2012 outbreak of acute haemorrhagic conjunctivitis in Indian Ocean Islands: identification of Coxsackievirus A24 in a returned traveller.

In May 2012, a Coxsackievirus A24 haemorrhagic conjunctivitis was diagnosed in Marseille, France, in a traveller returning from the Comoros Islands. This case allowed identification of the cause of an ongoing outbreak of haemorrhagic conjunctivitis in Indian Ocean Islands, illustrating that returning travellers may serve as sentinels for infectious diseases outbreaks in tropical areas where laboratory investigation is limited.

Isolation of Coxsackievirus A24 variant from patients with hemorrhagic conjunctivitis in Cuba, 2008-2009.

BACKGROUND: An outbreak of acute hemorrhagic conjunctivitis occurred in Cuba in 2008 and 2009. OBJECTIVE: To determinate the etiological agent associated with the Cuban outbreaks of acute hemorrhagic conjunctivitis during 2008 and 2009. STUDY DESIGN: Conjunctival swabs and/or faecal samples from 382 patients with clinical diagnosis suggestive of acute hemorrhagic conjunctivitis were subject to viral culture in HEp-2 human laryngeal epidermoid carcinoma cells. Positive samples were identified by a specific Coxsackievirus A24 variant PCR and the 3C protease region of 16 isolates was sequenced for phylogenetic analysis. RESULTS: Enterovirus cytopathic effect was observed in 138 cases (36%). A higher percent of CA24v was recovered from faecal samples, 19 out of 45 cases (42.2%), than from conjunctival swabs, 127 out of 355 samples (35.8%). All isolates were identified as Coxsackievirus A24 variant. Phylogenetic analysis revealed that 2008 and 2009 Cuban outbreaks were caused by the same virus strains and that isolates were closely related to those from Taiwan (2006-2007), China (2007-2008) and Singapore (2005) with a bootstrap value of 71%. CONCLUSIONS: Outbreaks of acute hemorrhagic conjunctivitis occurred in Cuba in 2008 and 2009 were caused by Coxsackievirus A24 variant. The faecal-oral route is another mode of transmission of CA24v in the acute hemorrhagic conjunctivitis outbreaks. Phylogenetic analysis of Cuban CA24v strains involved in an acute hemorrhagic conjunctivitis outbreak in 2008 and 2009 confirms a new introduction of the CA24 variant into the Americas from South-east Asia.

[Application of Susceptible-Infected-Recovered model in dealing with an outbreak of acute hemorrhagic conjunctivitis on one school campus].

To simulate intervention measures in controlling an outbreak of acute hemorrhagic conjunctivitis on one school campus by using the Susceptible-Infected-Recovered (SIR) model, to provide evidence for preparedness and response to the epidemic. Classical SIR model was used to model the epidemic. Malthusian exponential decline method was employed to estimate the infective coefficient ß for interventions. The initial value of parameters was determined based on empirical data. The modeling was implemented using Matlab 7.1 software. Without interventions, the outbreak was expected to experience three phrases: (1) early stage (the first 5 days) in which the epidemic developed slowly and could be intervened easily; (2) rapid growing stage (6 - 15 days) in which the number of infected cases increased quickly and the epidemic could not be well controlled; and (3) medium and late stage (16 days and later) in which more than 90% of the susceptible persons were infected but the intervention measures failed to prevent the epidemic. With the implementation of interventions, the epidemic was predicted to be controlled in the early stage, under the SIR model. The simulation based on the SIR model kept an acceptable consistency with the actual development of epidemic after the implementation of intervention measures. The SIR model seemed effective in modeling interventions to the epidemic of acute hemorrhagic conjunctivitis in the schools.

Notes from the field: acute hemorrhagic conjunctivitis outbreaks caused by coxsackievirus A24v --- Uganda and southern Sudan, 2010.

