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Travel advice for immunocompromised hosts

Travel advice for immunocompromised hosts
Literature review current through: May 2024.
This topic last updated: Feb 27, 2024.

INTRODUCTION — Immunocompromised hosts represent a broad spectrum of immune suppression. A first step in providing travel advice is determining the extent of infection risk, which must be considered on an individual basis. (See 'Assessing immune status' below.)

Immunocompromised hosts traveling overseas may be at higher risk for travel-related infections than immunocompetent individuals. In general, the vaccine response rate in these patients is diminished, and they may be more likely to have adverse effects from vaccines containing live attenuated virus. Guidelines on travel medicine and solid organ transplant recipients have been updated [1]. Latin America-specific travel recommendations for solid organ transplant recipients have also been published [2].

Issues related to travel-related vaccines in adult immunocompromised hosts without human immunodeficiency virus (HIV) will be reviewed here. Issues related to travel-related vaccines in immunocompetent hosts are discussed separately, as are issues related to routine immunizations for these groups. (See "Immunizations for travel" and "Immunizations in hematopoietic cell transplant candidates, recipients, and donors" and "Immunizations in adults with cancer" and "Immunizations in persons with HIV" and "Immunizations in solid organ transplant candidates and recipients".)

ASSESSING IMMUNE STATUS — Immunocompromising conditions and treatments include but are not limited to:

Active treatment for solid tumor and hematologic malignancies.

Receipt of solid organ transplant or an islet transplant and taking immunosuppressive therapy.

Receipt of chimeric antigen receptor (CAR)-T-cell therapy or hematopoietic cell transplant (HCT; within two years of transplantation or taking immunosuppressive therapy).

Moderate or severe primary immunodeficiency (eg, common variable immunodeficiency disease, severe combined immunodeficiency, DiGeorge syndrome, Wiskott-Aldrich syndrome).

Advanced HIV infection (people with HIV and CD4 cell count <200/mm3, history of an AIDS-defining illness without immune reconstitution, or clinical manifestations of symptomatic HIV) or untreated HIV infection.

Active treatment with high-dose corticosteroids (ie, 20 mg or more of prednisone or equivalent per day when administered for two or more weeks), alkylating agents, antimetabolites, transplant-related immunosuppressive drugs, cancer chemotherapeutic agents classified as severely immunosuppressive, tumor necrosis factor (TNF) blockers, and other biologic agents that are immunosuppressive or immunomodulatory (eg, B-cell-depleting agents).

Considerations in assessing the general level of immune competence in a patient include disease severity, duration, clinical stability, complications, comorbidities, and any potentially immune-suppressing treatment.

For additional information about the degree of immune suppression associated with different medical conditions and treatments, providers can consult the Advisory Committee on Immunization Practices' (ACIP) general best practices for vaccination of people with altered immunocompetence, the United States Centers for Disease Control and Prevention (CDC) Yellow Book, and guidance from the Infectious Diseases Society of America (IDSA) [3].

PURPOSE OF PRETRAVEL VISIT — Immunocompromised hosts planning to travel overseas should be evaluated by a travel medicine specialist familiar with the patient's immunocompromised state and medications [4-9]. Travel health specialists for complex patients should confer with the traveler's other providers as needed to develop an appropriate plan. Given the broad spectrum of immune compromise, an assessment of risk is an important part of the pretravel visit (table 1) [6,9].

Immunocompromised hosts may wish to defer travel until they are less immunocompromised (eg, until one year after solid organ transplant or two years after hematopoietic stem cell transplant). Weighing the risk and benefits of travel for these more vulnerable patients may be an important part of the visit. In addition, other essential parts of the visit may include discussing food and water precautions, hand hygiene, measures to undertake if illness develops, specific antimicrobial prophylaxis (ie, for malaria), self-treatment of diarrhea with antibiotics, and updating both routine and travel-related vaccines (or use of immunoglobulins if necessary). (See "Travel advice".)

Complexity of medication timing can be challenging for patients on a strict regimen and who are changing time zones, such as those who are on organ transplant-related medication or living with HIV. These patients may benefit from an explicit discussion regarding best approach to medication timing, to avoid toxicity or therapeutic gaps [10].

