Virus Infection In Transplant Recipients Research Articles

Transplant in the age of global warming: What is known about the impact of emerging tropical arbovirus infections

Climate change and human migration continue to impact the infectious risks of transplantation, as emerging infections are newly recognised in transplant candidates and recipients. Limited data about the risks of these novel pathogens in transplant make decisions about the optimal timing and safety of transplant challenging, particularly in areas experiencing the initial presentation of new arboviruses. This presentation will focus on information available about the clinical manifestations of Dengue, Chikungunya, and Zika virus infections in transplant recipients. The limitations and challenges of laboratory diagnosis in the transplant candidate and recipient will be discussed, and the existing data on clinical syndromes reviewed. Recommendations for patient management and infection avoidance will also be covered, along with current clinical guidelines regarding transplant donor and candidate eligibility for transplant in areas experiencing active arbovirus infection transmission. Some infectious risks are inherent to the transplant process, and widely acceptable due to the significant benefits of transplant. Understanding the implications of emerging infections on the immunocompromised transplant population remains a work in progress, and research in this area is essential to successfully mitigate risk. The morbidity and mortality of West Nile virus infection in transplant recipients demonstrates the potentially severe manifestations of arbovirus infection in this population, and the need to closely monitor outcomes whenever novel infectious agents initially present in unique immunosuppressed patient groups.

Viral infections in solid organ transplant recipients: novel updates and a review of the classics.

To summarize new discoveries in viral pathogenesis and novel therapeutic and prophylactic strategies in organ transplant recipients. For decades, prophylaxis of cytomegalovirus (CMV) has been the standard preventive strategy, but new clinical trials are expected to determine the advantages of preemptive therapy over prophylaxis. Novel anti-CMV agents, such as maribavir and letermovir, are being studied for the treatment of resistant/refractory CMV as alternatives to foscarnet and cidofovir. CMV immune monitoring may offer individualized management plans. Epstein-Barr virus infections in transplant recipients are difficult to prevent and treat, though recent data suggest possible merit to pretransplant rituximab among high-risk transplant recipients. We review the groundbreaking HIV-to-HIV organ transplant trials, which are expected to revolutionize the care of HIV-infected individuals. Finally, we review topical developments in human herpesvirus 8, Zika virus, RNA respiratory viruses, adenovirus, norovirus, and polyoma viruses in organ transplantation. Ongoing trials to optimize CMV prophylaxis and treatment, and outcomes of HIV-to-HIV organ transplantation in the United States, have significant implications to optimize management of these viruses in transplant recipients. Assessment of new antivirals and antiviral strategies, such as adoptive immunotherapy, is warranted for refractory viral infections.

Human Herpesvirus 7 in Allogeneic Hemopoietic Stem Cell Transplant Recipients in the Central Clinical Hospital in Warsaw: A Three-Year Survey

Objectives: Human herpesvirus 7 (HHV-7) is spread worldwide and has been described as a potential pathogen in immunosuppressed patients. Different clinical manifestations have been described including fever and skin rash; HHV-7 may also be a possible cofactor for cytomegalovirus disease in transplant recipients. Materials and Methods: A retrospective review of a group of 58 adult recipients of allogeneic hemopoietic stem cell transplantation was made. Serum samples taken in the range of 0–180 days after transplant were examined for presence of specific HHV-7 sequences using the quantitative real-time PCR method. Results: HHV-7 DNA was detected in plasma samples in 26 (45%) of the 58 recipients between day 20 and day 65 of transplantation. All of them developed fever of unknown origin; also HHV-5 DNA was detected in plasma samples collected from 11 HHV-7-positive patients. None of the described individuals died during detectable HHV-7 or HHV-5 viremia periods. Conclusions: There is a high frequency of detectable HHV-7 viral load in allogeneic stem cell transplant recipients in Poland. Limited availability and sensitivity of serological methods along with the necessity of rapid introduction of antiviral treatment has forced the development of molecular diagnostics. Furthermore, establishment of appropriate procedures for monitoring active HHV-7 infection is important to clarify the virus infection in transplant recipients.

Narrowing of T‐cell receptor beta variable repertoire during symptomatic herpesvirus infection in transplant patients

Primary infection or recrudescence of latent virus infection in transplant recipients can be manifested either as asymptomatic or symptomatic disease. Here we show that symptomatic human cytomegalovirus (HCMV) or Epstein-Barr virus (EBV) infection or recrudescence following solid organ transplantation (SOT) was coincident with a dramatic skewing of T-cell receptor beta variable (TRBV) repertoire, with expansions of monoclonal/oligoclonal clonotypes. As the clinical symptoms resolved, the peripheral blood repertoire reverted to a more diverse distribution. In contrast, SOT recipients with asymptomatic or no viral infection or recrudescence showed minimal or no skewing of the T-cell receptor repertoire to maintain peripheral blood repertoire diversity. More importantly, we show that large monoclonal/oligoclonal repertoire expansions are associated with the loss of HCMV-specific T-cell function observed in SOT patients undergoing symptomatic viral infection or recrudescence, whereas SOT recipients who maintain peripheral blood TRBV repertoire diversity and functional antigen-specific T-cell responses can resist clinical symptomatic disease in spite of high levels of viral load.

