As tourists continue to enter remote areas, you need to prepare them with the most up-to-date information on vaccinations, malaria prophylaxis, and other vital precautions. The job may not be over until long after the patient returns home.

Many travelers experience adverse health events during and after trips to the develaping world; some of these problems might have been preventable with careful planning. Make a special effort to identify travelers who are at high risk, including those venturing off the usual tourist routes, backpackers, long-term travelers, and foreign-born persons who are returning to visit family and friends. These people need to be carefully advised about the prevention and therapy of travelers' diarrhea, malaria, and other illnesses. Also, discuss their access to medical care during travel, and remind them to review their health insurance policies. Many companies will pay customary and reasonable hospital costs abroad, but very few will pay for medical evacuation back to the United States, which can cost as much as $10,000. Note that primary care physicians now have a vital role in preventing the spread of sudden acute respiratory syndrome (SARS) (see "Managing the SARS risk in travelers," page 51).

DISEASE PREVENTION

A consultation before travel is an excellent opportunity to update routine immunizations. Travelers to the developing world should have adequate immunity against measles, mumps, rubella, tetanus, diphtheria, pertussis, varicella, and influenza. If patients do not have adequate documentation of vaccinations and records cannot be located, consider these people susceptible and start them on the age-appropriate vaccination schedule. Serologic testing for immunity is an alternative to vaccination for certain infections, including measles, mumps, rubella, varicella, tetanus, diphtheria, hepatitis A, hepatitis B, and poliovirus.

Travelers to countries other than those in Western Europe who were born after 1956 and who have not had a measles vaccination since childhood will need another. Likewise, patients aged 7 years and older need at least 1 dose of adult diphtheria and tetanus toxoids every 10 years. Pay special attention to patients traveling to the new independent states of the former Soviet Union because a diphtheria epidemic has spread from Russia to these states. Travelers to Africa and certain parts of Asia should also have adequate immunity against poliovirus, which requires having at least 3 doses of the injectable poliovirus vaccine.

Typhoid

In general, people on short trips who observe strict water and food precautions do not need typhoid vaccine. Vaccination should be targeted at travelers at the highest risk: those going to South Asia, North and West Africa, or the more impoverished areas of Latin America for more than 3 to 4 weeks. Vaccination should also be considered for immunocompromised persons and those with severe atherosclerotic disease, internal prostheses, or cholelithiasis, since these people are most likely to have complicated or prolonged disease if infection occurs.

Cholera

An acute intestinal infection, cholera is prevalent in the populations of many of the developing countries of Africa and Asia, where sanitary conditions are suboptimal. Most recently, cholera outbreaks have occurred in some parts of Latin America. At the present time, the only licensed cholera vaccine in the United States has been discontinued because of the incomplete immunity it offered. The cholera vaccine is no longer an official requirement for travel anywhere in the world, but be aware that it has sometimes been an unofficial requirement in some developing countries, either because of ignorance or the desire of officials to extract a bribe from travelers who do not have a cholera stamp on their immunization records.

Hepatitis A and B

The hepatitis A vaccine is indicated for most non-immune travelers who cannot observe food and water precautions in developing countries. After a single dose of the vaccine, immunity develops in 95% of individuals within 4 weeks and persists for at least 6 to 12 months. Two doses provide long-term immunity. In persons who require immediate immunity and in children too young to receive the vaccine, IM immune globulin may be used to provide short-term protection against hepatitis A infection.

Hepatitis B vaccine is recommended for persons staying in an endemic area for 6 months or longer. All health care workers, regardless of their length of stay, should receive the vaccine. Other candidates include those who anticipate receiving local medical or dental care or who expect to have sexual contact with local residents. A combined vaccine--hepatitis A, inactivated; and hepatitis B, recombinant vaccine--is available for patients 18 years and older. Primary vaccination consists of 3 doses given on the same schedule as the single-antigen hepatitis B vaccine.

