Author(s): Camille Kotton, Andrew Kroger, David Freedman

Immunocompromised people make up 1%–2% of patients seen in US travel clinics, and they largely pursue itineraries like those of immunocompetent travelers. Pretravel preparation for people with a suppressed immune status, whether due to a health condition, medication, or other treatment, is complex. During the pretravel consult for an immunocompromised traveler, consider additional issues (e.g., the patient’s increased risk for travel-associated infections and diseases, the effects travel can have on the patient’s underlying condition, and the patient’s response or adverse reactions to pretravel vaccines and travel medications). Key points to emphasize with immunocompromised travelers during a pretravel visit are summarized in Box 3-01.

For more information on altered immunocompetence and vaccine administration, see the Advisory Committee on Immunization Practices (ACIP) General Best Guidelines for Immunization: Altered Immunocompetence.

Pretravel Considerations

Guidance regarding travel-related prophylaxis and vaccination for immunocompromised individuals is less evidence-based than routine guidance for travelers; the recommendations included here are based on the best available data and the practices of experienced clinicians.

Causes of Immunosuppression. Clinicians should recognize that different underlying conditions and medications produce varying degrees of immunocompromise.

Consultation with Other Providers. With permission, consider consulting with the traveler’s primary or specialty care provider(s) to identify whether the underlying medical condition is stable, to discuss fitness for travel, and to verify medications and doses. Travel medicine providers also can use such a consultation to evaluate whether any travel-related disease-prevention measures could destabilize the underlying medical condition, either directly or through drug interactions.

Contraindications & Other Health Risks. Providers should assess whether the traveler’s conditions, medications, and treatments constitute contraindications to, decrease the effectiveness of, or increase the risk for adverse events from any of the disease-prevention measures recommended for the proposed trip. Depending on the destination, prevention measures might include immunizations or medications for malaria chemoprophylaxis and/or self-treatment for travelers’ diarrhea. Providers also should assess whether health hazards at the destination could exacerbate any underlying conditions or cause more severe health outcomes in an immunocompromised traveler, and determine whether specific interventions are available to mitigate these risks.

Emergency Planning. All international travelers should have plans in place in the event they become ill overseas; this is an even more critical component of pretravel preparation for immunocompromised travelers. An immunocompromised traveler should have a plan for when and how to seek care overseas, including a plan for medical evacuation, if necessary, and a plan for how to pay for it. For more details, see the chapters in Sec. 6, Ch. 1, Travel Insurance, Travel Health Insurance & Medical Evacuation Insurance, and Sec. 6, Ch. 2, Obtaining Health Care Abroad.

Immune Status & Vaccinations. The traveler’s immune status is particularly relevant to vaccinations. Overall considerations for vaccine recommendations (e.g., destination, likely risk for exposure to disease) are the same for immunocompromised travelers as for other travelers. Providers should weigh the risk for severe illness or death from a vaccine-preventable disease against potential adverse events from administering a live vaccine to an immunocompromised patient. In some cases, an immunocompromised traveler might be unable to tolerate recommended immunizations, in which case the traveler should consider changing the itinerary, altering the planned travel activities, or deferring the trip.

Approach to Immunizations

Take a careful history and consider the nature of underlying diseases when preparing anyone for international travel. Keep in mind that not all medical conditions necessitate special considerations for pretravel immunizations (see Table 3-01). Recommend and provide all appropriate travel vaccines to those with chronic health conditions. Two categories of travelers requiring special consideration with regard to immunizations are those with limited immune deficits and those with severe immune compromise. Vaccine recommendations for different categories of immunocompromised adults are listed in Table 3-02 and Table 3-03.

Preparing Travelers with Limited Immune Deficits

Asplenia

Asplenia is associated with varying degrees of immune deficit. For vaccination purposes, people with asplenia generally are not considered immunocompromised, and live vaccines are not contraindicated. People with anatomic or functional asplenia (including those with sickle cell disease or complement deficiency) and people taking eculizumab or ravulizumab (complement inhibitors used to treat paroxysmal nocturnal hemoglobinuria and atypical hemolytic uremic syndrome) are susceptible to overwhelming and rapidly progressive sepsis with certain bacterial pathogens, despite indicated immunizations.

Although response to vaccines might be diminished compared with people who have a functioning spleen, immunization against Haemophilus influenzae type b, and meningococcal (MenACWY and MenB) and pneumococcal disease, is recommended for patients with asplenia, regardless of travel plans. Because age-appropriate dosing and schedules for this population differ from competent hosts, consult the recommended immunization schedules and the guidelines in Table 3-02 and Table 3-03.

