Molecular epidemiology of human enterovirus 71 at the origin of an epidemic of fatal hand, foot and mouth disease cases in Cambodia

Human enterovirus 71 (EV-A71) causes hand, foot and mouth disease (HFMD). EV-A71 circulates in many countries and has caused large epidemics, especially in the Asia-Pacific region, since 1997. In April 2012, an undiagnosed fatal disease with neurological involvement and respiratory distress occurred...

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Main Authors: Veasna Duong, Channa Mey, Marc Eloit, Huachen Zhu, Lucie Danet, Zhong Huang, Gang Zou, Arnaud Tarantola, Justine Cheval, Philippe Perot, Denis Laurent, Beat Richner, Santy Ky, Sothy Heng, Sok Touch, Ly Sovann, Rogier van Doorn, Thanh Tan Tran, Jeremy J Farrar, David E Wentworth, Suman R Das, Timothy B Stockwell, Jean-Claude Manuguerra, Francis Delpeyroux, Yi Guan, Ralf Altmeyer, Philippe Buchy
Format: Article
Language:English
Published: Taylor & Francis Group 2016-01-01
Series:Emerging Microbes and Infections
Subjects:
Online Access:https://www.tandfonline.com/doi/10.1038/emi.2016.101
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author Veasna Duong
Channa Mey
Marc Eloit
Huachen Zhu
Lucie Danet
Zhong Huang
Gang Zou
Arnaud Tarantola
Justine Cheval
Philippe Perot
Denis Laurent
Beat Richner
Santy Ky
Sothy Heng
Sok Touch
Ly Sovann
Rogier van Doorn
Thanh Tan Tran
Jeremy J Farrar
David E Wentworth
Suman R Das
Timothy B Stockwell
Jean-Claude Manuguerra
Francis Delpeyroux
Yi Guan
Ralf Altmeyer
Philippe Buchy
author_facet Veasna Duong
Channa Mey
Marc Eloit
Huachen Zhu
Lucie Danet
Zhong Huang
Gang Zou
Arnaud Tarantola
Justine Cheval
Philippe Perot
Denis Laurent
Beat Richner
Santy Ky
Sothy Heng
Sok Touch
Ly Sovann
Rogier van Doorn
Thanh Tan Tran
Jeremy J Farrar
David E Wentworth
Suman R Das
Timothy B Stockwell
Jean-Claude Manuguerra
Francis Delpeyroux
Yi Guan
Ralf Altmeyer
Philippe Buchy
author_sort Veasna Duong
collection DOAJ
description Human enterovirus 71 (EV-A71) causes hand, foot and mouth disease (HFMD). EV-A71 circulates in many countries and has caused large epidemics, especially in the Asia-Pacific region, since 1997. In April 2012, an undiagnosed fatal disease with neurological involvement and respiratory distress occurred in young children admitted to the Kantha Bopha Children’s Hospital in Phnom Penh, Cambodia. Most died within a day of hospital admission, causing public panic and international concern. In this study, we describe the enterovirus (EV) genotypes that were isolated during the outbreak in 2012 and the following year. From June 2012 to November 2013, 312 specimens were collected from hospitalized and ambulatory patients and tested by generic EV and specific EV-A71 reverse transcription PCR. EV-A71 was detected in 208 clinical specimens while other EVs were found in 32 patients. The VP1 gene and/or the complete genome were generated. Our phylogenetic sequencing analysis demonstrated that 80 EV-A71 strains belonged to the C4a subgenotype and 3 EV-A71 strains belonged to the B5 genotype. Furthermore, some lineages of EV-A71 were found to have appeared in Cambodia following separate introductions from neighboring countries. Nineteen EV A (CV-A6 and CV-A16), 9 EV B (EV-B83, CV-B3, CV-B2, CV-A9, E-31, E-2 and EV-B80) and 4 EV C (EV-C116, EV-C96, CV-A20 and Vaccine-related PV-3) strains were also detected. We found no molecular markers of disease severity. We report here that EV-A71 genotype C4 was the main etiological agent of a large outbreak of HFMD and particularly of severe forms associated with central nervous system infections. The role played by other EVs in the epidemic could not be clearly established.
