The Epidemic Dynamics And Related Influencing Factors Of Anthrax In Mainland China

Background: Anthrax is one of the ancient zoonoses caused by Bacillus anthracis. Bacillus anthracis is a sporulating Gram-positive bacterium that manifests a particular bimodal lifestyle: the vegetative phase and the spore phase. It is primarily a disease in herbivores and sometimes sparks outbreaks in human with potentially serious consequences. Human infection was usually a result of contacting ill animals during agricultural activities or processing contaminated animal products. Human anthrax can be classified into three forms: the cutaneous form, the gastrointestinal form, and the inhalational form. The disease occurs worldwide with an estimate of 20,000 to 100,000 new human cases each year. According to the World Health Organization, developing countries in Africa and those in central, southern Asia have the highest human incidences of anthrax. Because of its wide distribution, its potential use for bioterrorism and the emergence of “injectional anthrax” reported in Europe, anthrax is considered as a global public health threat. In the past twenty or thirty years, the modern information technologies have been widely applied in public health. It provided an effective technical support for the analyses of spatiotemporal distribution and associated agro-ecological, environmental and meteorological influencing factors of diseases. It has been pointed out that conditions in topsoil, meteorological factors may geographically regulate the distribution of anthrax infections in foreign literatures. However, studies in China mainly focused on local case-report, outbreak investigations, or the spatiotemporal distribution of cutaneous anthrax of human cases in China. The distributional characteristics of human and livestock anthrax, the underlying risk factors contributing to the temporal and spatial distributions of human anthrax, and the risk distribution of the disease remain poorly understood. Based on the above situation, we conducted a comprehensive and in-depth retrospective epidemiological study on the spatiotemporal dynamics and risk determinants of anthrax in mainland China.Objective:(1) To clarify the epidemic dynamics of human anthrax and livestock anthrax from 2005 to 2013 as well as to describe the epidemiological characteristics of anthrax from the aspects of time, space and demographics.(2) To identify the spatiotemporal clusters of human anthrax.(3) To clarify the driving effects of meteorological factors to the seasonality of human anthrax. Besides, To quantitatively analyze the influence of agro-ecological, environmental and meteorological factors contributing to the spatial distributions of the disease and to carry out transmission risk prediction of human anthrax.Methods:(1) The data of human anthrax and livestock anthrax from 2005 to 2013 was collected and then was geo-referenced and linked to a digital map of China at the county and province level. Combing the spatial analyses and statistical methods, we compared the epidemiological characteristics of human and livestock anthrax from the aspects of time, space and demographics. Besides, spatiotemporal and spatial cluster analyses of human anthrax were carried out to evaluate the endemic dynamics.(2) The data of human anthrax in Western China(Sichuan, Gansu and Qinghai) from 2012 to 2013 was collected and then was geo-referenced and linked to a digital map of China at the town level. We compared the epidemiological characteristics in the three provinces and conducted a spatial cluster analysis in each year.(3) Box plot and continuous wavelet transform analysis were used to explore the seasonality and periodicity of the monthly human anthrax incidence within the most likely cluster. And then the Spearman rank correlation was used to examine the association between each meteorological variable and the monthly human anthrax incidence. A boosted regression trees(BRT) model at the county level was conducted to assess the influencing factors associated with the spatial heterogeneity of the distribution of human anthrax. The software used in the study was listed as followed: Microsoft Office 2010, ArcGIS 9.2, SAS 9.3, STATA 11.1, Matlab, R Language.Results:(1) A total of 3,115 human anthrax cases were reported in mainland China during 2005–2013. Cutaneous anthrax accounted for 97.7% of all the cases. The disease mostly peaked in July or August, and males aged 30–49 years had higher incidence than other subgroups. Herdsmen and peasants accounted for 88.7% of all cases reported during 2010–2013. During 2005–2013, a total of 2,261 livestock anthrax cases were reported, the majority of which were cattle, sheep, goats and pigs. The epizootic curve of livestock anthrax was more fluctuating than the human epidemic curve but still showed an overall decreasing trend(Cochran-Armitage trend test, P < 0.01). It was significantly correlated with the epidemic of human anthrax, with a Spearman correlation coefficient of 0.38(95% CI: 0.20–0.54, P < 0.01). Human anthrax cases were distributed in 299 counties of 19 provinces with an average annual incidence of 0.39 per 100, 000 person years(range: 0.01–51.98). And about 56.34% of the cases distributed in pastoral areas or farming-pastoral areas. We found that the majority of human anthrax cases were located in six provinces in western and northeastern China(Sichuan, Xinjiang, Gansu, Qinghai, Guizhou and Inner Mongolia). Four provinces/autonomous regions(Gansu, Qinghai, Yunnan and Inner Mongolia) showed a rebound in the number of human cases in recent years, despite the overall decreasing trend in the whole China. Qinghai is the province that suffered the most from livestock anthrax during the study period. The spatial distribution of human anthrax was mostly consistent with that of livestock anthrax, except for Sichuan Province. The spatiotemporal scan statistic identified one most likely cluster and four secondary clusters during the entire study period(2005–2013). The most likely cluster consists of 34 counties on the junction of Sichuan, Gansu, Qinghai and Tibet provinces/autonomous regions, and spanned from January 2005 to January 2013, with a relative risk of 424.3. One of the secondary clusters was located at Southwestern China and the other three were located at Northeastern China. The most likely clusters identified by the spatial cluster analysis were persistently located on the eastern Qinghai-Tibet Plateau which is coinciding with the most likely cluster identified by spatiotemporal cluster analysis, whereas the locations of secondary clusters varied over time.