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Despite Sensitivities, Scientists Seek to Solve Haiti's Cholera Riddle

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Science  28 Jan 2011:
Vol. 331, Issue 6016, pp. 388-389
DOI: 10.1126/science.331.6016.388
Pointing fingers.

Haitian protesters have accused Nepalese peacekeepers of introducing cholera into the country.

CREDIT: REUTERS

When French epidemiologist Renaud Piarroux came back from a 3-week mission to Haiti in late November, he faced a dilemma. Piarroux, who had been invited by the Haitian government to investigate the country's explosive cholera outbreak, was convinced that the bacterium had been introduced by Nepalese soldiers taking part in the United Nations Stabilization Mission in Haiti (MINUSTAH)—and he wanted to present his evidence. At the same time, he was leery of exacerbating tensions in Haiti, where angry mobs had already demanded the departure of the Nepalese. Even after his confidential report for the Haitian government was leaked to the press, Piarroux didn't talk to reporters until he got permission from French authorities. “I was very concerned,” he says.

He's not alone. Several cholera experts told Science that nailing the source of the outbreak could potentially embarrass the United Nations, distract from the day-to-day fight to control the outbreak, and even lead to violence. So their passion for traditional shoe-leather epidemiology has been tempered by diplomatic and strategic concerns.

Indeed, prominent cholera scientists declined to discuss the issue with Science or would only speak off the record. The U.S. Centers for Disease Control and Prevention (CDC) in Atlanta is investigating the source, but a spokesperson referred questions about it to a panel charged by U.N. Secretary-General Ban Ki-moon with investigating the outbreak. (The panel's chair, Alejandro Cravioto of the International Centre for Diarrhoeal Disease Research, Bangladesh, in Dhaka says none of its four members will speak to the press until their job is finished in April.) Meanwhile, a recent editorial in The Lancet Infectious Diseases cautioned against “apportioning blame” and declared the hunt for the source “a matter of scientific curiosity for the future.”

Yet several scientists say that attitude is wrong-headed. Knowing how the outbreak started is very important, says Matthew Waldor of Harvard Medical School in Boston, because it could help prevent outbreaks from happening elsewhere. Besides, “if an epidemic killed 4000 people in Europe or the U.S., we would want to know exactly where it came from,” says Piarroux. “So why not when the same happens in Haiti?”

Ground zero?

Because the first cholera cases occurred in Meille, a French epidemiologist thinks the Nepalese base is the source.

CREDIT: ADAPTED FROM R. PIARROUX

Scientific results published in the past 2 months support an Asian origin for the outbreak but say nothing about Nepal. In November, CDC scientists reported in Morbidity and Mortality Weekly Report that pulsed-field gel electrophoresis—a widely used method to type microbial strains—showed that Haiti's cholera was indistinguishable from strains “found in countries in South Asia and elsewhere.”

Sequencing the strain's entire genome and comparing it with that of other strains can provide more detailed information, and a first stab at that came on 6 January in a paper by Waldor and 15 other researchers in The New England Journal of Medicine. The group sequenced two samples from Haiti, two from Bangladesh collected during 2002 and 2008 outbreaks, and a Peruvian strain from 1991. They found that the Haitian strains were closely related to those from Bangladesh but not to the one from Peru.

Like CDC, the group is now sequencing a much larger number of samples, including one taken in Nepal about 5 years ago, says Waldor, who's also trying to get his hands on a sample from the outbreak that occurred in Nepal last fall, the same time the peacekeepers departed for Haiti. But whether additional samples will provide a definitive answer is not clear, he says. Vibrio cholerae doesn't evolve quickly, so there may not be enough differences between strains from different countries to tell them apart.

But for Piarroux, a researcher at the University of the Mediterranean in Marseille who previously investigated several African cholera outbreaks, there's enough circumstantial evidence to clinch the case. Working with epidemiologists of Haiti's Ministry of Public Health and Population, he found that the very first wave of cholera cases occurred in a village in central Haiti called Meille, where many inhabitants collected their drinking water from a stream, also named Meille, just downriver from the Nepalese MINUSTAH camp. During the first days of the epidemic, the Haitians noticed a pipe carrying a nauseating liquid from a septic tank inside the camp to the stream. The pipe—which was mentioned in a Haitian report of which Science obtained a copy—was later removed, Piarroux says in his own report. (A paper he wrote about the outbreak is currently under review.)

Cholera can travel the world inside people's intestines, even unnoticed, because many infected people have few or no symptoms. But Piarroux does not believe that's what happened in Haiti. Based on the number of people who got sick in the first wave of the outbreak farther downriver, he calculated that the Nepalese must have had dozens of patients and dumped hundreds of liters of contaminated stool. As he wrote in his leaked report, there was a “massive contamination” of the Artibonite River that suggests a large outbreak inside the camp. A spokesperson for MINUSTAH did not respond to e-mailed questions, but the United Nations has denied that soldiers were sick.

Waldor says he finds Piarroux's evidence “suggestive but not absolutely conclusive.” There are ways to collect more evidence—for instance, by testing the Nepalese soldiers for antibodies against V. cholerae. “It may be getting late for that,” Waldor cautions, because antibodies peak after about a month.

Some scientists don't believe foreigners introduced cholera at all, despite the molecular clues. Most prominent among them is Rita Colwell, a veteran microbiologist at the University of Maryland, College Park. Colwell believes that most cholera outbreaks are caused by bacteria that lurk locally and proliferate when conditions are favorable—in this case, perhaps a climate event called La Niña. To Waldor, the idea that a microbe so closely resembling a South Asian strain would emerge in Haitian waters is “frankly absurd.” (Colwell e-mailed Science that she was “in Bangladesh working on cholera and unable to respond” to questions.)

If the Nepalese introduced cholera, says Waldor, several measures could be considered to prevent a repeat. Aid workers or peacekeepers from cholera-endemic countries who are sent to cholera-free but vulnerable places like Haiti could be screened in advance, for instance, or given prophylactic antibiotics.

But Harvard cholera scientist Edward Ryan counters that testing thousands of soldiers using rectal swabs would be time-consuming and costly—and that testing isn't very accurate. Prescribing antibiotics would pose problems, such as adverse reactions and cause drug resistance in V. cholerae and other microbes. What's more, says CDC epidemiologist Eric Mintz, businesspeople, visiting relatives, and tourists would also have to be tested. “It wouldn't be very practical,” Mintz says.

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