Turning the tide against cholera

Two hundred years ago, the first cholera pandemic emerged from these tiger-infested mangrove swamps.

It began in 1817, after the British East India Co sent thousands of workers deep into the remote Sundarbans, part of the Ganga River Delta, to log the jungles and plant rice. These brackish waters are the cradle of Vibrio cholerae, a bacterium that clings to human intestines and emits a toxin so virulent that the body will pour all of its fluids into the gut to flush it out.

Water loss turns victims ashen; their eyes sink into their sockets, and their blood turns black and congeals in their capillaries. Robbed of electrolytes, their hearts lose their beat. Victims die of shock and organ failure, sometimes in as little as six hours after the first abdominal rumblings.

Cholera probably had festered here for eons. Since that first escape, it has circled the world in seven pandemic cycles that have killed tens of millions. Artists of the 19th century often depicted it as a skeleton with a scythe and victims heaped at its feet. It stalked revelers at a masked ball in Heinrich Heine’s “Cholera in Paris” and kills the protagonist in Thomas Mann’s “Death in Venice.” Outbreaks forced London, New York and other cities to create vast public water systems, transforming civic life.

Today cholera garners panicky headlines when it strikes unexpectedly in places like Ethiopia or Haiti. But it is a continuing threat in nearly 70 countries. Now, thanks largely to efforts that began in cholera’s birthplace, a way to conquer the long-dreaded plague is in sight.

A treatment protocol so effective that it saves 99.9% of all victims was pioneered here. The World Health Organisation estimates that it has saved about 50 million lives in the past four decades.

Also, after 35 years of work, researchers in Bangladesh and elsewhere have developed an effective cholera vaccine. It has been accepted by the WHO and stockpiled for epidemics like the one that struck Haiti in 2010. Soon, there may be enough to begin routine vaccination in countries where the disease has a permanent foothold.

Merely creating that stockpile profoundly improved the way the world fought cholera, Dr Margaret Chan, secretary-general of the WHO, said last year. Ready access to the vaccine has made countries less tempted to cover up outbreaks to protect tourism, she said.

That has sped up emergency responses and attracted more vaccine makers, lowering costs. “More cholera vaccines have been deployed over the last two years than in the previous 15 years combined,” Chan said.

The treatment advances relied heavily on research and testing done at the International Centre for Diarrhoeal Disease Research, known as the ICDDR,B, Dhaka. While the centre’s upper levels are quiet and scholarly, its ground floor is the world’s largest diarrhoea hospital. Its vast wards treat 220,000 patients a year, almost all of whom recover within 36 hours. Doctors there save hundreds of lives a day.

The ICDDR, was originally the Cholera Research Laboratory, founded in 1960 by the US as part of that era’s “soft diplomacy.” Research hospitals were built in friendly countries both to save lives locally and to act as sentinels for diseases that might threaten America.

The wards, which in the rainy season extend into circus-size tents in the parking lot, contain long rows of “cholera cots.” On each iron or wood frame is a plastic sheet with a hole in the middle. A bucket beneath the hole catches diarrhoea, while another beside the cot fills with vomit. An IV pole completes the setup.

Defying expectations, the ward smells only of the antiseptic that the floors are constantly mopped with. Patients with severe watery diarrhoea arrive around the clock. A nurse sees each one immediately, and those close to death get an IV line inserted within 30 seconds. It contains a blend of glucose, electrolytes and water. Cholera spurs the intestines to violently flush themselves, but it does not actually damage the gut cells. If the fluid is replaced and the bacteria flushed out or killed, the patient is usually fine.

Within hours, patients start to revive. The techniques perfected here are so effective that the ICDDR,B has sent training teams to 17 cholera outbreaks in the past decade. Usually, the only patients who stay long in the hospital are infants so malnourished that another bout of diarrhoea would kill them. They live for up to a month in a separate ward with their mothers, who are taught how to cook nutritious porridges.

Vibrio cholerae travels from person to person via fecal matter. In 1854, epidemiologist John Snow famously traced cases to a single well dug near a cesspit in which a mother had washed the diaper of a baby who died of cholera and he convinced officials to remove the well’s pump handle. Because cholera is a threat to all people lacking safe drinking water in China, India, Nigeria, scientists have long sought a more powerful weapon: a cheap, effective vaccine. Now they have one.

Preventing plague

In the 1980s, a Swedish scientist, Dr Jan Holmgren, invented an oral vaccine that worked 85% of the time. But it was expensive to make and had to be drunk with a large glass of buffer solution to protect it from stomach acid.

Later, in 1986, a Vietnamese scientist, Dr Dang Duc Trach, asked for the formula, believing he could make a bufferless version. Holmgren and Dr John D Clemens, an American vaccine expert, obliged. “It’s just a bunch of killed cells, technology that’s been around since Louis Pasteur,” said Clemens, who is now the ICDDR,B’s executive director.

Seven years later, Dang notified them that he had made a new version of the vaccine that was 60% effective. In 1997, Vietnam became the first — and thus far, only — country to provide cholera vaccine to its citizens routinely, not just in emergencies. Cases dropped sharply, according to a 2014 study, and in 2003 cholera vanished from Hue, where the campaign focused heavily.

But Dang had not conducted a classic clinical trial, and Vietnam’s vaccine factory did not meet WHO standards, so no UN agency was allowed to buy his vaccine. In 1999, Clemens approached what is now the Bill and Melinda Gates Foundation. “I got a letter from Bill Gates Sr. It was very relaxed, sort of, ‘Here’s $40 million. Would you mind sending me a report once in a while?’

With that money, Clemens reformulated Dang’s vaccine, conducted a successful clinical trial in Calcutta and found an Indian company, Shantha Biotechnics, that could make it to WHO standards. Rolled out in 2009 under the name Shanchol, it came in a vial about the size of a chess rook, needed no buffer and cost less than $2 a dose. Even so, there was little interest, even from the WHO. The vaccine lacked the publicity campaign that pharmaceutical companies throw behind commercial products.

The impasse was broken only when Dr Paul Farmer, a founder of Partners in Health, began publicly berating the WHO for not moving faster. The WHO approved Shanchol in 2011, and since then, the vaccine has slowly gained acceptance. In 2013, an emergency stockpile was started, and the GAVI Alliance committed $115 million to raise it to 6 million doses.

Looking back on his long struggle to prove the vaccine’s value, and then to win acceptance, Clemens offered an explanation that blended wistfulness and cynicism. “If this disease had been in American kids, there would have been trials as fast as the Sabin polio vaccine.”