Front. Immunol. Frontiers in Immunology Front. Immunol. 1664-3224 Frontiers Media S.A. 10.3389/fimmu.2024.1472189 Immunology Systematic Review Rubella antibody levels in the healthy Chinese population: a meta-analysis Zhuo Yaning 1 † Lu Zhaojun 2 † Zhang Xuechao 2 Zhang Xiaoping 2 Yang Yingying 2 Han Jiayin 2 Du Jian 2 Xu Yuyang 2 Liu Yan 2 * Fu Chuanxi 3 * 1 School of Public Health, Zhejiang Chinese Medical University, Hangzhou, China 2 Department of Expanded Program on Immunization, Hangzhou Center for Disease Control and Prevention, Hangzhou, Zhejiang, China 3 The Institute of Infectious Disease and Vaccine, School of Public Health, Zhejiang Chinese Medical University, Hangzhou, China

Edited by: Pei-Hui Wang, Shandong University, China

Reviewed by: Stephen Crooke, Centers for Disease Control and Prevention (CDC), United States

Min-Hsin Chen, Centers for Disease Control and Prevention (CDC), United States

*Correspondence: Yan Liu, smileforever81@126.com; Chuanxi Fu, fuchuanxi@zcmu.edu.cn

†These authors have contributed equally to this work

 12 11 2024 2024 15 1472189 29 07 2024 21 10 2024 Copyright © 2024 Zhuo, Lu, Zhang, Zhang, Yang, Han, Du, Xu, Liu and Fu 2024 Zhuo, Lu, Zhang, Zhang, Yang, Han, Du, Xu, Liu and Fu

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 Objectives

To gain a comprehensive understanding of rubella seroprevalence in the healthy population in China and to offer data-driven support for the goal of rubella elimination.

 Methods

CNKI, Wanfang database, VIP database, CBM, PubMed, web of Science, and Embase databases were searched to collect studies reporting the positive rate of rubella antibody among the Chinese healthy populations between 2001 and 2022. We conducted a meta-analysis using R language, and data were combined using random effects model.

 Results

A total of 97 studies were included, encompassing a sample size of 103,018. Meta-analysis showed that the overall prevalence of rubella antibody positivity in the Chinese healthy population was 77.29% (95% CI: 75.26-79.33). The prevalence of rubella antibody varied significantly based on age and vaccination status. Among the age groups studied, the <1-year-old group exhibited the lowest positivity rate for rubella antibody at 47.87% (95% CI: 41.53-54.21),while the ≥50 years old group showed the highest positivity rate at 85.43% (95% CI: 81.01-89.85); individuals with a history of vaccination demonstrated a higher antibody positivity rate compared to those without vaccination history.

 Conclusions

The prevalence of rubella antibody in healthy Chinese population is relatively low. In order to establish a solid immunity threshold levels, it requires conducting timely immunization programs on key groups such as middle school students and the women of childbearing age on the basis of ensuring a high level of rubella-containing-vaccines (RCV) coverage, so as to achieve the goal of eliminating rubella.

 Systematic review registration

https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42024607949.

 rubella IgG antibody vaccination Chinese population meta-analysis section-in-acceptance Viral Immunology Introduction

Rubella is an acute infectious disease caused by the rubella virus, primarily transmitted through respiratory droplets and direct contact. The main clinical manifestations of rubella include fever, a generalized erythematous maculopapular rash, and lymphadenopathy. Complications may include arthralgia, arthritis, thrombocytopenic purpura, and encephalitis (1). While the general clinical symptoms of rubella are usually mild, the infection with the rubella virus during early pregnancy can lead to adverse outcomes such as spontaneous abortion, stillbirth, or congenital rubella syndrome (CRS) in newborns. Currently, there is no specific clinical treatment for CRS. The World Health Organization (WHO) estimates that approximately 100,000 cases of CRS occur worldwide annually, posing significant challenges to the advancement of public health. However, these adverse consequences of rubella can be prevented and controlled through the administration of RCV, potentially leading to eventual elimination of rubella (2).

In 1993, China introduced the rubella vaccine (RV); however, its availability for vaccination is limited to certain regions (3). In 2008, China included measles-rubella vaccine (MR) and measles-mumps-rubella vaccine (MMR) into the national expanded program on immunization, implementing a two-dose immunization schedule for eligible children (4). The coverage of RCV immunization has steadily increased and has consistently remained above 95% since 2012. The incidence of rubella in China decreased from 9.11/100,000 in 2008 to 0.12/100,000 in 2017. Nevertheless, there was a notable increase in rubella incidence during the years 2018 to 2019 (5). In this study, we employed meta-analysis to investigate the nationwide rubella seroprevalence utilizing data from rubella antibody surveillance among healthy populations conducted in various regions of China over multiple years, aiming to enhance rubella immunization strategies.

 Methods Data searches

Literature to be included in the meta-analysis was sought in the Chinese data base and English data base respectively. Chinese data bases included CNKI, Wanfang database, VIP database and CBM; English data bases included PubMed, Web of Science, Embase. The searching terms were (Rubella OR Rubellas OR Three Day Measles OR Three Day Measle OR German Measles) AND (Antibody positive rate OR seropositive OR seropositivity OR serosurvey OR serosurveillance OR seroprevalence) AND (Enzyme-linked immunosorbent assay OR ELISA) AND (China OR Chinese). The search period for this study spanned from the inception of the database up to December 31, 2023.

 Literature selection

①The study population consisted of physically healthy individuals; ②Seroprevalence were examined using enzyme-linked immunosorbent assay (ELISA), values≥20 IU/ml were considered positive, values of 10-20 IU/ml were considered equivocal, and values<10 IU/ml were considered negative; ③The positive rates were either directly reported or had data available for calculating the positivity rates.

 Data extraction and quality assessment

Two investigators independently evaluated the abstracts of the literature independently and screened them according to the literature selection and exclusion. Then read the full articles, which were scored based on the quality assessment criteria. When encountering differences, the investigators can consult with each other or seek resolution from a third investigator to reach a final decision regarding inclusion. After completing the literature screening process, data including the first author, publication year, age, gender, survey time, survey location, number of positive antibody individuals, sample size, antibody positive rate and immunization history were extracted from the articles.

The literature using the assessment criteria of the cross-sectional studies which recommended by Joanna Briggs institute (JBI) to assess their quality. The quality assessment tool includes 9 items. The specific content of each item is as follows: ①Does the sample represent the target population?②Is the sampling method appropriate for the study population? ③Is the sample size sufficient? (At least≥200 ) ④Are the study subjects and research settings described in detail? ⑤Do the subgroups in the sample have similar response rates to ensure sufficient coverage during data analysis? ⑥Is an effective method used to identify the health issue? ⑦Are standard and reliable methods used to assess the health issue in all study subjects? ⑧Is the data analysis method appropriate? ⑨Are the response rates sufficient? Are appropriate methods used to address low response rates?

The evaluation results are defined based on four dimensions: "yes," "no," "unclear," and "not applicable." A score of 1 is assigned for "yes," while all other responses receive a score of 0. The score below 5 is considered low-quality and excluded from the analysis (6, 7).

 Literature exclusion

①The study population included patients with rubella, suspected rubella cases, or with additional symptoms or diseases; ②The timing and method of seroprevalence testing of the study population are unspecified; ③The types of literature are conference papers, clinical trial studies, animal experiments, discussions on the prevalence of the disease and so on; ④The objective of the literature is to explore the effectiveness of the vaccine itself, such as the antibody conversion rate; ⑤The literature has a low-quality assessment score.

 Statistical analysis

The data analysis in this study utilized the "meta" package in R4.3.2 for conducting meta-analysis. The positive rate of the antibody served as the statistical analysis index, with the corresponding 95% confidence interval (CI) calculated according. We evaluate the heterogeneity among studies using the I2. If I2<50%, the heterogeneity among the studies was low, and a fixed-effects model was used for combining. Conversely, the random effects model was used. The Egger's test combined with a funnel plot was used to evaluate publication bias, and sensitivity analysis was conducted using a one-by-one exclusion approach. Two-sided tests will be performed with a significance level of α=0.05.

