EV-71 confirmed as cause of Cambodian outbreak

James M. Hughes, MD

An outbreak of severe unexplained illness in children with a high mortality rate is being investigated in Cambodia. Infectious agents and toxins come to mind as possible explanations. Much more clinical, epidemiologic, and laboratory information is needed, but preliminary laboratory results suggest that the illness may be hand, foot, and mouth disease caused by enterovirus 71. This virus has caused several large outbreaks of severe illness among children in Southeast Asia in recent years. This outbreak highlights the importance of disease surveillance, diagnostic laboratory capacity, and timely dissemination of public health information as emphasized by the International Health Regulations (IHR 2005). As the investigation involving national and international health agencies continues, it is important to maintain an open mind regarding the diagnosis until more definitive clinical and epidemiologic information and laboratory results are available.

José R. Romero, MD

Enterovirus 71 (EV-A71) is a small, non-enveloped RNA virus in the genus Enterovirus of the Picornaviriae family of viruses. Members of the genus Enterovirus are primarily transmitted via the fecal-oral route, although studies have suggested the EV-A71 may be primarily transmitted via the respiratory route though large droplets from the oral cavity. The virus can be also found in the stool and vesicular fluid of infected individuals. The majority of EV infections occur in the summer to early fall. Prolonged shedding of the EVs favor their spread among a susceptible population and asymptomatic infection is common in EV infections.

Phylogenetically, EV-A71 is most closely related to Coxsackievirus A16 (CV-A16) and, as with CV-A16, it can cause hand, foot and mouth disease (HFMD). EV-A71 has been associated with neurologic syndromes including aseptic meningitis, acute flaccid paralysis and a brain stem encephalitis (rhombencephalitis). The latter can be fatal when it results in neurogenic pulmonary edema. 

Outbreaks of EV-A71 associated with severe neurologic disease have been reported worldwide and primarily in the Asia-Pacific region. The largest of these occurred in 1998 in Taiwan and was associated with thousands of cases of HFMD, more than 400 cases of central nervous system (CNS) disease and 78 deaths in children. In the United States, EV-A71 has been associated with sporadic cases of CNS disease. 

Physicians should suspect EV-A71 (and CV-A16) infection in children with aseptic meningitis, acute flaccid paralysis or encephalitis immediately preceded by HFMD. The virus should be sought in throat secretions, stool, vesicular fluid and cerebrospinal fluid (CSF). Nucleic acid amplification testes may be particularly useful in detecting EV in CSF. However, current nuclear acid amplification tests used for detection of the EV cannot differentiate the individual serotypes. Management of CNS syndromes is symptomatic, as no specific therapy exists. No vaccine is currently available. Prevention of infection may be aided by good hand hygiene and avoidance of contact with respiratory secretions from infected individuals.