Coxsackievirus A6 associated hand, foot and mouth disease in adults: Clinical presentation and review of the literature

Ramírez-Fort, Marigdalia K.; Downing, Christopher; Doan, Hung Q.; F, Benoist; Oberste, M. Steven; Khan, Farhan; Tyring, Stephen K.

doi:10.1016/j.jcv.2014.04.023

Cited by 99 publications

(82 citation statements)

References 23 publications

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“…The virus has been responsible for severe atypical cases of HFMD often requiring hospitalization, characterized by extensive vesiculobullous and erosive cutaneous eruptions, eczema, purpuric lesions and onychomadesis with nail shedding. 80,81 CV-A6 infections have also led to fatal encephalitis/encephalopathy and myocarditis. 82,83 CV-A10-associated HFMD cases are characterized by high fever, vesicular rashes and oral ulcers 63 with occasional meningoencephalitic complications.…”

Section: Clinical Presentationmentioning

confidence: 99%

Is a multivalent hand, foot, and mouth disease vaccine feasible?

Klein¹,

Chong

2015

Human Vaccines & Immunotherapeutics

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Keywords: bivalent and multivalent vaccines, coxsackievirus A16, coxsackieviruses B3 and B5, echovirus 30, epidemiology, enterovirus A (EV-A), enterovirus A71, hand, foot and mouth diseases, inactivated whole virion vaccines, monovalent, EV-A71 vaccine Enterovirus A infections are the primary cause of hand, foot and mouth disease (HFMD) in infants and young children. Although enterovirus 71 (EV-A71) and coxsackievirus A16 (CV-A16) are the predominant causes of HFMD epidemics worldwide, EV-A71 has emerged as a major neurovirulent virus responsible for severe neurological complications and fatal outcomes. HFMD is a serious health threat and economic burden across the Asia-Pacific region. Inactivated EV-A71 vaccines have elicited protection against EV-A71 but not against CV-A16 infections in large efficacy trials. The current development of a bivalent inactivated EV-A71/CV-A16 vaccine is the next step toward that of multivalent HFMD vaccines. These vaccines should ultimately include other prevalent pathogenic coxsackieviruses A (CV-A6 and CV-A10), coxsackieviruses B (B3 and B5) and echovirus 30 that often co-circulate during HFMD epidemics and can cause severe HFMD, aseptic meningitis and acute viral myocarditis. The prospect and challenges for the development of such multivalent vaccines are discussed.

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Section: Clinical Presentationmentioning

confidence: 99%

Is a multivalent hand, foot, and mouth disease vaccine feasible?

Klein¹,

Chong

2015

Human Vaccines & Immunotherapeutics

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“…However, since the CV-A16-related outbreak of HFMD occurred in England in 1994 (3), accumulating evidence has demonstrated that CV-A16 infection can also cause severe neurological complications (4) and death (5,6). Recently, CV-A6 infection has also been increasingly associated with HFMD outbreaks around the world (7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17). Furthermore, EV-D68 has been linked to severe respiratory disease worldwide in recent years.…”

mentioning

confidence: 99%

Disruption of MDA5-Mediated Innate Immune Responses by the 3C Proteins of Coxsackievirus A16, Coxsackievirus A6, and Enterovirus D68

Rui

Wang

et al. 2017

J Virol

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Coxsackievirus A16 (CV-A16), CV-A6, and enterovirus D68 (EV-D68) belong to the Picornaviridae family and are major causes of hand, foot, and mouth disease (HFMD) and pediatric respiratory disease worldwide. The biological characteristics of these viruses, especially their interplay with the host innate immune system, have not been well investigated. In this study, we discovered that the 3C pro proteins from CV-A16, CV-A6, and EV-D68 bind melanoma differentiation-associated gene 5 (MDA5) and inhibit its interaction with MAVS. Consequently, MDA5-triggered type I interferon (IFN) signaling in the retinoic acid-inducible gene I-like receptor (RLR) pathway was blocked by the CV-A16, CV-A6, and EV-D68 3C pro proteins. Furthermore, the CV-A16, CV-A6, and EV-D68 3C pro proteins all cleave transforming growth factor ␤-activated kinase 1 (TAK1), resulting in the inhibition of NF-B activation, a host response also critical for Toll-like receptor (TLR)-mediated signaling. Thus, our data demonstrate that circulating HFMD-associated CV-A16 and CV-A6, as well as severe respiratory disease-associated EV-D68, have developed novel mechanisms to subvert host innate immune responses by targeting key factors in the RLR and TLR pathways. Blocking the ability of 3C pro proteins from diverse enteroviruses and coxsackieviruses to interfere with type I IFN induction should restore IFN antiviral function, offering a potential novel antiviral strategy.IMPORTANCE CV-A16, CV-A6, and EV-D68 are emerging pathogens associated with hand, foot, and mouth disease and pediatric respiratory disease worldwide. The pathogenic mechanisms of these viruses are largely unknown. Here we demonstrate that the CV-A16, CV-A6, and EV-D68 3C pro proteins block MDA5-triggered type I IFN induction. The 3C pro proteins of these viruses bind MDA5 and inhibit its interaction with MAVS. In addition, the CV-A16, CV-A6, and EV-D68 3C pro proteins cleave TAK1 to inhibit the NF-B response. Thus, our data demonstrate that circulating HFMDassociated CV-A16 and CV-A6, as well as severe respiratory disease-associated EV-D68, have developed a mechanism to subvert host innate immune responses by simultaneously targeting key factors in the RLR and TLR pathways. These findings indicate the potential merit of targeting the CV-A16, CV-A6, and EV-D68 3C pro proteins as an antiviral strategy.KEYWORDS MDA5, TAK1, MAVS, 3C protease, CV-A16, CV-A6, EV-D68, HFMD, innate immune response

