| Recently, drug-resistant tuberculosis (DR-TB), especially multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant TB (XDR-TB), has been emerging as one of the increasingly important issues. From the WHO report, DR-TB now is at record levels, it has spread to all over the world and has become a serious public health problem that poses a serious threat to human health and threatens the success of directly-observed treatment strategy (DOTS), the WHO-recommended treatment approach for detection and cure of TB, as well as global tuberculosis control. China, with very high prevalence of DR-TB, is one of the 27 high-burden MDR/XDR countries worldwide.As a serious public health and social problem in the whole world, the effective prevention and control of MDR-TB has become a hot issue studied by researchers both at home and abroad. While there are very large development space for the treatment of MDR-TB (drug therapy, physiotherapy, immunotherapy, gene therapy, etc), it is not that easy too. Therefore, synthetic prevention and control measures should be taken for MDR-TB.DR-TB is caused by various factors, including not only factors at individual level (e.g. sex, occupation, socioeconomic status, genetic susceptibility, previous treatment, etc.), but also factors at ecological level (i.e. environment factors, including natural factors and social factors). Study on ecological factors (ecology study) can provide clues for etiology study and helps for the effective prevention and control of disease. So it is of great significance for public health response, effective prevention and control of MDR-TB to explore the ecological factors of MDR-TB, which can provide guidance for formulating regional prevention and control strategies. However, at present, there are no specialized researches published to explore the ecological factors for MDR-TB and other DR-TB. Based on the above background, we carried out "the ecology study on risk factors of MDR-TB" financed by the National special science and technology major projects. Major objectivesThe major objectives of this study were to explore the complex relationship between ecological factors and the level of MDR-TB by utilizing MDR-TB surveillance data and the data of socioeconomic factors, health resource allocation, health service, TB prevention and treatment, climate and geography factors of surveillance county (district) participated in the anti-tuberculosis drug resistance surveillance projects;then try to analyze the space heterogeneity of the effects in provinces (cities). Based on the above analysis, some suggestions about the effective prevention and control of MDR-TB were put forward. MethodsTaking the baseline survey of anti-tuberculosis drug resistance, prevention and treatment of tuberculosis, socioeconomic conditions, geographical locations, etc into consideration, we conducted this study in Henan, Heilongjiang, Zhejiang, Chongqing and Tianjin, and used the questionnaire designed by research group to collect the data of MDR-TB and ecological factors of anti-tuberculosis drug resistance surveillance counties (districts) in surveillance year and 1 to 10 years ago. Then, the database was built by Excel 2007, and the software of SPSS 16.0, SAS9.1.3, SmartPLS2.0, ArcGIS 9.3 and SAM v4.0 was used to analyze data.On the basis of the preliminary statistical analysis of MDR-rate and ecological factors variables, exploratory factor analysis (EFA) based on latent variable theory was used to explore the latent structure hiding in ecological factors and extract latent synthetic risk factors firstly;secondly, partial least squares path modeling (PLS-PM) was constructed to analyze the complex relationship between ecological factors and MDR-rate, and estimate MDR factor and latent synthetic risk factors scores simultaneously;and then based on the Kriging spatial interpolation estimation, the local spatial regression model (GWR model) was built to analyze the local spatial heterogeneity in the estimated relationships between MDR factor and latent synthetic risk factors. Results1. There were obvious differences in the rates of MDR-TB (MDR-rates) of new TB cases and previously treated TB cases of five provinces (cities), which ranked as Henan, Heilongjiang, Zhejiang, Chongqing and Tianjin;significant difference was showed in MDR-rates of new TB cases and ecological factors variables of each county or district too.2. Correlations with different degrees and directions can be found between MDR-rates of new TB cases and its related ecological factors (year0-year10) in all counties or districts.3. Ten latent synthetic risk factors were extracted from ecological factors (social, economic, health resource allocation, health service, TB prevention and treatment, climate and geography, etc):Social-economic, Living condition, Health resource, Health service, Climate, Geography, TBreport, TBtreatment, TBresource and DOTS factor; these factors reflected the socioeconomic levels, living conditions, health resources allocations, quality of health services, temperatures and humidities, geography conditions, TB patients reported, human resources allocation of TB prevention and treatment, and DOTS implementation respectively. 4. The latent synthetic risk factors of different years (year0-year10) had different effects on the level of MDR-TB. which can explain about 20%(19.3%-27.9%) of the total variance of MDR-TB; it showed that the latent synthetic risk factors played an important role in drug resistance and had some lag effects on multidrug resistance, in which the latent synthetic risk factors between yearl and year5 had larger effects, while that of year6-yearlO factors were little.