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Virology

Frequent Occult Infection with Cytomegalovirus in Cardiac Transplant Recipients despite Antiviral Prophylaxis

Luciano Potena, Cecile T. J. Holweg, Marcy L. Vana, Leena Bashyam, Jaya Rajamani, A. Louise McCormick, John P. Cooke, Hannah A. Valantine, Edward S. Mocarski
Luciano Potena
1Departments of Medicine
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Cecile T. J. Holweg
1Departments of Medicine
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Marcy L. Vana
2Microbiology & Immunology, Stanford University School of Medicine, Stanford, California
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Leena Bashyam
2Microbiology & Immunology, Stanford University School of Medicine, Stanford, California
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Jaya Rajamani
2Microbiology & Immunology, Stanford University School of Medicine, Stanford, California
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A. Louise McCormick
2Microbiology & Immunology, Stanford University School of Medicine, Stanford, California
3Department of Microbiology & Immunology, Emory University School of Medicine, Atlanta, Georgia
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John P. Cooke
1Departments of Medicine
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Hannah A. Valantine
1Departments of Medicine
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Edward S. Mocarski
2Microbiology & Immunology, Stanford University School of Medicine, Stanford, California
3Department of Microbiology & Immunology, Emory University School of Medicine, Atlanta, Georgia
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  • For correspondence: mocarski@emory.edu
DOI: 10.1128/JCM.01362-06
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    FIG. 1.

    Kaplan-Meier analysis of the incidence of the first CMV DNA detection in PB cells and cardiac EMB samples from heart transplant recipients receiving anti-CMV prophylaxis. Results of qualPCR detection in PMNs (gray line), PBMCs (black line), and EMB specimens (dashed line) are shown.

  • FIG. 2.
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    FIG. 2.

    Differences in length of time to the first detection of CMV DNA based on cell type and CMV serostatus at transplant. (A) Time to first CMV detection in PBMCs versus PMNs in R+/D+ patients (P = 0.016 by Wilcoxon signed-rank paired analysis). (B) Time to first CMV detection in PBMCs versus PMNs in R−/D+ patients (P = 0.9 by Wilcoxon signed-rank paired analysis). (C) Time to first CMV detection in PBMCs versus PMNs in R+/D− patients (P = 0.5 by Wilcoxon signed-rank paired analysis). The thick line indicates the median, the lower and upper sides of the rectangles indicate 25th and 75th percentiles, respectively, and the bars indicate the 90th and 10th percentile limits.

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    FIG. 3.

    CMV DNA detection based on donor/recipient CMV serostatus at transplant. The Kaplan-Meier estimated incidence of CMV detection in PBMCs (A) or in PMNs (B) is shown. Determinations of the statistical significance of R+ and R−/D+ differences employed the log-rank test.

  • FIG. 4.
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    FIG. 4.

    Frequency of high-level CMV DNA in heart transplant recipients receiving anti-CMV prophylaxis. (A) Rate of samples showing >110 DNA copies/105 PMNs (high-grade infection) in the R−/D+ (open circles) and R+ (filled circles) patient groups over 16 months posttransplant. (Time periods were as follows: month 1, 14 to 45 days; month 2, 46 to 76 days; month 3, 77 to 105 days; month 4, 106 to 161 days; months 5 to 7, 162 to 208 days; months 8 to 10, 209 to 304 days; months 11 to 13, 305 to 426 days; months 14 to 16, 427 to 486 days). The standard prophylaxis period used for R+ patients is indicated by dark gray shading, and the aggressive prophylaxis period used for R−/D+ patients is indicated by light gray shading. (B) Distribution of patients developing low-grade (≤110 copies/105 cells) and high-grade (>110 copies/105 cells) infection according to CMV serological status.

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  • TABLE 1.

    Baseline patient characteristics according to CMV DNA levels

    No. of CMV DNA copiesRecipient age (yr; P = 0.96)a,bRecipient gender (males/females; P = 0.61)cDonor age (yr; P = 0.95)bDonor gender (males/females; P = 0.77)cCold ischemic time (min; P = 0.67)bProphylaxis protocol (P = 0.04)c
    Standard (no. [%] of R+/D+ and R+/D− patients; P = 0.04)cAggressive (no. [%] of R−/D+ patients)
    ≤110 (n = 46)49 ± 1435/1133 ± 1433/13203 ± 4428 (61)18 (39)
    >110 (n = 20)48 ± 1514/632 ± 1215/5212 ± 5717 (85)3 (15)
    • ↵ a Means ± standard deviations.

    • ↵ b Student's t analysis.

    • ↵ c Chi-square analysis.

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Frequent Occult Infection with Cytomegalovirus in Cardiac Transplant Recipients despite Antiviral Prophylaxis
Luciano Potena, Cecile T. J. Holweg, Marcy L. Vana, Leena Bashyam, Jaya Rajamani, A. Louise McCormick, John P. Cooke, Hannah A. Valantine, Edward S. Mocarski
Journal of Clinical Microbiology Jun 2007, 45 (6) 1804-1810; DOI: 10.1128/JCM.01362-06

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Frequent Occult Infection with Cytomegalovirus in Cardiac Transplant Recipients despite Antiviral Prophylaxis
Luciano Potena, Cecile T. J. Holweg, Marcy L. Vana, Leena Bashyam, Jaya Rajamani, A. Louise McCormick, John P. Cooke, Hannah A. Valantine, Edward S. Mocarski
Journal of Clinical Microbiology Jun 2007, 45 (6) 1804-1810; DOI: 10.1128/JCM.01362-06
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KEYWORDS

Antiviral Agents
cytomegalovirus
ganciclovir
Heart Transplantation
Immunoglobulins, Intravenous
Immunologic Factors
viremia

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