Descriptive analysis for respiratory infectious diseases
There were 537,506 cases of respiratory infectious diseases in total in Shandong Province over the study period. Table 1 shows the incidence of each respiratory infectious disease in study area during the study period. No cases were notified in diphtheria during the study period. Ten other respiratory infectious disease types were reported during the study period, with annual average incidences ranging from 0.001 to 36.450 per 100,000. It was difficult to analyze the spatial-temporal clusters of diphtheria and severe acute respiratory syndrome (SARS). Therefore, the two diseases were not incorporated in the next analysis.
The temporal distribution of respiratory infectious diseases
The monthly incidence of each respiratory infectious disease is shown in Fig. 1. The time series of influenza A (H1N1) indicated outbreaks of influenza A (H1N1) occurred in the winter of 2009, with the highest monthly incidence (1.96 per 100,000) in November 2009 and sporadic in other years (See Fig. 1A). The monthly incidence of measles had an obvious seasonal increase in spring and peaked in March 2008 (2.13 per 100,000). The incidence of measles dropped significantly after 2010 and then stabilized (See Fig. 1B). The monthly incidence rate of tuberculosis is between 4 per 100,000 and 5 per 100,000, which peaked in late winter and early spring, mainly from January to April. The incidence of tuberculosis gradually decreased since 2014 (See Fig. 1C). From 2005 to 2014, the monthly incidence of meningococcal meningitis showed a significant downward trend, with peaking in late spring, early summer (May-June) and winter (December, See Fig. 1D). The incidence of pertussis was stable and low during the study period (< 0.1 per 100,1000, See Fig. 1E). The monthly incidence of scarlet fever remained relatively stable in 2005–2009, but began to increase rapidly since 2010. The incidence of scarlet fever showed a bimodal seasonal pattern with a peak occurring in summer and a peak occurring in winter (See Fig. 1F). The incidence of influenza rapidly increased since 2009 with strong seasonality in winter, and its peak occurred in December 2009 (1.39 per 100,000, See Fig. 1G). The incidence of mumps was relatively stable during the study period with a fluctuation in 2012 (See Fig. 1H). The time series indicated outbreaks of rubella occurred in March 2006 with the monthly incidence rate of 1.65 per 100,000 (See Fig. 1I).
The spatial distribution of respiratory infectious diseases
The spatial distribution of respiratory infectious diseases in Shandong Province is shown in Fig. 2 and Fig. S2 (See Supplementary Fig. 2, Additional File 1). The incidence of influenza A (H1N1) was relatively dispersed, and the top three counties with the higher incidence were Sifang District in Qingdao (10.6 per 100,000), Fushan District in Yantai (8.6 per 100,000) and Taishan District in Taian (6.1 per 100,000, See Fig. 2A). After spatial empirical Bayesian smoothing, the highly incidence of influenza A (H1N1) occurred in Jinan and Northwest Shandong (See Supplementary Fig. 2A, Additional File 1). There were 13 counties in the incidence of influenza A (H1N1) with ER above 4, such as Wudi County and Huimin County in Dezhou, and there were 26 counties with ER greater than 1 and less than 4 (See Supplementary Fig. 3A, Additional File 1). The incidence of measles is high in Northwest and South Shandong with average annual incidence rate of 6.5 per 100,1000 to 15.0 per 100,1000 (See Fig. 2B). The result of measles after Bayesian smoothing was consistent with