Page 307 - Review of Medical Microbiology and Immunology ( PDFDrive )

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PART IV Clinical Virology
CMV also encodes a protein that functions as a chemo-
kine receptor. When this protein is released from CMV-
infected cells, the protein binds to chemokines thereby
preventing the chemokines from serving as a signal for host
immune cells to migrate to the site of CMV infection.
CMV infection causes an immunosuppressive effect by
inhibiting T cells. Host defenses against CMV infection
include both circulating antibody and cell-mediated
immunity. Cellular immunity is more important, because
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mebooksfree.com mebooksfree.com mebooksfree.com FIGURE 37–7 Cytomegalovirus—owl’s eye inclusion body. mebooksfree.com
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its suppression can lead to systemic disease.
Clinical Findings
Approximately 20% of infants infected with CMV during
gestation show clinically apparent manifestations of cyto-
megalic inclusion disease such as microcephaly, seizures,
deafness, jaundice, and purpura. The purpuric lesions
Arrow points to an “owl’s eye” inclusion body in the nucleus of an
resemble a “blueberry muffin” and are due to thrombocy-
infected cell. (Source: Dr. Edwin Ewing, Jr., Public Health Image Library, Centers
topenia. Hepatosplenomegaly is very common. Cytome-
for Disease Control and Prevention.)
galic inclusion disease is one of the leading causes of
mental retardation in the United States. Infected infants
can continue to excrete CMV, especially in the urine, for
Ganciclovir (Cytovene) is moderately effective in the treat-
several years. Treatment
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mebooksfree.com mebooksfree.com mebooksfree.com ganciclovir and valganciclovir have emerged, mostly due to mebooksfree.com
In immunocompetent adults, CMV can cause hetero-
ment of CMV retinitis and pneumonia in patients with
phil-negative mononucleosis, which is characterized by
AIDS. Valganciclovir, which can be taken orally, is also
effective against CMV retinitis. CMV strains resistant to
fever, lethargy, and the presence of abnormal lymphocytes
in peripheral blood smears. In immunocompromised
patients, systemic CMV infections, especially pneumoni-
mutations in the d gene that encodes the phosphokinase.
tis, esophagitis, and hepatitis, occur in a high proportion
Drug susceptibility testing can be done.
of those individuals (e.g., those with renal and bone mar-
Foscarnet (Foscavir) is also effective but causes more side
row transplants). In patients with acquired immunodefi-
effects. Unlike HSV and VZV, CMV is largely resistant to
ciency syndrome (AIDS), CMV commonly infects the
acyclovir. Cidofovir (Vistide) is also useful in the treatment
of CMV retinitis. Fomivirsen (Vitravene) is an antisense
intestinal tract and causes intractable colitis with diarrhea.
DNA approved for the intraocular treatment of CMV retini-
CMV also causes retinitis in AIDS patients, which can lead
tis. It is the first and, at present, the only antisense molecule
to blindness.
to be approved for the treatment of human disease.
Laboratory Diagnosis
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Prevention
The preferred approach involves culturing in special tubes
called shell vials coupled with the use of immunofluores-
There is no vaccine. Ganciclovir can suppress progressive
cent antibody, which can make a diagnosis in 72 hours. The
retinitis in AIDS patients. Infants with cytomegalic inclu-
virus obtained in the culture can then be used to determine
sion disease who are shedding virus in their urine should
the drug susceptibility to ganciclovir.
be kept isolated from other infants. Blood for transfusion to
Other diagnostic methods include fluorescent anti-
newborns should be CMV antibody-negative. If possible,
body and histologic staining of inclusion bodies in giant
only organs from CMV antibody-negative donors should
cells in urine and in tissue. The inclusion bodies are intra-
be transplanted to antibody-negative recipients. A high-
nuclear and have an oval owl’s eye shape (Figure 37–7). A
fourfold or greater rise in antibody titer is also diagnostic.
prevent disseminated CMV infections in organ transplant
PCR-based assays for CMV DNA or RNA in tissue or
body fluids, such as spinal fluid and amniotic fluid, are titer immune globulin preparation (CytoGam) is used to
also very useful.
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EPSTEIN–BARR VIRUS (EBV)
CMV antigenemia can be measured by detecting pp65
within blood leukocytes using an immunofluorescence
assay. pp65 is a protein located in the nucleocapsid of
CMV and can be identified within infected leukocytes
EBV causes infectious mononucleosis. It is associated with
using fluorescein-labeled monoclonal antibody specific
Burkitt’s lymphoma, other B-cell lymphomas, and naso-
for pp65.
pharyngeal carcinoma. EBV also causes hairy leukoplakia.
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