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A. Immunization [4]

  1. Non-Tropical
    1. Measles - anyone born after 1956 without history of illness or two vaccines should be given a booster immunization (usually MMR; this is a live virus vaccine)
    2. Polio - inactivated enhanced polio vaccine (IPV) series; single dose if needed within 4 weeks followed by booster subsequently
    3. Diphtheria + Tetanus - q10 years in all persons regardless of travel destination [2]
    4. Rotavirus vaccine (Rotashield®) also available (consider in children)
  2. Developing Countries [2,14]
    1. Hepatitis A Virus (HAV) Vaccine (Havrix®, Vaqta®) 1 dose then boos at 6-12 months [14]
    2. HAV immune globulin may also be used in emergency or for "rapid" coverage [14]
    3. HAV vaccination - anywhere outside USA, Canada, Western Europe, Australia, Japan, NZ
    4. Hepatitis B Virus (HBV) Vaccine (Recombivax HB®, Energix-B®) - usually for long stays, living among local population, receiving medical or dental care, undergo body piercing
    5. HBV Vaccination: 3 shots at 0,1,6 month OR 0,1,2 month boost at 12 months
    6. Combination HBV/HAV vaccine (Twinrix®) given 0,1,6 months or 0,1,3 weeks + 1 year
    7. Typhoid - S. typhi new single dose polysaccaride vaccine 2 weeks before travel [6]
    8. Yellow Fever - 10 year attenuated live virus, endemic areas, give 10 days pre-travel [5]
    9. Malaria - Malarone®, mefloquine or doxycycline prophylaxis
    10. Cholera - risk to traveler is low; vaccine not very effective'
  3. South America
    1. Yellow Fever - rural South America (see below)
    2. Measles - as above in persons born after 1956
    3. Typhoid - strongly recommended
    4. Hepatitis A - strongly recommended
    5. Influenza - consider vaccination between April and September
    6. Malaria prophylaxis may be required
  4. South Asian Travel [6]
    1. Malaria
    2. Typhoid and other enteric fever (especially Indian subcontinant) [8]
    3. Dengue
    4. Bubonic Plague
    5. Japanese Encephalitis
  5. Tuberculosis [17]
    1. Concerning in any region with epidemic or endemic tuberculosis
    2. Africa, Central America, South America, South Asia and Pacific, former Soviet states
    3. Overall incidence on visits to epidemic area is 2.8-3.5/1000 person-months of travel
    4. BCG vaccination or post-travel tuberculin skin testing should be considered
  6. Japanese B Encephalitis Vaccine (JE-Vax®)
    1. Consider for any travelers with >1 month in rural rice-growing areas in Asia
    2. Give on days 0,7, 30 or 0,7,14 (three doses are strongly recommended)
    3. However, efficacy of single dose SA 14-14-2 is >99% [16]
    4. South, Southeast, East Asia (India, Vietnam, China, Islands)
    5. Delayed anaphylactoid reactions may occur (up to 2 weeks post-vaccine) in ~0.5%
    6. Vaccine is effective for asbout 1 year
    7. Novel, purified inactivated JEV vaccine propagated in monkey (Vero) cells has improved tolerability compared with mouse brain-derived vaccine [26]
  7. Rabies [2,12]
    1. Remains a significant risk in Asia, India, Africa and Latin America [10]
    2. Three doses of vaccine can be given to persons at risk while travelling
    3. Children, field workers, and prolonged duration of stays are at increased risk
    4. Postexposure prophylaxis should be given to all persons following a risky animal bite
    5. Postexposure prophylaxis includes human rabies immune globulin (Imogam Rabies-HT®)
    6. A 1mL dose of one of the 3 available rabies vaccines should also be given
    7. For previously unvaccinated persons, repeat vaccines on days 3,7,14,28 after first dose
    8. If pre-exposure vaccination occurred, then boosters on days 0 and 3 recommended
    9. RabAvert (from chick embryos) has 100% efficacy and appears safer than others [12]
    10. Severe egg allergy is a contraindication to using RabAvert
  8. Yellow Fever Vaccination
    1. Endemic mosquito borne infection in Amazonian forest region
    2. Primarily restricted to jungle region; not found in coastal regions
    3. Yellow fever 17D or 17DD vaccines are live, attenuated, and highly effective
    4. These vaccines are extremely safe, but some multisystem organ failure and fatalities have occurred [20,21]
  9. Meningococcus (N. meningiditis)
    1. Nepal, Subsaharan Africa (Senegal and Guinea to Ethiopia), Mecca
    2. Quadrivalent single-dose vadccine (Menomune®) against serotypes A,C,Y, W135
    3. Protection afforded at least 3 years in adults
    4. Slightly less effective in children <5 years
  10. Plague (Yersinia pestis)
  11. Live vaccines should generally not be given to immunocompromised or pregnant patients
    1. However, measles vaccine is recommended for HIV-infected patients
    2. Yellow fever vaccine may be given to HIV and pregnant patients who can't avoid exposure

