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Chapter 8Advising Travelers With Specific Needs

Immunocompromised Travelers

Camille Nelson Kotton, David O. Freedman

APPROACH TO THE IMMUNOCOMPROMISED TRAVELER

The pre-travel preparation of travelers with immune suppression due to any medical condition, drug, or treatment must address several categories of concern:

  • Is the traveler’s underlying medical condition stable? The travel health provider may need to contact the traveler’s primary and specialty care providers (with the patient’s permission) to discuss the traveler’s fitness to travel, give specific medical advice for the proposed itinerary, and verify the drugs and doses composing the usual maintenance regimen.
  • Do the conditions, medications, and treatments of the traveler constitute contraindications to, decrease the effectiveness of, or increase the toxicity of any of the disease-prevention measures recommended for the proposed trip? Depending on the destination, these measures include, but are not limited to, immunizations and drugs used for malaria chemoprophylaxis and management of travelers’ diarrhea.
  • Could any of the disease-prevention measures recommended for the proposed trip destabilize the underlying medical condition, directly or through drug interactions?
  • Are there specific health hazards at the destination that would exacerbate the underlying condition or be more severe in an immunocompromised traveler? If so, can specific interventions be recommended to mitigate these risks?

The traveler’s immune status is particularly relevant to immunizations. Overall considerations for vaccine recommendations, such as destination and the likely risk of exposure to disease, are the same for immunocompromised travelers as for other travelers. The risk of a severe outcome from a vaccine-preventable disease must be weighed against potential adverse events from administering a live vaccine to an immunocompromised patient. In some complex cases when travelers cannot tolerate recommended immunizations or prophylaxis, the traveler should consider changing the itinerary, altering the activities planned during travel, or deferring the trip.

For purposes of clinical assessment and approach to immunizations, immunocompromised travelers fall into 1 of 4 groups, based on mechanism and level of immune suppression. Vaccine recommendations for different categories of immunocompromised adults are shown in Table 8-01.

Table 8-01. Immunization of immunocompromised adults

  HIV
INFEC-
TION, CD4 CELLS ≥200/
mm3
SEVERE IMMUNO-
SUPPRES-
SION
(HIV/
AIDS) CD4 CELLS <200/
mm3
SEVERE IMMUNO-
SUPPRES-
SION
(NOT HIV-
RELATED)
ASPLENIA RENAL FAILURE CHRONIC LIVER DISEASE, DIABETES
Live Vaccines
Bacillus Calmette
Guérin (BCG)
X X X U U U
Influenza, live attenuated (LAIV) X X X U X X
Measles-mumps-rubella (MMR) R1 X1 X1 U U U
Typhoid, Ty21a X X X U U U
Varicella (adults)2 U X X U U U
Yellow Fever3 P3 X3 X U W W
Zoster C4 X4 X U U U
Inactivated Vaccines
Haemoph-
ilus
influenzae
type b (Hib)
C5 C5 R R U U
Hepatitis A6 U U U U U U
Hepatitis B6 U7 U7 U7 U7 R8 U7
Influenza
(inacti-
vated)
R R R R R R
Japanese
encepha-
litis9
U U U U U U
Meningo-
coccal
conjugate
C10 C10 U R10 U U
PCV13 followed by PPSV2311 R R R R R C
Polio (IPV) U U U U U U
Rabies U U U U U U
Td or Tdap R R R R R R
Typhoid, Vi U U U U U U

