# 6424
Doctors may be closer today to identifying the `mystery disease’ that has killed – at last report – more than 60 children in Cambodia over the past couple of months (See Updating The Cambodian `Mystery’ Illness).
According to multiple media reports this morning (CNN, Bloomberg, RTHK) the Institut Pasteur in Cambodia has found Enterovirus-71 (EV71) in 15 out of 24 samples taken from victims of this disease.
While more testing is needed, and there may be other factors involved, the signs and symptoms being reported in this outbreak are consistent with severe cases of EV71 infection.
EV71 is one of more than 60 non-polio enteroviruses that have thus far been identified, and while it is most frequently linked to severe outbreaks of HFMD (Hand, Foot, & Mouth Disease), it is capable of producing other serious neurological illnesses as well.
Credit - CDC EID Journal
The classic rash & lesions associated with HFMD does not always manifest with EV71 infections, making diagnosis far more difficult. Additionally, HFMD is normally a mild illness, particularly when caused by the Coxsackie A16 virus.
An article that appeared in early 2001 in Clinical Infectious Diseases (cite Neurological Manifestations of Enterovirus 71 Infection in Children during an Outbreak of Hand, Foot, and Mouth Disease in Western Australia Peter McMinn, Ivan Stratov, Lakshmi Nagarajan, and Stephen Davis) describes its impact this way:
Children <4 years of age are particularly susceptible to the most severe forms of EV71-associated neurological disease, including meningitis, brain-stem and/or cerebellar encephalitis, and poliomyelitis-like paralysis.
The neurological complications of EV71 infection may occasionally cause permanent paralysis or death. Several large epidemics of severe EV71 infection in young children, including numerous cases of fatal brain-stem encephalitis, have recently been reported in Southeast Asia [10–12].
A 2007 study appearing in the American Journal of Tropical Medicine & Hygiene, looked at mortality rates among severe HFMD involving EV71 infection during an outbreak in Taiwan. Researchers found a crude mortality rate of roughly 16%, although that number varied considerably over the 8 year study.
And in recent years, we’ve seen increasing evidence of severe EV71 outbreaks - particularly across Asia. China, and most recently Vietnam, have been hard hit – as evidenced last May when the CDC Issues HFMD Travel Notice For Vietnam.
Two major genotypes of EV-71, EV-71 B and EV-71 C, have been identified as being responsible for a number of severe outbreaks in Australia, Japan, China, Malaysia, and Taiwan since 1997.
A couple of years ago, the Virology Journal, published an analysis of an EV-71 HFMD virus that caused a major disease outbreak in Fuyang City, China in 2008 that showed it was due to an emerging recombinant virus (see China: A Recombinant EV-71).
A reminder that viruses are always evolving, looking for an evolutionary advantage.
Researchers will no doubt be looking for any signs of change to the EV71 virus that has now been isolated from these Cambodian children.
For now there is no vaccine to prevent EV71 infection, although several pharmaceutical companies are working on one. There are no effective antivirals available to treat EV71 at this time, either (cite).
The PHAC (Public Health Agency of Canada) describes enterovirus 71 transmission:
EV 71 is transmitted through direct contact with discharge from the nose and throat, saliva, fluid from blisters or the stools of an infected person. Cases are most infectious during the first week of acute illness but may continue to shed virus in stool for weeks. The incubation period is three to five days. The epidemiological pattern varies by geographical region and climate, but the incidence of infection is higher in the summer and autumn months in temperate climates while remaining prevalent year-round in tropical climates.
There is increasing evidence, however, suggesting respiratory transmission of the virus as well. This was recently highlighted in a BMC Infectious Diseases article called:
Long persistence of EV71 specific nucleotides in respiratory and feces samples of the patients with Hand-Foot-Mouth Disease after recovery
Jun Han, Xue-Jun Ma, Jun-Feng Wan, Ying-Hui Liu, Yan-Ling Han, Cao Chen, Chan Tian, Chen Gao, Miao Wang and Xiao-Ping Dong
HFMD has been an important public health concern worldwide, especially in the Asia-Pacific region. Up to now, more than 900,000 HFMD cases have been reported in mainland of China. Enteroviruses can be isolated from both the lower and upper alimentary tract and can be transmitted by both fecal-oral and respiratory routes. Fecal-oral transmission may predominate in areas with poor sanitary conditions, whereas respiratory transmission may be important in more developed areas. The relative importance of the different modes of transmission probably varies with the particular EV and environmental setting.
Despite its discovery more than 40 years ago during an outbreak in California, EV71 remains a sometimes elusive diagnosis – particularly when atypical symptoms that are not consistent with HFMD are present.
While we are seeing outbreaks of EV71 primarily in Southeast Asia, an article published in Clinical Infectious Diseases back in 2007 warns that EV71 may be a largely unrecognized and potentially emerging disease here in the United States as well.
Outbreak of Neurologic Enterovirus Type 71 Disease: A Diagnostic Challenge
Carlos M. Pérez-Vélez,Marsha S. Anderson, Christine C. Robinson, Elizabeth J. McFarland, W. Allan Nix, Mark A. Pallansch, M. Steven Oberste, and Mary P. Glodé
An outbreak of neurologic EV71 disease occurred in Denver, Colorado, during 2003 and 2005. Likely, EV71 disease remains unrecognized in other parts of the United States, because EV-PCR of cerebrospinal fluid frequently yields negative results. EV-PCR of specimens from the respiratory and gastrointestinal tracts had higher diagnostic yields than did EV-PCR of cerebrospinal fluid. EV71 infection should be considered in young children presenting with aseptic meningitis, encephalitis, acute flaccid paralysis, or acute cardiopulmonary collapse. EV71 infection may be an underrecognized emerging disease in the United States.
We will have to await further laboratory tests over the coming days to see if any other factors may be involved in this outbreak in Cambodia.
Of particular interest will any evidence of genetic changes in the EV71 virus that might help explain the unusually high mortality rate that been attributed to this particular outbreak.
Stay tuned.
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