Increasing Human Brucellosis And Risk Factors Contributing To Its Spatial And Temporal Distribution In China

Background: Brucellosis is a zoonosis caused by bacteria of the Brucella spp. Inhumans it can cause an allergic reaction characterized by a1-2month incubationperiod followed by prolonged fever, night sweats, body aches, arthralgia, andweakness. Humans are infected by contact with infected animals or, more often,through consumption of raw milk or unpasteurized cheese. Person-to-persontransmission of Brucella is extremely rare. Farmers, shepherds, abattoir workers andveterinary workers have traditionally been regarded as the main groups at risk. Sheep,goats, swine, cattle and dogs, can all be infected, and B.melitensis, B.abortus, B.suisand B. canis often cause abortion and infertility in their natural hosts, goats and sheep,cattle, swine and canine, respectively. B.melitensis Rev.1is an effective commercialvaccine which prevents infection with B.melitensis in small ruminants, but there isstill no satisfactory vaccine against human infection. With the exception of certainindustrialized countries, brucellosis has a worldwide distribution in both humans andanimals. Strenuous efforts have been made by various governments and healthagencies to control brucellosis by methods such as the culling of infected animals andstrict regulations for safe disposal of infected material. Nevertheless, humanbrucellosis has taken a heavy toll on the health and economy of countries affected andit must still be regarded as a serious worldwide public health problem.At present, human brucellosis is endemic in25of32provinces or autonomousregions of the People’s Republic of China. Human brucellosis incidence hasfluctuated since the mid-1950s in China, the Inner Mongolia Autonomous Regionbeing the most severely affected since1999. Since the beginning of the21st century,human brucellosis incidence has risen dramatically. The number of reported casesincreased each year, up until2009in China, where the disease appeared in the top10of all notifiable infectious diseases during2000-2006.Brucellosis infection has previously been associated with habitat, occupation, hostdensity, socioeconomic status, travel and immigration. China has a great variety ofhabitats and we were particularly interested to find out which habitats were involvedin this dramatic increase. In this study, our aim was to characterize the epidemiological features of human brucellosis and to identify the environmental andsocioeconomic factors associated with the spatial pattern of the disease, and to explorethe meteorological factors associated with temporal trends of incidence of humanbrucellosis in mainland China from2004to2010.Objectives:①Characterize the epidemiological characteristics of humanbrucellosis, such as its temporal distribution, spatial distribution, occupationaldistribution and the distribution of animal epidemic;②Explore the risk factors ofhuman brucellosis transmission associated with environment and/or socio-economicfactors, such as animal host density, elevation, vegetation coverage (or Landover);③Analysis of climate factors of the human brucellosis incidence in severe endemicareas, such as Heilongjiang, Jilin, Inner Mongolia, Shanxi, Hebei and so on, andcreate a predictive model to reveal the regularity of brucellosis incidence changes.Methods: Data relating to human and animal brucellosis cases and environmentaland socioeconomic variables associated with the disease in China were collected forthe years2004-2010. Epidemiological features were characterized, and the potentialfactors relating to the spatial heterogeneity and the temporal trends of the disease wereanalyzed by Poisson regression analysis, Granger causality analysis andautoregressive distributed lag (ADL) models, respectively.Results:①Epidemiological features of human brucellosis in mainland China. Atotal of162,329cases were reported from2004to2010, distributed across1,201of2,922counties (41%). The annual incidence had sharply increased by approximately4times from0.63to2.72per100,000person years during the7-year period, and themonthly incidence showed a significant seasonal pattern peaking in the spring andsummer season, especially in the month of May each year.74.59%of all reportedcases occurred in males, and males had a significantly higher incidence than femalesin all age groups (P value <0.001). The bulk of the cases (51-54%) occurred in the30-49age group. In addition,88.78%of all cases came from peasant and herdsman,and patients’ occupations showed differences between northern and southern China.Mostly patients came from peasant and herdsman in northern, northeastern andnorthwestern China, especially in the pastoral and agricultural regions, while patientsfrom other occupations such as food services, city workers and retired workerspredominated in southern China or in more urban areas. The spatiotemporaldistribution map showed that human brucellosis was widely distributed in theprovinces of Inner Mongolia, Hebei and Shanxi in northern China, and Heilongjiang, Jilin and Liaoning provinces in northeastern China. Xinjiang Autonomous Region innorthwestern China also showed an increase in incidence over the7years. Otherprovinces, especially in eastern and southern China, showed a more sporadicoccurrence of the disease. At county level, the annual incidence ranged from0to1440cases per100,000person years with a mean of11. The three counties with highestaverage annual incidence were Sonidzuo Qi, Abag Qi and Xianghuang Qi in InnerMongolia (1,440,1,121and902per100,000person years, respectively). Thespatiotemporal map also showed that the extent of epidemic areas of humanbrucellosis had expanded since2005, especially in the western and northern areas ofChina, to reach the historic high in2009. Meanwhile, the extent of high incidence innorthern China had also tended to move southward. In addition, the map of livestockbrucellosis showed that outbreaks of sheep brucellosis occurred mainly in northernand western China, while outbreaks of bovine brucellosis were widely distributedover mainland China.