2015 Nobel Prize in Physiology or Medicine
William Campbell, Satoshi Omura
"for their discoveries concerning a novel therapy
against infections caused by roundworm
parasites“
Youyou Tu
"for her discoveries concerning a novel therapy
against malaria"
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Parasites and Parasitic Diseases
Parasite: An organism that lives on or in a host and gets its
food from or at the expense of its host.1
Protozoans
Plasmodium falciparum
(malaria)
Helminths
Roundworms,
tapeworms, etc.
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Ectoparasites
Ticks, fleas, lice, etc.
Source and vector of disease
1
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Onchocerciasis
(river blindness)
Infection with Onchocerca
volvulus (a roundworm),
transmitted by a fly. Mostly in
sub-Saharan Africa.
Symptoms: Intense cutaneous
itching and inflammation. Skin
nodules. Vision loss, due to
larval worms that migrate to
cornea. Immune response to
these causes irreversible
clouding of cornea.
25e6+ infected, 300K blind.
Department of Kinesiology and Applied Physiology
1
Onchocerciasis
(river blindness)
Treatment: 1 dose of ivermectin
every 6 or 12 months kills larval
worms. Ivermectin is taken
orally, has a wide safety margin,
and does not require
refrigeration.
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1
Ivermectin
Member of avermectin
family.
Mechanism of action:
Activates glutamate-gated
chloride channels =>
prevents action potentials in
larval nerve and muscle =>
paralysis & death of larvae.
Human Cl channels not
affected due to insensitivity
to drug and protection by
blood-brain barrier.
Department of Kinesiology and Applied Physiology
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Ivermectin Discovery
Satoshi Omura, Kitsato Institute,
Japan, 1975.
Omura and team at Kitasato
University developed methods
for rapid screening of
environmental samples for
biological activity, and for
isolation of active compounds
and bacteria from samples.
Thousands of samples screened
for biological activity. Many new
microbial species isolated.
Department of Kinesiology and Applied Physiology
1
Ivermectin Discovery
54 promising cultures sent to W.
Campbell at Merck in USA for
further study for veterinary
potential. Streptomyces
avermitilis yielded avermectin.
Effective vs equine Onchocerca
cervicalis, but significant side
effects.
Convert a double bond to single:
more effective, less side effects.
Campbell suggested testing in
humans, since related parasite,
O. volvulus, causes river
blindness. It worked.
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Lymphatic filariasis
(elephantiasis)
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1. “The Nobel Prize in Physiology or Medicine 2015”.
http://www.nobelprize.org/nobel_prizes/medicine/laureates/2015/press.html Retrieved
2.
3.
4.
5.
2015-10-06.
Burg, R.W., B.M. Miller, E.E. Baker, J. Birnbaum, S.A. Currie, R. Hartman, Y.-L. Kong,
R. Monaghan, G. Olson, I. Putter, J.B. Tunac, H. Wallick, E.O. Stapley, R. Oiwa, and
S. Omura. Avermectin,new family of potent anthelmintic agents: producing
organism and fermentation. Antimicrobial Agents and Chemotherapy 15: 361-367,
1979.
Egerton, J. R., Ostlind, D. A., Blair, L. S., Eary, C. H., Suhayda, D., Cifelli, S., Riek, R. F.
and Campbell, W. C. Avermectins, a new family of potent anthelmintic agents:
efficacy of the B1a component. . Antimicrobial Agents and Chemotherapy 15: 372378, 1979.
Tu et al., Yao Xue Xue Bao 16:366-370, 1981. (Chinese)
S. Omura. Philosophy of New Drug Discovery. Microbiological Reviews 50: 259279, 1986.
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6. “Parasites”. Center for Disease Control and Prevention. http://www.cdc.gov/parasites/
Retrieved 2015-10-05.
7. “Diagnostic parasitology”. Don Lehman [2008].
http://www.udel.edu/mls/dlehman/medt372/P-falcip.html Retrieved 2015-10-05.
8. “Ivermectin.” Stanford University.
http://web.stanford.edu/group/parasites/ParaSites2005/Ivermectin/ Retrieved 2015-10-06.
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