SPECIAL REVIEW
By Phil Fischer, MD
Sunny skies, a sparkling lake, springtime blossoms, stimulating science, and free chocolate greeted the 1360 participants from 68 countries who spent the last week of March 1997 in Geneva, Switzerland, at the Fifth International Conference on Travel Medicine. Some 330 scientific presentations were served in a full menu of over 60 different sessions. Workshops, symposia, discussions, and plenary sessions provided a variety of learning situations, and new research findings were presented in oral and poster formats. Readers of this report who desire a copy of the abstract book or further information about the hosting International Society of Travel Medicine may contact the Society by mail at P.O. Box 871089, Stone Mountain, GA 30087-0028, USA, by phone at (770) 736-7060, by fax at (770) 736-6732, or via electronic mail at: [email protected].
Pre-Travel Care
Travel medicine practitioners strive to provide helpful anticipatory guidance to foreign travelers. How are we doing? The conference included several presentations that helped identify who’s giving pre-travel care, where travelers seek help, and how well pre-travel advice is followed.
A 1996 survey assessed travel medicine services in Canada (abstract 23). Responses were obtained from 35% of the 15,430 physicians who received surveys. Slightly over half of responders provide travel advice and services (91% as general practitioners, 9% as travel medicine specialists). Generalists providing pre-travel care did so less than five times per week and lacked access to desired guidelines and resources.
In France, 3500 general practitioners were surveyed (abstract 80). Most provided at least occasional travel-related services, and 7% did so at least weekly. As in Canada, the French physicians desire practical education in tropical and travel medicine as well as ready access to up-to-date travel health information. Clearly, with generalists providing significant amounts of travel medicine services, ongoing support and education are not only desired but necessary. Literature and information about courses, conferences, and training programs were also available in Geneva. Of note, the Sixth International Conference on Travel Medicine will be held in Montreal in June 1999.
Not all travelers, however, receive advice from physicians prior to subjecting themselves to health risks in foreign countries. In San Francisco, 353 North American travelers were surveyed just before boarding flights to parts of Southeast Asia known to pose high risks to health (abstract 74). Of these travelers, 72% received no pre-travel medical advice, usually because they did not believe it was necessary. One-fourth of those who failed to get pre-travel advice cited time and financial constraints as being barriers to getting desired care. However, first-time travelers were more likely to seek pre-travel advice than were repeat travelers.
Similarly, 323 travelers returning home from the Tropics to New Zealand (identified by the investigator as a land of 3.6 million people and 50 million sheep) were surveyed (abstract 140). Forty percent of males and 24% of females had received no pre-travel health advice. Of those receiving advice, most received help from general practitioners. And, the source of advice was correlated with behavior before and during the trip. Travelers who consulted a physician prior to travel were more likely to receive hepatitis A vaccination, to use insect repellent, and to take anti- malarial chemoprophylaxis.
Though health care providers can provide helpful pre-travel care, they are not always consulted. Posing as potential travelers wanting advice about "shots or pills," Canadian investigators called 77 embassies of nations in Africa, Asia, and Central and South America (abstract 79). Thirty- eight percent of embassies did not give immunization recommendations in keeping with guidelines from the Centers for Disease Control and Prevention, and 68% failed to mention the need for anti-malarials. Despite the inadequate health advice given by many embassies, there had been marked improvements since a similar survey nine years ago.
What if travelers do get good advice? Does it make any difference? Approximately 400 return travelers who had received pre-travel care in France were interviewed (abstract 46). Advice concerning clothing was rarely followed on organized trips but was usually adopted by regular travelers. About 40% used insect repellents, but fewer than 4% used bed nets. (Similar experiences elsewhere stimulated broad-based concern at the Geneva meeting that a priority be placed on promoting wider application of personal protective measures to decrease contact with mosquitoes.) Ninety-two percent of travelers used anti-malarials, but 16% failed to comply with the proposed duration of chemoprophylaxis.
Similarly, in India (abstract 47), 29% of travelers studied failed to take appropriate chemoprophylaxis. Improper pre-travel advice and undesired side effects were commonly cited reasons for noncompliance.
What pre-travel advice should be given to parents to help prevent childhood earaches during flight? Prompted by a Travel Medicine Advisor Update review (1995; 5:1-2), an American team compared pre-flight pseudoephedrine with placebo in the prevention of air travel-associated ear pain in children (abstract 237). The treatment did not change apparent ear discomfort but was associated with increased drowsiness. Still, with no proven medicine to help make flights more comfortable for children, we are left with recommending jaw and throat movements (sucking, chewing, swallowing) and untested remedies to help open the eustachian tubes.
