Patients planning to travel to other countries often ask physicians for information about appropriate vaccines and prevention of diarrhea and malaria. More detailed advice for travelers is available from the Centers for Disease Control and Prevention (CDC) at www.cdc.gov/travel. Guidelines are also available from the Infectious Diseases Society of America (IDSA).1
Common travel vaccines are listed in Table 1 on page 84. In addition to travel-specific vaccines, all travelers (including children) should be up to date on routine vaccines. Guidelines for routine adult immunization have been published in a separate issue.2 Immunocompromised or pregnant patients generally should not receive live virus vaccines, such as those for measles and yellow fever, although in some situations the benefit might outweigh the risk.
CHOLERA — The risk of cholera in tourists is very low. The parenteral vaccine previously licensed in the US is no longer available. An oral, whole-cell recombinant vaccine called Dukoral is available in some European countries (Crucell/SBL Vaccines) and in Canada (Sanofi Pasteur). It is not currently recommended for routine use in travelers, but might be considered for those who plan to work in refugee camps or as healthcare providers in endemic areas.
HEPATITIS A — Hepatitis A vaccine, which is now part of routine childhood immunization in the US, is recommended for all unvaccinated travelers going anywhere other than Australia, Canada, western Europe, Japan or New Zealand.3
Vaccination of adults and children usually consists of two IM doses separated by 6-18 months. Additional booster doses are not needed.4,5 Two hepatitis A vaccines are available in the US: Havrix and Vaqta. Patients who received a first dose of one vaccine will respond to a second dose of the other. Second doses given up to 8 years after the first dose have produced protective antibody levels.6
Antibodies reach protective levels 2-4 weeks after the first dose. Even when exposure to the disease occurs sooner than 4 weeks after vaccination, the traveler is usually protected because of the relatively long incubation period of hepatitis A (average 28 days). For immunosuppressed patients and those with chronic liver disease who will be traveling to an endemic area in ≤2 weeks, immune globulin (0.02 mL/kg IM) should be given in addition to the initial dose of vaccine. The same dose should be given to children under 1 year of age and other travelers who cannot receive the vaccine if traveling for <3 months; a dose of 0.06 mL/kg IM should be given if traveling for ≥3 months. For travel durations of >5 months, the dose should be repeated.7
HEPATITIS B — Vaccination against hepatitis B is recommended for travelers going to intermediate- or high-risk areas (see Table 2 for low-risk areas). Travelers going anywhere who engage in behaviors that may increase the risk of transmission, such as unprotected sexual contact with new partners, dental treatment, skin perforation practices (tattoos, acupuncture, ear piercing) or invasive medical treatment (injections, stitching), should be immunized against hepatitis B.
Two hepatitis B vaccines are available in the US: Engerix-B and Recombivax-HB. Primary immunization usually consists of 3 doses given IM at 0, 1 and 6 months. An alternate schedule of 3 doses given at 0, 1 and 2 months, followed by a fourth dose at 12 months, is approved for Engerix-B in the US. A 2-dose schedule of adult Recombivax-HB at 0 and 4-6 months is approved in the US for adolescents 11-15 years old. An accelerated schedule of 0, 7 and 14 days, followed by a booster dose at 6 months, can also be used with either vaccine, but is not FDA-approved.
An interrupted hepatitis B vaccination series can be completed without being restarted. A 3-dose series started with one vaccine may be completed with the other. Post-vaccination serologic testing is recommended for healthcare workers, infants born to HBsAg-positive mothers, hemodialysis patients, HIV-infected and other immunocompromised patients, and sex- and needle-sharing partners of HBsAg-positive patients.
HEPATITIS A/B — A combination vaccine (Twinrix) containing the same antigenic components as pediatric Havrix and Engerix-B is available for patients ≥18 years old. It is given in 3 doses at 0, 1 and 6 months. An accelerated schedule of 0, 7 and 21-30 days with a booster dose at 12 months is also approved.8
The combination vaccine can be used to complete an immunization series started with monovalent hepatitis A and B vaccines. Twinrix Junior is available outside the US for children 1-15 years old.
