ArticlesApplication of viral-load kinetics to identify patients who develop cytomegalovirus disease after transplantation
Introduction
The post-transplant immunocompromised state provides an environment in which cytomegalovirus (CMV) can exert its full pathogenic potential.1 Disease manifestations include pneumonitis, hepatitis, gastrointestinal disease, and pyrexial debilitating illness, whose incidences and relative frequencies vary among transplant groups under consideration.2, 4 It has been known for many years that measurement of the serostatus of donor and recipient at the time of transplant provides prognostic information about the risk of developing CMV disease.5 Specifically, for solid-organ transplants, seropositive donors frequently transmit CMV to recipients6 whether they are themselves seronegative (primary infection) or seropositive (reinfection). Seropositive recipients frequently excrete CMV but have a low risk of CMV disease unless the donor is seropositive.7 After a bone-marrow transplant reactivation of endogenous CMV from a seropositive recipient provides the virus that causes CMV disease.8, 9
In a series of prospective studies, we have identified peak CMV load during active infection as a major risk factor that correlates with the development of CMV disease.10, 11, 12, 13 Furthermore, we showed by multivariate statistical methods that the classical risk factors of donor/recipient serostatus were entirely explained by viral load.10, 11, 12, 13 Thus, donor/recipient serostatus provides prognostic information because it identifies subgroups of patients who will develop high CMV loads post-transplant. However, while this observation helped to explain the pathogenesis of CMV in groups of patients, it did not have immediate practical applications for individuals because the peak viral load frequently occurs when the patient experiences CMV disease. We have therefore continued the analysis of data from these prospective studies to find out whether measurement of CMV viral load in the earliest available samples and calculation of the kinetics of viral replication can provide prognostic information.
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Patients
Our prospective studies to identify cases of CMV disease have previously been described for renal transplant,11, 13 liver transplant,10 and bone-marrow transplant12 populations. Patient recruitment occurred between 1992 and 1996 and no patient received prophylactic gangiclovir. In addition, 90% of patients received no pre-emptive ganciclovir therapy based upon laboratory markers of active CMV infection. In the case of the bone-marrow transplant recipients, prophylactic acyclovir was given
Relation between initial viral load and peak viral load
Initial CMV V loads ranged FROM 2·69 to 7·53 log10 genomes/mL (median 4·20); peak loads ranged from 2·70 to 7·57 log10 genomes/mL (median 4·50).
Both initial and peak CMV loads were lower in bone-marrow-transplant recipients compared with the other two patient groups (renal recipients-initial load 4·6 [2·9–6·5] log10 genomes/L, peak load 5·3 [2·9–7·5] log10 genomes/mL; liver recipients-initial load 4·6 [3·6–7·5] log10 genomes/mL, peak load 4·9 [3·6–7·5] log10 genomes/mL; bone marrow
Discussion
We have previously shown that peak viral loads correlate with CMV disease10, 11, 12, 13 and now show that the viral load in the first available sample and the rate of increase in viral load can identify patients at risk of developing high peak values and clinical disease. A two-dimensional contour map is provided, from which the disease risk for an individual can be estimated using factors calcualted from the first available measurement of CMV viral load. Thus, very early events surrounding the
References (25)
- et al.
Symptomatic cytomegalovirus infection in seropositive kidney recipients: reinfection with donor virus rather than reactivation of recipient virus
Lancet
(1988) - et al.
Impact of long-term acyclovir on cytomegalovirus infection and survival after allogeneic bone marrow transplantation
Lancet
(1994) - et al.
Lymphotropic herpes virus in allogeneic bone marrow transplantation
Blood
(1996) - et al.
Polymerase chain reaction monitoring reduces the incidence of cytomegalovirus disease and the duration of side effects on antiviral therapy after bone marrow transplantation
Blood
(1995) The indirect effects of cytomegalovirus infection on the outcome of organ transplantation
JAMA
(1989)- et al.
Effect of cytomegalovirus infection status on first-year mortality rates among orthotopic liver transplant recipients: The Boston Center for Liver Transplantation CMVIG Study Group
Ann Intern Med
(1997) - et al.
Association of specific cytomegalovirus genotypes with death from myelosuppression after marrow transplantation
Blood
(1999) - et al.
Clinical manifestations of renal allograft derived primary cytomegalovirus infection
Am J Dis Child
(1977) Reactivation and recombination of multiple cytomegalovirus strains from individual organ donors
J Infect Dis
(1989)- et al.
Molecular epidemiology of cytomegalovirus infections associated with bone marrow transplantation
Ann Intern Med
(1985)
Immune donors can protect marrow-transplant recipients from severe cytomegalovirus infections
Lancet
Interrelationships among quantity of human cytomegalovirus (HCMV) DNA in blood, donor-recipient serostatus, and administration of methylprednisolone as risk factors for HCMV disease following liver transplantation
J Infect Dis
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