Differences in the Preventive Effect of Subcutaneous Versus Intramuscular Administration of Seasonal Influenza Vaccine: A Prospective Cohort Observational Study on Influenza Incidence, Injection Pain Level, and Adverse Reaction

Abstract

In Japan, seasonal influenza vaccine is routinely administered subcutaneously. In contrast, intramuscular administration is recommended overseas because of the mild local adverse reaction and appropriate increase in the influenza antibody titer. Thus far, the difference in the preventive effect of the vaccine on influenza incidence and the level of pain experienced during the injection between the subcutaneous and intramuscular routes of administration have not been elucidated. Regarding the influenza vaccination at our hospital, staff and nursing students choose either a subcutaneous or an intramuscular route of administration. Therefore, in this prospective observational cohort study, we investigated the difference between the two routes of vaccine administration by comparing influenza incidence, level of pain during the injection, and postadministration adverse reaction. By law, influenza cases must be reported to the workplace or school. Hence, the incidence rate of influenza is calculated according to the number of reported cases. The incidence of influenza was 11.3% (65/574) and 8.2% (258/3147) among individuals who received the vaccine subcutaneously and intramuscularly, respectively. Furthermore, a univariate analysis showed a significantly lower incidence of influenza among individuals who received the intramuscular injection than among those who received the subcutaneous injection (P=0.02). Based on logistic regression adjusted for sex, age, cohabitation with people under 15 years of age, and measures to prevent infection, influenza incidence was significantly lower in the intramuscular injection group (odds ratio 0.73, P=0.04). Additionally, the level of pain during the injection and post-administration adverse reactions were assessed among 320 nursing students (subcutaneous administration, 77; intramuscular administration, 243). The median score of pain experienced during the injection (where 0 was defined as painless and 10 was defined as very painful)was 4 in the subcutaneous injection group and 2 in the intramuscular injection group. The intramuscular injection group experienced significantly less pain (P<0.001). Based on a multivariate regression analysis adjusted for fear of injection, the level of pain due to the injection was significantly lower in the intramuscular group (regression coefficient of -1.26, P<0.001). Postadministration pain and swelling were also milder in the intramuscular group. In conclusion, intramuscular administration of the influenza vaccine resulted in lower influenza incidence, less pain during injection, and less severe post-administration adverse reaction than the subcutaneous administration of the vaccine. As intramuscular administration of the influenza vaccine is generally considered an excellent method of administration, we hope that this method will become widely accepted in Japan.