B. Supplies

  1. Insect (Mosquito) Repellant (see below)
  2. Water Disinfectant
  3. Sun Screen
  4. Regular medications
    1. Should be very clearly labelled
    2. Official MD letter should accompany

C. Fever After International Travel [1]

  1. 3% of people traveling
  2. Malaria
  3. Dengue (see below)
  4. Spotted fever
  5. Scrub Typhus
  6. Infectious Diarrhea
  7. Typhoid Fever
  8. East African Trypanosomiasis
  9. Acute HIV Infection
  10. Fever with Hemorrhage
    1. Meningococcemia
    2. Leptospirosis
    3. Other bacterial infections
    4. Malaria
    5. Viral hemorrhagic fever
  11. Fever with Central Nervous System Involvement
    1. Meningococcal meningitis
    2. Other meningitis
    3. Encephalitis
    4. Rabies
    5. Typhoid and typhus
    6. Poliomyelitis
    7. East African Trypanosomiasis
  12. Fever with Respiratory Findings
    1. Influenza
    2. Legionellosis
    3. Acute histoplasmosis
    4. Acute coccidioidomycosis
    5. Q fever

D. Illnesses [2]

  1. Food-Borne
    1. Most common is "Traveler's Diarrhea" - Enterotoxigenic E. coli (see below)
    2. Avoid all green leafy vegetables and fresh fruits that can't be peeled, shellfish
    3. Tapwater and ice should be avoided
    4. Milk may contain Bovine TB and/or Brucella
    5. Cholera - sensitive to gastric acid; watch for patients on H-2 blockers, omeprazole
    6. Hepatitis A - fairly common; vaccine or Immune Globulin is effective [4]
  2. Water-Borne
    1. Schistosomiasis - avoid swimming in endemic areas
    2. Giardia
    3. Amoeba
  3. Insect-Borne
    1. Tick-Borne Disease: Ricketsial illness
    2. Malaria - doxycycline or mefloquine for suppression
    3. Dengue Fever
    4. Yellow Fever
    5. Encephalitis
  4. Mosquito Borne Infections
    1. Transmit arboviruses and protozoans
    2. Malaria
    3. Yellow Fever
    4. Dengue and Dengue hemorrhagic fever (see below)
    5. Japanese B encephalitis
    6. Other types of encephalitis
    7. Epidemic polyarthritis
  5. Bites
    1. Large animal bites
    2. Scorpion Envenomation (see below)
    3. Snake Bites

