Human adenoviruses (HAdVs) are an important cause of infections in both immunocompetent and immunocompromised individuals, and they continue to provide clinical challenges pertaining to diagnostics and treatment. The growing number of HAdV types identified by genomic analysis, as well as the improved understanding of the sites of viral persistence and reactivation, requires continuous adaptions of diagnostic approaches to facilitate timely detection and monitoring of HAdV infections. In view of the clinical relevance of life-threatening HAdV diseases in the immunocompromised setting, there is an urgent need for highly effective treatment modalities lacking major side effects. The present review summarizes the recent progress in the understanding and management of HAdV infections.

Adenovirus Infections in Immunocompetent and Immunocompromised Patients

Adenovirus infections following allogeneic stem cell transplantation: incidence and outcome in relation to graft manipulation, immunosuppression, and immune recovery

Molecular monitoring of adenovirus in peripheral blood after allogeneic bone marrow transplantation permits early diagnosis of disseminated disease.

Adenovirus (Ad) infections in immunocompromised hosts have increased in frequency as the number of patients with transplants of bone marrow, liver, kidney, heart and other organs increase in number and survive longer. The numbers of such patients have also increased because of the emergence of the HIV epidemic. Ad infections with the 51 different serotypes recognised to date have few pathognomonic signs and symptoms, and thus require a variety of laboratory-based procedures to confirm infection. These viruses have the ability to target various organs with relative serotype specificity and can cause diverse manifestations including serious life-threatening diseases characteristic of the organs involved. Ads have cytolytic and immunoregulatory properties. The clinical dilemma remains the prompt recognition of Ad-related disease, the differentiation of Ad infection from Ad disease and the differentiation from other causative agents. Since the armamentarium of effective antiviral agents available to treat Ads is unproven by controlled trials and the virus is often not acquired de novo, it is difficult to prevent reactivation in immunodeficient hosts or new acquisition from donor organs. Timely discontinuation of immunosuppressive agents is necessary to prevent morbid outcomes. The clinical diseases, diagnostic tests, antiviral agents and biological aspects of the Ads as pathogens in immunocompromised patients are discussed in the context of this review. Some of the newer diagnostic tests are based on the well-studied molecular biology of Ads, which also have been attenuated by selective viral DNA deletions for use as vectors in numerous gene therapy trials in humans.

The impact of adenovirus infection on the immunocompromised host

Cytotoxic T lymphocyte therapy with donor T cells prevents and treats adenovirus and Epstein-Barr virus infections after haploidentical and matched unrelated stem cell transplantation

The incidence of adenovirus (AV) infections following SCT was determined in a prospective multicenter trial. Over 1 year, 130 consecutive patients undergoing allogeneic SCT at Essen University Hospital were included and followed for 6 months. Source of stem cells was blood in 68 cases. Fifty-eight patients had HLA-identical sibling donors. Throat swabs, urine and stool samples were screened weekly for AV antigen and DNA by ELISA and nested PCR, respectively. In 35 cases adenovirus infection was detected. There was no seasonal variation. Throat swabs were positive in 24, urine in 12, and stool in 11 cases, resulting in a cumulative risk of infection of 29%. The incidences of AV infection of the respiratory, gastrointestinal and urinary tract were 19%, 10%, and 9%, respectively, and infections were diagnosed after a median (range) interval of 44 (-2-179), 37 (-2-168), and 53 (17-153) days after transplantation. On multivariate analysis, presence of AV antibody in the donor and acute graft-versus-host disease grade IV were found to be independent risk factors for AV infection. Eleven patients had AV isolated from more than one site and five patients had probable AV disease. We were not able to identify patients in whom AV infection was the leading cause of death. The majority of patients infected with AV suffered from severe acute graft-versus-host disease often accompanied by other opportunistic infections, such as aspergillosis or CMV reactivation. Nineteen out of 36 patients who died during the observation period had AV infection. In summary, AV infection after allogeneic SCT was observed in a substantial number of patients. In addition to well-known risk factors for viral infection after SCT we were able to demonstrate that a positive AV antibody test in the donor is an important risk factor for AV infection. Further studies are needed, however, before final conclusions on the clinical sequelae of AV infection can be made and the role of preventive and therapeutic strategies toward AV infection after allogeneic SCT can be defined.

Adenoviral infection after allogeneic stem cell transplantation (SCT): report on 130 patients from a single SCT unit involved in a prospective multi center surveillance study

K Renzing-Köhler

Papers

Adenoviral infection after allogeneic stem cell transplantation (SCT): report on 130 patients from a single SCT unit involved in a prospective multi center surveillance study