Yellow fever

Yellow fever is a rare but potentially fatal viral infection transmitted by day-biting mosquitoes in areas of Latin America and sub-Saharan Africa. Some African countries require evidence of vaccination from all entering travelers. Other governments may waive the requirement if the traveler is arriving from an area in which no yellow fever risk exists and is staying less than 2 weeks. For a CDC listing of countries requiring a certificate, see http://www.cdc.gov/travel/vaccinations/certrequirements2.htm.

Yellow fever vaccination must be given at an official yellow fever vaccination center, as designated by respective state health departments or the Division of Global Migration and Quarantine at the CDC. The accompanying certificate must be validated by the center that administers the vaccine. Persons for whom the vaccine is contraindicated should be issued a vaccination waiver.

Adverse reactions to yellow fever vaccination are rare, but a recent analysis of adverse events indicates that recipients aged 65 and older might be at increased risk for systemic adverse events compared with younger persons.1 Also, a new serious adverse reaction syndrome has been described among recipients of different yellow fever vaccines. Previously reported as febrile multiple organ system failure, it is now called yellow fever vaccine-associated viscerotropic disease. In July 2001, the first 7 case reports of the syndrome appeared in the scientific literature; 6 of these patients died.2 Subsequently, an additional 3 cases have been identified. Because of recent reports of vaccine-associated viscerotropic disease, practitioners should be careful to administer yellow fever vaccine only to persons truly at risk for exposure to yellow fever.

Japanese B encephalitis

Japanese B encephalitis is a mosquito-borne viral encephalitis that occurs in China, Japan, Korea, southeast Asia, and eastern areas of Siberia. Most infections are asymptomatic, but among people who develop a clinical illness, the case-fatality rate can be as high as 30%. Short-term travelers (those staying fewer than 30 days), especially those whose visits are restricted to major urban areas, are at lower risk for acquiring Japanese B encephalitis and generally should not be advised to receive the vaccine (for a listing of countries, regions, and seasons for risk of Japanese B encephalitis, see http://www.cdc.gov/travel/jenceph.htm)

The Japanese B encephalitis virus vaccine is associated with local reactions and mild systemic side effects (fever, headache, myalgia, and malaise) in about 20% of recipients. More serious allergic reactions, including generalized urticaria, angioedema, respiratory distress, and anaphylaxis, have occurred within minutes and up to 10 days after immunization. Such hypersensitivity reactions occur in approximately 0.6% of vaccinations.

Norwalk virus

Noroviruses are named after the original strain Norwalk virus, which caused an outbreak of gastroenteritis in a school in Norwalk, Ohio, in 1968. This group of single-stranded RNA, nonenveloped viruses causes acute gastroenteritis in humans. The CDC estimates that at least 50% of all food-borne outbreaks of gastroenteritis can be attributed to noroviruses. (3) The incubation period for norovirus-associated gastroenteritis in humans is usually between 24 and 48 hours, but cases can occur within 12 hours of exposure. Symptoms usually last 24 to 60 hours.

Noroviruses are highly contagious, and it is thought that an inoculum of as few as 10 viral particles may be sufficient to infect an individual. Immunity may be strain-specific and lasts only a few months; therefore, given the genetic variability of noroviruses, individuals are likely to be repeatedly infected throughout their lifetimes. This may explain the high attack rates in all age-groups reported in outbreaks. Recent evidence also suggests that susceptibility to infection may be genetically determined; people with type O blood seem to have the greatest risk for severe infection.

Noroviruses survive freezing, temperatures as high as 140[degrees]F (60[degrees]C), and have even been associated with illness after being steamed in shellfish. Moreover, noroviruses can survive in up to 10 parts per million chlorine, well in excess of levels routinely present in public water systems. Due to recent outbreaks of Norwalk-like viral infection on cruise ships, the CDC'S Vessel Sanitation Program has recommended aggressive sanitation measures. Other measures to prevent the spread of infectious diseases on cruise ships include frequent hand washing. Those with the illness should limit contact with the crew and other passengers.

