Vaccines for Travel

Key Points

Lifelong protection against pertussis (whooping cough) is important. The new vaccine (ADACEL©) provides on-going protection, not previously available, against pertussis (whooping cough), tetanus (lockjaw) and diptheria to adolescents and adults. ADACEL contains the same components as the childhood DTaP vaccine, but the diphtheria toxoid and one of the pertussis components are in reduced quantities. Introduction of Tdap vaccines may soon make it possible to maintain immunity after childhood against all three of these diseases with a single vaccine. It is likely that protection against these diseases will last 10 years.
Update on Polio: Polio continues to be present in sub-Saharan Africa, India, Pakistan and Afghanistan. It is surging again in Nigeria.
According to the Global Polio Eradication Initiative (GPEI), since 2006, only 4 countries (Afghanistan, India, Nigeria, and Pakistan) remain polio-endemic with indigenous poliovirus circulation. In four additional countries in Africa, imported wild poliovirus was either known (Angola, Chad) or suspected (Democratic Republic of the Congo, southern Sudan) to have persisted for >12 months as of mid-2009, leading to their designation as having “re-established” transmission. This designation is considered equivalent to polio-endemic countries for travel preparation purposes.

The following countries, however, have had imported polio cases or cases related to an imported poliovirus in the past 24 months: Angola, Benin, Burkina Faso, Burundi, Cameroon, Central African Republic, Chad, Côte d'Ivoire, the Democratic Republic of the Congo (DRC), Ethiopia, Ghana, Guinea, Kenya, Liberia, Mali, Mauritania, Nepal, Niger, Senegal, Sierra Leone, Sudan, Togo, and Uganda. The following countries are at risk for poliovirus importation because they are located near endemic or recently infected countries: Bangladesh, Bhutan, Congo, Djibouti, Equatorial Guinea, Eritrea, Gabon, Gambia, Guinea-Bissau, Namibia, Rwanda, Somalia, Tanzania, and Zambia. This updated notice includes changing the status of Burundi, Cameroon, Mauritania, Senegal, and Sierra Leone from “at risk for importation” to countries reporting cases. It also identifies Angola, Chad, Democratic Republic of the Congo, and southern Sudan as destinations with re-established transmission.
Vaccination (a single life-time booster dose of inactivated polio vaccine—if not previously received) is recommended by the CDC for all travelers to polio-endemic or epidemic areas. These areas include Africa, South Asia, Southeast Asia, and the Middle East.
The oral cholera vaccine Dukoral® (not available in the United States, but available in Canada) provides about 10-30% 3-month protection against diarrhea caused by enterotoxigenic E.coli (ETEC), the most frequent cause of travelers’ diarrhea.
Influenza vaccine should be considered routine for all travelers over the age of 6 months, including pregnant women.
Hepatitis A is one of the most important vaccine-preventable infections in travelers. Non-immune travelers (i.e., those who have never had the infection and have not been vaccinated), going even to "low-risk" countries should consider vaccination for general health maintenance. Hepatitis A can be transmitted by food handlers, children in daycare centers, and by men who have sex with men.
Three doses of Havrix Pediatric vaccine (1 dose every 2 mo. x 3 doses for ages ≥2 months) will fully protect infants against hepatitis A, although immune globulin (hard to obtain) is the usual recommendation for children <1 year of age. Most children under the age of 5 who acquire hepatitis A have no symptoms and remain well.
Typhoid vaccination is highly recommended for travelers returning to a lesser-developed country to Visit Friends and Relatives (VFRs)The available typhoid vaccines are an intramuscular polysaccharide vaccine and oral live attenuated vaccine. Neither protects against paratyphoid fever.
The maximum efficacy achieved by either of these vaccines is 75%, with cumulative three year efficacies of 50-60%. Protection wanes with time, and boosters are needed yearly with the oral vaccine and every three years with the polysaccharide vaccine.
In Canada and Europe, a new combination vaccine “Vivaxim” contains both hepatitis A and typhoid for injection in a single dose.
The new meningococcal vaccine (Menactra®) protects against all 4 types of meniningococcal infection (A,C,Y,W-35). It’s main advantage over Menomune® (a different vaccine that protects against the 4 types) is that it lasts longer (possibly 8 years) and prevents the infection from being carried in the nose, and then being brought home to infect household contacts. It is the vaccine of choice for travelers requiring protection against this potentially very serious infection.

What's New

In December 2008, the CDC warned that that a high proportion of influenza A (H1N1) viruses are resistant to the antiviral medication oseltamivir (Tamiflu®). Worldwide, the proportion of H1N1 viruses that are resistant to oseltamivir has been increasing.
- Health care providers are recommended to use the alternative antiviral medication zanamivir (Relenza®), or to use combination therapy of oseltamivir (Tamiflu) and rimantadine. Use of zanamivir or dual therapy with oseltamivir and rimantadine provides effective treatment against all circulating influenza viruses.
- The CDC recommends annual influenza vaccination as the first and best step in preventing the flu. It is not too late to get vaccinated and this year′s influenza vaccine is expected to be effective against currently circulating oseltamivir-resistant influenza A (H1N1) viruses.
The polysaccharide meningitis vaccine (Menomune®) is now recommended only if the conjugate meningitis vaccine (Menactra®) is not available. Menactra® is now approved for children 2 years of age and older. Neither vaccine, however, protects against Group B meningococcal meningitis.
Immune globulin is no longer recommended for protection against hepatitis A in healthy travelers departing imminently. However, travelers >40 years of age, immunocompromised travelers, and those with chronic liver disease or other chronic medical conditions who have less than 2 weeks before departure may receive a single intramuscular dose of immune globulin (0.02 mL/kg) at a separate anatomic site in addition to the initial dose of vaccine.
The CDC’s Advisory Committee on Immunization Practices (ACIP) now recommends expanding the use of the nasal influenza vaccine FluMist® to include healthy children ages 2-4 years old (24–59 months old) without a history of asthma or recurrent wheezing. The vaccine continues to be recommended for healthy persons ages 5–49 years who are not pregnant.
In March 2009, the U.S. Food and Drug Administration approved IXIARO, a vaccine to prevent Japanese encephalitis (JE) which is caused by a mosquito-transmitted virus found mainly in Asia. IXIARO will be the only vaccine for JE available in the United States. IXIARO is manufactured by Intercell Biomedical, Livingston, U.K.
The CDC's Advisory Committee o Immunization Practices has recommended dropping the number of post-exposure rabies vaccine doses from 5 to 4. This recommendation was due to vaccine shortages. Dosing on days 0, 3, 7 and 14 would be considered "off-label" since the FDA still only approves a 5-dose regimen.

Being up-to-date on your “shots,” or completing a vaccination (immunization) schedule before departure, is one of the most important steps you can take to prevent a travel-related disease. Immunizing travelers, however, has become increasingly complex because new vaccines (e.g., Menactra, for meningitis; Dukoral for travelers’ diarrhea and cholera) are being brought to market, whereas others (e.g., injectable cholera) are being phased out. In the meantime, new diseases for which vaccines are not yet available, such as SARS and avian influenza, have emerged.

Travelers may complicate the situation by not allowing enough time to be immunized according to established vaccination schedules or requirements. Of course, in some cases, their departures may be unscheduled, perhaps for business or personal reasons. Although some vaccines, such as the combined hepatitis A and B vaccine (Twinrix®), may be administered in an accelerated schedule over 3 weeks, some travelers may be forced to delay their trip, or forgo essential protection, if they are scheduled to depart on short notice. Therefore, travelers planning an itinerary should seek pre-travel health advice 6 to 8 weeks before departure to be sure there is enough time for multiple doses of one or more vaccines, if these are needed. Business travelers, or others, who have unpredictable schedules, should have their travel immunizations updated regularly to ensure that they are prepared for last minute travel, regardless of the destination.

