Travel Medicine Research—Tradition & Future Directions - April 28, 2000

Questions and Answers, 9:15 a.m. Session

DR. ERICSSON: Good morning. I thank both of the presenters for excellent presentations. I have one question. I think, as Lennart mentioned, when we here at the World Bank deal with this problem, we're dealing with two inflammatory processes; the first is the cascading series of events that leads actually to the deep venous thrombosis. This is followed by the secondary inflammatory process, which we call malignant e-mail-itis, which is all too common.

In an effort to perhaps stem this somewhat, I'd ask each of the presenters is there anything that you do, given the fairly rareness of this event, to try to identify individuals who may be more at risk than the average traveler?

And secondly, if a person has experienced DVT and you are responsible for their travel, do you clear them for future long-haul travel?

MR. [NOT KNOWN]: Yeah. Well, apparently, this person that I started with has had two episodes of DVT. And one of the things apparently that is important is that it's looked into the risk factors of these people in various aspects. Wherever they have had their diagnosis, that needs to be cleared out. And of course they need to have some pre medication for the flight. I think Patrick is better prepared to deal with the alternatives. For people that have not had previous DVTs, salicylic acid is definitely a good choice, I would say, due to the lack of side effects.

MR. [NOT KNOWN]: With regards to whether or not you would ban them from further flights, if they are anticoagulated they, I believe, are safer than the risks of the passengers on the plane. So there's no problem, once you've identified that somebody is at risk because they've had a previous DVT, if they're on anticoagulants when they get on the plane, it's not a problem.

MR. NEWMAN: My name is Carl Newman. I would like to make a comment about dehydration on airplanes. When you fly on airplanes, you feel like you are dehydrated because of the low humidity, which dries out the mucous membranes in your mouth and your throat. But as far as dehydration, that's another story.

I think there's some limited evidence that people after long flights have gained weight. So the problem is one of shift of fluid from one compartment to the other. And I don't know if there's any evidence that drinking a lot of fluids will help that. It may even worsen that. So this is especially important in children, where people are told to give them feedings every hour because they're dehydrated. They're not dehydrated, and they're probably crying because they're getting too much fluids.

But I'd like some of the people, and certainly you and the others who know about airplane travel, if dehydration really exists.

DR. KESTEVEN: Dr. Bagshaw has looked into this issue and done some research, so would you please like to comment on that?

DR. BAGSHAW: Thank you very much for asking me to respond to that.

The work done at the Institute of Aviation Medicine at Farnborough showed that if you put subjects into zero humidity for a period of 8 hours, the total fluid loss was 100 ml, and the plasma osmolality showed no change at all, although the urine osmolality, of course, did because of the central thing.

If you continue the dehydration beyond 8 hours, there is, indeed, then a slight weight gain due to exovascular fluid shifts, and you drink to compensate the thirst. And our advice is that dehydration is discomfort. So the dry skin and the dry eyes is a fact. But that's not indicative of a dehydration physiologically. So I just bear out what you've said, and we advise people to drink to be comfortable. But, of course, if you drink 4 liters a minute or whatever the current advice is, you induce a dehydration, and induce a diuresis which is then counter productive. So drink to be comfortable, apply the moisturizer creams to stop your skin itching, use eye drops if you've got sore eyes, but don't over hydrate because that's counter productive.

Thank you very much.

MR. [NOT KNOWN]: About the weight gain, there was a study about 1976, where some passengers were put on a plane, which didn't take off. But in all other respects, they simulated the flight, and they showed that you accumulate close to a liter in your legs if you just sit there overnight in a chair and that at the end of that trip, now, they weren't in a dehydrated atmosphere because this plane never took off, but they had accumulated fluid.

The study I showed there, it was based on the urine output, the conclusion that people were dehydrated.

DR. ERICSSON: In the front?

MR: John Horton, Travel Medicine Clinic near L.A.

