Vaccines for Specific Infections

The risk of poliomyelitis in the unprotected traveler mandates that the physician review the patient's vaccination status. Two types of polio vaccine are available in the United States: inactivated poliovirus vaccine (IPV), which is now being replaced by an enhanced form of IPV known as eIPV, and live attenuated oral poliovirus vaccine (OPV). Adults who have previously completed a full course of primary vaccination with OPV may receive a booster dose of oral polio vaccine, or a dose of eIPV as an alternative possibility, before departing for areas where poliomyelitis is endemic or epidemic. Adult travelers who have not received a primary vaccination series should be immunized with eIPV, since these adult travelers have a slightly increased risk of developing paralysis when given oral polio vaccine (estimated to occur at a rate of approximately one case per 9 million doses). Oral polio vaccine should not be given to patients who are significantly immunocompromised, whether from disease or drug treatment. In these situations, eIPV should be given instead. Although there are no compelling data to support the teratogenicity of polio vaccine, vaccination for nonimmunized pregnant women should be avoided unless the unvaccinated pregnant traveler will definitely be exposed to an epidemic situation.

A tetanus toxoid injection should be administered if more than ten years has elapsed since the last booster dose. The combined formulation Td (including tetanus toxoid and diphtheria toxoid) is recommended, since many adults lack circulating levels of protective antibodies against diphtheria, as well as tetanus. Nonimmunized patients require a full vaccine series.

Persons born prior to 1957 are assumed to be immune to measles virus, since measles was essentially universal before the measles vaccine became available. Persons born since 1957 should have documentation of having received live attenuated measles virus vaccine (given subcutaneously), since this vaccine is considered to provide longlasting immunity in more than 95% of vaccine recipients. Persons vaccinated during the period from 1963–1967 (up to one million United States citizens) may require revaccination, since those who received the killed measles vaccine may not be adequately protected. Unfortunately, killed measles vaccine lacks the enduring efficacy provided by the live attenuated measles vaccine.

Immunity to rubella in women of childbearing ages should be established by serologic proof prior to international travel, since the risk of infection is considerably greater in those countries where widespread rubella vaccination has not occurred. Remember that live measles and rubella vaccines should not be given during pregnancy, nor in individuals with immunodeficiency conditions.

Yellow fever vaccine may be indicated and in some instances required for travel to some areas of tropical Africa and Central and South America where the disease is endemic. Because areas of the world where active infection exists change frequently, up-to-date information must be obtained directly from the CDC or its publications. A single injection of attenuated live yellow fever vaccine provides immunologic protection against this infection for ten years, beginning approximately ten days following immunization. Unfortunately, there is a significant rate (5 to 10%) of adverse reactions including headache, fever, and myalgias, but the vaccine is considered safe and effective. Since the vaccine strain is raised in chick embryos, persons with a hypersensitivity to egg products should not receive the yellow fever vaccine. Furthermore, the vaccine is contraindicated for infants less than one year of age, pregnant women (unless at extreme risk), and persons with a preexisting immunodeficiency state. A letter written by the traveler's physician stating why the vaccine is contraindicated may be required before crossing borders. Yellow fever vaccine recipients are required to have an International Certificate of Vaccination, which can only be issued by an official vaccine center. This document includes information regarding the vaccine origin, batch number, and the name of the individual administering the vaccine. Improper validation may result in a requirement for revaccination at the time of entry into the arrival country.

The use of the cholera inactivated bacterial vaccine is controversial. In general, cholera is an extremely rare occurrence in U.S. travelers to endemic or epidemic areas. Endemic areas include Asia, Northern Africa, and at times Southern Europe. Travelers with normal gastric acidity are considered to be at very low risk for developing disease due to Vibrio cholerae. The risk for infection is clearly higher in persons who take antacids or histamine receptor antagonists and in postgastrectomy patients.

The cholera vaccine has been shown to be protective in only 50% of vaccinated persons for a duration of three to six months, beginning six days after immunization. Some countries require International Certificates of Vaccination against cholera, and a single dose of vaccine fulfills international health regulations. Cholera vaccine is rarely recommended except for travel to the few specific countries that require vaccination for entry and for immunization of individuals who are considered to be at especially high risk.

Parenteral typhoid vaccine is available in the United States and is thought to be protective in approximately 70% of recipients; however, the vaccine usually is recommended only for persons traveling to areas where a substantial risk of exposure to typhoid is anticipated. Such areas where typhoid fever is common include many regions of Africa, Asia, and Central and South America. The primary immunization series consists of two injections administered 4 weeks apart. Boosters are required every 2 to 3 years. These recommendations could change if either the orally administered live vaccine under current study (strain Ty21a) or the intramuscular single dose of purified Vi capsular polysaccharide vaccine, both of which appear to be highly effective, become available.

