Audio blog series

A Q&A with Dr David Sack on the History of Oral Cholera Vaccine (Part 3 of 3)

Dr. Sack Faculty Headshot, Photo: Johns Hopkins Bloomberg School of Public Health

Dr. Sack Faculty Headshot, Photo: Johns Hopkins Bloomberg School of Public Health

Previous research has shown the safety and immunogenicity of oral cholera vaccine (OCV) at elevated temperatures in vaccinated individuals. These findings suggest that hard to reach populations with endemic cholera have the ability to be vaccinated with limited cold chain capacity because larger doses of the vaccine can be transported without the constraints of being transported with heavy volumes of ice-packs. Listen to the audio below or read the transcripts to hear Dr. Sack share further insight into the vaccine cold chain and challenges of maintaining the vaccine at elevated temperatures.

Dr. Sack recently appeared as a guest lecturer for the online course, Current Issues in Public Health, at the Johns Hopkins Bloomberg School of Public Health. As part of the course, students had the opportunity to submit questions for Dr. Sack online.The audio and transcripts below capture the conversation between Dr. David Sack, Dr. Edyth Schoenrich, and the Teaching Assistant as Dr. Sack answers students’ questions.

Q: One thing that actually surprised me too was that this [the vaccine] is actually a treatment that needs to be kept cold. How much is that a barrier to getting it out to these [remote] areas versus just the normal travel times?

David Sack: Of course [the vaccine] needs to be provided to people who are living in remote areas where it’s going to be difficult to maintain a cold chain but I think perhaps the thinking was, well this is a vaccine and all vaccines need to be kept cold, so if other vaccines are cold, this one can just be kept cold also. The problem with that thinking is that this vaccine is not delivered through the normal EPI channels like the other childhood vaccines. So it was frustrating since we have pretty good information that the vaccine does not really need to be kept cold, that because of the way it’s registered and the agency has to look at the package insert and follow the instructions they would feel like they’d be blamed if they didn’t do it according to the package insert.

Q: So you were talking about resources and I think that brings us to some other questions in terms of health inequities and the poorest being at the highest risk and I was wondering if you could talk a little more about that – how is that showing?

DS:Within a community, the people who get cholera and particularly the people who die of cholera are certainly the ones who are the most vulnerable - the poorest of the poor. Frequently these are people who don’t have connections. We talk about access to care being important. People need connections. How do you actually know where to go if you’re sick? The most vulnerable may not even understand what the disease is or where they could go or even if they have the right to go seek treatment. Then the most vulnerable are those are those that live in very remote areas where there is no treatment available.

Q: Do you, in your experience, find that people are ignoring [the knowledge about the cold chain vaccines] knowing that it’s still efficacious if not kept cold or do they have to be pretty strict about it?

DS: Well, some have been very strict; MSF is much wiser than some of the others – they’ve bent the rules a little bit in the sense that they keep it cold until the day of the vaccine delivery. So at the central storage, it’s cold but then when they go into the field, they just put it in a normal box and take it and then at the end of the day if they have some left over, they bring it back, put it back into the cold, and then use those doses first thing the next day. There’s a whole science around the cold chain and this vaccine has what’s called a VVM 14, which theoretically means it could be kept at room temperature for 14 days. The VVM is the vaccine vial monitor which turns color if it's been exposed to too much heat. Q: Are people trying to overturn this? A: We’re trying to get it re-labeled as a VVM 30 and what that would allow us to do would be to allow community health workers to take the vaccine and deliver it to the communities and then it could be outside the cold chain for 2-3 weeks. I think that would make a huge difference to how convenient it is and getting back to the equity issue, I think we’d also reach the people who need to be reached.

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Dr. David Sack, M.D, is a professor of International Health at the Johns Hopkins Bloomberg School of Public Health. He has spent his career devoted to the control of infectious diarrheal diseases like cholera, rotavirus, and diarrhea due to enterotoxigenic E. coli. In addition to directing the Delivering Oral Vaccine Effectively (DOVE) project, he is also head of the Enteric Laboratory at the Johns Hopkins University Center for Immunization Research, which carries out clinical trials of new enteric vaccines. 

 

A Q&A with Dr David Sack on the History of Oral Cholera Vaccine (Part 2 of 3)

Dr. Sack Faculty Headshot, Photo: Johns Hopkins Bloomberg School of Public Health

Dr. Sack Faculty Headshot, Photo: Johns Hopkins Bloomberg School of Public Health

Cholera persists as an important public health problem in more than one-third of the world’s countries and is endemic in approximately 69 countries. A cholera outbreak can be extremely dangerous and can cause outbreaks affecting thousands within just a few days from the first case of infection. However, the global burden of cholera is not precisely known. The lack of accurate reporting is due to limited capacity for disease surveillance in cholera-affected countries, as well as social, political, and economic disincentives for reporting cholera. Listen to the audio or read the transcripts below to hear Dr. Sack expand on cholera hotspots and issues regarding cholera surveillance.