 Results Literature screening process

After conducting an initial database search using the specified search terms, a total of 1902 articles identified. Around 566 articles were removed due to the duplication. Following the inclusion and exclusion criteria, 97 articles were ultimately selected ( Figure 1 ). Among these, 94 were written in Chinese while 3 were in English.

Flow chart of the literature screening.

 Study characteristics

The 97 included papers are all cross-sectional studies published between 2003 and 2023, encompassing seven geographical regions in China. The maximum sample size of the literature was 11013 and the minimum sample size was 197. The literature quality scores ranged from 5 to 8, with the highest score being 8 and the lowest score being 5 ( Table 1 ).

Study characteristics.

Author Province The year of study Subjects Age(years) Relevant factor* Quality score
Akezhong et al. (2016) (8) Qinghai 2014 364 <20 — 5
Cai ZK et al. (2003) (9) Fujian 2001 342 1-19 a、b 6
Chen JH et al. (2009) (10) Fujian 2007 1296 0-44 b、c 5
Cao H et al. (2014) (11) Tianjin — 210 0-24 a、d 5
Cao Y et al. (2017) (12) Chongqing 2014 3230 2-15 b 6
Feng YF et al. (2021) (13) Guangdong 2020 238 ≥0 — 6
Wang HL et al. (2016) (14) Zhejiang 2014 2491 0-60 — 7
Zhang H et al. (2009) (15) Fujian 2007 477 0-44 a 6
Gong H et al. (2016) (16) Sichuan 2016 224 ≥0 a、c、d 6
Chen SJ et al. (2018) (17) Sichuan — 287 ≥0 — 5
Chen YW et al. (2022) (18) Fujian 2019 561 0-59 a、d 6
Li S et al. (2016) (19) Jiangxi 2015 307 0-9 — 6
Cheng J et al. (2011) (20) Hubei 2010 700 ≥0 — 6
Deng YB et al. (2016) (21) Xinjiang 2014 215 ≥0 a 5
Xianling Wang et al. (2010) (22) Tianjin 2007 608 0-57 — 6
Fan Y et al. (2020) (23) Sichuan 2018 2107 ≥0 a、d 5
Li L et al. (2022) (24) Guangdong — 389 ≥0 d 7
Geng LN et al. (2017) (25) Jiangsu 2012 500 0-40 d 5
Gu F et al. (2012) (26) Henan 2010 363 2-25 — 6
Guan TJ et al. (2013) (27) Guangdong — 359 ≥0 — 5
Guo W et al. (2013) (28) Shandong 2011 328 ≥0 — 5
Hao BY et al. (2023) (29) Tianjin 2020 290 0-44 a、d 7
He PQ et al. (2016) (30) Gansu 2015 585 0-49 6
He Q et al. (2023) (31) Guangdong 2020 1099 ≥0 a、b、c 8
Hu JYet al.(2008) (32) Shanghai 2005 714 0-40 — 5
Hu YL et al. (2017) (33) Henan — 1155 — — 6
Hu YG et al. (2018) (34) Sichuan 2012、2016 428 ≥0 — 6
Xing WY et al. (2018) (35) Jiangsu、Guangxi 2010 420 0-15 — 5
Huang C et al. (2023) (36) Guangxi — 1322 0-69 a、d 6
Yang C et al. (2019) (37) Guangxi 2017 322 0-20 — 6
Huang N et al. (2018) (38) Guizhou 2016 240 ≥0 d 6
Ye N et al. (2021) (39) Sichuan 2018 210 ≥0 a 6
Lan X et al. (2018) (40) Sichuan 2015 681 ≥0 a、b、c、d 6
Sheng WH et al. (2022) (41) Guangdong 2020 240 ≥0 — 7
Yang AX et al. (2016) (42) Xinjiang 2015 239 0-45 — 6
Li JM et al. (2016) (43) Xinjiang 2014 1056 0-59 a 6
Li JL et al. (2013) (44) Shandong 2011 320 ≥0 — 6
Li P et al. (2009) (45) Shanxi — 225 1-14 b 5
Li WX et al. (2012) (46) Shandong 2010 661 2-14 — 6
Liu XL et al. (2020) (47) Shanxi 2013 366 ≥0 a、b 5
Ling X et al. (2020) (48) Liaoning 2017 2430 ≥0 d 6
Liu DS et al. (2018) (49) Jiangsu 2016 314 0-40 — 6
Xu CH et al. (2020) (50) Sichuan 2018 1901 ≥0 — 5
Liu Y et al. (2020) (51) Zhejiang 2016-2018 996 ≥0 a、d 7
Liu Y et al. (2020) (52) Chongqing — 736 ≥20 a 6
Liu Y et al. (2020) (53) Chongqing 2018 2855 1-30 a 7
Liu Y et al. (2023) (54) Sichuan 2022 1448 0-6 a、d 7
Lu HM et al. (2016) (55) Shanghai 2013 360 0-40 a、c 6
Lv WY et al. (2017) (56) Henan 2016 449 ≥0 — 7
Lv WY et al. (2016) (57) Henan 2015 420 ≥0 — 7
Yang Y et al. (2016) (58) Shanxi 2014 505 2-5 a、b、d 7
Wu MX et al. (2017) (59) Fujian 2016 415 ≥0 — 6
Ma Y et al. (2019) (60) Shanxi 2017 960 0-50 b、d 7
Zhang FX et al. (2013) (61) Shanxi 2011 280 ≥0 — 6
Pang H et al. (2009) (62) Shanghai — 241 — c 6
Qi QR et al. (2019) (63) Henan 2018 2120 2-15 a 6
Wang AQ et al. (2013) (64) Shandong 2011 320 ≥0 — 5
Wang XB et al. (2014) (65) Sichuan 2012 210 ≥0 — 5
Ruan JW et al. (2023) (66) Guangdong 2021 287 15-24 a、c 7
Sheng WH et al. (2015) (67) Guangdong 2012 319 ≥0 a、b 8
Shi ZH et al. (2016) (68) Hebei 2014 197 0-19 — 5
Shu XD et al. (2016) (69) Zhejiang 2015 290 ≥0 a、c、d 7
Tang XM et al. (2013) (70) Guizhou 2011 639 ≥0 — 7
Tuerhong·musa et al. (2021) (71) Xinjiang 2018 839 0-6 a、b、d 7
Wang CY et al. (2013) (72) Shandong 2009-2010 4001 ≥0 a 6
Wang J et al. (2023) (73) Henan 2019-2021 996 0-79 d 8
Wang MC et al. (2010) (74) Shandong 2009 245 ≥0 — 5
Wang T et al. (2012) (75) Beijing 2007 220 ≥0 c 5
Wang WS et al. (2022) (76) Liaoning 2020 498 ≥0 a 6
Wang YL et al. (2012) (77) Zhejiang 2009 384 ≥0 — 6
Wu R et al. (2018) (78) Xinjiang 2016 288 ≥0 a 6
Hu Y et al. (2013) (79) Jiangsu 2012 1502 ≥0 — 5
Wu FY et al. (2021) (80) Jiangxi 2015-2020 11013 ≥0 — 8
Xing QM et al. (2016) (81) Guangdong 2014 241 ≥0 a 6
Xu Q et al. (2015) (82) Shandong 2011 1599 15-24 a、c 6
Xuehelaiti·bayiding et al. (2018) (83) Xinjiang 2016-2017 360 ≥0 — 7
Zhu HM et al. (2015) (84) Jiangsu 2013 500 ≥0 — 5
Yan R et al. (2023) (85) Zhejiang 2020 4455 0-59 a、c、d 7
Zhang RP et al. (2016) (86) Chongqing 2014 2179 6-15 a、b 6
Yang JP et al. (2018) (87) Shanghai 2014 363 ≥0 — 6
Yang YN et al. (2023) (88) Henan 2021 630 1-79 a、d 7
Wang J et al. (2016) (89) Sichuan 2014 310 ≥0 — 6
Yang YY et al. (2022) (90) Shanghai 2010-2020 10828 ≥0 — 6
Ye ZD et al. (2021) (91) Sichuan 2018 349 0-15 a、d 8
Zhang AN et al. (2019) (92) Jilin 2015-2016 3289 15-26 a、b、c 7
Zhang FX et al. (2011) (93) Shanxi 2005 311 0-64 — 6
Zhang LW et al. (2009) (94) Beijing 2007 220 0-61 d 6
Cheng JQ et al. (2010) (95) Guangdong 2008 1003 0-60 a 6
Sun TT et al. (2023) (96) Henan 2021 550 1-79 a、d 7
Zhu HL et al. (2016) (97) Zhejiang 2011 242 ≥20 a 6
Cheng H et al. (2016) (98) Heilongjiang 2015 1381 — — 5
Luo J et al. (2013) (99) Guizhou 2011 210 ≥0 a、d 6
Luo FJ et al. (2008) (100) Beijing — 303 ≥0 — 5
Lai ZW et al. (2023) (101) Hunan 2020-2022 2691 0-19 a、d 7
Lin WY et al. (2015) (102) Guangdong 2012 1017 ≥0 a、c 7
Wang J et al. (2022) (103) Zhejiang — 4362 ≥0 a、b 7
Wang XZ et al. (2023) (104) Zhejiang — 778 ≥0 a、b、d 7