INFLUENZA — Influenza may be a risk in the tropics year-round and in temperate areas of the Southern Hemisphere from April to September. Outbreaks have occurred on cruise ships and on organized group tours in any latitude or season.9
Seasonal influenza vaccine directed against strains in the Northern Hemisphere is sometimes available in the US until the end of June and the US Advisory Committee on Immunization Practices (ACIP) recommends that persons for whom seasonal influenza vaccine is indicated10 consider being vaccinated before travel to the Southern Hemisphere during influenza season or to the tropics at any season, or when traveling in a group with persons from the Southern Hemisphere during their influenza season (April-September).11 In some years, the vaccine strains are the same in both hemispheres. If the vaccine strains are different, high-risk patients from the Northern Hemisphere who travel to the Southern Hemisphere during that region’s influenza season could also consider being immunized on arrival because the vaccine active against strains in the Southern Hemisphere is rarely available in the Northern Hemisphere.
A monovalent vaccine is available to protect against the currently (2009) circulating pandemic influenza A (H1N1) virus.12 It can be given at the same time as the seasonal vaccine, except not the 2 live attenuated formulations together. Both the seasonal and monovalent influenza vaccines are prepared in eggs. Hypersensitivity reactions could occur.
There is no commercial influenza vaccine available for pathogenic strains of avian influenza (H5N1, H7N2, H9N2, H7N3, H7N7), but an inactivated vaccine against avian H5N1 is FDA-approved and is being included in the US Strategic National Stockpile.
JAPANESE ENCEPHALITIS — Japanese encephalitis is an uncommon but potentially fatal mosquito-borne viral disease that occurs in rural Asia, especially near pig farms and rice paddies. It is usually seasonal (May-October), but may occur year-round in equatorial regions. The attack rate in travelers has been very low.13
Vaccination is recommended for travelers >1 year old who expect a long stay (≥1 month) in endemic areas or heavy exposure to mosquitoes (such as adventure travelers) during the transmission season. Vaccination also should be considered for travelers spending less than a month in endemic areas during the transmission season if they will be sleeping without air conditioning, screens or bed nets, or spending considerable time outside in rural or agricultural areas, especially in the evening or at night.14 Some Medical Letter consultants suggest that, given the rarity of the disease in US residents, compulsive use of insect repellents and judicious avoidance of exposure to mosquitoes might be reasonable alternatives to vaccination for short-term travelers.
Two formulations are FDA-approved in the United States: JE-Vax, which is a mouse-brain preparation, and the recently approved Ixiaro, a non-mouse-brain vaccine, which is preferred for use in adults, but has not been approved for use in children in the US.15 In clinical trials, 2 doses of Ixiaro (one is not enough) appeared to be as effective as JE-Vax, and considerably safer.16
MEASLES — The measles vaccine is no longer available in a monovalent formulation. It is available as an attenuated live-virus vaccine in combination with mumps and rubella (MMR). Adults born in or after 1957 (1970 in Canada) and healthcare workers of any age who have not received 2 doses of live measles vaccine (not the killed vaccine that was commonly used in the 1960s) after their first birthday and do not have a physician-documented history of infection or laboratory evidence of immunity should receive two doses of MMR vaccine, separated by at least 28 days.17
Previously unvaccinated children ≥12 months old should receive 2 doses of MMR vaccine at least 28 days apart before traveling outside the US. Children 6-11 months old should receive 1 dose before traveling, but will still need two subsequent doses for routine immunization, one at 12-15 months and one at 4-6 years.
MENINGOCOCCAL — A single dose of meningococcal vaccine is recommended for adults and children ≥2 years old who are traveling to areas where epidemics are occurring, or to anywhere in the “meningitis belt” (semi-arid areas of sub-Saharan Africa extending from Senegal and Guinea eastward to Ethiopia) from December to June. Saudi Arabia requires a certificate of immunization for pilgrims during the Hajj. Immunization should also be considered for travelers to other areas where Neisseria meningitidis is hyperendemic or epidemic, particularly for those who will have prolonged contact with the local population, such as those living in a dormitory or refugee camp, or working in a healthcare setting.18-20
Two quadrivalent vaccines are available against N. meningitidis serogroups A, C, Y and W135. Menomune contains meningococcal capsular polysaccharides. Menactra, which contains capsular polysaccharides conjugated to diphtheria toxoid, is preferred, but Menomune is an acceptable alternative. Neither vaccine provides protection against serogroup B, which does not have an immunogenic polysaccharide capsule. Group B infections are rare in sub-Saharan Africa.
