Review
Quantification of cytomegalovirus viral load Expert Review of Anti-infective Therapy Downloaded from informahealthcare.com by UMEA University Library on 10/12/14 For personal use only.
Expert Rev. Anti Infect. Ther. 12(2), 193–210 (2014)
Sylvie Pillet*1,2, Xavier Roblin1,3, Je´roˆme Cornillon4, Christophe Mariat1,5 and Bruno Pozzetto1,2 1 Faculty of Medicine of Saint-Etienne, University of Lyon, Groupe Immunite´ des Muqueuses et Agents Pathoge`nes (GIMAP)-EA3064, 42023 Saint-Etienne, France 2 Laboratory of Bacteriology-VirologyHygiene, University Hospital of SaintEtienne, 42055 Saint-Etienne, France 3 Department of Gastro-Enterology, University Hospital of Saint-Etienne, 42055 Saint-Etienne, France 4 Department of Clinical Hematology, Institut de Cance´rologie Lucien Neuwirth, Saint-Etienne, France 5 Department of Nephrology, University Hospital of Saint-Etienne, 42055 Saint-Etienne, France *Author for correspondence: Tel.: +33 477 828 122 Fax: +33 477 828 460 [email protected]
www.expert-reviews.com
Cytomegalovirus (CMV), a member of the Herpesviridae family, is worldwide distributed. After the primary infection, CMV induces a latent infection with possible reactivation(s). It is responsible for severe to life-threatening diseases in immunocompromised patients and in foetuses and newborns of infected mothers. For monitoring CMV load, classical techniques based on rapid culture or pp65 antigenemia are progressively replaced by quantitative nuclear acid tests (QNAT), easier to implement and standardize. A large variety of QNAT are available from laboratory-developed assays to fully-automated commercial tests. The indications of CMV quantification include CMV infection during pregnancy and in newborns, and viral surveillance of grafted and non-grafted immunocompromised patients, patients with bowel inflammatory diseases and those hospitalised in intensive care unit. A close cooperation between virologists and clinicians is essential for optimizing the benefit of CMV DNA monitoring. KEYWORDS: congenital infection • cytomegalovirus • immunocompromised patients • molecular biology • quantitative nucleic acid test • standardization
Cytomegalovirus (CMV) is a member of the Herpesviridae family that includes enveloped double-stranded DNA viruses able to be transmitted by close contacts, to replicate during primary infection, to persist long life in cells where they establish a latent program and to reactivate in some situations. The viral latency takes place mainly in the endothelial cells, the myeloid lineage cells and the monocytes, leading to the presence of the viral DNA in the different organs. The reactivation ways of CMV are not completely understood but immune stimulation, inflammation and differentiation of myeloid cells and monocytes to macrophages play a major role in this process [1–3]. CMV is an important pathogen responsible for morbidity and mortality notably in case of materno-fetal transmission or immunosuppression (TABLE 1). From a virological point of view, three situations must be distinguished: CMV latency that implies the presence of viral genome without CMV replication, CMV infection that corresponds to evidence of CMV replication regardless of symptoms and CMV disease that is a symptomatic CMV infection (from viral syndrome to end-organ disease) [4]. With more patients undergoing transplants and the expanding indications for immunomodulating drugs, the number of patients at risk for
10.1586/14787210.2014.870887
developing CMV disease is currently increasing. Beyond the detection of the virus or its components, the quantification of CMV load has been shown to play a major role in the monitoring of patients with CMV disease in different clinical contexts involving a perturbation of the immune system, and notably in transplant patients – either solid organ transplant (SOT) or hematopoietic stem cell transplant (HSCT) – and in HIV-infected patients, and also in newborns, in intensive care units (ICUs) patients and in those exhibiting symptoms of inflammatory bowel disease (IBD). CMV is also associated with several inflammatory diseases and cancer [3] and with stigmata of immune senescence via successive CMV reactivation exhausting the adaptative immune response, notably in HIV-infected patients [5]. Currently, monitoring the CMV load in peripheral blood is routinely used for identifying patients at high risk of developing CMV disease; diagnosing an active infection, notably before the apparition of symptoms; determining when to initiate antiviral preemptive therapy and following the response to therapy. From the several techniques available for the monitoring of CMV load, quantitative nucleic acid testing (QNAT) assays are the most commonly used. However, these methods have
2014 Informa UK Ltd
ISSN 1478-7210
193
Review
Pillet, Roblin, Cornillon, Mariat & Pozzetto
Expert Review of Anti-infective Therapy Downloaded from informahealthcare.com by UMEA University Library on 10/12/14 For personal use only.
Table 1. Risk factors and clinical manifestation associated with direct and indirect effects of cytomegalovirus disease. Patient population
Risk factors for developing CMV infection or disease
Clinical manifestations
HIV-infected patients
CD4 count of
Quantification of cytomegalovirus viral load Expert Review of Anti-infective Therapy Downloaded from informahealthcare.com by UMEA University Library on 10/12/14 For personal use only.
