Sequential emergence of multiple adenovirus serotypes after pediatric stem cell transplantation.
BACKGROUND
Adenovirus infections after allogeneic stem cell transplantation (SCT), particularly in children, may be severe and protracted. Up to 51 different serotypes of adenovirus are presently recognized but serotyping is usually limited to initial viral isolates.


OBJECTIVE
A systematic and sustained analysis of adenovirus serotypes in a cohort of adenovirus-infected pediatric SCT recipients, correlated to transplant-associated variables.


METHODS
Eighty-three consecutive pediatric SCT recipients were studied by culture of feces and adenoviruses isolated were serotyped by neutralization. Upon persistent viral excretion, serotyping was repeated for at least two isolates of any infectious episode, including initial and final isolates, and patients with single and multiple serotypes were compared. In a subset of cases, serotyping of fecal isolates was compared to genotypic analysis.


RESULTS
In 33 patients, adenovirus was isolated at least once after SCT. Serotyping uncovered 49 different adenoviruses, including three isolates without an assigned serotype. In 16 patients, a single serotype was present for a sustained period, whereas 12 patients (36%) showed multiple serotypes. Comparison of these groups demonstrated more frequent non-malignant primary disease with multiple infections (p<0.01), but otherwise no significant differences were observed, although single serotype infections had a lower survival rate. Remarkably, serotype 31 appeared initially in 7 out of 12 patients with multiple infections. Genotyping by sequencing confirmed neutralization assays at least at the species level in 14 of 18 isolates.


CONCLUSIONS
In 36% of adenovirus infections after SCT more than one serotype could be detected by sequential analysis. Multiple serotypes occurred more often with non-malignant disorders. Adenovirus serotype 31 was often included. This finding is relevant for diagnostic purposes and immunotherapeutic interventions and provides insight into the pathogenesis of this problem.
Kroes
Aloys C M
AC
Department of Medical Microbiology, Leiden University Medical Center, Leiden, The Netherlands. kroes@lumc.nl <kroes@lumc.nl>
de Klerk
Erik P A
EP
Lankester
Arjan C
AC
Malipaard
Corry
C
de Brouwer
Caroline S
CS
Claas
Eric C J
EC
Jol-van der Zijde
Els C
EC
van Tol
Maarten J D
MJ
D000256:Adenoviridae / Q000145:classification* / Q000302:isolation & purification*; D000257:Adenoviridae Infections / Q000401:mortality / Q000821:virology*; D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D004279:DNA, Viral / Q000737:chemistry / Q000235:genetics; D005243:Feces / Q000821:virology; D005260:Female; D006402:Hematologic Diseases / Q000150:complications*; D006801:Humans; D007223:Infant; D008297:Male; D009500:Neutralization Tests; D017422:Sequence Analysis, DNA; D012703:Serotyping; D033581:Stem Cell Transplantation; D016019:Survival Analysis; D014776:Virus Cultivation
D004279:DNA, Viral