Journal Information
Vol. 16. Issue 2.
Pages 146-152 (March - April 2012)
Share
Share
Download PDF
More article options
Vol. 16. Issue 2.
Pages 146-152 (March - April 2012)
Open Access
Early HHV-6 replication is associated with morbidity non-related to CMV infection after kidney transplantation
Visits
7468
Regina Barbosa Schroeder
Corresponding author
rbs_schroeder@hotmail.com

Corresponding author at: Laboratório de Imunologia de Transplantes, Hospital Dom Vicente Scherer, Av. Independência 75, Porto Alegre, RS, 94035-075, Brazil.
, Tatiana Ferreira Michelon, Gabriela Garbin, Valter Garcia, Janaina Gomes da Silveira, Luciano Santos, Jorge Neumann, Elizete Keitel
Complexo Hospitalar Santa Casa de Misericórdia de Porto Alegre, Universidade Federal de Ciências Médicas de Porto Alegre, Porto Alegre, RS, Brazil
This item has received

Under a Creative Commons license
Article information
Abstract

Human herpesvirus type 6-(HHV-6) has been associated with morbidity after liver transplantation.

Objective

The aim of this study was to determine the HHV-6 seroprevalence among donorrecipient pairs, analyze the incidence of early active infection, its clinical manifestation, interaction with CMV, and the related morbidity in the first year after kidney transplantation.

Methods

46 donor-recipient pairs had IgG evaluated by ELISA before transplantation: HHV-6-(Pambio – USA) and CMV-(Roche – USA). A frozen whole blood sample collected weekly (from the 1st to the 6th week) was retrospectively tested for HHV-6 viral load (VL) determination by real time quantitative PCR (qPCR, Nanogen – Italy). Patients were preemptively surveyed for CMV by pp65 antigenemia (Ag, APAAP, immunohistochemistry, Biotest – Germany) from the 4th to the 12th week after transplantation. Active infection was defined as qPCR-HHV6+ (viral-load/mL-VL) and Ag+ (+cells/100.000 granulocytes), for HHV-6 and CMV, respectively. DCMV was defined as simultaneous positive antigenemia and suggestive signs/symptoms. Concerning +qPCR-HHV6, associated factors, clinical manifestation, interaction with CMV and morbidity were searched.

Results

Pre-transplant HHV-6 seroprevalence was significantly higher among kidney recipients compared to their donors (82.6×54.8%; p=0.005 [3.9 (1.4–10.4)]). Active infection by this virus occurred in 26.1% (12/46), with no association with previous IgG (p=0.412). Median VL was 125 copies/mL (53–11.264), and the median Ag was 21 +cells (2–740). There was no association between HHV-6 and CMV activation after transplantation (p=0.441), neither concerning DCMV (p=0.596). Median highest Ag+ and days of ganciclovir treatment were similar between qPCR-HHV6 + or − (p=0.206 and p=0.124, respectively). qPCR-HHV6+ was associated with higher incidence of bacterial (p=0.009) and fungal (p = 0.001) infections, and higher number (p=0.001) of hospital admission and longer duration of hospitalization over the first 6 and 12 months post-transplantation (p=0.033 and p=0.001).

Conclusion

Latent HHV-6 infection is more common among recipients than donors before transplantation. Early active infection by this pathogen after transplantation does not increase DCMV incidence or severity during the first 3 months of follow-up. However, early HHV-6 replication is associated with other infections and hospitalizations in the first year.