Advise asplenic travelers to seek immediate medical attention if they develop a fever and to be prepared to initiate broad-spectrum antibiotic self-treatment. Moreover, people with asplenia should consider avoiding travel to destinations lacking immediate access to high-standard medical care.

Asymptomatic HIV Infection

Asymptomatic adults with HIV and CD4+ T-lymphocyte counts of 200–499/mL are considered to have limited immune deficits and should be vaccinated according to the guidelines in Table 3-02 and Table 3-03. To categorize risk in people living with HIV, use CD4+ T-lymphocyte counts performed while the patient is receiving antiretroviral drugs, rather than nadir counts. The Advisory Committee on Immunization Practices (ACIP) recommends hepatitis A (HepA), hepatitis B (HepB), meningococcal (MenACWY), and pneumococcal vaccines for all HIV-positive patients, regardless of travel plans. Live attenuated influenza vaccine (LAIV) is contraindicated in all patients with HIV, regardless of CD4+ T-lymphocyte count. The Infectious Diseases Society of America (IDSA) has identified a knowledge gap in the optimal time to initiate vaccination after starting antiretroviral therapy. Many clinicians advise a 3-month delay after immune reconstitution (usually 6 months after initiation of antiretroviral therapy) if possible, before immunizations are administered in order to maximize the immune response to vaccination. Although seroconversion rates and geometric mean titers of antibody response to vaccines might be less than those measured in healthy controls, most vaccines can elicit protective antibody levels in HIV-infected patients in this category.

Transient increases in HIV viral load, which return quickly to baseline, have been observed after administration of several different vaccines; this generally does not occur in patients whose viral loads are well controlled on antiretroviral therapies. The clinical significance of these increases is not known, but the increases do not preclude the use of any vaccine.

Hepatitis A Vaccine

Because response to HepA vaccine might be reduced in people with HIV infection, perform postvaccination serologic testing on all people with HIV infection ≥1 month after they complete the HepA vaccine series. Consider repeating the vaccine series for patients with poor immune response (i.e., hepatitis A virus [HAV] IgG titer <10 mIU/mL), particularly those who later demonstrate improved immune status (e.g., increased CD4+ T-lymphocyte counts, decreased HIV viral load). If HAV IgG titers are still <10 mIU/mL ≥1 month after the revaccination series, additional vaccination is not recommended; instead, counsel the person on the need to receive HepA immune globulin after an exposure or for higher-risk travel.

Hepatitis B Vaccine

In a study of people infected with HIV who had no immune response to 1 or 2 courses of recombinant HepB vaccine, 2 doses of adjuvanted vaccine (Heplisav-B) were 87% effective in achieving seroprotection.

Intravenous Immunoglobulin

People with HIV might receive periodic doses of intravenous immunoglobulin (IVIG), which can interfere with the immune response to MMR and varicella vaccine. If considering vaccination with MMR or varicella vaccine, administer the vaccines ≈14 days before the next scheduled IVIG dose.

Measles-Mumps-Rubella Vaccine

Two doses of measles-mumps-rubella (MMR) vaccine are recommended for all HIV-infected individuals aged ≥12 months who do not have evidence of current severe immunosuppression (i.e., individuals aged ≤5 years must have CD4+ T-lymphocyte percentages ≥15% for ≥6 months; individuals aged >5 years must have CD4+ T-lymphocyte percentages ≥15% and CD4+ T-lymphocyte counts ≥200 lymphocytes/mL for ≥6 months). Specific recommendations are available for MMR vaccine in people living with HIV.

Chronic Diseases

Factors to consider when assessing the level of immune competence of patients with chronic diseases include clinical stability, comorbidities, complications, duration, severity, and any potentially immunosuppressing treatment (see Sec. 3, Ch. 3, Travelers with Chronic Illnesses). The pretravel health consultation is an opportunity to ensure that these individuals are vaccinated with recommended routine vaccinations (e.g., HepB and pneumococcal vaccines).

Complement Deficiencies

Patients with complement deficiencies can receive any live or inactivated vaccine.

Dysgammaglobulinemias

Many people with hypogammaglobulinemia or dysgammaglobulinemia receive periodic doses of IVIG, which can interfere with the immune response to MMR and varicella vaccine. If considering vaccination MMR or varicella vaccine, administer the vaccines ≈14 days before the next scheduled IVIG dose.