Immunization
Who were Ali Maow Maalin and Luis Fermin Tenorio? In October 1977, Ali was the last human to suffer from endemic smallpox. Luis, two years old in 1991, harbored the last known wild polio virus infection in the Western Hemisphere. There is no doubt that vaccines are eliminating diseases and saving lives around the world. Even as polio is being pushed toward the same fate as smallpox, though, travelers to developing areas of the world still face risks of vaccine- preventable diseases. Likewise, effective new vaccines are being developed.
Hepatitis A vaccines are now readily available, with several established brands in use in various parts of the world (satellite symposium). Clinically, hepatitis A is usually asymptomatic in pre- schoolers, with fewer than 10% of infected individuals becoming jaundiced. Children aged 6-14 years become symptomatic with about half of infections and take about three weeks to recover. Older individuals develop jaundice with three-fourths of infections and take about six weeks to recover. While the illness is usually self-limited, an overall mortality of 0.4% is reported. Available vaccines are more than 90% effective and are expected to provide protection for 20-30 years; serious adverse reactions are rare.
Who, then, should be vaccinated against hepatitis A? In Africa, the attack rate is reported to be comparable to that of malaria. For non-immune travelers making repeated trips to endemic areas, the vaccine is cost-effective. Many travel clinic patients, however, spent significant parts of their childhood in areas where hepatitis A is endemic and might already be immune. Investigators in Boston evaluated 80 pre-travel patients who had been born and raised in hepatitis A endemic areas; 63% were of African origin (abstract 280, updated since printing). Seventy-six of the 80 were already immune. In an institution where two doses of hepatitis A vaccine can cost as much as four screening serologic tests, pre-vaccination screening was indicated for individuals from endemic areas. A similar situation prevails in Portugal, where 77% of departing travelers already had protective levels of hepatitis A antibody (abstract 283). There, the likelihood of positive serology increased to 100% by age 50. In South Africa, hepatitis A seropositivity varied with race with white travelers having lower levels and thus being at greater risk of getting hepatitis while traveling (abstract 285).
Sadly, however, many travelers are unaware of the risk of getting hepatitis A. The vast majority of 502 Southeast Asian-bound travelers in San Francisco’s airport were unaware of the symptoms of, transmission of, and practicality of immunization for hepatitis A (abstract 281). Somewhat fewer than half of South Africa travelers similarly showed a lack of knowledge about hepatitis A (abstract 285). Travel-associated cases of hepatitis A continue to be reported in Montreal (abstract 282) and in France (abstract 284).
Knowledge about and immunity against hepatitis A is desired for all travelers to endemic areas. Who, then, should be vaccinated? With current costs, serologic testing is appropriate before vaccination of individuals whose age and geographic context place them in a group where seropositivity is greater than 35%. Then, vaccination would be reserved for non-immune people from high-risk groups (childhoods spent in highly endemic area or older age but in an area of moderate endemicity) and for low-risk travelers presumed to be non-immune. Since the risk of hepatitis A follows the duration of exposure, travelers planning long or repeated stays in endemic areas should receive particular guidance toward ensuring hepatitis A immunity.
Diarrheal Disease
Diarrheal disease is the target of active vaccine development (satellite symposium). The old, whole cell cholera vaccine has become obsolete due to limited efficacy, but new cholera vaccines are reaching clinical availability. A live Swiss vaccine, CVD103-HgR, seems in trials to provide 80-95% protection with a single oral dose. A Scandinavian vaccine, rCTB-WC, is also given orally (but in multiple doses). It provides good protection against cholera in adults but provides shorter term protection in children. Interestingly, this vaccine also provides some protection against disease due to enterotoxigenic E. coli. Each of these vaccines is licensed in some countries. While research continues with these and other cholera vaccines, there is some question about who should receive the vaccine. Some conference participants see the cholera vaccines as only useful in epidemic situations, while others see more widespread use for travelers.
Enterotoxigenic E. coli (ETEC) is a significant cause of travelers’ diarrhea in much of Central and South America, in most of Africa, and in parts of Asia, especially during summer months. ETEC vaccine development continues and could lead to a clinically useful vaccine within the next 1-2 years. A candidate vaccine currently seems to prevent about 80% of ETEC-associated diarrhea in recipients.
