Emergent US adenovirus 3 strains associated with an epidemic and serious disease

Background: Adenovirus type 3 (HAdV3) is one of the most prevalent serotypes detected globally. Variants of HAdV3 have been associated with outbreaks of severe disease. Objectives: To better understand genetic diversity of circulating HAdV3s and examine risk factors for severe disease. Study design: Restriction enzyme analysis for genomic characterization of clinical HAdV3 isolates detected by 15 collaborative US laboratories during the period July 2004 to May 2007. Multivariate modeling was employed for statistical analyses. Results: The most common HAdV3 types of 516 isolates studied were HAdV3a2 (36.9%), HAdV3a50 (27.1%), HAdV3a51 (18.0%), and HAdV3a17 (4.6%). Non-HAdV3a genome types were rare (1.2%). HAdV3a50 and HAdV3a51 are newly described variants which became more prevalent in 2006 and 2007 and have been associated with at least one epidemic. Their uniqueness was determined by specific banding profiles generated by digests with endonucleases BclI, BglII, and HindIII. Multivariable risk factor modeling demonstrated that children under 2 years of age (OR = 2.7; 95%CI 1.6-4.6), persons with chronic disease (OR = 5.1; 95%CI 2.6-9.8), persons infected with HAdV3a2 (OR = 3.0; 95%CI 1.5-6.0), with HAdV3a50 (OR = 2.5; 95%CI 1.2-5.2), or with multiple or rare strains (OR = 2.8; 95%CI 1.3-6.5) were at increased risk of severe HAdV3 clinical disease. Conclusions: In the study period considerable genetic diversity was found among US clinical HAdV3 strains. Novel variants emerged and became prevalent. One such emergent strain may be associated with more severe clinical disease.