I wanted to ask Dr. Ericsson about the malaria prophylaxis for the business traveler. This comes up an awful lot. And I think the common-sense thing is, as you said, someone is going to a city, and even in Asia or a lot of places that just protecting against mosquito bites at night because a lot of people are very reluctant to take larium, which is the mainstay in America. I'd like to have some more comments and perhaps some discussion about that.

Thank you.

DR. ERICSSON: I intended to be provocative, in terms of areas of research. I think, Jay, you're probably going to cover that in his risk assessment discussion, and we can have further discussions on it. It's very important, but I don't want to steal his thunder. And he can answer it a lot better than I can anyway.

In the back?

MR. [NOT KNOWN]: It was along the same lines, but at the expense of being repetitious, I think I just want to prove the point about the business traveler who is visiting main cities as a corporate traveler, then goes out into the rural areas to visit the plants on a regular basis, comes back from Asia. The next month he's in Africa, where here there's doxycycline, and here there's Mefloquine, who is doing it about three or four, five times in the year.

How do we prepare him? How do we keep it on an ongoing basis? You alluded to the fact that if somebody is a business traveler living in a major city, the exposure to malaria is little. You make the recommendation if he goes out to the plant. What if he does contract malaria somewhere along the lines? What is your liability as a travel medicine consultant, having provided that advice? That's one.

The second question is about the effectiveness of the existing cholera vaccine. My understanding is that it's not as effective, it's not been recommended, but yet it seems to be on the Royal Canadian Mounted Police recommendations for who's going to Bosnia.

And the third one is about, again, the business traveler who is going to be spending time in Austria, where there is Lyme disease out there, who wants that vaccination and who needs a lot of other vaccinations, and what vaccines mix and don't mix in the time frame?

And the question to the physician for the DVT, how do you clear a pilot who has developed DVT? Do you follow him with the duplex scan, and when would you clear him for flying, and what precautions?

Thank you.

DR. ERICSSON: Whew.

[LAUGHTER]

DR. ERICSSON: Let me just say a little bit to those because I think some of those things may actually be addressed in subsequent talks. As far as liability goes, my own stance on this is that I propose to travelers, as a rule, a risk-benefit equation, and they have to buy into that. If I suggest that somebody who is holing up during the evening hours in a hotel probably doesn't need to take malaria prophylaxis because they're only being exposed during the day, when they're likely not to be exposed to the mosquitoes. I don't tell them there is zero risk, and I certainly would be preoccupied, if they are doing that day-in and day-out for 2 months, in a place where malaria is prevalent, so that there's a cumulative risk.

So I think you just have to be logical about it and make sure that the subject understands that if they elect not to take malaria prophylaxis, it's not that they're not going to try to prevent malaria because they're going to spray themselves with a DEET containing insect repellent very assiduously or I've not done my job for them.

So liability doesn't preoccupy me. I think we probably have much more liability, in a way, by overemphasizing drugs with a lot of side effects, when the benefit to the patient is very low. I am preoccupied by having somebody not take some sort of medication if they are far away from medical care, even though the risk is low. But there I think the issue, and Jay will get into this is the potential for self-therapy. You still don't necessarily have to take medication in order to make the risk zero, when it's very, very low.

The cholera vaccine is a lousy vaccine. We have oral vaccines that are coming down the pike that will actually work a lot better, and reliably and safely, without a lot of side effects. But the question still is going to come up should you use them at all. And typically when travelers face certain countries where they seem to be preoccupied with it, we just sign off on it, to be honest with you. I haven't given cholera vaccine for years. I might give it in the future when I predict there will be cross-protection until we get the ETEC vaccine, cross-protection by the cholera vaccine against enterotoxigenic E.coli.

As far as business people going to Austria, no, I don't believe they need to be protected against the tick encephalitis, unless they also intend to trek in the woods for prolonged periods of time, as a leisure activity over and over again. And at any rate, if you have an exposure, there are gamma globulins that can be given right on the spot. And besides, if you did that, you would have to be vaccinated well in advance because it takes time to develop immunity, and we don't have the vaccine in many countries to be able to do that, as we send them over. So there's logistical problems involved with it as well. As a rule, I don't think people are doing the kinds of things that place them truly at risk.

