Virology and epidemiology analyses of global adenovirus-associated conjunctivitis outbreaks, 1953-2013

Abstract

This study aimed to compare the virology and epidemiology of epidemic keratoconjunctivitis (EKC), pharyngoconjunctival fever (PCF) and acute haemorrhagic conjunctivitis (AHC) outbreaks worldwide caused by the human adenovirus (HAdV) from 1953 to 2013. Eighty-three hexon sequences from 76 conjunctivitis outbreaks were analysed and subtyped using Mega 5.05, Clustal X and SimPlot software. Epidemiology was performed for the area, age and seasonal distribution. A phylogenetic analysis indicated that all the isolates could be divided into three subgenetic lineages, without a common ancestor. The major causes of the outbreaks were Ad8, Ad7 and Ad2 co-infection with enterovirus 70 (EV70) in EKC, PCF and AHC, respectively. The epidemiological findings suggested that EKC and AHC were circulating predominantly in Asia during the early winter and spring, whereas PCF was circulating mainly in China, Australia and the United States during the summer. This study suggests that EKC, AHC and PCF outbreaks have different circulating patterns throughout the world and are caused by different adenovirus serotypes. A global surveillance system should be established to monitor conjunctivitis outbreaks in the future.

Keywords: Adenovirus; conjunctivitis; ocular infection; outbreak; virology.

Fig. 1.

Phylogenetic tree based on the hexon gene of HAdV strains isolated from ocular, respiratory and vaccine strains retrieved from GenBank, listed in Supplementary Table S1. Subgroup 1, blue; subgroup 2, yellow; subgroup 3, purple).

Fig. 2.

Median-joining network depicting the relationships between the respiratory, ocular and vaccine strains between 1953 and 2013. The analysis is based on hexon gene sequences of 83 isolates deposited in GenBank from worldwide outbreaks between 1953 and 2013. The red points denote hereditary points. The yellow points denote hexon sequences. Information on the haplotype distribution is provided in Supplementary Table S2.

Fig. 3.

Prediction of the 3D structure of three protein query hexon sequences of (a), an ocular infection strain AB330133; (b), a respiratory infection strain F800905; and (c), a vaccine strain AY594254. The yellow sites indicate amino acids 103–111. The red sites denote amino acids 369–378. The green sites indicate amino acids 589–600.

Fig. 4.

The geographical distribution (a) and timeline (b) of the 48 EKC adenovirus outbreaks from 1953 to 2013 worldwide. (Note: shadow of the geographical distribution map denotes the number of EKC outbreaks in each area or country. The colours green, yellow and red denote a low, medium and high number of EKC outbreaks, respectively. The pie charts show the percentage of the serotype composition in the EKC outbreak areas or country.)

Fig. 5.

(a) Locations of the 48 HAdV-associated EKC outbreaks from 1953 to 2013. (b) The distribution of the 48 HAdV-associated EKC outbreaks from 1953 to 2013.