TIMING OF VACCINATION — Vaccination should be initiated several months prior to travel when possible to allow time for serologic testing and additional boosters if needed. Ideally, immunocompromised hosts should be vaccinated during periods of minimal or no exogenous immunosuppression to optimize the immunologic response (eg, before solid organ or hematopoietic stem cell transplant, before biologic immunomodulators are given, etc) [11,12]. Vaccination is least effective in the initial months after solid organ or hematopoietic stem cell transplant since this is usually the period of highest immunosuppression [13,14]. (See "Immunizations in solid organ transplant candidates and recipients".)

Timing of vaccination for patients on chronic immunosuppression is poorly studied; the clinician must weigh the benefits of reducing or suspending the immunosuppressive regimen with the risk of disease flare, organ rejection, and the subsequent potential need for more potent immunosuppression. Worsening of disease while traveling could become a medical emergency, requiring careful consideration and contingency planning.

In general, a fourfold increase in antibody titer (or titer above a designated threshold) is considered evidence of seroconversion. Immunocompromised hosts are less likely to have a significant immunologic response, although they may still benefit from partial protection.

Immune responses to vaccination may wane more rapidly in immunocompromised individuals than other hosts [14]. Booster doses of vaccine may be administered in the setting of low or undetectable antibody titers, although the efficacy for this has not been demonstrated.

The response to vaccination can be variable. Among 292 allogeneic transplant recipients, 89 percent of those who failed to mount a response to the recombinant hepatitis B vaccine mounted at least a threefold rise in polio titers following three doses of inactivated poliovirus [15]. Studies on the efficacy or seroconversion following most travel vaccines in immunocompromised hosts have not been performed.

VACCINES

Travel vaccines

Hepatitis A — Hepatitis A can be a devastating illness in immunocompromised hosts [16]. These patients have attenuated immunologic response and shortened durability of response to hepatitis A vaccine [17,18]. Seroconversion rates to vaccination may depend on immunosuppressive medications, medical comorbidities, and type of vaccine used [19-21]. In one series including 39 liver and 39 renal transplant recipients who received two doses of hepatitis A vaccine six months apart, response rates among liver transplant recipients were 41 and 97 percent, and response rates among renal transplant recipients were 24 and 72 percent [21]. Similar results were found in 53 patients with rheumatoid arthritis on methotrexate and/or tumor necrosis factor (TNF)-alpha treatment; at one and six months after the first dose, 10 and 33 percent had attained seroprotection, and, at one and six months after the second dose, 83 and 72 percent were seroprotected [22].

Thus, vaccination with two doses of hepatitis A vaccine 6 to 12 months apart may be most protective for immunocompromised hosts who are on a modest immunosuppressive regimen, if there is enough time before travel [23]. Titers may be checked to document seroconversion, although there is often insufficient time prior to travel. For patients without sufficient time for two separate doses of vaccine prior to travel, administration of a double dose of hepatitis A vaccine (followed by booster at six months) has been proposed as an alternative approach. Preliminary data among patients with rheumatoid arthritis treated with tumor necrosis factor inhibitors or methotrexate appear promising; further study is needed [24].

Intramuscular gamma globulin (consisting of pooled immunoglobulins) is 85 to 90 percent protective against hepatitis A infection; this effect lasts for up to several months, depending on the dose given. Immunocompromised hosts with hypogammaglobulinemia who receive routine intravenous immunoglobulin (IVIG) do not need additional antibody protection for hepatitis A, measles, or varicella.

Moderately to significantly immunosuppressed hosts who do not have sufficient time for immunization prior to travel or who are unlikely to respond to immunization can be given intramuscular immunoglobulin prior to travel [9,25]. For less immunocompromised hosts, vaccination alone may be adequate. (See "Hepatitis A virus infection: Treatment and prevention".)

Salmonella enterica serovar Typhi — Approximately 350 cases of typhoid fever are reported in the United States each year, although there are many more unreported cases, estimated to be 5700 infections of Salmonella enterica serovar Typhi; most are related to international travel [26,27] . Immunocompromised individuals may have severe complications during infection with Salmonella enterica serovar Typhi and should be immunized against typhoid prior to travel to endemic areas.