Detection of specific lytic and latent transcripts can help to predict the status of Epstein-Barr virus infection in transplant recipients with high virus load.

Epstein-Barr virus (EBV), a member of the family Herpesviridae, is widely spread in the human population and has the ability to establish lifelong latent infection. In immunocompetent individuals the virus reactivation is usually harmless and unnoticeable. In immunocompromised patients productive infection or type III latency may lead to EBV-associated post-transplant lymphoproliferative disorder (PTLD). The aim of our research was to investigate the utility of PCR-based methods in the diagnosis and monitoring of EBV infections in bone marrow transplant recipients. Thirty-eight peripheral blood leukocyte samples obtained from 16 patients were analysed, in which EBV DNA was confirmed by PCR. We used semi-quantitative PCR to estimate the viral load and reverse-transcription PCR (RT-PCR) to differentiate between latent and productive EBV infection. In 14 patients we confirmed productive viral infection. We observed a correlation between higher number of EBV genome copies and the presence of transcripts specific for type III latency as well as clinical symptoms.

Liver Transplantation Using Hepatitis B Core Antibody−Positive Grafts: Review and University of Tokyo Experience

Hepatitis B surface antigen-negative and hepatitis B core antibody-positive grafts were considered unsuitable for transplantation. The number of potential recipients for liver transplantation now exceeds that of potential donor organs, which has led us to reevaluate the feasibility of these grafts. Several strategies involving prophylactic administration of hepatitis B immunoglobulin and/or lamivudine to transplant recipients have been proposed. At the University of Tokyo, we have continued to use hepatitis B immunoglobulin monoprophylaxis with zero recurrence. In this article we report our experience with the use of hepatitis B surface antigen-negative/hepatitis B core antibody-positive grafts with hepatitis B immunoglobulin monotherapy. We conducted a review of the literature regarding the feasibility of these grafts to reconfirm optimal prophylactic strategies for preventing de novo hepatitis B virus infection in transplant recipients.

West Nile Virus Infection After Cardiac Transplantation

West Nile virus is a mosquito-borne RNA Flavivirus infection transmitted to humans and other vertebrates, mainly by the Culex species of mosquito. Since the mid-1990s, the frequency and apparent clinical severity of West Nile virus outbreaks have increased. We report the case of a patient who developed West Nile virus encephalitis shortly after undergoing cardiac transplantation. Clinicians should be aware of the possibility of West Nile virus infection in transplant recipients and in patients receiving blood transfusions.

Respiratory virus infections in transplant recipients after reduced-intensity conditioning with Campath-1H: high incidence but low mortality.

Respiratory virus infections can cause serious morbidity and mortality after conventional allogeneic stem cell transplantation. However, the incidence and outcome of these infections after reduced intensity conditioning has not been reported. Between 1997 and 2001, 35 episodes of respiratory virus infections were noted in 25 of 83 transplant recipients conditioned with fludarabine, melphalan and Campath-1H, and 80% of them received early antiviral therapy. Parainfluenza virus (PIV) 3 was the commonest isolate (45.7%) followed by respiratory syncytial virus (37%). Patients with myeloma were more susceptible to these infections [odds ratio (OR) 4.1, P = 0.01] which were often recurrent in patients with severe acute or chronic graft-versus-host disease (GVHD) (OR 10.6, P = 0.03). Infection within the first 100 d (OR 5.0, P = 0.05) and PIV 3 (OR 9.2, P = 0.01) isolation were risk factors for developing lower respiratory infection. Although more than half of the episodes progressed to lower respiratory infection, the mortality was only 8%. This could have been due to early initiation of antiviral therapy, but the attenuation of pulmonary damage due to the reduced-intensity conditioning, low incidence of GVHD and, paradoxically, the low CD4+ T-cell subset in this setting might also have been contributory factors.

Epstein-Barr Virus Infection in Transplant Recipients: Sumary of a Workshop on Surveillance, Prevention and Treatment

Diseases caused by the Epstein-Barr virus are of great significance among organ transplant recipients. One of these diseases, post-transplant lymphoproliferative disease, is a major complication among organ transplant recipients. Management of this entity is problematic due to the difficulties with laboratory surveillance, diagnosis, prevention and treatment. A group of Canadian and American experts was assembled to discuss these aspects of Epstein-Barr virus diseases in Canadian organ transplant recipients. This report summarizes the relevant background literature and levels of evidence in relation to the outcomes of the deliberations and recommendations by the expert panel.