Endemic Echovirus 11 Meningitis in Young Infants in Japan, Autumn 2024

To the Editors: Echovirus 11 (E-11) is a single-stranded RNA virus from the genus Enterovirus within the family Picornaviridae. Like other enteroviruses, E-11 infections can range from mild nonspecific symptoms to severe neurological disorders, including meningitis and encephalitis.1 Between July 2022 and April 2023, 9 neonates from 3 regions in France were hospitalized in pediatric intensive care units for suspected neonatal sepsis caused by E-11.2 All cases developed acute hepatocellular failure with severe cytolysis and disseminated intravascular coagulation within the first day of hospitalization. Additional E-11 cases have been reported to the World Health Organization from other European countries, including Croatia, Italy, Spain, Sweden and the United Kingdom.1 In Japan, a severe congenital E-11 infection was reported in 2023.3 Between August and November 2024, 4 cases of severe neonatal enterovirus infections requiring intensive care management were observed at the National Center for Child Health and Development, 3 of which were due to E-11. However, no widespread outbreaks have been reported.4 At the NHO Saitama Hospital, we observed an endemic of viral meningitis primarily caused by E-11 from August to November 2024. During this period, 53 infants under 90 days of age presenting with fever were admitted. A diagnostic flowchart is provided in Figure, Supplemental Digital Content 1, https://links.lww.com/INF/G85. Among these cases, 15 (28.3%) were diagnosed with viral meningitis, and 4 additional patients had enterovirus-positive cerebrospinal fluid (CSF) without pleocytosis. Multiplex polymerase chain reaction (PCR) testing using the FilmArray® Meningitis/Encephalitis Panel (bioMérieux, Marcy-l’Étoile, France) on CSF samples confirmed enterovirus positivity in all cases. Blood and CSF bacterial cultures were negative. Following positive multiplex PCR results, additional enterovirus-specific PCR tests were performed on CSF, blood, nasopharyngeal swabs, or stool samples. The results and patient characteristics are shown in Table 1. Among the 15 cases of enteroviral meningitis, 9 (60%) were caused by E-11. The median age of the affected infants was 59 (range, 30–76) days, with 44% of the cases being male. One infant had a history of preterm birth and low birth weight. No patients exhibited liver dysfunction. The clinical courses were mild, and all patients were discharged without sequelae. Table 1. - Clinical Characteristics of Patients Patient Number Date of Admission Sex Age at Admission (d) Duration of Hospitalization (d) Analysis of Cerebrospinal Fluid at Admission Results of Additional PCR Blood Exams at Admission Cell Count (/mm3) Results of Multiplex PCR WBC (/µL) CRP (mg/dL) T-Bil (mg/dL) AST (U/L) LDH (U/L) CK (U/L) 1 August 2024 M 6 10 181 Enterovirus Coxsackie B2 13,300 0.26 10.8 44 380 191 2 August 2024 M 27 6 355 Enterovirus Coxsackie A16 12,300 0.04 1.6 23 262 95 3 August 2024 M 14 6 225 Enterovirus Not detected 19,000 0.18 5.6 47 287 NA 4 August 2024 F 54 6 806 Enterovirus Echo 11 13,700 0.04 1 39 266 NA 5 September 2024 M 42 6 117 Enterovirus Coxsackie B3 15,600 0.25 0.6 26 271 NA 6 September 2024 F 46 6 23 Enterovirus Echo 11 4600 0.17 0.6 41 295 106 7 October 2024 F 6 7 635 Enterovirus Coxsackie B3 13,400 0.33 12.6 55 419 162 8 October 2024 F 40 5 125 Enterovirus Echo 11 9800 0.10 0.7 51 302 79 9 October 2024 F 74 6 19 Enterovirus Echo 11 12,000 0.13 0.3 27 291 109 10 October 2024 F 76 6 157 Enterovirus Echo 11 10,300 0.82 0.3 38 314 127 11 October 2024 M 59 6 311 Enterovirus Echo 11 6600 0.07 0.7 50 264 91 12 October 2024 M 70 8 220 Enterovirus Echo 11 7600 0.46 0.5 32 270 65 13 October 2024 F 69 5 26 Enterovirus Echo 18 10,100 0.51 0.5 39 252 149 14 October 2024 M 30 7 14 Enterovirus Echo 11 10,000 0.23 4.2 33 274 360 15 November 2024 M 61 7 91 Enterovirus Echo 11 9800 0.27 0.5 48 271 67 AST indicates aspartate aminotransferase; CK, creatine kinase; CRP, C-reactive protein; LDH, lactate dehydrogenase; T-Bil, total bilirubin; WBC, white blood cell. The E-11 endemic appeared to last from mid-August to early November 2024, with more than half of the cases occurring in October. Interestingly, a report from France described 2 epidemic waves of enterovirus-positive neonatal cases in 2022, each lasting ≈20 weeks.2 While their data were based on national surveillance, our findings represent a single-center experience. Nonetheless, both datasets suggest that E-11 outbreaks may span 3 to 4 months. The endemic that we observed has not been reported in other regions of Japan. However, because many facilities do not perform PCR testing, enterovirus infections may go undiagnosed. Fortunately, none of our cases presented with the severe septic-like syndrome reported in European cases. We did not conduct genomic sequencing of the E-11 strains, so it remains unclear whether our cases involved the novel variant identified in Europe. However, given the lack of specific antiviral therapy for echovirus infections, clinicians should remain vigilant for potential severe presentations associated with E-11. ACKNOWLEDGMENT The authors gratefully acknowledge the staffs of the Institute of Public Health in Saitama prefecture, Japan.