There are two vaccines available: Typhim Vi (Aventis Pasteur SA), an injectable polysaccharide vaccine, and Vivotif (Ty21a, Berna) an oral live attenuated vaccine. Both are generally well tolerated [28]. The inactive parenteral vaccine is recommended for immunocompromised individuals, as the oral typhoid vaccine is a live bacteria vaccine that could theoretically cause disseminated disease [9]. The immune response in immunocompromised hosts to either vaccine is usually poor, and efficacy in immunocompromised hosts is unknown. (See "Enteric (typhoid and paratyphoid) fever: Treatment and prevention".)

Polio — Poliomyelitis due to wild-type poliovirus has been eradicated from the Western hemisphere; wild-type virus exists in sub-Saharan Africa and Asia. Outbreaks of vaccine-associated poliomyelitis occasionally occur due to reversion of live attenuated poliovirus from the oral polio vaccine. Such outbreaks have occurred in Hispaniola (Haiti and the Dominican Republic), the Philippines, Madagascar, and Cape Verde.

Two forms of polio vaccine are available: the orally administered, live attenuated virus (OPV or Sabin) and the injected inactivated poliovirus vaccine (IPV or Salk). Immunocompromised hosts and household contacts of immunocompromised individuals should not receive OPV, since attenuated vaccine strain polioviruses may spread through fecal-oral contact. OPV is no longer distributed in many countries, including the United States and Canada.

In general, travelers should have received a primary series of polio vaccine during childhood and at least one booster as an adult. Some authorities recommend booster immunization if more than 10 years have elapsed since administration of the last polio vaccine, especially for individuals traveling to areas of the world with circulating wild-type polio viruses or a polio outbreak. Booster vaccination with the injectable nonlive IPV would seem prudent for immunocompromised hosts. In certain regions with active transmission of wild poliovirus, travelers should travel with an official certificate of vaccination that records their polio vaccination status within 4 to 52 weeks (such as the International Certificate of Vaccination or Prophylaxis).

Poliovirus immunity is relatively well maintained after revaccination among patients with allogeneic stem cell transplant (SCT). In a study of 134 patients who received three doses of inactivated polio vaccine beginning 12 months after hematopoietic stem cell transplantation (HSCT), the estimated probabilities of remaining immune to poliovirus at 5 and 10 years after vaccination were 94 and 94 percent for subtype 1, 98 and 94 percent for subtype 2, and 93 and 90 percent for subtype 3, respectively [29]. Patients with chronic graft-versus-host disease (GVHD) lost immunity more rapidly than those without GVHD. Response to vaccination after solid organ transplantation (SOT) has not been well studied. (See "Poliovirus vaccination".)

Meningococcus — Meningococcal disease has a high case-fatality rate (5 to 15 percent). The meningococcal vaccine is indicated for individuals traveling to areas of the world with known outbreaks of invasive meningococcal disease, to the meningitis belt of sub-Saharan Africa (especially during the dry winter months of December through June), and to Saudi Arabia for the Muslim pilgrimages of Hajj or Umrah, where proof of vaccination is required.

Immunocompromised hosts are at increased risk for morbidity and mortality from meningococcal disease; vaccination is appropriate for those with exposure to regions with active disease. In the United States, several quadrivalent meningococcal conjugate vaccine (MenACWY) formulations are available (Menactra, Menveo, MenQuadfi). Two doses of vaccine are recommended for immunocompromised hosts [30]. Two vaccines, MenB-FHbp (Trumenba) and MenB-4C (Bexsero), have been approved by the US Food and Drug Administration (FDA) to prevent invasive meningococcal disease caused by Neisseria meningitidis serogroup B. Similar vaccines are available in other regions. Individuals who were vaccinated previously and are at prolonged increased risk (ie, asplenia, other immunocompromised states) require booster doses (table 2 and table 3) [30].

Among 44 adult HSCT recipients randomized to receive polysaccharide meningococcal vaccine either 8 or 20 months after transplant, the majority had significant immune responses to serogroups A and C; these responses were lower in the former group (8 months) than the latter group (20 months) [31]. The immune responses declined sharply over the first 6 to 12 months after vaccination, suggesting revaccination should be performed for those at risk of exposure to meningococcal infection. Chronic GVHD had no influence on the vaccination response. In a trial of 67 autologous or allogeneic stem cell transplant recipients who were vaccinated with a single dose of conjugate quadrivalent meningococcal vaccine, the majority developed protective titers, although the authors suggested that they may benefit from receipt of a second dose [32].