Abbreviations: X, Contraindicated (per the Advisory Committee on Immunization Practices [ACIP]); U, Use as indicated for normal hosts; R, Recommended for all in this patient category; P, Precaution (per ACIP); W, Warning—medical conditions for which no data regarding YF vaccine exist but for which varying degrees of immune deficit might be present and could increase the risk of serious adverse events following vaccination; providers should carefully weigh vaccine risks and benefits before deciding to vaccinate such patients; C, Consider; PCV13, 13-valent pneumococcal conjugate vaccine; PPSV23, 23-valent pneumococcal polysaccharide vaccine.
1MMR vaccination should be considered for all symptomatic HIV-infected patients with CD4 counts ≥200/mm3 without evidence of measles immunity. Immune globulin may be administered for short-term protection of those facing high risk of measles and for whom MMR vaccine is contraindicated.
2Varicella vaccine should not be administered to people who have cellular immunodeficiencies, but people with impaired humoral immunity (including congenital or acquired hypoglobulinemia or dysglobulinemia) may be vaccinated. Immunocompromised hosts should receive 2 doses of vaccine spaced at 3-month intervals.
3See details in Chapter 3, Yellow Fever. YF vaccination is a precaution for asymptomatic HIV-infected people with CD4 cell counts of 200–499/mm3. YF vaccination is not a precaution for people with asymptomatic HIV infection and CD4 cell counts ≥500. YF vaccine is also considered contraindicated by ACIP for symptomatic HIV patients without AIDS and with CD4 counts ≥200/mm3.
4Also contraindicated by ACIP for symptomatic HIV patients without AIDS and with CD4 counts ≥200/mm3.
5Decision should be based on consideration of the individual patient’s risk of Hib disease and the effectiveness of the vaccine for that person. In some settings, the incidence of Hib disease may be higher among HIV-infected adults than among HIV-uninfected adults, and the disease can be severe in these patients.
6Routinely indicated for all men who have sex with men, people with multiple sexual partners, hemophiliacs, patients with chronic hepatitis, and injection drug users.
7Test for antibodies to hepatitis B virus surface antigen serum titer after vaccination, and revaccinate if initial antibody response is absent or suboptimal (<10 mIU/mL). HIV-infected nonresponders may react to a subsequent vaccine course if CD4 cell counts rise to 500/mm3 after institution of highly active antiretroviral therapy. See text for discussion of other immunocompromised groups.
8Use special double-dose vaccine formulation. Test for antibodies to hepatitis B virus surface antigen after vaccination and revaccinate if initial antibody response is absent or suboptimal (<10 mIU/mL).
9As with most inactivated vaccines, no safety or efficacy data exist regarding the use of Ixiaro in immunocompromised people. Immunocompromised people may have a diminished immune response to Ixiaro.
10Two doses ≥2 months apart for asplenic and HIV-infected patients.
11Previously unimmunized asplenic, HIV-infected, or immunocompromised adults aged ≥19 years should receive 1 dose of 13-valent pneumococcal conjugate vaccine (PCV13) followed by 1 dose of pneumococcal polysaccharide vaccine (PPSV23) ≥8 weeks later. People with these conditions previously immunized with PPSV23 should follow catch-up guidelines per ACIP.

 

MEDICAL CONDITIONS WITHOUT SIGNIFICANT IMMUNOLOGIC COMPROMISE

With regard to travel immunizations, travelers whose health status places them in one of the following groups are not considered significantly immunocompromised and should be prepared as any other traveler, although the nature of the previous or underlying disease needs to be kept in mind.

  1. Travelers receiving corticosteroid therapy under any of the following circumstances:
    • Short- or long-term daily or alternate-day therapy with <20 mg of prednisone or equivalent.
    • Long-term, alternate-day treatment with short-acting preparations.
    • Maintenance physiologic doses (replacement therapy).
    • Steroid inhalers.
    • Topical steroids (skin, ears, or eyes).
    • Intraarticular, bursal, or tendon injection of steroids.
    • If >1 month has passed since high-dose steroids (≥20 mg per day of prednisone or equivalent for >2 weeks) have been used. However, after short-term (<2 weeks) therapy with daily or alternate-day dosing of ≥20 mg of prednisone or equivalent, some experts will wait 2 weeks before administering measles vaccine.
  2. HIV patients with >500/mm3 CD4 T lymphocytes.
  3. Travelers with a history of cancer who received their last chemotherapy treatment ≥3 months previously and whose malignancy is in remission.
  4. Bone marrow transplant recipients who are >2 years posttransplant, not on immunosuppressive drugs, and without graft-versus-host disease.
  5. Travelers with autoimmune disease (such as systemic lupus erythematosus, inflammatory bowel disease, or rheumatoid arthritis) who are not being treated with immunosuppressive or immunomodulatory drugs, although definitive data are lacking.
  6. Travelers with multiple sclerosis (MS) who are not on immunosuppressive or immunomodulatory agents and those who are not experiencing an exacerbation of disease. Although the risks of using live-virus vaccines for those with MS have been debated, the National MS Society and CDC recommend following CDC guidelines for vaccination in those who lack prior immunity, who are not on immunosuppressive or immunomodulatory agents, and who are not experiencing an exacerbation of disease.

MEDICAL CONDITIONS AND TREATMENTS ASSOCIATED WITH LIMITED IMMUNE DEFICITS

Asymptomatic HIV Infection

Asymptomatic HIV-infected adults with CD4 cell counts of 200–500/mm3 are considered to have limited immune deficits. CD4 counts increased by antiretroviral drugs, rather than nadir counts, should be used to categorize HIV-infected people. The exact time at which reconstituted lymphocytes are fully functional is not well defined. To achieve a maximal vaccine response with minimal risk, many clinicians advise a delay of 3 months after reconstitution, if possible, before immunizations are administered. Although seroconversion rates and geometric mean titers of antibody in response to vaccines may be less than those measured in healthy controls, most vaccines can elicit seroprotective levels of antibody in most 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 to HIV-infected people. The clinical significance of these increases is not known, but they do not preclude the use of any vaccine.

