Enterovirus 71 infection and neurological complications

Abstract

Since the outbreak of the enterovirus 71 (EV71) infection in Malaysia in 1997, large epidemics of EV71 have occurred in the Asia-Pacific region. Many children and infants have died from serious neurological complications during these epidemics, and EV71 infection has become a serious public health problem in these areas. EV71 infection causes hand, foot and mouth disease (HFMD) in children, and usually resolves spontaneously. However, EV71 occasionally involves the central nervous system (CNS), and induces diverse neurological complications such as brainstem encephalitis, aseptic meningitis, and acute flaccid paralysis. Among those complications, brainstem encephalitis is the most critical neurological manifestation because it can cause neurogenic pulmonary hemorrhage/edema leading to death. The characteristic clinical symptoms such as myoclonus and ataxia, cerebrospinal fluid (CSF) pleocytosis, and brainstem lesions on magnetic resonance imaging, in conjunction with the skin rash of HFMD and the isolation of EV71 from a stool, throat-swab, or CSF sample are typical findings indicating CNS involvement of EV71 infection. Treatment with intravenous immunoglobulin and milrinone are recommended in cases with severe neurological complications from EV71 infection, such as brainstem encephalitis. Despite the recent discovery of receptors for EV71 in human cells, such as the scavenger receptor B2 and P-selection glycoprotein ligand 1, it is not known why EV71 infection predominantly involves the brainstem. Recently, 3 companies in China have completed phase III clinical trials of EV71 vaccines. However, the promotion and approval of these vaccines in various countries are problems yet to be resolved.

Nucleosides for the treatment of respiratory RNA virus infections

“…In rare cases of severe EV71 infection, respiratory illness can lead to pulmonary edema, hemorrhage, and lung failure. 32…”

The role of miR‐146a in viral infection

“…EV71 infection is sometimes related to aseptic meningitis, CNS inflammation and necrosis, large neuronal degeneration, and pulmonary edema or hemorrhage . The exact pathogenic mechanism of EV71 infection remains unknown, and it is thought that host mechanism especially the immune system responses, rather than this virus, is probably more significant determinants for the severity of the disease . Excessive pro‐inflammatory chemokine and cytokine responses contribute to the EV71 infection severity.…”

High-Throughput Sequencing of Putative Novel microRNAs in Rhesus Monkey Peripheral Blood Mononuclear Cells following EV71 and CA16 Infection

“…HFMD, which is mainly caused by EV71 and CA16, is a common childhood illness increasingly recognized as a significant health issue worldwide, particularly in the Asia-Pacific region [21]. Three inactivated EV71 vaccines have already been shown to provide substantial protection against EV71-HFMD and EV71-related diseases in clinical trials, but the current lack of an effective vaccine to treat HFMD induced by other enteroviruses, including CA16, highlights the importance of developing vaccines to prevent the transmission of the other causative agents [22].…”