The Immunosuppressed Traveler

https://doi.org/10.1016/j.idc.2012.06.003Get rights and content

Section snippets

Introduction: immunosuppression refers to loss in quality or quantity of cellular and/or humoral immune components

The human immune system is affected by age, disease, and medication. If a condition results in loss in numbers or functional defects of cellular and/or humoral immune components, the term immunosuppression or immunocompromised is used. Primary immunodeficiencies such as X-linked agammaglobulinemia, are inherited. When loss in quality or quantity results from disease or its therapy, the immunodeficiency is classified as secondary. This article focuses on travelers with secondary

The normal immune response: clonal proliferation is a central event in mounting an effective immune response

Only a few naive T and B cells are able to recognize a given antigen. This number is too small for a useful response against a vaccine or pathogen. In order to mount an effective immune response, it is crucial these few T- and B-cells clone and multiply in numbers.

During a primary immune response, when the immune system is exposed to antigens or pathogens for the first time, naive CD4+ T cells in lymph nodes or spleen recognize peptide antigens on the surface of dendritic cells and are

The way immunosuppressive drugs work: reducing numbers

Each of the steps discussed earlier can be the target of an immunosuppressive drug (Fig. 1): (1) destruction of reacting T and/or B cells, (2) interference with the costimulatory signals, (3) blocking the intracellular signal of the antigen-recognizing T-cell receptor, (4) inhibition of DNA synthesis and cell proliferation, and (5) modulation of the effector T-cell or B-cell response. The net result of all but the last step is that the clonal expansion is blocked.

As a result, the primary immune

Age-related involution of thymus and bone marrow results in incomplete immune reconstitution

From the first year of life, there is a gradual decrease of the thymic epithelial space where naive CD4+ helper, CD8+ cytotoxic, and CD4+CD25++ regulatory T cells are formed. At the age of 70 years, the thymic epithelial space has shrunk to 10% of the original thymic volume. It is estimated that, by the age of 105 years, the thymus will have ceased generating naive T cells.43

During this process of thymopoiesis (proliferation, maturation, and selection of T cells) a vast repertoire of different

Step 1. Determine the effect of the underlying condition and/or its immunosuppressive treatment on the likely immune response of the traveler

The theoretic outline given earlier can be used to determine whether and how the immunosuppressive treatment affects critical steps in the cellular and humoral immune response to pathogens and vaccines. If possible, restore the gastric acid barrier. Many patients on immunosuppressive treatment receive proton pump inhibitors. Antacids double the risk of traveler’s diarrhea.59 Consult the treating physician if treatment with antacids can be stopped safely.

Step 2. Is yellow fever vaccination required because of risk of infection?

Many travelers who have received yellow

Summary

Clonal proliferation of T and B cells is a central event in mounting an effective immune response against pathogens and vaccines. Most immunosuppressive drugs reduce the number of effector T and/or B cells by blocking this clonal expansion. Aging and injury to the thymus lead to a decreased output of naive T cells to the peripheral circulation. These age-related changes explain why immune reconstitution after high-dose chemotherapy, allogeneic hematopoietic cell transplantation, or during

First page preview

First page preview
Click to open first page preview
View PDF

References (61)

  • C.N. Kotton et al.

    Prevention of infection in adult travelers after solid organ transplantation

    Am J Transplant

    (2005)

  • Recommendations of the Advisory Committee on Immunization Practices (ACIP). General recommendations on immunization

    MMWR

    (2011)
  • P.F. Halloran

    Immunosuppressive drugs for kidney transplantation

    N Engl J Med

    (2004)
  • J.R. Ingelfinger et al.

    Immunosuppression — the promise of specificity

    N Engl J Med

    (2005)
  • K. Murphy et al.

    Janeway’s immunobiology

    (2008)
  • T. Rhen et al.

    Antiinflammatory action of glucocorticoids — new mechanisms for old drugs

    N Engl J Med

    (2005)
  • M. Perretti et al.

    Annexin A1 and glucocorticoids as effectors of the resolution of inflammation

    Nat Rev Immunol

    (2009)
  • C.K. Glass et al.

    Nuclear receptor transrepression pathways that regulate inflammation in macrophages and T cells

    Nat Rev Immunol

    (2010)
  • C.N. Serhan et al.