Planning Vaccinations

Vaccination recommendations are determined by a host of factors:

The traveler’s age, past medical history, vaccination history, travel history, country of birth, and country where he or she was raised.
The duration of planned travel, lifestyle activities during travel (e.g., possible unsafe sexual contact or drug use), high-risk occupational exposure (e.g., health-care or relief worker).
The traveler’s present health status. Individuals who have immunodeficiency diseases (such as AIDS) or who are taking immunosuppressive medications may be more susceptible to vaccine-preventable diseases, are at increased risk of dangerous virus replication from live vaccines and may have a diminished immune response to vaccines.
The current disease patterns in the specific localities of the country to be visited.
The types of accommodations and restaurants to be frequented.
The likely extent of close contact with local people. This may favor, for example, administering meningitis vaccine.
The traveler’s budget for vaccines. Unfortunately, for “budget” travelers, the cost of vaccines, in the United States in particular, can approach the budget for the entire trip. Although the cost of some vaccines may be covered by some insurance plans, most travel clinics operate on a cash payment basis.
Pregnancy: Vaccinating pregnant women requires expertise regarding the effect of the vaccine, if any, on the fetus, and the magnitude of the risk of exposure to the disease. In general, live-virus vaccines are not given to pregnant women. However, in the case of yellow fever, the risk of disease may outweigh the possible risk of vaccination.

The standard approach to travel immunization is to consider the “3 Rs:” (1) Routine, (2) Required, and (3) Recommended.

Routine immunizations are childhood or adult immunizations that should be updated regardless of travel (e.g., tetanus, polio, diphtheria, measles, mumps, rubella, etc.)
Required immunizations are those required by destination countries for entry according to international health regulations (e.g., yellow fever, meningococcal meningitis)
Recommended immunizations are those recommended according to risk of infection (e.g., hepatitis A and B, typhoid, Japanese encephalitis, rabies, etc.) Note that hepatitis A and B vaccines are now routinely given in childhood.

Travel medicine advisors carry out an individual risk assessment for each client in these three areas of immunization, taking into consideration the factors discussed above. A risk management program of immunization is then constructed to meet the needs, time available before departure, and financial resources of the traveler.

Vaccines for routine use and specialized vaccines for international travel are described subsequently. Table 3.2 contains specific information on dosing schedules, indications, booster doses, and precautions. Table 3.3 contains immunization guidelines in HIV-infected travelers. Childhood immunization schedules for the United States are found in Figure 3.2. Immunization during pregnancy is discussed in Chapter 20.

Checking Your Routine Immunizations

Vaccination Schedules for 2010

Catch-Up Immunization Schedule for Persons 4 Months Through 18 Years

Vaccine and Disease Summary

Chickenpox (Varicella)

Chickenpox is a viral infection caused by Varicella zoster. It is highly contagious and usually quite mild, although serious complications, even fatalities, may result, especially when the infection occurs in an adult. It is primarily a disease of children; in North America 90% of children will have been infected or vaccinated by age 10. New immigrants from Latin America and South Asia should be tested for varicella antibodies if the history of infection is unknown because in these areas of the world chickenpox tends to occur at an older age. The infection is spread by contact with infected objects and the respiratory route when there is close contact with an infected person. Those who have had this disease have lifelong immunity and do not need the vaccine prior to travel Note: A high-dose, live varicella vaccine (Zostavax) has recently been marketed by Merck for adults over age 60. This vaccine is indicated for those who have had chickenpox in the past but who have the potential to develop shingles ( a reactivation of chickenpox virus in nerves of the spinal cord or brain) in later life as a consequence of waning immunity against the varicella virus This vaccine should not be confused with the vaccine used to prevent chickenpox. Chickenpox vaccine is now a routine immunization for all children in the United States. All children should receive two doses of varicella vaccine; one dose of chickenpox vaccine between 12 and 15 months and a second dose at age 4-6 years. Adults and adolescents 13 years of age or older should receive two doses of the vaccine, 4 to 8 weeks apart. Chickenpox vaccine, which is a live virus vaccine, should not be given during pregnancy, and female patients should not become pregnant for at least 1 month after immunization.

International travelers of any age who have had neither the disease nor the vaccine should receive this vaccine prior to departure. This applies especially to female travelers of childbearing age who may become pregnant because varicella zoster may cause severe injury to the fetus.

See Table 3.2 for a summary of the varicella vaccine schedule, indications, precautions, and booster recommendations.

Cholera

Oral Cholera Vaccines Oral cholera vaccines provide better immunity and fewer side effects than the previously available injectable vaccine.

An oral, live attenuated vaccine is licensed in Canada (Mutachol®) and some European countries (Orachol®) for travelers over 2 years of age. It is at least 80% effective against cholera strains (serogroup 01 only) commonly found in the Western Hemisphere. It does not protect against serogroup 0139, found in India, Bangladesh, and Southeast Asia. Boosters are needed every 6 months. Production of the live, oral vaccine has been temporarily suspended by the manufacturer (Berna). The company states that the vaccine may be available in 18 months.
An inactivated bacterial vaccine (Dukoral®) is available in Canada, Australia, and countries in the European Union. The vaccine contains a large amount of killed whole cholera bacteria and a recombinant non-toxic (B subunit) part of cholera toxin. It is actually two vaccines in one.

It is 60% to 85% protective against cholera (serotype 01) for 4-6 months, with lower levels of protection continuing for 2-3 years.
It also gives 60-70% crossover protection against travelers' diarrhea caused by enterotoxigenic E. coli. This is because the heat-labile toxins elaborated by E. coli and V. cholerae bacteria share similarities.

To prevent cholera Cholera vaccine is not routinely recommended for travel to countries where cholera is reported active because the risk to the average international traveler of getting the disease is extremely low. The vaccine, however, is indicated for (1) people such as relief and healthcare workers operating in a high-risk environment—for example, working in a refugee camp or helping with disaster relief in an endemic or epidemic area, and (2) persons located in remote areas where cholera endemics or epidemics are occurring and there is limited access to medical care. An example might be someone doing archeological work in a remote endemic area.

To prevent travelers' diarrhea The use of the oral cholera vaccine containing recombinant cholera toxin B-subunit (Dukoral) to provide crossover protection against travelers' diarrhea caused by enterotoxigenic E. coli (ETEC) is discussed below.

Vaccination against Enterotoxigenic E. coli (ETEC)

The most frequent cause of travelers’ diarrhea is a toxin-producing bacterium, enterotoxigenic E. coli (ETEC). This bacterium accounts for up to 60% of travelers’ diarrhea worldwide. Because of similarities between the heat-labile toxin of ETEC and the cholera toxin, it has been proposed that the recombinant toxin-whole cell vaccine (Dukoral®) may also afford some protection against travelers' diarrhea.

To protect against ETEC the vaccine is administered in two doses, 1-6 weeks apart. If a booster dose is not given within 5 years, the two-dose schedule must be repeated. Travelers who would most benefit from the modest increase in protection provided by this vaccine include:

Those with underlying health problems such as diabetes mellitus, kidney disease, inflammatory bowel disease or other GI problems, and those with immune deficiencies due to HIV or other illness;
People with an increased risk of acquiring diarrhea due to lack of stomach acid caused by illness or acid-blocking medications;
Businesspersons, politicians, performance artists, elite athletes, or others who can't afford their schedules to be interrupted by illness;
People with a history of repeated, severe travelers' diarrhea.

Note: A recent study in the journal Lancet notes that while a median of 21% of travelers' stool samples are positive for ETEC, only 6% to 10% are of the heat-labile-toxin-producing type. Since Dukoral provides about 65% cross protection against the heat-labile-toxin-producing strains, Dukoral can be expected to provide only 7% or less protection against travelers' diarrhea caused by ETEC. However, it is important to note that other studies have shown that a greater proportion of those with travelers’ diarrhea are infected with ETEC heat-labile toxins (approximately 60%); therefore the protection against travelers’ diarrhea Dukoral vaccine provides may be as high as 30%. The vaccine should be considered only as an adjunct to dietary precautions and treatment with antibiotics. Even if you are vaccinated, you should not have a false sense of security; you should still carry Imodium and an antibiotic for the self-treatment of diarrhea.

See Table 3.2 for vaccine schedule, indications, precautions, and booster recommendations.

Diphtheria-Tetanus-Pertussis

Diphtheria, caused by the bacterium Corynebacteria diphtheriae, manifests with a severe sore throat (pharyngitis) and sometimes heart damage (myocarditis) from the diphtheria toxin. Diphtheria is spread person-to-person through close contact and respiratory secretions.

