Adenovirus in Solid Organ Transplant Recipients

Abstract

Adenoviruses are nonenveloped, double-stranded DNAviruses associated with a wide range of clinical syndromesin humans (1). There are 52 immunologically distinct typesof adenoviruses that are further classified into one of7 (A–G) subgroups based on hemagglutinin properties,DNA homology, oncogenic potential in rodents and clin-ical disease (Table 1) (2,3). Adenoviruses typically causeself-limited respiratory, gastrointestinal or conjunctival dis-ease throughout the year without significant seasonal vari-ation. Adenovirus infections are most common amongchildren, people living in close quarters (such as collegestudents and military recruits), and immunocompromisedpatients (1).Adenovirus is the third most important viral infection fol-lowing liver transplantation in children, occurring in 10%of 484 pediatric liver transplant recipients in one series(4). A single series has reported an incidence of 5.8%of 191 adult liver transplant recipients (5). Symptomaticdisease (ranging from self-limited fever, gastroenteritis orcystitis to devastating illness with necrotizing hepatitis orpneumonia) occurred in over 60% of the infected patients.Symptomatic infections typically occurred within the first3 months after transplantation. The frequency of invasiveadenovirus infections after pediatric liver transplantationappeared to decrease with use of tacrolimus-based im-munosuppression(6);similardataarenotavailableforadultliver transplant recipients.Adenovirus infection in other organ recipients is less wellcharacterized. A recent prospective study in adult SOT re-cipients demonstrated measurable adenovirus DNAemiain 7.2% of 263 recipients in the first posttransplant year;nearly 60% of these patients were completely asymp-tomatic with the remaining patients manifesting gastroin-testinal (primarily diarrhea), respiratory or vague, nonspe-cific symptoms (7). In contrast to outcomes found in thisprospective study, case reports and small series identifythe fact that adenoviral infection can be clinically signif-icant in these patients. Severe adenoviral infection hasbeen reported after lung transplantation often leading tofatal disease (8–10). The presence of adenovirus DNA incardiac biopsies after pediatric heart transplantation wassignificantly associated with poor graft survival in one se-ries (11). Adenovirus also has been associated with hemor-rhagiccystitisandgraftdysfunctioninadultrenaltransplantrecipients (12). It has also been found in high rates after pe-diatric intestinal transplantation, though frequently in theabsence of obvious clinical disease or associated pathol-ogy (13). As adenovirus, like cytomegalovirus (CMV), canbe latent and can reactivate asymptomatically, ascribing acausative role in the pathologic process may sometimesbe difficult.Sites and clinical manifestations of adenoviral disease intransplant recipients appear to vary according to the typeof organ transplanted, with frequent involvement of theallograft. In liver transplant recipients, infection with aden-ovirusserotype5typicallyresultsinhepatitiswithamedianonset of 55 days after transplant (4,5), while serotypes 1and 2 are more commonly associated with pneumonia.Adenoviral pneumonia is associated with graft loss, deathor progression to obliterative bronchiolitis for lung trans-plant recipients (8). In one study of pediatric heart trans-plant recipients, detection of adenoviral genome copies inmyocardial biopsy specimens was predictive of adverseclinical events including coronary vasculopathy and graftloss (OR 4.7 compared to adenovirus negative patients;95% confidence interval 1.3–17.1) (11). The strength ofthis association and its pathogenesis remain to be clari-fied. Enterocolitis occurs more commonly in small bowelrecipients and may mimic rejection (7,14). Hemorrhagiccystitis and nephritis are described in renal transplant re-cipients (15). Disease in other organ recipients has beendescribed rarely.