River Blindness,
Elephantaisis, and
Guinea Worm
- A quick look.
Dr. Charles E. Novitski
April 3, 2011
Overview Today
Earlier perspectives, avermectin and
milbemycin.
Merck & Co’s philanthropy.
River Blindness (onchocerciasis) &
Onchocerca volvulus; 1987.
Elephantiasis (lymphatic filariasis) &
Wuchereria bancrofti; 1998.
Guinea worm disease & Dracunculus
medinensis, 1986.
Goal of permanent erradication.
Previous
 Worked at Agrigenetics Advanced Sciences Company,
Madison, Wisconsin. 1984-1988. First plant biotech
startup company.
 Project goal: to protect plants against plant parasitic
nematodes, avoiding standard chemical pesticides.
 Approaches:
 Strongly root-colonizing bacterium, Pseudomonas cepacia,
method patented. (used commercially.)
 Mouse antibody genes expressed in transgenic plant cells,
intending to disrupt feeding cell interaction.
 Funded work on dissecting genes for milbemycin pathway in
Streptomyces species.
Previous
Observations at the time:
(1) Avermectins (similar chemically to
milbemycin) were identified by Merck in 1978.
These were highly effective against some
animal-parasitic nematodes, with low side
effects.
It was unfortunate that they were too expensive
for people in poorer countries, who needed them.
(2) Not unexpectedly, companies had the
attitude that they cannot spend money
developing a cure unless likely profits will
more than pay for the development.
Overview Today
Earlier perspectives, avermectin and
milbemycin.
Merck & Co’s philanthropy.
River Blindness (onchocerciasis) &
Onchocerca volvulus; 1987.
Elephantiasis (lymphatic filariasis) &
Wuchereria bancrofti; 1998.
Guinea worm disease & Dracunculus
medinensis, 1986.
Goal of permanent erradication.
Merck & Co.
 Avermectins.
 Avermectins were identified by Merck in 1978 and
published in 1979. These were highly effective
against some animal-parasitic nematodes, with low
side effects.
 Mectizan= ivermectin= avermectins B1a + B1b.
 Metabolite of the bacterium Streptomyces avermitilis.
 Recommended about 150-200 µg/kg body weight.
 Affinity for glutamate-gated and
gamma-aminobutyric acid (GABA) gated chloride
channels.
 Doesn’t cross the blood brain barrier in mammals,
but interferes with neurotransmission in some stages
in some nematodes.
Avermectins B1a and B1b
Merck & Co.
Philanthropic step, 1987, by Merck & CEO Dr.
Roy Vagelos:
Agreed to donate Mectizan for as long as it takes
to “control” onchocerciasis (river blindness).
The scope of the commitment appears to be due
in part to persuasion of former President Jimmy
Carter.
The funding behind the cost includes the River
Blindness Foundation and the money of John
Moores. And later also the Bill and Melinda Gates
Foundation. And Lion’s Club and others.
Overview Today
Earlier perspectives, avermectin and
milbemycin.
Merck & Co’s philanthropy.
River Blindness (onchocerciasis) &
Onchocerca volvulus; 1987.
Elephantiasis (lymphatic filariasis) &
Wuchereria bancrofti; 1998.
Guinea worm disease & Dracunculus
medinensis, 1986.
Goal of permanent eradication.
River Blindness
(Onchocerciasis)
Short Film Clip:
http://www.cartercenter.org/news/multi
media/HealthPrograms/PreservingVision
forFutureGenerations.html
3 minutes, 10 seconds.
River Blindness
(Onchocerciasis)
Itchy skin rashes; nodules in skin
Inflammation of the cornea, long term.
Thickening of the corneal stroma.
Leads to blindness
Cause is infections by filarial nematode
Onchocerca volvulus.
Mectizan kills microfilariae.
Mectizan does not kill adult worms, but does
sterilize adult females.
Adult worms do not cause symptoms.
Onchocerca volvulus
 Filarial nematode.
 Black fly, genus Simulium, host.
 Microfilariae: gut to flight muscles.
 L1 larvae
 L2 larvae
 L3 larvae: to proboscis & salivary gland and into bite of
human
 Obligate host: human
 L3 larvae into blood, to subcutaneous tissue, form nodules.
 Become Adults over 6-12 months.
 Then migrate to subcutaneous tissue to mate (males &
females). Can live 15 years.
 Females produce 1000 to 3000 microfilariae/day.