Dengue

Caused by a mosquito-borne flavivirus, dengue has become a major threat worldwide, accounting for an estimated 50 million cases and at least 12,000 deaths annually (4) Seasonal epidemics of dengue are now common in many tropical and subtropical areas, with recent outbreaks in Rio de Janeiro, Brazil; Singapore; Puerto Rico; and Hawaii. Dengue may be caused by any of 4 different serotypes of the virus and is transmitted by mosquitoes that inhabit primarily urban areas. After an incubation period of 4 to 7 days, dengue manifests as an influenzalike illness with fever, headache, and myalgia. In about 50% of infected persons, lymphadenopathy and a diffuse rash develop. (5) Patients traveling to areas with dengue should take precautions to avoid mosquitos.

Influenza

Influenza virus vaccine and chemotherapeutic agents should be considered for those at high risk for severe influenza who are traveling to the Southern Hemisphere from April through September. A large influenza A (H3N2) outbreak in Madagascar has caused widespread acute respiratory illnesses since June 2002. The majority of the 838 deaths occurred away from health facilities among persons living in the remote highland districts of Fianarantsoa Province in southeastern Madagascar. Influenza can occur in the tropics throughout the year. People planning travel to Madagascar, especially persons at high risk for complications from influenza, should receive the influenza vaccination.

Meningococcal disease

Meningococcal illness is an acute bacterial disease characterized by sudden onset with fever, intense headache, nausea, stiff neck, and a petechial rash with pink macules. Whenever a patient plans travel to Africa, check with the CDC about any recent outbreaks in the meningitis belt, which extends from Senegal into the western half of Ethiopia. Because of a lack of established surveillance and timely reporting from many of the countries in sub-Saharan Africa, travelers to the meningitis belt during the dry season (December through June) should be advised to receive meningococcal vaccine, especially if prolonged contact with the local population is likely Vaccination against meningococcal disease is not a requirement for entry into any country except to Saudi Arabia, during the annual Hajj.

MALARIA PROPHYLAXIS

Malaria caused by Plasmodium falciparum can be rapidly fatal and must be immediately ruled out in all febrile persons who have recently visited an area where malaria is endemic. Approximately 90% of P falciparum infections are acquired in sub-Saharan Africa, and 90% of travelers who are infected begin to experience symptoms within 1 month of their return. In contrast, more than 70% of cases of malaria due to Plasmodium vivax infection are acquired in Asia or Latin America, and only 50% of travelers infected with P vivax begin to have symptoms within 1 month of their return. In approximately 2% of travelers, fever develops more than 1 year after return. Persons who visit family and friends while traveling abroad are at particular risk and account for approximately 40% of reported cases of malaria in the United States population. (6)

Resistance to antimalarial drugs is widespread and increasing. Travelers to malaria-risk areas in South America, Africa, the Indian subcontinent, Asia, and the southwest Pacific should take one of the following drugs: mefloquine, doxycycline, or atovaquone/proguanil. Identify both the country and the specific region within the country before making a decision about which antimalarial drug to prescribe. For more information, see http://www.cdc.gov/ncidod/dpd/parasites/malaria/default.htm.

Atovaquone/proguanil

The newest antimalarial drug, atovaquone/proguanil, is indicated for prophylaxis against infection by P falciparum. The combination medication is prescribed in a fixed-dose tablet that is taken once daily starting 1 or 2 days before entering a malaria-endemic area and continuing while the traveler is in the malaria zone and for 7 days after leaving the area. Physicians may wish to prescribe it when a patient is noncompliant or known to have difficulty tolerating mefloquine, since the combination drug is better tolerated and may have fewer adverse effects. The most common side effects are abdominal pain, nausea, vomiting, and headache. Patients with severe renal impairment should not take atovaquone/ proguanil. A lower-dose pediatric tablet is available for children.