The combination measles, mumps, rubella, and varicella (MMRV) vaccine is contraindicated in anyone with HIV.

Multiple Sclerosis

Inactivated vaccines are generally considered safe for people with MS, although vaccination should be delayed during clinically significant relapses until patients have stabilized or begun to improve from the relapse, typically 4–6 weeks after it began. Administration of tetanus, hepatitis B, or influenza vaccines does not appear to increase the short-term risk of relapses in people with MS. However, published studies are lacking on the safety and efficacy of other vaccines (such as those against hepatitis A, human papilloma virus, meningitis, pertussis, pneumonia, polio, and typhoid). Inactivated vaccines are theoretically safe for people being treated with an interferon medication, glatiramer acetate, mitoxantrone, fingolimod, or natalizumab, although efficacy data are lacking.

A few published studies suggest that measles, rubella, varicella, and zoster vaccines may be safe in people with stable MS if administered 1 month before starting or 1 month after discontinuing immunosuppressive therapy. Modern MS therapy includes aggressive and early immunomodulatory therapy for almost all MS patients, even those with stable disease. Live-virus vaccines should not be given to people with MS during therapy with immunosuppressants, such as mitoxantrone, azathioprine, methotrexate, or cyclophosphamide; during chronic corticosteroid therapy; or during therapy with the agents listed in Table 8-02. However, patients on glatiramer acetate and interferons have more limited immune deficits. Yellow fever vaccine and smallpox vaccine have not been well studied in people with MS and should only be given if there is a compelling reason to do so (such as unavoidable direct exposure and the risks of potential adverse events are carefully weighed against the likelihood of exposure to these potentially fatal illnesses); these decisions should be made in consultation with the patient’s neurologist.

Other Chronic Conditions

Chronic medical conditions that may be associated with varying degrees of immune deficit include asplenia, chronic renal disease, chronic liver disease (including hepatitis C), diabetes mellitus, and complement deficiencies. Because no information is available regarding possible increased adverse events or decreased vaccine efficacy following administration of live, attenuated viral or bacterial antigen vaccines to patients with these diseases, caution should be used when considering the administration of live vaccines to such patients. Factors to consider in assessing the general level of immune competence of these patients include disease severity, duration, clinical stability, complications, and comorbidities (see the next section in this chapter, Travelers with Chronic Illnesses).

A blunted response to hepatitis B vaccine has been reported in patients with chronic liver disease; a decreased response to hepatitis B vaccine has also been observed in patients with diabetes. Additional doses of hepatitis B vaccine beyond the primary 3-dose series may be necessary. Double-dose hepatitis B vaccine preparations are used to promote optimal immunization of people with chronic renal failure and other patients with absent or suboptimal response to standard hepatitis B vaccine doses. Adjuvanted hepatitis B candidate vaccines undergoing clinical trials appear to be more effective for immunization of liver transplant patients and patients with renal insufficiency.

Asplenic patients are susceptible to overwhelming sepsis with encapsulated bacterial pathogens. Although response to vaccines may be less than in people with a functioning spleen, many clinical guidelines recommend immunization against meningococcal, pneumococcal, and Haemophilus influenzae disease in these patients, regardless of travel plans.

  • Limited data show that vaccine response in people who have had a splenectomy was more impaired if splenectomy was performed because of hematologic malignancy rather than for splenic trauma.
  • The meningococcal A/C/Y/W-135 conjugate vaccine is indicated for both pediatric and adult populations at risk.
  • The polysaccharide-protein conjugate vaccine against disease due to H. influenzae type b (Hib conjugate vaccine) appears to elicit an increased immune response and duration of protection in vaccine recipients, and many experienced clinicians recommend a single dose for splenectomized patients.
  • Streptococcus pneumoniae vaccine is recommended for asplenic patients (Table 8-01).

People with terminal complement deficiencies appear to have increased susceptibility to meningococcal infections and should be immunized against meningococcal disease.

MEDICAL CONDITIONS AND TREATMENTS ASSOCIATED WITH SEVERE IMMUNE COMPROMISE

Severe Immune Compromise (Non-HIV)

Severely immunocompromised people include those who have active leukemia or lymphoma, generalized malignancy, aplastic anemia, graft-versus-host disease, or congenital immunodeficiency; others in this category include people who have received recent radiation therapy, people who have had solid-organ or bone marrow transplants (within 2 years of transplantation), or transplant recipients who are still taking immunosuppressive drugs.

People with chronic lymphocytic leukemia have poor humoral immunity, even early in the disease course, and rarely respond to vaccines. Complete revaccination with standard childhood vaccines should begin 12 months after bone marrow transplantation. However, measles, mumps, and rubella (MMR) vaccine should be administered 24 months after transplant if the recipient is presumed to be immunocompetent. Experience using varicella vaccine in transplant recipients is insufficient; however, if a decision is made to vaccinate with varicella vaccine, the vaccine should be administered a minimum of 24 months after transplantation if the recipient is presumed to be immunocompetent. Influenza vaccine should be administered 6 months after transplant and annually thereafter.