*—represents the relevant data was not mentioned in the original literature. Among the relevant factors, "a" represents gender, "b" represents urban area, "c" represents household registration, and "d" represents immunization history.

 Overall rubella seroprevalence

A total of 97 papers reported the seroprevalence of rubella in the population. The study encompassing 103,018 individuals, among whom 79,091 tested positive for antibodies. The highest positive rate was 98.20% while the lowest was 45.90%. Based on the random-effects model, the estimated positive rate of rubella antibody in the healthy Chinese population was 77.36% (95%CI:75.30-79.42,I2 = 98.50%).

 Rubella seroprevalence in different age groups

A total of 96 papers were included in the analysis, reporting rubella seroprevalence across different ages groups. After integration of the data by age group that was previously set, the stratified comparison revealed a significant difference in the positive rate of rubella antibodies among different age groups (χ2 = 121.76,P<0.001). The<1-year-old group exhibited the lowest positive rate at 47.71% (95%CI:41.25-54.16), while the ≥50-years-old group showed the highest positive rate at 85.43% (95%CI:81.01-89.85) ( Table 2 ).

The analysis results of the positive rate of rubella antibodies in each subgroup.

Subgroup No. of studies Rubella positive Total 95%CI (%) Heterogenity χ2 P
I2 (%)
Age (y)
<1 54 2696 7714 47.71 (41.25,54.16) 95.7 121.76 <0.001
1-4 69 13699 15809 85.26 (82.21,88.30) 93.9
5-9 70 8473 11124 78.34 (75.17,81.51) 94.2
10-14 33 4033 5759 74.00 (66.78,81.22) 98
15-19 59 9119 11947 76.47 (71.68,81.27) 96.2
20-34 32 6941 8586 81.43 (78.54,84.32) 88.8
35-49 20 1614 2045 82.55 (78.67,86.44) 83.2
≥50 18 1287 1572 85.43 (81.01,89.85) 89.5
Gender
Male 46 20689 25912 78.28 (74.95,81.62) 97.7 0.15 0.7
Female 46 19490 24228 79.18 (76.10,82.26) 97.1
District
Urban 15 7606 9162 79.50 (73.49,85.50) 95.6 0.1 0.757
Rural 15 9367 11420 78.12 (71.75,84.49) 95.8
Registration
permanent population 13 8581 10868 79.45 (73.25,85.64) 98.7 0.24 0.63
migrant population 13 3245 4115 77.52 (72.87,82.17) 90.2
Regions of China
East China 24 28981 38673 77.68 (73.88,81.48) 98.8 6.62 0.358
Southwest 18 14131 18244 74.01 (68.75,79.27) 98.9
Northwest 14 5444 6593 80.40 (74.76,86.03) 95.2
South China 17 7790 9927 76.53 (71.32,81.73) 96.3
North China 7 2082 2804 77.16 (71.79,82.54) 91.3
Central China 12 14700 19515 79.13 (72.88,85.38) 99.4
Northeast 4 6181 7598 82.52 (77.55,87.48) 96.4
Immunization history
0dose 21 1744 3002 58.23 (47.20,69.25) 98.6 15.44 0.002
1dose 25 3068 3945 77.46 (73.01,81.92) 90.6
≥2dose 24 7922 9994 80.45 (76.36,84.55) 96.3
Unknown 12 3698 4723 80.61 (77.23,84.00) 82.8
The year of study
2001-2008 9 3709 5191 70.42 (62.17,78.68) 97.3 3.26 0.35
2009-2013 28 14808 18652 78.17 (74.28,82.25) 97.1
2014-2018 47 37413 48737 75.15 (71.79,78.51) 98.7
2019-2022 21 14581 20077 75.21 (70.38,80.04) 99.1
Rubella seroprevalence in different gender groups

A total of 46 papers reported the seroprevalence of rubella across genders. The analysis revealed the positive rate of rubella antibody of 78.28% (95%CI:74.95-81.62) in males and 79.18% (95%CI:76.10-82.26) in females. There was no significant difference observed in the positive rate of rubella antibodies between the different gender groups (χ2 = 0.15,P=0.70) ( Table 2 ).

 Rubella seroprevalence in different district groups

A total of 15 papers reported the seroprevalence of rubella in different districts. The results showed that the positive rate of rubella antibody was 79.50% (95%CI:73.49-85.50) in the urban population and 78.12% (95%CI:71.75-84.49) in the rural population. There was no significant difference in the positive rate of rubella antibodies in different district groups (χ2 = 0.10, P=0.76) ( Table 2 ).

 Rubella seroprevalence in different registration groups

A total of 13 papers reported the seroprevalence of rubella in different registrations. The results showed that the positive rate of rubella antibody was 79.45% (95%CI:73.25-85.64) in permanent population and 78.12% (95%CI:71.75-84.49) in migrant population. No significant difference was found in the positive rates of rubella antibodies between the different registration groups (χ2 = 0.24, P=0.63) ( Table 2 ).

 Rubella seroprevalence among different regions of China

The Chinese provinces were categorized into seven regions according to their geographical location. The analysis revealed no significant difference in the positive rate of rubella antibody among different regions (χ2 = 6.99,P=0.32). The lowest positive rate of rubella antibody was 74.01%(95%CI:68.75-79.27) in the southwest region, while the highest positive rate was 82.52%(95%CI:77.55-87.48) in the northeast region ( Table 2 ).

 Rubella seroprevalence among groups with different immunization history

There was a significant difference observed among the different immunization history groups (χ2 = 8.2, P=0.02). The lowest positive rate of rubella antibody was 58.23% (95%CI:47.2-69.25) in the population with no RCV vaccination history, and the highest positive rate was 80.45% (95%CI:76.36-84.55) in the population with histories of receiving at least 2 doses of RCV ( Table 2 ).

 Rubella seroprevalence among different the year of study

After integration of the data by the groups of study year that previously set, the results of integration showed that the lowest rubella antibody positive rate was 70.42% (95%CI:62.17-79.56) during 2001-2008, while the highest value was 78.17% (95%CI:74.28-82.05) during 2009-2013. There was no significant difference in the positive rate of rubella antibodies among different registration groups (χ2 = 3.26,P=0.35) ( Table 2 ).

 Sensitivity analysis and publication bias

By conducting sensitivity analysis involving the stepwise exclusion of included studies, the results remained consistent with the original findings, indicating the stability of the meta-analysis results. The publication bias was not found in this Meta-analysis, which was confirmed by using Egger's test (P=0.08) and shown in Figure 2 . (Each point represents the included article).