CDC was contacted on June 22, 2010, by the Ugandan Ministry of Health (MoH)/Uganda Virus Research Institute and on July 11 by the Government of Southern Sudan (GOSS) via the CDC Global Disease Detection Regional Center in Kenya to perform diagnostic laboratory testing on conjunctival swabs from persons with "red eye syndrome." Widespread, ongoing outbreaks of acute hemorrhagic conjunctivitis (AHC) have been observed in Uganda and Southern Sudan since spring 2010. AHC becomes a reportable condition in outbreak settings. Case numbers were estimated in Uganda after MoH confirmation of reported cases from district health facilities and, in Southern Sudan, after a medical record review in six health facilities. To date, 6,818 cases from 26 districts in Uganda, and 428 cases in Juba, Southern Sudan, have been counted; however, because most cases are not reported, these totals are considered underestimates.

[Enteroviruses responsible for acute hemorrhagic conjunctivitis]. / Les Enterovirus responsables de conjonctivite aiguë hémorragique.

Acute hemorrhagic conjunctivitis (AHC) is an epidemic form of highly contagious conjunctivitis, characterized by conjunctival hemorrhages. The first AHC outbreak was described in 1969 in Ghana, West Africa, and was called Apollo disease, from the Apollo landing on the moon. This outbreak was caused by Enterovirus 70 (EV70) together with a Coxsackievirus A24 (CVA24v) variant, which are the major etiological agents involved in AHC outbreaks worldwide. AHC is known to be directly transmitted by close person-to-person contact or indirectly through soiled ophthalmological materials or unsafe recreational water. Recently, a possible airborne virus spread was suggested which could explain the high transmission rate of the disease. In the absence of a specific antiviral therapy, a rapid diagnosis of the causative agent is required to distinguish AHC due to enteroviruses from other ocular infectious diseases, for there are active drugs, or to quickly implement proper public health measures to limit the extension of the outbreak. However, virus identification remains difficult and time-consuming. Moreover, virological diagnosis is difficult to implement in developing countries where AHC has recently become a major problem for public health.

[Fruit of the emergence of an enterovirus: acute haemorrhagic conjunctivitis]. / Fruit de l'émergence d'un entérovirus : la conjonctivite aiguë hémorragique.

First seen in Ghana and Indonesia in the early 70's, acute haemorrhagic conjunctivitis or "Apollo 11" disease is an eye infection caused by Enterovirus type 70 (EV70). The disease appeared to be a highly contagious conjunctivitis which spread rapidly all over the world. EV70 has been considered as an emerging virus and was classified as a new Enterovirus. No human or animal virus genetically similar to EV70 was known before the sudden outcome of the disease in Ghana, West Africa. EV70 appeared as a pretty demonstrative example of virus emergence and virus spreading. Studies of virus genetic mutations emphasized the variations of RNA virus within a short time period. The current review presents the EV70 infection and the genetic profile of the virus from its emergence to nowadays.

Laboratory results in ocular viral diseases: implications in clinical-laboratory correlation.

PURPOSE: To document etiology and predictive value of clinical diagnosis in laboratory confirmed viral diseases. METHODS: Reports of culture-positive cases of samples collected from patients presenting from January 1987 - December 2001 were evaluated. RESULTS: One thousand nine hundred and sixty-four (1964) cultures were submitted during 1987-2001. Twenty-six percent were positive (514). Human herpesvirus 1 was the most frequent agent isolated from all positive culture (56%). Adenovirus was the most common virus isolated from conjunctiva (66%), human herpesvirus 1 from lid and cornea (76%, 88%) and cytomegalovirus from vitreous (27%). Some unusual pathogens were recovered from conjunctiva as cytomegalovirus and from cornea as adenovirus, enterovirus and cytomegalovirus. Recognition of common viral syndromes was human herpesvirus 1 (88%), epidemic keratoconjunctivitis (88%), acute hemorrhagic conjunctivitis (70%) and varicella zoster virus (100%). However, some misdiagnosed cases were observed. Thirteen percent of conjunctivitis thought to be caused by herpes were due to adenovirus, 3.2% to Enterovirus, 3.2% to varicella zoster virus and 3.2% to human cytomegalovirus. Also, 5% of cases with a clinical diagnosis of herpes keratitis were caused by adenovirus and 2.7% by enterovirus. Finally, 4.8% of cases thought to be adenovirus conjunctivitis were herpes conjunctivitis. CONCLUSIONS: Human herpesvirus 1 remains the most frequently isolated virus from ocular sites in general (56%). Nonherpetic corneal isolates were in decreasing order: adenovirus, enterovirus and cytomegalovirus. Clinical and laboratory correlation was less than 90%. The most misdiagnosed cases were herpes conjunctivitis and keratitis, some cases of adenovirus conjunctivitis some cases of acute hemorrhagic conjunctivitis. It is essential that a rapid and specific diagnosis is offered under atypical viral presentation for the institution of specific antiviral therapy and to avoid complications that can be a result of misdiagnosis and inappropriate treatment. Also it is important to do viral testing in order to confirm clinical diagnosis, report emerging infections, resistance and change in the epidemiology.