The most common adverse reactions to Menactra have been headache, fatigue and malaise in addition to pain, redness and induration at the site of injection. The rates of these reactions are higher than with Menomune, but similar to those with tetanus toxoid. Guillain-Barré syndrome has been reported rarely in adolescents who received Menactra, but cause and effect have not been established.21
POLIO — Adults who have not previously been immunized against polio should receive a primary series of inactivated polio vaccine (IPV) if traveling to areas where polio is still endemic (Nigeria, India, Pakistan, Afghanistan) or to areas with documented outbreaks or circulating vaccine-derived strains (see Table 3).22 Previously unimmunized children should also receive a primary series of IPV.
If protection is needed within 4 weeks, a single dose of IPV is recommended, but provides only partial protection. Adult travelers to risk areas who have previously completed a primary series and have never had a booster should receive a single booster dose of IPV.
RABIES — Rabies is highly endemic in parts of Africa, Asia (particularly India) and Central and South America, but the risk to travelers is generally low. Preexposure immunization against rabies is recommended for travelers with an occupational risk of exposure, for those (especially children) visiting endemic areas where immediate access to medical treatment, particularly rabies immune globulin, tends to be limited, and for outdoor-adventure travelers.23,24 The 2 vaccines available in the US (Imovax, RabAvert) are similar; both are given in the deltoid (not gluteal) muscle at 0, 7 and 21 or 28 days.
After a bite or scratch from a potentially rabid animal, patients who received pre-exposure prophylaxis should promptly receive 2 additional doses of vaccine at days 0 and 3. Without pre-exposure immunization, the ACIP recommends rabies immune globulin (RIG) and is now recommending 4 doses (over 14 days) of vaccine instead of 5 doses (over 28 days). Patients with immunosuppression should still receive 5 doses of vaccine.25 The reduced vaccine dosing schedule may not be included in the prescribing information from the manufacturers of the approved vaccines. According to the CDC, cell culture rabies vaccines available outside the US are acceptable alternatives to FDA-approved vaccines; neural tissue vaccines have high rates of serious adverse effects.26 RIG is a blood product, and its purity and potency may be less reliable, if it is available at all, in developing countries.
TETANUS, DIPHTHERIA AND PERTUSSIS — Previously unimmunized children should receive 3 or (preferably) 4 doses of pediatric diphtheria, tetanus and acellular pertussis vaccine (DTaP) before travel. An accelerated schedule can be used beginning at age 6 weeks, with the second and third doses given 4 weeks after the previous dose, and the fourth dose 6 months after the third.
Adults with an uncertain history of primary vaccination should receive 3 doses of a tetanus and diphtheria toxoid vaccine. Two vaccines (Adacel; Boostrix) containing protein components of acellular pertussis combined with diphtheria and tetanus toxoids (Tdap) are available for adults ≤64 years of age.27 One of the 3 doses (preferably the first) should be Tdap. The first 2 doses should be administered at least 4 weeks apart and the third 6-12 months after the second. DTaP contains larger amounts of diphtheria and pertussis antigens than Tdap and is not licensed for use in adults.
Inactivated adsorbed (aluminum-salt-precipitated) tetanus and diphtheria toxoid (Td) has been the standard booster vaccine for adults. A booster dose of Td is recommended every 10 years. Persons 11-64 years old who have completed a primary childhood series and have not yet received Tdap should receive a single dose of Tdap at the time of their next scheduled routine Td booster. Tdap can be given less than 10 years after the last Td to provide pertussis protection before travel.
