Risk Behaviors & Travel-Related Illness - April 28, 2000

Jay S. Keystone, MD, FRCPC, Professor of Medicine, Tropical Disease Unit, Toronto General Hospital

DR. ERICSSON: Well, it gives me great pleasure to introduce our first speaker. If Mark Rosekind got the speaker's award yesterday for his lovely presentations, I think we can count on Jay Keystone to at least match him. And that's coming from a Canadian. So you know that that's quite an honor that I'm giving Jay.

[LAUGHTER]

DR. ERICSSON: Jay Keystone is a Professor of Medicine at the University of Toronto, Canada. He's the Director of the International Medical Graduate Program at the Ontario Ministry of Health and President of the Medical Alumni Association, University of Toronto. He was a past President of the International Society of Travel Medicine. And I aspire to even halfway fill his shoes—Canadian shoes, I might add.

The American Committee on Clinical Tropical Medicine and Traveler's Health of the International—well, on, and on and on. His research interests are in leprosy, travelers research done in South India, diarrhea, parasites, health. His claims to fame, and this I think his most important accomplishment is he was the first and the last attending physician to make rounds at the Toronto General Hospital on roller blades. And Dr. Keystone will give us a presentation on health risks to travelers.

Jay?

DR. KEYSTONE: Thank you. Thank you, Charlie. I must admit I really hate introductions like that. It kind of gives high expectations, and then you blow it. So I'm going to do my best here.

The problem with travel, of course, is that there are a variety of risks. And what I plan to talk about is the various risks to health with travel and try to give you the statistics and the risks, so that you, as health care providers, can make an appropriate risk assessment.

Now, I'm going to focus on vaccine-preventable infections, sexually transmitted disease, respiratory disease, traveler's diarrhea, and trauma.

If we take 100,000 travelers to the developing world for one month, 50,000 will have a health problem, 8,000 will see a physician, 5,000 will stay in bed, hopefully, with someone they know.

One thousand one hundred will be incapacitated in their work, 300 will be hospitalized during or after the trip, 50 will be air evacuated, and one will die.

And what will the problems be? Of course, half of that 100,000—50,000—may have traveler's diarrhea, 1,300 will contract malaria, a thousand with respiratory tract infections, 300 will contract Hepatitis A, 150 may have an animal bite that's a risk for rabies, 80 will contract Hepatitis B, 30 Typhoid, and that's primarily in India and Northwest Africa, 10 will contract HIV.

So I'm going to start off then to talk about immunizations for travel and the risk.

Well, Charlie alluded to the most important vaccine-preventable infections, and he was focusing, number one, on Hepatitis A; Hepatitis B about tenfold less; typhoid almost tenfold less; and cholera about a hundredfold less; and I've already spoken earlier about the very low risk of cholera, except perhaps for aid workers, and those going so far off tourist routes, where they may not have access to health care, and that might be an indication to give the oral cholera vaccine, rather than the injectable one.

But I want to focus on Hepatitis A, to begin with, to remind you how common this infection is. One case per thousand per week, even for those going to tourist resorts. And that I assume that would be World Bank personnel, for the most part. But if they go off the tourist routes into rural areas, one in 200 per week will develop Hepatitis A.

Now most of us think that Hepatitis A is a benign disease. We don't have to worry about it. You turn yellow. You have to find something to wear that'll match—

And then the jaundice goes away. Well, there is a serious problem, and let's look at the mortality rate. Over the age of 40, 1 percent over the age of 50, almost 3-percent mortality rate. Now, I don't know what the age of World Bank employees is, but I'll bet you many of them are over the age of 40, and that then makes Hepatitis A a very potentially dangerous disease.

Not only may you die from Hepatitis A, but about 10 percent will be hospitalized, 20 percent between 50 and 39. And here's the big issue, also, is time off work averages about 4 weeks. So the bottom line to this really is who needs Hepatitis A? Virtually everyone. Who doesn't? The one-time, short-term, first-class traveler with high sphincter tone, who's going to do everything right, probably doesn't need Hep A. But anyone else who's going to travel repeatedly needs Hepatitis A for travel.

What about the risk of Hep B? Unfortunately, our data on Hep B are not very good except for the expatriate long-stay community, averaging about one case per thousand per month, symptomatic about one in 2,000, and if we look at short-term travelers overall, probably about one in 5,000 per month of stay.