Multiple Sclerosis

Modern multiple sclerosis (MS) therapy often includes aggressive and early immunomodulatory therapy, even for patients with stable disease. Inactivated vaccines, including HepB, human papillomavirus, influenza, tetanus, and recombinant zoster vaccines generally are considered safe for people with MS. In the event of a clinical relapse, however, delay vaccination until patients have stabilized or begun to improve, typically 4–6 weeks after the relapse began. Although safety and efficacy data are lacking, inactivated vaccines are theoretically safe for people with MS being treated with interferon medication, glatiramer acetate, mitoxantrone, fingolimod, or monoclonal antibody class drugs (e.g., natalizumab, ocrelizumab, rituximab). Published studies are lacking on the safety and efficacy of other vaccines (e.g., HepA, meningococcal, pertussis, pneumococcal, polio, typhoid).

Live Vaccines

Do not administer live vaccines to people with MS during therapy with immunosuppressant drugs (e.g., azathioprine, cladribine, cyclophosphamide, methotrexate, mitoxantrone, ponesimod, teriflunomide); during chronic corticosteroid therapy; or during therapy with any immunosuppressive biologic agents, including alemtuzumab, nataluzimab, ocrelixumab, ocrelizumab, ofatumumab, ozanimod, rituximab, and siponimod. Although definitive studies of glatiramer acetate and interferon therapy are lacking, MS experts generally do not classify them as immunosuppressive medications, and their use does not preclude live vaccine administration. Published studies suggest that live viral MMR and varicella vaccines are safe for people with stable MS if administered 1 month before starting, or at the appropriate interval after discontinuing, immunosuppressive therapy (see Vaccine Considerations for Travelers with Severe Immune Compromise, later in this chapter).

Yellow Fever Vaccine

A small case series published in 2011 reported worsening of MS symptoms and plaques in 5 of 7 patients with relapsing-remitting MS who received yellow fever (YF) vaccine. In contrast, two other studies (published in 2020 and 2021) identified no exacerbations among 55 people with MS who received YF vaccine at different stages of their disease and who were taking a wide variety of medications. Before administering YF vaccine to people with MS who are receiving disease-modifying therapy or nataluzimab, consider the risk of YF virus infection at the destination, as well as potential vaccine-associated risks. Because the effects of YF vaccination in patients receiving disease-modifying therapy or nataluzimab have not been fully studied, decisions about YF vaccination should be made in consultation with the patient’s neurologist. For brief exposures (e.g., only a few days in a YF endemic area) vaccinating travelers with MS against YF likely should be avoided. Weigh the risks and benefits of vaccination for travelers anticipating more prolonged exposures.

Preparing Travelers with Severe Immune Compromise

Severely Immunocompromising Conditions

Severely immunocompromised people include those with aplastic anemia, graft-versus-host disease, symptomatic HIV/AIDS, some congenital immunodeficiencies, active leukemia or lymphoma, or generalized malignancy. Others with severe immune compromise include people who recently received radiation therapy or checkpoint inhibitor treatment (therapy of autoimmune complications of treatment is immunosuppressive); people receiving active immunosuppression for solid organ transplants; and both chimeric antigen receptor (CAR)-T cell and hematopoietic stem cell transplant (HSCT) recipients (≤2 years of transplantation or still taking immunosuppressive drugs).

In most cases, severely immunocompromised people should not receive live vaccines, and inactivated vaccines will likely be less effective. These patients should consider postponing travel until their immune function improves. For people likely to travel in the future, usual travel-related vaccines can be initiated before beginning immunosuppressive therapies, if feasible. Whenever possible, administer inactivated vaccines ≥2 weeks and live vaccines ≥4 weeks before immunosuppression.

Symptomatic HIV/AIDS

Clinicians need to know an HIV-infected traveler’s current CD4+ T-lymphocyte count for the pretravel consultation. People with HIV and CD4+ T-lymphocyte counts <200/mL, a history of an AIDS-defining illness without immune reconstitution, or clinical manifestations of symptomatic HIV are considered to have severe immunosuppression (see Sec. 5, Part 2, Ch. 11, Human Immunodeficiency Virus / HIV), and they should not receive live viral or live bacterial vaccines because of the risk that the vaccine could cause serious systemic disease. For MMR vaccine, severe immunosuppression is defined as CD4+ T-lymphocyte percentages <15% in any age group or CD4+ T-lymphocyte counts <200/mL in people >5 years old.

Recommend that newly diagnosed, treatment-naïve patients with CD4+ T-lymphocyte counts <200/mL delay travel pending reconstitution of CD4+ T-lymphocyte counts with antiretroviral therapy and, ideally, complete suppression of detectable viral replication. Delaying travel helps minimize the risk for infection and avoid immune reconstitution illness while away.

