-45
,49-50,52H,11,16-18,20-24H2,1-10H3;11-14,18,24-25,27,29-30,32-44,48-49,51H,
15-17,19-23H2,1-10H3/b13-12+,27-15+,32-14+;12-11+,26-14+,31-13+/t25-,26-,28-
,30-,31-,33+,34-,35-,36-,37-,38-,39-,40+,41-,42-,43+,44-,45+,47+,48+;25-,27-
,29-,30-,32+,33-,34-,35-,36-,37-,38-,39+,40-,41+,42-,43-,44+,46+,47+/m00/s1
Key:SPBDXSGPUHCETR-JFUDTMANSA-N
(what is this?) (verify)
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]
Contents
1Medical uses
1.1Arthropod
1.2Rosacea
2Contraindications
3Side effects
4Pharmacology
4.1Pharmacodynamics
4.2Pharmacokinetics
4.3Ecotoxicity
5History
6Brand names
7Veterinary use
8Research
9See also
10Notes and references
11External links
Medical 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:
Mites such as scabies:[16][17][18] It is usually limited to cases that prove
to be resistant to topical treatments or that present in an advanced state
(such as Norwegian scabies).[18]
Lice:[19][20] Ivermectin lotion (0.5%) is FDA-approved for patients six
months of age and older.[21] After a single, 10-minute application of this
formulation on dry hair, 78% of subjects were found to be free of lice after
two weeks.[22] This level of effectiveness is equivalent to other
pediculicide treatments requiring two applications.[23]
Bed bugs:[24] Early research shows that the drug kills bed bugs when taken
by humans at normal doses. The drug enters the human bloodstream and if the
bedbugs bite during that time, they will die in a few days.
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 o | B********n
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