Since 2014, acute flaccid myelitis (AFM), a long-recognized condition associated with polioviruses, nonpolio enteroviruses, and various other viral and nonviral causes, has been reemerging globally in epidemic form. This unanticipated reemergence is ironic, given that polioviruses, once the major causes of AFM, are now at the very threshold of global eradication and cannot therefore explain any aspect of AFM reemergence. Instead, the new AFM epidemic has been temporally associated with reemergences of nonpolio enteroviruses such as EV-D68, until recently thought to be an obscure virus of extremely low endemicity. This perspective reviews the enigmatic epidemiologic, virologic, and diagnostic aspects of epidemic AFM reemergence; examines current options for clinical management; discusses future research needs; and suggests that the AFM epidemic offers important clues to mechanisms of viral disease emergence.
In recent decades, new human infectious diseases such as HIV/AIDS, severe acute respiratory syndrome (SARS), and Nipah virus infection, among others have emerged. Well-known diseases also have reemerged because of human movement, crowding, and other population factors (e.g., dengue and dengue hemorrhagic fever), warfare and natural disasters (e.g., cholera), and viral evolution (e.g., poultry-adapted influenza A H5N1 and H7N9) (1). Joining this list is epidemic acute flaccid myelitis (AFM), characterized by sudden denervation-associated muscle paralysis of healthy children (and occasionally adults) in one or more limbs that mimics poliomyelitis but which is not caused by polioviruses (2). AFM was first recognized around 2010 as a seemingly novel condition (3, 4) and quickly grew into an alarming and important disease threat, with the first large outbreak occurring in 2014 (5). Since then, seasonal waves have occurred every other year in
the United States, the largest occurring in 2018 (Fig. 1) (6–8)). Because of its uncertain cause and pathogenesis, enigmatic epidemiology, and limited treatment options, the disease captured national attention and triggered considerable concern among parents of young children.