Pertussis, commonly called whooping cough, is caused by the bacterium Bordetella pertussis and is also spread by the respiratory route. Pertussis is the most frequent infectious cause of persistent cough lasting longer up to 12 weeks. It is also under-reported and under-diagnosed because most people believe, as they do about diphtheria, that the disease doesn’t occur, or is very rare, in adults.*Recent studies in the US and Canada show that whooping cause is on the rise in adolescents and young adults.*

Tetanus is not spread person-to-person; it is caused by a toxin secreted by Clostridium tetani a bacterium that is found in soil and acquired by contamination of an open wound or sore. It may be present as a localized infection commonly termed “lockjaw”—so-called because of the paralysis and spasm of muscles, including those of respiration.

The DTaP vaccine, which protects against diphtheria, tetanus, and pertussis, is a routine childhood immunization in the United States and Canada. It is a 5-dose series starting at 2 months of age and finishing at 4 to 6 years of age. It is frequently given in combination with the Haemophilus influenzae (Hib) vaccine. Following completion of the childhood DTaP series, the tetanus/diphtheria (Td) vaccine is used to maintain immunity against tetanus and diphtheria in adolescents and adults, with boosters recommended every 10 years. The Td vaccine, however, provides no on-going protection against pertussis, a disease that is making a resurgence among adolescents and young adults.

Until recently, DTaP vaccines were not administered after the seventh birthday; now, however, an acellular dTap vaccine is available in Canada for children over six years of age and adults who have not completed their basic immunization series and in the United States, the Food and Drug Administration (FDA) has approved an acellular pertussis Tdap vaccine (ADACEL®) for a single booster immunization against pertussis, in combination with tetanus and diphtheria, for adolescents and adults. (ADACEL contains the same components as the DTaP vaccine for infants and children, but the diphtheria toxoid and one of the pertussis components are in reduced quantities.) Introduction of trivalent Tdap vaccines will soon make it possible to maintain immunity after childhood against all three of these diseases with a single vaccine. See below for more information on ADACEL in the section on tetanus.

Haemophilus Influenzae Type b (Hib)

Haemophilus influenzae Type b is a bacterial infection primarily of children, that is spread by the respiratory route and causes meningitis. Hib vaccine is a routine childhood immunization in the United States. This is a four-dose series (it may be a three-dose series depending on the brand of Hib vaccine used) starting at 2 months of age and finishing at 12 to 15 months of age. Many pediatricians give this vaccine in combination with the DTaP vaccine. Because infection with H. influenzae is rare after 5 years of age, older children and adults do not routinely need this vaccine. H. influenzae type b disease is common in many countries of the world. Every child should be vaccinated against this disease before international travel.

Note: Haemophilus influenza type b disease and viral influenza (“the flu”) are different illnesses. The similarity of their names acknowledges their historical association. See Recommended Immunization Schedules for Persons Aged 0-18 Years for Hib vaccine schedule. recommendations.

Hepatitis A

Hepatitis A is a viral infection of the liver that is acquired by ingestion of contaminated food and water. It is very frequent in developing countries where personal hygiene and sanitation are substandard. Poorly cooked shellfish are an important source of infection because they may be grown in water that is contaminated by raw sewage.

Hepatitis A vaccine is recommended for all previously unvaccinated travelers older than 1 year of age going to lesser-developed countries with high or intermediate risk of hepatitis A. Hepatitis A is one of the most frequent vaccine-preventable diseases of travelers, and there are three vaccines available in the United States: Vaqta (Merck), Havrix (GlaxoSmithKline) and Twinrix (GlaxoSmithKline)—a combination of the hepatitis A and B vaccines. In Canada Avaxim (Sanofi-Pasteur) is available. The vaccines give rise to antibodies within 2 weeks after a single injection. A second dose, recommended 6 to 12 months later, dramatically boosts antibody levels and provides virtually 100% immunity—probably for life. If a person’s hepatitis A immune status is unknown, he or she may choose to be vaccinated or blood may be tested for existing immunity. People who have had the disease do not need vaccination; vaccinating people who are already immune, however, causes no harm.

Hepatitis A vaccine generates antibodies in about 2 weeks, soon enough to protect healthy people against clinical hepatitis, even if the traveler is exposed to the virus immediately upon arrival at his destination. In other words, vaccination, even at the last minute, is effective and immune globulin (IG) is not always necessary. In the United States is recommended that travelers over age 40, those with chronic liver disease and other chronic conditions, and immunocompromised persons, should receive an initial dose of vaccine and simultaneously be given IGs (see below) to provide extra protection.

Immune Globulin (IG)

Immune globulin (also known as IG, immune serum globulin, ISG, or gamma globulin) is not a vaccine but rather a high concentration of antibodies against a variety of infections, particularly hepatitis A. Although IG contains pooled human blood products, it has never been shown to transmit infectious disease, such as HIV. It is effective for preventing hepatitis A in international travelers (for 3 to 5 months, depending on the amount given), but it has been largely supplanted by hepatitis A vaccine for this purpose. Since the introduction of hepatitis A vaccine in 1995, the use of IG has markedly decreased.

Since hepatitis A vaccine is not approved for children younger than 1 year of age, they are usually given immune globulin or nothing at all since these children rarely develop symptoms if infected with HAV but do have the potential to pass the infection on to others. Older persons and immunocompromised travelers are less likely to respond to hepatitis A vaccine, as are those with chronic liver disease and other chronic illnesses; according to CDC recommendations they should receive IG, in addition to the vaccine. However, currently there is a shortage of IG, making it very difficult to obtain.

*If immune globulin is not available, infants can be given 3 doses of hepatitis A vaccine (Havrix Pediatric 720 units) which will result in 100% seroconversion. The off-label vaccination schedule for infants age >2 months is 3 doses at 2, 4, and 6 months.

Current Recommendations for Use of IG Travelers >40 years of age, immunocompromised persons, and those with chronic liver disease or other chronic medical conditions who have less than 2 weeks before departure may receive a single intramuscular dose of immune globulin (0.02 mL/kg) at a separate anatomic site in addition to the initial dose of vaccine.

Note: IG can interfere with replication of live viruses in vaccines. Experience has shown that this occurs only with measles, mumps, and rubella vaccine (MMR) and with the varicella vaccine, not with the hepatitis A vaccine. Therefore, these vaccines should not be administered in the period from 2 weeks before IG is administered until several months after the IG. If IG must be given soon after MMR or varicella, these vaccines must be repeated at a later date. See Table 3.2 for immune globulin schedule, indications, precautions, and booster recommendations.

Hepatitis B

Hepatitis B is a viral infection that attacks the liver. It is transmitted by contact with blood and body fluids through sexual activity, contaminated injection equipment (primarily needles and syringes), handling of blood products, and from an infected mother to child at birth.

Hepatitis B vaccine is a routine immunization for all infants, children, and adolescents in the United States who are 18 years of age and younger. The vaccines now used in the United States and Canada are produced by recombinant DNA technology. The duration of protection after three doses of vaccine is considered to be lifelong. Serum antibody levels are not routinely measured when the vaccine is administered for travel. However, if antibody levels are tested, and a traveler does not develop hepatitis B antibodies 1 month after the immunization series has been completed, he or she is considered to be a “non-responder.” If time is available, the administration of extra vaccine doses should be considered. It is important to understand that one-third of those who develop immunity (antibody levels >10 IU/mL) will lose their antibodies within 5 years and still be protected for life because of the body’s “immune memory.”

Increasingly, travel medicine advisors feel that all travelers to high-risk areas should be immunized against this infection because immunity is lifelong and one cannot predict when a serious illness or accident will necessitate an injection administered with unsterilized, contaminated equipment (e.g., needles/syringes).

The highest risk groups include:

Long-term/expatriate travelers (3 months or more)
Travelers likely to engage in unsafe sex or recreational drug-sharing activities
Travelers, especially young children, exposed to locals in high-risk areas who have open skin sores
Travelers with underlying health problems who may require medical or dental treatment involving injections and/or transfusions
Health-care and aid workers

See Table 3.2 for vaccine schedule, indications, precautions, and booster recommendations.

