PUBLIC HEALTH:

Sturdy cholera bug thrives as researchers look to stanch outbreak

The cholera bug lives on tiny sea crustaceans in the Bay of Bengal. The sea critters thrive in these tropical conditions, feeding on blooming phytoplankton. So too does the cholera bacterium.

It is the increasing flow of rivers carrying agricultural nutrients into oceans that promote phytoplankton, and by extension, cholera bugs in the environment, according to a new study published in The American Journal of Tropical Medicine and Hygiene.

Some had suggested a direct role for global warming, based on a paradoxical observation: In the Bay of Bengal, rising sea surface temperatures -- a key end point of climate change -- have been linked to a thriving population of phytoplankton. Everywhere else in the world, warmer water causes phytoplankton to die out.

The reason for this paradox is that rivers are discharging faster into the bay, bringing in nutrients from farming and other livelihoods, and leading to phytoplankton blooms, according to the study. Sea surface temperature appears to be a confounding variable. "There is no direct relationship between sea surface temperature and cholera," says Shafiqul Islam, a researcher at Tufts University and lead author of the study.

This does not mean that climate change is off the hook.

"There are relationships between flood and cholera and drought and cholera," Islam said. "If there is climate change, and that is translated to more frequent flood or more frequent drought, that will also lead to cholera."

The clarification comes as researchers are profiling the cholera bug and its environment and finding new ways to address the disease. Reported cases have risen by 130 percent since 2000, according to the World Health Organization's 2010 status report.

"I think the cholera situation has become worse," said Claire-Lise Chaignat, head of the WHO Global Task Force on Cholera. "Cholera is occurring in places that are more widespread."

There are outbreaks ongoing in West and sub-Saharan Africa. And cholera was detected exactly a year ago, for the first time in more than a century, in Haiti. It has since sickened more than 400,000 and caused 6,000 deaths, according to the United Nations.

In its wake, the policy world has lurched into controversy about the origins of the outbreak and the best ways to handle the disease during a humanitarian crisis. Thousands of lives could be saved if cholera vaccines -- at $1.85 a dose -- are easily available, scientists say. There are only enough doses in the world to vaccinate a few hundred thousand people, primarily travelers.

Fanning the controversy is the fact that cholera is nothing more than diarrhea caused by poor water and sanitation. No patient dies of infection; they die of dehydration. The primary protection against the disease is clean water availability, still out of reach for billions of people. The simple cure -- a saline solution -- could be available to the affected for mere cents. And yet, at least 100,000 people die from the disease yearly, according to the World Health Organization.

The most important defense in humanitarian situations ought to be more adequate water and sanitation, said Seth Berkley, CEO of the Global Alliance for Vaccines and Immunizations.

Still, the World Health Organization is currently exploring the possibility of stockpiling the cholera vaccine, said Pem Namgyal, coordinator at the Department of Immunization, Vaccines and Biologicals at the WHO.

A more virulent cholera bug

Edward Ryan has been working with cholera for two decades, so he was summoned when a 30-year-old man came to Massachusetts General Hospital in January with severe watery diarrhea. The patient had been at a party in the Dominican Republic where others had gotten cholera. The United States saw a rash of the disease in travelers this year.

"We treated him as though he was a probable cholera case from the get-on," said Ryan, director of the hospital's tropical medicine program.

Cholera is new to the Dominican Republic, and experts theorize it was brought into the country by people, or by food and water, from Haiti. "It's the exact same strain as the Haitian strain and by being on the same island as Haiti, presumably it was imported there," Ryan said.

The current pandemic of cholera started even farther away, with the first recorded case in Indonesia in 1960. It has been the longest in recorded history, and it is not ending, instead colonizing new places.

"This is not your grandfather's cholera," said Peter Hotez, dean of the new school of tropical medicine at the Baylor College of Medicine.

The latest incarnation of the bug is the El Tor strain, subtler than the classical version and able to stay hidden in people who become silent carriers. In some patients, the disease can be strikingly virulent. "People can die from the current cholera in 12 hours," said Matthew Waldor, a researcher at Harvard Medical School.

The rise of El Tor means it is time to rethink our response to the disease, Ryan said. "We have the same response we had in 1961, not taking into account that this really is a different beast than when the pandemic got started," he said.

While water and sanitation are incredibly important, these are not available to 13 percent of the world's population, he said.

Cholera in Haiti, one year on

Cholera continues to sicken people in Haiti as the bug has become endemic, said Jonathan Weigel, research assistant at Partners in Health.

"We are alarmed by the rising cases and departure of a lot of other health care workers and aid groups," he said. The nation was rocked by controversy over the origins of the epidemic, which has been linked to U.N. peacekeepers.

In its wake, experts have said vaccination after an outbreak begins is protective against the disease. WHO came to the same conclusion this year, Chaignat said.

"There are a couple of cholera vaccines; they are not fabulous in terms of efficacy but they are safe," said Berkley of GAVI. Cholera is often accompanied by a breakdown of water infrastructure caused by natural or other disasters. In these situations, a single dose, highly effective vaccine is easiest to administer. But those available today require two doses, which cannot be easily distributed to hard-to-reach communities.

Both vaccines are injections of killed bacterium that provoke a protective immune response. One is already pre-qualified by WHO and the other could get the certification before the end of the year, Chaignat said.

A catch-22 situation

The vaccines are not cheap. Dukoral, made by Crucell Sweden, costs $5 a dose, and Shanchol, made by Shantha Biotech, costs $1.80. The costs of administering two doses within a week without a proper public health system at the time of a humanitarian crisis could be significant, said WHO's Chaignat.

Partners In Health, which responded to the Haiti cholera outbreak, will soon conduct a study of how effective and easy the process is, said Weigel of Partners in Health.

"When Haiti happened, several people said, 'Why don't we deploy vaccines?' This was like in the first week," Waldor said. But there was not enough supply, with fewer than 400,000 doses available worldwide. Crucell Sweden said to the Financial Times that they offered to make a donation to Haiti but were turned down. Weigel said this was on ethical grounds -- with only enough doses for a few hundred thousand people, the selection of the recipients would be difficult.

Scientists have argued for a stockpile of vaccines to solve the supply issues and convince companies to produce more. "It's one of these nonstarter conversations," Weigel said. "You talk to manufacturers, they don't want to make it unless there's demand."

Namgyal of the WHO said stockpiling cannot create demand by itself. If about 10 million doses were stockpiled, the vaccines could reach the expiration date without being used in the absence of an emergency. A better way would be to have routine vaccinations in the 50 nations where the disease is endemic, he said.

The WHO is exploring ways to invest in vaccines, despite lack of funds, said Chaignet. "We'll have to find innovative solutions," she said.

Ryan's patient was easily cured, but hospitals and health care are not easily available in the developing world, he said. And cholera will never be eradicated.

"Cholera doesn't require us to survive," Ryan said. "If all the humans got wiped off the planet, the cholera will survive perfectly fine in its water environment as is."

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