Epidemic risks of measles and rubella in China: a systematic review and meta-analysis

Search results

A total of 841 studies on measles (794 in Chinese and 47 in English) and 493 studies on rubella (473 in Chinese and 20 in English) seroprevalence were retrieved, published between 2012 and 2023 and covering 31 provinces in the Mainland of China. After considering the exclusion criteria, 135 measles seroprevalence studies (123 in Chinese and 12 in English) and 77 rubella seroprevalence studies (73 in Chinese and 4 in English) involving 368,023 and 177,422 healthy individuals, respectively, were included in this study. Of these studies, 60% (81/135) and 49.4% (38/77) reported the GMC of measles and rubella antibodies, respectively (Supplementary Fig. 2).

For the studies on measles, the sampling period ranged from 2010 to 2021, with the largest sample size being 43,982 and the smallest being 100 (Supplementary Table 1). The reported positive rate of measles IgG antibody ranged from 37.00% to 99.51%, of which 37% were from infants aged < 8 months in a study from Shanghai, China [14]. For the studies on rubella, the sampling period ranged from 2010 to 2022, with the largest sample size being 47,935 and the smallest being 210 (Supplementary Table 2). The reported positive rate of rubella IgG antibodies ranged from 54.63% to 97.81%.

Overall meta-estimated positive rate for measles and rubella IgG antibodies

Significant heterogeneity was observed in both measles (I2 = 99.13%, P < 0.001) and rubella (I2 = 99.16%, P < 0.001) studies; therefore, a meta-analysis was performed using a random-effects model. The overall meta-estimated positive rate of measles IgG antibody was 88.8% (95% CI = 87.37–90.16), which was higher than that of rubella (79.91%, 95% CI = 77.83–82) (Fig. 2). However, no significant difference was observed between the pooled positive rates of both measles (P = 0.871) and rubella IgG antibodies (P = 0.751) in males and females.

Fig. 2figure 2figure 2figure 2

The forest plots of pooled positive rate of measles (a) and rubella (b) immunoglobulin G antibodies. CI confidence interval

Temporal and geographic trends in the pooled positive rate of measles and rubella antibodies

The pooled positive rate of measles IgG antibodies fluctuated between 2010 and 2021 (P = 0.021). It remained relatively high, at 90.21% (95% CI = 82.52–94.73) and 93.73% (95% CI = 91.44–95.44) between 2010 and 2014. Except for 2016 (91.35%, 95% CI = 89.79–92.70) and 2020 (90.29%, 95% CI = 85.31–93.70), the positive rate during 2015–2021 was less than 90%, ranging from 85.19% (95% CI = 79.77–89.36) in 2019 to 89.38% (95% CI = 85.56–92.28) in 2018. For studies included from urban (94) and rural (48) areas, the pooled positive rate in rural areas was 91.93% (95% CI = 90.15–93.41), which was slightly higher than that in the urban areas (89.01%, 95% CI = 87.28–90.52) (P = 0.012). Furthermore, the pooled positive rate of measles antibodies differed significantly across the seven geographical regions (P < 0.001), with two regions (Northeast and Southwest) exhibiting rates higher than 92%. The other five regions had a relatively low rate, ranging from 84.86% (95% CI = 80.90–88.12) in East China to 90.78% (95% CI = 86.56–93.76) in Central China. The pooled positive rate showed a decreasing trend with an increase in economic level, from 91.75% (95% CI = 89.98–93.23) at level 5 to 81.39% (95% CI = 73.48–87.35) at level 1 (P < 0.001) (Table 1).