Influenza

Influenza is a contagious viral disease that occurs worldwide, and travel increases exposure. Because the influenza viruses change continually and vary geographically, vaccines need to be reconstituted each year to reflect this change. In the Northern and Southern hemispheres influenza outbreaks occur during the cool winter months—whereas in the tropics, infection occurs year-round.

The influenza vaccine is now a routine immunization in the United States for children ages 6 to 23 months, adults 50 years of age and older, those with underlying medical problems—such as chronic obstructive lung disease, heart disease, diabetes, and malignancy, and women who expect to be pregnant during the flu season—but travelers of any age going to countries where influenza activity is reported should be immunized. In North America and Europe, the optimum time to receive this vaccine is annually from mid-October through November.

See Table 3.2 for influenza vaccine schedule, indications, precautions, and contraindications.

Southern Hemisphere Vaccine Travelers to Australia, New Zealand, South America, and South Africa between April and October, should consider vaccination at their destination site with the influenza vaccine formulated for the Southern Hemisphere. This vaccine is not licensed in the United States and has a slightly different formulation.

Note: Antiviral medication complements vaccination. As of 2006, the CDC is no longer recommends the anti-flu drugs amantadine or rimantadine for the prevention or treatment of influenza. This recommendation is based on laboratory testing by the CDC which showed that the predominant strain of influenza was resistant to these drugs. The CDC is currently recommending either Tamiflu or relenza be prescribed if an antiviral medication is needed for the treatment of prevention of influenza.

Table 3.1 Antiviral Agents for Influenza

Generic Name	Trade Name	Indications	Dosage	Comments
M2 Inhibitors-Influenza A
Amantadine	Symmetral	Treatment >1	100 mg bid X 7 days	Update from the CDC
		Prophylaxis > age 1	100 mg qd	On the basis of available antiviral testing results, CDC is recommending that neither amantadine nor rimantadine be used for the treatment or prophylaxis of influenza A. When influenza A viruses predominate, however, these drugs may still be useful if they are used in combination with a neuraminidase inhibitor, such as oseltamivir (TamiFlu®).
			Decrease if kidney function impaired
Rimantidine	Flumadine	Treatment > age 14	100 mg bid X 7 days	On the basis of available antiviral testing results, CDC is recommending that neither amantadine nor rimantadine be used for the treatment or prophylaxis of influenza A. When influenza A viruses predominate, however, these drugs may still be useful if they are used in combination with a neuraminidase inhibitor, such as oseltamivir (TamiFlu®).
		Prophylaxis > age 1	100 mg qd
Neuraminidase Inhibitors-Influenza A & B
Zanamivir	Relenza	Treatment >7	2 blisters bid X 5 days	Diskhaler inhalation devise. Now recommended as first-line treatment due to increasing resistance of influenza A to oseltamivir (Tamiflu)
				Pending indication: Prophylaxis > age 7
				May not be practical for debilitated patients or for younger children, and is contraindicated for those with reactive airway disease.
Oseltamivir	Tamiflu	Treatment > age 18	75 mg bid X 5 days	An increasing proportion of influenza A (H1N1) viruses are resistant to oseltamivir, the oral neuraminidase inhibitor, but not to zanamivir (Relenza®).
		*Prophylaxis (Adult)**	75 mg daily X 1-6 weeks	Prophylaxis > age 1: mild GI side effects
There is no vaccine against Avian Influenza, but Oseltamivir (Tamiflu) may be effective for treatment (here).

Japanese Encephalitis (JE)

Japanese encephalitis, a severe viral infection of the brain, is transmitted by an evening and night-biting mosquito in rural areas of South and Southeast Asia. Seasonal transmission occurs in northern areas (summer); whereas in the south, year-round transmission occurs.

The new IXIARO vaccine is now available. IXIARO is a second-generation JE vaccine that is indicated for active immunization against JE virus for persons 17 years of age and older. Ixiaro is a purified inactivated state-of-the-art JE vaccine that uses cell culture technology. It provides a good immune response while being well tolerated. It does not contain thiomersal, gelatin or any other stabilizers or preservatives in its formulation. The vaccine is provided as a ready-to-use liquid formulation in pre-filled syringes and is administered in two doses 28 days apart.

Clinical studies were conducted in more than 800 healthy men and women in the United States and Europe. Participants received either IXIARO or JE-VAX, another U.S.-licensed vaccine that is no longer being manufactured. The studies found that IXIARO produced sufficient levels of antibodies in the blood to protect against JE. IXIARO requires two doses instead of JE-VAX's three.

Side effects: The IXIARO vaccine is generally well tolerated. The most common adverse events include headache, muscle pain and pain, swelling, and tenderness at the injection site. No allergic reactions ahave been reported. Overall, this vaccine is more tolerable and had fewer side effects than the previous vaccine, JE-VAX.

See Table 3.2 for Japanese encephalitis vaccine schedule, indications, precautions, and contraindications.

Lyme Disease

No vaccine is currently available. A Lyme disease vaccine (LYMErix, GlaxoSmithBeecham) was licensed in the United States in 1998 but was withdrawn from the market in 2001.

Measles

Measles (rubeola) is a viral infection, spread by the respiratory route, that has the potential to cause severe illness in young children, especially those who are malnourished; it is one of the leading causes of death among children worldwide.

The World Health Organization is hopeful that measles (rubeola) will be eradicated worldwide by the year 2010. All cases now occurring in the United States originate abroad, brought in by travelers, many of them foreign students attending U.S. secondary schools and colleges. Measles continues to be a major health problem in many developing countries, especially in sub-Saharan Africa and on the Indian subcontinent. Travelers to less developed countries should be immune to measles, either by having had the disease, or by immunization. Occasionally, there are reports of measles in developed countries—such as recent outbreaks in Holland , Ireland. With the decreased uptake of measles vaccine (MMR) in the UK due to fear of vaccine side effects (unsubstantiated) measles is considered to be endemic in the UK once again.. Many adult travelers, however, may not be immune to measles. Measles vaccination in the United States began in the late 1950s. People born before 1957 (before 1970 in Canada) are assumed to have had the disease during childhood and therefore have lifelong immunity. In fact, even when measles was prevalent and “everyone got it,” some individuals escaped the disease and remain susceptible. This number is higher than is generally appreciated. The same is true for mumps, rubella, and varicella (chickenpox.). It should be noted that all of these diseases are far more severe when they occur in adults—making immunity especially important for older people.In the mid-1960s, when effective live virus vaccines were introduced, experts believed that one dose would provide lifelong immunity. But experience has shown that immunity from measles vaccine is all or none—a “take” or a “no take”—and one dose immunizes only about 90% of those vaccinated; the second dose immunizes most of the rest. Therefore, travelers born after 1957 in the U.S. or between 1970 and 1996 in Canada should have a second dose of measles vaccine if they have not already received two doses.

Measles vaccine (given as MMR—measles, mumps, rubella combination) is a two-dose series given on or after the first birthday and again at 4 to 6 years of age, but it is acceptable to give the two doses any time with as little as 1 month between them. The MMR vaccine should not be given during pregnancy, and female patients should not become pregnant for at least 3 months after immunization.

Note: It is not contraindicated to give MMR to a breastfeeding mother. For babies ages 6 to 11 months traveling to countries where measles is endemic (e.g., India), a single dose of monovalent measles (MMR is acceptable) is recommended. If the vaccine is given at ages 6 to 11 months, a routine MMR is still recommended at age 1 year or as soon after as practicable. Maternal-derived antibodies protect infants younger than 6 months of age.

See Table 3.2 for measles vaccine schedule, indications, precautions, and booster recommendations.

Meningococcal

Meningococcal disease, which usually presents clinically as meningitis, is caused by the bacterium Neisseria meningitidis. There are five meningococcal serogroups. A, B, C, Y, and W135 that can cause disease, and these vary geographically in their worldwide distribution. There is currently no vaccine that protects against serogroup B.

The quadrivalent meningococcal polysaccharide vaccine (Menomune®, Sanofi Pasteur) protects for 3 years against four serogroups: A, C, Y, and W135. In January 2005 the Food and Drug Administration licensed the quadrivalent conjugate vaccine Menactra® (Sanofi Pasteur). This vaccine is more immunogenic in infants, is longer lasting, and eliminates the nasal carriage of meningococcal bacteria—a critical factor in preventing the spread of disease. Menactra® is approved for ages 2 to 55, but the vaccine can be administered “off-label” to both younger (>3 months) and older travelers who are headed for meningitis endemic or epidemic areas.