Among 38 pediatric HSCT recipients, 100 percent response to polysaccharide meningococcal serogroup C was observed two to four weeks after vaccination [33]. Among 25 pediatric oncology patients, response to meningococcal C conjugate vaccine was variable; those with lower serologic response rates were more likely to be receiving chemotherapy or have lower B cell counts [34].

A study of 19 adolescent kidney transplant patients who underwent vaccination with meningococcal conjugate vaccine (MenACWY-D) showed that at four weeks postvaccination, 41 percent had seroconverted to all four serogroups, with seroconversion rates of 88, 53, 71, and 94 percent for serogroups A, C, W, and Y [35], suggesting a need for alternative dosing schedules. There are no published data regarding the response of adult solid organ transplant recipients to immunization with the polysaccharide or protein conjugate meningococcal vaccine. (See "Immunizations in solid organ transplant candidates and recipients", section on 'Meningococcus'.)

Yellow fever — Yellow fever is a mosquito-borne viral hemorrhagic fever that occurs in tropical regions of South America and sub-Saharan Africa. Case fatality may surpass 20 percent; no specific treatment exists.

In general, immunocompromised travelers should avoid regions where yellow fever is endemic [3]. The yellow fever vaccine contains a live attenuated viral strain and, as a rule, this vaccine should not be administered to immunocompromised hosts [9,36-40]. The CDC guidelines suggest that yellow fever vaccine can be given to those with asplenia, renal failure, chronic liver disease, and diabetes but not to those with more severe immunosuppression [9], including those on high-dose systemic corticosteroids, TNF-alpha inhibitors (such as etanercept), interleukin-1– and interleukin-6–blocking agents (such as anakinra and tocilizumab), other immunosuppressive monoclonal antibodies targeting immune cells (such as rituximab or alemtuzumab), alkylating drugs, and antimetabolites, as they are presumed to be at increased risk for yellow fever vaccine-associated serious adverse events [9]. Even in endemic regions, patients and clinicians may not be aware of this contraindication to vaccination [41].

After discontinuation of high-dose systemic corticosteroid therapy, clinicians should wait at least one month before administering a live-virus vaccine [9]. Some experts recommend waiting one month after discontinuing etanercept and three months after discontinuing the other TNF blockers before administering a live-virus vaccine [42]. Prolonged immunosuppression can occur with lymphocyte-depleting agents such as alemtuzumab and rituximab; the optimal time for vaccination before or after such agents is unknown. Reinitiation of immunosuppression after live-virus vaccination has not been studied; some experts would recommend waiting at least one month depending on the mechanism of immunosuppression [9].

Thymic dysfunction has been found to be an independent risk factor for the development of yellow fever vaccine–associated viscerotropic disease, and health care providers should ask about a history of thymus disorder, including myasthenia gravis, thymoma, or prior thymectomy [43]. Fatal myeloencephalitis following yellow fever vaccination have been reported in immunosuppressed individuals [44,45].

Immunocompromised travelers who cannot avoid travel to endemic regions should be counseled to avoid traveling during peak seasons for yellow fever transmission and minimize exposure to mosquitoes (ie, during the elevated risk period in rural West Africa during the end of the rainy season and the beginning of the dry season [usually July to October] and during the rainy season in South America [January to May, with a peak incidence in February and March]) [9].

Immunocompromised patients who previously underwent yellow fever vaccination appear to have durable neutralizing antibody responses, similar to normal hosts [46,47]. Given the World Health Organization (WHO) recommendation for a single dose of vaccine, it may be acceptable to presume immunity to yellow fever after a single lifetime dose, especially weighing the risks of revaccination in immunocompromised patients. It is not known whether prior vaccine may alter the risk of such complications.

Some mildly immunosuppressed individuals have tolerated the vaccine (including individuals with early HIV infection or a distant history of hematologic malignancy without recent immunosuppressive therapy) [48-51]. The CDC recommends that, for those with HIV and CD4 count <200/mm3, yellow fever vaccine is contraindicated, a medical waiver should be provided, and counseling on protective measures against mosquito bites should be emphasized [9]. For those with 200 to 500 CD4/mm3, the CDC recommends that vaccination may be considered with a plan for close monitoring, unless such vaccination is only to fulfill international travel requirements, in which case the individual should be excused from immunization and issued a yellow fever vaccine medical waiver. The CDC recommends that an asymptomatic HIV-infected person with no evidence of immune suppression and CD4 ≥500/mm3 can be administered yellow fever vaccine when indicated.