E. Traveler's Diarrhea [1,2,4]

  1. Organisms
    1. Usually caused by enterotoxigenic Escherichia coli
    2. Less common: Campylobacter, Shigella, Salmonella
    3. Viruses and parasites least common
  2. Prevention
    1. Important avoid the following in areas of poor hygiene
    2. Raw vegetables
    3. Fruit not peeled by person ingesting it
    4. Unpasteurized dairy products
    5. Cooked food not served steaming hot
    6. Tap water, including ice
  3. Self-treatment once symptoms begin usually preferable to prophylaxis
  4. Factors favoring prophylaxis prior to first episode
    1. Underlying chronic / acute medical process
    2. Lack of appropriate medical care in area to travel
    3. Traveler will not follow careful dietary restrictions
    4. Trip will be ruined if traveler has illness
  5. Prophylactic Agents
    1. Quinolones are first line given once daily:
    2. Norfloxacin 400mg OR ciprofloxacin 500mg OR levofloxacin 500mg OR ofloxacin 300mg
    3. Loperamide should not be used for prophylaxis
    4. Bismuth: Take two 262mg tabs QID with food (but resistance is increasing)
    5. Maximum prophylaxis for 3 weeks
    6. Azithromycin (Zithromax®) can be considered for pregnant women and children
    7. Rifaximin (Xifaxan®), a non-absorbed rifampin derivative, 200mg po bid or tid, prevents traveler's diarrhea without substantially changing fecal flora [24]
  6. Treatment
    1. Loperamide (Imodium®) 4mg po x 1, then 2mg po after each loose stool (max 16mg/24h)
    2. Diarrhea associated with fever, night sweats, or blood stools, or severe cases should be treated with antibacterial agents
    3. First line is 3 days of: ciprofloxacin 500mg po bid OR levofloxacin 500mg qd, OR norfloxacin 400mg bid OR ofloxacin 300mg bid (not for pregnancy)
    4. Azithromycin (Zithromax®) 1000mg single dose or 500mg qd x 3 for pregnant women
    5. Azithromycin also acceptable for children: 10mg/kg day 1, 5mg/kg days 2 and 3
    6. Azithromycin is drug of choice in areas of highly prevalent fluoroquinolone resistance
    7. TMP/SFX (Bactrim®): 1 DS po qd only for Mexico in summer (resistance increasing)
    8. Packets of oral rehydration salts mixed in water can help maintain electrolyte balance

F. Malaria Prophylaxis

  1. Mefloquine or atovaquone/proguanil are prophylactic agents of choice for travelers [18,19]
  2. Mefloquine (Lariam®)
    1. For use in areas of chloroquine resistance
    2. Not used on Thai-Myanmar and Thai-Cambodium borders (resistance; doxycycline used)
    3. Loading dose of 250mg qd x 3 days then weekly for persons entering area within 1 week
    4. Maintenance prophylactic dose
    5. Mefloquine and doxycycline had similar efficacy in Indonesian soldiers
    6. Contraindications: history of serious psychiatric illness, epilepsy, cardiac arrhythmia, or conduction abnormality
    7. Neuropsychiatric side effects risk is very low
  3. Doxycycline
    1. Recommended for persons who cannot take mefloquine
    2. Also recommended in mefloquine resistant areas, Thai borders with Cambodia / Burma
    3. Only useful for short term exposures in chloroquine resistant areas
    4. Begin 100mg po qd 1-2 days prior to travel, then 4 weeks after returning from area
    5. Similar efficacy to mefloquine in Indonesia and other areas
  4. Atovaquone
    1. Atovaquone inhibits parasite mitochondrial respiratory chain
    2. Atovaquone blocks subsequent de novo pyrimidine synthesis
    3. Effective against malaria, toxoplasmososis, and pneumocystis
    4. Atovaquone/proguanil (250mg/100mg po qd; Malarone®) combination preferred
    5. Malarone is as effective and better tolerated than mefloquine or chloroquine-proguanil
    6. Effective for prevention and cure of chloroquine resistant P. falciparum malaria
    7. Also effective in all other strains which cause human malaria
  5. Chloroquine (Aralen®) or Hydroxychloroquine (Plaquenil®)
    1. Drugs of choice in sensitive areas
    2. These include Central America, Carribean and parts of Middle East
    3. Most areas have chloroquine resistance (primarily by P. falciparum)
    4. Dose of chloroquine is 300mg q week
  6. Primaquine
    1. Post-exposure prevention for "relapsing" malaria
    2. Cannot be used in G6PD deficient persons (will cause massive hemolysis)
    3. Dose is 15mg base (26.3mg salt) qd x 14 days
    4. May be less effective for P vivax malaria (may increase dose to 30mg po qd x 14 d)
  7. Azithromycin 250mg qd po for 28 days after P. falciparum exposure prevents disease
  8. Other Preventative Measures
    1. Anti-malaria room sprays
    2. Mosquito Netting
    3. Insect repellents (see below)
  9. Travel [9]
    1. In 45% of cases in Israel, malaria symptoms developed >2 months after traveler's return
    2. Most late onset illness not prevented by blood phase schizonticides
    3. Additional agents acting on liver phase are required
  10. Additional information from CDC at 770-488-7788