Chronic Lymphocytic Leukemia & Hematopoietic Stem Cell Transplant

People with chronic lymphocytic leukemia have poor humoral immunity, even early in the disease course, and rarely respond to vaccines. Hematopoietic stem cell transplant (HSCT) recipients who received vaccines before their transplant should be revaccinated routinely afterward, regardless of the source of the transplanted stem cells. Begin complete revaccination with standard childhood vaccines 6 months after HSCT, with the caveat that MMR and varicella vaccines should be administered 24 months after transplant and only if the recipient is immunocompetent. Thus, HSCT recipients ideally should delay travel ≥2 years after transplant to allow for full revaccination.

Administer inactivated influenza vaccine beginning ≥6 months after HSCT and annually thereafter. A dose of inactivated influenza vaccine can be given ≥4 months after transplant if there is a community outbreak.

Solid Organ Transplant Recipients

For solid organ transplant recipients, the risk for infection is greatest in the first year after transplant; recommend to travelers that they should postpone trips to high-risk destinations until after that time.

Medications that Compromise the Immune System

A variety of medications and biologic agents compromise the immune system. Regard anyone taking these medications as severely immunocompromised. Doses of inactivated vaccines received while receiving immunosuppressive medications or during the 2 weeks before starting such medications should not be counted toward a primary vaccination series or relied upon to induce adequate immune responses. Patients should be revaccinated with all indicated inactivated vaccines at least 3 months after potent immunosuppressive therapy is discontinued.

Alkylating Agents

Regard anyone taking alkylating agents (e.g., cyclophosphamide) as severely immunocompromised.

Antimetabolites

Regard anyone taking antimetabolites (e.g., 6-mercaptopurine, azathioprine, methotrexate) as severely immunocompromised.

Biologic Agents

Immunosuppressive or immunomodulatory biologic agents can produce immunocompromise by the mechanisms outlined in Table 3-04. B cell–depleting agents (cladribine, ocrelizumab, ofatumumab, ozanimod, rituximab, siponimod) and lymphocyte-depleting agents (alemtuzumab, thymoglobulin) induce major immunosuppression. Consideration of the clinical context in which these were given is important, especially in hematologic malignancies.

Cancer Chemotherapeutic Agents

Cancer chemotherapeutic agents are classified as severely immunosuppressive, as demonstrated by increased rates of opportunistic infections and blunting of responses to certain vaccines among patient groups. Some of these agents are less immunosuppressive than others (e.g., tamoxifen and trastuzumab, given to breast cancer patients, are less immunosuppressive than alkylating agents or antimetabolites), but clinical data to support safety with live vaccines are lacking. Vaccination following immunotherapies (e.g., checkpoint inhibitors, CAR-T cell treatments) has not been well studied, and until additional data are available, avoid vaccinating patients receiving these treatments with live attenuated vaccines for 3–6 months after treatment or until they have had immune reconstitution.

High-Dose Corticosteroids

Most clinicians consider a dose of >2 mg/kg of body weight or ≥20 mg per day of prednisone (or its equivalent) in people who weigh >10 kg, when administered for ≥2 weeks, as sufficiently immunosuppressive to raise concern about the safety of vaccination with live vaccines. Furthermore, the immune response to vaccines could be impaired. Clinicians should wait ≥1 month after discontinuation of high-dose systemic corticosteroid therapy before administering a live-virus vaccine.

Transplant-Related Immunosuppressive Drugs

Regard anyone receiving transplant-related immunosuppressive drugs as severely immunocompromised. Examples of transplant-related immunosuppressive drugs include azathioprine, belatacept, cyclosporine, everolimus, mycophenolate mofetil, prednisone, sirolimus, and tacrolimus.

Tumor Necrosis Factor Blockers

Tumor necrosis factor (TNF) blockers (e.g., adalimumab, certolizumab pegol, etanercept, golimumab, infliximab) blunt the immune response to certain chronic infections and certain vaccines. When used alone or in combination regimens with other disease-modifying agents to treat rheumatoid disease, TNF blockers are associated with an impaired response to HepA, influenza, and pneumococcal vaccines, suggesting that for better protection, all doses in the HepA and pneumococcal series should be given before travel. The use of live vaccines is contraindicated for most people receiving these therapies.

Vaccine Considerations for Travelers with Severe Immune Compromise

Inform severely immunocompromised people that their response to vaccination might be muted. The immunosuppressive regimen does not predict the decrease in response to vaccination. No basis exists for interpreting laboratory studies of general immune parameters to predict vaccine safety or efficacy. Recent data in solid organ transplant recipients vaccinated before transplant suggest that a prolonged phase of protective antibody titers can exist after transplant. In general, serologic testing for response to most travel-related vaccines is not clinically recommended.

