Quantification of adenovirus species B and C viremia by real‐time PCR in adults and children undergoing stem cell transplantation

Abstract

Adenovirus infection during stem cell transplantation is associated with high morbidity and mortality. Adenovirus species B and C have been the main causes for these infections; however, epidemiological details about the species are still unclear. To clarify the contributions of species B and C adenovirus, the DNA was tested serially by quantitative real-time PCR in peripheral blood, stool and urine of 32 patients (16 adults and 16 children) undergoing stem cell transplantation. Adenovirus species B viremia was detected in 10 of 16 adult and 6 of 16 pediatric transplant recipients. Adenovirus species C viremia was also detected simultaneously in five adult and three pediatric recipients. The stool and urine of patients with adenovirus viremia were also positive for the same adenovirus species as in blood. In contrast, in none of 50 healthy adult controls was adenovirus species B or C viremia detected. Among patients who developed adenovirus viremia, one adult recipient developed disseminated disease and died from multiple organ failure. The remaining patients experienced fever of several degrees and/or diarrhea during the period of adenovirus viremia; however, they all recovered without antiviral therapy. The results indicated that stem cell transplantation was frequently associated with adenovirus species B or C viremia, although it did not always cause serious infectious complications.

Adenovirus Infections in Immunocompetent and Immunocompromised Patients

“…For example, in the transplant unit of St. Anna Children's Hospital, Vienna, Austria, HAdV species C accounts for about 80% of all adenoviral infections observed, and similar numbers were also reported from other transplant centers in different geographic regions (43,69,(71)(72)(73). Sequential or concomitant coinfections with different adenoviruses from the same or different species are quite commonly observed in both the immunocompetent and immunocompromised patient settings (74)(75)(76) and may thus play a role in the generation of recombinant HAdV types.…”

Latent Species C Adenoviruses in Human Tonsil Tissues

“…No evidence of nonreplicating adenoviral DNA from any other species was identified in these samples. It remains possible that other serotypes of adenovirus form latent or persistent infections in other tissues, such as species B serotypes in kidney (25,56,60), lung (35), or possibly brain (32), but because of different tissue tropism, these viruses were not detected in tonsil and adenoid tissue.…”

High lethality of human adenovirus disease in adult allogeneic stem cell transplant recipients with high adenoviral blood load

“…Four of these patients had localised HAdV dis- ease, such as haemorrhagic cystitis ( Table 2, patient numbers 9 and 19), gastroenteritis (patient 20) or diarrhoea which was clinically associated with GvHD (patient 24). In one of these patients HAdV may have contributed to the aetiology of pneumonia although this was clinically diagnosed as aspiration pneumonia (patient 18). Four examples of HAdV load kinetics are shown in supplementary Fig.…”

“…9 While the incidence of HAdV infections in paediatric SCT recipients varies widely between 8% and 50% in different studies, HAdV related mortality is consistently reported to be about 5% (3-7%). 10,11,[16][17][18][19][20][21] Since high HAdV blood loads are associated with the development of HAdV disseminated disease in paediatric patients, HAdV DNAaemia is monitored after allogeneic SCT in many paediatric SCT centres. 10,15,18,20 In contrast, data concerning the incidence of HAdV related disease and mortality in adults are limited.…”

“…10,11,[16][17][18][19][20][21] Since high HAdV blood loads are associated with the development of HAdV disseminated disease in paediatric patients, HAdV DNAaemia is monitored after allogeneic SCT in many paediatric SCT centres. 10,15,18,20 In contrast, data concerning the incidence of HAdV related disease and mortality in adults are limited. So far, the few studies published which used conventional detection methods (qualitative PCR, virus isolation and antigen detection) reported an incidence of HAdV infections/excretion in adults of 3-29% and a HAdV related mortality ranging from 0% to 3%.…”