Outbreak Of Acute Hemorrhagic Conjunctivitis Research Articles

Molecular characterization of coxsackievirus A24 variants isolated from an outbreak of acute hemorrhagic conjunctivitis

Acute Hemorrhagic conjunctivitis (AHC) is associated with CV A24v. Recently there was a severe outbreak of conjunctivitis in months of July and August, 2023 in India. This study emphasizes the identification of the distinct mutations in the CV A24v strains, which were isolated during the AHC outbreak and could have potentially played a role in the high transmission of AHC in India during the 2023 outbreak. A total of 71 conjunctivitis patients aged 1-75 years comprising 47 males and 24 females who attended Ophthalmology department of a tertiary care hospital of easternIndia were studied.RNA was extracted from all conjunctival swab samples and converted into cDNA. Subsequently, the viral 5' UTR was amplified and the PCR positive samples were subjected to sequencing. The newly isolated viral 5' UTR sequences were aligned with other worldwide sequences using the Clustal W tool to conduct mutational analysis. A phylogenetic tree was built using the MEGA software for viral genotype identification. All of the current outbreak strains belonged to genotype IV of CV A24v. The present outbreak strains formed a distinct clade in the phylogenetic tree and were different from previously reported Indian strains. Two persistent mutations, specifically in domain IV (T213C) and domain V (C475T), were exclusively detected within the internal ribosome entry site (IRES) of the 5' UTR of the current strains causing the outbreak. These two alterations have previously been shown to impact the virulence of another enterovirus (CV B3), but they have not been described in CV A24v until now. Finding of the present study highlights the possibility and the significance of the aforementioned two mutations in enhancing the transmissibility of the newer CV A24v strains. Hence, these two distinct mutations should be investigated further for developing antiviral therapies to combat future AHC outbreaks associated with CVA 24v.

An outbreak of acute hemorrhagic conjunctivitis due to Coxsackievirus A24 in a residential school, Naharlagun, Arunachal Pradesh: July 2023

PurposeAn acute conjunctivitis outbreak was investigated at a residential school in Naharlagun, Arunachal Pradesh, Northeast India, in July 2023. We aimed to identify the etiological agent and assess any complications in follow-up cases. MethodsWe used a structured questionnaire to record clinical findings and followed up with cases one-month post-conjunctivitis. Sixty-one cases were examined and eight conjunctival and oropharyngeal swab samples were collected after obtaining informed consent from guardians/school authorities. We screened for 33 viral and bacterial pathogens using an IVD-approved Real-time PCR assay. Further, the samples were subjected to nucleic acid sequencing. ResultsAmong 465 screened students and staff, 80 individuals (approximately 17.2%) showed acute hemorrhagic conjunctivitis symptoms among which 61 cases were available for clinical examination. We identified the Enterovirus responsible by targeted sequencing using next-generation sequencing. The etiological agent was found to be Coxsackievirus A24, a member of Enterovirus C, in seven out of eight samples subjected to sequencing. Common symptoms included conjunctival hyperemia and foreign body sensation (100%), bilateral eye involvement (73.8%), eye pain (70%), watery discharge (49.2%), and eyelid swelling (38%). Only 6.5% had purulent discharge. Most cases resolved within 5-6 days, with only 9.8% reporting abdominal symptoms post-conjunctivitis. No serious complications occurred within one month. Throat swabs aided in diagnosing enterovirus infections alongside eye swabs. ConclusionsThe outbreak of acute conjunctivitis was caused by Coxsackievirus A24, a member of Enterovirus C. Cases resolved spontaneously within 6-7 days, with no severe complications. Collecting oropharyngeal swabs alongside conjunctival swabs could improve enteroviral conjunctivitis diagnosis.

