©2014 American Society of Transplantation

American Society of Transplantation Infectious Disease Guidelines, 3rd Edition

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Travel Medicine SectionDeveloped by:Robin Avery, MD, Johns Hopkins John Baddley, MD, University of Alabama at BirminghamAST Infectious Disease Community of Practice

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General Travel Information

Vaccine Preventable

Illness

DPT/Pertussis

Hepatitis A/B

Rabies/JE

Meningococcus

Typhoid

Yellow Fever

Influenza/Strep. pneumioniaeNon-vaccine Preventable

Illness Traveler’s Diarrhea

Malaria and Dengue

Post-travel Illness

Patient Evaluation

Causes of Illness

Other Travel Issues

Sexually Transmitted Diseases

Food/Water Exposure

Transplant Tourism

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©2014 American Society of Transplantation

General Travel Information• Many travel-related illnesses can be prevented with immunizations and/or appropriate education. • Comprehensive information is found in the CDC’s Yellow Book at: http://

wwwnc.cdc.gov/travel/page/yellowbook-2012-home.htm• Visit to dedicated travel clinic familiar with immunocompromised patients ≥2 – 3 months in advance of

planned trip • Avoid travel to high-risk destinations during

– the first post-transplant year– times of intensified immunosuppression.

• Travelers should carry – summaries of their medical problems– updated and accurate medication lists– baseline EKG if abnormal– contact information for their transplant clinicians– adequate supplies of medications

• Travelers should – have evacuation insurance for transport to a major medical center in the event of severe illness.– Check all new prescriptions with their transplant team or a clinician experienced in transplantation

issues. • Travelers should avoid

– clinical settings where non-sterile needles or equipment may be used– blood transfusions or other blood products in areas of limited resources.

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Vaccine Preventable Illness

Non-vaccine Preventable IllnessPost-trave

l IllnessOther Travel Issues

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Vaccine Preventable Illness

DPT/Pertussis

Hepatitis A/B

Rabies/Japanese encephalitis

Meningococcus

Immunizations should be administered:• ≥ 2-3 months in advance of planned trip• Preferably by a dedicated travel clinic familiar with immunocompromised patients• General (routine) immunizations should be up to date

Check the CDC’s Yellow Book • General travel information http://wwwnc.cdc.gov/travel/page/vaccinations.htm• Destination-specific information http://wwwnc.cdc.gov/travel/destinations/list.htm

Check the AST ID Guidelines for recommended immunizations for SOT travelers (table 3)

Family members of transplant recipients should not receive • Oral polio vaccine• Nasal influenza vaccine• Smallpox vaccine

©2014 American Society of Transplantation

DPT/PertussisDPT/Pertussis• A tetanus/diphtheria booster should be administered if not

given within 10 years. – If the patient has never received Tdap vaccine (tetanus-

diphtheria-pertussis), substitute a 1-time Tdap dose for protection against pertussis.

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Hepatitis A/B (1 of 2)Hepatitis A vaccine • Recommended for

– All travelers if not received pre-transplant.– Vaccine administration

• 2 doses should be administered 6 – 12 months apart. • Check antibody titers after second vaccine

• If there is not enough time before planned travel for 2 doses of hepatitis A vaccine, intramuscular gamma globulin can be given at a dose of 0.02 ml/kg for short-term protection (up to 3 months), and at a dose of 0.06 ml/kg for longer-term protection, and should be repeated every 4 – 6 months

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©2014 American Society of Transplantation

Hepatitis A/B (2 of 2)Hepatitis B vaccine • Recommended for:

– Not previously HBV immune and at least 1 of following:• If they may have new sexual partners while traveling or • Will live in an endemic area for an extended period of time, or • May require transfusions or medical procedures while traveling.

• Vaccine administration– Administered at 0,1,6 months. However, accelerated schedules (such as 0,1,2 months, or

0,7,28 days could also be used; the benefit of these schedules is less well studied). Ideally, seroconversion (anti-HBs) should be checked. Seroconversion may be suboptimal on post-transplant immunosuppression, so post-exposure prophylaxis may still be required in the event of an exposure. Antibody titers can be checked to assess the adequacy of previous vaccination, and a booster dose and/or enhanced potency dose administered to non-converters.