that of Natural Break classification (See Supplementary Fig. 2B, Additional File 1). There were 60 counties in the incidence of measles with ER greater than 1 (See Supplementary Fig. 3B, Additional File 1). We can see that tuberculosis struck all counties, with a higher incidence in West Shandong, Northwest Shandong and Southeast Shandong from the thematic map and Bayesian smoothing map of tuberculosis (See Fig. 2C & See Supplementary Fig. 2C, Additional File 1). The highest annual incidence of tuberculosis was in Dongping County in Taian (62.7 per 100,000), followed by Qingyun County in Dezhou (60.6 per 100,000). ER above 1 covered 72 counties in the ER map of tuberculosis (See Supplementary Fig. 3C, Additional File 1). The incidence of meningococcal meningitis was relatively low in the whole Shandong, with a higher incidence in Liaocheng, Heze, Jining and Linyi (See Fig. 2D). After Bayesian smoothing, the incidence of meningococcal meningitis decreased in Northern and Central Shandong (See Supplementary Fig. 2D, Additional File 1). The ER map of meningococcal meningitis showed 55 counties with ER greater than 1 (See Supplementary Fig. 3D, Additional File 1). The incidence of pertussis was also relatively low in Shandong province, with a higher incidence in Northwestern Shandong and Southern Shandong (See Fig. 2E). After Bayesian smoothing, it showed that the incidence of pertussis decreased in Pingyuan County in Dezhou and increased in Central Shandong (See Supplementary Fig. 2E, Additional File 1). The ER of 49 counties was greater than 1 (See Supplementary Fig. 3E, Additional File 1). The spatial distribution of scarlet fever showed that the high incidence of scarlet fever was distributed in the eastern coastal area and Central Shandong, with a high incidence in Jinan, Zibo, Yantai and Yantai (See Fig. 2F). The result of scarlet fever after Bayesian smoothing was consistent with that of Natural Break classification (See Supplementary Fig. 2F, Additional File 1). The ER of 45 counties was greater than 1 (See Supplementary Fig. 3F, Additional File 1). The spatial distribution of influenza showed that West Shandong (such as Liaocheng, Dezhou, Heze and Jinan) had higher incidence of influenza than others and the counties with the top incidences of influenza were Pingyuan County in Dezhou (33.3 per 100,000), Central District in Jining (31.7 per 100,000) and Yucheng County-level city in Dezhou (29.2 per 100,000, Fig. 2G & See Supplementary Fig. 2G, Additional File 1). There were 45 counties in the incidence of influenza with ER above 1 (See Supplementary Fig. 3G, Additional File 1). A higher incidence of mumps was in Binzhou, Jinan and Taian. The top average annual incidences of mumps were in Guorao County in Dongying (44.3 per 100,000), Shizhong District in Jining (41.6 per 100,000) and Rencheng County in Jining (35.0 per 100,000, Fig. 2H & See Supplementary Fig. 2H, Additional File 1). The ER map of mumps showed 59 counties with ER greater than 1 (See Supplementary Fig. 3H, Additional File 1). The spatial distribution of rubella showed that the areas with high incidence of rubella were in northern Shandong and Middle Shandong, such as Binzhou, Dongying, Jinan and Binzhou. The highest average annual incidence of rubella was in Huantai County in Zibo (13.6 per 100,000, Fig. 2I & See Supplementary Fig. 2I, Additional File 1). The ER map of rubella showed there were 69 counties with ER above 1. Among them, the ERs of rubella in Changle County, Gaoqing County and Changdao County were higher than other counties (See Supplementary Fig. 3I, Additional File 1).
