Epidemiology and clinical features of breakthrough varicella in the 9 years after universal vaccination began in Japan

Objective: To elucidate the trends and clinical features of virologically diagnosed breakthrough varicella (BV) 9 years after implementation of the universal vaccination program in Japan. Patients and methods: Study participants were patients with suspected varicella less than 15 years of age who visited 1 of 15 pediatric clinics in the Nagoya VZV Study Group between September 2015 and August 2023. Practitioners collected patient samples and information such as background characteristics, clinical symptoms, and immunization status. All patients had varicella confirmed by real-time polymerase chain reaction assays. Results: Of 719 patients with suspected varicella, 512 had laboratory-diagnosed varicella and available information on vaccination status. They were divided into 3 groups: 167 with natural varicella, 250 with BV and 1 dose of vaccine, and 95 with BV and 2 doses. The monthly number of patients with varicella decreased gradually during the observation period. Typical seasonal peaks were observed until the 2019–2020 season. The proportion of patients with BV, particularly BV after 2 doses of vaccine, gradually increased. Patients with BV and 2 doses had a significantly lower median age (5 years) than those with 1 dose (6 years) (p < 0.001). The transmission route for BV was unknown in approximately 30–50 % of patients. Duration of fever was significantly longer (p = 0.0138) and the number of skin eruptions was also significantly higher (p = 0.0013) in the 1-dose group than in the 2-dose group. Conclusions: Although the number of pediatric patients with varicella declined after implementation of national immunization with 2 doses of varicella vaccine, the proportion of patients with BV, especially those who received 2 doses, gradually increased. Clinical symptoms were significantly milder in patients with BV and 2 doses. Laboratory diagnosis of varicella is becoming increasingly important due to an increase in the proportion of patients with BV who have mild symptoms.