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Waning Immunity And Cross-Protection Of One Dose Of Measle-Mumps-Rubella Vaccine Against Mumps Infection

Posted on:2022-03-13Degree:DoctorType:Dissertation
Country:ChinaCandidate:Y B LiuFull Text:PDF
GTID:1484306743497304Subject:Epidemiology and Health Statistics
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Mumps is an acute respiratory infectious disease caused by mumps virus,which mainly infects parotid gland with complications such as meningitis,orchitis and ovaritis.Since one dose of measles-mumps-rubella combined vaccine(MMR)was introduced in National Immunization Program(NIP)of China in 2008,the mumps incidence remained high.Understanding the waning immunity and cross-protection of one dose of MMR against mumps infection and optimizing the MMR immunization strategy is urgent with important theoretical and practical significance.Objective:To fully understand the changes of mumps epidemic characteristics since the introduction of once dose MMR,and to understand the waning immunity of one dose of MMR against mumps infection,and to explore the cross-neutralization effect of mumps virus strains with A genotype on dominant F genotype wild strains in China.Methods:The descriptive epidemiological method was used to analyze the incidence data of Mumps from 2004 to 2019,and to describe the distribution characteristics of time,region and population distribution.With prospective observation design,the participants were selected from the 3-7 years old cohort established in 2015 by multi-stage stratified cluster sampling method.Besides two rounds blood sampling surveys,venous blood samples were collected for the third time at the end of 2018 to detect Ig G serum antibody of mumps and the mumps cases were also followed up.The Ig G antibody of mumps from serum was detected by ELISA,and the changes of antibodies were analyzed longitudinally.Serum samples were collected from participants of 3 groups before and 28 months since MMR immunization: children aged 8 months who would receive first dose MMR,children aged 18 months who would receive first dose MMR,and children aged 18 months who would receive second dose MMR.The micro neutralization experiment was carried out to investigate the neutralization ability of genotype A against F viruses,and genotype A against A viruses.Results:The incidence rate in Jiangsu province among 2004-2019 fluctuated about 6.3-24.3/10 millions.After one dose of MMR introduced in 2008,the mumps incidence decreased only in 2009-2010,and then increased and maintained periodic epidemic.The incidence peaked from April to July every year;the incidence in Central Region of Jiangsu is lower than that in southern and Northern Region.The ratio of male to female is 1.7:1,the peak occurred in 5-9 years old,most of them are students,kindergartens and scattered children accounting for 91%.And two peaks were observed in 6 and 9 years old,respectively.A total of 3346 patients were enrolled with prospective follow-up,96.9% of them received one dose of MMR and 3.1% received two doses of Mu V.The mumps antibody level of 3-7 years old children in Central Region was significantly lower than that in southern and Northern Region.The risk of mumps infection was higher in primary schools,especially in senior grades.The GMC of mumps in 2015(242.3 U/ml),2016(186.8 U/ml)and 2018(192.5 U/ml)decreased significantly with time(P < 0.001).From 2015 to 2018,A significant decrease was observed in 3-year-old and 4-year-old children with 327.0u/ml vs.204.4 U/ml,379.9 U/ml vs.252.1U/ml,respectively.However,slowly decrease was observed at 6-year-old and 7-year-old children;GMC declined both in children with one dose of MMR and two doses of Mu V.The overall positive rate of this cohort declined over time in 2015(79.6%),2016(73.1%)and 2018(71.4%)(P < 0.001).The antibody positive rate of one dose decreased rapidly,but the antibody positive rate of two doses remained relatively stable in the four following years.GMC and antibody positive rate of 3-7-year-old children with one dose of MMR decreased with time in different regions,genders and ages.GMC decreased significantly while antibody positive rate changed relatively stable.GMC and positive rate of boys and girls decreased with time.The GMC of mumps antibody in 3-4 years old children declined faster than that in 6-7 years old children;however,the decline trend of positive rate in 4 age groups was relatively stable;the GMC in each age group declined rapidly in the first two years,then maintained stable.The GMC decreased in 3-4 years old children with 2 doses of MMR,but no decrease was found in the positive rate.In 2015,there were 2665 participants with positive results,of which 15.0% converted to negative in 2016 and 16.9% converted to negative in 2018;in 2016,there were 2445 participants with positive results,of which 13.5% converted to negative in 2018.From 2015 to 2018,the cumulative negative conversion rate was 26.9%.Among 3241 children aged 3-7 years who received one dose of MMR,the asymptomatic infection rate was 6.5% in 2015-2016,9.3% in 2016-2018,6.0% in 2015-2018,and cumulative asymptomatic infection rate was 15.9% in 2015-2018.The results showed that the positive conversion rates of 8-month-old and 18-month-old patients against F genotype with one dose of MMR were only 16.0% and 65.1%,which were lower than those of A genotype(22.4% vs.67.4%,P<0.05);for the children aged18 months with 2 doses of MMR,although the positive conversion rates against A genotype and F genotype were 98.6%,the GMT of the former was higher than that of the latter(56.4% vs.30.9%,P<0.05).ConclusionThe epidemiological characteristics of mumps changed with the introduction of one dose MMR strategy in China.The effect of one dose MMR on the mumps prevention and control is limited.The mumps antibody of 3-7 years old children who have completed one dose of MMR waned significantly,some of them converted to negative,and some of them developed asymptomatic infection.The second dose of MMR should be introduced into the NIP to decreased the epidemic of mumps in children.And the optimal time for the second dose of MMR should be explored or a novel mumps vaccine should be developed to prevent the outbreak of mumps in adolescents due to the antibody wanning.
Keywords/Search Tags:Mumps, measles mumps rubella combined vaccine, waning immunity, antibody
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