Dr. Sack recently appeared as a guest lecturer for the online course, Current Issues in Public Health, at the Johns Hopkins Bloomberg School of Public Health. As part of the course, students had the opportunity to submit questions for Dr. Sack online.The audio and transcripts below capture the conversation between Dr. David Sack, Dr. Edyth Schoenrich, and the Teaching Assistant as Dr. Sack answers students’ questions.

Q: Are there places where cholera is more endemic? Are there certain countries or regions where it’s known to always be or does it move around?

David Sack: There are certain areas where it is high risk. Just to point out - when you’re drawing maps of the world to show where a disease occurs, you paint the picture and for example, if cholera is occurring in the Democratic Republic of Congo, you paint all of Congo in one color. So, that doesn’t show you really where in Congo the problem is. In fact, most of the Democratic Republic of Congo is free of cholera. So I think many countries have these hotspots within the country, so you need to know much more about where the high risk area is.

Q: That actually leads to the questions we had about surveillance, which can be very difficult for different types of diseases. How can we improve surveillance? Do you have any experience with systems of village-elected trackers?

DS: It’s certainly something that we talk about; the official WHO case definition is if a person over the age of five develops severe, acute watery diarrhea leading to death or shock, then this would be suspected of being cholera. Of course to be confirmed cholera, you should have a culture to confirm that. These cases can occur in parts of the world where there’s no laboratory, there’s no physician to make that diagnosis and the idea of using community health workers and a lot of people are very interested in the use of cell phones and SMS messaging. This is the new frontier – how do you do this? The other part of that is a confirmation that is do you need a culture? After looking at data from South Sudan, when a specimen was taken at the hospital and sent for a culture, the average time for a report to be returned was two weeks. That’s not a very practical situation. So, one of the activities we’ve been working on is the use of a dipstick test, which seems to be working very well.

Q: How available is that (the dipstick test) in the greater global sense?

DS: Well, it’s commercially available. It costs about $2 per test. It’s not something you could have everywhere, but certainly something you might have in the regions or districts.

Q: Is that test something that’s necessary before you treat? How distinguishable is cholera; does it look like other diseases?

DS: You do not need a confirmed diagnosis to treat. If you have a patient with severe dehydrating diarrhea, you treat the patient for dehydration. Most facilities in the developing world know the standard methods (Plan A,B,C). You do not need to know the diagnosis; you treat according to the symptoms.

Q: What would trigger a quarantine or thinking that this is something more than what is usually seen?

DS: We don’t quarantine anymore, but if you have a cholera outbreak, that should stimulate a public health response. That facility, that district needs to be aware that they have to quickly set up the facilities for cholera treatment. If you treat people properly, nobody should die, but if you don’t have the treatment facilities available, the case fatality rate could be 50%. An outbreak could spread very quickly and if you can intervene quickly, you may be able to stop the spread, stop the transmission.

Q: What are the requirements for the protection of the health workers who deal with the patients in treating their dehydration?

DS: Interesting question, because frequently we see hospitals going overboard in their protection of health workers. That is, walking through chlorine to get into the cholera treatment center. Even putting the cholera ward at a distance from the main hospital. In general, these are not necessary. You do need proper hand washing, proper care. I worked on a cholera ward for 15 years and we used to treat about 50,000 patients a year with cholera and there was never a nurse or a doctor who ever got cholera.

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Dr. David Sack, M.D, is a professor of International Health at the Johns Hopkins Bloomberg School of Public Health. He has spent his career devoted to the control of infectious diarrheal diseases like cholera, rotavirus, and diarrhea due to enterotoxigenic E. coli. In addition to directing the Delivering Oral Vaccine Effectively (DOVE) project, he is also head of the Enteric Laboratory at the Johns Hopkins University Center for Immunization Research, which carries out clinical trials of new enteric vaccines. 

 

A Q&A with Dr David Sack on the History of Oral Cholera Vaccine (Part 1 of 3)

Dr. Sack Faculty Headshot, Photo: Johns Hopkins Bloomberg School of Public Health

Dr. Sack Faculty Headshot, Photo: Johns Hopkins Bloomberg School of Public Health

Oral cholera vaccine (OCV) can decrease the severity of a cholera outbreak, reduce rates of disease in endemic settings, and prevent cholera during humanitarian crises and emergencies. Listen to the conversation or read the transcripts below to hear Dr. David Sack, M.D., the Director of the Delivering Oral Vaccine Effectively (DOVE) project and professor of International Health at the Johns Hopkins Bloomberg School of Public Health, discuss the history of OCV and the potential for a single dose vaccine.

Dr. Sack recently appeared as a guest lecturer for the online course, Current Issues in Public Health, at the Johns Hopkins Bloomberg School of Public Health. As part of the course, students had the opportunity to submit questions for Dr. Sack online.The audio and transcripts below capture the conversation between Dr. David Sack, Dr. Edyth Schoenrich, and the Teaching Assistant as Dr. Sack answers students’ questions.

 



Q: Before this lecture, I did not know there was an oral vaccine for cholera. This seems to be something that’s not really on the radar for not only public health students, but also experts in public health and government. What’s the main reason for this resistance?

