Human adenovirus infection in Kawasaki disease: a confounding bystander?

Abstract

Background: Human adenovirus (HAdV) infection mimics Kawasaki disease (KD) but can also be detected in KD patients. Evidence suggests that HAdV-C species can persist in pediatric adenoids and/or tonsils. We sought to determine (1) the frequency of HAdV detection by real-time polymerase chain reaction in KD patients, (2) the differences in HAdV semiquantitative nasopharyngeal viral loads between KD patients with detectable HAdV vs those with HAdV disease, and (3) whether nasopharyngeal HAdV-C shedding is occurring in KD.

Methods: From August 2009 through April 2011, HAdV-positive patients were identified in 1 of the following groups: group I, complete or incomplete KD as defined by the American Heart Association (AHA); group II, treated for incomplete KD but not fulfilling AHA criteria; and group III, otherwise healthy children with some KD-like features ultimately diagnosed with HAdV disease.

Results: Among 77 KD patients diagnosed, 8.8% (5/57) of group I and 25% (5/20) of group II KD patients had HAdV detected. Viral loads were significantly lower in group I (n = 5) vs group III (n = 26; P = .034). Of the 13 specimens available for HAdV typing, 7 of 7 group III and 1 of 3 group II specimens were determined to be HAdV-B using viral culture. The remaining 5 KD samples were unable to be cultured and molecular typing showed either HAdV-C (n = 3) or were nontypeable (n = 2).

Conclusions: In KD, molecular-based HAdV detection is not uncommon, may represent persistence of HAdV-C, and should be interpreted with caution. Together, quantitative polymerase chain reaction and HAdV typing may aid in distinguishing HAdV disease mimicking KD from KD with concomitant HAdV detection.

Figure 1.

Classification of patients. Group I included complete or incomplete Kawasaki disease (KD) that met American Heart Association (AHA) criteria. Patients in group II were treated for incomplete KD but did not meet full AHA criteria, and group III consisted of patients who were not treated for KD but who had documented consideration of KD in the differential diagnosis. Abbreviations: DD, differential diagnosis; HAdV, human adenovirus; KD, Kawasaki disease.

Figure 2.

A, Comparison of human adenovirus (HAdV) cycle threshold (Ct) among 3 groups. Group I, HAdV-positive KD (all complete); group II, HAdV-positive KD (incomplete); and group III, HAdV disease. Group I Kawasaki disease (KD) patients had significantly higher Cts compared to those with Group III (mean, 34.4 ± 5.4 vs 27.0 ± 6.6; P = .034). There was no significant difference in the Cts between group II KD and group III (mean, 31.6 ± 9.3 vs 27.0 ± 6.6). B, Comparison of Ct values among patients with HAdV alone vs HAdV with another pathogen identified. All patients were immunocompetent, non-KD patients. Those with HAdV alone (n = 38) had significantly lower Cts compared to those with HAdV and another identifiable pathogen (n = 12; mean, 27.1 ± 1.1 vs 34.6 ± 6.9; P = .038). Abbreviations: Ct, cycle threshold; HAdV, human adenovirus; KD, Kawasaki disease.