Lee H, et al. J Korean Med Sci. 2021 Dec;37(1):e13. https://doi.org/10.3346/jkms.2022.37.e13

Objectives: The enterovirus EV71 is a major pathogen of hand, foot, and mouth disease (HFMD) in children. Aseptic meningitis is the most common neurologic complication of EV71-induced HFMD. Lumbar puncture is a crucial procedure in the diagnosis of aseptic meningitis. It is often performed based on physicians’ clinical suspicion. A diagnostic method that can aid in deciding whether this procedure should be performed is necessary. Cytokines are speculated to be associated with neurologic complications. In this study, we aimed to find an indicator of the presence of aseptic meningitis in children with EV71-induced HFMD. Methods: This cross-sectional study included children with EV71-induced HFMD. The children underwent lumbar puncture due to suspected aseptic meningitis. They were categorized into an aseptic meningitis complicated group (n = 54) and uncomplicated group (n = 47) based on the results of cerebrospinal fluid examination. Healthy children were included as controls (n = 51). The sample serum levels of tumor necrosis factor-α, interferon-γ, interleukin (IL)-1β, IL-2, IL-6, IL-8, IL-10, and IL-13 were detected using multiplexed fluorescent bead-based immunoassays. Results: The levels of all cytokines were significantly higher in children with EV71-induced HFMD complicated with aseptic meningitis than in children with uncomplicated EV71-induced HFMD and controls (p < 0.001). Binary logistic regression analysis demonstrated that IL-6 had the strongest association with aseptic meningitis of all cytokines examined. According to receiver operating characteristic analysis, the optimal cutoff value for IL-6 was 66 pg/mL with maximum sensitivity and specificity. Conclusions: The results of this study suggest the association between higher production of cytokine and aseptic meningitis among children with EV71-induced HFMD. IL-6 was also suggested as an indicator of aseptic meningitis. Rapid measurement of IL-6 could be useful in deciding whether physicians should perform lumbar puncture on children.

During the ongoing coronavirus disease (COVID-19) pandemic, hospitals have strengthened their guidelines on infection prevention and control (IPC), and a rigorous adherence to these guidelines is crucial. An infection control surveillance-working group (ICS-WG) and infection control coordinators (ICCs) team were created to monitor the IPC practices of the healthcare workers (HCWs) in a regional hospital in Korea. This study analyzed the surveillance results and aimed to identify what IPC practices needed improvement. During phase 1 (March to April 2020), the ICS-WG performed random audits, recorded incidences of improper IPC practices, and provided advice to the violators. During phase 2 (April to July), the ICCs inspected the hospital units and proposed practical ideas about IPC. The surveillance and proposals targeted the following practices: patient screening, usage of personal protective equipment (PPE), hand and respiratory hygiene, equipment reprocessing, environmental cleaning, management of medical waste, and social distancing. In phase 1, of the 127 violations observed, most (32.3%) corresponded to hand and respiratory hygiene. In phase 2, the highest proportion of violation per category was observed in the management of medical waste (37.8%); among these, a higher proportion of violation (71.4%) was observed in the collection of medical waste. Of the 106 proposals made by the ICCs, the most addressed practice was patient screening (28.3%). No case of nosocomial infection was reported during the study period. Adherence to proper hand and respiratory hygiene was inadequate at the early stage of the COVID-19 pandemic. The results indicate that more attention and further training are needed for the management of medical waste, particularly medical waste collection, and that continuous upgrading of the strategies for patient screening is essential. These results will be useful in helping other healthcare facilities to establish their IPC strategies.

Korean manufacturers have developed a new varicella vaccine, NBP608. This phase 3, randomized, double-blind, multicenter study aimed to compare the immunogenicity and safety of NBP608 in healthy children to those of Varivax^TM (control). Children aged 12 months to 12 years were randomized in a ratio of 1:1 to receive either NBP608 or the control vaccine. Serum samples were obtained before vaccination and within six to eight weeks after vaccination. In total, 499 participants (NBP608, n = 251; control, n = 248) were enrolled. The seroconversion rate (SCR) measured using a FAMA assay was 99.53% in the NBP608 group, and the lower limit of the 95% confidence interval (95% LCL) for the SCR difference (NBP608 minus the control) was 0.52%. This 95% LCL for the difference was higher than the specified non-inferiority margin of −15%. In an assessment using gpELISA, the SCR was 99.53% in the NBP608 group, and the 95% LCL for the SCR difference was 6.5%, which was higher than the specified non-inferiority margin of −15%. There were no significant differences between the NBP608 and control group with respect to the proportions of participants who demonstrated local and systemic solicited AEs. This study indicated that NBP608 had a clinically acceptable safety profile and was not immunologically inferior to Varivax^TM.

Hand, foot, and mouth disease (HFMD) is a pediatric public health concern in Asia. Surveillance data on the circulating serotypes of HFMD suggest that Enterovirus A71 (EV-A71) and coxsackieviruses A6, A10, and A16 (CVA6, CVA10, and CVA16) are the major serotypes causing HFMD. Asian countries, including Korea, are currently developing a multivalent vaccine targeting these serotypes. However, the immunity of children against specific serotypes, indicating past infection, should also be considered while selecting candidate serotypes for vaccine development. Therefore, we aimed to identify the age-stratified serological statuses of Korean children to determine candidate serotypes for HFMD vaccine development. This study included 220 participants, categorized into four age groups, 7 months–2 years, 3–5 years, 6–10 years, and 11–15 years. A neutralization test was performed to quantitate the neutralizing antibodies (NtAbs) in the sera of the participants. Only EV-A71 and CVA6 were found suitable as candidate serotypes for vaccine development, whereas further study is needed for CVA10 and CVA16. The highest seropositivity and NtAb titer ranges were observed for CVA6 in all age groups, suggesting that the participants had been predominantly exposed to CVA6. For EV-A71, seropositivity and NtAb titer ranges steadily increased with age, suggesting that children were currently exposed to EV-A71. For CVA10, the 3–5 years group showed the highest seropositivity rate and higher NtAb titer ranges than the older age groups, indicating that the exposure to CVA10 had mainly occurred in recent years. Future studies will identify whether the exposure to CVA10 was transient or will continue. For CVA16, seropositivity and NtAb titer ranges were generally low, indicating that only a few participants had been exposed to CVA16. We identified discrepancies between the sentinel surveillance data and our findings. This study provides a new perspective for HFMD vaccine development and policy making in Asian countries.