Andrew Maykuth Online
The Philadelphia Inquirer
June 3,  2004

A new front in the war on a disfiguring illness
Millions will get free Glaxo, Merck drugs.


Lakshmi Sambandam

CHENNAI, India -- The disease struck Lakshmi Sambandam 15 years ago when her right leg ballooned, followed by bouts of fierce fever. "Each time, the swelling became bigger and bigger," she said.

Sambandam, 54, had contracted lymphatic filariasis, which afflicts more than 120 million people worldwide, though it is rarely seen in the West. Sambandam's bloated lower leg soon resembled that of the animal from which the illness gets its common name: elephantiasis.

The grotesque, debilitating disease has defied remedy, but tomorrow, with major contributions from two companies with connections to the Philadelphia area, a major step will be taken to wipe the disease off the planet.

In the state of Tamil Nadu in southern India, all 23 million residents in the areas where the mosquito-borne parasite that causes the disease exists will receive one-day treatments, which are repeated annually over five years.

GlaxoSmithKline P.L.C., the British drugmaker whose U.S. headquarters are in Philadelphia, and Merck & Co. Inc. are donating two of the three drugs that are key ingredients in fighting the disease.

Glaxo "was looking for something big to make a difference," said Nancy Pekarek, a Glaxo representative in Philadelphia. "We have a social responsibility to do something like this."

In the last decade, the World Health Organization identified filariasis as one of the few diseases that can realistically be eliminated as a public-health threat - polio and leprosy are among the others. A campaign to stamp out filariasis by 2020 is in full swing in countries such as India, which accounts for about 40 percent of the world's cases.

"It's a very old disease, so in a lot of communities, people accept it as fate," said Dr. V. Kumaraswami, a filariasis expert in Chennai, a coastal city formerly known as Madras.

Then there are those who are suspicious of this dramatic sweep to eradicate a disease, wondering what lurks behind free drugs.

Glaxo has agreed to give albendazole, an anti-parasitical drug developed 27 years ago at its former Applebrook Research Center in Chester County. So far, Glaxo has donated 250 million tablets of the drug and is committed to maintaining the gift until the disease is eliminated.

Merck, based in Whitehouse Station, N.J., is donating the anti-parasitical drug Mectizan to fight filariasis in Africa. Mectizan is also used to combat onchocerciasis, or river blindness.

While many pharmaceutical companies donate their products to promote goodwill, the campaign to eliminate lymphatic filariasis presented the drugmakers with a unique public-relations opportunity - to help consign a single disease to history.

Glaxo estimates that its contribution will amount to $1 billion by the time the program is completed in 2020, or $50 million annually. Glaxo's pretax profits in 2003 were $12.3 billion.

Elephantiasis is all too familiar in the more than 80 countries where it is endemic. Some sufferers with massive legs and arms are regarded as so repulsive - and are so immobilized - that they become hermits in their homes. Many suffer from dramatically enlarged genitals, caused by the buildup of lymphatic fluid and dense tissue. "The whole village knows who has a huge scrotum," said Kumaraswami, deputy director of Chennai's tuberculosis research center.

Filariasis is fatal only in cases where the enlarged limbs become infected. But the disease exacts a substantial psychological and economic hardship on the estimated 40 million people who have severe cases.

Sambandam is among the more fortunate. When the disease struck, she was already married with children, unlike many younger sufferers who are shunned because of their deformities. She also works for the national government, whose insurance paid for two operations that reduced her enlarged leg. It is now about twice the normal size. Her leg is wrapped in a bandage and hidden beneath the long skirt of her sari.

But sometimes Sambandam misses work. "When the fever comes, I can't do anything," she said. The campaign to eliminate the disease requires treating broad populations, even though only a small percentage are infected. Everyone in the areas where the disease is prevalent - 1.2 billion people around the world - is targeted for drugs. And each person must take the medications once a year for five years to interrupt the parasite's breeding cycle.

"If the program works well, we just need five years to eliminate it from an area," said Dr. Francesco Rio, the WHO's chief lymphatic filariasis-elimination officer in Geneva, Switzerland. "But we need to treat more than a billion people, a fifth of the world population." About 350 million are targeted for treatment this year.

Researchers estimate that 80 percent of the endemic population must be treated to kill off the parasite. "Once you hit a threshold, and, biologically, it doesn't survive," said Dr. Eric A. Ottesen, head of the Emory University Lymphatic Filariasis Support Center in Atlanta.

In Tamil Nadu, health officials traditionally tried to contain the disease by attacking mosquitoes. But mosquito-control programs are insufficient.

About a decade ago, scientists introduced a new diagnostic test that allowed them to detect with a pin-prick whether a person's blood was infected with filariasis. Health officials then could precisely target areas for treatment.

Along with the new diagnostic tool, researchers gained a greater understanding of how new drugs attacked the parasite.

Until the 1990s, health officials treated filariasis with a generic drug called diethylcarbamazine, known as DEC. It is effective, but it cannot be used in mass campaigns in Africa, because it causes severe side reactions in patients with river blindness.

Researchers found that the Merck drug Mectizan, when combined with the Glaxo drug albendazole, was safe and effective against filariasis. So those two drugs are now used in Africa, which has a third of the world's filariasis cases.

In Asia, researchers found that albendazole increased DEC's effectiveness. The WHO now urges campaigns with the two-drug combination.

The WHO found willing partners when it enlisted Glaxo and Merck into the Global Alliance to Eliminate Lymphatic Filariasis.

Brenda Colatrella, Merck's senior director in the office of contributions, said the company agreed to readily donate Mectizan, whose generic name is ivermectin. "To not make the drug available would be out of the question," she said.

Merck also gets a tax break for some of its contribution. Glaxo, a British company, gets no U.S. tax benefit. The U.S. patents have expired on both drugs, so they are not as profitable as they once were.

In Tamil Nadu, local officials were enthusiastic about expanding their fight against filariasis.

State health officials had already established a pilot project to mix DEC into table salt sold to the public. Infection rates fell significantly, to less than a tenth of a percent of the population. But the disease persisted. The drug was not reaching enough people.

With WHO support, the state government launched annual one-day campaigns to distribute the drugs door to door.

Not everyone was receptive. Many Indians believe lymphatic filariasis is not a threat. Even in India, the disease is frequently dismissed as something that affects only the poor.

"In most public-health campaigns, fear is a motivating factor in the social mobilization," said Dr. D.J. Augustin, a local WHO officer. "So how do you make a healthy person swallow a drug to help someone else? It takes lots of publicity and personal selling."

Health officials also experienced unexpected resistance to albendazole from politicians who questioned Glaxo's motives for giving something away.

"People wonder: Is it addictive?" Augustin said.

Dr. P. Krishnamurthy, Tamil Nadu's director of public health, did not need to be convinced. "As a public-health official, I'm happy to be getting free drugs," he said. Albendazole is now used in about half the state's districts.

"We are on the verge of eliminating this disease," he said. "If we do a little more effort, we can eliminate it in a few years. We should not give up at this point."


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