MSU Plays Key Part in Effort To Eliminate River Blindness and Elephantiasis

An MSU researcher has worked extensively in Africa and South America to eliminate filarial diseases like elephantiasis and river blindness. He reports there is light at the end of the tunnel.

Some 140 million people worldwide suffer from filarial diseases, such as river blindness and elephantiasis.  These infectious, tropical diseases caused by parasitic worms have devastated populations, especially in equatorial Africa. 

But Dr. Charles Mackenzie, professor of veterinary pathology, believes he and his many colleagues can eliminate the disease by 2020.

“Yes, I really think it’s possible,” says Mackenzie, who has spent half his life in

African nations like Sudan, Tanzania and Cameroon, where filarial diseases are rampant.  “We’ve already succeeded in eliminating river blindness from Ecuador.”

Indeed, Ecuador, where some 86,000 people were affected by the parasite that can cause blindness, essentially wiped out the disease by 2007, after some 15 years of a program where academics, government ministries and drug manufacturers teamed up to attack the problem.

Mackenzie has recently received a $2 million grant to reformulate an existing drug that can stop these debilitating diseases in a much shorter time than traditional drugs.  The funding comes from a $13 million grant to the Washington University School of Medicine, St. Louis, MO, from the Bill and Melinda Gates Foundation.

“What happens in these diseases is that one’s body is infected by thread-like worms, which then deposit many baby worms in the blood stream,” he explains.  “In some cases, they can produce 100,000 baby worms in one millimeter of blood.  We have a drug that can kill off the baby worms, but we have to treat the patient every year for about 18 years, until the parent worm dies and stops reproducing.”

Indeed, ivermectin, produced by Merck, has proven effective at killing the baby worms that cause both river blindness and elephantiasis.

“Now if we had a drug that can kill the parent worm, then you can possibly cure the patient in a matter of three weeks,” says Mackenzie.  “It will take longer to take care of the entire population, but still, we could end the problem in a much shorter period of time.”

The scientists do not have to wait for a miracle drug.  In fact, it already exists.  Mackenzie recalls that when he was in Mexico in 1981, he had a drug—flubendazone, now made by Johnson and Johnson—that could kill the parent worm that causes river blindness.  But the drug was formulated in a way that could cause unwanted side effects.

“The problem is that those drugs were not properly formulated and could not be safely applied,” he explains.  “But since then, formulation science has changed  dramatically.  We now can apply some very clever science, including nanotechnology, and we can develop a brand new reformulated drug that can be easily used in the field and hopefully can kill the parent worms.”

For this to happen, he says, “a new drug needs to be safe, and it needs to work.”  Those in academia work to determine the drug’s efficacy—that is, whether it works.  As far as the safety, he says, “this is generally done by commercial entities, since it’s a very, very regulated business.”  Any new drug must receive approval from both the Federal Drug Administration and the equivalent European agencies.

“Those of us in academia—here at MSU and our colleagues at McGill University—can take care of the efficacy part,” says Mackenzie.  “Pharmaceutical companies, like Johnson and Johnson and our new partner DNDi, can take care of the approval.  Both of us then partner with health ministries on the field application.”

Mackenzie notes that the pharmaceutical companies have donated the drugs free-of-charge, something that has not been widely publicized.  “They deserve some credit,” he says. “They do a lot of good with these diseases and the public does not know.”

A Scotsman who came to MSU via Australia and England, Mackenzie considers himself equal parts pathologist, clinician and researcher.  He began to specialize in filarial diseases in 1978, when the MRC Mill Hill—Britain’s equivalent of the U.S. National Institute of Health—sent him to Cameroon to work on river blindness.

“I primarily did lab work,” he says. “I was trained as a pathologist, and as such, I always want to know why something works or why someone is sick.  My passion is for the clinical aspects of medicine.”

Mackenzie says people are sometimes puzzled that he is involved with the elimination of human diseases, when his primary degree is in veterinary medicine. But he notes that human drugs are first tested on animals, so it does not take a stretch to see how he might fit into the human picture.  He likes to tell stories of many of the patients he has observed in the filarial programs and how the programs succeeded over time.  He also likes to shed myths about parasitic diseases.

“It’s generally okay to live with parasites, and most of us do,” he notes.  “There’s nothing wrong with that.  In the cases of these diseases, they erupt when the baby parasites die.  River blindness is essentially skin disease, where the dead parasites cause an inflammation to the wrong area and kill off your retinal cells.”

He adds that elephantiasis is also essentially a skin disease, where people’s bodies swell and their skin changes to resemble elephant skin.  The problem arises when a secretion by the parasitic worms causes one’s lymphatic vessels to increase to many times their original size and to become dysfunctional and leak.  This often happens in the lower limbs and the scrotum of males.

Filarial diseases are transmitted by insects. Elephantiasis, or lymphatic filariasis, is spread via mosquitoes.  River blindness,  or onchocerciasis, is spread by black flies.  Mackenzie began working in the early ’80s on river blindness in Sudan, which he believes has the highest incidence of the blinding disease. At the time, there was no safe treatment. The team he worked with had to find a drug that killed the worm without making people blind. Eventually his team and others tried ivermectin, developed by Merck & Co., to kill roundworms and ectoparasites in animals. The treatment worked. It’s been used in West Africa and is on its way to eradicating the disease in that region.

“The onchocerciasis program was set up by Merck in 1987 and was very successful,” Mackenzie says. “By the end of the ’90s, countries, global health agencies and drug companies decided to try to do the same thing—mass treatment of everyone in the area affected—for elephantiasis.”
           

The two drugs used in Africa for the new elephantiasis program were the ivermectin from Merck and in addition albendazole donated by GlaxoSmithKline (GSK). In 1999, Mackenzie helped write the successful grant proposal for Gates funding, during the time he was the first Merck/GSK program director for the African program. That global program began in 2000 in Tanzania.
          

MSU, Washington University, Case Western Reserve University in Cleveland and McGill University in Montreal are all working on projects with funding from the grant and together form a Filariasis University Consortium. The research teams work closely with GSK and Merck, both of which have donated millions of dollars worth of medicine. The entire effort, in coordination with the World Health Organization, the ministries of health in more than 80 countries, and dozens of private and public donors and researchers, hopes to eliminate filarial diseases by 2020.
           

“Even though most of the work we’ve done in Africa has to do with eliminating the spread of elephantiasis by primarilypreventing the mosquito’s ability to transmit the infection, we’ve discovered unexpectedly that the elephantiasis patients living in areas involved in the mass treatment program actually are getting better,” notes Mackenzie, who has an ample photo album of before and after photos of patients. 

Mackenzie has spent a great deal of time in Sudan and also in Tanzania after beginning this work and is now the national advisor to the president in Tanzania. Some 19 million people exposed to filariasis have been treated so far, with 30 million to go. That could be even more daunting than it sounds if it were not for the country’s excellent health system and political system, Mackenzie says. “We developed a package that the Tanzanians follow for treatment. Because the drugs are so safe, we’ve had no problems. The Tanzanians have done a great job.”
           

One surprising result is that while Mackenzie and his fellow researchers expected the drug treatments to stop new infections of elephantiasis, it also helped those already affected with the disease.

“No one quite understands why, so we’re making careful observations on the outcomes of these public health programs,” says Mackenzie. “But overall, the treatment programs are now beyond the research phase, very safe and administered through public health systems. For someone who remembers what things were like decades ago, this seems miraculous.
           

“It’s changed the face of tropical medicine.  You can get health care to people that never would have received it.”