Global epidemiology of nonpolio enteroviruses causing severe neurological complications: A systematic review and meta‐analysis

Enteroviruses are RNA viruses found as commensals in the human gut and respiratory system, which may cause a wide spectrum of disease. Enteroviruses may cause severe neurologic complications including acute flaccid paralysis (AFP) and encephalitis and are the most commonly diagnosed agents of viral meningitis. Outbreaks of more severe disease are often associated with particular genotypes, such as enterovirus-A71 causing rhombencephalitis and AFP. There are more than 300 described genotypes of human enterovirus, with overlaps in clinical phenotypes between genotypes, and uncertainty about which genotypes are more prevalent in neurological manifestations. A systematic review of observational studies was conducted to evaluate the most prevalent enterovirus genotypes causing AFP, encephalitis, and meningitis. The genotyping methods and sampling sites were compiled as secondary outcomes. Sources included MEDLINE, Embase (publications until January 2019), and references selected from included studies. Meta-analyses using a random effects model were performed to calculate the pooled proportion of enterovirus genotypes in each disease. Ninety-six publications met the eligibility criteria, comprising 3779 AFP cases, 1140 encephalitis cases, and 32 810 meningitis cases. Enterovirus-A71 was most frequently associated with AFP (pooled proportion 0.12, 95% CI, 0.05-0.20) and encephalitis (0.77, 95% CI, 0.61-0.91). Echovirus 30 (0.35, 95% CI, 0.27-0.42) was the most predominant genotype in meningitis cases. Genotypes were most commonly determined using VP1 RT- reverse transcription-polymerase chain reaction, and most samples assessed were cerebrospinal fluid. With the emergence of enteroviruses as an increasing cause of neurological diseases, surveillance and testing need to increase to identify the aetiology of the most common and most severe disorders.