Evolutionary phylogeography reveals novel genotypes of coxsackievirus A24 variant and updates the spatiotemporal dynamics in the population with acute hemorrhagic conjunctivitis

ObjectivesThe coxsackievirus A24 variant (CVA24v) has raised a remarkable concern because of its main etiological role in acute hemorrhagic conjunctivitis. MethodsWe conducted a retrospective study to summarize CVA24v isolated from acute hemorrhagic conjunctivitis outbreaks and acute flaccid paralysis surveillance in Shandong province, China during 1988-2020. Phylogenetic and phylogeographic methods based on the VP1 coding region were used to determine the CVA24v origin, spatiotemporal dynamics, and evolution. Also, the positive selection sites in the VP1 gene were identified and exhibited in the tertiary structure. ResultsThe global CVA24vs were classified into eight genotypes (GⅠ-GⅧ). Here, 12 CVA24v isolates were detected, of which five strains were typed as two novel genotypes (GⅦ and GⅧ) and reported first in the world. The time to the most recent common ancestor of the global CVA24v was estimated around March 1965 and evolved with 5.573 × 10−3 substitutions/site/year. Four residues under positive selection were detected, and residue 146T might be adapted in the CVA24v pandemic. Phylogeographic analysis indicated that China was the main source sink for CVA24v dispersion in a long-lasting global pattern. ConclusionOur study updated the epidemiological characteristics of CVA24v and enabled a better understanding of the molecular mechanism underlying different genotypes. The results provided new insights into the CVA24v origin, spatiotemporal dynamics, and possibly, the determinants of viral tropism and pathogenicity.

Structure of Human Enterovirus 70 and Its Inhibition by Capsid-Binding Compounds.

ABSTRACTEnterovirus 70 (EV70) is a human pathogen belonging to the family Picornaviridae. EV70 is transmitted by eye secretions and causes acute hemorrhagic conjunctivitis, a serious eye disease. Despite the severity of the disease caused by EV70, its structure is unknown. Here, we present the structures of the EV70 virion, altered particle, and empty capsid determined by cryo-electron microscopy. The capsid of EV70 is composed of the subunits VP1, VP2, VP3, and VP4. The partially collapsed hydrophobic pocket located in VP1 of the EV70 virion is not occupied by a pocket factor, which is commonly present in other enteroviruses. Nevertheless, we show that the pocket can be targeted by the antiviral compounds WIN51711 and pleconaril, which block virus infection. The inhibitors prevent genome release by stabilizing EV70 particles. Knowledge of the structures of complexes of EV70 with inhibitors will enable the development of capsid-binding therapeutics against this virus.IMPORTANCE Globally distributed enterovirus 70 (EV70) causes local outbreaks of acute hemorrhagic conjunctivitis. The discharge from infected eyes enables the high-efficiency transmission of EV70 in overcrowded areas with low hygienic standards. Currently, only symptomatic treatments are available. We determined the structures of EV70 in its native form, the genome release intermediate, and the empty capsid resulting from genome release. Furthermore, we elucidated the structures of EV70 in complex with two inhibitors that block virus infection, and we describe the mechanism of their binding to the virus capsid. These results enable the development of therapeutics against EV70.

Molecular analysis of Coxsackievirus A24 variant isolates from three outbreaks of acute hemorrhagic conjunctivitis in 1988, 1994 and 2007 in Beijing, China.

Coxsackievirus A24 variant (CVA24v) is a major pathogen that causes continued outbreaks and pandemics of acute hemorrhagic conjunctivitis (AHC). In China, the first confirmed outbreak of CVA24v-related AHC occurred in Beijing in 1988, followed by another two significant outbreaks respectively in 1994 and 2007, which coincides with the three-stage dynamic distribution of AHC in the world after 1970s. To illustrate the genetic characteristics of CVA24v in different periods, a total of 23 strains were isolated from those three outbreaks and the whole genome of those isolations were sequenced and analyzed. Compared with the prototype strain, the 23 strains shared four nucleotide deletions in the 5′ UTR except the 0744 strain isolated in 2007. And at the 98th site, one nucleotide insertion was found in all the strains collected from 2007. From 1994 to 2007, amino acid polarity in the VP1 region at the 25th and the 32nd site were changed. Both the 3C and VP1 phylogenetic tree indicated that isolates from 1988 and 1994 belonged to Genotype III (GIII), and 2007 strains to Genotype IV (GIV). According to the Bayesian analysis based on complete genome sequence, the most recent common ancestors for the isolates in 1988, 1994 and 2007 were respectively estimated around October 1987, February 1993 and December 2004. The evolutionary rate of the CVA24v was estimated to be 7.45 ​× ​10−3 substitutions/site/year. Our study indicated that the early epidemic of CVA24v in Chinese mainland was the GIII. Point mutations and amino acid changes in different genotypes of CVA24v may generate intensity differences of the AHC outbreak. CVA24v has been evolving constantly with a relatively rapid rate.