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Rabies/JERabies vaccine • Pre-exposure prophylaxis (3 doses on days 0, 7, and 21 or 28) for

– Travelers who anticipate • Frequent contact with animals or; • Will reside for a prolonged time in an endemic area and/or; • Will be far from medical care in area where rabies is endemic.

• Post-exposure prophylaxis – Travelers in the event of an exposure

• Days 0 and 3 for previously vaccinated versus days 0,3,7,21, and 28 for those without prior immunization• Rabies immunoglobulin can be given to SOT recipients even if they have received pre-exposure prophylaxis as they

may not have mounted an adequate response to the vaccine. In these cases, some experts recommend rabies immunoglobulin in addition to vaccine.

– Information from CDC about use of a four-dose series (for immunosuppressed patients, post-exposure prophylaxis is still 5 doses)

Japanese encephalitis vaccine • For travelers to rural areas in certain parts of Asia• Administered on days 0 and 28

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MeningococcusMeningococcal vaccine • Administer to travelers to

– Sub-Saharan Africa, or – Saudi Arabia for the hajj or umra (proof of vaccination within the past 3 years

is required)• Single dose Meningococcal conjugate vaccine

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Typhoid

Typhoid vaccine• For travel to typhoid-endemic areas• Administer injected non-live typhoid vaccine, not the oral live vaccine

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Yellow Fever• Yellow Fever Vaccine is contraindicated• For countries that require yellow fever immunization for entry

– Provide letter of exemption from a physician• Letters should have the stamp of an official yellow fever immunization

center

• Discuss safety of travel to area with transplant recipient prior to travel

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Influenza/Strep. pneumoniaeSeasonal inactivated (injectable) influenza vaccine • Should be administered if not already received, even if travel planned for outside

of the winter season

Pneumococcal vaccine• For vaccine naïve patients:

– The 13-valent pneumococcal conjugate vaccine should be given if no prior pneumococcal vaccination– Following this, the 23-valent pneumococcal polysaccharide vaccine should be given at least 8 weeks

later

• For those who have received previous pneumococcal polysaccharide vaccine: – The 13-valent pneumococcal conjugate vaccine should be given at least one year after PPV– Following this, PPV booster should be given at least 5 years after the previous PPV

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Non-vaccine Preventable Illness

Traveler’s Diarrhea

Malaria and Dengue

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Traveler’s Diarrhea (1 of 2)Traveler’s diarrhea affects over half of travelers to some destinations

– Dehydration from diarrhea may result in compromise of renal function with altered metabolism of immunosuppressive medications

Minimizing risk of diarrhea– Instruct traveler in appropriate food and water precautions prior to international travel

• Summary of food and water precautions is available on the CDC website

– Patient instructions• Drink only boiled or bottled water and beverages not containing local water or ice• Avoid unpasteurized dairy products and food sold by street vendors• Avoid raw or undercooked foods (except fruit and vegetables that can be peeled)• Fluid replacement with clean water and oral rehydration solution if they develop diarrhea

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©2014 American Society of Transplantation

Traveler’s Diarrhea (2 of 2)• Antibiotics for traveler’s diarrhea

– Ciprofloxacin or azithromycin (depending on the local resistance patterns of Campylobacter and Salmonella species) for self-treatment of diarrhea • See AST ID Guidelines Table 4

– Start antibiotic therapy if more than 3 unformed stools in 24 hours and accompanying symptoms:• Fever or blood, pus or mucus in the stool• Seek medical attention as soon as possible if accompanying symptoms

– Consider drug interactions • See AST ID Guidelines Table 5

• Avoid– Doxycycline or trimethoprim/sulfamethoxazole for treatment of diarrhea (due to

resistance issues)– Anti-motility agents– Bismuth subsalicylate (i.e., Pepto Bismol), especially if renal dysfunction

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Malaria and Dengue (1 of 2)(Arthropod-borne illnesses)

Travelers to endemic areas should be counseled about how to minimize insect bites by utilizing all of the following:

– Repellents containing DEET (N,N-diethyl-3-methylbenzamide) or picaridin– Bed nets– Well-screened rooms or air conditioning– Protective clothing– Permethrin-impregnated clothing

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©2014 American Society of Transplantation

Malaria and Dengue (2 of 2)(Arthropod-borne illnesses)

Dengue fever • May result in severe illness in SOT• Check country-specific outbreak information • Avoid areas of outbreak

