Viral Infections In Transplant Recipients Research Articles

Development and validation of multiplex real-time PCR assays for rapid detection of cytomegalovirus, Epstein-Barr virus, and polyomavirus BK in whole blood from transplant candidates.

Transplant recipients are more susceptible to bacterial and viral infections. Cytomegalovirus (CMV), Epstein-Barr virus (EBV), and polyomavirus BK (BK) are risk factors for graft dysfunction. All three of them are latent viruses that can cause serious disease in immunocompromised patients. Mainly qualitative PCR tests are required for diagnosis and quantitative monitoring, which are used to follow the response to transplantation. We developed a multiplex real-time PCR (qPCR) method to detect these viruses during blood screenings of transplant recipients. We also validated analytical and clinical performance tests using the developed multiplex qPCR. The limit of detection (LOD) was 100, 125, and 183 copies/ml for CMV, EBV, and BK, respectively. These results had high linearity (R2 = 0.997) and reproducibility (CV range, 0.95-2.38%, 0.52-3.32%, and 0.31-2.45%, respectively). Among 183 samples, we detected 8 samples that were positive for CMV, while only 6 were positive for EBV, and 3 were positive for BK. Therefore, the viral infection prevalence in transplant candidates was 4.40% for CMV, 3.29% for EBV, and 1.64% for BK. This multiplex qPCR method should be used widely for diagnosing and monitoring latent viral infections in transplant recipients.

Rare and Emerging Viral Infections in Transplant Recipients

Emerging viral pathogens include newly discovered viruses as well as previously known viruses that are either increasing, or threatening to increase in incidence. While often first identified in the general population, they may affect transplant recipients, in whom their manifestations may be atypical or more severe. Enhanced molecular methods have increased the rate of viral discovery but have not overcome the problem of demonstrating pathogenicity. At the same time, improved clinical diagnostic methods have increased the detection of reemerging viruses in immunocompromised patients. In this review, we first discuss viral diagnostics and the developing field of viral discovery and then focus on rare and emerging viruses in the transplant population: human T-cell leukemia virus type 1; hepatitis E virus; bocavirus; KI and WU polyomaviruses; coronaviruses HKU1 and NL63; influenza, H1N1; measles; dengue; rabies; and lymphocytic choriomeningitis virus. Detection and reporting of such rare pathogens in transplant recipients is critical to patient care and improving our understanding of posttransplant infections.

Évaluation de la plate-forme de PCR en temps réel LightCycler ® 480 pour la mesure des charges virales CMV, EBV, HHV-6 et BKV dans le sang total

Objective The Roche LightCycler ® 480 (LC480) system was evaluated for quantitative molecular diagnosis of opportunistic viral infections caused by human cytomegalovirus (CMV), Epstein-Barr virus (EBV), human herpesvirus 6 (HHV-6), and BK virus (BKV), in comparison with “in-house” real-time PCR assays. Patients and methods A total of 253 whole blood specimens obtained from transplant recipients were tested. Results Both the “in-house” and the LC480 methods were highly correlated (Spearman correlation coefficient Rho ≥ 0.85; p < 0.0001) with an excellent overall qualitative agreement (90.5 %) and no significant quantitative difference between both techniques for the four viruses tested. The accuracy of the LC480 protocols were confirmed further by the results obtained with the 44 samples from the Quality Control for Molecular Diagnosis (QCMD) 2008 proficiency panel. Conclusion The LC480 system constitutes a suitable and versatile real-time PCR platform in a routine laboratory setting for the diagnosis and monitoring of opportunistic viral infections in transplant recipients, by measuring HCMV, EBV, HHV-6, and BKV loads in whole blood samples.

Use of the Roche LightCycler ® 480 system in a routine laboratory setting for molecular diagnosis of opportunistic viral infections: Evaluation on whole blood specimens and proficiency panels

The Roche LightCycler ® 480 (LC480) system was evaluated for quantitative molecular diagnosis of opportunistic viral infections caused by human cytomegalovirus (HCMV), Epstein–Barr virus (EBV), human herpesvirus 6 (HHV-6) and BK virus (BKV), in comparison with “in-house” real-time PCR assays. A total of 253 whole blood specimens obtained from transplant recipients were tested. Both the “in-house” and the LC480 methods were highly correlated (Spearman correlation coefficient Rho ≥ 0.85; p < 0.0001) with an excellent overall qualitative agreement (90.5%) and no significant quantitative difference between both techniques for the four viruses tested. The accuracy of the LC480 protocols were confirmed further by the results obtained with the 44 samples from the Quality Control for Molecular Diagnosis (QCMD) 2008 proficiency panel. The LC480 system constitutes a suitable and versatile real-time PCR platform in a routine laboratory setting for the diagnosis and monitoring of opportunistic viral infections in transplant recipients, by measuring HCMV, EBV, HHV-6, and BKV loads in whole blood samples.

Respiratory viral infections in transplant recipients

A wide range of viruses affect the respiratory tract of transplant recipients, including adenovirus, influenza, human metapneumovirus, parainfluenza virus, respiratory syncytial virus (RSV) and rhinovirus. Prospective studies using contemporary diagnostic techniques have recently improved our understanding of the epidemiology and importance of these respiratory viruses among transplant recipients. From these studies, rhinovirus, in particular, has been shown to be one of the most common causes of infection in stem cell and lung transplant recipients. In addition to epidemiological data, recent studies have also advanced our understanding of management of influenza, adenovirus, and RSV infections among transplant recipients.