Decreased incidence of acute hemorrhagic conjunctivitis associated with enhanced public health intervention during the COVID-19 epidemic in China, 2020.

Outbreaks of acute hemorrhagic conjunctivitis (AHC) are associated with a high disease burden. In this study, we investigated the association between enhanced public health intervention and the incidence of AHC during the COVID-19 pandemic in China. A total of 212,526 AHC cases were reported in China during 2015–2020. The overall yearly incidence rate and number of AHC cases decreased by 23.08% and 22.15%, respectively, during the COVID-19 epidemic, compared with the previous 5 years (all p < 0.001). Significant reductions in AHC incidence were found both during the emergency period and after the relaxation of emergency measures in 2020 compared to the previous 5 years (22.22% and 28.00% reduction, respectively; p < 0.001). Enhanced public health initiatives during the COVID-19 pandemic in China were therefore associated with lower transmission of pathogens causing AHC.

Long-term effects of weather condition and air pollution on acute hemorrhagic conjunctivitis in China: A nationalwide surveillance study in China

BackgroundGlobal climate change could have potential impact on enterovirus (EV)-induced infectious diseases. However, the environmental factors promoting acute hemorrhagic conjunctivitis (AHC) circulation remain inconclusive. This study aimed to quantify the relationship between the environment and AHC. MethodsWe retrieved the monthly counts and incidence of AHC, meteorological variables and air quality in mainland China between 2013 and 2018. Exposure risks were evaluated by multivariate distributed lag nonlinear models. ResultsA total of 219,599 AHC cases were reported in 31 provinces of China, predominantly in southern and central China, seasonally increased in summer. AHC incidence increased by 7% between 2013 and 2018, from 2.6873 to 2.7570 per 100,000 people. A moderate positive correlation was seen between AHC and monthly mean temperature, relative humidity (RH) and precipitation. Each unit increment was associated with a relative risk for AHC of 1.058 at 17°-32 °C at lag 0 months, 1.017 at 65–71% RH at lag 1.4 months, and 1.039 at 400–569 mm at lag 2.4 months. By contrast, a negative correlation was seen between monthly ambient NO2 and AHC. ConclusionLong-term exposure to higher mean temperature, RH and precipitation were associated with an increased risk of AHC. The general public, especially susceptible populations, should pay close attention to weather changes and take protective measures in advance to any AHC outbreak as the above situations occur.

Molecular Characterization of Coxsackievirus A24v from Feces and Conjunctiva Reveals Epidemiological Links.

Coxsackievirus A24 variant (CVA24v), the main causative agent of acute hemorrhagic conjunctivitis (AHC), can be isolated from both the eyes and lower alimentary tract. However, the molecular features of CVA24v in feces is not well-documented. In this study, we compared the VP1 and 3C sequences of CVA24v strains isolated from feces during AHC epidemics in Cuba in 1997, 2003, and 2008–2009 with those obtained from conjunctival swabs during the same epidemic period. The sequence analyses of the 3C and VP1 region of stool isolates from the three epidemics showed a high degree of nucleotide identity (ranging from 97.3–100%) to the corresponding conjunctival isolates. The phylogenetic analysis showed that fecal CVA24v isolates from the 1997 and 2003 Cuban outbreaks formed a clade with CVA24v strains isolated from conjunctival swabs in Cuba and other countries during the same period. There were three amino acid changes (3C region) and one amino acid change (VP1 region) in seven CVA24v strains isolated sequentially over 20 days from fecal samples of one patient, suggesting viral replication in the intestine. Despite these substitutions, the virus from the conjunctival swab and fecal samples were genetically very similar. Therefore, fecal samples should be considered as a reliable alternative sample type for the routine molecular diagnosis and molecular epidemiology of CVA24v, also during outbreaks of AHC.