And then there was a DVT question, but I forget.

[LAUGHTER]

DR. KESTEVEN: I remember the DVT question. Unfortunately, I don't have to clear pilots at all, so I can't answer that aspect. But was the question how long you should keep these people on anticoagulants? It's a moot point at the moment. If there's an obvious risk factor which precipitated the venous thrombosis, which is now being removed, and surgery is a good example of that, 3 months is considered adequate. However, if somebody has had what appears to be a spontaneous DVT; in other words, there's no obvious risk factor, the feeling now is that it's going to be about 12 months' worth of treatment.

Michael, do you want to talk about clearing pilots?

DR. BAGSHAW: I thought I was on this afternoon's panel.

The question with pilots, as in any safety occupation, is the risk of incapacitation. That's all you are concerned with. And the figure we use in the U.K. is a 1-percent risk. If the risk is better than 1 percent, they will be cleared to fly. If the risk is worse than 1 percent, they will not be cleared to fly. So you are looking, first of all, at the risk from the disease, and we've treated that and then the risk of the side effects from the treatment.

So if the pilot has no further risk of DVT, as far as we can tell, and if the treatment is stable, and there's no risk of a bleed, and his risk of incapacitation is less than 1 percent, he would probably be cleared to fly.

DR. ERICSSON: In the back?

DR. KEYSTONE: Jay Keystone. We remind you that the oral cholera vaccine is available in Canada. We welcome you to cross-border shop because our economy is, as though of you in the World Bank know, it sucks.

[LAUGHTER]

DR. KEYSTONE: But the oral cholera vaccine that is available from Bern, in fact, provides 86-percent protection against all diarrhea for about 6 months, and 100-percent against severe diarrhea, which is a liter, defined as a liter per day, which is about as much as I get with my Metamucil in the morning. So, in fact, the oral cholera vaccine is very good for short periods. However, I agree with you entirely that the risk for travelers is about 1 in 500,000 overall and very few people would need the cholera vaccine, except the RCMP that fight better on their feet than their seat, I suspect. I think that's probably why they have it.

Thank you.

DR. ERICSSON: Thanks. In the front?

MS. [NOT KNOWN]: Just a question for Dr. Kesteven.

Can you describe the risk factor or combination of risk factors that make you consider subcutaneous low molecular weight Heparin prophylaxis for a traveler, somebody in whom we may not have a full knowledge of their hematology?

DR. KESTEVEN: Not easy. The main one is a previous venous thrombosis. And the next most common in our group was a strong family history. And a strong family history would get me to perform a thrombophilia screen on these people.

Active treatment for malignancy is also highly risky. Estrogen therapy, probably not, if there are no other risk factors, and pregnancy is usually not an issue.

MS. [NOT KNOWN]: Thanks.

DR. ERICSSON: In the back?

MR. [NOT KNOWN]: I've got a couple of cases I want to talk about that present a diagnostic dilemma, I guess, and really demonstrate a complexity of travel medicine. I had a couple of cases about 15 years ago/14 years ago, when I was working out in Seattle for an airplane manufacturer. There was an airplane crash in South America in the Andes above La Paz in about April, March or April. Because of the winter, we had two people assigned to go down in the spring thaw there, which would have been the fall. These were 50-year-old guys, who trained climbing vertically 5,000 feet per weekend mountain climbing just to get fit.

They left from Seattle to go to Miami, long flight, long flight to La Paz. Probably slept on the plane. They got there, and La Paz I think is about 17,000 feet. Their departure point was about 2,000 feet above that, where they were to meet several people who took off ahead of them. So they were left by themselves and bivouacked there. And they subsequently got what was diagnostically thought to be pneumonia, and they were hospitalized for 5 days in the consulate hospital in an oxygen tent, treated with antibiotic injections three times a day, and I communicated with the physician there.