Rapid diagnosis of acute hemorrhagic conjunctivitis due to coxsackievirus A24 variant by real-time one-step RT-PCR.

Coxsackievirus A24 variant is, together with enterovirus 70 and adenoviruses, the major etiological agent involved in acute hemorrhagic conjunctivitis outbreaks worldwide. However, the standard virus isolation method followed by serotyping or VP1 region sequencing is time-consuming. A rapid method for the detection of coxsackievirus A24 variant from conjunctival swab specimens would be useful in the context of explosive and extensive outbreaks. A one-step real-time RT-PCR assay based on TaqMan technology was thus developed and assessed on 36 conjunctival swabs from outbreaks of conjunctivitis in Morocco in 2004 due to a coxsackievirus A24 variant and in Corsica in 2006 due to adenovirus type 3, and 83 virus strains including 41 coxsackievirus A24 variant collected in French Guiana and Guadeloupe in 2003, in the Democratic Republic of the Congo in 2003, in Morocco in 2004 and 42 other virus species genetically close or known to be responsible for conjunctivitis. All the conjunctival swabs from coxsackievirus A24 variant related outbreak and the 41 coxsackievirus A24 variant strains were tested positive by the RT-PCR assay within 4h. This novel single-tube real-time RT-PCR assay is sensitive and specific, and consists in a reliable and faster alternative to the viral culture for recent and future acute hemorrhagic conjunctivitis outbreaks caused by coxsackievirus A24 variant.

Laboratory results in ocular viral diseases: implications in clinical-laboratory correlation

PURPOSE: To document etiology and predictive value of clinical diagnosis in laboratory confirmed viral diseases. METHODS: Reports of culture-positive cases of samples collected from patients presenting from January 1987 - December 2001 were evaluated. RESULTS: One thousand nine hundred and sixty-four (1964) cultures were submitted during 1987-2001. Twenty-six percent were positive (514). Human herpesvirus 1 was the most frequent agent isolated from all positive culture (56 percent). Adenovirus was the most common virus isolated from conjunctiva (66 percent), human herpesvirus 1 from lid and cornea (76 percent, 88 percent) and cytomegalovirus from vitreous (27 percent). Some unusual pathogens were recovered from conjunctiva as cytomegalovirus and from cornea as adenovirus, enterovirus and cytomegalovirus. Recognition of common viral syndromes was human herpesvirus 1 (88 percent), epidemic keratoconjunctivitis (88 percent), acute hemorrhagic conjunctivitis (70 percent) and varicella zoster virus (100 percent). However, some misdiagnosed cases were observed. Thirteen percent of conjunctivitis thought to be caused by herpes were due to adenovirus, 3.2 percent to Enterovirus, 3.2 percent to varicella zoster virus and 3.2 percent to human cytomegalovirus. Also, 5 percent of cases with a clinical diagnosis of herpes keratitis were caused by adenovirus and 2.7 percent by enterovirus. Finally, 4.8 percent of cases thought to be adenovirus conjunctivitis were herpes conjunctivitis. CONCLUSIONS: Human herpesvirus 1 remains the most frequently isolated virus from ocular sites in general (56 percent). Nonherpetic corneal isolates were in decreasing order: adenovirus, enterovirus and cytomegalovirus. Clinical and laboratory correlation was less than 90 percent. The most misdiagnosed cases were herpes conjunctivitis and keratitis, some cases of adenovirus conjunctivitis some cases of acute hemorrhagic conjunctivitis. It is essential that a rapid and...