Malaria • For prophylaxis against malaria, consult the CDC Yellow Book, which provides country-specific

guidelines• Malaria prophylaxis options can be found in the AST ID Guidelines Table 4• It is important to note that drug interactions of antimalarial medicines and transplant-related

medicines may be present, as summarized inAST ID Guidelines Table 5

Leishmania endemic regions• Precautions should be taken against sand fly bites

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Post-travel Illness

Causes of Illness

Patient Evaluation

• 15-70% of international travelers returning to the US have a travel-related illness– 5% will become sick enough to seek medical care, usually for

• Diarrhea• Fever• Respiratory symptoms, or • Skin lesions.

• Indications for post-travel follow-up at the transplant center or by a healthcare provider specializing in travel medicine:– If any new symptoms develop during or following their return or – If away for prolonged periods or – If potential exposure to blood-borne pathogens or other high-risk situations

• A summary of post-travel evaluation can be found in chapter 5 of the CDC Yellow Book

©2014 American Society of Transplantation

Patient Evaluation• Transplant recipients should

– Report the details of their trip – Consider the following factors when assessing risk:

• Past medical history and medications• Travel destinations and duration of visits; • Types of accommodation; • Pre-travel immunizations and prophylaxis (medications, insect repellant, etc.)• Activity and exposures (food and water consumptions, sexual contacts, insect bites, • Water exposures, animal exposures, hospitalization or medical care)

• Initial laboratory evaluation considerations in febrile returning travelers (refer to Chapter 5 of CDC Yellow Book):– Complete blood count with differential– General chemistries, liver-function studies– Urinalysis– Cultures of blood, urine, stool– Chest radiography– Malaria diagnostic testing (blood smears)– Risk-specific assays, dependent on travel (HIV testing, infection serologies, etc.)

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Causes of Illness (1 of 3)• Even with careful precautions and full immunizations, infections can be acquired during travel,

and may not manifest until weeks or even months after return from the trip.

• Causes of fever in this setting include: malaria, dengue, typhoid, rickettsial diseases (including Mediterranean spotted fever and typhus), acute schistosomiasis, filariasis, leptospirosis, chikungunya virus infection, acute histoplasmosis, coccidioidomycosis, bartonellosis, Q fever, legionellosis, African trypanosomiasis, brucellosis, tuberculosis, viral encephalitis, amebic liver abscess, or visceral leishmaniasis.

• Additional information about causes of fever in returning travelers, including tables of common causes of fever, may be found in the CDC Yellow Book in chapter 5.

• Hepatitis A, B, or E may be acquired during travel and may present with fatigue, nausea, and jaundice 2 – 9 weeks after exposure.

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©2014 American Society of Transplantation

Causes of Illness (2 of 3)• Malaria, especially falciparum malaria, can progress rapidly and should be sought immediately in

any febrile traveler in order to institute treatment promptly. Having taken malaria prophylaxis does not rule out this diagnosis.

• Traveler’s diarrhea may manifest either during or after a trip, and may be due to a variety of viral,

bacterial, or parasitic pathogens. Patients should be aware of the need for prompt evaluation for diarrhea that does resolve, as the dehydration that accompanies diarrhea may have harmful effects particularly to a renal allograft.

• However, a significant percentage of infections in returning travelers will be less exotic: urinary tract infections, bronchitis, pneumonia, influenza. For SOT recipients, transplant pyelonephritis (in kidney or kidney pancreas recipients), cytomegalovirus viremia, and other common causes of fever should be suspected.

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©2014 American Society of Transplantation

Causes of Illness (3 of 3)• Acute HIV infection may present with fever, with or without rash and a mononucleosis-like

syndrome. Patients with fever should report new sexual contacts that occurred during travel. Primary Epstein-Barr virus infection, cytomegalovirus infection, and toxoplasmosis may also present with a mononucleosis-like syndrome.

• Transplant recipients who acquire infection with Strongyloides stercoralis are at risk of fulminant dissemination. Suspect strongyloidiasis in transplant recipients who have had extensive rural tropical contact particularly with activities such as barefoot outdoor sports.