In a retrospective study of 70 patients with rheumatologic conditions who received the yellow fever vaccine in Brazil, 23 percent reported some minor adverse effect; this rate is comparable to adverse reactions among immunocompetent individuals [52].

Final decision regarding vaccination should be made with careful consideration of risks and benefits. For patients who cannot avoid travel to endemic regions but do not receive vaccination, a physician's letter stating contraindications to vaccination with the stamp of an approved yellow fever immunization center is acceptable to most governments . Some countries may deny entry without immunization; patients should be aware that deportation might be preferable to receipt of yellow fever vaccine at the destination. (See "Yellow fever: Epidemiology, clinical manifestations, and diagnosis".)

Rabies — Candidates for pre-exposure immunization against rabies include travelers expecting intense animal exposure, travelers planning to be far from medical care, and long-term travelers.

Immunocompromised hosts may not mount adequate antibody responses to the rabies vaccine (titers >0.5 international units [IU]/mL); efficacy data for rabies data are minimal in SOT and HSCT recipients. It may be reasonable to administer rabies vaccination to individuals with significant exposure risks factors, although human rabies immunoglobulin should also be administered after all risk exposures [53]. (See "Indications for post-exposure rabies prophylaxis".)

Japanese encephalitis — Immunization against Japanese encephalitis (JE) with the inactivated vaccine (Jepect/Ixiaro) rather than the live Imojev vaccine (which would be contraindicated) is appropriate for individuals traveling to rural areas of Asia where JE is endemic, especially during periods of increased transmission [9,54]. (See "Japanese encephalitis".)

Bacille Calmette-Guérin — Bacille Calmette-Guérin (BCG) is a live attenuated strain of Mycobacterium bovis for the prevention of tuberculosis. BCG should not be administered to immunocompromised host as it can cause disseminated infection.

Immunocompromised hosts may wish to wear masks when in health care settings in areas endemic for tuberculosis. Pre- and post-travel tuberculosis skin tests with the purified protein derivative may be performed but are likely to be negative in the immunocompromised population. Interferon-gamma release assays for tuberculosis are generally more sensitive in this population. (See "Use of interferon-gamma release assays for diagnosis of tuberculosis infection (tuberculosis screening) in adults".)

Routine vaccines — Travel advice encounters provide the opportunity to review routine immunizations that may have been overlooked. Information on routine vaccinations in immunocompromised hosts is summarized in the tables (table 4 and figure 1 and figure 2 and table 5 and table 6) and discussed in detail separately. (See "Immunizations in solid organ transplant candidates and recipients" and "Immunizations in hematopoietic cell transplant candidates, recipients, and donors" and "Immunizations in adults with cancer".)

The pretravel clinic visit is a good opportunity to update routine vaccines. It is only necessary to administer a routine vaccine if it has not been previously received, appropriately updated, or if there is reason to think that immunity has waned such revaccinating is necessary.

Tetanus — Tetanus boosters should be up to date before traveling. Tetanus is rare in the industrialized world where vaccination rates are quite good; the prevalence is much higher in resource-limited settings, although it is rare among travelers. Vaccination is appropriate for travelers to regions where tetanus is endemic who were vaccinated more than 10 years previously. (See "Tetanus-diphtheria toxoid vaccination in adults".)

Diphtheria — Diphtheria is common in resource-limited settings. Vaccination is appropriate for travelers to regions where diphtheria is endemic who were vaccinated more than 10 years previously or whose titers are below >0.1 international units/mL . In practice, boosters are frequently given without checking titers. Diphtheria antibody levels could be measured ≥4 weeks after vaccination for immunocompromised travelers traveling to endemic areas. (See "Tetanus-diphtheria toxoid vaccination in adults".)

Pertussis — Booster vaccination for pertussis is warranted for previously vaccinated adults. Acellular Tdap vaccines have been formulated for adults with reduced quantities of the diphtheria and pertussis to reduce side effects (available as Boostrix or ADACEL). Thus far, this vaccine has not been studied in immunocompromised hosts but may be used in the setting of exposure risk. (See "Pertussis infection in adolescents and adults: Treatment and prevention".)