Molecular evolution of coxsackievirus A24v in Cuba over 23-years, 1986\u20132009

Coxsackievirus A24 variant (CVA24v) is a major causative agent of acute hemorrhagic conjunctivitis outbreaks worldwide, yet the evolutionary and transmission dynamics of the virus remain unclear. To address this, we analyzed and compared the 3C and partial VP1 gene regions of CVA24v isolates obtained from five outbreaks in Cuba between 1986 and 2009 and strains isolated worldwide. Here we show that Cuban strains were homologous to those isolated in Africa, the Americas and Asia during the same time period. Two genotypes of CVA24v (GIII and GIV) were repeatedly introduced into Cuba and they arose about two years before the epidemic was detected. The two genotypes co-evolved with a population size that is stable over time. However, nucleotide substitution rates peaked during pandemics with 4.39 × 10−3 and 5.80 × 10−3 substitutions per site per year for the 3C and VP1 region, respectively. The phylogeographic analysis identified 25 and 19 viral transmission routes based on 3C and VP1 regions, respectively. Pandemic viruses usually originated in Asia, and both China and Brazil were the major hub for the global dispersal of the virus. Together, these data provide novel insight into the epidemiological dynamics of this virus and possibly other pandemic viruses.

Community-based surveillance advances the Global Health Security Agenda in Ghana

Ghana Health Service (GHS) has strengthened community-based surveillance (CBS) to facilitate early detection and rapid reporting of health events of all origins. Since June 2017, GHS has employed an event-based surveillance approach at the community level in a phased manner. CBS coverage has broadened from 2 to 30 districts across Ghana. Through this effort, capacity was built across all administrative levels in these districts to detect, report, triage, and verify signals, and to perform risk assessment and investigate events. Data were collected and analyzed during an evaluation of initial 2-district implementation in March 2018 and during expanded 30-district implementation in March 2019. Between September 2018 and March 2019, 317 health events were detected through CBS. These events included vaccine-preventable disease cases, acute hemorrhagic conjunctivitis outbreaks, clusters of unexpected animal deaths, and foodborne illness clusters. Eighty-nine percent of the 317 events were reported to district-level public health staff within 24 hours of detection at the community level, and 87% of all detected events were responded to within 48 hours of detection. CBS detected 26% of all suspected vaccine-preventable disease cases that were reported from implementing districts through routine disease surveillance. GHS strengthened CBS in Ghana to function as an early warning system for health events of all origins, advancing the Global Health Security Agenda.

Epidemiological Characteristics and Spatiotemporal Analysis of Acute Hemorrhagic Conjunctivitis from 2004 to 2018 in Chongqing, China

Chongqing is one of the five provinces in China that has the highest incidence of acute hemorrhagic conjunctivitis (AHC). Data of AHC cases from 2004 to 2018 were obtained from National Notifiable Diseases Reporting Information System (NNDRIS). Descriptive statistical methods were used to analyze the epidemiological characteristics; incidence maps were used to reflect incidence trends in each district; spatial autocorrelation was used to identify hotspot regions and spatiotemporal patterns of AHC outbreaks; spatiotemporal scan were conducted to identify AHC clusters. A total of 30,686 cases were reported with an annual incidence of 7.04 per 100,000. The incidence rates were high in 2007 and 2014, and large epidemics were observed in 2010 with the seasonal peak in September. Individuals aged 10–19 years, males, students and farmers were the prime high-risk groups. Except for 2012 and 2013, the spatial distribution of AHC did not exhibit significant global spatial autocorrelation. Local indicators of spatial association showed that the high-risk regions are Chengkou and Wuxi. The spatiotemporal scan indicated that all clusters occurred in September 2010, and the high-incidence clusters were mainly distributed in the northeast of Chongqing. The results could assist public health agencies to consider effective preventive measures based on epidemiological factors and spatiotemporal clusters in different regions.