The funnel plots assessing the publication bias in the study of rubella antibody levels in the healthy Chinese population.

 Discussion

In 2012, WHO established the goal of rubella elimination as part of the "Global Measles and Rubella Strategic Framework 2012-2020". In 2015, the WHO Region of the Americas verified that 35 countries and regions within that region were eliminated rubella. The World Health Organization's Western Pacific Region (WPRO), to which China belongs, set a goal for rubella elimination in 2014 (3). As of 2021, several WPRO member countries and regions, including Australia, Brunei, New Zealand, South Korea, Macau, and Hong Kong, have declared rubella elimination (105, 106). In the “Global Measles and rubella Strategic Framework 2021-2030” issued by WHO in 2021, it is pointed out that strengthening the control and elimination of rubella can be combined with measles. The framework aims to achieve and maintain regional elimination of measles and rubella by 2030 (107). While seroepidemiological survey data can reflect the epidemiological characteristics of rubella, routine monitoring of rubella seroprevalence has not been conducted in China. It is resulting in a lack of comprehensive and dynamic control and understanding. This paper conducted a meta-analysis to explore the level of rubella antibody in healthy people in China from the whole to the extraction of relevant influencing factors.

The WHO has indicated that achieving the rubella seroprevalence of over 83% to 85% is necessary to establish robust herd immunity (80). Our study showed that the rubella seroprevalence in healthy people in China was 77.36%, lower than the standard recommended by WHO. Weak immunity threshold levels can lead to an increased incidence of rubella in high-risk populations and an increased risk of CRS in children.

To enhance rubella prevention and control efforts, RCV was incorporated into the immunization program in China in 2008, and the positive rate of rubella antibody has increased significantly since 2009. From this study, it can be seen that when there was no large-scale introduction of RCV, the rubella seroprevalence can be as low as 45.9% (9). The introduction of the vaccine has significantly increased the rubella seroprevalence in the population. It was found that the rubella seroprevalence increased with the increase in vaccination dose, which was consistent with the results of Wang Jun et al. (73). Similarly, a study in Beijing on the detection of measles and rubella seroprevalence in children aged 18-24 months after multiple doses of the MMR vaccine found that the antibody positive rate and antibody Geometric mean concentration (GMC) increased significantly after multiple doses. The positive rate of rubella antibody increased from 97.22% to 100%, and the GMC reached (283.52 ± 90.83)IU/ml (108). Although a single dose of MMR can obtain more than 95% long-term immunity (109), the annual decline rate of seroprevalence of a single dose vaccine is 0.014 (0.012-0.017), showing an exponential attenuation. After receiving two doses of MMR, the decline rate of seroprevalence decreased to 0.012 (0.010-0.014) (110). Multiple doses of vaccine, such as two or more, can enhance the seroprevalence and promote immune persistence in healthy individuals.

Several factors influence the level of rubella antibody. Based on the findings of this study, age and vaccination history emerge as significant factors that impact the level of rubella antibody. The modified immunization schedule has significantly contributed to the variations in rubella seroprevalence across different age groups.

The rubella immunization schedule in China involves administering the RCV at 8 months and 18 months of ages, respectively (111). The majority of children aged 1-4 years have a history of RCV, leading to a higher positive rate of antibodies. Conversely, children below 8 months of age have not yet reached the age for RCV and depend on maternally-derived antibodies. Additionally, Zhu Q et al. showed that newborn measles and rubella antibody levels increased with the increase of maternal antibody levels (118). However, since the mothers of infants included in this analysis were born in the period when rubella vaccine was not widely administered, fewer were vaccinated, most of which were immune after tacit infection with rubella virus (119). Consequently, the level of maternal antibodies has decreased, which is associated with the low antibody positivity rate observed in children under 1-year-old. Since the current RCV program primarily focuses on children, the positive rate of rubella antibody starts to decrease after the age of 5. Studies have shown that individual antibody levels decrease over time in the absence of widespread virus transmission (121). This finding may be one of the reasons why antibody levels drop after age of 5. The relevant studies have demonstrated that the risk of rubella will increase with time (112), and the use of rubella vaccine in children cannot reduce the incidence of rubella in adolescents and adults (113). Currently, the main affected population for rubella in China is concentrated among middle school students (3), and in the outbreak of rubella in 2018-2019, the age of onset was concentrated in the 10-29 age group (105). In response to this phenomenon, Zhejiang Province implemented intensified RCV immunization for the third-year middle school students. After enhanced immunization of 15-19 age group, the positive rate of rubella antibody and GMC were significantly higher than those of 10-14 age group (114). Therefore, administering RCV to rubella-susceptible populations, such as adolescents and adults who failed to respond to the primary vaccination, can compensate for the immunological gap created by basic childhood immunity (3, 117). This could prevent and control adult rubella epidemics (114). Individuals aged 35 and above, who were born before the inclusion of RCV in the national expanded immunization program have had more opportunities for exposure to infectious sources, which has led to higher levels of naturally acquired antibodies. According to the data of a study on the introduction of RCV in the immunization program, the annual incidence of rubella decreased from 91.09 cases per million to 3.31 cases per million after the vaccine was widely used. This means that most people at that time had a higher risk of exposure to rubella, which may be one of the reasons for the high positive rate of rubella in older age groups (120). It may be one of the reasons for the high positive rate of rubella in older age groups.

There was no statistically significant difference in rubella seroprevalence between genders, which is consistent with the majority of findings in the Chinese literature (29, 71, 94). Our study with age-specific subgroup analysis revealed a relatively low prevalence of rubella seropositivity among women of reproductive age. It may lead to an increased risk of CRS infection, and there is a need to strengthen the immunity threshold levels in this age group (115). The reduction of CRS occurrence in the United States was achieved by recommending one dose of MMR for adults, based on the implementation of two doses of MMR for children (115). Similarly, a 75% reduction in the number of cases of CRS in schoolgirls vaccinated with the RCV was achieved in the United Kingdom (116). These findings suggest that women of childbearing age who are either unvaccinated or do not have sufficient evidence of rubella-specific immunity may benefit from receiving the RCV to boost their seropositive level.

Our study has several limitations. First the included studies were predominantly cross-sectional, which are susceptible to measurement bias and non-response bias. Second, some primary studies lacked adequate analysis of study factors, had small sample sizes, or focused on narrow age groups, contributing to increased heterogeneity in the literature. Third, our study adopts the commonly used definition in the literature of antibody positive rate, which is more than 20 IU/ml. However, there are variations in definitions across studies, with some using a threshold of more than 10 IU/ml or lacking a clear definition altogether, potentially leading to non-unique meta-analysis results. In view of these issues, we adopted a strategy of expanding the number of papers and broadening the coverage of time and geographical dimensions to minimize the impact on the results and uphold scientific rigor to a certain extent.

 Conclusion

In conclusion, to achieve the goal of rubella elimination, China needs to implement a comprehensive strategy that integrates rubella disease surveillance and serological testing. This approach should be built upon a high vaccination coverage rate for RCV within the immunization program. Furthermore, it is crucial to timely targeted immunization efforts for high-risk groups, such as middle school students and women of childbearing age, to enhance their immunity against rubella. By establishing a robust rubella immunity threshold levels, significant reductions can be achieved in the harm caused by rubella and its associated complications.

 Data availability statement

The datasets presented in this article are not readily available because you need to send an email request before using this data. Requests to access the datasets should be directed to smileforever81@126.com.

 Author contributions

YZ: Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Resources, Software, Validation, Visualization, Writing – original draft, Writing – review & editing. ZL: Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Resources, Software, Validation, Writing – original draft, Writing – review & editing. XCZ: Investigation, Methodology, Writing – review & editing. XPZ: Investigation, Methodology, Writing – review & editing. YY: Writing – review & editing, Data curation, Formal analysis, Software. JH: Data curation, Formal analysis, Software, Writing – review & editing. JD: Formal analysis, Software, Validation, Writing – review & editing. YX: Project administration, Software, Validation, Writing – review & editing. YL: Conceptualization, Supervision, Writing – review & editing. CF: Conceptualization, Supervision, Writing – review & editing.

 Funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This study was supported by Zhejiang Provincial Basic Public Welfare Research Projects (grant number: LGF22H260013).

 Conflict of interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

 Publisher’s note

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

 References Winter AK Moss WJ . Rubella. Lancet (London England). (2022) 399:1336–46. doi: 10.1016/S0140-6736(21)02691-X Lambert N Strebel P Orenstein W Icenogle J Poland GA . Rubella. Lancet (London England). (2015) 385:2297–307. doi: 10.1016/S0140-6736(14)60539-0 Su QR . Study on the supplementary immunization strategy to eliminate measles and rubella in China. China: Chinese Center for Disease Control and Prevention (2018). The National Health Commission of the People's Republic of China . The National Health Commission of the People's Republic of China on the issuance of the implementation plan of the Expanded Programme on lmmunization Vol. 03). China: Gazette of the National Health Commission of the People's Republic of China (2008) p. 17–21. Li YQ Ma C Hao LX Wang FZ Wen N Yang H . Epidemiology of rubella in China, 2018-2019. Chin J Vaccines Immunization. (2021) 27:62–6. doi: 10.19914/j.CJVI.2021003 Hu YH Luo XF Lyu M Yin DP . A Meta-analysis on varicella-zoster virus seroprevalence in healthy population in China. Chin J Epidemiol. (2021) 09):1650–61. doi: 10.3760/cma.j.cn112338-20210308-00185 Li MM Yuan DF Liu YX Liu YB Wang B . Meta analysis on mumps virus seroprevalence and evaluation of immunization effect in Chinese healthy population. Chin J Epidemiol. (2022) 07):994–1003. doi: 10.3760/cma.j.cn112150-20220402-00313 Kezhong A YJ Z SC Z LX F WP Z Qi GH . Analysis on measles and rubella seroprevalence among Healthy population in Huangyuan County and Guide County in 2014. J Med Pest Control. (2016) 32:832–4+7. doi: 10.7629/yxdwfz201608003 Cai ZK Pan WY Yang XH Zhou Y Zhang HR . Surveillance of rubella immunity in urban and rural population aged 1-19 years in Fujian Province. Strait J Prev Med. (2003) 9:58. doi: 10.3969/j.issn.1007-2705.2003.04.031 Chen JH Zhang H Cai XQ . Results Analysis on Monitoring seroprevalence of Rubella among Health Population in Fuzhou City in 2007. Occupation Health. (2009) 25:2201–3. doi: 10.13329/j.cnki.zyyjk.2009.20.031 Cao H . Survey on Epidemiological Characteristics and the seroprevalence of Measles, Rubella and Mumps among the Healthy Population. China: Tianjing Medical University (2015). Cao Y Tian YQ Yang DM Kang XL Zhang RP Yang F . Surveillance on measles, rubella and mumps seroprevalence and measures for disease prevention of children in Fuling district, Chongqing. Modern Prev Med. (2017) 44:1232–5,47. doi: CNKI:SUN:XDYF.0.2017-07-020 Feng YF Zeng XY . Surveillance and analysis of measles, rubella and varicella lgG seroprevalence in healthy people in Liwan District, Guangzhou City in 2020. Prog Microbiol Immunol. (2021) 49(05):67–70. doi: 10.13309/j.cnki.pmi.2021.05.011 Wang HL Zhang H Gong HX Huang LJ Cheng JB . Monitoring measles, rubella, mumps and varicella seroprevalence in healthy people in Zhoushan. Int J Epidemiol Infect Disease. (2016) 43(1):39–42. doi: 10.3760/cma.j.issn.1673-4149.2016.01.010 Zhang H Huang XX Cheng JH . Analysis on measles and rubella seroprevalence in migrant population in Fuzhou City, 2007. Chin J Viral Diseases. (2009) 11(5):347–9. doi: 10.16505/j.2095-0136.2009.05.022 Gong H Zhang B Chen X C . Measles antibody and rubella seroprevalence among healthy population in 2016 in chenghua district in chengdu city. J Prev Med Inf. (2018) 34(05):660–3. doi: CNKI:SUN:YFYX.0.2018-05-029 Chen SJ . Analysis of the monitoring results of measles, rubella and mumps seroprevalence in healthy people in a certain area. Health Guide. (2018) 2018:368. doi: 10.3969/j.issn.1006-6845.2018.47.361 Chen YW Jia HM Miu L . Results Analysis on Monitoring seroprevalence of measles and rubella among Health Population in Fuzhou City in 2019. J Appl Prev Med. (2022) 28:533–5. doi: 10.3969/j.issn.1673-758X.2022.06.009 Li S Tan CS Chen JH . Analysis of the seroprevalence of the vaccine against the disease in pingxiang children under the age of 10. Drug Evaluation. (2016) 13(21):41–4. doi: 10.3969/j.issn.1672-2809.2016.21.010 Cheng J Huo XX Zhang C Zhan FX Yang BF Zhan JB . Analysis of immune levels against measles, rubella and mumps in healthy population in Hubei province. Chin J Health Lab Technology. (2011) 21:2737–8,41. doi: CNKI:SUN:ZWJZ.0.2011-11-057l Deng YB Sheng RL Tang SP . Results Analysis on Monitoring seroprevalence of Measles and Rubella among Health Population in Jinghe County. Endemic Dis Bulletin(China). (2016) 31:40–1,72. doi: 10.13215/j.cnki.jbyfkztb.1512022 Wang XL Ding YX . The antibodies levels of measles, mumps and rubella in residents, Tianjin. Chin Prev Med. (2010) 11(5):491–4. doi: 10.16506/j.1009-6639.2010.05.014 Fan Y He WQ Liu YQ Wen XY . Monitoring result of measles and rubella igG seroprevalence in healthy population in mianyang city in 2018. Occup Health Damage. (2020) 35:168–72. li Li Wang Y QR Y Liu Y Fang QY . Investigation of seroprevalence of measles, rubella and mumps in Huizhou, Guangdong province. Modern Dis Control Prev. (2022) 33(12):939–42. doi: 10.13515/j.cnki.hnjpm.1006-8414.2022.12.014 Geng LN Suan GW Wu SN . Evaluation of rubella seroprevalence in health people in Xinyi City. Chin J School Doctor. (2017) 31:751–3. doi: CNKI:SUN:XIYI.0.2017-10-015 Gu F Wang X Wei WQ Zhao XL Lei CL . Surveillance on immunity levels of hepatitis B, measles, rubella, Japanese encephalitis, epidemic cerebrospinal meningitis among healthy populations in wolong district, nanyang city, 2010. Prev Med Tribune. (2012) 18:676–8. doi: 10.16406/j.pmt.issn.1672-9153.2012.09.019 Guan TJ Huang H Zheng YK Zhu HX . Surveillance on immunity levels of rubella among populations in zhuhai city. Med Information. (2013) 7):254. 