Stephen Calderwood Discusses the Infectious Mechanisms of Cholera
Special Topic of Cholera Interview, July 2011
But some of the technical capabilities of what's doable in these more resource-limited settings are not the same as what could be done here in the US. A lot of our international collaborative research grant has been focused on building capacities in Bangladesh and/or figuring out ways to get the samples shipped from there to here in a way that doesn't perturb what we're trying to observe.
The capacity-building involves both equipment and people. We have a number of training grants that bring people from Bangladesh here for a year or sometimes longer for training, to learn specific techniques so that when we do set up a piece of equipment or a new procedure back in Bangladesh, there's a person with the expertise to set it up and get it running.
What do you consider the major issues or unanswered questions in cholera research today?
There is certainly a reservoir of cholera in the environment. It's not as easy to find in the water as you might expect. So I think we have to better understand the relationship between cholera and its environmental reservoir. That is very important. A lot of people are working on that. It's important that we understand how the first person in an outbreak actually gets infected. Because we assume that the infectious dose from water is very high, how does that first person ingest a large enough amount of the organism to actually get an infection? There are certainly some good theories on that, but I think that still needs more work.
The idea of transmission person-to-person with hyperinfectivity is a key issue. But the question you asked earlier is very important: there may be people who shed organisms that are more or less hyperinfective, depending on their own host genetics and maybe their microbiomes, the other microorganisms present in the intestine. If you remember the outbreak of SARS back in 2003, there was a subset of patients called super-spreaders, people who were able to transmit the organism to others much more rapidly than others. It's possible that for cholera such differences exist and we don't know them.
Of course, knowing how to provide clean water to people who don't have it is a key issue. Everyone understands that. And that's a problem not just for cholera but for all of the diarrheal illnesses.
The role of vaccination has to continue to be explored. I think the current vaccines available should be used more broadly, now that they're cost effective. The technology for one of the killed cholera vaccines was transferred to India and they now make a vaccine that's awaiting prequalification by the WHO, and this vaccine will be available for under $2 US a dose. This is quite affordable compared to the other vaccines. So I think the role of vaccines in both endemic settings like Bangladesh and epidemic settings like Haiti, for example, needs to be further explored, as well as better improvements in vaccines to get longer lasting protection.
Another important question is the relationship of all the diarrheal pathogens to the other organisms that are present in the intestine, the human microbiome.
One issue we haven't addressed is the outbreak of cholera in Haiti last October. It was evident after sequencing, that that strain was brought to Haiti from South Asia. We don't know exactly the mechanism, but we know it didn't arise de novo from strains that were there pre-existing.
Haiti raises a number of important questions. This is an opportunity to study what happens to a population that hasn't seen cholera in decades and compare and contrast it to a population like Bangladesh that sees cholera all the time. Understanding differences between these populations is likely to be very important as we look at vaccines.
"It's important that we understand how the first person in an outbreak actually gets infected."
This also represents an opportunity to look at cholera in a different genetic background. Haitians are mostly of African descent, whereas Bangladesh is of an Asian descent. There may be quite different genes predisposing to cholera in these two different genetic backgrounds. Lastly, we have not studied the interaction of cholera and HIV very much, and I think HIV may have an impact on immune responses that follow cholera, and therefore immune responses that might follow a vaccination. And so the outbreak in Haiti, since HIV is more prevalent there than in Bangladesh, gives an opportunity to try to answer that question.
When we spoke to John Mekalanos, he was very outspoken about the need for the WHO and the public health community to act on making more vaccine and making more available in situations like Haiti, before an epidemic hits. Do you feel the same way?
There has been a lot of debate on the issue of whether a vaccine should have been available in larger numbers to intervene at an early point in Haiti. I do think this has really been a wake-up call to the public health system to make sure that we have a better response planned in advance to outbreaks like this—to make sure both clean water and vaccination are available.
Haiti is really an important lesson that cholera is not a disease somewhere over there, and somehow in the past. We recently had two patients with cholera here in Boston. It turned out that an extended Venezuelan family had a wedding in the Dominican Republic. Several members of the family lived in Boston and they attended the wedding. A large number of the wedding guests got cholera afterward. It's not entirely clear what the vehicle was, but part of what was served at the wedding was lobster and it's possible that the lobster might have come from off the waters of Haiti. Two patients were cared for here in Boston. Several others went elsewhere in the US and several went to Venezuela. So this is not a problem of yesterday or somewhere else. It's a problem of today.
Stephen B. Calderwood, M.D.
Massachusetts General Hospital
Boston, MA, USA
STEPHEN CALDERWOOD'S MOST CURRENT MOST-CITED PAPER IN ESSENTIAL SCIENCE INDICATORS:
Mylonakis E, Calderwood SB, "Medical progress: Infectious endocarditis in adults," N. Engl. J. Med. 345(18): 1318-30, 1 November 2001 with 347 cites. Source: Essential Science Indicators from Clarivate .
KEYWORDS: CHOLERA, ANIMAL MODELS, HUMAN INFECTIONS, INTERNATIONAL RESEARCH, COLLABORATION, HUMAN STOOL, HOST, ORGANISM, GENE EXPRESSION, TRANSMISSION, HYPERINFECTIVITY, PILUS, EPIDEMIOLOGY, PANDEMICS, EL TOR, BIOTYPE, ENVIRONMENTAL SURVIVAL ADVANTAGES, REINFECTION PROTECTION, VACCINATION STRATEGY, POLYMORPHISM, IMMUNOLOGIC EVENTS, VITAMIN A, BANGLADESH, WATER, HAITI, RESPONSE PLAN.