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A total of 2,220 HFRS cases were reported in Qingdao City from 2010 to 2022, and the average annual number of cases was 171. The annual incidence fluctuated between 0.75/100,000 and 3.35/100,000, and the average annual incidence was 1.89/100,000. The total number of deaths was 56, with a case fatality rate of 2.52% (Figure 2). From 2010 to 2019, the annual HFRS incidence in Qingdao was higher than that in Shandong Province, and the incidence in Shandong Province was higher than that in China (Figure 3).
Figure 2. Annual incidence and mortality of HFRS in Qingdao from 2010 to 2022. The figure above indicates the annual number of cases and incidence rate, and the below figure indicates the annual of death and fatality rate.
A total of 14 patients had been vaccinated against HFRS, including one patient who experienced vaccine breakthrough and 13 patients who received post-infection vaccination.
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Among the 2,220 HFRS cases, the peak incidence was 295 cases in 2012, and the minimum number of cases was 71 in 2020. The fall-winter peak (from October to January) was observed every year. The spring peak (from March to June) was not obvious, and a peak was not observed in several years (2010, 2018, and 2020; Figures 2 and 4).
Figure 4. Spatial distribution of cumulative HFRS cases in county/district level of Qingdao City from 2010 to 2022. The figure left indicates the cumulative number of HFRS case; the figure right indicates of the cumulative incidence rates of HFRS cases.
Male cases numbered 1,639 (73.8%), and the male: female ratio ranged from 3.7:1 in 2019 to 2.2:1 in 2013. A total of 75.3% (1,671/2,220) of patients with HFRS were between 16 and 60 years of age (Table 1). Most patients with HFRS were farmers (75.3%, 1,671/2,220), followed by workers (7.4%, 165/2,220) and homemakers/unemployed individuals (4.2%, 94/2,220; Table 2).
Year Gender Age Male (%) Female (%) <16 (%) 16-60 (%) >60 (%) 2010 142 (75.5) 46 (24.5) 3 (1.6) 149 (79.3) 36 (19.1) 2011 181 (77.4) 53 (22.6) 2 (0.9) 186 (79.5) 46 (19.7) 2012 211 (71.5) 84 (28.5) 4 (1.4) 235 (79.7) 56 (19.0) 2013 169 (68.7) 77 (31.3) 2 (0.8) 197 (80.1) 47 (19.1) 2014 152 (70.0) 65 (30.0) 3 (1.4) 169 (77.9) 45 (20.7) 2015 119 (76.8) 36 (23.2) 4 (2.6) 112 (72.3) 39 (25.2) 2016 73 (75.3) 24 (24.7) 0 (0) 75 (77.3) 22 (22.7) 2017 96 (76.2) 30 (23.8) 3 (2.4) 88 (69.8) 35 (27.8) 2018 135 (76.7) 41 (23.3) 4 (2.3) 129 (73.3) 43 (24.4) 2019 86 (78.9) 23 (21.1) 1 (0.9) 74 (67.9) 34 (31.2) 2020 54 (76.1) 17 (23.9) 0 (0) 53 (74.6) 18 (25.4) 2021 151 (72.9) 56 (27.1) 2 (1.0) 141 (68.1) 64 (30.9) 2022 70 (70.7) 29 (29.3) 1 (1.0) 63 (63.6) 35 (35.4) Total 1639 (73.8) 581 (26.2) 29 (1.3) 1671 (75.3) 520 (23.4) Note. HFRS, hemorrhagic fever with renal syndrome. Table 1. Characteristics of all 2220 HFRS cases in Qingdao City, 2010–2022
Occupation Number of cases Proportion (%) Farmer 1672 75.3 Worker 165 7.4 Housework/unemployment 94 4.2 Student 53 2.4 Cadre/staff 52 2.3 Migrant worker 49 2.2 Retired personnel 31 1.4 Self-employed 21 0.9 Business service 18 0.8 Others 65 2.9 Total 2220 100.0 Table 2. Occupational classification of all 2220 HFRS cases in Qingdao City, 2010–2022
Information on clinical symptoms was recorded between 2020 and 2022. Fever was the most common symptom (87.5%, 272/311), followed by fatigue (83.3%, 259/311) and rapid onset (66.9%, 208/311). Sixty-one (19.6%, 61/311) cases had typical “three redness” symptoms of blush, neck redness, and chest redness; 83 (26.7%, 83/311) cases had typical “three pain” symptoms of headache, orbital pain, and low back pain; and 36 cases (11.6%, 36/311) had both “three red” and “three pain” symptoms (Tables 3 and 4).