Malaria
Several sessions and presentations dealt with malaria. Since the last travel medicine conference two years ago in Acapulco, the focus on malaria in travelers has shifted. The conference in Switzerland was characterized by an increased concern for personal protective measures (session 43) and by less worry about side effects of mefloquine in individuals without a positive neuropsychiatric history. There was also significant discussion about appropriate emergency self- treatment and about risk-benefit analysis to individualize chemoprophylaxis regimens.
Impregnated bed nets provide documented decreases in both morbidity and mortality in communities who use them (presentation 211). They not only protect individuals but also help control disease. In settings such as Gambia, bed nets are generally accepted. While use of nets varies some with age and ethnicity, it does not seem to be affected by educational level or socioeconomic status. Studies have documented favorable effectiveness of insecticide use, mosquito coils and sprays, and impregnated bed nets. In other settings, however, personal protective measures are not widely used. Even American soldiers and flight attendants are reported to comply poorly with mosquito avoidance measures.
There has been public concern about DEET (N-N-Diethyl-M-Toluamide) toxicity. Extensive literature and poison center reviews (presentation 212) show that nearly all cases of DEET toxicity result from oral ingestion. Topical use has been linked (though causality could be questioned) to neurologic symptoms (encephalopathy and/or seizures) in 12 children (3 died) and to cardiovascular symptoms in one adult and to psychosis in another adult. Studies with radio-labeled DEET show that the little DEET that is absorbed is no longer detectable in the blood four hours later. No actual proof of a postulated increase in DEET absorption in children has been found. So, with widespread, long-term use of DEET and only rare reports of toxicity with topical use, conference participants were advised to: 1) limit DEET use to exposed areas of skin and clothing (though permethrin is probably better for use on clothing); 2) avoid DEET concentrations greater than 50% on the skin; 3) exercise extreme caution to avoid oral ingestion and ocular inoculation of DEET; 4) wash DEET off skin when no longer in contact with mosquitoes; and 5) consider limiting pediatric use to light applications of 30% DEET.
Regimens of malaria chemoprophylaxis vary from country to country, and the WHO "yellow book" gives 11 helpful guidelines for prescribers (session 14). (Note also the typographical error omitting "per kg" in the pediatric dose for mefloquine in the smallest size category in the CDC’s 1996-1997 Health Information for International Travel.) Especially with very brief visits and with prolonged expatriate stays in malaria-endemic regions, some conference participants might modify "standard" prophylactic plans. If emergency self-treatment is advised, it should be stressed that it applies to times when the patient is en route to medical care rather than as a substitute for medical care.
In dealing with a febrile, returned, semi-immune traveler, practitioners are reminded to be careful in assuming that malaria parasitemia indicates that malaria is the cause of the fever (session 61). Many semi-immune individuals tolerate low-level parasitemia well. A positive malaria smear in a semi-immune traveler should not completely preempt consideration of other causes of fever.
Malaria continues to kill over 1 million people per year (mostly in Africa), and drug resistance is increasing, especially in Southeast Asia (session 22). In areas of Thailand with some quinine resistance, quinine must be used in conjunction with tetracycline and might be initiated with a larger loading dose. In children, the quinine dose can be increased during the last three days of treatment to compensate for progressively increasing clearance.
Atovaquine combined with proguanil is effective as a daily prophylactic (session 30). If further studies confirm initial impressions that this combination is effective against hepatic phases of Plasmodium, then it might be possible to stop prophylaxis soon after leaving a malaria-endemic area.
New malaria drugs are being developed and tested (session 30). Etaquine (WR238605) holds promise as a weekly chemoprophylactic; randomized, controlled, blinded studies are beginning. Other medicines being developed as therapies for opportunistic infections such as toxoplasmosis and pneumocystis in immunocompromised patients also hold promise as antimalarials. Further combination and dosing schemes involving artemesinin derivatives are helping improve the efficacy of that family of drugs.
Displaced People
One of the best presentations of the conference dealt with humanitarian emergencies (presentation 203). The main killers in refugee camps are: 1) measlesmostly in children under five years of age, risk of high case fatality ratio, amenable to vaccination; 2) diarrheal disease accounts for about half of camp deaths, usually due to shigellosis, cholera, and E. coli O157 infectiondeaths preventable with appropriate oral fluids and efforts to establish good hygiene; 3) acute respiratory infections; and 4) malaria. HIV is also an issue that suggests that screening of transfused blood is vital, as are "universal precautions" with bodily fluids, educational efforts, and, it was suggested, condom distribution. When the refugee population is stable and the major acute killers are under control, tuberculosis becomes a priority.