OBJETIVOS: Documentar a etiologia e prever a importância do diagnóstico clínico em doenças virais oculares confirmadas em laboratório. MÉTODOS: Todos os relatórios de pacientes com cultura viral positiva durante o período de janeiro 1987 - dezembro 2001 foram analisados. RESULTADOS: Quinhentos e quatorze (514) casos foram encontrados. Em geral, herpesvírus 1 humano foi o agente mais freqüentemente isolado. Adenovírus foi o vírus mais comumente isolado da conjuntiva (66 por cento), herpesvírus 1 humano das pálpebras e córnea (76 por cento, 88 por cento respectivamente) e citomegalovírus do vítreo (27 por cento). Alguns agentes não usuais foram isolados da conjuntiva como citomegalovírus e da córnea como adenovírus, enterovírus e citomegalovírus. Reconhecimento das síndromes virais comuns foi: herpervírus 1 humano (88 por cento), ceratoconjuntivite epidêmica (88 por cento), conjuntivite aguda hemorrágica (70 por cento). Porém, alguns casos com diagnóstico incorreto foram observados. Treze por cento das conjuntivites com diagnóstico de herpes foram causadas por adenovírus, 3,2 por cento por enterovírus, 3,2 por cento por varicella zoster vírus e 3,2 por cento por citomegalovírus. Também, 5 por cento dos casos com diagnóstico clínico de ceratite herpética eram adenovírus e 2,7 por cento enterovírus. Além disso, 4,8 por cento dos casos em que se pensaram em conjuntivite por adenovírus, eram conjuntivite por herpes. Finalmente, 30 por cento dos casos em que se diagnosticaram conjuntive hemorrágica aguda, o agente etiológico era adenovírus. CONCLUSÃO: Em geral herpesvírus humano 1 continua a ser o vírus mais comum encontrado nas infecções oculares (56 por cento). Agentes não herpéticos isolados da córnea foram em ordem decrescente: adenovírus, enterovírus e citomegalovírus. A correlação entre o diagnóstico clínico e laboratorial foi menor do que 90 por cento. Um diagnóstico rápido e específico é essencial em casos de apresentações virais atípicas...

An outbreak of acute haemorrhagic conjunctivitis in Melaka, Malaysia.

This paper reports a second outbreak of acute haemorrhagic conjunctivitis due to coxsackievirus A24 in peninsular Malaysia. Between June 2002 and early October 2003, 10,327 patients, comprising 3,261 children and 7,066 adults, were treated for acute conjunctivitis in 11 government health clinics in the Melaka Tengah district of the state of Melaka. The figure grossly underestimates the size of the outbreak; as no patients treated in private clinics in the same district were included. Institution and household surveillance showed that the commonest presenting clinical feature of the illness was eye-discharge (91.2%), followed by foreign body sensation (81.8%), pain (78.3%) and subconjunctival haemorrhage (74.4%). The mean duration of illness was 6.5 and five days for patients with and without subconjunctival haemorrhage respectively.