Complete genome sequence of a coxsackievirus type A24 variant causing an outbreak of acute haemorrhagic conjunctivitis in southeastern Mexico in 2017.

Cases of acute haemorrhagic conjunctivitis (AHC) caused by a coxsackie virus A24 variant (CV-A24v) in Mexico have been reported since 1987; however, no molecular data on the causative strains have been available. Here, we report the identification of the etiological agent responsible for the most recent AHC outbreak in southeastern Mexico (at the end of 2017) as well as the complete genome sequences of seven isolates, using next-generation sequencing (NGS). Phylogenomic analysis of the CV-A24v sequences reported here showed similarity to contemporary strains causing AHC outbreaks in French Guiana and Uganda, forming a novel clade related to genotype IV. Moreover, a specific mutational pattern in the non-structural proteins was identified in the 2017 isolates. This is the first report of genetic characterization of CV-A24v isolates obtained in Mexico.

Transmissibility of acute haemorrhagic conjunctivitis in small-scale outbreaks in Hunan Province, China

Acute haemorrhagic conjunctivitis (AHC) outbreaks are reported frequently in China. However, the transmissibility of AHC remains unclear. This study aimed to calculate the transmissibility of the disease with and without interventions. An AHC outbreak dataset from January 2007 to December 2016 in different schools was built in Hunan Province. A Susceptible-Infectious-Recovered (SIR) model was adopted to calculate the effective reproduction number (Reff) of AHC. Reff was divided into two parts (Runc and Rcon) where Runc and Rcon represent the uncontrolled and controlled Reff , respectively. Based on Runc and Rcon, an index of effectiveness of countermeasures (Ieff) was developed to assess the effectiveness of countermeasures in each outbreak. During the study period, 34 AHC outbreaks were reported in 20 counties of 9 cities in Hunan Province, with a mean total attack rate of 7.04% (95% CI: 4.97–9.11%). The mean Runc of AHC outbreaks was 8.28 (95% CI: 6.46–10.11). No significance of Runc was observed between rural and urban areas (t = −1.296, P = 0.205), among college, secondary, and primary schools (F = 0.890, P = 0.459), different levels of school population (F = 0.738, P = 0.538), and different number of index cases (F = 1.749, P = 0.180). The most commonly implemented countermeasures were case isolation, treatment, and health education, followed by environment disinfection, symptom surveillance, and school closure. Social distance, prophylaxis, and stopping eye exercises temporary were implemented occasionally. The mean value of Rcon was 0.16 (range: 0.00–1.50). The mean value of Ieff was 97.16% (range: 71.44–100.00%). The transmissibility of AHC is high in small-scale outbreaks in China. Case isolation, treatment, and health education are the common countermeasures for controlling the disease.

Re-emergence of a coxsackievirus A24 variant causing acute hemorrhagic conjunctivitis in Brazil from 2017 to 2018.

A large outbreak (over 200,000 cases) of acute hemorrhagic conjunctivitis (AHC) took place in Brazil during the summer of 2017/2018, seven years after a nationwide epidemic, which occurred in 2011. To identify the etiological agent, 80 conjunctival swabs from patients with a clinical presentation suggestive of AHC were analyzed at the national enterovirus laboratory. Real-time RT-PCR for human enteroviruses was performed, and enterovirus RNA was detected in 91.25% (73/80) of the specimens. Twenty-nine swab fluids were used to inoculate cell cultures (RD and Hep2C), and 72.4% (21/29) yielded a cytopathic effect. Genotype IV coxsackievirus A24v (CV-A24v) was identified as the causative agent of the outbreak. Phylogenetic analysis based on the VP1 gene revealed that Brazilian isolates were genetically related to strains that caused an outbreak in French Guiana in 2017. Our results show the re-emergence of CV-A24v causing AHC outbreaks in Brazil between the end of 2017 and the beginning of 2018.