Table 1 Subgroup analysis results of the pooled positive rate of measles and rubella IgG antibodies

For rubella studies, a significant difference was found between the pooled positive rate of rubella IgG antibodies in the sampling years (P < 0.001). Between 2010 and 2012, the pooled positive rate of rubella IgG antibody ranged from 75.13% (95% CI = 70.46–79.81) to 79.16% (95% CI = 72.54–85.79), peaking in 2013 at 92.10% (95% CI = 88.37–95.84). Although the rate remained between 80.41% (95% CI = 75.33–85.49) and 83.98% (95% CI = 78.15–89.81) from 2014 to 2017, it reached its lowest level in 2018 (69.79%, 95% CI = 61.41–78.17). After a short recovery in 2019 (76.79%, 95% CI = 68.46–85.12) and 2020 (82.86%, 95% CI = 76.38–89.33), the rate was approximately 78% between 2021 and 2022. Among the included studies from urban (54) and rural (23) areas, no significant difference was observed between the pooled positive rates of the two areas (P = 0.806). The analysis based on geographical regions showed that the pooled positive rates ranged from 74.12% (95% CI = 67.97–80.27) in Southwest China to 85.76% (95% CI = 80.33–91.19) in Northeast China (P = 0.035), with only one region having rates higher than 85%. A difference was observed in the pooled positive rates among the different economic level groups (P = 0.030); however, no correlation was found between the economic level and pooled positive rate (Table 1).

Pooled positive rate of measles and rubella antibodies varied between age groups

Based on the age groups, data on the pooled positive rate of measles IgG antibodies were available for 103 of the 135 measles studies involving 109,628 healthy individuals. A significant difference between the pooled positive rates of the 12 age groups was observed (P < 0.001), with infants aged < 1 year having the lowest rate at 70.47% (95% CI = 65.25–75.44). Among the remaining 11 age groups, children aged 1–2 years (94.27%, 95% CI = 92.29–96.00), 3–4 years (94.26%, 95% CI = 92.70–95.66), and the elderly > 60 years (94.70%, 95% CI = 92.54–96.54) had relatively high pooled positive rates. Individuals aged 7–9 years (89.77%, 95% CI = 87.05–92.22) and 15–49 years [range: 88.97% (95% CI = 86.76–91.01)–90.83% (95% CI = 88.39–93.02)] had a pooled positive rate below 92% (Table 1).

Analysis based on each sampling year over the period of 2010–2021 showed that the pooled positive rates varied by age groups, with the lowest rates in infants aged < 1 year in all the sampling years, ranging from 53.69% (95% CI = 49.35–58.00) to 80.83% (95% CI = 69.62–90.04). For the other 11 age groups, a relatively lower pooled positive rate was found mainly in those aged 20–29 years between 2010 and 2012, ranging from 76.41% (95% CI = 60.37–87.32) to 89.08% (95% CI = 58.78–97. 90), and in those aged 30–39 years in 2010 (85.33%, 95% CI = 48.41–97.30) and 2011 (80.39%, 95% CI = 67.25–89.11). The pooled positive rate for both age groups has been below 92% since 2016, ranging from 80.91% (95% CI = 72.48–87.21) to 91.39% (95% CI = 89.35–93.24). Notably, a pooled positive rate of < 92% was observed in most age groups between 2018 and 2021. For example, in 2021, the rates for those aged 5–59 years were all lower, ranging from 69.82% (95% CI = 65.41–74.05) to 89.90% (95% CI = 69.56–97.20) (Fig. 3a).

Fig. 3figure 3

The 3D plots of pooled positive rate of measles (a) and rubella (b) immunoglobulin G antibodies based on different age groups and sampling years

Based on the age groups, the data on the pooled positive rate of rubella IgG antibodies were available from 63 out of 77 rubella studies involving 71,866 healthy individuals. Similar to measles, the meta-estimated positive rate for rubella IgG antibody varied significantly across the ten age groups (P < 0.001), with the lowest rate observed in infants aged < 1 year (49.49%, 95% CI = 41.67–57.32) and the higher rates in children aged 1–2 years (92.42%, 95% CI = 89.75–94.74) and 3–4 years (88.38%, 95% CI = 85.38–91.09). However, after the age of 5 years, the pooled positive rate gradually decreased with age and reached a relatively lower rate in children aged 10–14 years (76.76%, 95% CI = 71.79–81.39). From the age group of 15–19 years (80.78%, 95% CI = 76.89–84.41), the rate gradually increased and remained above 80%, while adults aged 20–29 years had higher rates (85.20%, 95% CI = 82.61–87.63) (Table 1).