Keywords:
Cytomegalovirus infections
Herpesvirus 6, human
DNA virus infections
Clinical diagnosis
Polymerase chain reaction
Full text is only aviable in PDF
References
[1.]
L. De Bolle, L. Naesens, E. De Clercq.
Update on human herpesvirus 6 biology, clinical features, and therapy.
Clin Microbiol Rev, 18 (2005), pp. 217-245
[2.]
D.M. Zerr, A.S. Meier, S.S. Selke, et al.
A population-based study of primary human herpesvirus 6 infection.
N. Engl J. Med, 342 (2005), pp. 768
[3.]
R. Schroeder, T. Michelon, I. Fagundes, et al.
Cytomegalovirus disease latent and active infection rates during the first trimester after kidney transplantation.
Transplant Proc, 36 (2004), pp. 896-898
[4.]
N. Singh, D. Peterson.
Encephalitis caused by human herpesvirus-6 in transplant recipients.
Transplantation, 69 (2000), pp. 2474-2479
[5.]
D.C. Brennan.
Highlights From The Sixth Annual Ast Winter Symposium — Transplantation meets infection: microbes, rejection, atherosclerosis, and malignancy.
Medscape Transplantation, 3 (2002), pp. 1-14
[6.]
C. Tianssheng, D. Hudnall.
Anatomical mapping of human herpesvirus reservoirs of infection.
Mod Pathol, 19 (2006), pp. 726-737
[7.]
P. Lusso.
Human herpesvirus 6 (HHV-6).
Antiviral Research, 31 (1996), pp. 1-21
[8.]
A.C. Schmidt, F. Wilborn, K. Weiss, et al.
A prospective study of human herpesvirus type 6 detected by polymerase chain reaction after liver transplantation.
Transplantation, 61 (1995), pp. 662
[9.]
N. Benito, A. Moreno, M. Pumarola, et al.
Virus del herpes humano tipo 6 y tipo 7 em receptores de transplante.
Enferm Infecc Microbiol Clin, 21 (2003), pp. 424-432
[10.]
J. Rogers, S. Rohal, D. Carrigan, et al.
Human herpesvirus-6 in liver transplant recipients.
Transplantation, 6 (2000), pp. 2566-2573
[11.]
V. Ratnamohan, J. Chapman, H. Howse.
Cytomegalovirus and human herpesvirus 6 both cause viral disease after renal transplantation.
Transplantation, 66 (1998), pp. 877-882
[12.]
J.A. Desjardin, E. Cho, S. Supran, et al.
Association of human herpesvirus 6 reactivation with severe cytomegalovirusassociated disease in orthotopic liver transplant recipients.
Clin Infect Dis, 33 (2001), pp. 1358-1362
[13.]
R. Schroeder, T. Michelon, I. Fagundes, et al.
Antigenemia for cytomegalovirus in renal transplantation: choosing a cutoff for the diagnosis criteria in cytomegalovirus disease.
Transplant Proc, 37 (2005), pp. 2781-2783
[14.]
I. Lautenschlager, K. Linnavuori, K. Hockerstedt.
Human herpesvirus-6 antigenemia after liver transplantation.
Transplantation, 69 (2000), pp. 2561-2566
[15.]
S. Reddy, P. Manna.
Quantitative detection and differentiation of human herpesvirus 6 subtypes in bone marrow transplant patients by using a single real-time polymerase chain reaction assay.
Biol Blood Marrow Transplant, 11 (2005), pp. 530-541
[16.]
A.M. Visser, G.J. Van Doornum, J.J. Coernelissen, et al.
Severe amnesia due to HHV-6 Encephalitis after allogenic stem cell transplantation.
Eur Neurol, 54 (2005), pp. 233-234
[17.]
D. Boutolleau, C. Duros, P. Bonnafous, et al.
Identification of human herpesvirus 6 variants A and B by primer-specific realtime PCR may help to revisit their respective role in pathology.
J Clin Virol, 35 (2006), pp. 257-263
[18.]
Al Komaroff, S. Jacobson.
Highlights from 5th international conference on HHV-6 and -7.
Herpes, 13 (2006), pp. 81-82
[19.]
D. Deborska-Materkowska, Z. Lewandowski, A. Sadowska, et al.
Fever, human herpesvirus 6 (HHV-6) seroconversion, and acute rejection episodes as a function of the initial seroprevalence for HHV-6 in renal transplant recipients.
Transplant Proc, 38 (2006), pp. 139-143
[20.]
I. Lautenschlager, M. Harma, K. Hockerstedt, et al.
Human herpesvirus-6 infection is associated with adhesion molecule induction and lymphocyte infiltration in liver allografts.
J Hepatol, 37 (2002), pp. 648-654
[21.]
J.C. Mendez, D.H. Dockrell, M.J. Espy, et al.
Human betaherpesvirus interactions in solid organ transplant recipients.
J Infect Dis, 183 (2001), pp. 179-184
[22.]
M. Ohashi, K. Sugata, M. Ihira, et al.
Human herpesvirus 6 infection in adult living related liver transplant recipients.
Liver Transpl, 14 (2008), pp. 100-109
[23.]
A. Humar, A. Asberg, D. Kumar, et al.
An assessment of herpesvirus co-infection in patients with CMV disease: correlation with clinical and virologic outcomes.
Am J Transplant, 9 (2009), pp. 374-381
[24.]
J.A. Desjardin, L. Gibbons, E. Cho, et al.
Human herpesvirus 6 reactivation is associated with cytomegalovirus and syndromes in kidney transplant recipients at risk for primary cytomegalovirus infection.
J Infect Dis, 178 (1998), pp. 1783
[25.]
A.S. Pacsa, S. Essa, A. Voevodin, et al.
Correlation between CMV genotypes, multiple infections with herpesviruses (HHV-6,7) and development of CMV disease in kidney recipients in Kiwait.
FEMS Immunol and Med Microbiol, 35 (2003), pp. 125-130
[26.]
S. Yang, R.E. Rothman.
PCR-based diagnostics for infectious diseases: uses, limitations, and future applications in acutecare settings.
Lancet Infect Dis, 4 (2004), pp. 337-348
[27.]
M.J. Espy, J.R. Uhl, L.M. Sloan, et al.
Real-time PCR in clinical microbiology: applications for routine laboratory testing.
Clin Microbiol Rev, 19 (2006), pp. 165-256
[28.]
R.N. Gunson, T.C. Collins, W.F. Carman.
Practical experience of high throughput real-time PCR in the routine diagnostic virology setting.
J Clin Virol, 35 (2006), pp. 355-367
[29.]
R. Schroeder, T. Michelon, R. Adamy, et al.
Infection after kidney transplantation: comparison between pp65 antigenemia and real time PCR. (resumo PO135).
Programa e resumos: IX Congresso Luso Brasileiro de Transplantacao,
Copyright © 2012. Elsevier Editora Ltda.. All rights reserved
The Brazilian Journal of Infectious Diseases
Article options
Tools