For most adult travelers, prophylaxis against hepatitis A can be obtained by a single intramuscular injection of immune serum globulin, the dose depending upon the length of stay in the tropical or developing country. Passive immunization must be repeated approximately every 5 months, and the injection should be given as close as possible to the time of departure, since protection is mediated by antibodies which have a finite half-life. Pregnancy is not a contraindication to prophylaxis with immunoglobulin against hepatitis A.

The need for other immunizations (e.g., vaccines for hepatitis B, rabies, meningococcus, influenza) should be determined by the needs and plans of the individual traveler. Hepatitis B is highly endemic in many areas of the world, but there are currently no clear indications as to which travelers should be vaccinated. Nonetheless, hepatitis B vaccine may well be appropriate for persons traveling to populations where the prevalence of hepatitis B carriers is especially high (e.g., China, Indonesia, parts of the Caribbean, South Pacific, and Africa). If exposure to blood is likely, such as with health care workers, or if intimate sexual contact is anticipated with the resident population in an endemic region, hepatitis B vaccine may be an important prophylactic measure. In addition to the foregoing groups, travelers who plan extended stays of 6 months or longer in a country where the prevalence of hepatitis B carriage is especially high should be vaccinated. These areas of high prevalence currently include parts of Asia, Sub-Saharan Africa, and the interior Amazon basin.

Rabies vaccine is recommended only for (1) persons visiting or living for prolonged periods of time in countries where rabies is present and (2) those individuals who will have frequent contact with animals likely to be infected with rabies (e.g., trappers or anthropologists). Despite the low risk for most travelers, all should be informed about rabies, since animal rabies is endemic in many areas of Latin America, the Far East, and Africa. When exposure to rabies is thought to occur, health care must be sought promptly so that postexposure prophylaxis can be started if it appears indicated. Children are particularly prone to rabies exposure and need to be wary of possible rabid animals.

Meningococcal vaccine rarely is required for U.S. travelers but should be given to those going to areas where epidemic meningococcal disease is occurring. Recently such areas have included Nepal, Saudi Arabia, Sub-Saharan Africa, the New Delhi region of India, and limited areas of South America. Inquiries for updated information from the CDC will help keep physicians abreast of indications for such vaccines.

Malaria

Malaria prophylaxis remains one of the most important albeit complex and confusing travel medicine issues for physicians. Malaria is present in many parts of the world and is caused by various species of Plasmodium via the bite of certain anopheles mosquitoes. The risk for malaria and the presence of chloroquine-resistant malaria is noted in Health Information for International Travel. The approach required is one that combines protection against the bite of mosquitoes, the use of safe and effective drugs for prophylaxis, and plans for medical care if malaria occurs. The choice of adequate prophylaxis is dependent upon the area of travel and, since no prophylactic regimen is 100% effective, even travelers who are taking appropriate prophylactic antimicrobials must be advised that prompt medical attention is required for any acute febrile illness that may be malaria.

Chemoprophylaxis for travel to areas endemic for chloroquine-sensitive Plasmodium falciparum, Plasmodium ovale, Plasmodium vivax, or Plasmodium malariae consists of weekly doses of oral chloroquine (300 mg base) beginning 1 week prior to departure and continuing for 6 weeks after return. Terminal prophylaxis with primaquine is sometimes prescribed to eradicate the hepatic phase of strains of malaria (P. vivax and P. ovale) in travelers who do not have glucose-6-phosphodiesterase deficiency and are not pregnant, since chloroquine has no effect on the hepatic phase.

In areas where travelers are at risk for acquiring chloroquine-resistant P. falciparum, there are several alternative suggestions for prophylaxis, the choices being continuously revised as efficacy and safety are evaluated. In general, a weekly dose of chloroquine (300 mg of base) is recommended, but a single dose of Fansidar (pyrimethamine and sulfadoxine) is also given to the traveler to use in the event that medical help is not immediately available and a febrile, flulike, possible malarial illness occurs. Fansidar has unfortunately been associated on rare occasions with fatal cutaneous reactions, such as the Stevens–Johnson syndrome (approximately 1 in 20,000 users). Travelers must be informed of this potential risk, therefore, if Fansidar is prescribed. (See Table 227.2 for more detail.)

A drug that may be effective in the treatment of chloroquine- and Fansidar-resistant malaria is mefloquine. Though not currently available in the United States, this drug is recommended by the World Health Organization for prophylaxis in East Africa and Southeast Asia and can be readily obtained in those areas of the world or in much of Europe. Weekly chloroquine and daily doxycycline are another regimen that has been suggested for travelers to rural regions of Southeast Asia and the Amazon region of South America, where confirmed chloroquine and/or Fansidar resistance has occurred.

Women who are pregnant or likely to become so should avoid travel to areas where chloroquine-resistant malaria is present and where prophylaxis with pyrimethamine/sulfadoxine (Fansidar) or some of the other newer regimens is needed. Chloroquine prophylaxis appears safe when used by pregnant women and is quite acceptable for prevention of chloroquine-sensitive malaria. Chloroquine does not provide complete protection against chloroquine-resistant falciparum malaria, however.