For solid-organ transplants, the risk of infection is highest in the first year after transplant, so travel to high-risk destinations should be postponed until after that time.

Vaccine doses received while concurrently receiving immunosuppressive therapy or during the 2 weeks before starting therapy are not considered valid. At least 3 months after therapy is discontinued, patients should be revaccinated with all vaccines that are still indicated. People taking any of the following categories of medications are considered severely immunocompromised:

  • High-dose corticosteroids—Most clinicians consider a dose of either >2 mg/kg of body weight or ≥20 mg per day of prednisone or 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-virus vaccines. Furthermore, the immune response to vaccines may be impaired. Clinicians should wait ≥1 month after discontinuation of high-dose systemic corticosteroid therapy before administering a live-virus vaccine.
  • Alkylating agents (such as cyclophosphamide)
  • Antimetabolites (such as azathioprine, 6-mercaptopurine)
  • Transplant-related immunosuppressive drugs (such as cyclosporine, tacrolimus, sirolimus, mycophenolate mofetil, and mitoxantrone)
  • Cancer chemotherapeutic agents, excluding tamoxifen but including low-dose methotrexate weekly regimens, are classified as severely immunosuppressive, as evidenced by increased rates of opportunistic infections and blunting of responses to certain vaccines among patient groups. Limited studies show that methotrexate monotherapy had no effect on the response to influenza vaccine, but it did impair the response to pneumococcal vaccine.
  • Tumor necrosis factor (TNF) blockers such as etanercept, adalimumab, certolizumab pegol, golimumab, and infliximab blunt the immune response to certain vaccines and certain chronic infections. When used alone or in combination regimens with methotrexate to treat rheumatoid disease, TNF blockers were associated with an impaired response to influenza vaccine and to pneumococcal vaccine.
    • Despite measurable impairment of the immune response, postvaccination antibody titers were often sufficient to provide protection for most people; therefore, treatment with TNF blockers does not preclude immunization against influenza and pneumococcal disease.
    • The use of live vaccines is contraindicated according to the prescribing information for most of these therapies.
  • Other biologic agents that are immunosuppressive or immunomodulatory, as outlined in Table 8-02.

Severe Immune Compromise Due to Symptomatic HIV/AIDS

Knowledge of the HIV-infected traveler’s current CD4 T-lymphocyte count is necessary for pre-travel consultation. HIV-infected people with CD4 cell counts <200/mm3, history of an AIDS-defining illness, or clinical manifestations of symptomatic HIV are considered to have severe immunosuppression (see Chapter 3, HIV Infection) and should not receive live attenuated viral or bacterial vaccines because of the risk that the vaccine could cause serious systemic disease. The response to inactivated vaccines also will be suboptimal; thus, vaccine doses received by HIV-infected people while CD4 cell counts are <200/mm3 should be ignored, and the person should be revaccinated ≥3 months after immune reconstitution with antiretroviral therapy.

In newly diagnosed, treatment-naïve patients with CD4 cell counts <200/mm3, travel should be delayed pending reconstitution of CD4 cell counts with antiretroviral therapy. This delay will minimize risk of infection and avoid immune reconstitution illness during the travel.

Household Contacts

Household contacts of severely immunocompromised patients may be given live-virus vaccines such as yellow fever, MMR, or varicella vaccines but should not be given the live attenuated influenza vaccine. Immunocompromised patients should be aware of the risk of transmission of oral polio vaccine virus by the fecal-oral route in parts of the world where that vaccine is still given. Smallpox vaccine (mostly in military personnel) is also transmissible to immunocompromised patients.

Table 8-02. Immunosuppressive biologic agents that preclude vaccination against yellow fever, measles-mumps-rubella, varicella, or zoster1