G. Dengue [7,13]

  1. Mosquito-Transmitted Viral Disease
    1. ~75 million cases of dengue fever (DF) annually, worldwide
    2. ~250,000 cases of dengue hemorrhagic fever (DHF) annually
    3. ~25,000 deaths annually, mainly in DHF and dengue shock patients
    4. Typically transmitted by Aedes aegypti and Aedes albopictus mosquitos
    5. Southeast Asian travel is major risk factor (Thailand, Malaysia, Indonesia, Vietnam)
  2. Flavivirus (Arbovirus) Infection [5]
    1. Closely related set of Dengue Viruses (DEN)
    2. Four distinct viral serotypes, DEN 1 through 4
    3. Infection with one serotype provides lifelong immunity only to that serotype
  3. Clinical Syndromes Overview
    1. Asymptomatic
    2. Dengue Fever (DF)
    3. Dengue Hemorrhagic Fever (DHF)
    4. Dengue Shock
    5. Majority of infections in children are asymptomatic
  4. DF
    1. Incubation period is typically 4-7 days (always <14 days)
    2. Acute febrile illness with headache, retro-ocular pain and other symptoms
    3. Influenza-like symptoms
    4. Fever, arthralgia, myalgia, rash, nausea and vomiting
    5. Lymph node enlargement can occur
    6. Leukopenia and/or mild thrombocytopenia occur
    7. Elevated leukocyte or platelet count rule out DF
    8. Symptoms persist for ~5 days
    9. Fevers lasting >2 weeks are not due to dengue
    10. A small minority of patients with DF will develop neurological disease [15]
    11. In these patients, seizures and delirium can occur
  5. DHF
    1. Symptoms of DF with major or minor bleeding and <100K/µL platelets
    2. Evidence of plasma leakage to extravascular space (major hallmark of DHF)
    3. Evidence includes increased HCT by >20%, pleural or other effusions, hypoalbuminemia
    4. Fluid extravasasation occurs through endothelial gaps, without necrosis or inflammation
    5. Fever is typically high (38-40°C) and continues 2-7 days
    6. Petechiae due to thrombocytopenia (infrequently severe with major hemorrhage)
    7. Increased activated partial thromboplastin time (APTT) and reduced fibrinogen
    8. Increased risk for progression to Dengue Shock
    9. Patients with DHF should be hospitalized and carefully monitored
  6. Dengue Shock
    1. Defined as DHF with signs of circulatory failure
    2. Signs include narrowed pulse pressure (<20mmHg), hypotension, or frank shock
    3. Liver enzymes usually elevated
    4. Severe vascular leakage with disordered hemostasis
    5. Includes endothelial cell glycocalyx dysfunction
    6. Venous pooling without systolic congestive heart failure (reduced pulse pressure)
    7. Fatality rate with frank shock is 12-44%
    8. Overall mortality ~5% with patients who meet definition
  7. Diagnosis
    1. High clinical suspicion in endemic / epidemic areas
    2. Leukopenia and thrombocytopenia with elevated liver transaminases is fairly specific
    3. Diagnosis confirmed by rising serum antibody titers
    4. Probable disease: IgM Ab (ELISA) will become positive 4-5 days after symptom onset
    5. Single serum sample titer at least 1:1280 with hemagglutination or IgG test
    6. Confirm diagnosis with virus isolation, >4X increase in serum IgG/IgM, or PCR positive test
    7. Polymerase chain reaction (PCR) is available and is positive in 90% in early disease
    8. PCR test sensitivity rapidly declines 7 days after onset of illness
    9. PCR test is not routinely available
  8. Differential Diagnosis
    1. Malaria
    2. Typhoid fever
    3. Leptospirosis
    4. Chikungunya
    5. West Nile Virus
    6. Measles
    7. Rubella
    8. Epstein-Barr Virus
    9. Viral hemorrhagic fevers
    10. Rickettsial diseases
    11. Early severe acute respiratory syndrome (SARS)
    12. Early acute HIV infection
  9. Treatment
    1. Supportive care is only available treatment to date
    2. Oral and/or intravenous fluids - Ringer's Lactate
    3. Analgesics
    4. Antipyretics - acetaminophen preferred given thrombocytopenia
    5. Ringer's lactate is indicated for children with moderately severe Dengue shock [25]
    6. For those children with Dengue shock who require colloid, 6% hydroxyethyl starch is better tolerated than Dextran 70 [25]
  10. Prevention
    1. Mosquito control measures (prevent insect bite) will help reduce incidence
    2. Tetravalent vaccine is in development