Influenza — Vaccination against influenza should occur annually in most immunocompromised hosts; exceptions include those who underwent transplantation, treatment for rejection, or other profound immunosuppression in the few months prior to vaccination. Influenza immunity wanes and it is not known whether immunocompromised travelers should be given booster vaccines prior to travel, although it may be reasonable in certain higher risk settings. Given the year-round influenza activity in the tropics, in general, standard practice is to revaccinate with inactivated vaccine prior to travel if it has been more than 12 months since the last influenza vaccine; reducing this to an interval of over six months may be reasonable in immunocompromised hosts.

The live attenuated influenza vaccine is contraindicated in most immunocompromised hosts. The approach to influenza vaccination in immunocompromised hosts is discussed further separately. (See "Seasonal influenza vaccination in adults".)

Pneumococcus — The pneumococcal vaccine should be given to immunocompromised hosts (table 7) [55].

Issues related to pneumococcal vaccination are discussed further separately. (See "Pneumococcal vaccination in adults".)

Measles, mumps, and rubella — Vaccination against measles, mumps, and rubella (MMR) in the United States is usually performed with a trivalent live virus vaccine (MMR vaccine). Primary and acquired immunodeficiency states are contraindications to MMR vaccination, including patients who are immunosuppressed with HIV, cellular immune deficiencies, hypogammaglobulinemic and dysgammaglobulinemic states, or who are on immunosuppressive therapy, including biologic therapy [9,36,56,57]. Measles inclusion body encephalitis, pneumonitis, and death as a direct consequence of disseminated measles vaccine virus infection have been reported in immunocompromised individuals inadvertently vaccinated with measles-containing vaccine [58].

MMR vaccine may be administered to patients with asplenia, renal failure, chronic liver disease, and diabetes but not to those with more severe immunosuppression [9]. Prior to travel to endemic areas, serologic evidence of immunity against measles, mumps, and rubella should be evaluated in transplant recipients. Immune globulin should be considered for seronegative immunosuppressed travelers to areas where measles is endemic [9]. (See "Measles, mumps, and rubella immunization in adults".)

Immunocompromised hosts with hypogammaglobulinemia or other medical conditions and who routinely receive IVIG do not usually need additional intramuscular gamma globulin protection for measles, as IVIG is likely to provide higher titer protection than other preparations. Clinicians caring for such patients should evaluate the immunoglobulin dose to determine whether dose adjustment is needed for additional protection. Depending on the formulation, dose, and frequency of IVIG administration, an adjustment in dose or frequency may be indicated to optimize protect against measles in some individuals; refer to the drug monograph included within UpToDate for additional information.

Hepatitis B — Immunization against hepatitis B is appropriate for certain immunocompromised hosts including hematopoietic cell transplant (HCT) recipients (given their exposure to blood products), diabetics, those who will have new sexual partners while traveling, those living in endemic areas for extended periods, or those who are likely to need transfusions or medical procedures while traveling.

The efficacy of standard hepatitis B vaccination is reduced when the vaccine is administered following transplantation [36,56,59]. Response rates appear to be adversely affected by age ≥18 years and history of prior chronic graft-versus-host disease but not by donor type, T-cell depletion, adoptive immunotherapy, or rituximab [15].

The serologic response rate can sometimes be improved by administering extra doses of vaccine. Some favor the following regimen for immunocompromised hosts: immunization with a vaccine containing 40 mcg of hepatitis B surface antigen (ie, two 1 mL Engerix-B vaccines, each containing 20 mcg, or a special formulation of Recombivax-HB) at one site, in a three- or four-dose schedule [9,60]. A single higher dose vaccine may provide some protection for those who are nonimmune and vaccinated close to the time of departure (with a plan for follow-up vaccination after travel). Intradermal vaccination may be considered for nonresponders [61].