The length of time clinicians should wait after discontinuation of immunosuppressive therapies before administering a live vaccine is not uniform and depends on the therapy. For cancer chemotherapy, radiation therapy, and highly immunosuppressive medications (exclusive of lymphocyte-depleting agents and organ transplant immunosuppression), the waiting period is 3 months. For lymphocyte-depleting agents (alemtuzumab, rituximab), the waiting period is ≥6 months, although IDSA guidelines suggest that the waiting period should be ≥1 year. For immunosuppressive corticosteroid regimens, the waiting period is 1 month. Restarting immunosuppression after live vaccination has not been studied, but some experts would recommend waiting ≥1 month. Special considerations for travelers with severe immune compromise apply for several travel-related vaccines.

Cholera

The safety and effectiveness of the oral live attenuated bacterial cholera vaccine, Vaxchora, has not been established in immunocompromised people. An older formulation of CVD 103-HgR vaccine was not associated with serious or systemic adverse events in patients with HIV, although the data are limited.

Ebola

Safety and efficacy of Ebola Zaire live recombinant vaccine (ERVEBO, rVSV-ZEBOV vaccine [Merck Sharp & Dohme Corp.]) has not been adequately assessed in immunocompromised adults. A small number of adults living with HIV have been vaccinated with ERVEBO, and additional studies are ongoing to investigate its use in people living with HIV without severe immune compromise. The risk from vaccination with ERVEBO in immunocompromised people should be weighed against the risk for Ebola virus disease.

Hepatitis A

Data indicate that immunocompromised people, notably those being treated with immunosuppressive drugs, can have inadequate or slow seroconversion after a single dose of HepA vaccine. Limited data also suggest that modified dosing regimens, including a doubling of the standard antigen dose or administration of additional doses prior to travel, might increase response rates.

Solid organ transplant candidates who are unvaccinated, undervaccinated, or seronegative for HepA should receive a 2-dose HepA vaccine series. People with immunocompromising conditions should start a 2-dose HepA vaccine series as soon as travel is considered. Immunocompromised people traveling in <2 weeks should simultaneously receive the initial dose of HepA vaccine and HepA immune globulin (IG); administer the vaccine and the IG in separate limbs. Testing for the presence of HAV antibody after vaccination is recommended for immunocompromised people whose subsequent clinical management depends on knowledge of their immune status and people for whom revaccination might be indicated. Because response to HepA vaccine might be reduced in people with HIV infection, perform postvaccination serologic testing on all people with HIV infection ≥1 month after they complete the HepA vaccine series.

Hepatitis B

The humoral immune response to HepB vaccine is reduced in immunocompromised children and adults. Limited data indicate that modified dosing regimens could increase response rates. As with dialysis patients, use a 3-dose series of 40 µg Recombivax HB at 0, 1, and 6 months, or a 4-dose series of 40 µg Engerix-B at 0, 1, 2, and 6 months. Heplisav-B (HepB-CpG) is an adjuvanted vaccine and is administered as 2 doses, 1 month apart, in people ≥18 years old. Postvaccination serologic testing after any HepB vaccination series is recommended to confirm response and guide the need for revaccination in immunocompromised people.

Japanese Encephalitis

Although recommended for numerous destinations (see Sec. 5, Part 2, Ch. 13, Japanese Encephalitis), no data are available on the safety or efficacy of Japanese encephalitis (JE) vaccines in immunocompromised patients. JE vaccine should be given to at-risk travelers. As with other vaccines, immunocompromised patients likely will have decreased intensity and durability of protection, and more frequent booster doses might be indicated.

Rabies

Immunocompromised people deemed at risk for vaccine-preventable rabies should receive a 3-dose series of vaccine on days 0, 7, and 21 or 28, but not the 2-dose series (day 0 and day 7) recommended in 2021 for immunocompetent people. Furthermore, administer the vaccine as an intramuscular injection, not as an intradermal injection as recommended by some authorities outside the United States. Serologic postvaccination testing might be indicated. For postexposure rabies prophylaxis, all severely immunocompromised people should generally receive rabies vaccine at days 0, 3, 7, 14, and 28, plus human rabies immune globulin, regardless of previous vaccination history.

Smallpox / Monkeypox

JYNNEOS (Imvamune, Imvanex) is an approved by the US Food and Drug Administration (FDA) vaccine for prevention of smallpox and monkeypox, but it is not commercially available. JYNNEOS is a live, attenuated, nonreplicating, virus-derived vaccine that is indicated for first responders participating in smallpox or monkeypox outbreaks. Unlike the live, replication-competent smallpox vaccine (ACAM2000), JYNNEOS is not contraindicated for use in immunocompromised people and should be safe. Immunocompromised people might, however, have a diminished immune response to the vaccine.

Tick-Borne Encephalitis

Immunocompromised people might have a diminished immune response to killed tick-borne encephalitis vaccine, which is FDA-approved and safe for this population.