Now, the problem, of course, is Hepatitis B can be even more serious than A, with 1-percent fulminant Hepatitis, and 10 percent of adults become chronic carriers. The older you are, the more likely you are to become a chronic carrier. Ninety-five percent of neonates will be chronic carriers, but about 60 percent of adults over the age of 60 will also become chronic carriers. The good thing is, they may not live long enough to develop a chronic cirrhosis and carcinoma which, of course, occurs in about 15 to 25 percent of those chronic carriers of Hep B.

I just want to remind you that you don't have to be adventurous to acquire hepatitis. If we look at missionaries living in Sub-Saharan Africa and follow them over a long period of time, you'll notice that Hep A increased by threefold before and after service, and Hep B increased by about eightfold, with long-stay service. So it means your long-stay employees especially need Hepatitis B, and of course everyone needs Hepatitis A.

The real question is do the short-term business travelers need Hepatitis B, the ones who are cruising in and out of the tropics? And the question is why should short-term travelers get Hepatitis B? Well, partly because they may be accident prone, they may have underlying chronic problems that may require injections or blood transfusions, have close contacts with locals. And in that case, I don't mean sexual contact, but repeated close contact. This is mostly young children sharing secretions and excretions.

And, finally, of course, and I think probably the greatest risk factor for the business traveler is sexual activity

All right. So I want to then talk about the issue of sexually-transmitted disease.

Now, many of you are going to say, well, why do we need Hepatitis B? We have condoms. Condoms will protect against Hep B and especially from HIV. Well, let me show you an interesting study done in Nottingham, the sex capital of the U.K., in which they did an anonymous survey of adults, found that about 5 percent had casual sex during travel. That's about right for the U.K. It's much higher in other hotter countries.

The U.K. is pretty conservative. But here's the important point. Seventy-one percent carry condoms, and 71 percent had sex without a condom once. That means just because you carry them, doesn't mean you're going to use them. And as I think—yesterday I wasn't here, but someone was talking about the risk of alcohol, and trauma, and alcohol and sex, and this clearly may be one of the risk factors.

There have been a variety of studies of casual sex during travel. Again, the U.K. is about the same as the Swiss. They're pretty conservative. But if you take high-risk Swiss travelers, 82 of them here, 67 percent of them were sexually active during travel, only 27 percent over the age of 40.

The U.S. military, a very high-risk group, 50 percent casual sex, 73 percent use condoms regularly. But the big group also are the long-stay travelers. Thirty-one percent of Dutch workers had causal sex, but only 25 percent use condoms regularly, and Belgian workers, 51 percent had casual sex abroad, 31 percent with prostitutes. So this is a very common problem, particularly among long-stay travelers.

We did a study in Canada, which I thought was very interesting. We're about to publish it. And it's basically about what is the likely risk of blood and body fluid contact within a short trip? And we were very, very surprised. This averaged about a month. The travelers were about 20 to 30 years old. And we looked at their risk factors then for both Hep B and, of course, Hep C, HIV, and you can see here that 4 percent received injections or blood transfusions; 1 to 2 percent had acupuncture, tattooing and piercing, sharing of razors, injury and sexual activity.

And you will notice here that in Ontario, of British stock, about the same, 4 percent; Quebec, which is European stock, Southern European, 14 percent.

And, of course, when I was asked the question by the Canadian press what do you think about that, three times higher in Quebec? All I could say is I think I'm living in the wrong province.

Anyway, the important point about this study is that 15 percent of travelers, short-term travelers, had the risk of blood and body fluids. And those are remarkably high numbers and indicate why Hepatitis B is so important.

And this, I think, is the message that you need to be giving to your business travelers.

What about trauma? Well, it's very interesting. There are very little data on accidents and injuries. This is a U.K. study looking at insurance company reports which showed that 31 percent reported trauma in terms of recovering health costs overseas. Notice 32 percent falling from standing, which is rather an interesting statistic. I'm assuming they may have been drunk or fell off the curb.

Falling from height was another interesting one. I don't know whether that was a spouse pushing another spouse over a balcony, 2 percent assault. So trauma is an important issue, particularly motor vehicles. This slide says, "If you don't like the way I drive, get off the sidewalk." That's the way my son drives. And if we look at trauma, motor vehicle accidents, 8-percent occupants; mopeds, motorcycles have always been a major problem. In fact, the Peace Corps have banned motorcycles—

Now I doubt that World Bank employees use this approach for tattooing but to remind you that tattooing is, clearly, a high risk factor.

