EV-A71 Vaccines Effective Against Hand, Foot, and Mouth Disease

Investigators in China observed a substantial decrease in the number of severe cases after the arrival of the EV-A71 vaccine.

A recent population-based study from China detailed the epidemiology of hand, foot, and mouth disease (HFMD) before and after the introduction of the EV-A71 vaccine.

Previous studies observed that inactivated monovalent EV-A71 vaccines were highly effective against HFMD associated with EV-A71.

However, the vaccines were not effective against HFMD with other etiologies, leading to the hypothesis that the introduction of the EV-A71 vaccines could change the pathogen spectrum and epidemiological trend of the disease.

As such, investigators led by Zhijie Zhang, PhD, Department of Epidemiology and Health Statistics at Fudan University, China, detailed the epidemiology of the disease in mainland China, focusing on the changes in demographic, seasonal, and geographical patterns before and after the introduction of the vaccine.

The Methods

The investigators retrieved data on all HFMD cases reported between January 1, 2013 and December 31, 2019 from the Chinese Center for Disease Control and Prevention, in addition to the annual population sizes during the 6-year study period.

To detail the changes in HFMD epidemiology over time, the study period was classified into 3 sub-periods including baseline (2013-2015), prior to implementation of the EV-A71 vaccine, the transition year (2016), and implementation of the EV-A71 vaccination program (2017-2019).

The frequency and proportion of cases for different age groups, sex, severity, and serotypes were calculated for each year, as were age-specific rates of incidence, severe illness, and mortality.

Heat maps were utilized in the study to describe seasonal patterns of HFMD by province, and the proportion of cases identified in each week of the year were then standardized by the number of annual cases.

The median values of the proportion of cases in each week of the year from 2013 to 2019 were plotted as the seasonal distribution of cases of HFMD.

The cumulative incidence of the disease in all provinces during the study period was estimated and stratified by vaccination phase and virus serotypes, which illustrated the changes in the geographical distribution ranges of HFMD in China.

The Findings

Nationally, a total of 15,316,710 cases of HFMD were reported to the China CDC surveillance system during the study period, with 787, 197 cases being laboratory confirmed and 76,982 being defined as severe.

Severe cases of the disease represented 58.1% and 39% of all severe cases before and after the launch of the vaccine, respectively.

Investigators observed a large decrease (60.7%) in the number of severe cases after the arrival of the EV-A71 vaccine. After the introduction of the vaccine, the median age of patients with HFMD infected with the EV-A71 serotype were mainly older.

There was a lower proportion of HFMD patients under 3 years of age in addition to a large decrease in the proportion of patients under 5 years of age infected with EV-A71.

After the launch of the vaccine, the severe illness rate and mortality rate of HFMD patients across all age groups decreased to 62.2% and 83.78% respectively, with a considerable decrease (60.7%) of severe cases.

Additionally, the risk of becoming a severe case for EV-A71 serotype was decreased, though that risk increased for Coxsackie virus A16 (CV-A16) from 0.17 (95% CI:0·16, 0.18) to 0.23 (95% CI:0·21, 0·25).

The study represented the first comprehensive description of the epidemiology of laboratory-confirmed cases of HFMD both before and after the launch of the EV-A71 vaccine. As such, investigators called for continued research on the disease and preventative benefits of the vaccine.

“More broadly, further research is needed to quantify the contribution of EV-A71 vaccine to HFMD prevention and control. Factors other than vaccine should also be considered in further studies,” the team wrote.

The study, "Changing epidemiology of hand, foot, and mouth disease in China, 2013−2019: a population-based study," was published online in The Lancet Regional Health.