Typhoid Fever

CDC recommends administering injectable Vi capsular polysaccharide vaccine (Typhim Vi, ViCPS) rather than live, oral Salmonella typhi vaccine Ty21A (Vivotif) for at-risk, immunocompromised patients. Data on the safety and efficacy of typhoid vaccines in immunocompromised patients are lacking.

Yellow Fever

Contraindications

In general, strongly discourage unvaccinated travelers with severe immune compromise from traveling to destinations where infection with YF virus is a risk. Severe immunosuppression is a contraindication to YF vaccination because these patients are at increased risk of developing a serious adverse event (e.g., life-threatening YF vaccine–associated viscerotropic disease, YF vaccine–associated neurologic disease). Additionally, YF vaccination is contraindicated in people with a history of a thymus disorder associated with abnormal immune cell function (e.g., myasthenia gravis or thymoma); this contraindication applies regardless of whether the person has undergone therapeutic thymectomy (see Sec. 5, Part 2, Ch. 26, Yellow Fever). No data are available to support IgA deficiency as a contraindication to YF vaccination.

If patients are unable to avoid travel to areas where YF vaccination is recommended (see Maps 5-10 and 5-11) and the immunocompromised traveler is previously unvaccinated, inform them of YF risk, carefully instruct them in methods to avoid mosquito bites, and provide them with a vaccination medical waiver in their International Certificate of Vaccination or Prophylaxis (see 

International Certificate of Vaccination or Prophylaxis, and Sec. 5, Part 2, Ch. 26, Yellow Fever). Travelers falling into this category might choose to travel during periods of lower disease activity. Warn travelers that some countries with YF vaccine entry requirements might not honor YF vaccination waiver documents and that the traveler might be refused entry or quarantined.

Precautions (Relative Contraindications)

ACIP considers certain conditions with limited immune deficits (e.g., asymptomatic HIV infection) to be precautions (as opposed to contraindications) to administration of YF vaccine. For these patients, offer YF vaccine if travel to YF-endemic areas is unavoidable, and monitor vaccine recipients closely for possible adverse effects. If country entry requirements, and not true exposure risk, are the only reasons to vaccinate a traveler with asymptomatic HIV infection or a limited immune deficit, the physician should provide a waiver (see /travel/page/icvp, and Sec. 5, Part 2, Ch. 26, Yellow Fever). Studies show that higher CD4+ T-lymphocyte counts and suppressed HIV viral loads seem to be the key determinants for developing protective neutralizing antibodies after YF vaccination. Patients with undetectable viral loads respond well to YF vaccination regardless of CD4+ T-lymphocyte counts, although data are limited in those with CD4+ T-lymphocyte counts <200/mL. Because vaccine response might be suboptimal, such vaccinees are candidates for serologic testing 1 month after vaccination. For information about serologic testing, contact the state health department or CDC’s Division of Vector-Borne Diseases at 970-221-6400. Current data from clinical and epidemiologic studies are insufficient to evaluate the actual risk for severe adverse effects associated with YF vaccine among recipients with limited immune deficits.

Booster Doses

Because a single dose of YF vaccine provides long-lasting protection, ACIP no longer recommends booster doses for most travelers. Additional doses of YF vaccine are recommended, however, for some people who might not have as robust or sustained immune response to YF vaccine.

People who received HSCT after receiving a dose of YF vaccine and who are sufficiently immunocompetent to be safely vaccinated should be revaccinated if travel puts them at risk for YF. People infected with HIV when they received their last dose of YF vaccine should receive a dose every 10 years if they continue to be at risk for YF and if their current CD4+ T-lymphocyte counts do not indicate precautions or contradictions. Recent data suggest that YF vaccination before solid organ transplant, even long before transplant, generally provides protective antibody levels after transplant.

Zoster

Although no extra pretravel indication exists, many travel clinics administer zoster vaccines. In 2021, the FDA approved the use of recombinant zoster vaccine (RZV), now the only available preparation in the United States, for all immunocompromised people ≥18 years of age.

ACIP recommends 2 doses of recombinant zoster vaccine for all adults ≥19 years old who are or who will be immunodeficient or immunosuppressed due to disease or therapy, regardless of travel plans. Qualifying underlying conditions include, but are not limited to, HSCT or solid organ transplant recipients, hematologic and or generalized cancer, HIV, and people receiving immunosuppressive therapy.