TICK-BORNE ENCEPHALITIS (TBE) — TBE occurs in temperate areas of Europe and Asia, from eastern France to northern Japan, and from northern Russia to Albania.28,29 The risk is greatest from April to November. Humans acquire the disease through the bite of a tick or, rarely, from eating unpasteurized dairy (mostly goat) products. Immunization is recommended only for travelers who will spend extensive time outdoors in rural areas. The vaccine, which is not approved in the US but is available in Canada and Europe (Encepur – Novartis; FSME-Immun – Baxter AG), is usually given in 3 doses over 9-12 months, but can be given (Encepur) over 3 weeks (0, 7 and 21 days). FSME-Immun can be obtained in Canada by contacting the Special Access Programme, Health Canada (613-941-2108).
The usual duration of protection after the primary series is 3 years; with the accelerated schedule of Encepur, it may be only 12-18 months. Boosters give 5 years of protection for patients <50 years old and 3 years for those ≥50 years old.
TYPHOID — Typhoid vaccine is recommended for travelers to South Asia and other developing countries in East and Southeast Asia, Central and South America, the Caribbean and Africa, especially if they will be visiting friends or relatives or traveling outside routine tourist destinations.30,31
A live attenuated oral vaccine (Vivotif) is available for adults and children ≥6 years old. It is taken every other day as a single capsule (at least 1 hour before eating) for a total of 4 capsules, beginning no later than 2 weeks before departure; it protects for about 5 years. The capsules must be refrigerated. Antibiotics should be avoided for at least 72 hours before the first capsule. A purified capsular polysaccharide parenteral vaccine (Typhim Vi) for adults and children ≥2 years old is given as a single IM dose at least 2 weeks before departure. Re-vaccination is recommended every 2 years (3 years in Canada).
A combined hepatitis A/typhoid vaccine (Vivaxim – Sanofi Pasteur) is available in Canada.
YELLOW FEVER — Yellow fever vaccine (YFVax), a single-dose attenuated live virus vaccine prepared in eggs, should be given at least 10 days before travel to endemic areas, which include much of tropical South America and sub-Saharan Africa between 15°N and 15°S.32 Some countries in Africa require an International Certificate of Vaccination against yellow fever, or a physician’s waiver letter, from all entering travelers; other countries in Africa, South America and Asia require evidence of vaccination from travelers coming from or traveling through endemic or infected areas. The vaccine is available in the US only from providers certified by state health departments.33 Boosters are given every 10 years, but immunity probably lasts much longer. If other injectable or intranasal live vaccines are not administered simultaneously with yellow fever vaccine, administration should be separated by one month to avoid a diminished immune response to the vaccines.
Yellow fever vaccine is contraindicated in travelers who have symptomatic HIV infection (and possibly in those with CD4 counts <200 cells/mm3), are immunocompromised or have egg allergy. Yellow fever vaccine- associated viscerotropic disease, a severe systemic illness that can cause fatal organ failure, has been reported rarely. It has occurred only in first-time recipients, especially those with thymus disorders. Vaccine-associated neurologic disease (encephalitis, Guillain-Barré, Bell’s palsy) has also occurred. The vaccine should be avoided if possible in infants <9 months old and it is contraindicated in infants <6 months old.34 Travelers >60 years of age also have a relatively high risk of systemic adverse effects.35
The most common cause of travelers’ diarrhea, usually a self-limited illness lasting several days, is infection with noninvasive enterotoxigenic (ETEC) or enteroaggregative (EAEC) strains of Escherichia coli. Infections with Campylobacter, Shigella, Salmonella, Aeromonas, viruses and parasites are less common. Children tend to have more severe illness and are particularly susceptible to dehydration. Travelers to areas where hygiene is poor should avoid raw vegetables, fruit they have not peeled themselves, unpasteurized dairy products, cooked food not served steaming hot, and tap water, including ice.
Treatment – For mild diarrhea, loperamide (Imodium, and others), an over-the-counter synthetic opioid (4-mg loading dose, then 2 mg orally after each loose stool to a maximum of 16 mg/d for adults), often relieves symptoms in <24 hours. It should not be used if fever or bloody diarrhea are present, and some patients complain of constipation after use. Loperamide is approved for use in children >2 years old.