10.3969/j.issn.1006-1959.2013.07.250 Guo W Wang Y Yu H Yu XQ Wang J Wang ZY . Survey on levels of measles, rubella and mumps antibodies among normal population, dezhou city. Prev Med Tribune. (2013) 19:106–7+11. doi: 10.16406/j.pmt.issn.1672-9153.2013.02.012 Hao BY Lu HZ Shao HM Zhang JL Ren L Wang LJ . Monitoring and analysis of measles, mumps and rubella seroprevalence among healthy people in binhai new area of tianjin in 2020. Med Information. (2023) 36:60–3. doi: 10.3969/j.issn.1006-1959.2023.17.011 He PQ Wang YM . Investigation on measles, rubella seroprevalence in Anding district of Dingxi city, 2015. Chin J Public Health Management. (2016) 32:504–6. doi: 10.19568/j.cnki.23-1318.2016.04.027 He Q Xu Y Li YL Luo L Zhu PT . seroprevalence against measles, rubella, and mumps among healthy people in Guangzhou: a cross-sectional survey in 2020. Chin J Vaccines Immunization. (2023) 29:392–6. doi: 10.19914/j.CJVI.2023067 Hu JY Sheng J Tang SW Wang JG . Analysis on immunity to rubella among healthy people in Shanghai. Int J Biologicals. (2008) 31:200–2. doi: 10.3760/cma.j.issn.1673-4211.2008.05.003 Hu LY Cheng GJ Li FK Xing ZH . Investigation of seroprevalence of measles and rubella in the urban of Nanyang City. Modern Dis Control Prev. (2017) 28:516–7. doi: 10.13515/j.cnki.hnjpm.1006-8414.2017.07.013 Hu YG Wang AB Guo J Gao Y luan RS . Surveillance of the antibodies against five vaccine-preventabl diseases among healthy population in Deyang City. Int J Virology. (2018) 25:349–53. doi: 10.3760/cma.j.issn.1673-4092.2018.05.017 Xing WY Gao L Zhu LS Zhao PB Xu WB Hu RP . A retrospective survey of rubella seroprevalence among 0-15 year old healthy children and new mothers in two regions of China. Chin J Vaccines Immunization. (2018) 24(4):412–6. doi: 10.19914/j.cjvi.2018.04.009 Huang C Tang JF Liang LZ Gan WY Nong CS . Investigation of seroprevalence to measles, rubella and mumps in healthy populations of Nanning City in 2017-2019. J Community Med. (2023) 21:599–605. doi: 10.19790/j.cnki.JCM.2023.12.01 Yang C Pei JX Liang BY Qing JQ Nong CS Huang C . Surveillance and control strategies of measles and rubella mumps’ seroprevalence in healthy population in Nanning in 2017. Chin J Health Lab Technology. (2019) 29(23):2825–27,2832. doi: CNKI:SUN:ZWJZ.0.2019-23-003 Huang N . Results Analysis on Monitoring seroprevalence of Rubella among Health Population in Changshun County in 2016. Diet Health. (2018) 5:281–2. doi: 10.3969/j.issn.2095-8439.2018.19.348 Ye N Zhou YS Huang QJ . seroprevalence of measles, rubella and mumps in healthy population in renshou county in 2018. Occup Health Damage. (2021) 36(5):286–90. Lan X Wei XP Zhou XL Huang XM . Rubella seroprevalence in healthy people in panzhihua city in 2015. J Prev Med Inf. (2018) 34(2):169–72. doi: CNKI:SUN:YFYX.0.2018-02-012 Shen WH Lv YL Liao MT Lun XE Jian MT . Survey on seroprevalence of rubella and pertussis in whole population of zhaoqing city in 2020. Chin Community Doctors. (2022) 38(19):151–3. doi: 10.3969/j.issn.1007-614x.2022.19.051 Yang AX Li F . Analysis of immune level of EPI targeted diseases in Kuitun, Xinjiang. Bull Dis Control Prevention(China). (2016) 31(2):22–4,43. doi: 10.13215/j.cnki.jbyfkztb.1510030 Li JM Li X Huang YL . Monitoring and analyzing the levels of measles and rubella antibodies among healthy people in Karamay in 2014. Modern Prev Med. (2016) 43(18):3409–12. doi: CNKI:SUN:XDYF.0.2016-18-037 Li LJ Qiu DS Guan EF . Survey on levels of measles, rubella and mumps antibody among healthy population, weifang city,2011. Prev Med Tribune. (2013) 19:28–9. doi: 10.3969/j.issn.1005-5673.2013.01.012 Li P Si Y Guang RH . Levels of antibodies of measles,mumps and rubella in children of Shaanxi. Chin J Public Health. (2009) 25:1229–30. doi: 10.11847/zgggws2009-25-10-40 Li WX Wang CY Song LZ Fang XQ Xu Q . Survey on levels of measles, mumps and rubella antibodies among normal children in the west of shandong province,2010. Prev Med Tribune. (2012) 18:184–6. doi: 10.16406/j.pmt.issn.1672-9153.2012.03.013 Liu XL Hu GX Liang LL . Epidemiological characteristics of rubella and seroprevalence in healthy population in Tongchuan City, Shaanxi Province, China. Chin J Biologicals. (2020) 33(11):1276–9,1291. doi: 10.13200/j.cnki.cjb.003198 Lin Q Zhang M Zhang Y . Survey on establishment of rubella immune barrier in natural population in Dalian City. Occupation Health. (2020) 36:371–4. 10.13329/j.cnki.zyyjk.2020.0098 Liu DS Song XZ Liu XY . Survey on seroprevalence of measles, rubella and mumps in healthy population in suining county in 2016. Chin J School Doctor. (2018) 32:112+4. doi: CNKI:SUN:XIYI.0.2018-02-014 Xu CH He JL Tong WB Liu L . Levels of antibody to measles, rubella and mumps viruses in a healthy population in Sichuan province in 2018. Chin J Exp Clin Virology. (2020) 34(01):29–32. doi: 10.3760/cma.j.issn.1003-9279.2020.01.006 Liu Y Xu YY Zhang XC Yuan HY Suan XJ Chen J . IgG seroprevalence against rubella among a healthy population in Hangzhou city, 2016-2018. Chin J Vaccines Immunization. (2020) 26:517–20. doi: 10.19914/j.cjvi.2020.05.007 Liu Y Li WW Zhang YY . Surveillance on measles and rubella seroprevalence among couples in a preconception care program in Hechuan District of Chongqing Municipality. Pract Prev Med. (2022) 29:112–4. doi: 10.26914/c.cnkihy.2023.035263 Liu Y Wu YY Wang Q . seroprevalence of measles and rubella among healthy population aged 1-30 years in Chongqing municipality. Pract Prev Med. (2020) 27:1220–2. doi: 10.3969/j.issn.1006-3110.2020.10.016 Liu Y Liu Y Li YQ Liu JJ Liu LJ Yang Q . Measles, rubella, and mumps seroprevalence among 0-6-year-old children in Sichuan province in 2022. Chin J Vaccines Immunization. (2023) 29:508–11. doi: 10.19914/j.CJVI.2023088 Lu HM Sheng JH Cheng WH Zhu Q Gu SK . Surveillance of measles, rubella and mumps seroprevalence in healthy population in Songjiang District, Shanghai. Chin J Biologicals. (2016) 29:51–6. doi: 10.13200/j.cnki.cjb.001201 Lv WY Shi LB Wang Y Feng DX Li GW Yang JH . seroprevalence of measles, rubella and mumps in a healthy population in Henan province,2016. Chin J Vaccines Immunization. (2017) 23:393–6,418. doi: 10.19914/j.cjvi.2017.04.009 Lv WY Wang Y Shi LB Feng DX Li GW Yang JH . Antibody levels of measles, rubella and mumps in a healthy population in Henan Province in 2015. Chin J Vaccines Immunization. (2016) 22:530–2,14. doi: 10.19914/j.cjvi.2016.05.011 Yang Y Cheng ZJ Hou TJ Wu R Liu JF Ma CF . Seroprevalence of Antibody against Measles and Rubella among Children Aged 2-5 Years in Xi'an City of Shaanxi Province. Chin J Vaccines Immunization. (2016) 22(04):395–8+394. doi: 10.19914/j.cjvi.2016.04.008 Wu MX Li JY Ma SS . Analysis of Immune level of Measles and Rubella in Huli district in 2016. Strait J Prev Med. (2017) 23(6):3. doi: CNKI:SUN:HXYF.0.2017-06-020 Ma Y Hu WJ Lv T Zhang XY Liu CS Zhang XH . Measles, rubella and mumps seroprevalence in healthy people in Shaanxi province, 2017. Chin J Vaccines Immunization. (2019) 25:405–8+35. doi: 10.19914/j.cjvi.2019.04.010 Zhang FX Li HC Si Y Ma Y . Survey on seroprevalence of measles, rubella and mumps in healthy population in zhidan county. Chin J Dis Control Prev. (2013) 17(11):2. doi: CNKI:SUN:JBKZ.0.2013-11-026 Pang H Zhang ZS Liu HL Xu YS . Investigation of measles, rubella and varicella igG seroprevalence among migrant and native pupils in changning district of shanghai. Chin J Vaccines Immunization. (2009) 15:223–5. doi: 10.19914/j.cjvi.2009.03.014 Qi QR Yang ZJ Sun LN . Surveillance and analysis of rubella seroprevalence in school-age children in Hualong district, Puyang City. Appl Prev Med. (2019) 25(1):2. doi: CNKI:SUN:GXYX.0.2019-01-020 Wang AQ Cheng GZ Qiu DS . Survey on the seroprevalence of measles, rubella and mumps among the normal healthy population in Weifang. Prog Microbiol Immunol. (2013) 41(01):52–4. doi: 10.3969/j.issn.1005-5673.2013.01.012 Qiu XB He G . Analysis of measles, rubella and mumps seroprevalence in healthy people in Suining City. J Prev Med Information. (2014) 30:682–3. doi: CNKI:SUN:YFYX.0.2014-08-029 Ruan JW Hong LC Hu PW Yu JT Yu MH Cheng H . Investigation on seroprevalence of measles, rubella, and mumps among freshmen in Shenzhen in 202. Modern Prev Med. (2023) 50:3999–4003. doi: 10.20043/j.cnki.MPM.202305505 Sheng WH Kong DL Li BH Zhu BL Liao TM Li YH . Investigation of seroprevalence of Measles, Rubella and Mumps among Whole Population in Zhaoqing, Guangdong Province, 2012. Chin J Vaccines Immunization. (2015) 21:519–23,42. doi: 10.19914/j.cjvi.2015.05.010 Shi ZH Niu HM Li Q Huo T . Monitoring and analysis of measles and rubella IgG seroprevalence in healthy people in Gaobeidian city in 2014. Electronic J Clin Med Literature. (2016) 3:7273–4. doi: 10.16281/j.cnki.jocml.2016.36.122 Shu XD Zhao H Ping JM Xu LR . Analysis of the serum seroprevalence of measles and rubella in healthy population of Yinzhou District, Ningbo. Chin J Health Lab Technology. (2016) 26:3306–9,22. doi: CNKI:SUN:ZWJZ.0.2016-22-037 Tang XM Zhu Q Ye XF Ren G Xu F . Investigation of rubella seroprevalence in healthy population in rural area of Guizhou Province. Guizhou Med J. (2013) 37:348–50. doi: 10.3969/j.ISSN.1000-744X.2013.04.024 Turhong MUSA Ayiguzaili SIMAYI Liu SD Wu M . Surveillance of seroprevalence of measles and rubella among healthy children aged from 9 months to 6 years. Bull Dis Control Prevention(China). (2021) 36:50–3. doi: 10.13215/j.cnki.jbyfkztb.2010001 Wang CY Xu Q Song LZ Fang XQ Li WX Xu AQ . Analysis on serum levels of rubella antibodies among healthy people in shandong province. Chin J Vaccines Immunization. (2013) 19(4):4. doi: CNKI:SUN:ZGJM.0.2013-04-014 Wang J Yuan YL . Surveillance of seroprevalence of measles, rubella and mumps in healthy people in Jiaozuo city of Henen province, 2019-2021. Modern Dis Control Prev. (2023) 34:452–6. doi: 10.13515/j.cnki.hnjpm.1006-8414.2023.06.012 Wang MC Bu JQ Miao W Hu SF Song YJ Li R . Investigation on seroprevalence of measles, rubella and epidemic mumps in rizhao healthyPopulation. Occupation Health. (2010) 26:1980–1. doi: 10.13329/j.cnki.zyyjk.2010.17.016 Wang T . Monitoring of rubella and mumps seroprevalence among healthy population in changping district beijing. Pract Prev Med. (2012) 19:45–7. doi: 10.3969/j.issn.1006-3110.2012.01.015 Wang WS An XH Zhu LJ Zhao L Han LX Fang X . Serological analysis on antibody levels to measles, rubella and mumps in healthy people in different age groups in Liaoning, 2020. Dis Surveillance. (2022) 37:1290–3. doi: 10.3784/jbjc.202203210110 Wang YL Ling GW . Surveillance results of measles and rubella immunity in Xianju County. Zhejiang Prev Med. (2012) 24:30–1. doi: 10.19485/j.cnki.issn1007-0931.2012.07.009 Wu R Xue SF Zhang YT Kang JJ Zhang WQ . seroprevalence of measles and rubella in a healthy population in Bole city of Xinjiang Uygur Autonomous Region, 2016. Chinese. J Vaccines Immunization. (2018) 24:422–+8. doi: 10.19914/j.cjvi.2018.04.011 Hu Y Lu PS Deng XY Liu YB Leng HY Wu Y . Analysis of measles, rubella and mumps seroprevalence in healthy people in Jiangsu province in 2012. Chin J Health Laboratory. (2013) 23(12):2650–4. doi: CNKI:SUN:ZWJZ.0.2013-12-032 Wu FY He RW Wu ZL Xu F Zheng M Zhao HP . Measles and rubella seroprevalence in healthy population of JiangXi, 2015-2020. Modern Prev Med. (2021) 48:1160–4. Xing QM Su N Wu DP . Surveillance on immunity levels of measles, rubella, tetanus, varicella among healthy populations in Panyu district, GuangZhou. J Med Pest Control. (2016) 32:723–5+8. doi: 10.7629/yxdwfz201607005 Xu Q Wang CY Fang XQ Song LZ Li WX Liu XD . Analysis on serum level of antibodies of measles and rubella among college students in shandong. Chin J Vaccines Immunization. (2015) 21(5):515–8. doi: CNKI:SUN:ZGJM.0.2015-05-011 Xuehelaiti· B Yeerjiang· B . Comparative Analysis of seroprevalence of Measles, Rubella and Mumps among Different Healthy People in Qapqal County. World Latest Med Information. (2018) 18:7–8+43. doi: 10.19613/j.cnki.1671-3141.2018.69.004 Zhu HM Pan YZ Xue M . Investigation on the seroprevalence of measles rubella and mumps in Wujin district of ChangZhou City. Zhejiang Prev Med. (2015) 27(01):55–56+59. doi: 10.19485/j.cnki.issn1007-0931.2015.01.015 Yan R Li JR Zhou Y He HQ Deng X Tang XW . Rubella seroprevalence among 0-59-year-old healthy people of Zhejiang province in 2020. Chin J Vaccines Immunization. (2023) 29:300–4. doi: 10.19914/j.CJVI.2023051 Zhang RP Yang DM Tian YQ Cao Y Kang XL Wang XM . Surveillance on measles, rubella and mumps seroprevalence of primary and secondary school students in Fuling district of Chongqing. Chin J School Health. (2016) 37(5):721–3. doi: 10.16835/j.cnki.1000-9817.2016.05.025 Yang JP Li XJ Xu HQ Wang Y Wang Y Yang XT . Surveillance of measles, rubella and mumps seroprevalence in healthy population in Baoshan District, Shanghai. Chin J Biologicals. (2018) 31:276–9+86. doi: 10.13200/j.cnki.cjb.002120 Yang YN Tong ZQ Yang S . Monitoring of measles and rubella seroprevalence among people aged 1-79 years in a district of Luoyang city, Henan province in 2021. Modern Dis Control Prev. (2023) 34(4):280–2,302. doi: 10.13515/j.cnki.hnjpm.1006-8414.2023.04.010 Wang J Gan L He AX Yang YF . Analysis of seroprevalence of measles, rubella, mumps of healthy population in Yingshan in 2014. J North Sichuan Med College. (2016) 31:126–9. doi: 10.3969/j.issn.1005-3697.2016.01.36 Yang YY Tang SW Tang W Fan JL Li Z Yang JW . seroprevalence of measles, rubella and mumps viruses in healthy population in Shanghai from 2010 to 2020. Chin J Prev Med. (2022) 56:1095–100. doi: 10.3760/cma.j.cn112150-20211116-01057 Ye ZD Zhang X Chen X Zhang J Yuan P . Measles, rubella and mumps seroprevalence in healthy population under 15 years in zigong city in 2018. J Prev Med Information. (2021) 37:472–7. Zhang AN . Investigation on the seroprevalence of