Molecular epidemiology of acute hemorrhagic conjunctivitis caused by coxsackie A type 24 variant in China, 2004-2014

Abstract

To understand control interventions, the molecular epidemiology of acute hemorrhagic conjunctivitis (AHC) was investigated from 2004 to 2014.A total of 613,485 AHC cases (annualized cases 55,771) with two deaths were included. Our findings showed that AHC was reported in all provinces, predominantly in Southern and Eastern China. The incidence rates were highest in 2007 (5.65/100,000) and 2010 (21.78/100,000) respectively. A clear seasonal pattern was identified with a peak from August to October. AHC cases occurred in all age groups; however, five to 14 years was the predominant group [23.06%, 133, 510/578,909]. The median age was 24 years (one month~97 years). The median duration from onset to diagnosis was 1.5 days, and there was no difference between the <15, 15~60 and >60-year-old patients [p = 0.0653]. The phylogenetic analysis of 100 nonstructural proteins (3C) and 84 structural proteins (VP1) revealed that AHC outbreaks were caused by Coxsackievirus A24 variant. Genotypes G4-c5a, G4-c5b, and G4-c3 co-circulated with both temporal and geographical overlaps. In conclusion, despite the overall steady decline in the number of AHC cases since the peak in 2010, it still remains a serious public health problem in Southern and Eastern China that targets on the school aged children under 15 years old.

Figure 1. Heatmap of AHC surveillance data from 2004 to 2014 by Chinese province.

The provinces were ordered by latitude from northernmost (top) to southernmost (bottom). Time series of weekly AHC cases standardized by the incidence of annual cases. Notes: A heat map created using the gplot package in R software (https://cran.r-project.org/web/packages/gplots/index.html).

Figure 2. Timeline by illness onset month of AHC cases from 2004 to 2014 in China.

There was an obvious seasonal fluctuation of AHC with a single peak.

Figure 3. Geographic distributions of AHC cases from 2004 to 2014 in China.

(A) for 2004; (B) for 2007; (C) for 2010; (D) for 2014. The numbers and colors in the legend represent the incidence of AHC cases. These maps were generated using the software ArcGIS (ArcMap, version10.2; ESRI Inc., Redlands, CA, USA, https://www.qgis.org/en/site/forusers/download.html). The world (http://openstreetmapdata.com/data/land-polygons) and China (https://mapzen.com/data/borders/) basemaps we used are all from OpenStreetMap. The cartography in the OpenStreetMap map tiles is licensed under CC BY-SA (www.openstreetmap.org/copyright). The license terms can be found on the following link: http://creativecommons.org/licenses/by-sa/2.0/.

Figure 4. Ring map of AHC cases from 2004-2014 standardized by the incidence of annual cases in Chinese provinces.

Notes: The ring map toolbox in ArcGIS (Generated by ArcGIS 10.2, URL: http://www.esri.com/software/arcgis/arcgis-for-desktop, ESRI Inc., Redlands, CA, USA) was developed by the co-author Ta-Chien Chan. The toolbox was freely available from the website (http://www.esri.com/esri-news/arcuser/fall-2013/looking-at-temporal-changes). The world (http://openstreetmapdata.com/data/land-polygons) and China (https://mapzen.com/data/borders/) basemaps we used are all from OpenStreetMap. The cartography in the OpenStreetMap map tiles is licensed under CC BY-SA (www.openstreetmap.org/copyright). The license terms can be found on the following link: http://creativecommons.org/licenses/by-sa/2.0/.

Figure 5. Age distribution of AHC cases in China from 2004–2014.

Figure 6. Phylogenetic analyses based on the representative strains of the nonstructural protein 3C and the VP1 gene of Cox A24 viruses in China from 1985–2014.

(A) for 3C (n = 113); (B) for VP1 gene (n = 119).