They escaped to an airplane from that—they were supposed to climb to 20,000 feet. The reason they were going was for insurance purposes, to get a part of the airplane to document that it was that aircraft. They escaped to an airplane, where they were effectively treated by pressurization at 5- to 6,000 feet, where their pneumonia symptoms disappeared. And their diagnosis originally was confounded because at this bivouac spot they were essentially exposed to freeze-dried feces at that altitude. So the pneumonia wasn't a bad diagnosis, but subsequently flying back to Seattle, their HMO physicians did a good work up, and found that they had pulmonary emboli.

Now, I guess the question is that this is a kind of an interesting altitude, infectious disease, combination of travel, which really ended up being, with their achy calves, a deep vein thrombosis. But the reliability on sometimes diagnosis, which we get caught in as clinicians with international diagnosis and treatment, where sometimes people come back and are found to have different things, sometimes complicates the treatment and maybe even the studies.

And I was just, the question really is that the ability to rely on some of the diagnostic or to do studies when there can be complexity with other diagnoses in even the deep vein thrombosis studies. I am just interested in some comments because these couple of cases kind of demonstrates several things that might complicate that diagnosis.

DR. ERICSSON: I'll kick off a comment. In listening to the story, the first thought that crossed my mind is that they had acute mountain sickness and just needed to get down. And it seems like you're telling me their symptoms substantively went away, and I'm not so sure that doesn't explain everything. But you superimposed immobility in there somehow that may have been related to the DVT and the pulmonary embolism that they had.

I'm not aware that the studies in Kathmandu and other places on mountain sickness have intentionally looked hard for DVTs as a comorbidity because they use definitions that are pretty standard for acute mountain sickness, and a certain numbering criteria and so forth. And usually it's sort of self-evident in what's going on. I just don't know, but the experts here might be able to answer further about whether that is seen, whether there's any risk factor built into mountain sickness.

DR. KESTEVEN: Not that I know of, other than constriction of the circulating volume. I just don't know of any studies. And I have to endorse, from listening to the story, it did sound like acute mountain sickness. And even in my own hospital, diagnosing a pulmonary embolus is extraordinarily difficult. And unless you're going to do angiography, you are very rarely absolutely certain.

DR. ERICSSON: A question here in the front?

DR. JARRIS: Not a question, just a comment. And something relatively new to me—Ray Jarris, in Seattle—that we're using chest CT now. With the new scanners, in 2 minutes you have a very good visualization, just a new tool.

DR. ERICSSON: As I understand, that picks up emboli in about the first three or so bifurcations. You might miss a very tiny one, but clinically significant ones you can pick up. I'm not a radiologist, but there are some limitations, I suppose. Pulmonary angiography, if you're into the studies, probably is still the gold standard.

Lennart, before we break, I just would like to ask one question. At first when you were presenting your data, I was concerned that maybe you were going to try to make a relationship to travel and DVT. And you rightly interpret the data, even though there were relative risks that seemed above, you know, above one, the overlap of the confidence intervals in all cases was over one. But what preoccupies me, in listening to both of you, is that the incidence may be low enough that the association to travel may require a huge study in order to power it enough to recognize these relative risks.

Would you comment?

DR. DIMBERG: Yeah, that is certainly the case. I mean, we have had only a handful of cases that relate, timewise, to the travel of 30 days, within 30 days. And this is a limitation, of course, of our study, although the World Bank has the largest number of travelers, I would guess, of any organization. So at least we have pointed out some estimate. But the decision whether this is a travel-related disease or not cannot be answered by our study.

DR. ERICSSON: I think the take-home message is even if you are able to do a study to finally show statistically the relationship, it's not a very big relationship compared to all of the causes of DVT, as I read it.

DR. DIMBERG: That's absolutely so. And if you wanted to do a prospective study and pick up people before they got the DVT, you'd need to screen about 50 jumbo loans, a hell of a study, and even then you'd probably get one DVT. However, you could do what the postoperative researchers have done, which is look for some sort of surrogate marker. You look for activation of the clotting system. It's not quite the same thing, but apparently that's much more common.

DR. ERICSSON Thank you everybody.

[APPLAUSE]

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