Molecular epidemiology of a post-influenza pandemic outbreak of acute respiratory infections in Korea caused by human adenovirus type 3

Abstract

An outbreak of upper respiratory tract infections associated with human adenovirus (HAdV) occurred on a national scale in Korea from September to December 2010, following a major H1N1 influenza pandemic. Data from the Korea Influenza and Respiratory Surveillance System (KINRESS) showed an unusually high positive rate accounting for up to 20% of all diagnosed cases. To determine the principal cause of the outbreak, direct polymerase chain reaction (PCR) amplification followed by sequence analysis targeting parts of the hexon gene of HAdV was performed. Serotypes of 1,007 PCR-diagnosed HAdV-positive samples from patients with an acute upper respiratory tract illness were determined and epidemiological characteristics including major aged group and clinical symptoms were analyzed. The principal symptom of HAdV infections was fever and the vulnerable aged group was 1-5 years old. Based on sequence analysis, HAdV-3 was the predominant serotype in the outbreak, with an incidence of 74.3%. From the beginning of 2010 until May, the major serotypes were HAdV-1, 2, and 5 (70-100%) in any given period. However, an outbreak dominated by HAdV-3 started between July and August and peaked in September. Phylogenetic analysis revealed that there was no genetic variation in HAdV-3. The results demonstrated that an outbreak of upper respiratory illness followed by H1N1 influenza pandemic in Korea was caused mainly by emerged HAdV-3. J.

Keywords: human adenovirus; molecular epidemiology; post-pandemic outbreak.

Figure 1

Monthly positive rates of HAdV infections in 2008 and 2010. The 2‐year distribution of HAdV‐positive rates (left y‐axis; bars) out of the total incidence of respiratory viruses (right y‐axis; lines) was significantly different (P = 0.009). In 2010, number of specimens were maintained certain level over the year, however the positive rate of HAdV was drastically increased from Jun to Nov.

Figure 2

Positive rates of HAdV infections in five consecutive years. The median positive rate of adenoviruses detected in the baseline periods (previous 3‐year average) was 2.0% (straight dotted line; range 1.0–5.0%). However, during the outbreak period, from June to December 2010, the positive rate increased significantly to 16.7%.

Figure 3

Age distribution of HAdV‐3 positive patients in each age group; 80.9% of patients were aged less than 5 years old.

Figure 4

Serotypes of HAdVs based on the partial hexon gene sequence information. HAdV types 1 and 2 were the leading serotype in 2008 whereas HAdV‐3 was responsible for one‐third of HAdV infections in 2010. Of note, HAdV type 41 was identified in a patient with acute respiratory illness in 2010.

Figure 5

Clinical symptoms of HAdV‐3 infected patients in 2008 and 2010. The leading clinical symptom of HAdV infection was fever. Coughing, runny nose, and nasal congestion were significantly diminished in 2010 (P < 0.001).

Figure 6

Phylogenetic analysis of 1,007 HAdV‐positive cases based on the partial hexon gene sequence information. Mega 4 software was used to generate a phylogenetic tree; 1,000 replicates were performed for bootstrap analysis and values are shown at each branch node. Reference strains for each genotype obtained from GenBank are marked with closed circles (●). Triangular symbols indicate positive cases of HAdVs corresponding with each reference strain.