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

PURPOSE: An 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. METHODS: We 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. RESULTS: Among 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. CONCLUSIONS: The 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.

OBJECTIVES: The coxsackievirus A24 variant (CVA24v) has raised a remarkable concern because of its main etiological role in acute hemorrhagic conjunctivitis. METHODS: We 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. RESULTS: The 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. CONCLUSION: Our 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.

Epidemiological Investigation and Risk Factor Analysis of Acute Hemorrhagic Conjunctivitis in Huangshi Port District, Huangshi City.

Objective: This study is aimed at investigating the epidemiology and risk factors of acute hemorrhagic conjunctivitis (pinkeye) in Huangshi Port District of Huangshi City. Methods: A total of 593 cases of acute hemorrhagic conjunctivitis from January 2019 to December 2021 were selected as the observation group. The epidemiological characteristics (age of onset, season, occupation, clinical manifestations, and etiological characteristics) were analyzed. A total of 425 healthy subjects (nonacute hemorrhagic conjunctivitis) were selected as the control group. The general data of the two groups were compared, and the risk factors affecting the occurrence of acute hemorrhagic conjunctivitis were analyzed by logistic regression. Results: The onset age of acute hemorrhagic conjunctivitis was mainly concentrated in 0-20-year-old and 60-year-old age groups, and the onset season was mainly concentrated in April to August, with the highest incidence in May. The proportions of middle school students and workers in patients with acute hemorrhagic conjunctivitis were higher than those of other occupations (both P < 0.05). Ocular conjunctival congestion, tingling, and foreign body sensation were the main clinical manifestations of patients with acute hemorrhagic conjunctivitis. Among the 593 conjunctival swab samples collected in this study, the positive rates of HEV70 and CVA24v were higher than those of adenovirus nucleic acid (both P < 0.05). The proportion of people aged ≤40 years old, male, working outdoors, using potable water equipment, contact history of patients with acute conjunctivitis, history of chemical substances entering eyes, combined with immune system diseases, and public toilet utilization rate ≥ 1 times/d in the observation group was higher than that in the control group (all P < 0.05), and the proportion of people washing hands before eating and after toilet was lower than that in the control group (P < 0.05). Multiple logistic regression analysis showed that working place outdoors, use of potable water equipment, contact history of patients with acute conjunctivitis (all P < 0.05), and use of public toilets ≥ once a day were risk factors for the occurrence of acute hemorrhagic conjunctivitis, and washing hands before eating and after toilet was a protective factor (P < 0.05). Conclusion: The onset age of acute hemorrhagic conjunctivitis was mainly concentrated in 0-20-year-old and 60-year-old age; the onset season was mainly concentrated in summer and autumn; adenovirus is the main pathogenic bacteria; ocular conjunctivitis congestion, tingling, and foreign body sensation were the main clinical manifestations; working place outdoors, use of potable water equipment, contact history of patients with acute conjunctivitis (all P < 0.05), and use of public toilets ≥ once a day were risk factors for the occurrence of acute hemorrhagic conjunctivitis, while washing hands before eating and after toilet was a protective factor.

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 â€‹× â€‹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.

Epidemiological trends and sociodemographic factors associated with acute hemorrhagic conjunctivitis in mainland China from 2004 to 2018.

