Chapter 8 Advising Travelers with Specific Needs
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:
- What is the cause of the immune suppression? Different conditions and medications produce widely varying degrees of compromise, and there are many unknowns in this field. Guidance regarding vaccination of immunocompromised travelers is less evidence based than guidance for other categories of travelers but is the best available.
- Is the traveler’s underlying medical condition stable? The travel health care 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 their usual maintenance regimen.
- Do the conditions, medications, and treatments of the traveler constitute contraindications to, decrease the effectiveness of, or increase the risk for adverse events 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?
- If an immunocompromised traveler were to become ill while traveling, what would be the health care options (see Chapter 2, Obtaining Health Care Abroad for the Ill Traveler)? What would the traveler do should medical evacuation be required? An immunocompromised traveler must have a plan for when and how to seek care overseas and how to pay for it.
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 severe illness or death 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 8-08.
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.
- 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 still wait 2 weeks before administering live vaccines.
- HIV patients without severe immunosuppression (for definitions of severe immunosuppression, see the individual vaccine recommendations at http://www.cdc.gov/vaccines/hcp/acip-recs/index.html).
- Travelers with a history of cancer who received their last chemotherapy treatment ≥3 months previously and whose malignancy is in remission.
- Hematopoietic stem cell transplant recipients who are >2 years posttransplant, not on immunosuppressive drugs, with no evidence of ongoing malignancy, and without graft-versus-host disease.
- 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.
- 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.
1 The Infectious Diseases Society of America suggests a 1-month interval between low immunosuppressive corticosteroids/alternate-day dosing corticosteroids and live vaccines, but this is controversial.
Table 8-08. Immunization of immunocompromised adults
TION, CD4 CELLS ≥200/
AIDS) CD4 CELLS <200/
|ASPLENIA||RENAL FAILURE||CHRONIC LIVER DISEASE, DIABETES|
|Influenza, live attenuated (LAIV)||X||X||X||U||P||P|
influenzae type b (Hib)
|Hepatitis A8||U||U||U||U||U||U (diabetes), R (liver disease)|
|PCV13 followed by PPSV2314||R||R||R||R||R||C|
|Td or Tdap||R||R||R||R||R||R|
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); OC, Other considerations; C, Consider; ND, No data; PCV13, 13-valent pneumococcal conjugate vaccine; PPSV23, 23-valent pneumococcal polysaccharide vaccine.
1MMR vaccination is recommended for all HIV-infected patients with CD4 counts ≥200/mm3 for ≥6 months if they are 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.
4No data suggest increased risk of serious adverse events after use of YF vaccine in people with these conditions; however, varying degrees of immune deficit might be present, and providers should carefully weigh vaccine risks and benefits before deciding to vaccinate people with these conditions.
5Also contraindicated by ACIP for symptomatic HIV patients without AIDS and with CD4 counts ≥200/mm3.
6Recipients of a hematopoietic stem cell transplant should be vaccinated with a 3-dose regimen 6–12 months after a successful transplant, regardless of vaccination history; at least 4 weeks should separate doses.
7Only recommended for asplenic adults who have not previously received Hib vaccine.
8Routinely indicated for all men who have sex with men, people with multiple sexual partners, hemophiliacs, patients with chronic hepatitis, injection drug users, and others.
9Hepatitis B vaccination is indicated for people at risk for infection by sexual exposure, including sex partners of hepatitis B surface antigen (HBsAg)–positive people, sexually active people who are not in a long-term, mutually monogamous relationship, people seeking evaluation or treatment for a sexually transmitted disease, men who have sex with men, people at risk for infection by percutaneous or mucosal exposure to blood, current or recent injection-drug users, household contacts of HBsAg-positive people, residents and staff of facilities for developmentally disabled people, health care and public safety workers with reasonably anticipated risk for exposure to blood or blood-contaminated body fluids, people with end-stage renal disease, international travelers to regions with high or intermediate levels (HBsAg prevalence >2%) of endemic HBV infection, people with chronic liver disease, and people with HIV infection.
10Adult patients receiving hemodialysis or with other immunocompromising conditions should receive 1 dose of 40 μg/mL Recombivax HB administered on a 3-dose schedule at 0, 1, and 6 months or 2 doses of 20 μg/mL (Engerix-B) administered simultaneously on a 4-dose schedule at 0, 1, 2, and 6 months. Test for antibodies to hepatitis B virus surface antigen serum 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.
11People with diabetes who are younger than 60 years as soon as feasible after diagnosis; people with diabetes who are age 60 years or older at the discretion of the treating clinician based on the likelihood of acquiring HBV infection, including the risk posed by an increased need for assisted blood glucose monitoring in long-term care facilities, the likelihood of experiencing chronic sequelae if infected with HBV, and the likelihood of immune response to vaccination; all people with chronic liver disease not caused by hepatitis B. At present, routine testing of antibody response after vaccination in people with diabetes or chronic liver disease is not recommended.
