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Infectious diseases Board Review Manual
Statement of
Editorial Purpose
The Hospital Physician Infectious Diseases Board
Review Manual is a study guide for fellows and
practicing physicians preparing for board exam­
inations in infectious diseases. Each manual
reviews a topic essential to current practice
in the subspecialty of infectious diseases.
The Hospital Physician® Infectious Diseases
Board Review Manuals are published by
Turner White Communications, Inc., an
independent medical publisher dedicated to
serving the information and education needs
of clinical trainees and practicing physicians.
PUBLISHING STAFF
PRESIDENT, Group PUBLISHER
Bruce M. White
Senior EDITOR
Robert Litchkofski
executive vice president
Viral Infections in the
Immunocompromised .
Patient: Herpesviruses
Series Editor:
Varsha Moudgal, MD
Infectious Diseases Fellowship Program Director, St. Joseph Mercy
Hospital, Ann Arbor, MI; and Assistant Professor of Medicine, Wayne
State University School of Medicine, Detroit, MI
Contributor:
Gregory M. Anstead, MD, PhD Associate Professor of Medicine, University of Texas Health Science Center
at San Antonio, San Antonio, TX; Director, Immunosuppression and
Infectious Diseases Clinics, South Texas Veterans Health Care System,
San Antonio, TX
Barbara T. White
executive director
of operations
Jean M. Gaul
Table of Contents
Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
Factors Associated with Specific Infections. . . . . . . . . . . . . . . . 4
NOTE FROM THE PUBLISHER:
This publication has been developed with­
out involvement of or review by the Amer­
ican Board of Internal Medicine.
The Herpesviruses. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
Copyright 2012 by Turner White Communications Inc., Wayne, PA. All rights reserved.
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Infectious Diseases Volume 13, Part 3 Infectious Diseases Board Review Manual
Viral Infections in the
Immunocompromised Patient:
Herpesviruses
Gregory M. Anstead, MD, PhD
INTRODUCTION
Immunocompromised patients are at risk for infection from a variety of opportunistic viral pathogens
and may also suffer more severe manifestations from
common community-acquired viruses. For the purposes of this review, immunocompromised patients
include recipients of solid organ transplants (SOT),
bone marrow transplants (BMT), and hematopoietic
stem cell transplants (HSCT); those on immunomodulator therapy; and patients with HIV infection. In
part 1 of this 2-part review on viral infections in immunocompromised patients, infections due to viruses
of the family Herpesviridae will be addressed; these
viruses include human herpesviruses 1 and 2 (HSV-1,
HSV-2), varicella zoster virus (VZV), cytomegalovirus
(CMV), Epstein-Barr virus (EBV), and human herpesviruses-6 and -8 (HHV-6, HHV-8). The second part of the
review will focus on infections due to other major viral
pathogens: parvovirus B19, the respiratory viruses, the
JC and BK viruses, lymphocytic choriomeningitis virus,
rabies virus, and West Nile virus (WNV). These reviews
will not cover infection with the human papillomavirus
and the hepatitis viruses A, B, C, D, and E.
The broad range of pathogens and the potential
for rapid progression of disease mandates a prompt
diagnostic approach in the immunosuppressed patient with suspected viral infection. General diagnostic
techniques for viral infections include biopsy with
histopathologic/cytologic exam as well as viral culture,
polymerase chain reaction (PCR), and antigen detection performed on tissue and/or body fluids, depending on the specific virus. Also, in the case of suspected
disease due to a specific pathogen, empiric treatment
may be necessary, pending a definitive diagnosis. For
infections in transplant patients for which a specific
antiviral medication is not available, the patient may
benefit from modification of the immunosuppressive
regimen.1
Hospital Physician Board Review Manual
Factors Associated with Specific
Infections
Immunosuppressive Regimens
The susceptibility of a transplant patient to infection depends on his or her particular immunosuppressive regimen. Cytotoxic agents such as cyclophosphamide and azathioprine are associated with
high risk for CMV reactivation.2 Corticosteroids have
broadly immunosuppressive effects, but the introduction of calcineurin inhibitors, such as cyclosporine
and tacrolimus, has allowed a dose reduction of
corticosteroids, with fewer infectious disease complications.3 No differences in overall infection rate have
been observed among patients receiving cyclosporine
or tacrolimus4; however, tacrolimus is suspected to increase the risk of BK virus nephropathy as compared
to cyclosporine.5 Mycophenolate mofetil (MMF) is
a selective inhibitor of purine biosynthesis, preventing the proliferation of T and B cells; it has largely
replaced azathioprine in transplant immunosuppressive regimens.5 However, MMF use is associated with
a higher risk of CMV infection.4 Tacrolimus and MMF
have been associated with an increased risk for parvovirus B19 infection.6
Polyclonal antilymphocyte serums and antithymocyte globulins (lymphocyte-depleting antibodies) are
used in transplant induction regimens and to treat rejection. However, these agents cause increased risk of
CMV disease and post-transplant lymphoproliferative
disease due to EBV.7,8 It has been suggested that when
these agents are used to treat rejection, anti-CMV prophylaxis is appropriate.9 Recently, non–lymphocyte
depleting monoclonal antibodies, such as daclizumab
and basiliximab, directed specifically against activated
T-cells have been employed as immunosuppressants;
these agents pose less risk for CMV reactivation than
the lymphocyte-depleting antibodies.8
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