Now, in terms of both Hepatitis A and B, Charlie mentioned, the new combined hepatitis A and B vaccine, Twinrix. And, of course, I wanted to show you a picture of my twin brother and myself. He's Ed, the one with the bullet hole.

And to remind you that in the United States within the next probably month or two, probably in July, Twinrix will be released in the United States, a combined Hepatitis A and B vaccine. You'll notice it has half the Hepatitis A antigen. We have a pediatric dose in Canada. I don't think you will initially in the U.S. It'll be a 3-dose vaccine, 0-1 in 6 months. Very rapid seroconversion to A, slower to B, particularly in the older age group. But you'll notice by 2 months in those under the age of 40, a seroconversion rate of about 84 percent, which is very good when you consider that for Hepatitis B the minimum incubation period is about 60 days.

So this will be a very useful combined vaccine for those who haven't yet had A or B. But my understanding, in terms of cost, it will be A, plus B equals C. In other words, it will not be less than A plus B. It will be an additive, not a synergistic combination.

What about risk factors with travel in aircraft? And certainly there's been a lot of concern about infection acquired during travel. And I just wanted to go over the TB information with you because I think that's the information that's most concerning.

CDC has reported seven episodes of tuberculosis associated with air travel. Only two out of seven has there been evidence of transmission, and I'll just show you what the two of them were. One was a flight attendant with cavitary TB, who had been coughing for 6 months. Positive tuberculin skin tests were seen in 25 percent of the exposed crew, compared to 1.6 percent of the unexposed. We have no idea whether there was transmission to travelers, but at least there was certainly transmission among crewmembers.

The only case that was reported in association with travelers was in 1994, a traveler going from Honolulu to Chicago for 8 1/2 hours infected six travelers, in terms of skin test conversion, four of those six were in the same cabin. So, yes, tuberculosis can be transmitted, as I'm sure those of you know, upper-respiratory tract infections and flu. You sit beside someone who's coughing, and 2 days later you're sick. But the point is tuberculosis has been a relatively rare incidence cause of transmission within aircraft, and these, as I said, are the only two documented cases.

Well, what about vector-borne diseases? Says,. First of all, Japanese encephalitis, I really want to remind you of two things: Number one, that, in fact, most cases occur in young children and that the risk is about 1 in 5,000 per month of travel in a rural area off the tourist routes—1 in 5,000. That's the number you need to know.

You also need to know that if you become ill with J.E. and only 1 in 250 people who acquire it actually get sick, but if you do get sick with J.E., there's about a 50-percent mortality, and a 30-percent permanent neurological sequelae. So it's a bad disease. And the indications then for immunization are those spending a month or more in rural areas, in J.E. areas, during the season of transmission, which in the Southern areas is year round and the temperate areas only seasonally.

What about malaria? Well, malaria is the number one life-threatening infection of travelers. It's estimated that about a thousand North American—well, a thousand U.S. travelers a year, 30,000 total European and North American. The mortality rate can be up to 4 percent in younger travelers, and it's more like 30 percent over the age of 60. So the older you are, the higher the risk for death from malaria.

Now, Charles already showed us the map of the world, where chloroquine resistance occurs. These are the chloroquine-sensitive areas, these are the chloroquine-resistant areas, of course, and on the borders of Thailand, Mefloquine and chloroquine resistance.

Now, I think this is probably one of the most important slides for the business traveler. This slide gives a relataive risk of malaria and shows that Oceania and Africa are the highest-risk areas. This is the risk of malaria for a 1-month stay, a 1-month stay without chemoprophylaxis. Oceania, about 1 in 5; Africa, 1 in 50; Sub-Saharan Africa, Southeast Asia, 1 in 250; Southeast Asia, 1 in 1,000; South America, 1 in 25; and Mexico and Central America, 1 in 10,000.