Trivia
Chicago claims the world’s busiest airport, with 67 million passengers in 1995 (presentation 202). The volume of air traffic doubles each 15 years. The proportion of foreign travel originating from Asia has increased markedly this decade, but the United States still leads, with 37% of air travel originating in America, 27% in Europe, and 24% in Asia.
Long-Term Expatriates
Many travel medicine practitioners find the management of long-term travelers to be difficult and controversial (session 12). Much care of expatriates should be coordinated through their sending agencies. There is some controversy about long-term malaria chemoprophylaxis. Research is needed to determine favorable, cost-effective outcomes to drive practices, but it seems that TB screening, stool exam for parasites, and STD screening are appropriate for people with long-term contacts in disease-endemic areas of the world.
Post-Travel Screening
A survey of travel medicine practitioners over the Internet evaluated screening practices in return travelers (abstract 25). There was much variation in what people would do. For an asymptomatic returnee from a rugged, short trip, 75% of survey responders would do no screening tests; others would perform a blood count and stool exam. For a family residing for several years in Africa, most respondents would do a blood count and a tuberculosis skin test. Stool exam, urinalysis, and helminth serology were chosen by one-half to two-thirds of responders. Perhaps ongoing risk research will help provide a basis for standardization of practice habits. Canadian investigators did confirm that tuberculosis is a risk for travelers with seven new infections found in 86 of 509 patients who returned for post-travel screening (abstract 248).
How good is your lab? A quality control program in the United Kingdom found that the accuracy of microscopic exams for parasites in stools and blood was only 80-90%, and sometimes worse than that (abstract 249). Perhaps the real solution lies in the continued development of rapid, accurate, non-microscopic tests.
N-acetyl-5-methoxytryptamine
What’s that? It’s a chemical compound touted by the lay press to slow aging, help depression, treat insomnia, cure cancer, and prevent jet lag. Perhaps you know it as melatonin (presentation 320).
Melatonin is a hormone secreted by the pineal gland that relates to serotonin and the circadian rhythm. Exposure to light suppresses secretion, and darkness stimulates both synthesis and release. Levels rise at night, especially in young people who achieve relatively high levels.
There is large individual variation in how people respond to oral melatonin, but levels usually peak 30-60 minutes post-ingestion and return to baseline following 4-8 hours. An oral dose of about 0.2 mg during the day gives a peak level similar to the physiologic nighttime level.
So what? In animals, supplemental melatonin is inversely related to aging and even lowers cholesterol. In human studies, no clinically significant change has been identified when melatonin is used to treat seasonal affective disorder, the insomnia of Parkinsonism, or cancer.
A few studies of the past 10 years suggest that melatonin helps decrease jet lag symptoms and increased sleep quality in many (but not all) patients. It does not seem to adversely affect ability to drive (abstract 234) or to have other undesirable side effects. About 8% of people note sedation when using melatonin, and 1-7% have some headache. An informal survey at the Geneva meeting showed that about half of the travel medicine practitioners there have used it themselves; most were pleased with the results. It is sometimes combined with a sedative. No definitive dose can be suggested, but oral doses of 1-5 mg are often used. As a non-drug, it is not subject to rigorous quality control during the manufacturing process.
What else can be done for jet lag? One study suggested that symptoms of jet lag increase with perceived family stress related to the travel (abstract 235). Perhaps avoiding family turmoil around the time of trips would help fight jet lag. Dietary changes have not been shown to help. Light exposure cycle changes (perhaps related to light’s influence on melatonin) have been tried. Hypnotics at bedtime change sleep but do not alter the resynchronization to a new time zone.
The Next Millennium
As the Geneva conference drew to a close, the outgoing Society president left participants with a challenge to look beyond the travelers we care for to the world they visit (presentation 322). It is a shame that while we treat travelers to keep them well, we remain largely unable to treat the populations of the countries being visited in such a way that we could reduce the burden of contagious disease to which our travelling patients are exposed. Each seven seconds, a child dies a vaccine-preventable death. The Expanded Program for Immunization is saving millions of lives each year. As travel medicine practitioners, we should keep working through the Children’s Vaccine Initiative to improve health for children, families, and visitors in the developing world.
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