Vibrio cholerae travels from person to person via fecal matter. In 1854, the 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 nd convinced officials to remove the well’s pump handle.
Because cholera is a constant threat to hundreds of millions of people lacking safe drinking water in China, India, Nigeria and many other countries, scientists have long sought a more powerful weapon: a cheap, effective vaccine.
Now they have one.
Preventing a Plague
Injected cholera vaccines were first invented in the 1800s and were long required for entry into some countries. But many scientists suspected they did not work, and in the 1970s studies overseen by the ICDDR,B confirmed that.
In the 1980s, a Swedish scientist, Dr. Jan Holmgren, invented an oral vaccine that worked an impressive 85 percent 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.
Transporting tanks of buffer was impractical. Making matters worse, it was fizzy, and poor Bangladeshi children who had never tasted soft drinks would spit it out as soon as it tickled their noses.
In 1986, a Vietnamese scientist, Dr. Dang Duc Trach, asked for the formula, believing he could make a bufferless version. Dr. Holmgren and Dr. John D. Clemens, an American vaccine expert who at the time was a research scientist for the ICDDR,B, obliged.
“This isn’t an elegant vaccine — it’s just a bunch of killed cells, technology that’s been around since Louis Pasteur,” said Dr. Clemens, who is now the ICDDR,B’s executive director.
He and Dr. Holmgren lost touch with Dr. Dang, largely because of Vietnam’s isolation in those days. But seven years later, Dr. Dang notified them that he had made a new version of the vaccine. He had tested it on 70,000 residents of Hue, in central Vietnam, and had found it to be 60 percent effective.
Although his was not as effective as Dr. Holmgren’s, it cost only 25 cents a dose. If enough people in an area can be made immune through vaccination, outbreaks often stop spontaneously.
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 most heavily.
But Dr. Dang had not conducted a classic clinical trial, and Vietnam’s vaccine factory did not meet W.H.O. standards, so no United Nations agency was allowed to buy his vaccine.
Because no pharmaceutical company had an incentive to pay for trials or factories, his invention languished in “the valley of death” — the expensive gap between a product that works in a lab and a factory-made version safe for millions.
In 1999, Dr. Clemens approached what is now the Bill & Melinda Gates Foundation, which was just getting organized.
“They were literally operating out of a basement then,” he said. “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?’
“But without that,” Dr. Clemens continued, “this wouldn’t have seen the light of day.”
With that money, Dr. Clemens reformulated Dr. Dang’s vaccine, conducted a successful clinical trial in Calcutta and found an Indian company, Shantha Biotechnics, that could make it to W.H.O. 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 W.H.O.
The vaccine lacked the publicity campaign that pharmaceutical companies throw behind commercial products, and “cholera ward care” was saving many lives — when it could be organized. The new vaccine was not used in a cholera outbreak in Zimbabwe in 2009, or initially in Haiti’s explosive outbreak in 2010.
The “valley of death” lengthened: Without customers, Shantha could not afford to build a bigger factory. The impasse was broken only when Dr. Paul Farmer, a founder of Partners in Health, which has worked in central Haiti since 1987, began publicly berating the W.H.O. for not moving faster.
The agency 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 six million doses.
The vaccine is now used in Haiti, and has been deployed in outbreaks in Iraq, South Sudan and elsewhere. A second version, Euvichol, from South Korea, was approved in 2015.
And later this year, Bangladesh — where it all began — hopes to begin wiping out its persistent cholera. A local company has begun making a domestic version of the vaccine, called Vaxchol. Dr. Firdausi Qadri, a leading ICDDR,B researcher, estimated last year that success there would require almost 200 million doses.
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