②Factors associated with spatial pattern of human brucellosisincidence. Univariate Poisson regression analyses revealed that human brucellosisincidence was significantly associated with the number of sheep, goats and swine, ingrassland areas of average elevation. It was not significantly associated with thenumber of cattle, and the percentage area occupied by croplands and forests.Multivariate analysis including all co-variables with a P <0.20in univariate analysis,demonstrated that five variables-number of sheep, number of goats, number of swine,average elevation and the percentage area occupied by grassland, were significantlyassociated with human brucellosis outbreaks. The table shows the adjusted figuresbetween human brucellosis incidence and livestock. The IRR for the number of sheep,goats and swine were1.42(95%CI=1.28–1.57, P <0.001),1.15(95%CI=1.01-1.32, P=0.033) and0.80(95%CI=0.66–0.96, P=0.016) respectively. Brucellosisincidence was also influenced by elevation and vegetation, and the counties withmoderate elevation (800-1,600meters) and more grassland showed a higher IRR.③Meteorological factors associated with the temporal trend of incidence of humanbrucellosis. Cross-correlation analyses showed that the monthly incidence of humanbrucellosis was significantly correlated with climatic variables, including temperature,rainfall, HS, RH and WV in all provinces. In the four counties provinces with highestincidence a cumulative effect was observed with lag times ranging from0to7months.With the exception of WV, the climatic variables showed negative correlation withdisease incidence. Monthly average temperatures with a4-month lag time were found to have the highest correlation with the incidence of human brucellosis, followed byRainfall, HS, RH, and WV. Longer lag times were found for temperature, rainfall andHS (3-4months lags), than for RH and WV (1-2months lags). Temperature, HS andrainfall showed the highest probabilities of influencing brucellosis transmission in thefour provinces according to the Granger causality tests. The ADL time-seriesregression analyses revealed that the incidence of the disease was significantlyassociated with temperature or HS, or both, with lags of1–7months in all fourprovinces. The two variables, rainfall and WV, were excluded from the final (ormultivariate) ADL models, because of their minimal contribution to monthlyincidence. This model yielded the best fit according to the root mean square error(RMSE). In the inner Mongolian region, the model (Model II, including only HS inthe model), incidence was significantly associated with HS, with lag times from0to5months (β from-0.03to0.11per10hours change, approximately1day)(Table4). InHeilongjiang and Jilin provinces, Model I, which included temperature in the model,yielded the best fit and showed that monthly incidence of human brucellosis wassignificantly associated with temperature at lags from0to6and from0to7months,respectively (β from-0.05to-0.002in Heilongjiang per1°C change, and β from-0.004to-0.001in Jilin). Model III including both factors with lags from0to7months in the model showed the best fit in Shanxi province (β from-0.003to-0.007for temperature with lags from0to5months per1°C change, and β from-0.007to-0.006for HS with lags from0to7months per10°C change). The validation of theseADL models using data from January to December of2010demonstrated a good fitbetween observations and predictions, and the high predictive powers of these modelswere achieved using the12-month observations in all four provinces.However, we recognize that there are certain limitations to the study. First, passivesurveillance data are not as good as data collected from active surveillance. Somecases may go unreported because of their milder clinical symptoms, or some could bedelayed in reporting because of delayed diagnosis in rural settings. In addition,tourism and general population movement could be complicating the reported patternof transmission of human brucellosis. However, with the data available we haveprovided a comprehensive overview of the epidemiological features of humanbrucellosis in mainland China, and our findings provide hints as to where futureintervention could be most effective.Conclusions: In this study, we characterized the epidemiological features of human brucellosis and identified the environmental and socioeconomic factorsassociated with the spatial variations and the temporal trends of the disease. Ourresults indicate that attention should be focused on sheep and goat farming economiesin areas of grassland with moderate elevation, especially in years when winter andspring are colder or have less sunshine than usual. Furthermore, the methodology wehave employed may be helpful as a means of providing valuable information for riskevaluation of human brucellosis epidemics in the future.