Chloroquine

Travelers to malaria-risk areas in Mexico, Haiti, the Dominican Republic, and certain countries in Central America and the Middle East, as well as central Asia, should take chloroquine as prophylaxis against P falciparum. The chloroquine regimen starts 14 days before arrival in the malaria-risk area. It is taken once a week while in the area and for 4 weeks after leaving. Adverse effects include dizziness, blurred vision, and itching. Chloroquine resistance is extremely widespread and now affects sub-Saharan Africa, Southeast Asia, the Indian subcontinent, and large areas of South America.

Mefloquine

Mefloquine is considered by the CDC and other experts to be a first-line antimalarial drug because it can be taken once weekly. Reports of adverse neurologic effects associated with mefloquine are increasing. New warnings have been added to mefloquine's label stating that if a patient taking the drug prophylactically develops psychiatric symptoms such as acute anxiety, depression, restlessness, or confusion, these symptoms "may be considered prodromal to a more serious event," and that the drug should be stopped and replaced with another medication. Other contraindications include a history of epilepsy, seizures, or cardiac arrhythmias.

Doxycycline

Doxycycline is the drug of choice for travelers to regions that have both chloroquine- and mefloquine-resistant organisms, such as the areas of Thailand bordering Cambodia and Myanmar, as well as the western provinces of Cambodia and eastern provinces of Myanmar. Mefloquine resistance has been reported in these areas, and either doxycycline or atovaquone/proguanil is recommended for visitors there. Travelers take doxycydine starting 2 days before arrival, once daily while staying in the malaria zone, and continuing daily for 4 weeks after leaving. Adverse effects include photosensitivity, nausea, and vaginal yeast infections.

PRECAUTIONS

Advise patients to take care to prevent mosquito bites. Anopheles mosquitoes, which spread malaria and usually bite between dusk and dawn, should be avoided. Recommend using an insect repellent that contains 20% to 30% diethyltoluamide (DEET) and wearing long-sleeved clothing and long pants. Clothing should be sprayed with permethrim, and travelers should use permethrim-treated mosquito netting over beds.

A variety of other hazards could make a patient's travels uncomfortable or dangerous, including diarrhea, altitude illness, and sexually transmitted diseases (STDs). Travelers may want to pack a supply of loperamide for treating travelers' diarrhea, an analgesic and antipyretic drug, an anti-inflammatory agent, an antihistamine, and an antifungal cream. Prednisone is recommended for persons with chronic obstructive pulmonary disease or asthma.

Recommend that travelers obtain the names of physicians and clinics in the destination cities. The US Department of State's Web site (http://www.state.gov) provides suggestions. Or contact the International Association for Medical Assistance to Travelers at http://www.iamat.org.

Diarrhea

Remind patients to avoid drinking local tap water or using it to make ice cubes or brush their teeth. They should drink only sealed bottled water or tea or coffee made with water that has been boiled for 3 minutes. Raw fruits and vegetables should be avoided, especially those grown in or near ground that may have been fertilized with raw sewage. Foods from street venders should be avoided, as should any food that cannot be peeled or cooked.

Physicians may consider proactively prescribing antidiarrheal medications such as loperamide or bismuth subsalicylate. Avoid prescribing trimethoprim because some bacteria are resistant to it. Warn patients not to take an antimotility agent if the diarrhea is accompanied by a fever or if blood if present in the stool. Also consider prescriptions for ciprofloxacin or other antibiotics to be taken if severe diarrhea develops. Advise patients to fill prescriptions before leaving the United States, since the quality of medications in other countries may be inadequate. Because of the danger of precipitating hemolytic uremic syndrome in a child infected with enterohemorrhagic Escherichia coli, warn travelers not to give their children antibiotics for diarrhea, especially if the diarrhea is bloody and not accompanied by fever.

