Fighting leprosy's spread

by Steven Ford

June 17, 2001 Orlando Sentinel

Modern pharmaceutical advances have helped humans overcome, or at least control, a host of once-deadly diseases.

Thanks to modern drugs and vaccines, historical maladies such as typhoid and tuberculosis no longer carry the specter of certain death for people in industrialized nations. Even AIDS, the contagion of modern times, often can be controlled for multiple years under a regimen of anti-HIV drugs, the so-called AIDS drug cocktails.

But one disease from antiquity still rears its head in many parts of the world. It is a disease that, along with AIDS, carries with it one of the darkest stigmas and a long history of misunderstanding.

Leprosy.

To say the word is to conjure images of biblical outcasts, pitiful beggars and Medieval victims forced to roam the countryside with wooden clappers, telling all who approach that they draw near to the very embodiment of uncleanliness.

Many people in Western industrial nations might be surprised to learn that the disease is still a serious epidemic in many parts of the world, primarily in impoverished areas of India, Africa and Central and South America. Even in the United States, there are on average about 100 to 120 cases reported each year.

A Central Florida microbiologist's research is being studied by two companies hoping to produce effective anti-leprosy drugs. Separate pharmaceutical companies in Switzerland and Japan are conducting human clinical testing of drug derivatives that have been studied extensively by Dr. Arvind Dhople at the Florida Institute of Technology in Melbourne. The human testing of these drugs is about halfway through the companies' 10-year testing cycle.

Leprosy is caused by the bacterium Mycobacterium leprae, which is similar to the rod-shaped tuberculosis bacterium. There are two major forms of the disease. Tuberculoid leprosy brings well-defined and numb skin lesions. Lepromatous leprosy's symptoms include inflamed tissue under the skin and more widespread lesions. It is the most severe form of the disease. Both forms cause nerve damage in the extremities.

Many myths surround the disease. For instance, it is not easy to contract. And the disease does not cause limbs to rot and fall off infected individuals. Instead, the malady destroys the nerve endings in infected sufferers. Without tactile sensations in infected extremities, leprosy patients often will mutilate themselves accidentally. Over time, these repeated incidences of damage can severely and adversely affect the hands, feet and other parts of infected victims.

Scientists think that the disease is spread through droplets of nasal mucus, though they are not certain.

Leprosy also is known as Hansen's disease, named after Norwegian physician Armauer Hansen, who first discovered the leprosy bacterium in 1874. Until then, many people mistakenly thought the disease was hereditary. Hansen was the first to conclude that the disease was infectious.

A peculiar aspect of the disease is that it grows and spreads best in cooler parts of the body. Because of this, it often strikes fingers and ears first.

Currently, three drugs are used to fight the disease, Rifampin, Dapsone and Clofazimine. Often they are administered in conjunction with one another to better prevent the human body from developing a resistance to the drugs. This isn't always effective, though, so pharmaceutical companies are looking at how analogues -- or derivatives -- of these drugs can increase effectiveness.

"Now what is happening is, even for these drugs," said Florida Tech's Dhople, is that ". . . people are developing resistance that we have seen in the last five years. So the drug that the Swiss pharmaceutical company is developing is the [derivative] of Rifampin."

Rifampin attacks the DNA-dependent RNA polymerase of the organism. [Polymerase refers to any of various enzymes that promote the process of connecting simple molecules to form a more complex molecule.] This interferes with the bacterium's RNA synthesis, effectively killing the organism.

The Japanese pharmaceutical company is studying the effects of a derivative of Dapsone. This drug works to kill the leprosy bacterium's enzyme that metabolizes nutrients.

"So when this enzyme is completely destroyed," Dhople said, "the bacterium cannot function."

Both of the clinical studies being used on the two different drugs have benefited from laboratory modeling developed by Dhople, who has studied leprosy for the past 30 years.

One of the biggest obstacles to developing anti-leprosy treatments is that the leprosy organism can't be easily replicated in the test tube.

"It has a very strange requirement for growth," Dhople said, adding that "it needs a very, very tiny amount of oxygen."

Unlike the tuberculosis bacterium, which needs a lot of oxygen to replicate, "this leprosy organism needs oxygen, but in minute quantities," he said.

Dhople said that, in the late '80s, he had limited success in getting the leprosy bacterium to grow in the test tube.