12No safety or efficacy data exist regarding the use of Ixiaro in immunocompromised people. In general, inactivated vaccines can be administered safely to people with altered immunocompetence, using the usual doses and schedules, but the effectiveness might be suboptimal. The inactivated, Vero cell–derived JE vaccine, Ixiaro, is the only Japanese encephalitis vaccine available in the United States; other types of Japanese encephalitis vaccines, including live vaccines, are available internationally but are not included here.
13Two doses ≥2 months apart for asplenic people and people with terminal complement deficiency.
14Previously 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.
(Updated September 4, 2015)
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 and should be vaccinated according to the guidelines in Table 8-08. (More specific recommendations are available for MMR [measles-mumps-rubella] vaccine. Detailed information is available at http://www.cdc.gov/mmwr/preview/mmwrhtml/rr6204a1.htm and http://www.cdc.gov/mmwr/preview/mmwrhtml/rr6002a1.htm.) CD4 counts while on 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 immune reconstitution, if possible, before immunizations are administered. (For MMR vaccine, the recommendation is ≥6 months on antiretroviral therapy with the age- and CD4-based criteria in footnote 2.) 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 many 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 asymptomatic HIV-infected people. The clinical significance of these increases is not known, but they do not preclude the use of any vaccine.
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.
Modern MS therapy often includes aggressive and early immunomodulatory therapy for many 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 immune-suppressing biologic agents. Patients on glatiramer acetate and interferons have more limited immune deficits.
A few published studies suggest that mumps, 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. One study suggests yellow fever vaccine can exacerbate symptoms in MS patients; this risk should be considered in consultation with the patient’s neurologist before administering the vaccine.
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), and diabetes mellitus. These patients should be vaccinated according to the guidelines in Table 8-08. Patients with complement deficiencies can receive any live or inactivated vaccine. Factors to consider in assessing the general level of immune competence of patients with chronic diseases include disease severity, duration, clinical stability, complications, comorbidities, and any potentially immune-suppressing treatment (see the next section in this chapter, Travelers with Chronic Illnesses).
Adults aged ≥19 years with immunocompromising conditions (including chronic renal failure and nephrotic syndrome), those on the immunocompromising drugs listed below, transplant recipients, and those with functional or anatomic asplenia, malignancy, cerebrospinal fluid leaks, or cochlear implants who have not previously received the 13-valent pneumococcal conjugate vaccine (PCV13) or the 23-valent pnuemococcal polysaccharide vaccine (PPSV23) should receive a single dose of PCV13 followed by a dose of PPSV23 ≥8 weeks later; those who have previously received ≥1 dose of PPSV23 should receive a dose of PCV13 ≥1 year after the last PPSV23 dose was received. For adults who require additional doses of PPSV23, the first such dose should be given no sooner than 8 weeks after PCV13 and ≥5 years after the most recent dose of PPSV23.
A blunted response to hepatitis B vaccine has been reported in patients with chronic renal 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 series may be necessary. Higher-dose hepatitis B vaccine preparations are used to promote optimal immunization of people undergoing hemodialysis and those with other immunocompromising conditions.
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 Menactra meningococcal A/C/Y/W conjugate vaccine is indicated for both pediatric and adult populations at risk, with 2 doses separated by ≥2 months in asplenic patients; booster vaccinations should be repeated every 5 years if risk is ongoing.
- The Menveo meningococcal A/C/Y/W conjugate vaccine is recommended on a 2-dose schedule for asplenic adults and a 4-dose schedule at ages 2 and 12–15 months.
- 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 supplemental doses for splenectomized patients with incomplete Hib vaccination histories.
- PCV13 vaccine is recommended for asplenic patients and should be followed by PPSV23 8 weeks and 5 years later (see above and Table 8-08).
People with terminal complement deficiencies and those receiving eculizumab 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, those who have had solid-organ transplants and who are on active immunosuppression, and hematopoietic stem cell transplant recipients (within 2 years of transplantation or still taking immunosuppressive drugs). People who are severely immunocompromised may not receive live vaccines, and inactivated vaccines are not likely to be effective; these patients should consider postponing travel until their immune function improves.
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 hematopoietic stem cell transplantation. However, MMR and varicella vaccines should be administered 24 months after transplant if the recipient is assumed to be immunocompetent. Inactivated influenza vaccine should be administered beginning ≥6 months after hematopoietic stem cell transplant and annually thereafter; a dose of inactivated influenza vaccine can be given as early as 4 months after transplant, although a booster dose should be considered in this situation.
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.
Doses of inactivated vaccines received while concurrently receiving potent immunosuppressive therapy (see below) 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 inactivated 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 cyclophos-phamide).
- Antimetabolites (such as azathioprine, 6-mercaptopurine).