Varicella — Serologic evidence of immunity against varicella should be evaluated in transplant recipients prior to travel to endemic areas. In general, the attenuated live Oka strain vaccine formulations for varicella should not be used in immunocompromised hosts until there are more data regarding their safety. The varicella vaccine may be administered to individuals with asplenia, renal failure, chronic liver disease, diabetes, and some on low-dose immunosuppression, but not to those with more severe immunosuppression [9]. Similarly, zoster vaccine should be avoided in more immunocompromised hosts [62]. (See "Measles, mumps, and rubella immunization in adults".)

Immune globulin or antiviral prophylaxis should be considered for seronegative, severely immunosuppressed travelers to areas where varicella is endemic [9]. Immunocompromised hosts with hypogammaglobulinemia who receive routine IVIG do not need additional antibody protection for varicella, measles, or hepatitis A.

Close contacts and live vaccines — Healthy individuals who undergo vaccination with live attenuated vaccine strains can transmit infection to immunocompromised hosts. In general, use of certain live virus vaccines (including oral polio, live attenuated [nasal] influenza, and smallpox vaccine) should be deferred in close contacts of immunocompromised hosts [9]. Other live vaccines such as measles, mumps, rubella, yellow fever, oral Salmonella, varicella (Varivax), and zoster (Zostavax) vaccines are much less likely to be transmitted and may be given to close contacts of immunocompromised hosts [63].

ANTIMICROBIAL PROPHYLAXIS — When prescribing medications for prevention of travelers' diarrhea and malaria, drug interactions and potential for additive toxicities should be considered (table 8).

Calcineurin inhibitors and mTOR inhibitors have significant interactions with coadministered drugs that alter CYP3A4 and/or P-gp function. These interactions are discussed in detail separately. (See "Pharmacology of calcineurin inhibitors" and "Pharmacology of mammalian (mechanistic) target of rapamycin (mTOR) inhibitors".)

Use of a drug interaction database, such as the drug interactions program, is advised. If there are any concerns about the safety of adding a medication, the patient's transplant center team should be consulted.

Travelers' diarrhea — Diarrhea affects 10 to 60 percent of travelers to developing regions. Travelers' diarrhea may be life threatening for immunocompromised hosts [64]. Dehydration may compromise renal function and increase toxicity of immunosuppressants such as tacrolimus. Complications of diarrhea may include bacteremia and altered intestinal absorption (with concomitant alterations in the absorption of oral immunosuppressive medications).

Travelers should be counseled regarding appropriate food and water precautions [9]. In general, travelers should drink boiled or bottled beverages and avoid raw foods (except fruit and vegetables that can be peeled). (See "Travel advice".)

Travelers should carry antimicrobials such as azithromycin for self-treatment of diarrheal illness lasting more than one to two days (table 8). Potential drug interactions should be considered when starting new antibiotics. Patients with fever, vomiting, and/or bloody stools should consider seeking medical attention. Trimethoprim-sulfamethoxazole is not effective against travelers' diarrhea due to microbial resistance.

Antimotility agents may delay clearance of toxins from the gut. Bismuth subsalicylate (ie, Pepto-Bismol) is converted to salicylic acid and insoluble bismuth salts in the gastrointestinal tract; immunocompromised hosts with decreased renal function may be at higher risk for salicylate toxicity. (See "Travelers' diarrhea: Epidemiology, microbiology, clinical manifestations, and diagnosis" and "Travelers' diarrhea: Treatment and prevention".)

Malaria — Malaria is a significant risk for travelers to endemic areas. Asplenic patients should be aware of their potential increased morbidity and mortality from malaria. There is no evidence that malaria is significantly more common or severe in other immunocompromised hosts apart from HIV-infected individuals; issues related to malaria and HIV infection are discussed in detail separately [65]. (See "Prevention of malaria infection in travelers".)

Immunocompromised hosts should be instructed on ways to minimize insect bites, including use of repellents containing DEET (N,N-diethyl-3-methylbenzamide), bed nets, protective clothing, and permethrin-impregnated clothing [9]. Prophylaxis against malaria should be based on the travel itinerary; this is discussed in detail separately (table 8). (See "Prevention of malaria infection in travelers".)

Drug interactions and QT prolongation may occur in these patients with complex medication regimens; use of a drug interaction calculator is warranted.