If diarrhea is moderate to severe, persists >3 days or is associated with high fever or bloody stools, self-treatment for 1-3 days with ciprofloxacin, levofloxacin, norfloxacin or ofloxacin is usually recommended.36 Azithromycin, taken as a single 1000-mg dose or 500 mg daily for 1-3 days, is an alternative37,38 and is the drug of choice for travelers to areas with a high prevalence of fluoroquinolone-resistant Campylobacter, such as Thailand and India.39,40 Azithromycin can be used in pregnant women and children (10 mg/kg/d x 3d), and in patients who do not respond to a fluoroquinolone in 48 hours.
A non-absorbed oral antibiotic derived from rifampin, rifaximin is approved for treatment of travelers’ diarrhea caused by noninvasive strains of E. coli in travelers ≥12 years of age. In clinical trials in patients with diarrhea mostly caused by E. coli, it has been similar in efficacy to ciprofloxacin, with fewer adverse effects.41 It should not be used in infections associated with fever or blood in the stool or those caused by C. jejuni, Salmonella, Shigella or other invasive pathogens, or during pregnancy.
One meta-analysis found that combinations of an antibacterial plus loperamide were more effective than an antibacterial alone in decreasing the duration of illness.42
Packets of oral rehydration salts (Ceralyte, ORS, and others) mixed in potable water can prevent and treat dehydration, particularly in children and the elderly. They are available from suppliers of travel-related products and some pharmacies in the US, and from pharmacies overseas.
Prophylaxis – Medical Letter consultants generally do not prescribe antibiotic prophylaxis for travelers’ diarrhea, but rather instruct the patient to begin self-treatment when symptoms are distressing or persistent. Some travelers, however, such as immunocompromised patients or those with time-dependent activities who cannot risk the temporary incapacitation associated with diarrhea, might benefit from prophylaxis.43 In such patients, ciprofloxacin 500 mg, levofloxacin 500 mg, ofloxacin 300 mg or norfloxacin 400 mg can be given once daily during travel and for 2 days after return and are generally well tolerated. In one 2-week study among travelers to Mexico, rifaximin (200 mg 1-3x/d) was effective in preventing travelers’ diarrhea. 44 Bismuth subsalicylate (Pepto-Bismol, and others) can prevent diarrhea in travelers who take 2 tablets 4 times a day for the duration of travel, but it is less effective than antibiotics. It is not recommended for children <3 years old.
No drug is 100% effective for prevention of malaria; travelers should be told to take protective measures against mosquito bites in addition to medication.45 Countries with a risk of malaria are listed in Table 5.
Some countries with endemic malaria transmission may not have malaria in the most frequently visited major cities and rural tourist resorts. Travelers to malarious areas should be reminded to seek medical attention if they have fever either during their trip or up to a year (especially during the first 2 months) after they return. Travelers to developing countries, where counterfeit and poor quality drugs are common, should consider buying antimalarials before travel.
CHLOROQUINE-SENSITIVE MALARIA — Chloroquine is the drug of choice for prevention of malaria in the few areas that still have chloroquine-sensitive malaria (see Table 5, footnotes 4, 6 and 7). Patients who cannot tolerate chloroquine should take atovaquone/proguanil, doxycycline, mefloquine or, in some circumstances, primaquine in the same doses used for chloroquine-resistant malaria (see Table 6).
CHLOROQUINE-RESISTANT MALARIA — Three drugs of choice with similar efficacy, listed with their dosages in Table 6, are available in the US for prevention of chloroquine-resistant malaria.
