Pathologic Studies of Fatal Enterovirus 71 Encephalitis in the United States.
Wun-Ju Shieh, Julu Bhatnagar, Christopher D Paddock, Sherif R Zaki. Centers for Disease Control and Prevention, Atlanta, GA
Background: Enterovirus 71 (EV71) is a member of the human enterovirus species A in the family of Picornaviridae. It is one of the etiologic agents of hand-foot-mouth disease (HFMD) and has been associated with neurologic disorders, such as aseptic meningitis, encephalitis, myelitis, and a syndrome of acute febrile paralysis similar to poliomyelitis. Since the late 1990s, outbreaks of EV71 encephalitis with severe neurologic complications or fatal outcome among young children have occurred in many Asian countries. In the United States, only sporadic cases or localized small outbreaks of EV71-associated illnesses have been reported and very few fatal cases have been studied by postmortem examination. We present pathologic studies on a series of U.S. fatal cases of EV71 encephalitis in this report.
Design: From 1997 to present, 933 cases of central nervous system infection of unknown etiology were submitted to the Infectious Diseases Pathology Branch at CDC for evaluation. Eight fatal cases caused by EV71 from 5 different U.S. states were identified and included in this study. Autopsy tissue samples of these cases were evaluated by histopathologic examination, immunohistochemical assay (IHC), and molecular techniques.
Results: The median age of the patients in this study was 2 years, ranging from10 months to 6 years. The most prominent histopathologic findings included neuronal necrosis, neuronophagia, glial nodules, and inflammatory infiltrates in parenchyma, perivascular areas, and meninges. Histopathologic changes were most severe in the brainstem and spinal cord. Viral antigens were usually observed by IHC in infected neurons, neuronal processes, glial nodules, and areas of necrosis. The presence of EV71 RNA in the central nervous system was detected by a nested-RT PCR assay targeting the VP1 gene of EV71 and sequencing of amplicons.
Conclusions: EV71 has emerged as an important pathogen in recent years, causing multiple outbreaks of HFMD with severe neurological complications among young children in the Asia-Pacific region. Its role in central nervous system infections is not well recognized in the U.S. because of relatively low incidence. Nevertheless, EV71 is an important etiologic agent of acute meningoencephalomyelitis, with high rates of morbidity and mortality in pediatric population. Our studies highlight the histopathologic features of fatal EV71 cases and underscore the importance of performing IHC and RT-PCR assays on autopsy samples. More studies are needed to further understand the pathogenesis of EV71 infection.
Wednesday, March 2, 2011 1:00 PM
Poster Session VI # 226, Wednesday Afternoon