    Resolving inflammation: dual anti-inflammatory and pro-resolution lipid mediators

    Nat Rev Immunol

    (2008)
  • S. Edsbäcker et al.

    Pharmacokinetics of budesonide (Entocort EC) capsules for Crohn’s disease

    Clin Pharmacokinet

    (2004)
  • P. Rutgeerts et al.

    A comparison of budesonide with prednisolone for active Crohn's disease

    N Engl J Med

    (1994)
  • C.J. Dunn et al.

    Cyclosporin: an updated review of the pharmacokinetic properties, clinical efficacy and tolerability of a microemulsion-based formulation (Neoral®)1 in organ transplantation

    Drugs

    (2001)
  • M.A. Hooks

    Tacrolimus, a new immunosuppressant–a review of the literature

    Ann Pharmacother

    (1994)
  • A.W. Thomson et al.

    Immunoregulatory functions of mTOR inhibition

    Nat Rev Immunol

    (2009)
  • K. Mahalati et al.

    Clinical pharmacokinetics of sirolimus

    Clin Pharmacokinet

    (2001)
  • G.I. Kirchner et al.

    Clinical pharmacokinetics of everolimus

    Clin Pharmacokinet

    (2004)
  • N.K. de Boer et al.

    Drug insight: pharmacology and toxicity of thiopurine therapy in patients with IBD

    Nat Clin Pract Gastroenterol Hepatol

    (2007)
  • A. Anstey et al.

    Azathioprine; clinical pharmacology and current indications in autoimmune disorders

    BioDrugs

    (1998)
  • M.L. Ritter et al.

    Mycophenolate mofetil: effects on cellular immune subsets, infectious complications, and antimicrobial activity

    Transpl Infect Dis

    (2009)
  • C.E. Staatz et al.

    Clinical pharmacokinetics and pharmacodynamics of mycophenolate in solid organ transplant recipients

    Clin Pharmacokinet

    (2007)

    • Cited by (47)

    • Enhanced metabolic activation of and platelet response to clopidogrel in T cell-deficient mice through induction of Cyp2c and Cyp3a and inhibition of Ces1

      2023, Journal of Thrombosis and Haemostasis

    • Health Care Maintenance in Patients with Crohn's Disease

      2022, Gastroenterology Clinics of North America

    • Practical Management of patients on anti-IL6R therapy: Practical guidelines drawn up by the Club Rhumatismes et Inflammation (CRI)

      2021, Joint Bone Spine

    • Practical management of patients on anti-IL17 therapy: Practical guidelines drawn up by the Club Rhumatismes et Inflammation (CRI)

      2021, Joint Bone Spine
      Citation Excerpt :

      Secukinumab and ixekizumab can be carried when travelling. However injection should be delayed if there is just one week wait [132,133]. In other cases, the patient should keep their therapy with them (between 2 and 8°C) but not frozen (i.e. in cabin baggage and not in hold baggage, if travelling by air).

    • PRACTICAL MANAGEMENT of patients on anti-TNF therapy: Practical guidelines drawn up by the Club Rhumatismes et Inflammation (CRI)

      2021, Joint Bone Spine

    • Travel patterns, risk behaviour and health problems of travellers with rheumatic diseases compared to controls: A multi-centre, observational study

      2020, Travel Medicine and Infectious Disease
      Citation Excerpt :

      All participants were aged 18 years and above. If patients took one of the following medications in the respective time period they were classified as immunosuppressed: systemic corticosteroids, methotrexate, or etanercept within the past month; azathioprine within the past two months; other conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs), adalimumab, certolizumab, golimumab, infliximab, and other biological DMARDs within the past three months; leflunomide within the past six months; and rituximab in the past 12 months [21,22]. The study was approved by the Aargau-Solothurn, Bern, Geneva, Nordwestschweiz, St. Gallen and Zurich Ethics committees (Reference numbers EK Aargau-Solothurn: 2013/062, Bern: 182/13, CCER 2016-00218, EKNZ 257/13, EKSG 13/138, KEK-ZH 2013-0188).

    View all citing articles on Scopus

    Conflicts of interest: L.G. Visser has served on speakers’ bureaus for Abbott, Crucell and Sanofi.

    View full text
    Copyright © 2012 Elsevier Inc. All rights reserved.