Microfilariae can live 1 to 2 years.
 Taken up by black fly bite blood meal.
River Blindness
Eradication Efforts
1987 Merck donations began.
Merck donations extended to all needy
communities. 530 million treatments.
Bill & Melinda Gates Foundation recent help.
Mectizan 150 µg/kg once a year sufficient for
patients. Twice a year better for eradication.
World eradication not currently likely, but in
the Western hemisphere, eradication is
planned by the Carter Center by 2012 or soon
thereafter.
Overview Today
Earlier perspectives, avermectin and
milbemycin.
Merck & Co’s philanthropy.
River Blindness (onchocerciasis) &
Onchocerca volvulus; 1987.
Elephantiasis (lymphatic filariasis) &
Wuchereria bancrofti; 1998.
Guinea worm disease & Dracunculus
medinensis, 1986.
Goal of permanent eradication.
Elephantiasis
(Lymphatic filariasis)
Short Film Clip:
http://www.cartercenter.org/news/multi
media/HealthPrograms/AlleviatingSuffer
ingEndingShame.html
4 minutes, 37 seconds.
Elephantiasis
(Lymphatic filariasis)
Swelling of legs (& arms) due to damaged
lymph system.
Hardening and thickening of the skin, called
elephantiasis.
In Africa, the cause is a filarial nematode,
Wuchereria bancrofti.
Common vector in Africa is the mosquito
genus Anopheles.
In Asia, LF is also caused by nematodes
Brugia malayi and Brugia timori.
Wuchereria bancrofti
Filarial nematode.
Mosquito, genus Anopheles, host.
Microfilariae: gut to flight muscles.
L1 larvae
L2 larvae
L3 larvae: to proboscis & salivary gland and into
bite of human
Human host (or veterbrate host).
L3 larvae migrate to lymphatic vessels and lymph
nodules.
Become Adults.
Then migrate to subcutaneous tissue to mate
(males & females). Can live several years.
Females produce many microfilariae.
Lymphatic Filariasis
Elimination Efforts
1998 Merck donations began for lymphatic
filariasis.
Treatment is by Mectizan (Merck) 150 µg/kg
plus albendazole (donated by
GlaxoSmithKline), once a year. Plus bed nets
to control mosquitos.
Lymphatic Filariasis Control
& Elimination Efforts
120 million people in 80 countries are
infected.
With 26 million treatments since 1998,
infection rates have decreased 90%.
Overview Today
Earlier perspectives, avermectin and
milbemycin.
Merck & Co’s philanthropy.
River Blindness (onchocerciasis) &
Onchocerca volvulus; 1987.
Elephantiasis (lymphatic filariasis) &
Wuchereria bancrofti; 1998.
Guinea worm disease & Dracunculus
medinensis, 1986.
Goal of permanent eradication.
Guinea Worm
(Dracunculiasis)
Short Film Clip:
http://www.cartercenter.org/health/gui
nea_worm/mini_site/gallery.html
2 minutes, 34 seconds.
Guinea Worm
(Dracunculiasis)
Painful sores appear. Female nematode
Guinea worm larvae up to 3 feet long release
larvae into water.
Cause is the nematode, Dracunculus
medinensis.
The second host are copepods (crustaceans),
that leave larvae in unclean water.
Dracunculus medinensis
Nematode.
Copepod (crustacean), “water fleas”, host.
L1 larvae from female nematode from human
“eaten” by copepod.
L2 larvae
L3 larvae, released to water.
Human host.
L3 larvae in water penetrate stomach and intestine
walls.
Become Adults and mate (males & females).
Males die.
Females then migrate to subcutaneous tissue.
After one year, females, from hole in skin, release
L1 larvae when in contact with water. Cycle
complete.
Guinea Worm The Approach
1986 Carter Center began.
Use of only clean water by cloth filtering out
the water fleas,
Or by water treatment (BASF-donated ABATE
larvicide) against water fleas.
Or water by well.
Female worm removal from patient by stick.
No drug treatment used for humans. No
vaccines available.
Guinea Worm Elimination Efforts
1986, 3.6 million cases in 20 countries.
2010, only 1797 cases in 4 African countries
(Sudan, Mali, Ethiopia, and Ghana.) Down
more than 99%.
The Carter Center anticipates worldwide
complete elimination of Guinea worm within a
few years.
This will be the second human disease ever
completely eradicated, since small pox was
eliminated permanently in 1979.