A fixed-dose combination of atovaquone and proguanil (Malarone) taken once daily is generally the best tolerated prophylactic,46 but it can cause headache, insomnia, GI disturbances and mouth ulcers. Single case reports of Stevens-Johnson syndrome and hepatitis have been published. Atovaquone/proguanil should not be given to patients with severe renal impairment (CrCl <30 mL/min). There have been isolated case reports of treatment-related resistance to atovaquone/ proguanil in Plasmodium falciparum in Africa, but Medical Letter consultants do not believe there is a high risk for acquisition of resistant disease. 47-50 In one study of malaria prophylaxis, atovaquone/ proguanil was as effective and better tolerated than mefloquine in nonimmune travelers.51 The protective efficacy of atovaquone/proguanil against P. vivax is variable ranging from 84% in Indonesian New Guinea52 to 100% in Colombia.53 Some Medical Letter consultants prefer other drugs if traveling to areas where P. vivax predominates.
Mefloquine has the advantage of once-a-week dosing, but is contraindicated in patients with a history of any psychiatric disorder (including severe anxiety and depression), and also in those with a history of seizures or cardiac conduction abnormalities.54 Dizziness, headache, insomnia and disturbing dreams are the most common CNS adverse effects. The drug’s adverse effects in children are similar to those in adults. If a patient develops psychological or behavioral abnormalities such as depression, restlessness or confusion while taking mefloquine, another drug should be substituted. Mefloquine should not be given together with quinine, quinidine or halofantrine due to potential prolongation of the QT interval; caution is required when using these drugs to treat patients who have taken mefloquine prophylaxis.
Doxycycline (Vibramycin, and others), which frequently causes GI disturbances and can cause photosensitivity and vaginitis, offers an inexpensive once-daily alternative. Doxycycline should not be taken concurrently with antacids, oral iron or bismuth salts.
A fourth drug, primaquine phosphate, can also be used for prophylaxis, especially in areas where P. vivax is the predominant species, but in other areas should be reserved for travelers unable to take any other drug; it is somewhat less effective than the alternatives against P. falciparum. However, several studies have shown that daily primaquine can provide effective prophylaxis against chloroquine-resistant P. falciparum and P. vivax.55 Some experts also prescribe primaquine for prophylaxis after departure from areas where P. vivax and P. ovale are endemic (see Table 6, footnote 3).
Primaquine can cause hemolytic anemia in patients with glucose-6-phosphate dehydrogenase (G-6-PD) deficiency, which is most common in African, Asian, and Mediterranean peoples. Travelers should be screened for G-6-PD deficiency before treatment with the drug. Primaquine should be taken with food to reduce GI effects.
MEFLOQUINE-RESISTANT MALARIA — Doxycycline or atovaquone/proguanil is recommended for prophylaxis against mefloquine-resistant malaria, which occurs in the malarious areas of Thailand and in the areas of Myanmar and Cambodia that border on Thailand. It has also been reported on the borders between Myanmar and China, and Laos and Myanmar, and in southern Vietnam.
PREGNANCY — Malaria in pregnancy is particularly serious for both mother and fetus; prophylaxis is indicated if travel cannot be avoided. Chloroquine has been used extensively and safely for prophylaxis of chloroquine-sensitive malaria during pregnancy. Mefloquine is not approved for use during pregnancy. It has, however, been reported to be safe for prophylactic use during the second or third trimester of pregnancy and possibly during early pregnancy as well.56,57 The safety of atovaquone/proguanil in pregnancy has not been established, and its use is not recommended. However, outcomes were normal in 24 women treated with the combination in the second and third trimester,58 and proguanil alone has been used in pregnancy without evidence of toxicity. Doxycycline and primaquine are contraindicated in pregnancy.