Current recommendation Use the conjugate vaccine Menactra® for all immunizations against meningitis. Only use the polysacharide vaccine, Menomune®, if Menactra®, is not available.

A bivalent meningococcal vaccine against serogroups A and C is available in Europe and the United Kingdom and two conjugate group C vaccines (Menjugate, Neisvac) are available in Canada. Because of their limited coverage (one or two serogroups only), these vaccines are not ideal for travelers. A quadrivalent vaccine (Menomune or Menactra), covering all four serogroups is recommended for travelers going to countries within the meningitis belt of sub-Saharan Africa (serogroups A, C, W-135 prevalent), or to outbreak areas, and is a requirement for travel to Saudi Arabia.

Meningococcal serogroup W-135 has recently emerged as an important cause of meningitis in Saudi Arabia. All travelers to Hajj or Umrah will be asked by the Saudi Arabian embassy for proof of meningitis ACYW-135 vaccination on applying for their visa. The embassy requires that the vaccine should be administered at least 10 days before travel. Proof of vaccination is currently valid for a period of three years, but this is likely to change with the introduction of the longer-lasting conjugate vaccine.

Two doses of meningococcal ACWY vaccine are required for children ages six months to two years, with an interval of three months between the two doses. The vaccinating center must provide a vaccination booklet or letter completed with the traveler’s name, vaccine, date of administration, and signature.

Note: Meningococcal vaccine is usually not recommended for children under two years of age but under special circumstances (e.g., travel to Saudi Arabia) may be administered to infants as young as 3 months. The conjugate vaccine should be used, if available.

The CDC no longer recommends the meningococcal vaccine for routine travel to Nepal, India, Mongolia, Kenya, Burundi, or Tanzania. In June 2005, however, an outbreak of meningococcal meningitis was reported in Delhi, India.

See Table 3.2 for meningococcal vaccine schedule, indications, precautions, and booster recommendations.

Pertussis (Whooping Cough)

Pertussis, caused by Bordetella pertussis is a bacterial infection transmitted by the respiratory route that produces whooping cough. Pertussis infects an estimated 60 million people worldwide annually, causing 600,000 deaths, mostly children in developing countries. It can be a serious disease, especially in infants, and it is highly contagious. Pertussis is characterized by choking and coughing—often prolonged for many weeks.

Pertussis vaccine is administered to children as the DTaP vaccine (diphtheria, tetanus, and acellular pertussis). However, the vaccine is not 100% protective, and vaccinated children may still become infected (although the disease tends to be milder), making it important to limit exposure to the disease. Immunity from vaccination lasts about 10 years, making older teenagers and adults susceptible, but for a generally milder form of the disease. CDC now recommends that all adults, whether or not they are traveling, should be given at least one dose TdaP (Adacel) in place of their 10-year booster of Td. See Table 3.2 for DTaP vaccine schedule, indications, precautions, and booster recommendations. See Diphtheria-Tetanus-Pertussis for an update on pertussis vaccines for adolescents and adults. Until now, a pertussis vaccine for adolescents and adults was not available.

Polio (Poliomyelitis)

Poliomyelitis is a highly contagious infection caused by poliovirus, which is transmitted person-to-person through exposure to fecal material or respiratory secretions containing the virus. Polio has been eradicated from much of the world, including the Western Hemisphere, Europe, and Southeast Asia, but there has been a recent resurgence of polio in Africa, chiefly in Nigeria. Polio has been spreading from northern Nigeria since 2003, when vaccination campaigns there were halted because of rumors that the vaccine could make people sick, or cause AIDS. Most cases from the outbreak have been in the Muslim Sahel, the band of arid land south of the Sahara stretching from Mali to Ethiopia. Polio has now appeared in Saudi Arabia and Yemen. The remaining pockets of polio in the world are in Pakistan, northern India, Afghanistan, Egypt, and Indonesia.

Persons who have received a complete series of polio vaccine, either IPV (inactivated polio vaccine) or OPV (oral polio vaccine) should receive an additional single dose of vaccine (one lifetime dose only) if they are 18 years of age or older and are traveling to a polio-endemic area. These areas include Africa, the Middle East, and the Indian subcontinent. This additional (booster) dose of polio vaccine is necessary only once in adulthood. Only inactivated polio vaccine (IPV) should be used for this dose.

OPV can, very rarely, cause paralytic polio in the recipient, or nonimmune persons in contact with the recipient. Therefore, OPV is no longer manufactured or administered in the United States—only injectable polio vaccine (IPV) is used. OPV, however, is still widely used in the rest of the world. The only circumstances in which OPV should be used are the following:

For an unvaccinated child who will be traveling in fewer than 4 weeks to areas of the world where wild poliovirus still exists.
For the third or fourth dose of polio vaccination series for children whose parents will not accept the additional number of injections required to complete the series with IPV.
In mass vaccination campaigns to control outbreaks.

See Table 3.2 for polio vaccine schedule, indications, precautions, and booster recommendations.

Rabies

Rabies is a uniformly fatal viral infection of the brain transmitted by the bite of an animal, usually a dog or monkey in the developing world, and by bats, skunks, foxes, and raccoons in North America. Rabies vaccine is recommended for long-stay travelers to endemic areas, particularly children, who are often attracted to animals and who are less likely to report a bite or scratch.

The primary series of rabies vaccine is a total of three injections given at intervals of 0, 7, and 21 or 28 days. For travelers, two boosters are required only when an individual is potentially exposed to the virus. Veterinarians and spelunkers should receive a booster every 2 to 3 years. The main advantage of giving pre-exposure rabies vaccine is to eliminate the need for rabies immune globulin (to inject into the bite-site) at the time of the exposure. Rabies immune globulin is often very scarce in the developing world, whereas rabies vaccine is usually readily available. Therefore, an animal bite could be a trip-ending experience if one is forced to fly to another city or country, or even home, to obtain rabies immune globulin. Also, pre-exposure vaccination reduces the number of doses of post-exposure vaccine, and possibly lengthens the safe interval between animal exposure and the onset of treatment. It does not preclude the essential step of proper wound cleansing with soap and water.

Rabies intradermal vaccine is not recommended when travelers are taking chloroquine or mefloquine for malaria prevention. The intramuscular formulation should be used. The intradermal rabies vaccine series, if used, should be started 30 days before the administration of either chloroquine or mefloquine. Three types of rabies vaccine, all equally effective, are available in the United States. See Table 3.2 for rabies vaccine schedule, indications, precautions, and booster recommendations.

See Table 3.2 for rabies vaccine schedule, indications, precautions, and contraindications.

Rubella (German measles)

Rubella, or German measles, caused by the rubella virus, is usually a mild infection in children but a very serious infection if it occurs during pregnancy because of severe damage to the developing fetus. Most Americans and Canadians are immune to rubella, either by having had the disease, or by vaccination with the measles-mumps-rubella (MMR—Merck) vaccine. For the past 2 decades, nearly all children have been receiving two doses of MMR vaccine. The only travelers who need the rubella component of the vaccine are women who may become pregnant and whose rubella immunity status is unknown. These women should consider receiving one dose of MMR. One dose of the rubella component immunizes virtually 100% of recipients for life.

Rubella Vaccine and Arthritis About 10% to 25% of postpubertal women report joint pain after receiving rubella vaccine and about 10% report arthritis-like signs and symptoms. When joint symptoms occur, they generally begin 1 to 3 weeks after vaccination, persist for 1 day to 3 weeks, and rarely recur.

Tetanus/Diphtheria (Td)

Tetanus is an infectious complication of wounds, caused by the toxin of Clostridium tetani bacteria. This organism is found worldwide in the soil and in the feces of various animals and some humans. When wounds become contaminated with soil containing the spores of C. tetani; the spores germinate and the resulting bacteria produce a toxin that is absorbed into the central nervous system, resulting in severe muscle contractions and spasms, respiratory paralysis, and sometimes death. Tetanus is a global health problem, occurring particularly among infants and young children in developing countries. In the United States, most infections are seen in the elderly who have never received a primary series of injections.