GENERIC NAME TRADE NAME MECHANISM/TARGET OF ACTION
Abatacept Orencia CTLA-4
Adalimumab Humira TNF blocker
Alefacept Amevive CD2
Alemtuzumab Campath Anti-CD52
Anakinra Kineret IL-1
Basiliximab Simulect IL-2R/CD25
Bevacizumab Avastin VEGF
Certolizumab pegol Cimzia TNF blocker
Cetuximab Erbitux EGFR
Daclizumab Zenapax IL-2R
Etanercept Enbrel TNF blocker
Glatiramer acetate Copaxone Immunomodulatory; target unknown
Golimumab Simponi TNF blocker
Ibritumomab tiuxetan Zevalin CD20 with radioisotope
Imatinib mesylate Gleevec, STI 571 Signal transduction inhibitor/
protein-tyrosine kinase inhibitor
Infliximab Remicade TNF blocker
Interferon alfa Pegasys, PegIntron Block hepatitis C viral replication
Interferon beta-1a Avonex, Rebif Immunomodulatory; target unknown
Interferon beta-1b Betaseron Immunomodulatory; target unknown
Natalizumab Tsabri α4-integrin
Panitumumab Vectibix EGFR
Rilonacept Arcalyst IL-1
Rituximab Rituxan CD20
Sunitinib malate Sutent Multikinase inhibitor
Tocilizumab Actemra IL-6
Tositumomab Bexxar CD20 with radioisotope
Trastuzumab Herceptin Human EGFR 2 (HER2)
Ustekinumab Stelara IL-12, IL-23

Abbreviations: CTLA, cytotoxic T-lymphocyte antigen; TNF, tumor necrosis factor; CD, cluster of differentiation; IL, interleukin; VEGF, vascular endothelial growth factor; EGFR, epidermal growth factor receptor.

1This table is based primarily on conservative expert opinions, given the lack of clinical data. Numerous agents are often given in combination with other agents (especially chemotherapy) and are immunosuppressive when given together. The list provides examples but is not inclusive of all biologic agents that suppress or modulate the immune system. Not all therapeutic monoclonal antibodies or other biologic agents result in immunosuppression; details of individual agents not listed here must be reviewed before determining whether live viral vaccines can be given. Some of these agents are less immunosuppressive than others; specifically, interferon used for hepatitis C and interferon and glatiramer acetate given to multiple sclerosis patients are immunomodulators, but clinical data to support safety with live-virus vaccines are lacking. The period of time clinicians should wait after discontinuation of these before administering a live-virus vaccine is not specified by the Advisory Committee on Immunization Practices (ACIP) or other authoritative guidelines. Consultation with the prescribing physician (and possibly a hospital pharmacist) is recommended for management of individual patients and guidance in estimating a particular patient’s degree of immunosuppression. No basis exists for interpreting laboratory studies of immune parameters with vaccine safety or efficacy. Some experts recommend waiting 1 month after discontinuing etanercept and 3 months after discontinuing the other TNF blockers. Lymphocyte-depleting agents such as alemtuzumab and rituximab may cause prolonged immunosuppression. Restarting immunosuppression after live-virus vaccination has not been studied, but some experts would recommend at least a 1-month period.

SPECIAL CONSIDERATIONS FOR IMMUNOCOMPROMISED TRAVELERS

Yellow Fever Vaccine

Travelers with severe immune compromise should be strongly discouraged from travel to destinations that present a true risk for yellow fever (YF). They should not undergo YF vaccination, as there is a risk of developing a serious adverse event, such as life-threatening yellow fever vaccine-associated viscerotropic disease. If travel to an area where YF vaccine is recommended (see Maps 3-16 and 3-17) is unavoidable and the vaccine is not given, these travelers should be informed of the risk of YF, carefully instructed in methods to avoid mosquito bites, and be provided with a vaccination medical waiver (see Chapter 3, Yellow Fever).

Patients with conditions that the Advisory Committee on Immunization Practices considers precautions to administration of YF vaccine, such as asymptomatic HIV (see “Precautions” in Chapter 3, Yellow Fever), may be offered YF vaccine if travel to YF-endemic areas is unavoidable; recipients should be monitored closely for possible adverse effects. As vaccine response may be suboptimal, such vaccinees are candidates for serologic testing 1 month after vaccination. For information about serologic testing, contact your state health department or CDC’s Division of Vector-Borne Diseases at 970–221-6400. Data from clinical and epidemiologic studies are insufficient at this time to evaluate the actual risk of severe adverse effects associated with YF vaccine among recipients with limited immune deficits.

If international travel 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 letter. Travelers should be warned that vaccination waiver documents may not be accepted by some countries; if the waiver is rejected, the option of deportation might be preferable to receipt of YF vaccine at the destination.

Response to Vaccination

Response to vaccination may be muted in immunocompromised hosts, and potential travelers should be informed about this. The decrease in response to vaccination is not particularly predictable based on the immunosuppressive regimen. In general, serologic testing for response to most travel-related vaccines is neither clinically recommended nor readily available to practicing clinicians.

Malaria Chemoprophylaxis

Immunocompromised travelers to malaria-endemic areas should be prescribed appropriate drugs for malaria chemoprophylaxis and receive counseling about mosquito bite avoidance—the same as for immunocompetent travelers (see Chapter 3, Malaria). However, special concerns for immunocompromised travelers include any of the following possibilities:

  • Drugs used for malaria chemoprophylaxis may interact with drugs in the traveler’s maintenance regimen.
  • The underlying medical condition will predispose the immunocompromised traveler to more serious disease from malaria infection.
  • A malaria infection and the drugs used to treat the malaria infection may exacerbate the underlying disease.