(2) A total number of 247 anthrax cases was reported in western China(Sichuan, Gansu and Qinghai) from 2012 to 2013, with an average annual incidence of 0.11 per 100, 000. And 1 death was confirmed with a fatality rate of 0.40%. Sichun, Gansu and Qinghai have reported 127 cases, 64 cases and 56 cases during the two years, respectively. Majority of the cases were cutaneous anthrax and most of them were clinically confirmed. Most cases occurred in the summer or autumn, and the distribution of anthrax was significantly different in space. Human anthrax cases were distributed in 115 towns of 40 counties with an average annual incidence of 18.84 per 100, 000 person years(range: 2.07–112.71). There are three towns in Sichuan acquired the highest average annual incidence. They were Rangu in Dege, Tangke in Ruogaier and Dege in Aba, with the average annual incidence of 112.71 per 100, 000, 107.82 per 100, 000, and 106.44 per 100, 000, respectively. There was no significant difference in the age distribution of human anthrax cases among the three provinces(Kruskal-Wallis H test, P=0.24). The pathogen commonly affected the herdsmen in 20–49 years old. The spatial scan statistic showed that the most likely cluster stayed stable, mainly located at the junction of the three provinces with a slight movement to the west from 2012 to 2013. Anthrax incidence was significantly and positively correlated with the percentage of grassland, and negatively correlated with the percentage of forests and croplands within clusters.(3) Box plot and continuous wavelet transform analysis showed an obvious seasonality and a significantly annual cycle of the monthly human anthrax incidence in the most likely cluster identified by the spatiotemporal cluster analysis. Besides, Spearman rank correlation explored that monthly human anthrax incidence was positively correlated with monthly average temperature, relative humidity and monthly accumulative rainfall at lags of 0–2 months. A boosted regression trees(BRT) model at the county level reveals that densities of cattle, sheep and human, coverage of meadow, coverage of typical grassland, elevation, coverage of topsoil with pH > 6.1, concentration of organic carbon in topsoil, and the meteorological factors have contributed substantially to the spatial distribution of the disease. The risk rose quickly with higher elevations in the range of 500–1500 m, and plateaued or dropped for elevations above 1500 m. The probability of occurrence of human cases increased with higher values of densities of cattle and sheep, coverage of meadow, and concentration of organic carbon in topsoil. In addition, the probability of occurrence of human anthrax cases was negatively associated with the density of human population, and the meteorological index. On the basis of the average predicted probability of occurrence of human cases for each county in 2012–2013. the high-risk areas of human anthrax were mainly distributed in four regions:(1)the central-west high-risk region that contains most of the Qinghai-Tibetan Plateau, and covers eastern Qinghai, northwestern Sichuan, southwestern Gansu, and central Tibet;(2) the southwest high-risk region that consists of Yunnan, Guizhou and western Guangxi provinces;(3)the northwest high-risk region that covers western and northwestern Xinjiang;(4)the north high-risk region that covers central and eastern Inner Mongolia, western and eastern Heilongjiang, and Jilin provinces. Coinciding with the most likely cluster, the eastern part of the central-west high-risk region has the highest risk of occurrence of human cases.Conclusions: The study focused on the epidemic dynamics and related influencing factors of anthrax based on the modern information technologies, spatial analyses and statistical methods. On one hand, we provided a comprehensive epidemiological description from the aspects of time, space and demographics as well as investigated the distribution and hotspots from different geographical levels. On the other hand, we identified related influencing factors associated with human anthrax from the temporal and spatial dimensions, and carried out the risk prediction which can be helpful for prioritizing surveillance and control programs in the future. Anthrax in China was characterized by significant seasonality and spatial clustering. Males in herdsmen and peasants aged in 30–49 year-old were the main part of the disease. The seasonality of human anthrax was driven by temperature, relative humidity and rainfall, and the spatial heterogeneity was largely affected by livestock husbandry, human density, land cover, elevation, topsoil features and climate. Although anthrax underwent an overall decreasing trend during the 9 years, cases rebounded in recent years in some provinces which implying the necessary to strengthen the prevention and control of human anthrax in key areas. Cases in human were more than that in livestock and the mild correlation was found between them which implying the need to strength the monitoring for livestock. Anthrax exists in China with persistence. It is urgently necessary to improve surveillance programs for anthrax and to expand it to cover livestock, human, and environmental samples, a “One Health” approach. Only in this way can we prevent anthrax from the source of the disease.