Further analysis of each sampling year from 2010 to 2022 showed that the pooled positive rates of rubella IgG antibodies varied across all age groups in the different sampling years. Overall, the pooled positive rates were low in all age groups, except for the age groups 1–2 and 3–4 years. The lowest rates were found in infants aged < 1 year in each sampling year except for 2013, ranging from 28.81% (95% CI = 2.65–43.14) to 66.67% (95% CI = 34.40–88.41). In addition, the pooled positive rate for children aged 7–14 years was below 85% in all the sampling years, especially after 2017, when the rates remained at a low level of 57.37% (95% CI = 35.28–76.86) to 78.56% (95% CI = 61.13–91.96). Similarly, the rates among adolescents aged 15–19 years were lower after 2015, with a maximum of 81.73% (95% CI = 68.70–91.94) in 2020. Meanwhile, the rate in the 20–39 age group had a decreasing trend after 2019 from 81.54% (95% CI = 67.58–92.38) to 74.21% (95% CI = 68.45–79.23) (Fig. 3b).

Pooled positive rate is significantly affected by vaccination history

The pooled positive rates of both measles and rubella IgG antibodies were significantly influenced by vaccination history. The pooled positive rate of measles antibody was significantly lower in the unvaccinated population (59.44%, 95% CI = 49.95–68.60) compared to those vaccinated with only one dose (89.58%, 95% CI = 86.90–92.00) and those who had received more than two doses of vaccine (92.99%, 95% CI = 91.33–94.50) (P < 0.001). Similar to measles, the rate of rubella antibody in the unvaccinated population (52.84%, 95% CI = 40.76–64.75) was lower than in the population vaccinated with only one dose (80.48%, 95% CI = 75.55–84.99) and with more than two doses (85.85%, 95% CI = 81.53–89.69) (P < 0.001) (Table 1).

Estimated GMC of measles and rubella antibodies showed a U-shaped structure

The reported GMC of measles IgG antibody from 81 studies ranged from 288.78 to 1616.61 mIU/mL. The overall estimated GMC of measles IgG antibodies was 804.01 mIU/mL in a healthy population. For rubella IgG antibody, the reported GMC from 38 studies ranged from 19.24 to 146.10 U/mL, and the overall estimated GMC of rubella IgG antibody was 43.53 U/mL in a healthy population. No significant differences were observed between the GMC of measles and rubella IgG antibodies based on the sampling years, sex, urban and rural areas, geographical regions, and economic levels of the provinces, except for age group (P < 0.001) and vaccination history (P < 0.001) (Table 2).

Table 2 Geometric mean concentrations of measles and rubella antibodies based on the temporal, spatial, and population distribution

Among all age groups, infants aged < 1 year had the lowest estimated GMC for measles and rubella antibodies, with 569.38 mIU/mL and 15.86 U/mL, respectively. In contrast, the estimated GMC of measles and rubella antibodies in the other age groups showed a similar trend, with a U-shaped structure of high values at both ends. The highest GMC of measles and rubella antibodies was 1268.17 mIU/mL and 84.66 U/mL, respectively, in the age group of 1–2 years. Following this peak, the GMC gradually declined, reaching relatively lower levels in the 15–19 age group for measles (714.09 mIU/mL) and the 5–6 age groups for rubella (40.62 U/mL). However, the GMC of measles and rubella antibodies increased again, reaching higher levels in individuals aged > 50 years for measles (1160.46 mIU/mL in the 50–59 age group; 1088.92 mIU/mL in those aged ≥ 60 years) and in the 30–39 age group for rubella (58.42 U/mL) (Table 2).

Analysis based on vaccination history showed that the estimated GMC in the unvaccinated population was significantly lower (measles: 382.38 mIU/mL; rubella: 23.16 U/mL) than that in the vaccinated population (measles: 960.30 mIU/mL for one dose and 979.26 mIU/mL for two or more doses; rubella: 53.24 U/mL for one dose and 55.09 U/mL for two or more doses) (Table 2).

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