The severity of malaria is increased in HIV-infected people: malaria infection increases HIV viral load and thus may exacerbate disease progression. There is a lack of published data on the safety and efficacy of CDC-recommended antimalarial regimens in the HIV-infected traveler taking highly active antiretroviral therapy (HAART) while traveling to malaria-endemic areas. Table 8-03 gives some examples of potential interactions between drugs used for malaria chemoprophylaxis and those used in HAART regimens:

  • Tetracyclines have no clinically significant interactions expected with the protease inhibitors and nonnucleoside reverse transcriptase inhibitors, so doxycycline might be a reasonable recommendation for malaria chemoprophylaxis in a traveler on HAART going to a malaria-endemic area.
  • Atovaquone-proguanil might be a reasonable malaria chemoprophylaxis choice for a traveler whose HAART regimen includes nelfinavir (protease inhibitor) and nevirapine (nonnucleoside reverse transcriptase inhibitor). Atovaquone is not expected to have any significant interaction with common nucleoside reverse transcriptase inhibitors, although no data are available for proguanil.
  • New classes of antiretroviral drugs include entry inhibitors and integrase inhibitors, and little data are available. Since new drugs and drug combinations for HIV treatment are under continuous development, clinicians are encouraged to review the most current information regarding possible drug interactions. An interactive web-based resource for checking on drug interactions involving HAART drugs is found at the University of Liverpool website (www.hiv-druginteractions.org).

Artemisinin combination therapy, consisting of 6 oral doses of artemether-lumefantrine taken over 3 days, is one of the recommended treatments for uncomplicated malaria due to Plasmodium falciparum. For severe malaria infections, intravenous artesunate is available in the United States through an investigational new drug protocol by CDC (see Chapter 3, Malaria). Limited data have raised concerns that parasite clearance of P. falciparum after therapy with artemisinins may be delayed in malaria patients coinfected with HIV compared with those who are HIV seronegative, raising the possibility that the host’s immunity affects the efficacy of antimalarial drug treatment. The use of quinidine (and by implication quinine) in patients taking nelfinavir or ritonavir is contraindicated because of potential cumulative cardiotoxicity. However, if a patient has severe and complicated malaria, there may be no choice. In these circumstances, as in others, quinidine should be used only with close monitoring. In addition, careful monitoring should accompany quinidine therapy in patients taking amprenavir, delavirdine, or the lopinavir-ritonavir combination. Although the clinical significance, if any, is not known, several protease inhibitors have been shown in laboratory testing to inhibit the growth of malaria parasites.

Similarly, organ transplant recipients may have drug interactions between their chronic immunosuppression and agents used for malaria prophylaxis and treatment. Mefloquine, doxycycline, chloroquine, and primaquine may increase calcineurin inhibitor levels (tacrolimus and cyclosporine A), and sulfadoxine-pyrimethamine may decrease their levels. Some travel-related prophylactic medications need to be dose-adjusted according to altered hepatic or renal function.

Some clinical case reports suggest that asplenic people may be at higher risk of acquisition and complications of malaria, so asplenic travelers to malaria areas should be counseled to adhere conscientiously to the malaria chemoprophylaxis regimen prescribed for them.

Enteric Infections

Many foodborne and waterborne infections, such as those caused by Salmonella, Campylobacter, Giardia, and Cryptosporidium, can be severe or become chronic in immunocompromised people. Enteroaggregative Escherichia coli is an emerging enteric pathogen causing persistent diarrhea among children, adults, and HIV-infected people.

Safe food and beverage precautions should be followed by all travelers, but travelers’ diarrhea can occur despite strict adherence. Selection of antimicrobials to be used for self-treatment of travelers’ diarrhea may require special consideration of potential drug interactions among patients already taking medications for chronic medical conditions. Fluoroquinolones and rifaximin are active against several enteric pathogens and are not known to have significant interactions with HAART drugs. However, macrolide antibiotics may have significant interactions with HAART drugs (Table 8-04) and with organ transplant–related immunosuppression. Emerging therapies for diarrhea in HIV/AIDS patients may involve probiotics such as Lactobacillus rhamnosus GR-1, L. reuteri RC-14, and others.

Waterborne infections might result from swallowing water during recreational activities. To reduce the risk for cryptosporidiosis and giardiasis, patients should avoid swallowing water during swimming and should not swim in water that might be contaminated (with sewage or animal waste, for example).

Attention to hand hygiene, including frequent and thorough handwashing, is the best prevention against gastroenteritis. Hands should be washed after contact with public surfaces and also after any contact with animals or their living areas.