Now why is this slide important? Because if you've got a business traveler who is spending one or two days out of the city in Latin America or South America, you probably don't need to put them on prophylaxis. But if you've got somebody in Sub-Saharan Africa or Oceania, where the risk rates are much higher, than even a short stay in a risk area, you might seriously consider using chemoprophylaxis. And this slide says, "I feel a lot better since I ran out of those pills you gave me." what I want to focus on, of course, is the drug that has already been mentioned, Lariam. Mefloquine has had an undeserved bad rap. I think that the severe neuropsychiatric side effects from Mefloquine are exaggerated by the media. The data in the literature show, that about 1 in 200 to 1 in 500 will have disabling neuropsychological side effects. Severe anxiety, irritability, nightmares, depression, but not psychosis and not seizures. Those are the severe ones which affect 1:10,000-1:13,000 who use mefloquine for prophylaxis.IN North America, about 3 percent will discontinue their Mefloquine whereas in the U.K., this number is 15 percent, but the latter has to do with media hype and several U.K. proponents who are, for reasons that I cannot comprehend, strongly biased against mefloquine. I don't know that people in the U.K. become more psychotic than the rest of the world, although I suspect it's a debatable point.

Now, what about severe problems? Only one in 10,000 to 1 in 13,000 will develop psychosis or seizures, most of whom had a previous history of neuropsychiatric problems and shouldn't have been on the drug in the 1st place. And, therefore, they could have been screened out if you had known that and taken the appropriate history. I think that's an important point to remember. Note however,that 1 in 100 to 1 in 1,1500 will develop severe side effects when you use Mefloquine for treatment.

I want to remind you of two drugs that you can use asalternatives to Mefloquine, drugs that you can start a day before you go and stop a week after you come back. You don't need to use them for 4 weeks. That's a real advantage for the corporate business traveler.

One of them is Primaquine This drug works on the liver phase. You take two tablets a day while you're exposed, and one week after departure. Studies have shown about 85- to 90-percent efficacy in areas of the world where there is chlororquine resistant falciparum malaria, and these studies have been performed in in nonimmune individuals. The important thing about primaquine is that you must do a G6PD level before you administer it. That's the downside. The other is that it should be taken with food to reduce GI upset. I must say, those of us who have used it, and I have, find the drug to be very safe, very effective and the data in the literature in control trials show that. Note that It would be off-label use in the United States.

The other drug, which will be available in the United States probably in the next 2-3 months is a drug called Malarone,a combination of atovaquone and proguanil. This, too, acts on the liver phase. You basically take one tablet daily during exposure and for one week after departure. The adverse events when you take it for prophylaxis are minimal. In fact, no difference in adverse events was noted between drug and placebo. When the drug is used for treatment, about 10 to 15 percent will have vomiting. But I must tell you that I think that Malarone will replace mefloquine, and quinine plus doxycycline for the treatment of uncomplicated falciparum malaria.The treatment dose is four tablets once a day for 3 days.

Now, this pediatric dosing in your handout is a little bit off because in Canada we don't have a pediatric tablet. You will in the United States. It will be one-quarter of the adult dose, and it will probably be licensed for both treatment and prophylaxis. To date the studies with Malarone have all been done in partial immunes but the likelihood is that this drug will be effective for non-immunes and will replace many of the other antimalarials for short-stay travelers. Why not for long stay? Because it will cost $2.60 U.S. a day or $500 Canadian per tablet at the current exchange rate.

So for the long-stay traveler, $2.60 U.S. is a lot, but for the short-stay traveler, it will be very cost effective.

And remember, that dengue is another vector-borne disease that is an important problem for travelers. Although we don't have very good data on dengue in travelers it is the number one arbovirus risk for the corporate traveler. Why? Because dengue is an urban disease, not a rural disease, and it is seen primarily in Southeast Asia, Central and South America.It is a day-biting, not a night-biting mosquito, that bites in the early morning and late afternoon. There is no vaccine, and there is no drug to treat it.

Bottom line: early morning, late afternoon insect protection big time in Bangkok and other cities in Southeast Asia. We know that the rates of dengue have increased dramatically in the past 10 years because of overcrowding, pollution and breeding of the dengue mosquito in small water containers like used tires and tin cans.To recap, in case you were asleep and missed my message, for the corporate traveler, dengue would be the number one vector-borne disease.

Now, what can you prevent it with? Those of you who are concerned about the safety of DEET, let me remind you, that in 30 years of use there have been only 30 reported cases of severe adverse events-mostly in young children who have been kind of "sheep-dipped" into deet; where you have a large surface area to body mass, such as in children, DEET should be used especially sparingly.

But for adults, the risk is remarkably low. If you want to read an excellent article on deet and insect repellents, Fraden, in the Annals of Internal Medicine, 1998, wrote a wonderful review on DEET and other insect repellents.

