| Objective Several epidemiological studies have found that live attenuated vaccines may have a non-specific effect.It may reduce the risk of non-vaccine target diseases in children,with a particularly significant protective effect against lower respiratory tract infections diseases.The paper aims to analyze the non-specific effects and influencing factors of Japanese encephalitis vaccine on children’s lower respiratory infectious diseases to provide a new measure to improve people’s healthy and to provide a reference for the formulation of immunization planning procedures.Methods A retrospective cohort study was used to collect socio-demographic,underlying health impairment-related diseases,vaccination information of the children who are born between January 1,2017 and December 31,2017 by using the Yinzhou District Health Data Platform in Ningbo City to analyze the lower respiratory tract infectious diseases such as influenza and pneumonia during the 25-35 months period by inoculating live attenuated Japanese encephalitis vaccine in 24 months with follow-up until December 31,2019.The study is mainly divided into two parts(1)effect analysis:①The last inoculation type of Japanese encephalitis vaccination was used as exposure factor during the observation period,the children who received the Japanese encephalitis live attenuated vaccine are the exposed group and the children who received the Japanese encephalitis inactivated vaccine are the non-exposed group.The incidence density and length of hospitalization of lower respiratory infectious diseases were analyzed in the two groups.②The Andersen-Gill model was constructed to analyze the effect of live attenuated Japanese encephalitis vaccine on hospital admissions for lower respiratory infectious diseases in children aged 25-35 months,using the number of lower respiratory infectious disease episodes as the dependent variable,and gender,age group,gestational age,birth weight and others as covariates.The results of the study were also stratified by gender.(2)Sensitivity analysis:According to the whole course of Japanese encephalitis vaccination,the subjects were divided into four groups,of which who received Japanese encephalitis live attenuated vaccine only,children who received Japanese encephalitis inactivated vaccine after Japanese encephalitis live attenuated vaccination,children who received Japanese encephalitis live attenuated vaccine after Japanese encephalitis inactivated vaccination,and children who received Japanese encephalitis inactivated vaccine only.The incidence of lower respiratory tract infectious diseases in the four groups was analyzed and the results would be compared with the findings of the main analysis to verify the nonspecific effect of live attenuated Japanese encephalitis.Results(1)A total of 810 children born in 2017 were enrolled in Yinzhou District,Ningbo City with 585 of the 810 study subjects received live attenuated Japanese encephalitis vaccine and 225 received Japanese encephalitis vaccine.The two groups of children were balanced and comparable in demographic characteristics such as gender,birth weight,and the number of hospital admissions before 24 months(2)85 of the subjects were diagnosed with lower respiratory tract infectious diseases during 25-35m,with a total of 310 cases and an incidence density of 0.383 per person-year(95%CI:0.349-0.417),and the incidence density was lower in female than in male(0.297 vs 0.458,P=0.0002),lower in the high age group(25-27 months vs 28-31 months vs 32-35 months:1.169 vs.0.353 vs.0.083,P<0.0001),lower in those without comorbid health impairment-related diseases than in those with(0.340 vs 1.167,P<0.0001),and lower in those with 1 parity than in those with 2 parities(0.342 vs 0.459,P=0.0274).In addition,4 of 85 people were diagnosed with influenza with an incidence density of 0.019 per person-year(0.010-0.030);8 people were diagnosed with pneumonia with an incidence density of 0.033 per person-year(0.022-0.048);73 people were diagnosed with acute bronchitis with an incidence density of 0.331 per person-year(0.299-0.344).(3)In the effect analysis,182 and 128 lower respiratory tract infections diseases were reported in the exposed group and the nonexposed group,respectively.The incidence density in the exposed group was lower than that in the non-exposed group(0.311 vs 0.568,P<0.0001).The same results were found in the subgroups such as sex,age group,presence of health impairment-related diseases,and parity.(4)Live attenuated Japanese encephalitis vaccine can reduce the risk of lower respiratory tract infectious diseases during 25-35m(HR=0.537,95%CI:0.416-0.693),pneumonia(HR=0.501,95%CI:0.393-0.638)and acute bronchitis(HR=0.525,95%CI:0.396-0.698).In addition,the NSE effect of live attenuated Japanese encephalitis vaccine on lower respiratory tract infectious diseases is evident in females(HR=0.305,95%CI:0.198-0.469),without health impairmentrelated diseases(HR=0.553,95%CI:0.420-0.729),and 1 parity infants(HR=0.361,95%CI:0.255-0.511),the number of admission before 24 months(HR=0.163,95%CI:0.091-0.290),the number of hospitalized children with infectious diseases(HR=0.058,95%CI:0.017-0.202)were especially obvious.(5)Sensitivity analysis:It was found that,the incidence of LRTI disease was lower in those who received the whole course of live attenuated Japanese encephalitis vaccine compared with those who received inactivated vaccine throughout the course after excluding the bias caused by simultaneous inoculation of live attenuated Japanese encephalitis vaccine and inactivated Japanese encephalitis vaccine(0.604 vs 0.316 per personyear).It was also found that children who received the whole course of live attenuated Japanese encephalitis vaccine could reduce the risk of LRTI disease(HR=0.512,95%CI:0.396-0.662).Conclusion Live attenuated Japanese encephalitis vaccine has an NSE effect that can reduces the density of lower respiratory tract infectious diseases,and this effect is particularly pronounced in children who are female,have no health impairment-related diseases,have 1 parity,and have a high number of hospital admissions or hospital admissions for infectious diseases before the 24 months. |
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