Consulting the CDC, the State Health Department, or an emporiatric specialist may be necessary in making some of the more complex travel medicine decisions, especially with the increase in chloroquine-resistant malaria and when multi-drug-resistant malaria organisms are known to be present in countries listed on the traveler's itinerary.

Some Important Protozoal Infections

Entamoeba histolytica can be an important cause of dysentery, other gastrointestinal symptoms, hepatic diseases, and occasionally a variety of other serious complications such as subdiaphragmatic infection, empyema, pericarditis, and peritonitis. Giardia and cryptosporidia are important enteric pathogens in travelers to many areas of the world and can be avoided to some degree by proper handling of food and water. Leishmania can cause infections in various parts of the world and is spread by sand fleas and flies. Visceral leishmaniasis can be acquired rapidly in India and occasionally in the Mediterranean area, East Africa, and South America. Cutaneous and mucocutaneous forms of the disease may also occur. Infection with leishmania can be partially prevented by taking measures to help decrease the incidence of insect bites.

Some Important Helminthic Infections

Prevention of schistosomal infections focuses on avoidance of swimming in unchlorinated fresh water in Africa, the Caribbean, Latin America, and the Far East. Strongyloides and hookworms are widespread soil inhabitants in tropical areas, and infection can be prevented by avoiding barefoot walking and by practicing other good hygienic measures.

Intestinal Infections

Diarrhea occurs in approximately 50% of persons traveling to high risk areas from industrialized regions. The most common cause of traveler's diarrhea in high risk areas is enterotoxigenic Escherichia coli, followed by strains of shigella, salmonella, campylobacter, and E. coli capable of producing disease by other mechanisms than enterotoxin production. Less common causes include giardia, cryptosporidia, and rotavirus. Amebiasis is a less common but potentially severe cause of gastrointestinal infection in travelers.

Individuals may experience illness either during their travels or soon after they return home. The severity of the diarrhea, the presence of blood or mucus in the stool, and the presence or absence of fever help to determine the most likely etiologies and, in turn, lead to the most helpful therapy. Febrile illnesses are more likely to be associated with invasive pathogens, as opposed to those that produce their effect primarily by enterotoxin formation. Diarrhea that is short-lived is usually bacterial or viral, whereas a chronic disease course is more likely to be due to protozoal (e.g., amoebic, giardial, or cryptosporidial infection) or helminthic (e.g., coccidiosis, ascaris, or trichuria) infections or infestations. At times, a sprue-like illness or a disaccharidase deficiency may be present, producing diarrhea and malabsorption for some months even after the traveler has returned home.

The frequency of travelers" diarrhea can be diminished by selecting food and beverages carefully, especially when traveling to Latin America, Asia, or Africa. Items that usually are considered to be safe include peeled citrus fruit, any food served steaming hot, bread, or bottled beverages. Similar guidelines should be followed when eating meals prepared on commercial airlines that originate from such areas.

Bismuth subsalicylate (Pepto-Bismol) is effective in the prevention of travelers" diarrhea when taken in the appropriate dose and frequency. Patients who take this medication should be warned in advance of possible side effects such as black stools, which can be mistaken for melena. Generally speaking, the use of prophylactic antibiotics such as the quinolones should not be recommended for most tourists. Although prophylactic antibiotics are effective in approximately 80% to 90% of travelers, they are not usually recommended for most travelers, since the risks of antibiotic prophylaxis for prevention of diarrhea probably outweigh the benefits. In some travelers, however, antibiotic prophylaxis may be extremely helpful. Travelers going to high risk areas for less than two weeks who have an increased susceptibility to diarrhea (e.g., those with achlorhydria, a gastric resection, or hypoglobulinemia) who are receiving drugs like lithium, diuretics, or digitalis may benefit from prophylaxis. Similarly, patients on antacids or cimetidine-like drugs may have serious problems if they become dehydrated and thus are candidates for prophylactic antibiotics. A business traveler on a short trip who cannot "afford to spend time" in the restroom may also be a candidate for antibiotic prophylaxis.

If diarrhea does occur, it is nearly always self-limited. Careful attention to proper fluid and electrolyte replacement with a variety of balanced, sometimes premixed, oral, or, rarely, parenteral solutions is adequate for most situations. Any traveler who develops significant fever, chills, bloody stools, or in whom diarrhea persists for more than 3 days should be evaluated by a physician if possible. Oral ciprofloxacin is effective against the majority of the bacterial pathogens that have been isolated but is not effective in parasitic or viral gastroenteritis. Loperamide or other antimotility drugs may be effective in relieving severe abdominal discomfort and severe diarrhea but can prolong the illness caused by shigella and other invasive enteric pathogens. Therefore, antimotility drugs should be avoided if possible, especially if fever or bloody mucoid diarrhea is present.