Spatial autocorrelation analysis
The result of global spatial autocorrelation analysis showed that the Moran’s I of average annual incidence of each respiratory infectious disease in Shandong Province ranged from 0.062 to 0.353. This result indicated that there was an evident spatial correlation blinding the cases of respiratory infectious diseases except meningococcal meningitis (Table 2). Only those counties whose local Moran’s I had reached the significance level of 0.05 were presented on the LISA cluster maps. The local spatial autocorrelation analysis showed that the incidence of each respiratory infectious disease in Shandong Province had an obvious clustering (See Fig. 3). The LISA result of influenza A (H1N1) showed that there were 5 HH cluster regions (i.e., hotspots), which were mainly concentrated in Qingdao and Jinan. While there were 14 LL cluster regions (i.e., coldspots), which were mainly concentrated in Yantai, Weifang and Linyi (See Fig. 3A). As seen in Fig. 3A, Gaomi, Jimo, Longkou and Penglai were LH cluster regions, and municipal district of Heze, municipal district of Jining, municipal district of Dezhou were HL cluster regions. For measles, the 23 HH cluster regions were mainly located in South Shandong and Dezhou, while the 34 LL cluster regions were mainly located in Northeast Shandong (See Fig. 3B). As seen in Fig. 3B, Zaozhuang and Linyi displayed a LH cluster feature, and municipal district of Zibo, Jimo, municipal district of Yantai displayed a HL cluster feature. We identified 24 HH cluster regions for tuberculosis, which were primarily concentrated in Binzhou, Liaocheng and Linyi. While 30 LL cluster regions were identified for tuberculosis, which were primarily concentrated in Weifang, Zibo and Yantai (See Fig. 3C). As seen in Fig. 3C, the LH cluster regions of tuberculosis were scattered in Dezhou, Heze and Jining, and the HL cluster regions were mainly distributed in Yantai. For meningococcal meningitis, we identified 4 HH cluster regions, 18 LL cluster regions, 8 LH cluster regions and 6 HL cluster regions (See Fig. 3D). There were 20 HH cluster regions for pertussis, mainly distributed in North Liaocheng and South Dezhou, Ju County, Juancheng County, Yuncheng County, Cangshan County and Central District of Zaozhuang. While, there were 46 LL cluster regions, mainly distributed in Northeast Shandong. We also identified 7 LH cluster regions and a HL cluster region (See Fig. 3E). The 8 HH cluster regions and 31 LL cluster regions for scarlet fever were mostly from counties in Qingdao, Weifang, Laiwu, South Shandong and Dezhou. Some counties in Qingdao, Weifang, Jinan, Rizhao and Dezhou were identified for LH or HL cluster regions (See Fig. 3F). The LISA result of influenza showed that there were 14 HH cluster regions, which were mainly concentrated in Dezhou and Jining. While there were 25 LL cluster regions, which were mainly concentrated in Yantai, Weifang and Qingdao (See Fig. 3G). And 10 LH cluster regions and 3 HL cluster regions were identified for influenza (See Fig. 3G). For mumps, the 10 HH cluster regions were mainly located in Dongying, while the 22 LL cluster regions were mainly located in Yantai, Weifang, Rizhao (See Fig. 3H). For rubella, we identified 7 HH cluster regions, 21 LL cluster regions, 8 LH cluster regions and 5 HL cluster regions (See Fig. 3I).
Spatial-temporal scanning analysis
Fig. 4 and Table S1(See Supplementary Table 1, Additional File 1) show that respiratory infectious diseases in Shandong Province had a non-random spatial and temporal distribution. The most likely cluster times for respiratory infectious diseases were in winter-and-spring during the study period except pertussis and mumps (See Supplementary Table 1, Additional File 1). But the most likely clusters in space were somewhat different for different respiratory infectious diseases (See Fig. 4).
The most likely cluster time for influenza A (H1N1) was November 2009, and the most likely cluster areas were mainly concentrated in Central Shandong and Eastern Shandong (74 counties in total), such as Zhucheng County-level city, Penglai County-level city, Rongcheng County-level city, Lijin County, municipal district of Weihai, etc. The cluster center was located at 36°77’ N, 119°22’ E, the cluster radius was 199.83 km, the average annual rate within this range was 27.1 per 100,000, and the RR was 39.79 (P<0.001, See Fig. 4A).
The most likely cluster time for measles was March 2008, and the most likely cluster areas were mainly concentrated in Southwest Shandong (66 counties in total), such as Laoling County-level city, Ningjin County, Huimin County, Ling County, Shanghe County, etc. The cluster center was located at 35°28’ N, 115°08’ E, the cluster radius was 292.83 km, the average annual rate within this range was 34.0 per 100,000, and the RR was 13.38 (P<0.001, See Fig. 4B).
The most likely cluster time for tuberculosis was January 2007, and the most likely cluster areas were mainly concentrated in Central Shandong and Northwest Shandong (58 counties in total), such as Wucheng County, Xiajin County, Pingyuan County, Gaotang County, Ling County, etc. The cluster center was located at 37°17’ N, 116°43’ E, the cluster radius was 183.32 km, the average annual rate within this range was 82.1 per 100,000, and the RR was 2.32 (P<0.001, See Fig. 4C).