The tetanus/diphtheria vaccine (Td vaccine) is a routine immunization in the United States. Following completion of the DTaP (Diphtheria, Tetanus, and acellular Pertussis) series (by the seventh birthday), Td is given at 11 to 12 years of age if at least 5 years have elapsed since the last dose of DTaP. Subsequent Td boosters are recommended every 10 years. The schedule for tetanus immunization is identical to that for diphtheria, and the two vaccines are generally combined in one product.

Table 3.2 Immunizations for International Travel

Vaccine	Type/Brand			Primary Series		Booster	Indications for Travelers	Comments and Precautions
Cholera, Oral	Live, attenuated bacterial(Mutachol® in Canada, Orachol® in Europe) Currently not available from the manufacturer (Berna) Not licensed in the United States			Single dose orally for adults and children > 2 years of age		Every 6 months	Cholera vaccine is usually recommended only for people, such as relief workers or health care personnel, who are working in a high-risk endemic area under less than adequate sanitary conditions, or travelers who work or live in remote, endemic or epidemic areas and who don’t have ready access to medical care.	The live, attenuated vaccine should not be given to people with disorders of the immune system, those with liver disease, or during pregnancy Does not protect against serogroup 0139 (Bengal strain) Does not have any protective effect against ETEC
Cholera, Oral To prevent cholera	Killed, whole-cell cholera bacteria plus recombinant cholera toxin B subunit (rCTB) (Dukoral) Not licensed in the United States			2-dose series, at least 1 week but <6 weeks apart, in adults and children >6 years of age. Children aged 2 to 6 years: 3 doses at least 1 week but <6 weeks apart.		1 dose after 2 years in adults and children >6 years. For children aged 2 to 6 years, 1 dose after 6 months	Same as above	Killed vaccine, safe in pregnancy Does not protect against serogroup 0139 (Bengal strain)
Cholera (ETEC), Oral To prevent travelers' diarrhea due to ETEC*	Killed, whole-cell cholera bacteria plus recombinant cholera toxin B subunit, rCTB (Dukoral®) Not licensed in the United States			Adults and children aged >2 years: 2 doses, 1-6 week apart		Every 3 months. Repeat 2-dose series if there is a gap > 5 years since last dose	Travelers who need to reduce any risk of travelers’ diarrhea because of: chronic illness; lack of protective stomach acid; decreased immunity; history of severe travelers' diarrhea. Travelers such as athletes, performance artists, businesspeople, politicians, or others needing to avoid any illness.	Reduces by 50%-60% travelers’ diarrhea caused by enterotoxigenic E. coli (ETEC) that produce the heat labile toxin. Actual protection may be only a 7% to 10% over-all reduction in travelers' diarrhea, making the vaccine of limited benefit.
Hepatitis A	Inactivated viral (VAQTA) (Havrix) (AVAXIM) (EPAXAL)			Two-dose series, 6-12 mos. apart for adults and children aged ≥1 year. A single dose of hepatitis A vaccine, given to healthy travelers, is sufficient to provide immediate protection, even when given at departure. Off-label use for infants age ≥2 months: 3 doses, administered at 2-month intervals.(Havrix Pediatric 720)		None	Hepatitis A is transmitted primarily through contaminated food and water. Travelers who will have access to safe food and water are at lower risk. Those at higher risk include travelers visiting friends and relatives, long-term travelers, and those visiting areas of poor sanitation. Recommended for all travelers >1 year of age, not previously immunized, going to countries of high and intermediate endemicity for hepatitis A. The Health Guide recommends vaccination for all travelers, regardless of destination. (There is still some risk in "low-risk" countries, and this disease is 100% vaccine-preventable.)	Persons >40 years of age, immunocompromised persons, and those with chronic liver disease or other chronic medical conditions may receive a single intramuscular dose of immune globulin (0.02 mL/kg) in addition to the initial dose of vaccine.
Hepatitis B	Inactivated viral (Recombivax) (Engerix-B)			Three-dose series, at 0, 1, and 6 mos; Engerix-B may be given at 0, 1, and 2 mos; booster at 12 mos.	Not routinely given (May be needed in immune- compromised people who have insufficient antibody response to the vaccine)		Routine immunization for children 0-18 years; recommended for travel to medium- to high-risk endemic areas, especially for: persons who will have casual/unprotected sex with new partners; sexual tourists; injecting drug users; long-term visitors; expatriates, and anybody wanting increased protection against the hepatitis B virus, regardless of destination.		Not necessary to measure antibody response to the vaccine unless the traveler is immuno-compromised or will be at high-risk, e.g., health care worker who may sustain accidental needle stick. If you don't have enough time to complete the series of injections, even 1 of dose of vaccine will help "prime" your immune system.
Hepatitis A & B	Inactivated viral TWINRIX® [Hepatitis A Inactivated & Hepatitis B (Recombinant) Vaccine]			3-dose series at 0, 1, 6 mos. For adults (18 years of age or older)	None		As above. Travel to developing countries; anyone at risk for exposure to blood or body fluids. For anybody wanting protection against hepatitis A/B.		Accelerated schedule: 0, 7, 21 days, and a booster at 12 mos. Not recommended for "last minute" hepatitis A protection unless single-antigen hepatitis A vaccine in unavailable.
Immune globulin (IG)	Pooled human immunoglobulins			One dose 0.02 mL/kg IM/ for 3-month protection; 0.06 mL/kg IM for 5-mo protection	3–5 mo intervals, depending on initial dose		Single visit <5 months to endemic area; use for travelers with impaired immune response to vaccine. No longer used to provide immediate protection against hepatitis A for the healthy traveler <40 years of age.		Give measles >2 wks before or >3 mos after IG; give varicella >3 wks before or >5 mos after IG
Influenza Injectable	Iintramuscular trivalent inactivated vaccine (TIV) Inactivated viral, whole and split			One dose annually	None		All travelers >6 months of age, including pregnant women		Consider Southern Hemisphere vaccine for summer travel to Australia, New Zealand, S. Africa
Influenza Nasal spray (FluMist®)	Live, attenuated, intranasal vaccine (LAIV)			One dose annually	None		For healthy children 2 years of age and older, LAIV is an acceptable alternative to TIV. (LAIV can be given to healthy persons 5-49 years of age.)		Avoid in pregnancy
Japanese B encephalitis		Inactivated viral (IXIARO)	Two doses, 0 and 28 days		3 yrs		>30 days to endemic areas, especially near rice paddies and pig farms		Contraindicated: pregnancy; age <17 yr. Minor risk of side effects from vaccine.
Measles, mumps, rubella		Live viral monovalent or combined MMR	Two doses, at least one mo apart		None		Routine childhood immunization; travelers to endemic countries should be fully immunized		Contraindicated in immunocompromised people; pregnancy
Meningococcal (Meningitis) for Serogroups A,C,Y,W-135		Inactivated bacterial-polysaccharide (Menomune)	One dose for adults and children ≥2 of age		For children vaccinated <4 years of age, revaccination in 2-3 years should be considered. For children vaccinated ≥4 years of age revaccination should be considered in 5 years if they remain at high risk.		Travel to meningitis belt of Africa; travel to new epidemic areas; travel to Saudi Arabia for Hajj; absence of spleen. Use this vaccine (Menomune®) only if the meningococcal conjugate vaccine, Menactra®, is not available		Does not protect against Group B meningococcal meningitis Duration of immunity is unknown, but appears to be at least 5 years in those ≥4 years of age. Revaccination after 2-3 years should be considered for children first vaccinated at <4 years of age who continue to be at high risk.
Meningococcal (Meningitis) for Serogroups A,C,Y,W-135		Inactivated bacterial-conjugate (Menactra)	One dose for adults and children ≥2 to 55 years of age Can also use in infants >3 months of age and travelers >55 when they are traveling to meningitis endemic or epidemic regions		Duration of immunity expected to be longer (>5 years) than the polysaccharide vaccine (Menomune).		Routine childhood immunization at age 11-12 and for college students Vaccinating with meningococcal conjugate vaccine (Menactra-MCV4) is preferred to meningococcal polysaccharide vaccine (Menomune-MPSV4) for travel to countries in which the disease is hyperendemic or epidemic; for children who have terminal complement component deficiencies; for people who have anatomic or functional asplenia (loss of spleen).		Does not protect against Group B meningococcal meningitis. More immunogenic in infants and children. Improved immunologic memory. Prevents nasal carriage and limits person-to-person transmission.
Pneumococcal (PPV-23)		Inactivated bacterial	One dose		Consider dose if >5 yrs since primary dose and primary dose given < age 65		Routine immunization age >65; absence of spleen; immunocompromised		Also boost immune- deficient and people without spleens
Poliomyelitis, oral* (OPV)		Oral live viral	Three-dose series; 2nd dose 6-8 wks after 1st, 3rd dose 8-12 mos after 2nd		One-time booster for foreign travel in adult if >10 years since primary series		Used for mass polio eradication programs. Single dose of either OPV or IPV may be used when <4 weeks before departure. Not available in the U.S. due to the risk of vaccine-associated paralytic polio.		No longer in use in the U.S. For use when IPV is not available. Contraindicated in immune-deficient people.
Poliomyelitis, injectable (IPV)		Inactivated viral	As above		As above		Travel to countries where polio is epidemic or endemic		Use for immune- deficient people and their close contacts. Either IPVor OPV can be given to the pregnant traveler.
Rabies		Inactivated viral HCDV (available in ID & IM formulations); PCEC; RVA	Pre-exposure: Three-dose series at 0, 7, and 21-28 days		None for most travelers; 2 yrs for high-risk groups (spelunkers) if antibodies decline		Rabies vaccine is recommended for: persons anticipating an extended stays in endemic areas; for those whose work or activities may bring them into contact with animals; for people going to rural or remote locations where medical care is not readily available; for travelers desiring extra protection.		If ID rabies vaccine is not completed before starting chloroquine or mefloquine, use IM vaccine. Pre-exposure vaccination eliminates need for rabies immune globulin, but not the need for 2 additional (booster) doses of rabies vaccine.
Rabies			Post-exposure		If you completed a pre-departure rabies vaccination series, you will need 2 additional doses of intramuscular vaccine (given on days 0 and 3).				Inject vaccine into deltoid muscle or antero-lateral thigh muscle (children). Avoid gluteus (buttock) injection. Do NOT administer rabies immune globulin (RIG) if previously immunized.
Rabies			Post-exposure: 4-dose series on days 0, 3, 7, and 14 for people NOT previously immunized. Rabies immune globulin (RIG) is required.						RIG dosage: 20 IU/kg (human RIG) or 40 IU/kg (equine RIG). The entire calculated dose of rabies immune globulin (either human or equine) should be injected directly into the bite(s) and the tissue around the bite(s). If there are large or multiple bites, RIG can be diluted with normal saline if more volume is needed to infiltrate all wound areas. If it is not anatomically feasible to inject the entire volume of RIG into the wound(s), any remaining volume should be injected intramuscularly at a remote site, usually into the deltoid or anterolateral thigh muscles.
Tetanus- diphtheria (Td)		Bacterial toxoid	Three-dose series, 2nd dose 4-8 wks after 1st dose, 3rd dose 6-12 mos later		Every 10 yrs or 5 yrs with dirty wound		Routine immunization; nonimmune		Diphtheria protection also important, especially in older travelers
Tetanus-diphtheria-pertussis (Tdap- adult)		Bacterial toxoid, reduced acellular pertussis (ADACEL)	One dose		None		One-time booster that also provides protection against pertussis (whooping cough) in adolescents and adults. Can be used once in place of a regular Td booster		Risk of pertussis and diphtheria are often overlooked in older travelers.. ADACEL approved for ages 11 to 55 but can be used in older travelers as well.
Typhoid, oral		Attenuated live bacterial Ty21a (Vivotif)	One capsule at 0, 2, 4, and 6 days (3 sachets at 0, 2, and 4 days in Canada)		3-5 yrs Varies by country labeling		Travel to a developing country, especially Indian sub-continent, South America		Contraindicated: immunocompromised; pregnancy; concurrent antibiotic use; age. Does not protect against paratyphoid.
Typhoid, injectable		Bacterial polysaccharide (Typhim Vi)	Single dose		2-3 yrs Varies by country labeling		Travel to developing country		Contraindicated: age <2 yrs . Does not protect against paratyphoid.
Tick-borne encephalitis		Inactivated viral Encepur FMSE-IMMUN(Vienna, Austria)	3-dose series on day 0, 4-12 weeks, and a booster in 9-12 months. The second dose should be given at least 2 weeks before departure. Accelerated schedules: for Encepur: 3-doses given on days 0, 7, and 21 and a booster in 1 year. for FMSE-IMMUN: Give second dose 2 weeks after the first dose.		Every 3-5yrs When using the FMSE-IMMUN accelerated schedule, give a booster 12-18 months after the third dose.		Rural travel with high-risk tick exposure (extensive hiking, camping) in endemic areas during peak transmission season (March though November)		Not licensed in the United States. Available in Europe and Canada. Persons previously vaccinated against yellow fever may have an enhanced antibody response to the TBE vaccine. There have been no reported cases of TBE in vaccinated individuals.
Varicella		Live viral	One dose at 12 mos– 12 yrs, 2 doses 4-8 wks apart, ages 13 and older		None		Routine childhood immunization <13 yrs old; likely exposure in non-immune adolescent or adult		Contraindicated: immuno-compromised; pregnancy; concurrent aspirin use; neomycin allergy
Yellow fever		Live viral	Single dose		10 yrs		Travel to endemic areas of Africa and South America; required for entry by some countries		Contraindications: thymectomy; immunocompromised; pregnancy; age <9 mos; use with caution over age 65