Symptom 2020 2021 2022 2020-2022 Number of cases Proportion (%) Number of cases Proportion (%) Number of cases Proportion (%) Number of cases Proportion (%) Rapid onset 40 76.9 105 63.3 63 67.7 208 66.9 Fatigue 41 78.8 145 87.3 73 78.5 259 83.3 Fever 49 94.2 139 83.7 84 90.3 272 87.5 Headache 31 59.6 106 63.9 51 54.8 188 60.5 Low back pain 25 48.1 87 52.4 29 31.2 141 45.3 Orbital pain 24 46.2 62 37.3 17 18.3 103 33.1 Blush 29 55.8 66 39.8 28 30.1 123 39.5 Neck redness 20 38.5 46 27.7 20 21.5 86 27.7 Chest redness 17 32.7 36 21.7 14 15.1 67 21.5 Joint pains 11 21.2 42 25.3 21 22.6 74 23.8 Whole body pains 9 17.3 63 38.0 20 21.5 92 29.6 Abdominal pain 12 23.1 45 27.1 30 32.3 87 28.0 Diarrhea 11 21.2 54 32.5 36 38.7 101 32.5 Constipation 9 17.3 2 1.2 4 4.3 15 4.8 Nausea 15 28.8 74 44.6 41 44.1 130 41.8 Vomiting 12 23.1 67 40.4 39 41.9 118 37.9 Conjunctival congestion 18 34.6 29 17.5 16 17.2 63 20.3 Puffy eyelids 12 23.1 27 16.3 16 17.2 55 17.7 Jaundice 5 9.6 4 2.4 6 6.5 15 4.8 Skin bleeding spots in the armpits, upper arms, chest, or other areas 14 26.9 25 15.1 10 10.8 49 15.8 Bleeding spots in the oral and nasal mucosa 6 11.5 12 7.2 1 1.1 19 6.1 Little or no urination 18 34.6 57 34.3 35 37.6 110 35.4 Hypotension 6 11.5 27 16.3 26 28.0 59 19.0 Shock 4 7.7 9 5.4 5 5.4 18 5.8 Normal leukocyte count 10 19.2 21 12.7 12 12.9 43 13.8 Increased leukocyte count 22 42.3 60 36.1 34 36.6 116 37.3 Decreased leukocyte count 4 7.7 3 1.8 5 5.4 12 3.9 Thrombocytopenia 22 42.3 71 42.8 43 46.2 136 43.7 Urinary protein 15 28.8 14 8.4 17 18.3 46 14.8 Urinary membrane/tubular urine/hematuria 2 3.8 5 3.0 3 3.2 10 3.2 Table 3. The main clinical symptoms among HFRS cases in Qingdao City in 2020-2022
Typical symptoms 2020 2021 2022 2020-2022 Number of cases Proportion (%) Number of cases Proportion (%) Number of cases Proportion (%) Number of cases Proportion (%) Three red 17 32.7 32 19.3 12 12.9 61 19.6 Three pain 19 36.5 51 30.7 13 14.0 83 26.7 Three red and three pain 11 21.2 21 12.7 4 4.3 36 11.6 Table 4. The main typical clinical symptoms among HFRS cases in Qingdao City in 2020-2022
Among the 56 cases of deaths, none of whom had been vaccinated, 41 were men (73.2%) and 15 were women (26.8%). The minimum, maximum, and median ages were 14, 85, and 53 years, respectively. Farmers, accounted for 75.0% of deaths. The shortest and longest courses of disease were 2 days and 44 days, respectively, and the maximum distribution was 7 and 8 days, which together accounted for 32.1% of all the deaths.