"What we have done is, by controlling the amount of oxygen and also providing some special nutrients to this organism, we are able to grow this organism" with about a 100-fold increase, he said.

Such an increase was a milestone, but it still is not considered a large enough increase to qualify the effort as a complete success. Another needed criterion for the experiment to be considered scientifically successful is that scientists need to be able to take the new growth of the organism and inject it into a "fresh medium" and have it grow. This, too, has not been achieved on a large and statistically quantifiable scale.

Still, Dhople thinks that it is something that may be accomplished in the near future.

"We are working on it," he said. "I would say that, in the next five to 10 years, we should be able because we know now what the problems are."

Another obstacle to developing anti-leprosy treatments is its slow growth rate.

For example, E. coli bacteria doubles every 15 to 20 minutes, Dhople said, and the tuberculosis microbe doubles every five to seven hours. The leprosy bacterium, though, doubles only every 21 to 28 days.

"It is an extremely slow process. And that is why you will see that not many people are working in this particular area of research," Dhople said.

This slow spread of the leprosy bacterium also delays successful testing in laboratory mice, Dhople said. Scientists at the Centers for Disease Control and Prevention created effective mice-testing procedures for growing leprosy bacterium in the 1960s. About 5,000 leprosy organisms could be injected into the rear footpads of mice and, within eight to 12 months, scientists would find that the organisms had multiplied into as many as a million organisms. Still, eight to 12 months is a long time to efficiently conduct such a study.

Dhople's research took anti-leprosy drugs that worked in the test tube and applied them to lab mice that had been injected with the leprosy organism. Instead of waiting eight to 12 months to determine if the organism was multiplying, he was able to examine the effect of the drug in his test-tube model in just four weeks instead.

According to the World Health Organization, leprosy thrives in the so-called "poverty belt" of the globe. India Myanmar and Nepal have 70 percent of the world's cases. Other parts of the world where the disease is strong are Africa, Central and South America and some islands in the Pacific.

"Leprosy is like any other infectious diseases. It's a disease of poor counties," Dhople said.

But between 100 and 120 new cases of leprosy are reported in the United States, too. About 85 percent come from imported cases, Dhople said.

However, there is another possible source of infection in this country, Dhople said, and it is one that possibly could affect Florida in the future.

"In the last 10 to 15 years, we are seeing cases in Texas and Louisiana in which people are handling armadillos," he said, adding that about eight to 10 cases of leprosy a year are attributed to this.

Scientists say that leprosy is able to thrive in armadillos because the animal's core body temperature is cooler than in most mammals.

And the Texas-Louisiana region is susceptible to being endemic of leprosy for a variety of reasons, including proximity to Mexico (and, thus, exposure to infected people from Central and South America traveling through Mexico and across the border into Texas). Another reason is that Southeast Louisiana once was home to one of the nation's primary and longest-run leprosariums. The Gillis W. Long Hansen's Disease Center, better known as the Leper Home, was a 320-acre complex in Carville that was opened in 1894 and operated until the mid-1990s.

Scientists have theorized that armadillos in this region have somehow been exposed to human leprosy victims or perhaps have at one time had contact with discarded bandages used by human carriers.

From there, infected animals transmitted the bacterium to other armadillos.

About 3,000 armadillos from the Lake Okeechobee area have been examined, Dhople said, but none have been found to carry the leprosy bacterium. But this doesn't mean that Florida is not at risk. If armadillos from Louisiana were to migrate eastward into the Panhandle, the armadillo population in Florida could be infected, thereby raising the risk of exposure to humans in the Sunshine State.

"When I say that we have not seen [the infection] in Florida, that doesn't mean that we won't get it," Dhople said, adding that the infected armadillo population might be seen in the next 20 to 40 years.

"And one infected armadillo in the area is enough to spread leprosy," he said.

Feedback | Site Index | Archive | Newsroom Contacts | Terms of Service | Work For Us Advertise Online | Advertise in the Newspaper | Start a Newspaper Subscription © 2001 OrlandoSentinel.com

Powered by Genuity

-- (Paracelsus@Pb.Au), June 18, 2001

Answers

A fellow in old Amarillo

kept a pet armadillo

off fell his nose

his fingers and toes

A leprosy peccadillo

-- (euthanasia@Father.Julian's), June 18, 2001.