David Sack: Don’t feel bad. This is very common, unfortunately, even among very knowledgeable policy makers. Public health professionals have a lot on their plate – they’re dealing with all kinds of issues and cholera seems to be a detail among the many problems they deal with. I think particularly, public health workers oftentimes spend so much time on the administration of public health that new developments like this can go by and they miss it. Don’t feel bad. But on the other hand, there needs to be ways to inform people that these opportunities do exist.

 

Q: You said that there’s a difference between efficacy and the public health piece. Can you talk a little more about that?

DS: Maybe I can illustrate that with a statement that came from WHO after the first trial of this oral cholera vaccine. We did a trial of the oral cholera vaccine in 1985, so by 1990, we had the results of that and the efficacy was in the neighborhood of 70% for 3 years. The statement that was made then by WHO was that this vaccine did not have sufficiently high efficacy to be of public health benefit. Now, if you dissect that sentence, it’s internally inconsistent. What I mean is that efficacy and public health benefit are two different things. How do you measure public health benefit? It’s through the number of cases averted, the number of lives saved, that’s the public health benefit. Efficacy is an evaluation in a particular setting of how much the rate was decreased as a result of the vaccine. In fact, the major determinants of a public health benefit would be things like predicting cost benefit – how much does the vaccine cost, what is the rate of disease etc. If it’s a very common disease then a vaccine that has relatively lower efficacy still might prevent a huge number of cases. That’s certainly the case with Rotavirus vaccine right now. Where in developing countries it’s only about a 50% vaccine. But the disease is so common that even saving 50% is a huge benefit. That’s the case now we are thinking about with Malaria vaccine that maybe 30%. And yet they are still thinking about implementing that. So, efficacy and public health benefit are really two different outcomes. They’re both important but efficacy is not the only thing.

Q: Can you walk us back to 1985 where you said you were working on this oral vaccine and by 1990, had discovered that this was potentially something that could be very useful; yet it’s not until 2010 that the WHO said yes, this is something we’d like to recommend that people use on a global scale. What happened during that 25-year span?

DS: You wish you could go back and say, “Are you guys crazy? Why didn’t we do this?” Number one: it took money. The vaccine that we used in 1985 still had problems. One of the students asked what about Dukoral, which actually does provide some protection against the toxigenic E.Coli. The problem with that one is it’s more expensive so that makes it less cost-effective. The major problem is that it includes the binding subunit of the cholera toxin. So it provides protection against both the bacterial wall as well as the toxin. That’s good and it has this cross-protection against the toxigenic E.Coli. It’s acid-labile – if you drink it without a buffer, it gets destroyed in your stomach; so, you need to give it with a buffer and that buffer just adds to the logistical complications. It’s just not practical to think you can use this on a large-scale.

Q: Another question that came up a couple times was this idea of natural disasters and types of diseases we see that come out of that. One example mentioned was the earthquake in Haiti and seeing cholera come out (afterward). We do know that certain things like this are going to happen after natural disasters. Is cholera vaccine part of a response in natural disasters or is this something that’s being talked about as being a regular response?

DS: Certainly we’re trying to improve our ability to predict high-risk settings. So, I think simply because you have an earthquake or a flood doesn’t necessarily mean that your risk for cholera goes up. If there’s a history of cholera in the area, if the flood is associated with total deterioration of water sanitation, each one of these elements when they go up…if you then have a collapse of the medical care system, each one of these things adds to the risk. I’ll give you an example – you’re probably aware that there’s been an ongoing civil war in South Sudan and huge numbers of people are in internally displaced camps, the water sanitation is very bad, flooding was occurring, and that was a setting where there was a decision to preemptively vaccinate the camps. Shortly thereafter, a cholera outbreak did occur and the people in the camps were pretty much protected. It was a very wise decision and it was an example of where it showed the power of the vaccine in really benefiting the people in the camps.

Q: How long are you protected once you’ve had the vaccine?

DS: The study in Kolkata showed five years. We did have some discussion about use of the single dose and we know that single dose can protect, we don’t know the duration for single dose. If it’s given as the standard two doses, it did protect for five years.

Q: Is there, on the horizon, a chance that this would change the one-dose? Are there studies being done to show that this might be as efficacious or efficacious enough to do one-dose?

DS: We need more evidence to change that and I think rather than changing the general recommendation, it’s more of a question of when is a single-dose appropriate and when is a two-dose appropriate? I think we’re going to learn more in certain situations, particularly an outbreak in an area where you don’t normally have outbreaks, a single-dose may be enough that you don’t need long-term protection you just need to control the outbreak as opposed to a place like Bangladesh where you do need longer-term protection. So there you may need at least 2 doses. And we still haven’t worked out how to administer booster doses so that’s another question.

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Dr. David Sack, M.D, is a professor of International Health at the Johns Hopkins Bloomberg School of Public Health. He has spent his career devoted to the control of infectious diarrheal diseases like cholera, rotavirus, and diarrhea due to enterotoxigenic E. coli. In addition to directing the Delivering Oral Vaccine Effectively (DOVE) project, he is also head of the Enteric Laboratory at the Johns Hopkins University Center for Immunization Research, which carries out clinical trials of new enteric vaccines.