All the 10 districts or counties in the city had HFRS cases. The cumulative number of cases in the top three districts or counties was 757 in Huangdao District, 427 in Pingdu City, and 340 in Jiaozhou City, with cumulative incidences of 3.86/100,000, 2.41/100,000, and 2.92/100,000, respectively (Figure 4). All the 2,220 cases were distributed in 83.3% (120/144) of the streets/townships of Qingdao City, whereas the remaining 16.7% (24/144) streets/townships did not have cases. The top five streets/townships with the highest cumulative number of cases were Jiudian Town (Pingdu City, 78), Poli Town (Huangdao District, 74), Zhangjialou Town (Huangdao District, 72), Liuwang Town, (Huangdao District, 62), and Nancun Town (Pingdu City, 62; Figure 5 and 6).
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The seasonal trend was explored with a season-trend decomposition analysis using R software (Figure 7). A rhythmic vibration was observed in the raw data from 2010 to 2022. Seasonality and trend components from the raw data were isolated, and part of the random noise or reminder component was also eliminated. The HFRS epidemic showed two-peak seasonality each year, with a primary fall-winter peak and a minor spring peak. In addition, the HFRS epidemic showed a downward trend and periodic variation of decreasing amplitude and magnitude.
By summarizing the number of HFRS cases each year, we drew season index distribution and radar charts to more clearly visualize the monthly changes in the number of HFRS cases. The months with the largest seasonal indices were November and October, followed by December (Figure 8); these months represented the peak HFRS period. The period between January and September had a smaller seasonal index and showed a trough in HFRS cases.
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A global spatial autocorrelation analysis was performed based on street/township-level HFRS cases in Qingdao City. The annual global Moran’s I indexes, which ranged from 0.15 to 0.66, all passed the significance level test (P < 0.05), indicating that the spatial distribution of the HFRS epidemic was not random from 2010 to 2022 and showing t-shaped spatial autocorrelation characteristics at street/township-level scale. Moran’s I indexes showed an upward trend from 2010 to 2013, then an overall downward trend from 2014 onward. The distribution of the HFRS epidemic was significantly heterogeneous in Qingdao City from 2010 to 2022. (Table 5)
Year Moran’s I Z-value P-value 2010 0.43 5.80 0.001 2011 0.42 5.27 0.001 2012 0.66 8.18 0.001 2013 0.66 8.18 0.001 2014 0.30 4.38 0.001 2015 0.23 3.35 0.009 2016 0.18 2.35 0.017 2017 0.32 4.58 0.002 2018 0.42 5.49 0.001 2019 0.35 4.60 0.001 2020 0.15 2.18 0.02 2021 0.27 3.82 0.002 2022 0.16 2.42 0.013 Table 5. Global spatial autocorrelation analysis of reported HFRS cases in Qingdao City, 2010– 2022
A local indicators of spatial association analysis was performed to detect local (street/township-level) spatial clusters of the HFRS epidemic. From 2010 to 2022, the range of HFRS hot spots (High–High cluster area) in Qingdao City showed dynamic changes that were mostly distributed in Huangdao, Pingdu, and Jiaozhou (Figure 9).
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The incidence of HFRS was aggregated through space and time using Kulldorff’s spatio-temporal scan statistics. All the three significant clusters detected were located in the southern parts of Huangdao. The first cluster (RR = 3.14, log likelihood ratio [LLR] = 27.49) was in a 41.58 km radius from October to November 2012 and included 13 streets/townships; the expected case number was 20.1, and the observed case number was 61. The second cluster (RR = 4.55, LLR = 6.09) was in a 14.73 km radius from October to November 2017 and included four of the 13 streets/townships in the first and second clusters; the expected case number was 6.09, and the observed case number was 27. The third cluster (RR = 2.86, LLR = 11.61) was in a 49.16 km radius from October to November 2021 and included the same 13 streets/townships as the first cluster; the expected case number was 11.61, and the observed case number was 32. The spatio-temporal scanning results from 2010 to 2022 showed that the three cluster areas in Qingdao City were located in the south of Huangdao District during the fall-winter peak (Figure 10 and Table 6).
Figure 10. Spatio-temporal clusters of HFRS cases in Qigndao city at the street/township level, 2010–2022. The spatio-temporal scanning from 2010 to 2022 was conducted in three time periods. The left figure shows the results from 2010 to 2015, the middle figure shows the results from 2014 to 2019, and the right figure shows the results from 2018 to 2022. Most likely cluster: p-value<0.05.
