Department of Kinesiology and Applied Physiology 1

2016 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"

Department of Kinesiology and Applied Physiology 1

Parasites and Parasitic DiseasesParasite: An organism that lives on or in a host and gets its food from or at the expense of its host.1

ProtozoansPlasmodium falciparum

(malaria)

HelminthsRoundworms,

tapeworms, etc.

EctoparasitesTicks, fleas, lice, etc.

Source and vector of disease

Department of Kinesiology and Applied Physiology 1

Department of Kinesiology and Applied Physiology 1

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.

Department of Kinesiology and Applied Physiology 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 1

Ivermectin DiscoverySatoshi 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 Discovery54 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.

Department of Kinesiology and Applied Physiology 1

1. “The Nobel Prize in Physiology or Medicine 2015”. http://www.nobelprize.org/nobel_prizes/medicine/laureates/2015/press.html Retrieved 2015-10-06.

2. 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.

3. 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: 372-378, 1979.

4. Tu et al., Yao Xue Xue Bao 16:366-370, 1981. (Chinese)5. S. Omura. Philosophy of New Drug Discovery. Microbiological Reviews 50: 259-

279, 1986.

Department of Kinesiology and Applied Physiology 1

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.