Now, in Canada, we're a much kinder-gentler country, and so we don't like to kill our mosquitos. We don't like to kill anything. We don't have guns. Anyway, what we have, our approach is to trap them with these little leg-hold traps, and you will find Canadians walking around with these little leg-hold traps on their clothing. You will know they're Canadian. We then open the trap, and we let the mosquitos go, mostly to New York state.

Let me finish up this afternoon with the problem that many—many of you have eaten in restaurants with signs like this one. It says, "Fecal Matter Burgers." The problem that I am referring to is traveler's diarrhea, which, of course, is the most important for corporate travelers.

The issue here, is that the risk varies according to where you travel. The highest risk in tropical countries, less in European and Caribbean countries, and of course low in North America and other industrialized countries.

Now, what's important about traveler's diarrhea is not the mortality rate, which is incredibly low. What is important is the fact that 40 percent have to modify their activities, 20 percent are confined to bed, 1 percent are hospitalized, 8 to 15 percent will have diarrhea more than a week, and 2 percent will develop chronic diarrhea more than a month. This could be very disabling, especially if the World Bank has a major meeting in which you are discussing global finances, and you can't think properly because you can only focus on the john most of the time; this could be a serious problem for the global economy.

You need to understand that probably 80 to 90 percent of traveler's diarrhea will be due to bacterial causes. Even though we've only isolated 50 to 75 percent, there's still an unknown 10 to 40 percent. Parasites are an uncommon cause of traveler's diarrhea, viruses even lower.

This slide shows fluoroquinolone resistance to campylobacter in Thailand. And in 1995, it was 84 percent. By now it is probably close to 95 percent. This is pretty frightening because the quinolones have been the antibiotic of choice that we have been using for traveler's diarrhea. Also, since about 50 percent of traveler's diarrhea in Thailand is due to campylobacter, half of the cases are going to be resistant to quinolone.

Charlie pointed out another important fact. "Boil it, peel it, cook it or forget it." But Lawrence Green added to that "easy to remember, impossible to do." We know that 97 percent of travelers make a food faux pas—that's French—within 72 hours of travel. So it doesn't matter what we recommend, food or beverage errors are bound to occur in the majority of travelers. And that brings me to the issue of what you do.

The bottom line here, so to speak, is that Imodium is very helpful in reducing traveler's diarrhea, and we can get in later in the discussion about whether you should slow the gut down or use "nature's way". Of course, when you're on a bus that's not stopping for 10 hours, "nature's way" is not practical.

Antibiotics, however, are very practical. And I'm sure Charlie Ericcson would agree that every traveler to the developing world should carry self-treatment for traveler's diarrhea and utilize either single-dose therapy or 3 days of therapy. In fact, single-dose therapy has been shown to be just as good as multi-dose therapy. That's a real advantage to the corporate traveler and especially when used with loperamide or Imodium, a very good combination.

Well, as we pointed out, this is a very dangerous world, and the greatest danger to the traveler is death. Dr. Ericsson has pointed out at this meeting that the major cause of death is cardiovascular disease, probably very difficult to prevent among corporate travelers. But it is the injury side that is the most important, and I would focus here on motor vehicle accidents. Although you could say, "Make sure that a local driver is driving you," I don't know, Charlie, I've driven with some pretty scary local drivers, and I would only say that there are three major rules of the road: Never, ever drive in rural areas after dark, never ride on a motorcycle, and try to avoid overcrowded public vehicles. So let me summarize: Traveler's diarrhea is the most frequent cause of illness. Hepatitis A is the most frequent vaccine-preventable infection. Malaria is the most frequent infectious cause of death. And motor vehicle accidents are the most frequent cause of death.

Now, I'm showing you a picture of my children to remind you that it's very difficult to communicate with travelers to ensure that they follow your advice concerning the rules for safe travel. Try communicating to this group. I love them dearly—you just wouldn't want to live with them.

However, the point here is that you need to communicate travel advice in a very succinct and clear way. In your handouts, I've explained that and now summarize succinctly the key pieces of advice in the following 5 lines which I have stolen from Dr. David Smith at the University of Toronto Health Service. This is travel medicine for dummies: Don't get bit, don't get hit, don't get lit, don't do "it", and... don't eat shit!

Thank you very much.

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