Respiratory tract infections

After diarrhea, respiratory tract infection is the most common illness affecting travelers. Persons with underlying cardiopulmonary conditions may be predisposed to severe illness. Immunocompromised persons and those with marginal cardiopulmonary reserve may benefit from carrying an appropriate antibiotic for self-treatment.

Altitude illness

Travelers visiting high-altitude regions should be cautioned to prepare for altitude illness, which affects more than 25% of persons who rapidly ascend to 8200 ft or higher. Acute mountain sickness usually manifests as headache, nausea, and light-headedness. The risk of altitude illness may be reduced by graded ascent and the appropriate use of prophylactic medications such as acetazolamide. Although effective, dexamethasone and nifedipine have limited roles in preventing altitude illness because of the risk of adverse events. Travelers planning to trek or climb mountains to altitudes exceeding 11,500 ft should be fully evaluated by a physician with experience in conditions affected by high altitude.

STDs

Travelers who plan to engage in sexual activity should use condoms and take safer-sex precautions. AIDS is a major problem in sub-Saharan Africa, parts of the Caribbean, India, and Southeast Asia. The disease is emerging in the populations of South Pacific, Central and South America, and eastern Europe. Travelers should assume that contact with any commercial sex worker could expose them to an STD, including HIV infection.

After returning home

Advise patients who have a fever to come in for a checkup immediately because breakthrough malaria is possible even if the patient has taken chemoprophylaxis. Careful assessment of the travel history, associated signs and symptoms, duration of fever, and use or nonuse of an antimalarial chemoprophylactic regimen, suggests the diagnosis. Initial investigations may include prompt evaluation of peripheral blood for malaria; complete and differential blood counts; liver function tests; urinalysis; culture of blood, stool, and urine; chest radiography; and specific serologic assays, such as those for arboviruses, rickettsiae (caused by arthropods and detected by a painless eschar at the inoculation site), schistosomiasis, leptospirosis, and HIV infection.

REFERENCES

(1.) Martin M, Weld LH, Tsai TF, et al. Advanced age a risk factor for adverse events temporally associated with yellow fever vaccination. Emerg Infect Dis. 2001;6:945-951.

(2.) Adverse events associated with 170-derived yellow fever vaccination--United States, 2001-2002 MMWR Morb Mortal Wkly Rep. 2002:51:980-993.

(3.) Respiratory and Enteric Viruses. Available at: http://www.cdc.govncidod/dvrd/revb/gastro/norovirus.htm. Accessed April 16, 2003.

(4.) Dengue prevention and control. Wkly Epidemiol Rec. 2002;77:41-44.

(5.) Ryan ET, Wilson ME, Kain KC. Illness after international travel. N Engli Med. 2002:347:505-516.

(6.) Newman RD. Barber AM. Roberts J. et al. Malaria surveillance-United States, 1999. MMWR Surveill Summ. 2002;51(SS-1);5-28.

RELATED ARTICLE: This article at a glance

Preventing disease

* A new combined vaccine for both Hepatitis A and B has recently become available.

* Infection-acquired immunity to the Norwalk virus may be strain-specific and last only a few months.

* Those traveling with a large tour group at any time of the year or to the Southern Hemisphere from April through September should have an influenza vaccine.

Malaria prophylaxis

* Mefloquine is contraindicated in people with a recent history of depression, generalized anxiety disorder, psychosis, sdhizophrenia or other major psychiatric disorders.

* Atovaquone/proguanil can be prescribed when mefloquine is contraindicated or if the patient has difficulty tolerating mefloquine.

"Update on travel medicine," Patient Care, June 2003.