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“…En mayo de 2016, la Dirección de Salud del Callao lanzó una alerta epidemiológica en el que daba cuenta de 21 casos en Lima y seis en Callao, de niños de instituciones educativas con EMPB (8) . Sin embargo, en nuestra serie la mitad fueron adultos, similar a lo que se ha venido reportando desde el 2008 en asociación a infección por CA6, causante de brotes más severos y atípicos en niños y adultos (1) .…”

Section: Discussionunclassified

“…De esta forma, creemos que los casos ocurridos en nuestro hospital pertenecen a cuadros típicos asociados al CA16, a pesar de presentarse también en adultos. Mientras tanto, otras revisiones dan cuenta de que las formas en adultos se asocian al CA6 (1) . Se han descrito cambios en las uñas y en la piel luego de la etapa aguda de la enfermedad: descamación de las plantas y palmas después de unas semanas; onicomadesis 3 a 8 semanas después del diagnóstico (media de 52 días), y líneas de Beau (15) .…”

Section: Discussionunclassified

“…La enfermedad de mano, pie y boca (EMPB) es una enfermedad viral frecuente durante los meses de verano, en niños de 0 a 4 años; sin embargo, se han descrito en la literatura casos en niños mayores, adolescentes y adultos (1,2) . Clásicamente, inicia con malestar general y odinofagia, seguidos de fiebre, dolor bucal, dolor abdominal y síntomas respiratorios.…”

Section: Introductionunclassified

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Enfermedad de mano, pie y boca en un hospital del Callao, 2016

Rodríguez-Zúñiga

Vértiz-Gárate

Cortez-Franco

et al. 2017

Rev Peru Med Exp Salud Publica

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RESUMENLa enfermedad de mano, pie y boca (EMPB) es una enfermedad exantemática viral, causada principalmente por Coxsackie A16, con una sintomatología típica consistente en fiebre; exantema pápulo-vesicular en manos, pies y genitales; y un enantema ulceroso en boca. En el verano del 2016 se presentó una diversidad de casos en un hospital del Callao en niños y adultos, con una sintomatología compatible con EMPB; el diagnóstico fue clínico, se aplicó terapia de soporte con resolución final de síntomas. En la última década se han presentado reportes en algunos países con una afectación atípica causada por el Coxsackie A6, produciendo lesiones más extensas y en adultos. Sin embargo, el diagnóstico sigue siendo clínico, solo necesitando confirmación virológica en casos atípicos o cuando el diagnóstico no es claro. La importancia de este reporte radica en describir los casos del Callao ocurridos en el verano del 2016, para servir de apoyo a los profesionales de la salud en el diagnóstico y manejo de pacientes con similar sintomatología. HAND, FOOT, AND MOUTH DISEASE IN A HOSPITAL IN CALLAO IN 2016 ABSTRACTHand, foot, and mouth disease (HFMD) is an exanthematous viral disease caused mainly by Coxsackie A16 with a typical symptomatology of fever, papulovesicular rash on the hands, feet, and genitals, and an ulcerous enanthem in the mouth. In the summer of 2016, a variety of cases presented at a hospital in Callao in children and adults with a symptomatology consistent with HFMD. A clinical diagnosis was made, and support therapy was applied, resulting in the resolution of symptoms. In the last decade, reports have emerged in some countries of an atypical involvement caused by Coxsackie A6, producing lesions that are more widely distributed in adults. However, the diagnosis remains clinical, only requiring virological confirmation in atypical cases or when the diagnosis is unclear. The importance of this report stems from its description of the cases in Callao that occurred in the summer of 2016 and serve as an example for health professionals in the diagnosis and management of patients with similar symptomatology.

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Coxsackievirus A6 associated hand, foot and mouth disease in adults: Clinical presentation and review of the literature

Cited by 99 publications

References 23 publications

Is a multivalent hand, foot, and mouth disease vaccine feasible?

Is a multivalent hand, foot, and mouth disease vaccine feasible?

Disruption of MDA5-Mediated Innate Immune Responses by the 3C Proteins of Coxsackievirus A16, Coxsackievirus A6, and Enterovirus D68

Enfermedad de mano, pie y boca en un hospital del Callao, 2016

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