The strain of cholera currently sweeping through post-earthquake Haiti originated in South Asia, conclude scientists who did a rapid genetic analysis of bacteria collected from Haitian patients. The finding supports the notion that the cholera bacteria fueling the outbreak arrived on the island via recent visitors.
"The mostly likely explanation for the sudden appearance of cholera in Haiti is transmission of V. cholera by an infected human, food, or other contaminated item from a region outside of Latin America to Haiti," conclude Howard Hughes Medical Institute (HHMI) investigator Matthew Waldor and co-authors in the New England Journal of Medicine (NEJM), which fast-tracked and published the genetic analysis online December 9, 2010.
While cholera is endemic in many parts of the world, including regions of Latin America, until October, Haiti had historically been spared from the intestinal disease. But in mid-October, an outbreak flared in northern Haiti and quickly swept across the country. By December 3, the bacteria had sickened more than 93,000 people, killing some 2,100. The World Health Organization anticipates that the outbreak will last a year or longer.
"The scientific question for us was, 'How did cholera come to Haiti?' It hadn't been there for more than a hundred years," says Waldor, a microbiologist and infectious disease specialist whose laboratory at Brigham and Women's Hospital studies cholera and other pathogenic gut bacteria.
Waldor obtained two samples of Vibrio cholerae, the bacterium that causes cholera, from two Harvard Medical School colleagues, Stephen Calderwood and Jason Harris, who traveled to Haiti in November to assess the outbreak. Waldor then established a collaboration with Pacific Biosciences, which manufactures powerful DNA sequencing machines that can rapidly scan and identify millions of bases of genetic material. A team of scientists there, led by Eric Schadt, sequenced the complete genomes of the cholera bacteria in the samples. Waldor received the V. cholera samples on November 8 and had the bacterial DNA sequence from Pacific Biosciences in hand by November 12.
The DNA readout showed that the two Haitian strains of V. cholera – isolated from different patients – were essentially identical, supporting the idea of a single origin of the nation-wide outbreak. The two strains were also essentially identical to three other Haitian outbreak samples that had been sequenced (but not analyzed) by the Centers for Disease Control and Prevention (CDC). The HHMI, Harvard, and Pacific Biosciences team then compared the genome of the Haitian strain to the genomes of 23 other V. cholera strains from various parts of the world that were stored in the genetic data repository GenBank. Surprisingly, the Haiti strain bore the strongest resemblance to strains that are currently circulating in South Asia. Conversely, the Haitian strains differed significantly from the bacteria currently circulating in Latin America. Some cholera experts had suggested that endemic Latin American V. cholera – found in Peru and elsewhere – was the most likely source of the Haitian outbreak.
"The big conclusion is that the Haiti cholera epidemic is caused by a strain that was most likely introduced into Haiti from South Asia, and not from some strain that washed up environmentally from Latin America," Waldor says.
Waldor and colleagues then examined the genes of the Haitian bacteria for clues to the potency of its toxin production and antibiotic resistance. Interestingly, they found that the strain contains a version of the gene that produces cholera toxin – and hence, the symptoms of the disease – that differs from that found in strains from Latin America at three amino acid locations. Two of these three amino acid changes were present in the now extinct 'classical' V. cholerae, a type of V. cholera that characteristically produces more severe disease. The team concluded from these data that the Haitian strain may be more virulent than the average strain of V. cholerae. That means the strain may cause more severe diarrhea and lead to a higher death rate than usually seen. But examination of the antibiotic resistance genes showed some good news: The strain should be responsive to tetracycline antibiotics. Rehydration is the first-line of therapy, but antibiotics, which are currently being used sparingly in Haiti, can help shorten the length of illness as well as limit the dissemination of the pathogen and so are also an important treatment option.
Waldor says that the CDC assessed Haiti's public health system after the earthquake in January 2010 and concluded that the risk of a cholera outbreak was low because there is no endemic cholera in Haiti. "That thinking obviously was not correct," he says, "because the possibility of transfer of virulent V. cholera strains by human activities wasn't considered." Waldor adds that world health officials should consider measures to prevent the introduction of the cholera bacterium into other disaster sites worldwide, which often suffer from inadequate sanitation, a key factor in the spread of cholera, which is transmitted via feces.
"I think we could prevent future 'Haitis' by restricting travel from regions where cholera is epidemic to the disaster zone," says Waldor. "Alternatively you could give vaccines or antibiotics to people from endemic areas, regardless of symptoms, so they couldn't inadvertently transmit cholera."
Waldor also advocates a vaccination campaign throughout Haiti and neighboring Dominican Republic to stanch the current epidemic, a point he made with colleagues in an editorial published in the November 24, 2010, issue of NEJM. Waldor says such a campaign would require manufacturers to ramp up production of the vaccine, which is currently in limited supply, but could damp down the outbreak and prevent it from escaping the island into Latin America. In early December, Waldor discussed a vaccination campaign on a conference call with 80 other cholera experts from the World Health Organization, the National Institutes of Health, and other institutions and non-profit organizations. "I think we got some traction," Waldor says. "There are logistical and cost and other issues for any large vaccination campaign. But there was a lot of enthusiasm for the idea."
Journal
New England Journal of Medicine