Wednesday, August 29, 2018

EID Journal: Emerging Enteroviruses In China 2010-2016


Non-polio Enteroviruses (NPEV's) - of which there are literally scores - typically spread in the summer and early fall, and generally produce mild or even asymptomatic infections, mostly in children under the age of 10. 

Symptomatic cases can range from just a mild fever or a runny nose - to Hand Foot Mouth Disease (HFMD), a generally mild childhood disease characterized by blisters on the hand, feet, and mouth - to (in rare cases) a polio-like paralysis and sometimes even death. 
For several decades - particularly in Asian and Western Pacific nations - we've monitored yearly NPEV epidemics, with the most severe illness linked to Human Enterovirus 71 (EV-71).
  • In 2009 China reported 1,155,525 HFMD cases, including 13,810 severe cases and 353 deaths. Among laboratory confirmed cases, EV71 was responsible for 41% of cases, 82% of severe cases, and 93% of the deaths (cite WHO HFMD Guide Pg.6).
  • In 2012, we saw an outbreak of EV-71 in Cambodia that claimed the lives of dozens of children (see Updating The Cambodian EV71 Story).
  • In 2013 in Australia: Acute Flaccid Paralysis & EV71, we looked at a report that described 5 cases of acute flaccid paralysis (AFP) in children who tested positive for the EV71 virus.
Less well known, but rapidly coming up in the ranks, is Coxsackievirus A6  (CV-A6) which was only first described about a decade ago. In 2009, the CDC’s EID Journal carried a dispatch regarding an outbreak of HFMD in Finland due to an unusual, and apparently emerging, viral cause; the CV-A6.
Since then, we’ve seen a growing number of reports of HFMD outbreaks around the world attributed to this emerging coxsackievirus, including outbreaks in Europe, Asia and North America (see Nevada: HFMD Coxsackievirus A6 Outbreak).
Earlier this year we looked at a Virology journal report that indicated CVA6 has overtaken both EV71 and CV-A16 as the primary cause of HFMD in China, and that it continues to evolve.

Today we've a new report in the EID Journal, that confirms that CV-A6 has emerged as a substantial driver of severe enterovirus infection in China since 2010.

Emerging Enteroviruses Causing Hand, Foot and Mouth Disease, China, 2010–2016

Yu Li1, Zhaorui Chang1, Peng Wu1, Qiaohong Liao, Fengfeng Liu, Yaming Zheng, Li Luo, Yonghong Zhou, Qi Chen, Shuanbao Yu, Chun Guo, Zhenhua Chen, Lu Long, Shanlu Zhao, Bingyi Yang, Hongjie Yu2, and Benjamin J. Cowling


Coxsackievirus A6 emerged as one of the predominant causative agents of hand, foot and mouth disease epidemics in many provinces of China in 2013 and 2015. This virus strain accounted for 25.9% of mild and 15.2% of severe cases in 2013 and 25.8% of mild and 16.9% of severe cases in 2015.

Hand, foot and mouth disease (HFMD) is a common childhood infectious disease caused by enteroviruses (1). In China, HFMD cases must be reported to the Notifiable Infectious Diseases Reporting Information System. Apart from clinical and demographic information, case notifications also include etiologic results, if available, classified into 3 categories: enterovirus A71 (EV-A71), coxsackievirus (CV) A16, and other enteroviruses.

However, not all cases have etiologic results, the Notifiable Infectious Diseases Reporting Information System (NIDRIS) does not indicate cases that tested negative for enteroviruses, and testing methods vary among hospitals (2). To capture more information on the etiologic spectrum of HFMD in China, a laboratory surveillance network has been established in provincial-level centers for disease control and prevention (CDCs).

EV-A71 and CV-A16 were previously believed to be the main causative viruses for HFMD in Asia, but several studies have suggested that other enteroviruses appear to be increasing since 2008 (39).
Nevertheless, these past studies in China could not provide an overview at the national level because of limitations in geographic locations or study settings; furthermore, none of them systematically examined proportions of specific enteroviruses testing positive among tested HFMD cases. We analyzed data from this laboratory network to examine causative pathogens of HFMD cases and epidemiologic differences associated with various pathogens.



Data from national laboratory network surveillance of HFMD in China show that detection of enteroviruses other than EV-71 and CV-A16 has been increasing in both mild and severe cases and that CV-A6 has been emerging as another predominant serotype recently, but not in every province.

Serotyping of individual enteroviruses apart from currently tested EV-71 and CV-A16 is suggested for routine virologic surveillance. Further studies may be needed to investigate potential cross immunity between EV-A71 and other enteroviruses such as CV-A6, CV-A10, and others.
Dr. Li is a doctoral candidate at School of Public Health, The University of Hong Kong. His primary research interests include epidemiology and transmission dynamics of zoonotic and vectorborne diseases, and hand, foot and mouth disease.

Although outbreaks of CV-A6 in the United States have been limited, in 2012, in EID Journal: HFMD Cluster Due To CVA6 we looked at a report on cluster of 8 patients who were treated CVA6 HFMD at Boston Children’s Hospital.

The authors cautioned:
Given the numerous CVA6 outbreaks in multiple countries in 2008 and a US population that may be relatively naïve to this serotype, CVA6 is likely to spread throughout North America.
In 2014 a North American outbreak of another emerging enterovirus - EV-D68 - was linked to a concurrent spike in AFP (Acute Flaccid Paralysis) cases across the United States, and since then we've seen a number of EV-D68 outbreaks around the world (see here, here & here).
While a causal link between EV-D68 and AFM hasn't been fully established, last January's Eurosurveillance Review: Association Between Acute Flaccid Myelitis (AFM) & Enterovirus D68 (EV-D68), presented a pretty good argument for causation.
Just as with influenza, these non-polio enteroviruses continue to evolve - and while not as deadly as flu - they are fully capable of causing large epidemics. 
Some of my earlier blogs NPEVs include:

MMWR: Cluster of Acute Flaccid Myelitis in Five Pediatric Patients - Arizona, 2016

CDC Acute Flaccid Myelitis Update - January 2017

EID Journal Upsurge In EV-D68 In The Netherlands, 2016

ECDC: Rapid Risk Assessment On Recent Enterovirus Outbreaks In Europe

EID Journal: New Introductions Of EV-71 Subtype C4 To France – 2012

No comments: