Molecular typing of clinical adenovirus specimens by an algorithm which permits detection of adenovirus coinfections and intermediate adenovirus strains.
BACKGROUND
Epidemiological data suggest that clinical outcomes of human adenovirus (HAdV) infection may be influenced by virus serotype, coinfection with multiple strains, or infection with novel intermediate strains. In this report, we propose a clinical algorithm for detecting HAdV coinfection and intermediate strains.


METHODS
We PCR amplified and sequenced subregions of the hexon and fiber genes of 342 HAdV-positive clinical specimens obtained from 14 surveillance laboratories. Sequences were then compared with those from 52 HAdV prototypic strains. HAdV-positive specimens that showed nucleotide sequence identity with a corresponding prototype strain were designated as being of that strain. When hexon and fiber gene sequences disagreed, or sequence identity was low, the specimens were further characterized by viral culture, plaque purification, repeat PCR with sequencing, and genome restriction enzyme digest analysis.


RESULTS
Of the 342 HAdV-positive clinical specimens, 328 (95.9%) were single HAdV strain infections, 12 (3.5%) were coinfections, and 2 (0.6%) had intermediate strains. Coinfected specimens and intermediate HAdV strains considered together were more likely to be associated with severe illness compared to other HAdV-positive specimens (OR=3.8; 95% CI=1.2-11.9).


CONCLUSIONS
The majority of severe cases of HAdV illness cases occurred among immunocompromised patients. The analytic algorithm we describe here can be used to screen clinical specimens for evidence of HAdV coinfection and novel intermediate HAdV strains. This algorithm may be especially useful in investigating HAdV outbreaks and clusters of unusually severe HAdV disease.
McCarthy
Troy
T
Center for Emerging Infectious Diseases, Department of Epidemiology, University of Iowa College of Public Health, Iowa City, IA, USA. troy-mccarthy@uiowa.edu
Lebeck
Mark G
MG
Capuano
Ana W
AW
Schnurr
David P
DP
Gray
Gregory C
GC
D000258:Adenovirus Infections, Human / Q000821:virology*; D000260:Adenoviruses, Human / Q000145:classification* / Q000235:genetics* / Q000302:isolation & purification; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D036022:Capsid Proteins / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D019411:Clinical Laboratory Techniques; D004279:DNA, Viral / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction / Q000379:methods; D012150:Polymorphism, Restriction Fragment Length; D011995:Recombination, Genetic; D017422:Sequence Analysis, DNA; D055815:Young Adult
D036022:Capsid Proteins; D004279:DNA, Viral; C018315:hexon capsid protein, Adenovirus