• Tuberculosis is unlikely to be acquired during a short trip to an endemic area, but may occur in transplant recipients with protracted stays or residence in such area. TB may manifest in atypical fashion (undifferentiated fever, gastrointestinal or central nervous system without pulmonary manifestations, or dissemination). Tests for TB, including the PPD skin test and interferon-gamma release assays (IGRA), may be less sensitive in patients with impaired cellular immunity.

• Noninfectious causes of fever in this setting may include pulmonary emboli (particularly after lengthy air or ground travel) and medication reactions.

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Other Travel Issues

Sexually Transmitted Diseases

Food/Water Exposure

Transplant Tourism

©2014 American Society of Transplantation

Sexually Transmitted Diseases (1 of 2)• STDs are an under-recognized cause of illness in travelers

– Transplant recipients are at higher risk for severe or atypical presentations

• Prior to travel, remind patients of risks of unprotected sexual intercourse– HIV– HBV– Gonorrhea, chlamydia– Syphilis– HSV– Chancroid and lymphogranuloma venereum

• Prior to travel, remind patient to avoid– Contact with commercial sex workers– Going on trips for the purpose of sexual tourism

• Absence of visible genital lesions, or self-reported lack of an STD history, is no guarantee of absence of an STD.

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©2014 American Society of Transplantation

• Prevention of STDs– Condoms should always be worn in sexual contacts outside of long-term monogamous

relationships– Avoid use of illicit drugs and excessive consumption of alcohol

• Sexual assault is a risk in many parts of the world – Avoid solitary travel, travel at night and secluded or poorly-lit areas

• Seek rapid medical attention at a reliable health care center with attention to post-exposure prophylaxis including HIV post-exposure prophylaxis if there is a concern for STD– http://aidsinfo.nih.gov/contentfiles/NonOccupationalExposureGL.pdf

• Be aware of antimicrobial resistance issues when treating STDs– Refer to CDC revised guidelines published in June 2015

Sexually Transmitted Diseases (2 of 2)

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©2014 American Society of Transplantation

Food/Water Exposure• Patients should be advised to avoid

– Food from street vendors– Fresh fruits and vegetables (unless these can be peeled or cooked)– Raw or undercooked foods– Unpasteurized dairy products– Tap water and ice cubes (unless made from safe water)

• Drink only boiled water or bottled beverages

• More information on food and water precautions is available on the CDC website

See also: Traveler’s Diarrhea section

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Transplant Tourism• “Transplant tourism” (involving travel of either the organ donor or

recipient strictly for purposes of organ transplantation), conveys significant infectious disease risks

• Given their commercial and sometimes illegal nature, many of these organ transplants are not recorded in databases, so the incidence of infection in donors or recipients is unknown

• The extent and quality of the pretransplant evaluation of the donor and recipient is likely to be quite variable

• Read full details in the AST ID Guidelines

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InformationView the full AST ID Guidelines 3rd Edition online

Technical DifficultiesPlease email info@myAST.org.

Questions about the ContentPlease email Lara.Danziger-Isakov@cchmc.org.

Copyright InformationThe ID Guideline, 3rd Edition were published as a special supplement to the American Journal of Transplantation, the journal of the American Society of Transplantation (AST) and the American Society of Transplant Surgeons (ASTS). The copyright to the full contents of the Guidelines is owned by AST and ASTS. The copyright to this interactive guide is owned by AST. Reproduction of any portion of this guide or the full Guidelines without written permission from AST (and ASTS) is unlawful.

DisclaimerThe content, information, opinions, and viewpoints contained in this educational material are those of the authors or contributors of such materials. While the American Society of Transplantation (AST) and its committees take great care to screen the credentials of the contributors and make every attempt to review the contents, AST MAKES NO WARRANTY, EXPRESSED OR IMPLIED, as to the completeness or accuracy of the content contained in the educational materials or on this website. The reader of these materials uses these materials at his or her own risk, and AST shall not be responsible for any errors, omissions, or inaccuracies in these materials, whether arising through negligence, oversight, or otherwise. Reliance on any information appearing in this material is strictly at your own risk. Read AST’s full educational disclaimer online.