Household Contacts

Routine Vaccines

Three live vaccines (MMR, rotavirus, and varicella) should be administered to susceptible household contacts and other close contacts of immunocompromised patients when indicated. If a varicella vaccine recipient has a rash after vaccination, direct contact with susceptible household contacts with altered immunocompetence should be avoided until the rash resolves. Educate immunocompromised patients about the risk for fecal–oral transmission of poliovirus in countries where the oral polio vaccine is used, since there have been reports of reversion to wild type virus with associated clinical disease.

For influenza vaccination, choose inactive influenza vaccine (IIV); household and other close contacts of mildly or moderately immunocompromised patients can safely receive LAIV if they are unable to receive IIV. LAIV is contraindicated in close contacts and caregivers of severely immunocompromised people who require a protected environment.

Smallpox / Monkeypox Vaccine

ACAM2000 is a live, replicating smallpox vaccine, indicated for use in military personnel and laboratory workers with potential exposure to the virus. Recipients of the vaccine can transmit the virus to household and intimate contacts; therefore, vaccinated family or household members should implement infection control measures, particularly those with immunocompromise. JYNNEOS is an FDA-approved but not commercially available live nonreplicating smallpox/monkeypox vaccine that would not be contraindicated in immunocompromised individuals or their contacts.

Yellow Fever Vaccine

Yellow fever vaccine can be administered to household contacts when indicated.

Malaria Prophylaxis & Treatment

Malaria infection and the drugs used to treat it can exacerbate an immunocompromised traveler’s underlying condition. Moreover, asplenia, HIV, and some immunosuppressive regimens can predispose travelers to more serious malaria infection. For these reasons, stress the need for malaria prophylaxis and strict adherence to mosquito bite avoidance to immunocompromised travelers to malaria-endemic areas (see Sec. 2, Ch. 5, Yellow Fever Vaccine & Malaria Prevention Information, by Country; Sec. 4, Ch. 6, Mosquitoes, Ticks & Other Arthropods; and Sec. 5, Part 3, Ch. 16, Malaria).

People Infected with HIV

Malaria is more severe in people infected with HIV; malaria infection increases HIV viral load and could exacerbate disease progression. In addition, take extra care when researching potential drug interactions in people with HIV who are receiving antiretroviral therapy. The University of Liverpool offers an interactive web-based resource for assessing possible drug interactions (mobile application also is available).

Chemoprophylaxis

Some older maintenance regimens for HIV have been noted to interact with drugs used for malaria chemoprophylaxis. Notably, chloroquine, mefloquine, and primaquine can interact with older maintenance regimens for HIV, particularly those containing protease inhibitors (PIs). Efavirenz lowers serum levels of both atovaquone and proguanil, but no evidence suggests clinical failure of these agents when used concurrently. Efavirenz also potentially can increase the production of hemotoxic primaquine metabolites.

Most current first-line regimens for HIV (integrase and entry inhibitors) have few drug interactions. Commonly used integrase inhibitors (bicetegravir, cabotegravir, dolutegravir, elvitegravir, raltegravir), and nucleoside/nucleotide reverse transcriptase inhibitor (NRTI) combinations (brand names include Descovy-Tivicay, Truvada-Tivicay) have no known interactions with CDC-recommended malaria chemoprophylactic drugs; the cobicistat booster co-formulated with elvitegravir (Stribild, Genvoya) theoretically could increase mefloquine levels. The emtricitabine, rilpivirine, tenofovir alafenamide (TAF)/tenofovir disoproxil fumarate (TDF) combinations (Odefsey and Complera) similarly have no interactions with antimalarial drugs.

Treatment

Malaria treatment regimens, including artemisinin derivatives, quinine/quinidine, lumefantrine (part of the artemether/lumefantrine combination, Coartem), and atovaquone and proguanil potentially could have interactions with many non-nucleoside reverse transcriptase inhibitors (NNRTIs), PIs, and the CCR5 receptor antagonist, maraviroc. Seek advice from CDC or other malaria experts when treating patients for malaria who are also on antiretrovirals.

Organ Transplant Recipients

In organ transplant recipients, atovaquone-proguanil might be the most appropriate malaria prophylactic agent because other antimalarials can interact with calcineurin inhibitors and mTor inhibitors (cyclosporine, everolimus, sirolimus, tacrolimus). Chloroquine, doxycycline mefloquine, and primaquine can elevate calcineurin inhibitor levels. Chloroquine and mefloquine can interact with calcineurin inhibitors to prolong the QT interval. Some travel-related medications need to be dose-adjusted according to altered hepatic or renal function.

Enteric Infections

Many foodborne and waterborne infections (e.g., those caused by Campylobacter, Cryptosporidium, Giardia, Listeria, Salmonella, or Shigella) can be severe or become chronic in immunocompromised people. Provide all travelers with instruction on safe food and beverage precautions; travelers’ diarrhea can occur despite strict adherence. Meticulous hand hygiene, including frequent and thorough handwashing with soap and water, is the best prevention against gastroenteritis. Travelers should wash hands after contact with public surfaces, after any contact with animals or their living areas, and before preparing or eating food.