- Transplant-related immunosuppressive drugs (such as cyclosporine, tacrolimus, sirolimus, azathioprine, and mycophenolate mofetil).
- 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, certolizumabpegol, 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 hepatitis A, influenza, and pneumococcal vaccines.
- 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 hepatitis A, influenza, and pneumococcal disease. If possible, both doses in the hepatitis A series should be given before travel.
- 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 may result in significant immunocompromise. In particular, certain monoclonal antibodies, such as rituximab or alemtuzumab, are more significantly immunosuppressive, and neither inactivated or live vaccines should be administered for at least 6 months—and perhaps longer—after cessation of therapy with these agents.
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 without immune reconstitution, 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. Such postponement helps minimize risk of infection and avoid immune reconstitution illness during travel.
2 For MMR vaccine, severe immunosuppression is defined as CD4 percentages <15% at any age or CD4 count <200/mm3 for people aged >5 years. See http://www.cdc.gov/mmwr/preview/mmwrhtml/rr6204a1.htm.
Household contacts of severely immunocompromised patients may be given live-virus vaccines such as yellow fever, MMR, or varicella/zoster 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 for military personnel) is also transmissible to immunocompromised household and intimate contacts.
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 is unavoidable to an area where YF vaccine is recommended (see Maps 3-16 and 3-17) 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 might 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. Encouragingly, recent data in solid organ transplant recipients vaccinated before transplant suggests that a prolonged phase of protective antibody titers can exist after transplant. In general, serologic testing for response to most travel-related vaccines is neither clinically recommended nor readily available to practicing clinicians.
Immunocompromised travelers to malaria-endemic areas should be prescribed drugs for malaria chemoprophylaxis and receive counseling about mosquito bite avoidance—the same as for immunocompetent travelers (see Chapter 3, Malaria). 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, including leading to prolongation of the cardiac QTc interval, arrhythmia, and death.
- The underlying medical condition or immunosuppressive regimen may 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.
People with HIV on HAART face particularly large numbers of potential drug interactions with drugs prescribed for malaria chemoprophylaxis. Table 8-09 highlights potential interactions for the most commonly used HAART combinations, but it should be emphasized that these are based on pharmacokinetic or metabolism considerations only and not on any evidence of clinical failure.
- Integrase inhibitor (raltegravir, dolutegravir, elvitegravir)/NRTI combinations have no known interactions with CDC-recommended chemoprophylactic drugs, although the cobicistat booster co-formulated with elvitegravir may theoretically increase mefloquine levels.
- Concurrent use of emtricitabine/tenofovir/efavirenz (Atripla) with chloroquine, mefloquine, or doxycycline has not been associated with drug interactions. Efavirenz lowers serum levels of both atovaquone and proguanil, but there is no evidence for clinical failure of these agents when used concurrently.
- Protease inhibitor (PI)-containing combinations are associated with many drug interactions. Lopinavir/ritonavir (Kaletra) used in combination with tenofovir/emtricatabine (Truvada) or any other PI-containing combination can lower serum levels of both atovaquone/proguanil and mefloquine. Doxycycline is a preferred antimalarial chemoprophylactic agent in patients on such a regimen.
- For less commonly used combinations or drugs not specifically included in Table 8-09, 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).
Antimalaria treatment regimens including artemisinin derivatives, quinine/quinidine, lumefantrine (part of the artemether/lumefantrine combination, Coartem), and atovaquone and proguanil may have potential interactions with many NNRTIs, PIs, and with the CCR5 receptor antagonist maraviroc. Expert advice should be sought when treating patients for malaria who are also on HAART.
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.
Table 8-09. 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: 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 8-10. Potential interactions between antibiotics for travelers’ diarrhea and HIV1 or transplant-related2 drugs
|DRUG||PROTEASE INHIBITORS||NRTIs||NNRTIs||CALCINEURIN INHIBITORS (TACROLIMUS, CYCLOSPORINE A)|
|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.
Many foodborne and waterborne infections, such as those caused by Salmonella, Campylobacter, Giardia, Listeria, and Cryptosporidium, can be severe or become chronic in immunocompromised people.
Safe food and beverage precautions should be followed by all travelers; travelers’ diarrhea can nonetheless 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 bacterial pathogens and are not known to have significant interactions with HAART drugs. Macrolide antibiotics may have significant interactions with HAART drugs (Table 8-10) and with organ transplant–related immunosuppression. Waterborne infections might result from swallowing water during recreational activities. To reduce the risk of 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). Travelers with liver disease should avoid direct exposure to salt water that may contain Vibrio spp.
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, Mycobacterium tuberculosis antigen-specific interferon-γ assay, or chest radiograph.
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).
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- Barte HL, Horvath TH, Rutherford GW. Yellow fever vaccine for patients with HIV infection. Cochrane Database Syst Rev. 2014 Jan 23;1:CD010929.
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- Page last updated: September 04, 2015
- Page last reviewed: July 10, 2015
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