A coxsackievirus A2 herpangina outbreak in a kindergarten in Shenzhen, China: evidence chain from dispersed clinical labels to class-date clustering and VP1 confirmation

Background Herpangina is a frequent enterovirus-associated illness in childhood, but it is not subject to statutory notification in China. In kindergartens, outbreak signals may first appear as dispersed clinical labels, non-specific symptoms, and illness-related absences rather than as formal disease reports. We investigated a coxsackievirus A2 (CV-A2) herpangina outbreak in a kindergarten in Shenzhen, China, to describe an evidence chain linking heterogeneous outpatient diagnoses, class-date clustering, and VP1-based etiological confirmation. Methods Operational case definitions were developed, and cases were searched using attendance lists, illness-related absence follow-up records, morning/noon health-check logs, interviews, and medical-visit information. Combined throat/anal swabs from cases and environmental swabs were tested for enterovirus nucleic acid by real-time RT-PCR. Eligible positive specimens underwent VP1 amplification, bidirectional Sanger sequencing, typing, and phylogenetic analysis. Attack rates were compared with Pearson chi-square tests, with a fixed-margin Monte Carlo exact test for the class-level comparison. Results Sixty-eight outbreak-definition cases were found, all in children. The kindergarten-wide attack rate was 22.08% (68/308), and the child attack rate was 26.15% (68/260). Cases occurred in all 10 classes. Class-specific attack rates varied significantly (chi-square = 25.50, P = 0.002), with the highest rate in Junior Class 1 (52.38%, 11/21). Fever (65 cases, 95.59%), sore throat (40 cases, 58.82%), and pharyngeal redness (38 cases, 55.88%) were the most common manifestations. Among 42 medically attended children, herpangina and acute upper respiratory tract infection were each recorded in 15. Fourteen of 15 case swabs were enterovirus-positive; 13 VP1 amplicons were sequenced and typed as CV-A2. The outbreak sequences shared 99.83%-100.00% nucleotide identity and grouped together phylogenetically. Conclusions This multi-class kindergarten outbreak of herpangina was associated with closely related CV-A2 strains. More importantly, the investigation illustrates a practical recognition pathway for a non-notifiable childhood enterovirus illness: dispersed clinical labels were integrated with class- and date-based health-monitoring signals, and VP1 typing provided etiological confirmation. Routine aggregation of health-check, observation, absence, and symptom records can be critical for identifying abnormal clustering before laboratory confirmation is available.