Travelers’ Diarrhea

Selecting antimicrobial drugs for appropriate self-treatment of travelers’ diarrhea (see Sec. 2, Ch. 6, Travelers’ Diarrhea) requires special consideration of potential drug interactions in patients already taking medications for chronic medical conditions. Fluoroquinolones, rifaximin, and rifamycin SV are active against several enteric bacterial pathogens and are not known to have major interactions with highly active antiretroviral therapy (HAART) drugs. Macrolide antibiotics can, however, interact with HAART drugs. Fluoroquinolones and azithromycin are generally well tolerated in combination with calcineurin inhibitors and mTor inhibitors, but in rare instances increase a prolonged QT interval (caution in those >500 ms).

Waterborne Diseases

To reduce the risk for cryptosporidiosis, giardiasis, and other waterborne infections, immunocompromised travelers should avoid swallowing water during swimming and other water-based recreational activities and should not swim in water that might be contaminated with sewage or animal waste. Travelers with liver disease should consider avoiding direct exposure to salt water because of the risk for Vibrio spp. exposure, and all immunocompromised people should avoid raw seafood. Patients and clinicians should be aware of the risk for infection or colonization with multidrug-resistant organisms during travel; remind immunosuppressed travelers who become ill to report recent travel to their doctors.

Reducing Risk for Other Diseases

Geographically focal infections that pose an increased risk for severe outcomes for immunocompromised people include visceral leishmaniasis (see Sec. 5, Part 3, Ch. 15, Visceral Leishmaniasis) and inhaled fungal infections such as Talaromyces marneffei (formerly Penicillium marneffei) in Southeast Asia, and coccidioidomycosis (see Sec. 5. Part 4, Ch. 1, Coccidioidomycosis / Valley Fever) and histoplasmosis (see Sec. 5, Part 4, Ch. 2, Histoplasmosis) in the Americas.

Coronavirus Disease 2019

People with immunocompromising conditions or who are on immunosuppressive therapy are at increased risk for severe illness, hospitalization, and death if infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID-19). Moreover, moderately or severely immunocompromised people might routinely shed infectious virus for ≤20 days (see Sec. 5, Part 2, Ch. 3, COVID-19).

Counsel moderately and severely immunocompromised people to be up to date with their COVID-19 vaccinations before travel. Because people who are immunocompromised might have a less robust immune response to COVID-19 vaccines, even those whose vaccinations are up to date should maintain awareness of the COVID-19 situation at their destination. In the pretravel consultation, discuss the possible options of reconsidering travel or delaying travel to destinations where COVID-19 transmission is currently high and risk for infection is greater.

CDC also provides COVID-19 cruise ship information. SARS-CoV-2 spreads easily on cruise ships; outbreaks can overwhelm onboard medical capacity, and ship-to-shore medical evacuations can be challenging (see Sec. 8, Ch. 6, Cruise Ship Travel).

In addition to helping ensure that moderately and severely immunocompromised travelers are up to date with their COVID-19 vaccinations, provide information on the importance of taking protective measures (e.g., wearing a well-fitting mask or respirator while in public indoor spaces, avoiding spending time in poorly ventilated indoor locations). Suggest to immunocompromised travelers that they also consider wearing a well-fitting mask or respirator when outdoors during sustained close contact with others. Advise close contacts (e.g., household members, caregivers) of immunocompromised people to adhere to the same precautions. See the latest guidance and recommendations regarding COVID-19 vaccinations, boosters, and therapeutic options.

Tuberculosis

Establishing the tuberculosis status of immunocompromised travelers going to regions endemic for tuberculosis can be helpful in the evaluation of subsequent illness (see Sec. 5, Part 1, Ch. 23, . . . perspectives: Testing Travelers for Mycobacterium tuberculosis Infection). Depending on the traveler’s degree of immune suppression, the baseline tuberculosis status might be assessed by a tuberculin skin test, Mycobacterium tuberculosis antigen–specific interferon-γ assay (i.e., QuantiFERON-TB Gold or T-SPOT TB, both generally more sensitive in immunocompromised patients than skin testing), or chest radiograph. The need for posttravel testing (often 3 months after travel) depends on exposure risk during the trip, medical conditions, and other factors.

People with HIV and transplant recipients might require primary or secondary prophylaxis for opportunistic infections (e.g., Mycobacterium, Pneumocystis, and Toxoplasma spp.). Adherence to all indicated prophylactic regimens should be confirmed before travel.