①The climate and geography factors of each county (district) had changed little during year0-year10, so the relationships between these ecological factors in different years and MDR-rate were in substantial agreement, namely the higher the temperature and humidity, the weaker the sunlight and wind speed is, the lower the level of MDR-TB is;the larger the proportion of mountains and hills is, the higher the level of MDR-TB is.②The implementation time of DOTS strategy and MDR-rate had negative relationship.③Health resource allocation status of year0-year10and MDR-rate had significant positive relationship.④Health service status of yearO had positive relation to MDR-rate, but no close relationship was found between health service of year1-year10 and MDR-rate, which showed that health service factor didn’t have lag effect on MDR-TB.⑤TB patients report of yearO and MDR-rate had positive relationship, while negative lag effect showed between TB patient reported of yearl-year2 and MDR-rate.⑥TB treatment of year0, year3-year5 had negative relation to MDR-rate, which showed TB treatment factor had negative lag effect on MDR-TB.⑦Socioeconomic conditions, living conditions and human resources allocations of TB prevention and treatment of year0-year10 all had little effect on MDR-TB.5. The distribution of MDR factor and latent synthetic risk factors of counties (districts) of Henan showed distinct spatial variability, namely MDR-rate and ecological factors in different regions had spatial heterogeneity.6. The Radj2 of GWR model of each county (district) in Henan ranged between 0.2839 and 0.8800, which showed that the effects of latent synthetic risk factors on MDR-TB had obvious spatial variability. Recommendations1. Strengthen the human resource development of TB control professional organizations, equip professional team for TB prevention and control with reasonable structure, and improve the quality of TB prevention and control, and enhance the level of discovering, curing and managing for TB cases, and intensify the discovering of MDR-TB and other DR-TB simultaneously.2. Optimize regional health resource allocation, and give full play to the important role of medical institutions at various levels in TB control, accomplish the collaboration between general hospital and TB dispensary roundly and cogently, and increase the discovery rate of TB and DR-TB by fully utilizing the available resources.3. Analyze the problems existed in implementing DOTS and Stop TB strategy in different regions, and then take comprehensive measures to improve the implementation quality which can be a help to the effective control of tuberculosis and the prevention and control of the occurrence of drug resistance.4. Follow "surveillance guidelines of the Global Project" strictly, we should conduct a nationwide epidemiological surveillance for MDR-TB regularly and persistently, understand the epidemic status of MDR-TB in different regions and explore its epidemic trend and cause, which can provide guidance to allocate health resource reasonably, formulate and implement local surveillance planning and prevention and control measures. Innovations and limitationsThe innovations include that:1. The thesis is novel. There are no specialized researches published to explore the ecological factors for MDR-TB now. The present study explored the ecological factors of MDR-TB deeply and investigated the lag effects of the ecological factors for the first time by using data of MDR-rate and ecological factors of surveillance counties (regions).2. The methods are nontrivial. In this study, we proposed a broadly new analysis strategy based on the characteristics of data, combined latent variable theory, geographic epidemiology, spatial epidemiology with spatial statistics, and explored the global and local relationship between MDR-rate and ecological factors deeply by using PLS path modeling and GWR model respectively. This analysis strategy can not only make up the disadvantages of tranditional regression methods when using in this study and to utilize the data information fully, and it will provide a methodological reference for other similar studies simultaneously.3. The conclusions are innovative. The ecological influencing modes and degrees of the latent synthetic risk factors on MDR-TB are all different. There are obvious spatial distribution characteristics of MDR-TB and ecological factors in studied counties (regions) of Henan province, and the influences show obvious spatial variability. These findings can provide guidance for reasonable layout of monitoring point and the regionalized effective prevention and control of MDR-TB.The limitations include that:1. MDR-TB is caused by various factors;the present study only analyzed part of its ecological factors due to the feasibility of research, and didn’t include more potential factors, which needs to be further investigated in the future.2. Taking Henan as an example, we tried to analyze the local relationship between MDR factor and latent synthetic factors by GWR model to reflect the space differentiation of the effect of latent synthetic risk factors of different areas on MDR factor; but the study region is rather small, which can have some effects on study results. Therefore, further study should include other provinces (cities) and their counties (districts), and use their surveillance data and relevant ecological factors data to explore the relationship nationally. |
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