PREVENTION OF INSECT BITES
To minimize insect bites, travelers should wear light-colored, long-sleeved shirts, pants, socks and covered shoes. They should sleep in air conditioned or screened areas and use insecticide-impregnated bed nets. Mosquitoes that transmit malaria are most active between dusk and dawn; those that transmit dengue fever bite during the day, particularly during early morning and late afternoon.59
DEET —The most effective topical insect repellent is N, N-diethyl-m-toluamide (DEET).60 Applied on exposed skin, DEET repels mosquitoes, as well as ticks, chiggers, fleas, gnats and some flies. DEET is available in formulations of 5-100% even though increasing the concentration above 50% does not seem to improve efficacy. Medical Letter consultants prefer concentrations of 30-35%. A long-acting DEET formulation originally developed for the US Armed Forces (US Army Extended Duration Topical Insect and Arthropod Repellent – EDTIAR) containing 25-33% DEET (Ultrathon) protects for 6-12 hours. A microencapsulated sustained-release formulation containing 20% DEET (Sawyer Controlled Release) is also available and can provide longer protection than similar concentrations of other DEET formulations. According to the CDC, DEET is probably safe in children and infants >2 months old; the American Academy of Pediatrics recommends use of concentrations containing no more than 30%. One study found that applying DEET regularly during the second and third trimesters of pregnancy did not result in any adverse effects on the fetus.61 DEET has been shown to decrease the effectiveness of sunscreens when it is applied after the sunscreen; nevertheless, sunscreen should be applied first because it may increase the absorption of DEET when DEET is applied first.62
PICARIDIN — Picaridin has been available in Europe and Australia for many years. Data on the 7% and 15% formulations (Cutter Advanced) currently sold in the US are limited. The 20% formulation (Natrapel 8 Hour; GoReady) has been shown to protect for up to 8 hours; in clinical trials it has been about as effective as 20% DEET.63-65
PERMETHRIN — An insecticide available in liquid and spray form, permethrin (Duranon, Permanone, and others) can be used on clothing, mosquito nets, tents and sleeping bags for protection against mosquitoes and ticks. After application to clothing, it remains active for several weeks through multiple launderings. Using permethrin-impregnated mosquito nets while sleeping is helpful when rooms are not screened or airconditioned. If bednets or tents are immersed in the liquid, the effect can last for about 6 months. The combination of DEET on exposed skin and permethrin on clothing provides increased protection.
SOME OTHER INFECTIONS
DENGUE — Dengue fever is a viral disease transmitted by mosquito bites that occurs worldwide in tropical and subtropical areas, including cities. Epidemics have occurred in recent years in Southeast Asia (especially Thailand), South Central Asia, sub-Saharan Africa, the South Pacific and Australia, Central and South America and the Caribbean. It has also been reported in travelers from the US vacationing at popular tourist destinations in Puerto Rico, the US Virgin Islands and Mexico.66 Prevention of mosquito bites during the day, particularly in early morning and late afternoon, is the primary way to protect against dengue fever; no vaccine is currently available.
LEPTOSPIROSIS — Leptospirosis, a bacterial disease that occurs in many domestic and wild animals, is endemic worldwide, but the highest incidence is in tropical and subtropical areas. Transmission to humans usually occurs through contact with fresh water or damp soil contaminated by the urine of infected animals. 67 Travelers at increased risk, such as adventure travelers and those who engage in recreational water activities, should consider prophylaxis with doxycycline 200 mg orally once a week, beginning 1-2 days before and continuing throughout the period of exposure. No human vaccine is available in the US.
NON-INFECTIOUS RISKS OF TRAVEL
Many non-infectious risks are associated with travel. Injuries, particularly traffic accidents and drowning, which account for the majority of travel-related deaths, and sunburn occur in many travelers.
HIGH ALTITUDE ILLNESS — Rapid exposure to altitudes >8,000 feet (2500 meters) may cause acute mountain sickness (headache, fatigue, nausea, anorexia, insomnia, dizziness); pulmonary and cerebral edema can occur.68 Sleeping altitude appears to be especially important in determining whether symptoms develop. The most effective preventive measure is pre-acclimatization by a 2- to 4-day stay at intermediate altitude (6000-8000 feet) and gradual ascent to higher elevations.
Acetazolamide, a carbonic anhydrase inhibitor taken in a dosage of 125-250 mg twice daily (or 500 mg daily with the slow-release formulation Diamox Sequels) beginning 1-2 days before ascent and continuing at high altitude for 48 hours or longer, decreases the incidence and severity of acute mountain sickness.69 The recommended dose for children is 5 mg/kg/d in 2 or 3 divided doses. Although acetazolamide, a sulfone, has little cross-reactivity with sulfa drugs, hypersensitivity reactions to acetazolamide are more likely to occur in those who have had severe (life-threatening) allergic reactions to sulfa drugs.70
Symptoms can be treated after they occur by descent to a lower altitude or by giving supplemental oxygen, especially during sleep. When descent is impossible, dexamethasone (Decadron, and others) 4 mg q6h, acetazolamide 250-500 mg q12h, or the two together, may help. Nifedipine (Procardia, and others), 20-30 mg twice daily may also be helpful.