Radius (Km) Occurrence time (year/month) Observed number of cases Expected number of cases LLR RR P Value Number of streets/townships 41.58 2012/10-2012/11 61 20.10 27.49 3.14 < 0.001 13 14.73 2017/10-2017/11 27 6.09 19.58 4.55 < 0.001 4 49.16 2021/10-2021/11 32 11.61 12.41 2.86 < 0.001 13 Table 6. Spatio-temporal clusters analysis of reported HFRS cases in Qingdao City, 2010– 2022
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A total of 4,081 rodents and shrews were captured using 111,154 valid snap-traps that were set between 2011 and 2015. The average capture rate of hosts was 3.56%, and the average hantavirus infection rate of hosts was 8.82% from 2011 to 2015 (Table 1). The R-squared values of the linear fit to the trend lines for the incidence of HFRS versus Rattus norvegicus density and total host density were 0.75 and 0.58, respectively (Figure 11).
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An overall decreasing trend in the incidence of HFRS in China has been observed in recent years[15,16,40,41]. However, HFRS has persisted under the current preventive measures that include rodent control and high-risk populations vaccination. The HFRS incidence rate in Qingdao is higher than that in Shandong Province and China (Figure 3). However, because the epidemic’s characteristics and the dynamic spatio-temporal distribution of HFRS in Qingdao City have not been systematically explored, this study analyzed these elements using case surveillance data from 2010 to 2022 at the street/township level in Qingdao.
The study revealed that the distribution of HFRS over the past 13 years in Qingdao City was regional, periodic and seasonal—consistent with the characteristics of the previous distribution of HFRS in Qingdao[28,38]. The top three districts or counties in the cumulative number of cases were Huangdao District, Pingdu City, and Jiaozhou City. Similarly, the results of the spatial autocorrelation analysis suggested spatial heterogeneity in the distribution of HFRS in Qingdao, with “high-high” clusters mostly dynamically distributed in Huangdao, Pingdu, and Jiaozhou. HFRS had a periodic epidemic peak approximately every 10 years. Results of this study showed that Qingdao had epidemic peaks in 2012 and 2021, which was roughly in line with a 10-year periodic distribution. The spatio-temporal scanning clusters were distributed in the south of Huangdao District at the time of the fall-winter peak, which conformed to the periodic distribution characteristics of HFRS. The Huangdao District consists of low-lying hills with forests and farmlands—a typical niche for the presence of hantavirus animal hosts. Consistent with the findings of previous studies, our results showed that each year, the incidence of HFRS in Qingdao City had a major epidemic season (October to January) and a minor seasonal peak (March to June) that corresponded to the epidemic peaks of HTNV-type HFRS and SEOV-type HFRS, respectively. These bi-peaks may be associated with the living habits of local mice. There is a trend of linear correlation between the incidence rate and the density of host (Figure 11 and Table 7). However, we have lacked systematic and refined host surveillance data until now to totally confirm these assumptions. Therefore, continuous and uninterrupted research is needed in host surveillance and causative agent detection in Qingdao City to guide targeted HFRS prevention and control strategies.
Year HFRS incidence Capture rate of hosts (%) hantavirus-positive rate (%) Apodemus agrarius Rattus norvegicus Mus musculus Rattus rattus Sorex araneus Cricetulus triton Cricetulus arabensis Total Apodemus agrarius Rattus norvegicus Mus musculus Rattus rattus Sorex Araneus Cricetulus triton Cricetulus arabensis Total 2011 2.68 0.05 1.11 0.74 0.42 0 0 0.02 2.34 0 0.54 0 0 0 0.54 2012 3.35 0.88 1.73 1.36 0.02 0.35 0.62 0.15 5.11 6.5 3.1 3.26 0 0 0 0 12.86 2013 2.77 0.84 0.97 1.19 0 0.61 0.69 0.01 4.31 3.3 5.4 2.31 0 0 0 11.01 2014 2.42 0.49 1.15 1.22 0.16 0.21 0.31 0.02 3.56 5.06 2.17 2.56 0 0 0 0 9.79 2015 1.72 0.45 0.77 0.98 0 0.06 0.1 0.14 2.5 2.78 6.5 0.64 0 0 0 9.92 Average 2.59 0.54 1.15 1.1 0.12 0.25 0.34 0.07 3.56 3.52 3.54 1.75 8.82 Table 7. Data of annual human HFRS incidence and host surveillance in Qingdao City, 2011–2015
HFRS is a natural infectious disease, and its main transmission occurs when people come into contact with mice and their excreta during work and life. Climate change, environmental alteration, and rapid urbanization and economic activities largely influence the HFRS incidence[42-44]. Physical labor in the fields, agricultural operations, and underdeveloped socioeconomic conditions are associated with the disease. The main susceptible population remains male farmers between 16 and 60 years of age. The higher risk of infection in male farmers compared with other groups may be attributable to their increased opportunity for contact with rodents. Given that most (75.3%) patients are farmers, strengthening the monitoring of the rodent situation and promoting education about HFRS prevention and control in rural areas are necessary. In addition, increasing residents' awareness of HFRS, actively conducting rodent prevention and control activities, and taking protective measures when engaging in high-risk behaviors can reduce disease occurrence.
