Sunday, May 16, 2010

China: A Recombinant EV-71


# 4571




In 2008 we saw reports of an unusually severe outbreak of HFMD (Hand Food & Mouth Disease) among young children in China.  Some of the coverage here from two years ago includes:


China Sounds Alert Over EV-71 Virus
China: EV71 Claims 28th Victim, Authorities Warn of Possible `Mass Outbreak'
HFMD Outbreak In China Spreads To 25,000 Children


After a relatively normal HFMD season last year, China once again is reporting large numbers of infections in 2010 (see HFMD Rising In China)



HFMD is a very common and generally mild viral infection, mainly of children under the age of 10 (adults are vulnerable as well) caused by several of the non-polio enteroviruses.


The 60+ non-polio enteroviruses identified to date are among the most prevalent viral infections in the world, probably only second to the myriad and ubiquitous variants of Rhinovirus (`common cold’) that circulate every year.


The two most common causes of HFMD are the Coxsackie A16 virus, and the Enterovirus-71 (EV-71).  


The disease caused by the Coxsackie A16 virus is generally the milder of the two, rarely cause serious illness, and outbreaks are not uncommon in childcare facilities.  EV-71 HFMD is most commonly found in Asia, with serious outbreaks recorded over the past dozen years in places like China, Malaysia, and Hong Kong.


This week, in the Virology Journal, we get an analysis the virus that caused a major  2008 outbreak of HFMD in Fuyang City, China showing that it was due to an emerging recombinant virus.


The (slightly reformatted) Abstract, along with the link to the provisional PDF file.



An emerging recombinant human enterovirus 71 responsible for the 2008 outbreak of Hand Foot and Mouth Disease in Fuyang city of China


Yan Zhang, Zhen Zhu , Weizhong Yang, Jun Ren, Xiaojuan Tan, Yu Wang , Naiying Mao , Songtao Xu , Shuangli Zhu, Aili Cui, Yong Zhang , Dongmei Yan , Qun Li ,Xiaoping Dong, Jing Zhang , Yueping Zhao , Junfeng Wan , Zijian Feng , Junling Sun , Shiwen Wang, Dexin Li  and Wenbo Xu

Virology Journal 2010, 7:94doi:10.1186/1743-422X-7-94

12 May 2010

Abstract (provisional)

Hand, foot and mouth disease (HFMD), a common contagious disease that usually affects children, is normally mild but can have life-threatening manifestations. It can be caused by enteroviruses, particularly Coxsackieviruses and human enterovirus 71 (HEV71) with highly variable clinical manifestations.


In the spring of 2008, a large, unprecedented HFMD outbreak in Fuyang city of Anhui province in the central part of southeastern China, resulted in a high aggregation of fatal cases.


In this study, epidemiologic and clinical investigations, laboratory testing, and genetic analyses were performed to identify the causal pathogen of the outbreak. Of the 6,049 cases reported between 1 March and 9 May of 2008, 3023 (50%) were hospitalized, 353 (5.8%) were severe and 22 (0.36%) were fatal. HEV71 was confirmed as the etiological pathogen of the outbreak.


Phylogenetic analyses of entire VP1 capsid protein sequence of 45 Fuyang HEV71 isolates showed that they belong to C4a cluster of the C4 subgenotype. In addition, genetic recombinations were found in the 3D region (RNA-dependent RNA polymerase, a major component of the viral replication complex of the genome) between the Fuyang HEV71 strain and Coxsackievirus A16 (CV-A16), resulting in a recombination virus.


In conclusion, an emerging recombinant HEV71 was responsible for the HFMD outbreak in Fuyang City of China, 2008.



The ongoing evolution of these enteroviruses has led to changes in the dominant HFMD virus circulating in China over the past decade. 


From the provisional PDF.


Based  on  the  phylogenetic  analyses,  Fuyang  isolates  belonged  to  C4a cluster of the subgenotype C4 and showed high homology with the isolates circulating in other provinces of the mainland of China between 2007 and 2008, including those from  the HFMD  outbreak  in  Linyi  city  in  Shandong  province  in  2007[8].


The  C4 subgenotype of HEV71 was  initially  identified  in Guangdong province  in 1998 and has  been  continuously  circulating  for  at  least  10  years[10],  which may  reflect  the pattern of endemic circulation of subgenotype C4 viruses.


Interestingly, C4b viruses were the predominant circulating strain in mainland of China prior to 2004. Since then, however,  C4a  viruses  have  become  the  predominant  strains,  which  have  been continuously circulating and causing epidemic in the mainland of China so far [8].  



Relatively benign diseases - like HFMD - can sometimes mutate or pick up genetic material from other viruses and become more virulent or more transmissible. 


Of course, evolutionary changes to viruses can make them lose virulence, or even disappear, over time.


The only constant here is change. 


Sometimes we even see something new - or at least previously unidentified -  emerge - like SARS, Ebola, HIV, Lyme, Hendra or Nipah.


Nature’s laboratory is open 24/7 - and unlike public health, scientific research, and surveillance programs - operates without budgetary constraints.


Which is why good surveillance and research that help us understand the evolution of viruses are crucial if we hope to deal with the ever growing list of emerging infectious diseases.