BACKGROUND: Acute hemorrhagic conjunctivitis (AHC) is classified as a class C notifiable infectious disease in China and poses a great threat to public health. This study aimed to investigate the epidemiological trends and hotspots of AHC in mainland China. Sociodemographic factors that could contribute to early warning of AHC were further explored. METHODS: Yearly and monthly incidences of acute hemorrhagic conjunctivitis by date and region from 2004 to 2018 were extracted from the Data Center of China Public Health Science. Joinpoint regression and spatial autocorrelation analysis were performed to explore the epidemiological trends and hotspots of AHC. A generalized linear model was then applied to explore the relationship between sociodemographic factors and AHC incidence. RESULTS: The average annual AHC incidence was 3.58/100,000 in mainland China. The first-level spatial and temporal aggregation areas were distributed in Guangxi, Hainan, Guangdong, Guizhou, Hunan, Jiangxi, Fujian, Chongqing, Hubei, Anhui, and Zhejiang, with gathering times from 2010/1/1 to 2010/12/31 (RR = 20.13, LLR = 474,522.89, P < 0.01). After 2010, the AHC incidence was stable (APC = - 8.37, 95% CI: - 23.02-9.06). However, it was significantly increased in low- and middle-income provinces (AAPC = 10.65, 95% CI: 0.62-21.68, AAPC = 11.94, 95% CI: 0.62-24.53). The peak of AHC occurred during the August to October period. Children who age 0-3 years are identified as high-risk group with AHC incidence significantly increased (APC = 31.54, 95% CI: 0.27-72.56). Birth rate, population ages 0-14 (% of total population), passenger traffic, and urban population (% of total population) were positively associated with the AHC incidence, while per capita gross domestic product was negatively associated with the AHC incidence. CONCLUSION: Overall, the AHC incidence was stable after 2010 in China, but it was significantly increased in low- and middle-income provinces. Regions with a high birth rate, population ages 0-14 (% of the total population), passenger traffic, urban population (% of the total population) and low per capita gross domestic product are at high risk of incidences of AHC. In the future, public health policy and resource priority for AHC in regions with these characteristics are necessary.

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.

BACKGROUND: Global 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. METHODS: We 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. RESULTS: A 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. CONCLUSION: Long-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 evolution of coxsackievirus A24v in Cuba over 23-years, 1986-2009.

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.

Forecasting the incidence of acute haemorrhagic conjunctivitis in Chongqing: a time series analysis.

Acute haemorrhagic conjunctivitis is a highly contagious eye disease, the prediction of acute haemorrhagic conjunctivitis is very important to prevent and grasp its development trend. We use the exponential smoothing model and the seasonal autoregressive integrated moving average (SARIMA) model to analyse and predict. The monthly incidence data from 2004 to 2017 were used to fit two models, the actual incidence of acute haemorrhagic conjunctivitis in 2018 was used to validate the model. Finally, the prediction effect of exponential smoothing is best, the mean square error and the mean absolute percentage error were 0.0152 and 0.1871, respectively. In addition, the incidence of acute haemorrhagic conjunctivitis in Chongqing had a seasonal trend characteristic, with the peak period from June to September each year.

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.

Effects of Floods on the Incidence of Acute Hemorrhagic Conjunctivitis in Mengshan, China, from 2005 to 2012.

This study aimed to examine the association between floods and the morbidity of acute hemorrhagic conjunctivitis (AHC) in Mengshan, China. Relying on the longitudinal data, a generalized additive model (GAM) was applied to quantify the relationship between the morbidity of AHC and floods from 2005 to 2012, controlling for other meteorological variables. Years lived with disability (YLDs) and attributable YLDs were used as the measure of the burden of AHC because of the floods. Multivariable analysis showed that floods were significantly associated with an increased risk of the morbidity of AHC (rate ratio [RR] = 2.136, 95% CI: 2.109-2.163). The total YLDs per 1,000 in Mengshan was 0.2001, although the value in females was higher than that in males (0.2351 versus 0.1686). The YLD per 1,000 of AHC in Mengshan was highest between the ages of 5 and 14 years (0.6530), followed by the age of 0-4 years (0.3325). The attributable YLD per 1,000 of AHC due to the floods in Mengshan was 0.0434 (95% CI: 0.0425-0.0442). Our study confirms that floods have significantly increased the risks of AHC in the selected study area. Females and youngsters may be the vulnerable populations to develop the flood-related disease.

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.