Emerging viral infections in transplant recipients

Transplant patients are uniquely predisposed to emerging infections for a number of reasons. Two outbreaks, West Nile virus and severe acute respiratory syndrome, have recently provided important lessons on how transplant patients are affected, and how transplant programmes must adapt and evolve in the face of emerging infections. An update of emerging infections in transplant patients, using West Nile virus and severe acute respiratory syndrome as specific examples, is summarized here. Exogenous immunosuppression, specific allograft factors, and extensive contact with the healthcare system all predispose transplant patients to emerging infections. Transplant patients may acquire West Nile virus through blood transfusion, donor transmission, or community exposure. Seroprevalence data in transplant populations suggest the risk of severe neurological disease is several fold higher in transplant recipients who acquire West Nile virus compared with immunocompetent individuals. Prevention strategies are critical in this population. These include nucleic acid testing of blood products and potentially also screening organ donors in a similar manner. During the outbreak of severe acute respiratory syndrome, transplant patients with severe and rapidly progressive disease were reported. Higher viral burdens appeared to be present in transplant patients and may have implications for the increased infectivity of these patients. Transplant programmes in severe acute respiratory syndrome areas were also adversely affected because of donor concerns, recipient issues and resource problems. Transplant patients are uniquely predisposed to emerging infections. Lessons learned from West Nile virus and severe acute respiratory syndrome in transplantation should be applicable to future outbreaks of other emerging infectious diseases.

Common viral infections in transplant recipients, Part 2. Respiratory viruses, polyomaviruses, and erythroviruses

Abstract Transplant recipients are at increased risk of morbidity and mortality from viral infections. Common respiratory virus infections, including influenza, parainfluenza 1 to 3, respiratory syncytial virus, adenovirus, rhinovirus, and human metapneumovirus, can cause significant disease and can be acquired through both nosocomial and community spread. In addition, reactivation of viruses, including non-respiratory tract adenoviruses and BK virus, has been associated with hemorrhagic cystitis and acute graft rejection, while reactivation or acute infection with human parvovirus B19 can cause red cell aplasia in transplant recipients. Clinicians need to have a high index of suspicion to properly diagnose and treat these common illnesses.

Common viral infections in transplant recipients, part 1. herpesviruses (continued)

Herpesviruses are common opportunistic infections in transplant recipients. Recent diagnostic and therapeutic advances have improved the prognosis of these infections in transplant patients. Among these, the introduction of quantitative PCR and other molecular assays, dissemination of antiviral susceptibility tests, and upgrading of serologic tests represent the most significant diagnostic improvements in the last 10 years. The use of pre-emptive and prophylactic therapies, coupled with the availability of new oral antivirals, represents the most significant change in the treatment arena.

Common viral infections in transplant recipients, part 1. Herpesviruses

Abstract Herpesviruses are common opportunistic infections in transplant recipients. Recent diagnostic and therapeutic advances have improved the prognosis of these infections in transplant patients. Among these, the introduction of quantitative PCR and other molecular assays, dissemination of antiviral susceptibility tests, and upgrading of serologic tests represent the most significant diagnostic improvements in the last 10 years. The use of pre-emptive and prophylactic therapy, coupled with the availability of new oral antivirals, represents the most significant change in the treatment arena.

Respiratory Viral Infections in Transplant Recipients

A wide range of viruses affect the respiratory tract of transplant recipients, including adenovirus, influenza, human metapneumovirus, parainfluenza virus, respiratory syncytial virus (RSV) and rhinovirus. Prospective studies using contemporary diagnostic techniques have recently improved our understanding of the epidemiology and importance of these respiratory viruses among transplant recipients. From these studies, rhinovirus, in particular, has been shown to be one of the most common causes of infection in stem cell and lung transplant recipients. In addition to epidemiological data, recent studies have also advanced our understanding of management of influenza, adenovirus, and RSV infections among transplant recipients.

BK Virus in Kidney Transplantation: A Case Study

Prevention as well as treatment of viral infections in transplant recipients relies on minimal immunosuppressive therapy consistent with graft survival and the use of antiviral therapies in proportion to perceived risk. BK virus creates an even greater challenge in posttransplant management and graft survival because of difficulty in diagnosing and treatment. BK nephropathy develops in 1% to 5% of transplant recipients, with loss of allograft function occurring in 50% of the cases. We present a case of a 67-year-old man who developed BK virus allograft nephropathy 9.5 months after transplantation. His allograft function was extended through rigorous treatment with an antiviral agent, reduction of immunosuppressant, and monitoring in an outpatient setting.

BK virus in kidney transplantation: a case study

Prevention as well as treatment of viral infections in transplant recipients relies on minimal immunosuppressive therapy consistent with graft survival and the use of antiviral therapies in proportion to perceived risk. BK virus creates an even greater challenge in posttransplant management and graft survival because of difficulty in diagnosing and treatment. BK nephropathy develops in 1% to 5% of transplant recipients, with loss of allograft function occurring in 50% of the cases. We present a case of a 67-year-old man who developed BK virus allograft nephropathy 9.5 months after transplantation. His allograft function was extended through rigorous treatment with an antiviral agent, reduction of immunosuppressant, and monitoring in an outpatient setting.

Fatal disseminated adenovirus infection in a renal transplant recipient

A 61 year old woman died of diffuse interstitial adenovirus pneumonia 55 days after receiving a cadaveric renal allograft. The adenovirus was serologically distinct from the 33 known human adenovirus serotypes and appears to represent a new human adenovirus. Pathologic and virological findings indicate that the pneumonia was only one manifestation of a disseminated infection, the source of which may have been a latent adenovirus infection preexisting in the donor kidney. The establishment of the etiologic diagnosis in this case, which was complicated by the presence of oculocutaneous and esophageal herpes simplex virus infection as well as focal pulmonary aspergillosis, required coordinated histopathologic and virological investigation. Our findings demonstrate that severe viral infections in transplant recipients are not caused exclusively by members of the herpesvirus group.