ADENOVIRUSES DETECTED IN AUTOPSIES, NEW YORK, 2007

Background:  Recent mainstream news articles and an MMWR have highlighted the potential seriousness of adenovirus infections, with reports centered on the newly reported highly virulent strain of serotype 14 (Ad-14).  However, one potential implication of the recent coverage is that the other 50 types of adenoviruses pose no fatality threat.  This study retrospectively investigated the subtypes of adenoviruses previously detected in autopsy specimens referred for testing to the Wadsworth Center, New York State Department of Health during 2007.

Methods:  The adenovirus-positive autopsy specimens were first tested for the presence of the highly virulent Ad-14 by a type 14 specific real-time PCR assay. Specimens negative for Ad-14 were subtyped and sequenced by two nested conventional PCR assays in the hypervariable region of the hexon gene.  The nested primer sets are degenerate in order to detect all 51 serotypes of adenovirus. 

Results:  The Wadsworth Center received 24 autopsy samples, from 15 cases, that were positive for adenovirus by real-time PCR.  Of these 24 samples, ­­3 were also positive by conventional virus culture and were serotyped by antibody neutralization.  The other 21 were unable to be isolated in culture and were the stimulus for this study.  The 21 samples were found negative for Ad-14 by type-specific real-time PCR assay and were typed by conventional PCR using the two nested PCR primer sets.  Both sets of outer and nested primers worked equally well, yielding nested PCR products in 16 of the 21 specimens that were successfully sequenced and analyzed.  Additionally, the three specimens that were originally subtyped by neutralization assay were also sequenced and analyzed.  The typing results obtained by sequence analysis matched those obtained by antibody neutralization in all cases.  Therefore, 19 specimens in total were typed by sequence analysis.  Of these 19 specimens, 13 were respiratory specimens, 4 were stool specimens, 1 specimen was from brain/spinal cord tissue and 1 specimen was genital. The results of the sequencing were two type 1, nine type 2, two type 3, one type 4, one type 11, one type 37 and three type 41.  Three patients had multiple specimens: two patients had two specimen types, both positive for serotype 2; one patient had three specimen types, all positive for serotype 41.

Conclusions:  Adenoviruses can cause significant disease in both immunocompromised and immunocompetent populations.  Although serotype 14 was not detected in any of these cases, several other serotypes of adenoviruses were detected in the autopsy specimens.  Serotypes 1, 2, 11 and 37 were found in patients with a preexisting condition unrelated to the adenovirus infection.  Interestingly, serotypes 2, 3 and 4 were found in patients with no serious preexisting condition.  Furthermore, serotypes 2 and 4 were found in cases of sudden unexpected death.  It must be noted that autopsy records have not been reviewed and the exact correlation between the presence/detection of these adenoviruses and cause of death is unknown.  However, while it is important to be vigilant in investigating potential infections with adenovirus serotype 14, it should also be noted that other serotypes can cause sporadic, fatal disease.