H. Scorpion Bites [15]

  1. Common in tropical and subtropical regions
  2. North Africa, Latin America, India, Middle East
  3. Clinical Features
    1. Localized reactsion occur in ~97% of persons
    2. Includes
    3. Systemic manifestations occur in ~3%
    4. Systemic reactions include fever, sweating, hypertension, vomiting
    5. Cardiogenic shock anbd pulmonary edema are leading causes of death (~0.3%)
  4. Supportive care and antivenom have been used
  5. However, no benefit to routine of administration of scorpion antivenom after sting

I. Insect Repellents [11,22,23]

  1. DEET containing repellants are most effective
    1. N,N-diethyl-3-methylbenzamide (previously called) N,N-Diethylmetatoluamide (DEET)
    2. Effective against mostquitoes, chiggers, ticks, fleas, biting flies
    3. No topical repellent yet effective against bees and wasps
    4. Broad spectrum repellant available for general use since 1957
    5. HourGuard® is slow release, high strength 35% DEET used by public and by military
    6. HourGuard® has a duration of action of over 6 hours
  2. Picardin [3,22]
    1. Picardin (7% solution, Cutter Advanced®) may be as effective as DEET and is better tolerated [3]
    2. Available in Europe and Australia as19.2% (Bayrepel, Autan Repel®) appears to be as effective as DEET [22]
  3. Other Repellents
    1. Most are marginally or not effective at preventing mostquito bites
    2. Citronella also has activity; derived from a plant; duration of action ~2 hours
    3. Bite Blocker® is a plant based repellant with ~3 hour duration of action
    4. Permethrin can be applied to clothing, tents, etc. and blocks insect nervous system
    5. Permethrin is highly effective for at least 2 weeks when applied to equiptment
  4. Spray cloths with permethrin (Repel Permanone®) - more effective than DEET against ticks (~0.3%)
  5. Supportive care and antivenom have been used
  6. However, no benefit to routine of administration of scorpion antivenom after sting