Role of enhanced receptor engagement in the evolution of a pandemic acute hemorrhagic conjunctivitis virus

Acute hemorrhagic conjunctivitis (AHC) is a painful, contagious eye disease, with millions of cases in the last decades. Coxsackievirus A24 (CV-A24) was not originally associated with human disease, but in 1970 a pathogenic "variant" (CV-A24v) emerged, which is now the main cause of AHC. Initially, this variant circulated only in Southeast Asia, but it later spread worldwide, accounting for numerous AHC outbreaks and two pandemics. While both CV-A24 variant and nonvariant strains still circulate in humans, only variant strains cause AHC for reasons that are yet unknown. Since receptors are important determinants of viral tropism, we set out to map the CV-A24 receptor repertoire and establish whether changes in receptor preference have led to the increased pathogenicity and rapid spread of CV-A24v. Here, we identify ICAM-1 as an essential receptor for both AHC-causing and non-AHC strains. We provide a high-resolution cryo-EM structure of a virus-ICAM-1 complex, which revealed critical ICAM-1-binding residues. These data could help identify a possible conserved mode of receptor engagement among ICAM-1-binding enteroviruses and rhinoviruses. Moreover, we identify a single capsid substitution that has been adopted by all pandemic CV-A24v strains and we reveal that this adaptation enhances the capacity of CV-A24v to bind sialic acid. Our data elucidate the CV-A24v receptor repertoire and point to a role of enhanced receptor engagement in the adaptation to the eye, possibly enabling pandemic spread.

Molecular epidemiology of acute hemorrhagic conjunctivitis caused by coxsackie A type 24 variant in China, 2004\u20132014

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.

Adenovirus Isolated from an Outbreak of Acute Hemorrhagic Conjunctivitis

Adenovirus Isolated from an Outbreak of Acute Hemorrhagic Conjunctivitis

Dynamic modelling of strategies for the control of acute haemorrhagic conjunctivitis outbreaks in schools in Changsha, China (2004-2015).

Outbreaks of acute haemorrhagic conjunctivitis (AHC) - a rapidly progressing and highly contagious infection - often occur in schools during summer and autumn. We used dynamic modelling to evaluate the efficacy of interventions to control AHC outbreaks in schools. A susceptible-infected-recovered (SIR) model was built to simulate AHC outbreaks in Chinese schools, with isolation or school closure added into the model. We used outbreak data from the period 2004-2015 in our models to estimate the effective reproduction number and assess the efficacy of interventions. The median effective reproduction number (uncontrolled) of AHC outbreaks was 7·00 (range 1·77-25·87). The median effective reproduction number (controlled) of AHC outbreaks was 0·16 (range 0·00-2·28). Intervention efficacy is affected by the timing of isolation; earlier isolation is associated with a lower morbidity peak and smaller total attack rate (TAR). School closures were not effective; TARs were almost 100% and did not change even when different school closure durations were adopted. Isolation and school closure as a combined intervention strategy was used to simulate outbreak control, but the efficacy was the same as isolation alone. An isolation programme could be an effective primary intervention during AHC outbreaks in schools. However, school closure is not recommended.

A major outbreak of conjunctivitis caused by coxsackievirus A24, Réunion, January to April 2015.

From January to April 2015, Réunion experienced a major outbreak of acute haemorrhagic conjunctivitis (AHC) caused by coxsackievirus A24, which heavily impacted the healthcare system. According to the general practitioners' (GP) sentinel network, the number of medical consultations due to conjunctivitis during this period was estimated at ca 100,000. This report describes the characteristics of the outbreak, which were obtained through several different yet complementary surveillance systems on the island. These included the network of hospital emergency departments (OSCOUR network), the GPs' sentinel network, an Internet-based population cohort ('Koman i lé') participating in a survey on distinct symptoms including 'red eyes' and the monitoring of eye drop sales. Overall the results of the different surveillance approaches were in good agreement regarding the outbreak dynamic. A peak of patients with conjunctivitis was detected in the first 15 days of March (week 10 and 11), coinciding with increased eye drop sales on the island. Strains recovered from outbreak cases belonged to genotype IV and were most closely related to strains identified in AHC outbreaks in China, Egypt and Japan since 2010. Continued surveillance of AHC in Réunion remains important not only locally, but also because frequent exchanges between the island and mainland France may lead to introduction of this virus in Europe.

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

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.