measles and rubella in college students in jilin province. China: Jilin University (2019). Zhang FX He L Wu RQ Wu JN Yang WL Yang XD . Monitoring Result of rubella seroprevalence in healthy population in Yanan city. Chin Prev Med. (2011) 12:454. doi: CNKI:SUN:ZGYC.0.2011-06-002 Zhang LW . Surveillance on rubella seroprevalence in healthy population in Changping district in Beijng, 2007. Dis Surveillance. (2009) 24:181–2. doi: 10.3784/j.issn.1003-9961.2009.03.09 Cheng XZ Li SG Ma HW Shan FX Mo J Lin LQ . Rubella seroprevalence among immigrant workers in Shenzhen. Chin J Public Health. (2010) 26(10):1330–1. doi: 10.11847/zgggws2010-26-10-66 Sun TT Zhang YJ . Investigation on seroprevalence of 6 vaccines preventabl diseases among healthy people in a county of Zhumadian city, 2021. Bull Dis Control Prevention(China). (2023) 38(3):17–20. doi: 10.13215/j.cnki.jbyfkztb.2303024 Zhu HL Ji JM He B . Epidemiological characteristics and control effect of rubella in jiaxing city, Zhejiang province, 2004-2013. Chin Rural Health Service Administration. (2016) 36:749–51. doi: CNKI:SUN:ZNWS.0.2016-06-025 Cheng H Guo MY Wang Y Jiang QL . Analysis of four kinds of seroprevalence in healthy people in Qiqihaer City. Sci Technological Innovation. (2016) 35):78. doi: 10.3969/j.issn.1673-1328.2016.35.066 Luo J Wu GX Tang XM . Monitoring Result of rubella seroprevalence in healthy population in Changshun County in 2011. World Latest Med Information. (2013) 29):215–,7. doi: 10.3969/j.issn.1671-3141.2013.29.184 Luo FJ Liu F Zhang XX Zhang J Wang C Wang HW . Investigation on the seroprevalence of rubella and mumps among the floating population in Chaoyang District, Beijing. Chin J Epidemiol. (2008) 07):741–2. doi: 10.3321/j.issn:0254-6450.2008.07.031 Lai WZ Zhang SJ Fang ML Li FC Nie Y Li H . Rubella seroprevalence in a healthy population 0-19 years of age in three counties of Hunan province, 2020-2022. Chin J Vaccines Immunization. (2023) 29:655–60. doi: 10.19914/j.CJVI.2023114 Lin W Wang D Xiong Y Tang H Liao Z Ni J . Rubella seroprevalence among the general population in dongguan, China. Japanese J Infect diseases. (2015) 68:192–5. doi: 10.7883/yoken.JJID.2014.255 Wang J Xu Y Wang X Liu Y Zhang X Du J . Epidemiological characteristic of rubella by age group during 12 years after the national introduction of rubella vaccine in Hangzhou, China. Hum Vaccines immunotherapeutics. (2022) 18:2054208. doi: 10.1080/21645515.2022.2054208 Wang X Xu Y Zhang X Zhang X Du J Che X . Do adolescents need a rubella vaccination campaign Rubella serosurvey among healthy children in Hangzhou, China. Hum Vaccines immunotherapeutics. (2023) 19:2254536. doi: 10.1080/21645515.2023.2254536 Liu Y Xu WB Zhu Z . Progress in control and elimination of rubella in China. Natl Med J China. (2021) 48):3981–6. doi: 10.3760/cma.j.cn112137-20211009-02229 Plotkin SA . Rubella eradication: not yet accomplished, but entirely feasible. J Infect Dis. (2021) 224:S360–s6. doi: 10.1093/infdis/jiaa530 World Health Organization . Measles and rubella strategic framework 2021-2030. Geneva: World Health Organization (2020). Available at: https://www.who.int/publications/i/item/measles-and-rubella-strategic-framework-2021-2030. Wang FS Peng XR Xiao L Liu Y Wang HJ Li B . Monitoring and analysis of successful rate of basic mumps immunization as well as multiplecropping effects of measles and rubella induced by measles-mumps-rubella vaccine in Shunyi District, Beijing, China in 2015. Chin J Biologicals. (2016) 29:844–6. doi: 10.13200/j.cnki.cjb.001429 Zhan HC Chen YH Huang CH Chen WT . The analysis of epidemiology of rubella in Quanzhou province China, 2008-2015. J Dis Monitor Control. (2016) 10:903–5. Schenk J Abrams S Theeten H Van Damme P Beutels P Hens N . Immunogenicity and persistence of trivalent measles, mumps, and rubella vaccines: a systematic review and meta-analysis. Lancet Infect diseases. (2021) 21:286–95. doi: 10.1016/S1473-3099(20)30442-4 National Health Commission of the People's Republic of China . Circular of the National Health Commission on lssuing the lmmunization Procedures and Instructions for Children Under the National lmmunization Program(2021 edition) Vol. 02). China: Gazette of the National Health Commission of the People's Republic of China (2021) p. 13–22. Xu Q Xu AQ Song LZ Zhang L Xiao ZK Wang CY . Analysis on the changing of age patterns among rubella patients after rubella vaccine immunization for children in Shandong province, China. Chin J Epidemiol. (2005) 11):33–5. doi: 10.3760/j.issn:0254-6450.2005.11.007 A.Orenstein W A.Offit P M.Edwards K Stanley A . Plotkin. In: Plotkin's vaccines, 8th Edition. Elsevier, UK (2023). He HQ Xie SY Li Q Yan R Zhou Y Deng X . Serologic and Epidemiological Effect of Rubella-containing Vaccine lmmunization Activities among Third-year Students of Middle School in Some Areas of Zhejiang Province. Chin J Vaccines Immunization. (2016) 22:20–3. doi: 10.19914/j.cjvi.2016.01.004 World Health Organization . Rubella vaccines:WHO position paper-July 2020 (2020). Available online at: https://www.who.int/publications/i/item/WHO-WER9527. (Accessed July 3, 2020) Ding YX Liu Y Xu EY Chang LM Su QR Gou HC . lmmunogenicity and safety of measles, mumps and rubella combined attenuated live vaccine in revaccination of children and in vaccination of childbearing-age women. Chin J Vaccines Immunization. (2017) 23:365–8. doi: 10.19914/j.cjvi.2017.04.002 Chen ZF Zhou Y Yang XH Chen JL Li D Zhang SH . Epidemiological characteristics of rubella before and after introduction of rubella vaccine into the immunization program in Fujian province. Chin J Vaccines Immunization. (2019) 25(01):37–40+53. doi: 10.19914/j.cjvi.2019.01.009 Zhu Q Hu TJ Shen JW Shen JH Chen WH Gu SK . A study on measles and rubella antibody level in 319 pairs of mothers and infants in Songjiang District of Shanghai. Chin Med J. (2019) 53:388–93. doi: 10.3760/cma.j.issn.0253-9624.2019.04.011 Ma R Xu GZ Ma C An ZJ Xu HJ Ma YH . Change of rubella antibody transferred by mother in infants. Chin J Vaccines Immunization. (2009) 15:429–31. doi: 10.19914/j.cjvi.2009.05.016 Su Q Ma C Wen N Fan C Yang H Wang H . Epidemiological profile and progress toward rubella elimination in China. 10 years after nationwide introduction of rubella vaccine. Vaccine. (2018) 36:2079–85. doi: 10.1016/j.vaccine.2018.03.013 Huzly D Hanselmann I Neumann-Haefelin D Panning M . Performance of 14 rubella IgG immunoassays on samples with low positive or negative haemagglutination inhibition results. J Clin Virol. (2016) 74:13–8. doi: 10.1016/j.jcv.2015.11.022