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spelling doaj.art-e6c5363df12c4990951c6ee1058079552023-09-21T12:27:55ZengTaylor & Francis GroupEmerging Microbes and Infections2222-17512016-01-01511910.1038/emi.2016.101Molecular epidemiology of human enterovirus 71 at the origin of an epidemic of fatal hand, foot and mouth disease cases in CambodiaVeasna Duong0Channa Mey1Marc Eloit2Huachen Zhu3Lucie Danet4Zhong Huang5Gang Zou6Arnaud Tarantola7Justine Cheval8Philippe Perot9Denis Laurent10Beat Richner11Santy Ky12Sothy Heng13Sok Touch14Ly Sovann15Rogier van Doorn16Thanh Tan Tran17Jeremy J Farrar18David E Wentworth19Suman R Das20Timothy B Stockwell21Jean-Claude Manuguerra22Francis Delpeyroux23Yi Guan24Ralf Altmeyer25Philippe Buchy26Pasteur Institute in Cambodia, Phnom Penh 12000, CambodiaPasteur Institute in Cambodia, Phnom Penh 12000, CambodiaPasteur Institute, Paris 75724, FranceState Key Laboratory of Emerging Infectious Diseases, School of Public Health, The University of Hong Kong, Hong Kong, ChinaPasteur Institute in Cambodia, Phnom Penh 12000, CambodiaInstitut Pasteur in Shanghai, Shanghai 200025, ChinaInstitut Pasteur in Shanghai, Shanghai 200025, ChinaPasteur Institute in Cambodia, Phnom Penh 12000, CambodiaPathoQuest, Paris 75015, FrancePasteur Institute, Paris 75724, FranceKantha Bopha Hospital, Phnom Penh 12000, CambodiaKantha Bopha Hospital, Phnom Penh 12000, CambodiaKantha Bopha Hospital, Phnom Penh 12000, CambodiaKantha Bopha Hospital, Phnom Penh 12000, CambodiaMinistry of Health, Phnom Penh 12000, CambodiaMinistry of Health, Phnom Penh 12000, CambodiaOxford University Clinical Research Unit, Hospital for Tropical Diseases, Ho Chi Minh P1Q5, VietnamOxford University Clinical Research Unit, Hospital for Tropical Diseases, Ho Chi Minh P1Q5, VietnamOxford University Clinical Research Unit, Hospital for Tropical Diseases, Ho Chi Minh P1Q5, VietnamJ. Craig Venter Institute, Rockville, MD 92037, USAJ. Craig Venter Institute, Rockville, MD 92037, USAJ. Craig Venter Institute, Rockville, MD 92037, USAPasteur Institute, Paris 75724, FrancePasteur Institute, Paris 75724, FranceState Key Laboratory of Emerging Infectious Diseases, School of Public Health, The University of Hong Kong, Hong Kong, ChinaInstitut Pasteur in Shanghai, Shanghai 200025, ChinaPasteur Institute in Cambodia, Phnom Penh 12000, CambodiaHuman enterovirus 71 (EV-A71) causes hand, foot and mouth disease (HFMD). EV-A71 circulates in many countries and has caused large epidemics, especially in the Asia-Pacific region, since 1997. In April 2012, an undiagnosed fatal disease with neurological involvement and respiratory distress occurred in young children admitted to the Kantha Bopha Children’s Hospital in Phnom Penh, Cambodia. Most died within a day of hospital admission, causing public panic and international concern. In this study, we describe the enterovirus (EV) genotypes that were isolated during the outbreak in 2012 and the following year. From June 2012 to November 2013, 312 specimens were collected from hospitalized and ambulatory patients and tested by generic EV and specific EV-A71 reverse transcription PCR. EV-A71 was detected in 208 clinical specimens while other EVs were found in 32 patients. The VP1 gene and/or the complete genome were generated. Our phylogenetic sequencing analysis demonstrated that 80 EV-A71 strains belonged to the C4a subgenotype and 3 EV-A71 strains belonged to the B5 genotype. Furthermore, some lineages of EV-A71 were found to have appeared in Cambodia following separate introductions from neighboring countries. Nineteen EV A (CV-A6 and CV-A16), 9 EV B (EV-B83, CV-B3, CV-B2, CV-A9, E-31, E-2 and EV-B80) and 4 EV C (EV-C116, EV-C96, CV-A20 and Vaccine-related PV-3) strains were also detected. We found no molecular markers of disease severity. We report here that EV-A71 genotype C4 was the main etiological agent of a large outbreak of HFMD and particularly of severe forms associated with central nervous system infections. The role played by other EVs in the epidemic could not be clearly established.https://www.tandfonline.com/doi/10.1038/emi.2016.101Cambodiaepidemichand foot and mouth diseasehuman enterovirus 71severe disease
spellingShingle Veasna Duong
Channa Mey
Marc Eloit
Huachen Zhu
Lucie Danet
Zhong Huang
Gang Zou
Arnaud Tarantola
Justine Cheval
Philippe Perot
Denis Laurent
Beat Richner
Santy Ky
Sothy Heng
Sok Touch
Ly Sovann
Rogier van Doorn
Thanh Tan Tran
Jeremy J Farrar
David E Wentworth
Suman R Das
Timothy B Stockwell
Jean-Claude Manuguerra
Francis Delpeyroux
Yi Guan
Ralf Altmeyer
Philippe Buchy
Molecular epidemiology of human enterovirus 71 at the origin of an epidemic of fatal hand, foot and mouth disease cases in Cambodia
Emerging Microbes and Infections
Cambodia
epidemic
hand foot and mouth disease
human enterovirus 71
severe disease
title Molecular epidemiology of human enterovirus 71 at the origin of an epidemic of fatal hand, foot and mouth disease cases in Cambodia
title_full Molecular epidemiology of human enterovirus 71 at the origin of an epidemic of fatal hand, foot and mouth disease cases in Cambodia
title_fullStr Molecular epidemiology of human enterovirus 71 at the origin of an epidemic of fatal hand, foot and mouth disease cases in Cambodia
title_full_unstemmed Molecular epidemiology of human enterovirus 71 at the origin of an epidemic of fatal hand, foot and mouth disease cases in Cambodia
title_short Molecular epidemiology of human enterovirus 71 at the origin of an epidemic of fatal hand, foot and mouth disease cases in Cambodia
title_sort molecular epidemiology of human enterovirus 71 at the origin of an epidemic of fatal hand foot and mouth disease cases in cambodia
topic Cambodia
epidemic
hand foot and mouth disease
human enterovirus 71
severe disease
url https://www.tandfonline.com/doi/10.1038/emi.2016.101
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