*ETEC = Enterotoxigenic E.coli

Tetanus/Diphtheria/Pertussis (Tdap)

(Adacel contains the same components as the DTaP vaccine for infants and children, but the diphtheria toxoid and one of the pertussis components are in reduced quantities.) Introduction of trivalent Tdap vaccines will soon make it possible to maintain immunity after childhood against all three of these diseases with a single vaccine.

See Table 3.2 for Tdap vaccine schedule, indications, precautions, and contraindications.

Tick-Borne Encephalitis (TBE)

Tick-borne encephalitis is a serious viral infection of the brain transmitted by tick bites, usually after travel to rural or forested areas from spring to fall. The disease may also be acquired by ingesting unpasteurized dairy products.

There are two subtypes of TBE:

Western subtype (or Central European encephalitis) transmitted by Ixodes ricinus ticks. This subtype occurs in the forested areas of Central, Eastern, and Northern Europe.
Eastern subtype (or Russian spring/summer encephalitis) transmitted by Ixodes persulcatus ticks. This subtype occurs in the former USSR, east of the Ural Mountains, and also in areas of China, Japan, and Korea.

There are three vaccines for tick-borne encephalitis:

FSME Immun (Baxter) is an inactivated viral vaccine manufactured in Austria and available in Europe, and Canada but not in the United States. In Canada, the vaccine may be obtained through the Emergency Drug Release Program at 613-941-2108 or at the Bureau of Biologics at 613-941-2114. A full series consists of three doses over a 1-year period (at intervals of 0, 1, and 12 months).
Encepur (Chiron) is manufactured in Germany and also available in Europe. Three doses are administered over a 1-year period.
A third vaccine for tick-borne encephalitis is produced in Russia.

Accelerated Schedule Two doses of vaccine, 1 week apart, probably give adequate protection. A third dose should be given 3 to 4 weeks later, followed by a fourth dose in 1 year’s time.

The vaccine is recommended for travelers to endemic forested areas during warm months where they are likely to be exposed to ticks during extensive outdoor activities—such as camping, cycling, or work. Even a brief trip may put a traveler at risk.

See Table 3.2 for TBE vaccine schedule, indications, precautions, and contraindications.

Tuberculosis (BCG-Bacille Calmette Guérin)

Tuberculosis (TB), a bacterial infection spread by cough and caused by Mycobacterium tuberculosis, is now recognized as the most frequent infectious cause of death globally. It is estimated that more than one-third of the world’s population are infected with the bacterium, the majority of whom have a silent (latent) infection that will never cause disease. However, tuberculous lung disease is very common in AIDS patients as their immunity wanes.