The incidence (11.6%) of co-occurrence of typical “three red” and “three pain” between 2020 and 2022 was low. In contrast, consistent with the findings of previous studies[13,14,45,46], the proportion of gastrointestinal symptoms was relatively high (nausea 41.8%, vomiting 40.4%, and diarrhea 32.5%). HFRS is easily misdiagnosed because of the complex and diverse clinical symptoms in the early disease stages. Therefore, during the peak period of epidemic HFRS, clinicians should consider the possibility of HFRS if a suspicious or clear history of rodent contact exists and initial symptoms are mainly high fever with or without digestive symptoms.
Vaccination is the most effective measure for preventing epidemic HFRS[1,10]. Since 2008, China has included HFRS immunization in the expanded immunization plan, targeting high-risk townships in high-risk provinces and providing routine immunization to people aged 16–60 years. The population aged 60 years and above accounted for 23.4% of patients between 2010 and 2022, illustrating a shift in the high-prevalence age group of HFRS to above 60 years[16,22,43,44]. Broadening the age range of the vaccinated group is recommended. Among the 14 patients who were vaccinated against HFRS, 13 were vaccinated after infection, indicating that residents in areas with a high incidence of HFRS have insufficient awareness of the importance of HFRS vaccination. Therefore, strengthening HFRS vaccine knowledge is also necessary.
In the endeavor to prevent and control HFRS, several pivotal measures also should be undertaken. Firstly, there is an urgent need to bolster education and awareness regarding HFRS, especially during periods of peak incidence. This endeavor necessitates the elevation of public knowledge and comprehension of the disease, with a specific emphasis on high-risk regions, such as the southern area of Huangdao, where the frequency and intensity of promotional activities ought to be augmented. Secondly, rodent control measures must be vigorously implemented and seamlessly integrated with patriotic hygiene campaigns to forge a cohesive strategy for disease prevention. Regular rodent monitoring is also imperative to maintain vigilance and swiftly respond to any indications of rodent activity. Moreover, citizens must actively participate in daily preventative measures, emphasizing the significance of household hygiene and efficacious rodent control practices. It is of utmost importance to steer clear of potential sources of infection, such as contact with rodent urine or feces, and to adopt appropriate safety precautions when engaging in activities in rodent-dense areas.
Some limitations should be considered when interpreting our findings. First, because HFRS cases were identified by a passive surveillance system and we did not differentiate HTNV from SEOV infections, some bias may have been introduced. Second, given the gradual decrease in the area of cultivated land, the main occupation of many farmers is no longer agriculture; some farmers may also engage in other types of work. Thus, error may have been introduced during classification by occupation.
Epidemic Characteristics and Spatio-temporal Patterns of HFRS in Qingdao City, China, 2010–2022
doi: 10.3967/bes2024.092
- Received Date: 2023-10-27
- Accepted Date: 2024-04-29
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Key words:
- Hemorrhagic fever with renal syndrome /
- Epidemic characteristics /
- Spatio-temporal distribution
Abstract:
Citation: | LI Ying, LU Run Ze, DONG Li Yan, SUN Li Tao, ZHANG Zong Yi, ZHAO Ya Ting, DUAN Qing, ZHANG Li Jie, JIANG Fa Chun, JIA Jing, MA Hui Lai. Epidemic Characteristics and Spatio-temporal Patterns of HFRS in Qingdao City, China, 2010–2022[J]. Biomedical and Environmental Sciences. doi: 10.3967/bes2024.092 |