The most likely cluster time for meningococcal meningitis was February 2005, and the most likely cluster areas were mainly concentrated in Southwest Shandong (56 counties in total), such as municipal district of Dezhou, Qihe County, municipal district of Jinan, Linqing County-level city, Changqing County, etc. The cluster center was located at 34°80’ N, 116°08’ E, the cluster radius was 230.36 km, the average annual rate within this range was 0.5 per 100,000, and the RR was 23.49 (P<0.001, See Fig. 4D). We also obtained one secondary cluster for meningococcal meningitis, which consisted of 37 cluster counties. The secondary spatial-temporal clusters were mainly in Central Shandong and Eastern Shandong (such as Lijin County, Laixi County-level city, Boxing County, Huantai County, municipal district of Zibo, etc.) during March 2005 (See Fig. 4D & See Supplementary Table 1, Additional File 1).
The most likely cluster time for pertussis was July 2007, and the most likely cluster areas were mainly concentrated in Southwest Shandong (22 counties in total), such as Yutai County, Jinxiang County, Tengzhou County-level city, etc. The cluster center was located at 35°00’ N, 116°65’ E, the cluster radius was 98.58 km, the average annual rate within this range was 3.5 per 100,000, and the RR was 21.44 (P<0.001, Fig. 4E). We also obtained two secondary clusters for pertussis, which consisted of 12 cluster counties. The secondary spatial-temporal clusters were mainly in Northwest Shandong (such as Pingyuan County, Ling County, Yucheng County-level city, etc.) during June 2010 and June 2005 (See Fig. 4E & See Supplementary Table 1, Additional File 1).
The most likely cluster time for scarlet fever was December 2011, and the most likely cluster areas were mainly concentrated in Central Shandong and North Shandong (64 counties in total), such as Zibo, Binzhou, Laiwu, Jinan, etc. The cluster center was located at 36°70’ N, 118°82’ E, the cluster radius was 168.54 km, the average annual rate within this range was 21.2 per 100,000, and the RR was 9.34 (P<0.001, See Fig. 4F).
The most likely cluster time for influenza were November 2009, and the most likely cluster areas were concentrated in Shizhong District and Rencheng District in Jining. The cluster center was located at 35°42’ N, 116°58’ E, the cluster radius was 0 km, the average annual rate within this range was 751.6 per 100,000, and the RR was 310.29 (P<0.001, See Fig. 4G). We also obtained three secondary clusters for influenza, which consisted of 77 cluster counties. The secondary spatial-temporal clusters were mainly in Northwest Shandong, Penglai County-level city, municipal district of Qingdao, Jiaozhou County-level city, etc. during December 2013, March 2010 and September 2009 (See Fig. 4G & See Supplementary Table 1, Additional File 1).
The most likely cluster time for mumps was June 2012, and the most likely cluster areas were mainly concentrated in Central Shandong and Northwest Shandong (72 counties in total), such as Lijin County, Qingyun County, Laoling County-level city, Ningjin County, Yangxin County, etc. The cluster center was located at 37°73’ N, 117°23’ E, the cluster radius was 239.96 km, the average annual rate within this range was 51.8 per 100,000, and the RR was 4.84 (P<0.001, See Fig. 4H). We also obtained one secondary cluster for mumps, which consisted of 1 cluster county. And the cluster time was July 2005 (See Fig. 4H & See Supplementary Table 1, Additional File 1).
The most likely cluster time for rubella was May 2005, and the most likely cluster areas were mainly concentrated in West Shandong (56 counties in total), such as Xiajin County, Gaotang County, Linqing County-level city, Wucheng County, Pingyuan County, etc. The cluster center was located at 36°85’ N, 115°70’ E, the cluster radius was 230.36 km, the average annual rate within this range was 190.5 per 100,000, and the RR was 122.07 (P<0.001, See Fig. 4I).