Expert Rev. Anti Infect. Ther. 12(2), 193–210 (2014)
Sylvie Pillet*1,2, Xavier Roblin1,3, Je´roˆme Cornillon4, Christophe Mariat1,5 and Bruno Pozzetto1,2 1 Faculty of Medicine of Saint-Etienne, University of Lyon, Groupe Immunite´ des Muqueuses et Agents Pathoge`nes (GIMAP)-EA3064, 42023 Saint-Etienne, France 2 Laboratory of Bacteriology-VirologyHygiene, University Hospital of SaintEtienne, 42055 Saint-Etienne, France 3 Department of Gastro-Enterology, University Hospital of Saint-Etienne, 42055 Saint-Etienne, France 4 Department of Clinical Hematology, Institut de Cance´rologie Lucien Neuwirth, Saint-Etienne, France 5 Department of Nephrology, University Hospital of Saint-Etienne, 42055 Saint-Etienne, France *Author for correspondence: Tel.: +33 477 828 122 Fax: +33 477 828 460 [email protected]
www.expert-reviews.com
Cytomegalovirus (CMV), a member of the Herpesviridae family, is worldwide distributed. After the primary infection, CMV induces a latent infection with possible reactivation(s). It is responsible for severe to life-threatening diseases in immunocompromised patients and in foetuses and newborns of infected mothers. For monitoring CMV load, classical techniques based on rapid culture or pp65 antigenemia are progressively replaced by quantitative nuclear acid tests (QNAT), easier to implement and standardize. A large variety of QNAT are available from laboratory-developed assays to fully-automated commercial tests. The indications of CMV quantification include CMV infection during pregnancy and in newborns, and viral surveillance of grafted and non-grafted immunocompromised patients, patients with bowel inflammatory diseases and those hospitalised in intensive care unit. A close cooperation between virologists and clinicians is essential for optimizing the benefit of CMV DNA monitoring. KEYWORDS: congenital infection • cytomegalovirus • immunocompromised patients • molecular biology • quantitative nucleic acid test • standardization
Cytomegalovirus (CMV) is a member of the Herpesviridae family that includes enveloped double-stranded DNA viruses able to be transmitted by close contacts, to replicate during primary infection, to persist long life in cells where they establish a latent program and to reactivate in some situations. The viral latency takes place mainly in the endothelial cells, the myeloid lineage cells and the monocytes, leading to the presence of the viral DNA in the different organs. The reactivation ways of CMV are not completely understood but immune stimulation, inflammation and differentiation of myeloid cells and monocytes to macrophages play a major role in this process [1–3]. CMV is an important pathogen responsible for morbidity and mortality notably in case of materno-fetal transmission or immunosuppression (TABLE 1). From a virological point of view, three situations must be distinguished: CMV latency that implies the presence of viral genome without CMV replication, CMV infection that corresponds to evidence of CMV replication regardless of symptoms and CMV disease that is a symptomatic CMV infection (from viral syndrome to end-organ disease) [4]. With more patients undergoing transplants and the expanding indications for immunomodulating drugs, the number of patients at risk for
10.1586/14787210.2014.870887
developing CMV disease is currently increasing. Beyond the detection of the virus or its components, the quantification of CMV load has been shown to play a major role in the monitoring of patients with CMV disease in different clinical contexts involving a perturbation of the immune system, and notably in transplant patients – either solid organ transplant (SOT) or hematopoietic stem cell transplant (HSCT) – and in HIV-infected patients, and also in newborns, in intensive care units (ICUs) patients and in those exhibiting symptoms of inflammatory bowel disease (IBD). CMV is also associated with several inflammatory diseases and cancer [3] and with stigmata of immune senescence via successive CMV reactivation exhausting the adaptative immune response, notably in HIV-infected patients [5]. Currently, monitoring the CMV load in peripheral blood is routinely used for identifying patients at high risk of developing CMV disease; diagnosing an active infection, notably before the apparition of symptoms; determining when to initiate antiviral preemptive therapy and following the response to therapy. From the several techniques available for the monitoring of CMV load, quantitative nucleic acid testing (QNAT) assays are the most commonly used. However, these methods have
2014 Informa UK Ltd
ISSN 1478-7210
193
Review
Pillet, Roblin, Cornillon, Mariat & Pozzetto
Expert Review of Anti-infective Therapy Downloaded from informahealthcare.com by UMEA University Library on 10/12/14 For personal use only.
Table 1. Risk factors and clinical manifestation associated with direct and indirect effects of cytomegalovirus disease. Patient population
Risk factors for developing CMV infection or disease
Clinical manifestations
HIV-infected patients
CD4 count of