Managing the SARS risk in travelers

For physicians in the United States, the most pressing question about severe acute respiratory syndrome (SARS) is what to do when a patient may have been exposed to SARS, either because of travel to an area where the infection is widespread or because of close contact with an infected person. Scientists agree that rapid identification and isolation of people who may be infected is crucial to halting the spread of SARS, especially during the summer months, when it may be possible to take advantage of a natural dip in viral transmission to slow the epidemic (see the algorithm). The most up-to-date information on all aspects of SARS is available at the World Health Organization and CDC Web sites: http:// www.who.int/en/ and http://www.cdc.gov/ncidod/sars/, respectively.

Where to get up-to-date travel information

Travel health recommendations change frequently, and the best information can usually be obtained from your state health department or the CDC. Check these sources before administering vaccines. Don't assume that last month's advice still holds true.

CDC/National Center for Infectious Diseases: Travelers' Health home page

http://www.cdc.gov/travel/

CDC International Traveler's Voice Information Service

(404) 332-4559

CDC/National Center for Infectious Diseases: Travelers' Health online Yellow Book

http://www.cdc.gov/travel/yb/index.htm

The Yellow Book contains information for health care professionals who advise overseas travelers. Because it is published every 2 years, it must be used in conjunction with the updated information on the CDC Web site.

CDC/National Center for Infectious Diseases: Travelers' Health online Blue Sheet

The Blue Sheet posts outbreak notices and lists countries with areas infected with quarantinable diseases according to the World Health Organization (WHO)

http://www.cdc.gov/travel/blusheet.htm

CDC/National Center for Environmental Health: Vessel Sanitation Program and Green Sheet

This site post information on recent illness outbreaks aboard cruise boats and sanitation scores for individual vessels.

http://www.cdc.gov/nceh/vsp/default.htm

International Society of Travel Medicine (ISTM)

Among other services, this site maintains a world-wide directory of travel clinics.

http://www.istm.org

International Association for Medical Assistance to Travelers

http://www.iamat.org

US Department of State, Bureau of Consular Affairs, American Citizens Services

This site provides information on countries in which travelers could be in danger because of wars or civil strife, or criminal activity.

http://travel.state.gov/travel_warnings.html

Drugs mentioned in this article

Acetazolamide (Dazamide, Diamox)

Atovaquone/proguanil (Malarone)

Bismuth subsalicylate (Pepto Bismol)

Chloroquine (Aralen Phosphate)

Ciprofloxacin (Cipro)

Dexamethasone (Decadron, Hexadrol)

Doxycycline Loperamide (Imodium)

Mefloquine (Lariam)

Nifedipine (Adalat, Procardia)

Prednisone Trimethoprim (Proloprim, Primsol, Trimpex)

VACCINES

Diphtheria and tetanus toxoids, adsorbed

Hepatitis A vaccine, inactivated (Havrix, Vaqta)

Hepatitis A, inactivated, and hepatitis B, recombinant vaccine (Twinrix)

Hepatitis B vaccine (Engerix-B, Recombivax HB)

Immune globulin Influenza virus vaccine Japanese encephalitis virus vaccine, inactivated (JE-VAX)

Measles-mumps-rubella vaccine, trivalent (MMR)

Meningococcal polysaccharide vaccine (Menomune-A/C/Y/M-135)

Poliovirus vaccine, inactivated (IPOL) Typhoid vaccine live oral Ty21a (Vivotif Berna)

Typhoid Vi polysaccharide vaccine (Typhim Vi)

Yellow fever vaccine

KEITH B. ARM ITAGE, MD, Attending Physician, Travelers' HealthCare Center, University Hospitals of Cleveland: and Vice Chair for Education, Department of Medicine, Case Western Reserve University, Cleveland, Ohio. He is also a member of the Patient Care Board of Editors.

MARTIN S. WOLFE, MD, Director, Travelers Medical Service, Washington, DC; and Clinical Professor of Medicine, George Washington University and Georgetown University Medical Center, Washington, DC.

Record Number: A104670440

SOURCE:
Keith B. Armitage, Martin S. Wolfe. Patient Care.  June 2003 v37 i6 p46(8).

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