Reducing Risk for Other Diseases

Geographically focal infections that pose an increased risk of severe outcome for immunocompromised people include visceral leishmaniasis and several fungal infections acquired by inhalation (such as Penicillium marneffei infection in Southeast Asia and coccidioidomycosis in the Americas). Many developing areas have high rates of tuberculosis (TB), and establishing the TB status of immunocompromised travelers going to such destinations may be helpful in the evaluation of any subsequent travel-associated illness. Depending on the traveler’s degree of immune suppression, the baseline TB status may be assessed by obtaining a tuberculin skin test, chest radiograph, or Mycobacterium tuberculosis antigen-specific interferon-γ assay.

Patients with advanced HIV and transplant recipients frequently take either primary or secondary prophylaxis for one or more opportunistic infections (such as Pneumocystis, Mycobacterium, and Toxoplasma spp.). Complete adherence to all indicated regimens should be confirmed before travel (see Chapter 3, HIV Infection).

Table 8-03. Potential interactions between malaria drugs and HIV1,2 or transplant-related3 drugs

DRUG PROTEASE INHIBITORS NRTIs NNRTIs CALCINEURIN INHIBITORS (TACROLIMUS, CYCLOSPORINE A)
Mefloquine Potential interaction with all protease inhibitors No available data Decreased levels of mefloquine with efavirenz and nevirapine Could cause prolonged QT interval or elevated calcineurin inhibitor levels
Atovaquone-proguanil

Atovaquone: potential interactions with indinavir, ritonavir, lopinavir, atazanavir, darunavir, tipranavir

Proguanil: potential interactions with ritonavir and lopinavir

Atovaquone: no clinically significant interaction expected

Proguanil: no available data

Atovaquone: potential interaction with efavirenz

Proguanil: potential interaction with efavirenz

No available data
Doxycycline No clinically significant interactions expected No available data No clinically significant interactions expected Could cause elevated calcineurin inhibitor levels
Chloroquine Potential interaction with ritonavir only No available data No clinically significant interactions expected Could cause prolonged QT interval or elevated calcineurin inhibitor levels
Primaquine No clear data No available data No available data Could cause elevated calcineurin inhibitor levels

Abbreviations: NRTI, nucleoside reverse transcriptase inhibitor; NNRTI, nonnucleoside reverse transcriptase inhibitor.
1Adapted from Table 2 in Bhadelia N, Klotman M, Caplivski D. The HIV-positive traveler. Am J Med. 2007 Jul;120(7):574–80, and information available at www.hiv-druginteractions.org.
2All potential interactions within an HIV drug class are noted in the table. There are no drug combinations with absolute contraindications to coadministration.
3Adapted from Table 3 in Kotton CN, Hibberd PL. Travel medicine and the solid organ transplant recipient. Am J Transplant. 2009 Dec;9 Suppl 4:S273–81.

Table 8-04. Potential interactions between antibiotics for travelers’ diarrhea and HIV1 or transplant-related2 drugs

DRUG PROTEASE INHIBITORS NRTIs NNRTIs CALCINEURIN INHIBITORS (TACROLIMUS, CYCLOSPORINE A)
Fluoroquin-
olones
No clinically significant interactions No clinically significant interactions No clinically significant interactions Could cause prolonged QT interval or elevated fluoroquinolone levels; dose per renal function
Macrolides Possible increased levels of clarithromycin with ritonavir, atazanavir, and lopinavir Decreased levels of zidovudine with clarithromycin; no data available for azithromycin Possible interactions with clarithromycin, efavirenz, and nevirapine Possible increased levels of calcineurin inhibitors
Rifaximin No available data No available data No available data No available data; could decrease levels of calcineurin inhibitors

Abbreviations: NRTI, nucleoside reverse transcriptase inhibitor; NNRTI, nonnucleoside reverse transcriptase inhibitor.
1Adapted from Table 2 in Bhadelia N, Klotman M, Caplivski D. The HIV-positive traveler. Am J Med. 2007 Jul;120(7):574–80.
2Adapted from Table 3 in Kotton CN, Hibberd PL. Travel medicine and the solid organ transplant recipient. Am J Transplant. 2009 Dec;9 Suppl 4:S273–81.