VENOUS THROMBOEMBOLISM — Prolonged immobilization, particularly during air travel, increases the risk of lower extremity deep vein thrombosis (DVT). Travelers with risk factors for thrombosis (past history of thrombosis, obesity, malignancy, increased platelets) are at even higher risk. Nevertheless, flightrelated symptomatic pulmonary embolism is rare.71 To minimize the risk, travelers should be advised to walk around or, if necessary, exercise while sitting by flexing/extending ankles and knees, to drink extra fluids, and to avoid alcohol and caffeine. Compression stockings can decrease the risk of asymptomatic DVT.72 Giving a single dose of a low-molecularweight heparin as prophylaxis to travelers at high risk reduced the incidence of DVT in a clinical trial.73
JET LAG — Disturbance of body and environmental rhythms resulting from a rapid change in time zones gives rise to jet lag, which is characterized by insomnia, decreased quality of sleep, loss of concentration, irritability and GI disturbances. It is usually more severe after eastward travel.74
A variety of interventions have been tried, but none is proven to be effective. Shifting daily activities to correspond to the time zone of the destination country before arrival along with taking short naps, remaining well hydrated, avoiding alcohol and pursuing activities in sunlight on arrival may help. The dietary supplement melatonin (0.5-5 mg started on the first night of travel and continued for 1-5 days after arrival) has been reported to facilitate the shift of the sleep-wake cycle and decrease symptoms in some patients. A program of appropriately timed light exposure and avoidance in the new time zone may adjust the “body clock” and reduce jet lag.75 In one study, zolpidem (Ambien, and others) started the first night after travel and taken for 3 nights was helpful.76
MOTION SICKNESS — Therapeutic options for motion sickness remain limited.77 A transdermal patch or oral formulation of the prescription cholinergic blocker scopolamine can decrease symptoms. Transderm Scop is applied to the skin behind the ear at least 4 hours before exposure and changed, alternating ears, every 3 days. The oral 8-hour tablet (Scopace) is taken 1 hour before exposure. Oral promethazine (Phenergan, and others) is a highly sedating alternative. Over-the-counter drugs such as dimenhydrinate (Dramamine, and others) or meclizine (Bonine, and others) are less effective, but may be helpful for milder symptoms.
7. Advisory Committee on Immunization Practices (ACIP) Centers for Disease Control and Prevention (CDC). Update: prevention of hepatitis A after exposure to hepatitis A virus and in international travelers. Updated recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep 2007; 56:1080.
14. ACIP provisional recommendations for the use of Japanese encephalitis virus vaccines, June 24, 2009. Available at www.cdc.gov/vaccines/recs/provisional/downloads/je-july2009-508.pdf. Accessed October 5, 2009.
17. ACIP Provisional Recommendations for measles-mumps-rubella (MMR) ‘evidence of immunity’ requirements for healthcare personnel. Available at: www.cdc.gov/vaccines/recs/provisional/default.htm. Accessed October 5, 2009.
19. OO Bilukha and N Rosenstein; National Center for Infectious Diseases, Centers for Disease Control and Prevention (CDC). Prevention and control of meningococcal disease. recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2005; 54 (RR-7):1.
25. ACIP provisional recommendations for the prevention of human rabies. July 10, 2009. Available at www.cdc.gov/vaccines/recs/provisional/downloads/rabies-July 2009-508.pdf. Accessed October 5, 2009.
40. DR Tribble et al. Traveler’s diarrhea in Thailand: randomized, double-blind trial comparing single-dose and 3-day azithromycin-based regimens with a 3-day levofloxacin regimen. Clin Infect Dis 2007; 44:338.
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