BCG vaccine is used very rarely in travelers; the risk for acquiring the disease while traveling is low. The CDC states: “To become infected, a person usually would have to spend a long time in a closed environment where the air was contaminated by a person with untreated tuberculosis (TB) who is coughing and has numerous TB bacteria in secretions from the lung.” Recent studies have shown that the risk of tuberculosis in travelers is approximately 3% per year of stay in a high-risk area. BCG is routinely given to children in many countries, both developed and developing. In the United States, TB control is based on identifying and treating infected individuals and BCG vaccine is not given.

BCG may be appropriate for young children (children of missionaries, for example) who have prolonged and close contact with local populations in remote areas of developing countries with high incidences of TB. In children younger than 5 years of age, BCG is more effective in preventing severe complications (meningitis and disseminated infection) than in preventing the infection itself. In the United States, current recommendations for individuals at risk are not to use BCG vaccine but to perform TB skin testing before and after exposure (including travel) and to treat individuals who convert their skin test from negative to positive. The ideal time to perform a TB skin test is 3 months after the last possible exposure.

Typhoid

Typhoid fever, a bacterial infection caused by Salmonella typhi, is a potentially serious systemic illness characterized by prolonged fever, headache, cough, and constipation. Infection occurs from ingestion of contaminated food and water, or close contact with an infected person (fecal-oral transmission).

Two typhoid vaccines are available. The efficacy of both vaccines is 55% to 72% in different studies.

Type 21a oral live typhoid vaccine is available in two forms: a capsule form that is available in the United States and Canada as well as in Europe, and a suspension form (sachets) that is currently available in Europe and Canada. In the United States, a four-dose regimen is followed (1 capsule on alternate days). In Europe and Canada, a three-dose regimen of either capsules or suspension is followed—1 sachet (packet) on alternate days for a total of 3 doses. A booster dose is recommended in 3 to 7 years, depending on country labeling. The capsules and sachets must be refrigerated and taken with a cool liquid approximately 1 hour before eating.

Protection is achieved seven days after the last dose. Side effects are uncommon and may include abdominal discomfort, nausea, and rash or hives. Oral typhoid vaccine should not be taken with antibiotics, because they may interfere with effectiveness. If all doses are not taken, the entire series must be restarted to achieve protection.

Typhim Vi is a single-dose (0.5 mL intramuscular injection) vaccine used in persons 2 years of age or older. Side effects, which are uncommon, may include discomfort at the injection site, fever, and headache. A booster dose is recommended in 2 years in the United States and 3 years in Canada.
Vivaxim, recently marketed in Canada, is a combined vaccine containing hepatitis A vaccine (Avaxim) and Typhim Vi in a single dose. The duration of immunity corresponds to the individual vaccines.

Because the majority of cases of typhoid fever in the United States originate in immigrants from developing countries, the vaccine is strongly recommended for VFRs (immigrants returning to their country of birth to visit family, friends, and relatives), particularly those returning to Latin America, South Asia, and Southeast Asia.

See Table 3.2 for typhoid vaccine schedule, indications, precautions, and booster recommendations.

More typhoid vaccine information is here.

Yellow Fever

Yellow fever is a severe viral infection of the liver found only in Sub-Saharan Africa, South America, and Panama; transmission occurs from a day-biting mosquito that feeds primarily at dusk and dawn. The risk of yellow fever (in unvaccinated people) in both urban and rural areas of Africa ranges from 1:250 per two-week stay during epidemics to 1:2,500 between epidemics. In South America the risk is primarily in rural areas and is lower at 1:25,000 per 2-week stay.

Yellow fever is the only vaccine that may be required for entry into certain countries. (Vaccine requirements are listed here, by country.) After vaccination (by a travel clinic or local health department authorized to administer the vaccine) an International Certificate of Vaccination is issued which will meet entry requirements for all persons traveling to or arriving from countries where there is active, or a potential for, yellow fever transmission. If there is a medical reason (e.g., infants younger than 4 months old, pregnant women, persons hypersensitive to eggs, and those who are thymectomized or have an immuno-suppressed condition) not to receive the vaccine, most countries will accept a medical waiver. The CDC recommends obtaining the waiver from a consulate or embassy before departure.

Note: Some countries require a Certificate of Yellow Fever Vaccination from ALL arriving travelers.

Yellow fever vaccine is a live attenuated viral vaccine. A single dose confers immunity lasting 10 years or more. The vaccine is considered to be protective 10 days after the initial dose and immediately after booster doses. If the first dose of vaccine has not been given 10 days before entry to a country that requires the vaccine for entry, travelers may be refused entry until the 10 days are completed.

Vaccine Precautions The vaccine generally is associated with few side effects: fewer than 5% of vaccinees develop mild headache, muscle pain, or other minor symptoms 5 to 10 days after vaccination. However, several groups of individuals should not receive the vaccine, while others should be closely evaluated.

The vaccine is contraindicated for three groups:

Yellow fever vaccine should never be given to infants under 4 months of age due to a risk of developing viral encephalitis. In most cases, vaccination should be deferred until 9 to 12 months of age.
Pregnant women should not be vaccinated because of a theoretical risk that the developing fetus may become infected from the vaccine. However, the vaccine should be offered to pregnant women planning to travel in endemic areas because recent studies have shown that the vaccine was safe when it was inadvertently given to pregnant women ( in the first trimester) during mass vaccination campaigns in the tropics.
Persons who have a hypersensitivity e to eggs should not receive the vaccine because it is prepared in embryonated eggs.

Other groups that should be closely evaluated before administering the vaccine include:

Persons with an immunosuppressed condition associated with AIDS or HIV infection, or those with immune systems altered by other diseases, such as thymectomy, leukemia and lymphoma, or receiving drugs and/or radiation. People with asymptomatic HIV infection who have CD4 counts above 250 cells/mL may be vaccinated if they are at risk.
Elderly travelers (>65 years of age). Recent studies have shown that this group may be at significantly greater risk of severe adverse reactions to the vaccine. Therefore, a careful risk/benefit assessment should be carried out in this group. The risk in the elderly of severe reactions increases to 1:50,000 from 1:350,000 in younger-aged groups. However, it should be noted that this risk occurs only with the first dose and not with booster doses.

Figure 3.1A South America Yellow Fever Endemic Zones from CDC's Traveler's Health, Yellow Book

Figure 3.1B Africa - Yellow Fever Endemic Zones from CDC's Traveler's Health, Yellow Book

Table 3.3 Immunizations for the HIV-Positive Traveler

Vaccine

Recommendation

Comments

Cholera (oral)

Probably safe

Use only inactivated bacterial vaccine

H. influenza type b

Recommended

Consider one dose of conjugated vaccine

Hepatitis A

Recommended

The expected immune response may not be obtained in people with advanced disease

Hepatitis B

Recommended

Test for preexisting immunity

Influenza

Recommended

Administer annually

Japanese encephalitis

Recommended

Mosquito-bite prevention is an adjunct

Measles (MMR)

Recommended for persons not severely compromised

Not recommended for persons severely compromised

Meningococcal

Recommended

Booster in 3-5 years

Pneumococcal (PPV-23 vaccine)

Recommended

Booster after 5 years

Polio

Use only inactivated vaccine (IPV)

The live oral polio vaccine (OPV) is contraindicated

Rabies

Recommended

Administer by IM route only to ensure better immune response

Tetanus/diphtheria/pertussis

Booster every 10 years; advise 1 booster dose of ADACEL vaccine to provide pertussis protection

Diphtheria, pertussis immunity may be diminished or absent

Typhoid

Use Typhim Vi

Avoild live oral typhoid vaccine

Varicella

Recommended for some asymptomatic individuals

Not recommended for symptomatic persons

Yellow fever

Recommended for asymptomatic patients if risk of disease is unavoidable (>250 CD4 count)

Letter of waiver if vaccine not administered. Strict mosquito-bite protection advised

*Medical waivers—Most countries will accept a medical waiver for persons with a health reason for not receiving the yellow fever vaccination. The CDCrecommends obtaining written waivers from consular or embassy officials before departure, but travel clinics hardly ever recommend doing this. Instead, a physician’s letter that states the reason for withholding the vaccination and that is written on letterhead stationery usually suffices. The letter should bear the stamp used by a health department or official immunization center to validate the International Certificate of Vaccination (Yellow Card).