Pathogen surveillance of acute conjunctivitis reveals recent emergence of coxsackievirus A24 variants and high genotypic diversity of human adenoviruses in Shenzhen, China, 2018–2024

Acute conjunctivitis caused mainly by viral pathogens is an extremely frequent ophthalmological disease in people of all ages [1]. Viral conjunctivitis involves various infectious diseases, among which acute hemorrhage conjunctivitis (AHC), epidemic keratoconjunctivitis (EKC) and pharyngoconjunctival fever (PCF) are the three common diseases [2]. AHC is characterized by the sudden onset of ocular pain, swelling of the eyelids, a "foreignbody" sensation or irritation, epiphora (excessive tearing), eye discharge, and photophobia [1]. The typic symptoms of EKC include bulbar conjunctival reddening, foreignbody feeling, photophobia and tearing, and EKC frequently complicates with pseudomembranes [3]. PCF is an acute and highly contagious disease characterized by fever, pharyngitis, rhinitis, follicular conjunctivitis, and regional lymphoid hyperplasia with tender preauricular adenopathy [3]. The identification of pathogenic agents contributes to the differential diagnosis of these three infectious diseases. Coxsackievirus A24 variant (CVA24v) and enterovirus D70 (EV-D70), belonging to the genus Enterovirus in the family Picornaviridae, are implicated as the major pathogens involved in AHC [4], [5]. Since the beginning of the 21st century, CVA24v has caused outbreaks of AHC in many countries, including China in Asia [6], Spain in Europe [7], Brazil in America [8] and Gambia in Africa [9]. EKC is associated with various human adenoviruses (HAdVs) infections [2]. HAdVs belong to the genus Mastadenovirus in the family Adenoviridae, which are double-strand DNA viruses and exhibit high species diversity and diversification of pathogenicity [10]. Based on genome-wide phylogenetic relationship, HAdVs are classified into seven groups, HAdV-(A–G) [10]. To date, a total of 116 HAdV genotypes have been identified in these seven species, with HAdV-D containing the most members (http://hadvwg.gmu.edu/). PCF principally attributes to HAdV-B infections, particularly type B3 [3]. Apart from conjunctivitis, HAdV infections are also related to respiratory tract disease, gastroenteritis, hemorrhagic cystitis, pneumonia, hepatitis and plastic bronchitis [11], [12], [13].

China experienced the two large outbreaks of CVA24v associated with AHC in 2007 and 2010 [6], [14]. However, no CVA24v was detected in the acute conjunctivitis surveillance system in past decade in Shenzhen until 2023 when the third nationwide outbreak of AHC occurred in mainland China [15]. In the same period, CVA24v outbreaks also occurred in neighboring countries, India and Vietnam [16], [17]. Information about prevalence and genotype distribution of HAdV-associated with acute conjunctivitis is lacking in recent years in China. Herein, we summarize the hospital-based surveillance for acute conjunctivitis associated with CVA24v, EV-D70 and HAdV infections in Shenzhen, China during 2018–2024, and investigate the molecular characteristics of CVA24v that emerged in 2023 and genotypic diversity of HAdV circulating during 2020–2024.

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