BIBLIOGRAPHY

  1. Agarwal N, Ollington K, Kaneshiro M, Frenck R, Melmed GY. Are immunosuppressive medications associated with decreased responses to routine immunizations? A systematic review. Vaccine. 2012 Feb 14;30(8):1413–24.
  2. Anukam KC, Osazuwa EO, Osadolor HB, Bruce AW, Reid G. Yogurt containing probiotic Lactobacillus rhamnosus GR-1 and L. reuteri RC-14 helps resolve moderate diarrhea and increases CD4 count in HIV/AIDS patients. J Clin Gastroenterol. 2008 Mar;42(3):239–43.
  3. Beran J. Safety and immunogenicity of a new hepatitis B vaccine for the protection of patients with renal insufficiency including pre-haemodialysis and haemodialysis patients. Expert Opin Biol Ther. 2008 Feb;8(2):235–47.
  4. Bhadelia N, Klotman M, Caplivski D. The HIV-positive traveler. Am J Med. 2007 Jul;120(7):574–80.
  5. Boerbooms AM, Kerstens PJ, van Loenhout JW, Mulder J, van de Putte LB. Infections during low-dose methotrexate treatment in rheumatoid arthritis. Semin Arthritis Rheum. 1995 Jun;24(6):411–21.
  6. Brinkman DM, Jol-van der Zijde CM, ten Dam MM, teBoekhorst PA, ten Cate R, Wulffraat NM, et al. Resetting the adaptive immune system after autologous stem cell transplantation: lessons from responses to vaccines. J Clin Immunol. 2007 Nov;27(6):647–58.
  7. CDC. Vaccination of persons with primary and secondary immune deficiencies. In: Atkinson W, Wolfe S, Hamborsky J, editors. Epidemiology and Prevention of Vaccine-Preventable Diseases. 12th ed. Washington, DC: Public Health Foundation; 2012. p. A-23 [cited 2012 Sep 30]. Available from: http://www.cdc.gov/vaccines/pubs/pinkbook/downloads/appendices/A/immuno-table.pdf.
  8. Cohen C, Karstaedt A, Frean J, Thomas J, Govender N, Prentice E, et al. Increased prevalence of severe malaria in HIV-infected adults in South Africa. Clin Infect Dis. 2005 Dec 1;41(11):1631–7.
  9. Eigenberger K, Sillaber C, Greitbauer M, Herkner H, Wolf H, Graninger W, et al. Antibody responses to pneumococcal and hemophilus vaccinations in splenectomized patients with hematological malignancies or trauma. Wien Klin Wochenschr. 2007;119(7–8):228–34.
  10. Farez MF, Correale J. Yellow fever vaccination and increased relapse rate in travelers with multiple sclerosis. Arch Neurol. 2011 Oct;68(10):1267–71.
  11. Geretti AM, Doyle T. Immunization for HIV-positive individuals. Curr Opin Infect Dis. 2010 Feb;23(1):32–8.
  12. Kamya MR, Gasasira AF, Yeka A, Bakyaita N, Nsobya SL, Francis D, et al. Effect of HIV-1 infection on antimalarial treatment outcomes in Uganda: a population-based study. J Infect Dis. 2006 Jan 1;193(1):9–15.
  13. Kaplan JE, Benson C, Holmes KH, Brooks JT, Pau A, Masur H, et al. Guidelines for prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from CDC, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. MMWR Recomm Rep. 2009 Apr 10;58(RR-4):1–207.
  14. Kotton CN, Hibberd PL, AST Infectious Diseases Community of Practice. Travel medicine and the solid organ transplant recipient. Am J Transplant. 2009 Dec 9;(Suppl 4):S273–81.
  15. Laurence JC. Hepatitis A and B immunizations of individuals infected with human immunodeficiency virus. Am J Med. 2005 Oct;118 Suppl 10A:75S–83S.
  16. Loebermann M, Winkelmann A, Hartung HP, Hengel H, Reisinger EC, Zettl UK. Vaccination against infection in patients with multiple sclerosis. Nat Rev Neurol. 2011;8(3):143–51.
  17. Matulis G, Juni P, Villiger PM, Gadola SD. Detection of latent tuberculosis in immunosuppressed patients with autoimmune diseases: performance of a Mycobacterium tuberculosis antigen-specific interferon gamma assay. Ann Rheum Dis. 2008 Jan;67(1):84–90.
  18. Mishra LC, Bhattacharya A, Sharma M, Bhasin VK. HIV protease inhibitors, indinavir or nelfinavir, augment antimalarial action of artemisinin in vitro. Am J Trop Med Hyg. 2010 Jan;82(1):148–50.
  19. Nevens F, Zuckerman JN, Burroughs AK, Jung MC, Bayas JM, Kallinowski B, et al. Immunogenicity and safety of an experimental adjuvanted hepatitis B candidate vaccine in liver transplant patients. Liver Transpl. 2006 Oct;12(10):1489–95.
  20. Skinner-Adams TS, McCarthy JS, Gardiner DL, Andrews KT. HIV and malaria co-infection: interactions and consequences of chemotherapy. Trends Parasitol. 2008 Jun;24(6):264–71.
  21. Visser LG. TNF-α antagonists and immunization. Curr Infect Dis Rep. 2011 Jun;13(3):243–7.
 
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