Forecast of the trend in incidence of acute hemorrhagic conjunctivitis in China from 2011-2019 using the Seasonal Autoregressive Integrated Moving Average (SARIMA) and Exponential Smoothing (ETS) models.

BACKGROUND: This study aimed to explore the demographic and distributive features of acute hemorrhagic conjunctivitis (AHC). We constructed seasonal autoregressive integrated moving average (SARIMA) and exponential smoothing (ETS) models to predict its trend in incidence in mainland China and provided evidence for the government to formulate policies regarding AHC prevention. METHODS: Data regarding the distribution and demographic characteristics of AHC in China from 2011-2016 were retrieved from the Public Health Scientific Data website. Monthly AHC data from January 2011 to June 2019 were used to establish and evaluate the SARIMA and ETS models. RESULTS: During 2011-2016, a total of 213,325 cases were reported; 46.01% were farmers, patients aged ≤9 years had the highest risk, and the male:female ratio was 1.31:1. Guangxi and Guangdong had the highest number of reported AHC cases. The SARIMA (0, 0, 1) (2, 0, 0) 12 model with the minimum root mean squared error and mean absolute percentage error were finally selected for in-sample simulation. CONCLUSIONS: AHC remains a serious public health problem in Southern and Eastern China that mainly affects farmers and children younger than 9 years. It is recommended that the health administration strengthen the publicity and education regarding AHC prevention among farmers and accelerate the development of related vaccines and treatment measures.

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.

Impact of Drinking Water Quality on the Development of Enteroviral Diseases in Korea.

Enterovirus diseases are fecal-orally transmitted, and its transmission may be closely related with the drinking water quality and other environmental factors. This study aimed to assess the association between environmental factors including drinking water quality and the incidence of enteroviral diseases in metropolitan provinces of Korea. Using monthly number of hand-foot-mouth disease (HFMD), aseptic meningitis (AM) and acute hemorrhage conjunctivitis (AHC) cases, generalized linear Poisson model was applied to estimate the effects of environmental factors on the monthly cases. An increase of mean temperature was associated with an increase of enteroviral diseases at 0⁻2 months lag, while an increase of turbidity was associated with increase in HFMD at 1 month lag and a decrease in AHC. An increase of residual chlorine in municipal drinking water was associated with a decrease in HFMD and AHC 2 and 3 months later. An increase of pH was associated with a maximum increase in AM 3 months later. The meta-analysis revealed the effects of the provincial and pooled variation in percent change of risks of environmental factors on HFMD, AM, and AHC cases at specific selected lags. This study suggests that the drinking water quality is one of the major determinants on enteroviral diseases.

Costs of Conjunctivitis Outbreak, Réunion Island, France.

During January-April 2015, a major outbreak of conjunctivitis on Réunion Island caused a large public health impact. On the basis of general practitioner consultations, emergency department visits, and eye medication sales during the 13-week epidemic, we estimated a total healthcare cost of €3,341,191 from the outbreak.

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.

An outbreak of acute haemorrhagic conjunctivitis associated with coxsackievirus A24 variant in The Gambia, West Africa.

OBJECTIVE: An outbreak of acute haemorrhagic conjunctivitis occurred in The Gambia, West Africa in 2011. Affected individuals presented with conjunctival haemorrhages, swelling and ocular discharge. In an effort to identify a causative agent of the disease, ocular swabs were taken from patients during the acute and convalescent phases. Total RNA was extracted from all samples and reverse-transcriptase PCR performed using primers specific for all enteroviruses. Resulting amplicons were sequenced and data compared to known sequences using the BLAST algorithm. RESULTS: Forty-eight swabs were included in the analysis. Of these, 21 acute and 9 convalescent swabs (65% of the total) gave positive PCR results. Sequence analysis of the resulting amplicons indicated 99% sequence identity with coxsackievirus A24 variant identified during independent outbreaks of acute haemorrhagic conjunctivitis around the world and suggest the Gambian outbreak was due to this virus.