I. Insect Repellents [11,22,23]

  1. DEET containing repellants are most effective
    1. N,N-diethyl-3-methylbenzamide (previously called) N,N-Diethylmetatoluamide (DEET)
    2. Effective against mostquitoes, chiggers, ticks, fleas, biting flies
    3. No topical repellent yet effective against bees and wasps
    4. Broad spectrum repellant available for general use since 1957
    5. HourGuard® is slow release, high strength 35% DEET used by public and by military
    6. HourGuard® has a duration of action of over 6 hours
  2. Picardin [3,22]
    1. Picardin (7% solution, Cutter Advanced®) may be as effective as DEET and is better tolerated [3]
    2. Available in Europe and Australia as19.2% (Bayrepel, Autan Repel®) appears to be as effective as DEET [22]
  3. Other Repellents
    1. Most are marginally or not effective at preventing mostquito bites
    2. Citronella also has activity; derived from a plant; duration of action ~2 hours
    3. Bite Blocker® is a plant based repellant with ~3 hour duration of action
    4. Permethrin can be applied to clothing, tents, etc. and blocks insect nervous system
    5. Permethrin is highly effective for at least 2 weeks when applied to equiptment
  4. Spray cloths with permethrin (Repel Permanone®) - more effective than DEET against ticks

References

  1. Ryan ET, Wilson ME, Kain KC. 2002. NEJM. 347(7):505 abstract
  2. Advice for Travelers. 2002. Med Let. 44(1128):33 abstract
  3. Picardin Insect Repellent. 2005. Med Let. 47(1210):46 abstract
  4. Immunizations. 1996. Med Let. 38(969):18
  5. Gould EA and Solomon T. 2008. Lancet. 371(9611):500 abstract
  6. Zenilman JM. 1997. JAMA. 278(10):847 abstract
  7. Wilder-Smith A and Schwartz E. 2005. NEJM. 353(9):924 abstract
  8. Mermin JH, Townes JM, Gerber M, et al. 1998. Arch Intern Med. 158(6):633 abstract
  9. Schwartz E, Parise M, Kozarsky P, Cetron M. 2003. NEJM. 349(16):1510 abstract
  10. Noah DL, Drenzek CL, Smith JS, et al. 1998. Ann Intern Med. 128(11):922 abstract
  11. Fradin MS. 1998. Ann Intern Med. 128(11):931 abstract
  12. Rabies Vaccines. 1998. Med Let. 40(1029):64 abstract
  13. Halstead SB. 2007. Lancet. 370(9599):1644 abstract
  14. Levy MJ, Herrera JL, DiPalma JA. 1998. Am J Med. 105(5):416 abstract
  15. Solomon T, Dung NM, Vaughn DW, et al. 2000. Lancet. 355(9209):1053 abstract
  16. Bista MB, Banerjee MK, Shin SH, et al. 2001. Lancet. 358(9284):791 abstract
  17. Cobelens FGJ, van Deutekom H, Draayer-Jansen IWE, et al. 2000. Lancet. 356(9228):461 abstract
  18. Hogh B, Clarke PD, Camus D, et al. 2000. Lancet. 356(9245):1888 abstract
  19. Atovaquone/Proguanil for Malaria. 2000. Med Let. 42(1093):109 abstract
  20. Vasconcelos PFC, Luna EJ, Galler R, et al. 2001. Lancet. 358(9276):91 abstract
  21. Martin M, Tsai TF, Cropp B, et al. 2001. Lancet. 358(9276):98 abstract
  22. Insect Repellents. 2003. Med Let. 45(1157):41 abstract
  23. Fradin MS and Day JF. 2002. NEJM. 347(1):13 abstract
  24. DuPont HL, Jiang ZD, Okhuysen PC, et al. 2005. Ann Intern Med. 142(10):805 abstract
  25. Wills BA, Dung NM, Loan HT, et al. 2005. NEJM. 353(9):877 abstract
  26. Touber E, Kollaritsch H, Korinek M, et al. 2007. Lancet. 370(9602):1847 abstract