Serotype-specific immunity explains the incidence of diseases caused by human enteroviruses

Abstract

Human enteroviruses are a major cause of neurological and other diseases. More than 100 serotypes are known that exhibit unexplained complex patterns of incidence, from regular cycles to more irregular patterns, and new emergences. Using 15 years of surveillance data from Japan (2000-2014) and a stochastic transmission model with accurate demography, we show that acquired serotype-specific immunity can explain the diverse patterns of 18 of the 20 most common serotypes (including Coxsackieviruses, Echoviruses, and Enterovirus-A71). The remaining two serotypes required a change in viral characteristics, including an increase in pathogenicity for Coxsackievirus-A6, which is consistent with its recent global rise in incidence. On the basis of our findings, we are able to predict outbreaks 2 years ahead of time (2015-2016). These results have implications for the impact of vaccines under development.

Neutralizing Antibodies against Enteroviruses in Patients with Hand, Foot and Mouth Disease

“…In contrast to the observed data for homotypic viruses, seropositive rates for heterotypic viruses were recorded in <57% of the patients during the course of illness. Furthermore, at follow-up, only a small proportion (3%-23%) of the patients had seroconverted for heterotypic viruses, suggesting that cross-neutralization among EV-A71, CVA6, CVA10, and CVA16 is absent or occurs in only a small proportion of patients (24,25). It cannot, however, be ruled out that these seropositive and seroconverstion rates, especially among CVA6 patients, were attributable to previous exposure or co-infection with other serotypes (e.g., CVA16 in the case of CVA6 patients), which may have been undetected by PCR.…”

Panel Data Analysis via Mechanistic Models

“…Since the Gaussian distribution has short tails, ignoring truncation is practically equivalent to truncation at a large multiple of the standard deviation. Unlike an alternative theoretical framework using Stein's lemma to approximate derivatives via perturbed parameters and SMC (Doucet, Jacob and Rubenthaler, 2015;Dai and Schön, 2016) Ranjeva et al, 2017Ranjeva et al, , 2018Pons-Salort and Grassly, 2018). We used the R implementation of MCAP from Ionides et al (2017) with an algorithmic smoothing parameter λ loess = 0.9 determining the fraction of profile points used to construct the neighborhoods for locally weighted quadratic regression smoothing.…”

Report on the 2018 Acute Flaccid Myelitis Outbreaks in the USA

“…Clusters of EV-D68 have also been reported in New York, however none of these cases have exhibited symptoms associated with AFM (45). Other evidence suggests non-polio enterovirus seasonality may be driven by a waning of seroprevalence in the population and the emergence of immunologically naïve newborns (46).…”