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Cholera Drug Tested Successfully, but Pandemic Advances


Researchers in Bangladesh have tested a drug that cures cholera in most patients, showing that it is a useful new weapon in an arsenal that has grown weak against the cholera organism's growing drug resistance. But, drugs alone cannot halt the advance of cholera across the globe.

The world is in the midst of a cholera pandemic that began 45 years ago in Indonesia. Cholera is an infectious disease of the small intestine that causes watery diarrhea, vomiting and muscle cramps. In severe cases, rapid loss of body fluids leads to dehydration and shock. Without treatment, death can occur within hours. The disease thrives in contaminated water and United Nations figures show that one-sixth of humanity, one billion people, do not have access to clean water. Another 2 1/2 billion are without sanitation. The World Health Organization says that by 1992, the cholera pandemic feeding on these conditions had swept across the developing world, invading regions that had not seen it in a century.

But medicines that have been a mainstay against this diarrheal illness are growing less effective because of overuse. Physician Michael Bennish of the University of Oxford in England says the vibrio bacterium that causes epidemic cholera has been adapting to the drugs.

"Resistance is developing faster than we can identify new agents and new treatments. We don't have many options left. It's a very meager set of options at this point," he said.

Just 10 years ago, Bennish and colleagues found that a single dose of an antibiotic called ciprofloxacin was very effective in treating severe cholera in adults in Bangladesh. But like other cholera drugs, it has weakened against the disease since then, causing the team to test a newer antibiotic called azithromycin.

The results published in the New England Journal of Medicine are hopeful. A single 95-cent dose of azithromycin ended watery diarrhea in two days for three-fourths of the patients who took it. In contrast, ciprofloxacin succeeded in only one-fourth of patients.

"The good news is that we've found a new, effective antimicrobial regimen that is inexpensive and appropriate for use in developing countries, safe for use in children and adults, well-tolerated, and extremely effective," added Bennish. "The bad news is that the drug that we've come to rely on for the last 15 years, ciprofloxacin, has all of a sudden proved ineffective because resistance has developed to it."

But time may be running out for azithromycin, too. Bennish says the vibrio bacterium is starting to become resistant to this newer drug -- at least in Bangladesh.

"If we get widespread resistance to both azithromycin and ciprofloxacin, we're really in a very, very difficult position and there is no easy answer," he said.

Bennish says there is a great need to develop new affordable drugs. But he and others acknowledge that drugs cannot hold the line against cholera in a world where billions live in unclean conditions.

The director of the University of Virginia's Center for Global Health, Dr. Richard Guerrant says the sanitation revolution of the 19th and early 20th centuries eliminated cholera in Europe and North America, but in developing countries, there is too much emphasis on antimicrobial drugs and oral rehydration therapy -- a solution of salts and other substances, such as sugars, which is administered orally.

"Clearly, the problem is one of lack of adequate water and sanitation. That has created the huge need not only for oral rehydration, but for the antimicrobials that we are rapidly losing. The antibiotic approach is obviously life-saving and tremendously important. Oral rehydration therapy is perhaps the greatest medical advance and perhaps also the greatest indictment of 20th century medicine because we have basically done that instead of the sanitary revolution," he explained.

Six years ago, United Nations member states set a goal of reducing the percentage of people lacking clean water and sanitation by half as one of several Millennium Development Goals to be met by 2015.

But an analysis by the Center for Strategic and International Studies in Washington says the effort is underfunded and will require an extra $15- to 30-billion in addition to the $30 billion already invested each year in development.