PREVENTIVE MEASURES

Respiratory infection — Endemic fungal pulmonary infections such as histoplasmosis and coccidioidomycosis (in North America) and penicilliosis due to Penicillium marneffei infection (in Southeast Asia) could be acquired during travel [66]. Solid organ transplant (SOT) recipients are at increased risk for invasive fungal infection and should avoid activities such as spelunking and excavating, which have been associated with exposure to Cryptococcus neoformans or endemic fungi. Use of masks may be helpful.

Sun exposure — Transplant recipients have a markedly increased risk of skin cancer, which correlates with the intensity of sun exposure. It is important to recommend the use of hats, sunglasses, protective clothing (also useful for arthropod-borne infections), and sun protection lotions with ultraviolet A and B protection.

TRANSPLANT TOURISM — Transplant tourism refers to travel for the purpose of receiving or donating a transplanted organ [67]. The number of transplants for United States national waiting list candidates performed in foreign countries has been increasing [68]. Between 2001 and 2006, 373 patients were removed from United States national waiting lists due to transplants performed abroad; 89 percent were kidney transplants. Recipients received foreign transplant in 35 countries, led by China, the Philippines, and India [68]. The majority are "commercial transplants," which include payment to the donor. International transplant organizations have made efforts to decrease purchase and sale of organs on ethical grounds [69].

The extent and quality of the pretransplant evaluation of the donor and recipient may be variable and the quality of serologic evaluation may be substandard, and prophylactic measures may be incomplete [45]. Foreign-born transplant recipients who return to their country of origin for organ transplants are at risk both for reactivation of latent infections as well as acquisition of new infections [45,70-76]:

In a study comparing 540 recipients of commercial renal transplants in India with 75 recipients of living donor renal transplants in the Middle East, the incidence of both HIV infection and hepatitis B virus infection was increased (5 and 8 percent versus 0 and 1 percent, respectively) [71]

Among 115 recipients of commercial renal transplants in India, Iraq, and Iran, the posttransplant course was complicated by malaria (10 cases), invasive fungal infections (5 cases), tuberculosis (5 cases), and pneumonia due to various opportunistic pathogens [73]

When commercial transplant recipients return to transplant centers in industrialized countries, it is prudent to screen for blood-borne pathogens (including HIV, hepatitis B virus, and hepatitis C virus), as well as bacteremia, urinary tract infection, and other endemic pathogens depending on their clinical course (malaria, tuberculosis, Chagas disease, etc). Optimizing their posttransplant prophylaxis against infection and obtaining further information about their surgical procedure(s) and immunosuppression may also help optimize their care.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Travel medicine".)

SUMMARY

Immunocompromised hosts are vulnerable to infection and may have a diminished immunologic response to vaccination. Such patients planning to travel overseas should be evaluated by a travel medicine specialist familiar with the patient's immunocompromised state and medications. (See 'Introduction' above and 'Purpose of pretravel visit' above.)

Travel advice encounters provide the opportunity to review routine immunizations that may have been overlooked. These include tetanus, diphtheria, pertussis, influenza, pneumococcus, measles, mumps, rubella, hepatitis B, and varicella. (See 'Routine vaccines' above.)

Appropriate travel vaccines depend on the individual itinerary but may include typhoid, polio, meningococcus, rabies, and Japanese encephalitis. (See 'Travel vaccines' above.)

The following live vaccines are generally contraindicated in immunocompromised hosts: measles, mumps, rubella, varicella, yellow fever, and Bacille Calmette-Guérin. Immunoglobulin may provide protection against measles, mumps, rubella, varicella, hepatitis A, and rabies when vaccination is contraindicated or there is insufficient time to develop immunity. (See 'Routine vaccines' above and 'Travel vaccines' above.)

Prophylactic and preventive measures are warranted for illnesses that cannot be prevented by vaccination. These include travelers' diarrhea, malaria and other arthropod-borne illnesses, respiratory infection, sun exposure, and altitude. (See 'Antimicrobial prophylaxis' above.)

Transplant tourism (travel for the purpose of receiving or donating a transplanted organ) is increasing. When commercial transplant recipients return to transplant centers in industrialized countries, it is prudent to screen for blood-borne pathogens (including HIV, hepatitis B virus, and hepatitis C virus), as well as bacteremia, urinary tract infection, and other endemic pathogens depending on their clinical course (malaria, tuberculosis, Chagas disease, etc). (See 'Transplant tourism' above.)

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Topic 3896 Version 33.0

References

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