Identification of Adenoviruses in Specimens from High-Risk Pediatric Stem Cell Transplant Recipients and Controls

Abstract

Adenovirus infection is an important cause of morbidity and mortality in stem cell transplant recipients. We report species and type-specific analysis from a prospective study of high-risk adenovirus infections following hematopoietic progenitor cell transplantation prior to, during, and after treatment with cidofovir, as well as species analysis of contemporaneously collected samples from control patients. Nine different adenovirus types representing all six recognized species were identified, and mixed infections were commonly found in this group of patients. Adenovirus (ADV) infections are common in childhood.The 51 different currently recognized ADV serotypes are divided into six species (A through F) which have similar genetic and biological properties (3). ADVs commonly cause respiratory, gastrointestinal, and urinary tract disease. In the immunocompromised host, ADV infections can cause severe disease and death. In a recent review, Chakrabarti et al. (3) noted that ADV species B and C account for the majority of clinical isolates in hematopoietic progenitor cell transplantation (HPCT) recipients.In this study, we determined the types of ADVs infecting seven pediatric stem cell transplant recipients prior to, during, and after treatment with cidofovir, as previously described (1), and compared them with 25 consecutive ADV isolates from nontransplant pediatric patients collected contemporaneously to determine the type-specific epidemiology of ADV infections in HPCT recipients and controls. A companion paper (1) examined the epidemiology of ADV infections in HPCT recipients and the effectiveness (if any) of cidofovir against these infections. This study was approved by the IRB of the Children's Memorial Research Center, Children's Memorial Hospital, Chicago, IL.HPCT recipients and specimens. Patients underwent HPCT between 8 September 2003 and 1 December 2005 at our institution. Urine, stool, and throat samples were screened for ADV by viral culture (see below). Plasma was referred to ViraCor (Lee's Summit, MO) for quantitative ADV detection by PCR. Specimens were obtained weekly through the first 100 days (14 weeks) and then monthly until 1 year from the HPCT. A patient was defined as having a high-risk ADV infection (HRAI) if they had (i) a positive blood ADV PCR with or without symptoms, (ii) two or more positive ADV cultures from separate peripheral sites with or without symptoms, or (iii) one positive peripheral culture for ADV plus compatible clinical evidence of ADV (1). As previously described, 7 of the 38 children developed HRAI and received cidofovir treatment (1). Two additional asymptomatic patients had ADV identified transiently from a single body site only without clinical symptoms and were not further studied.Specimens from other patients. Twenty-five consecutive pediatric specimens from nontransplanted patients submitted to our virology laboratory during routine clinical care that grew ADV also had ADV species identification performed. These specimens included those from the respiratory trac...

Nucleic acid amplification-based diagnosis of respiratory virus infections

“…The prevalence of adenovirus respiratory infection in children has ranged from 2 to 14% [87,88]. Adenoviruses are increasingly important in both solid organ and bone marrow transplant patients [89,90] and infections with adenovirus in pediatric transplant patients can exceed 22% with mortality rates as high as 60% [90]. Adenovirus can be shed from the eye, upper respiratory tract or gastroenteric tract for 1-6 weeks and diagnostic tests must be capable of detecting low levels of virus.…”

Molecular diagnosis of respiratory virus infections

“…Historically 1-5% of all respiratory infections have been caused by adenovirus 14 . The prevalence of adenovirus respiratory infection in children has ranged from 2-14% 147,148 . Adenoviruses are increasingly important in both solid organ and bone marrow transplant patients 149,150 ; infections with adenovirus in pediatric transplant patients can exceed 22%, with mortality rates as high as 60% 150 Adenovirus can be shed from the eye, upper respiratory tract, urine and the gastrointestinal tract for one to six weeks and diagnostic tests must be capable of detecting low levels of virus.…”

Adenovirus Infections in Immunocompetent and Immunocompromised Patients

“…Moreover, latent HAdV infections were described to occur in intestinal T lymphocytes and in lung epithelial cells, where they seem to play a role in the pathogenesis of obstructive airway disease (104). Other sites of HAdV persistence have also been suggested, but the experimental evidence is limited (105)(106)(107).…”

“…For the selection of optimal treatment, HAdV typing is currently of lesser importance because, with the exception of ribavirin (see below), available therapeutic strategies are independent of the HAdV species present. However, in view of the fact that different HAdV species and types may occur contemporaneously or sequentially in individual patients (52,53,72,107,208), typing may permit a better understanding of the dynamics and evolution of HAdV infection (Fig. 4).…”