Conjuntivitis hemorrágica aguda en Costa Rica y el origen del Enterovirus 70 en humanos / Acute hemorrhagic conjuntivitis in Costa Rica and the origen of enterovirus 70 in humans

Este estudio presenta la evidencia clínica y serológica de la epidemia de conjuntivitis hemorrágica aguda (CHA) que ocurrió en Puriscal, entre de 1981 y 1982 además de presentar la epidemiología en los años siguientes a su primera aparición y se discute sobre el origen del enterovirus 70, el agente etiológico más frecuente de esta entidad clínica. Las características clínicas encontradas fueron similares a otros estudios. En todas las personas estudiadas, al igual que en el personal de campo y de laboratorio, se detectó seroconversión, e infección subclínica. Seis meses después del primer caso de CHA, se determinó un 43 por ciento de seropositividad en 100 sueros recolectados de la población general en Puriscal. Esta virosis se presenta en forma endémica en Costa Rica, presentándose los picos endememicos cada dos o tres años, con una estacionalidad marcada en los meses de octubre, noviembre y diciembre. Existen varias posiblidades sobre el origen del enterovirus 70; uno de ellas es que el virus se haya derivado de algún otro enterovirus humano que afecte la conjuntiva, o pudo haber existido como una forma no patogénica. También se ha sugerido que el EV-70 pudo haberse derivado de un picornavirus de un invertebrado con un insecto, ya que este virus tiene diferencias muy importantes con el resto de los enterovirus humanos. Hasta el momento no hay evidencia para probar ninguna de estas posibilidades, pero en todo caso, el virus tuvo que haber sufrido una mutación para adquirir la patogenicidad en humanos. Estudios filogénticos han demostrado que el enterovirus 70 se origina de un ancestro común y en la actualidad circulan diferentes cepas que varían antigénicamente entre sí. Palabras claves: Conjunivitis hemorrágica aguda, Enterovirus 70, endémico y estacional, Costa Rica, zoonosis.

Hemorrhagic viral keratoconjunctivitis in Taiwan caused by adenovirus types 19 and 37: applicability of polymerase chain reaction-restriction fragment length polymorphism in detecting adenovirus genotypes.

PURPOSE: Acute keratoconjunctivitis with prominent subconjunctival hemorrhage (SCH) is usually perceived by a clinician as acute hemorrhagic conjunctivitis (AHC) associated with enteroviruses; however, SCH can also be an adenoviruses infection. A rapid and sensitive laboratory diagnosis is helpful for differential diagnosis. Therefore, the sensitivity and applicability of polymerase chain reaction (PCR) and reverse transcription (RT)-PCR diagnoses were evaluated for keratoconjunctivitis associated with viral infection. METHODS: Conjunctival swabs from patients with acute conjunctivitis were tested using a PCR-restriction fragment length polymorphism (PCR-RFLP) for adenovirus detection and RT-PCR for enterovirus detection. The results were compared with those using the culture isolation and neutralization test; also, the clinical findings of the patients were analyzed with special attention to SCH patterns. RESULTS: Neither coxsackievirus A type 24 variant (CA24v) nor enterovirus type 70 (EV70) was detected in 113 patients with acute conjunctivitis. The positive results of adenovirus (Ad) were 39.9% by the PCR method and 37.1% by culture isolation. For the patients with adenoviral conjunctivitis, 68.1% was owing to Ad37 and 19.2% was owing to Ad19. SCH was present in 51.5% of the positive cases, and 44.7% of the Ad-positive patients had secondary illnesses. CONCLUSIONS: SCH can be a predominant presentation of Ad19 and Ad37 keratoconjunctivitis and may herald a new stage in the evolution of adenoviruses. PCR and PCR-RFLP are rapid and reliable methods for Ad detection and typing; however, if the amplified genes and restriction enzymes are not properly selected, they may not be able to detect new genotypes of adenoviruses or the evolution of these viruses.

Identification of a new strain of fastidious enterovirus 70 as the causative agent of an outbreak of hemorrhagic conjunctivitis.

A 1994 outbreak of acute hemorrhagic conjunctivitis in Israel was caused by an enterovirus 70 strain that was distinct from previously reported strains. Characterization was by electron microscopy (eye washes), reverse transcription-PCR (RT-PCR; eyewash, specimens, eye swabs, and tears), and sequence analysis of RT-PCR-amplified fragments from the 5' noncoding region and VP1.