©2014 American Society of Transplantation

References• Comprehensive information is found in the CDC’s Yellow Book at: http://wwwnc.cdc.gov/travel/page/yellowbook-2012-home.htm• http://wwwnc.cdc.gov/travel/yellowbook/2014/chapter-8-advising-travelers-with-specific-needs/immunocompromised-travelers• http://wwwnc.cdc.gov/travel/page/traveler-information-center• Destination-specific information http://wwwnc.cdc.gov/travel/destinations/list.htm• Boggild AK, Sano M, Humar A, et al. Travel patterns and risk behavior in solid organ transplant recipients. J Travel Med 2004; 11:37-43.• Uslan DZ, Patel R, Virk A. International travel and exposure risks in solid-organ transplant recipients. Transplantation 2008; 86: 407-412.• Roukens AH, van Dissel JT, de Filter JW, Visser LG. Health preparations and travel-related morbidity of kidney transplant recipients

traveling to developing countries. Clin Transplant 2007; 21:567-570. • Danziger-Isakov L, Kumar D; AST Infectious Diseases Community of Practice. Vaccination in solid organ transplantation. Am J Transplant.

2013 Mar;13 Suppl 4:311-7. doi: 10.1111/ajt.12122.• Rubin LG1, Levin MJ, Ljungman P, Davies EG, Avery R, Tomblyn M, Bousvaros A, Dhanireddy S, Sung L, Keyserling H, Kang I,

Infectious Diseases Society of America. 2013 IDSA clinical practice guideline for vaccination of the immunocompromised host. Clin Infect Dis. 2014 Feb;58(3):309-18. doi: 10.1093/cid/cit816.

• DuPont HL1. Systematic review: the epidemiology and clinical features of travellers' diarrhoea.See comment in PubMed Commons below• Aliment Pharmacol Ther. 2009 Aug;30(3):187-96. • Al-Abri SS1, Beeching NJ, Nye FJ. Traveller's diarrhoea. See comment in PubMed Commons belowLancet Infect Dis. 2005 Jun;5(6):349-60.• http://www.cdc.gov/malaria/travelers/index.html• Travel-associated Dengue surveillance - United States, 2006-2008.See comment in PubMed Commons belowMMWR Morb Mortal Wkly

Rep. 2010 Jun 18;59(23):715-9. Centers for Disease Control and Prevention (CDC).• http://www.cdc.gov/Dengue/• Guidelines for the Treatment of Malaria. 2nd edition. Geneva: World Health Organization; 2010.

WHO Guidelines Approved by the Guidelines Review Committee.

©2014 American Society of Transplantation

References (continued)• http://wwwnc.cdc.gov/travel/yellowbook/2014/chapter-5-post-travel-evaluation/general-approach-to-the-returned-traveler• Hagmann SH1, Han PV2, Stauffer WM3, Miller AO4, Connor BA5, Hale DC6, Coyle CM7, Cahill JD8, Marano C9, Esposito DH2, Kozarsky PE

10; GeoSentinel Surveillance NetworkTravel-associated disease among US residents visiting US GeoSentinel clinics after return from international travel. Fam Pract. 2014 Dec;31(6):678-87.

• Gautret P1, Gaudart J, Leder K, Schwartz E, Castelli F, Lim PL, Murphy H, Keystone J, Cramer J, Shaw M, Boddaert J, von Sonnenburg F, Parola P; GeoSentinel Surveillance Network. Travel-associated illness in older adults (>60 y). J Travel Med. 2012 May-Jun;19(3):169-77.

• Zenilman J, “From Boudoir to Bordello: Sexually Transmitted Diseases and Travel.” In Infections of Leisure (4th Edition), ed. David Schlossberg, ASM Press, Washington, DC, 2009.

• http://www.cdc.gov/std/treatment/2010/default.htm• Matteelli A1, Schlagenhauf P, Carvalho AC, Weld L, Davis XM, Wilder-Smith A, Barnett ED, Parola P, Pandey P, Han P, Castelli F;

GeoSentinel Surveillance Network. Travel-associated sexually transmitted infections: an observational cross-sectional study of the GeoSentinel surveillance database. See comment in PubMed Commons belowLancet Infect Dis. 2013 Mar;13(3):205-13.

• http://wwwnc.cdc.gov/travel/page/food-water-safety• See comment in PubMed Commons below• Kotton CN1, Hibberd PL; AST Infectious Diseases Community of Practice. Travel medicine and transplant tourism in solid organ

transplantation. Am J Transplant. 2013 Mar;13 Suppl 4:337-47. doi: 10.1111/ajt.12125.

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