The use of bacillary tuberculosis information system central files for special-purpose data search

The automated information system for surveillance of bacillary tuberculosis (ISBT) was put into operation in 1981, with the objective to record, store and process all mycobacterial positivity data reported by the network of specialized mycobacteriological laboratories in the Czech socialist republic. Here are described the newly developed data processing programs which allow it to carry out some special-purpose searches for the stored epidemiological data important for surveillance of tuberculosis. Further improvement of the national system of tuberculosis surveillance is believed to lie in the future compatibility of the two computerized systems operating at present in Czechoslovakia, i.e. ISBT and the Register of Tuberculosis.     

Use of the insertion element IS6110 for DNA fingerprinting of Mycobacterium tuberculosis isolates presenting various profiles of drug susceptibility

Abstract IS 6100 is an insertion sequence of the IS3 family and it is present in multiple copies in the chromosome of Mycobacterium tuberculosis . Four to 15 copies are present in various strains of M. tuberculosis . In this study, the value of IS 6110 as an epidemiological marker of tuberculosis was examined. Unrelated clinical strains from Greek patients presented, in restriction fragment length polymorphism analysis, a high degree of polymorphism, whereas patterns of related clinical strains from familial outbreaks were identical. Since RFLP analysis with acetylaminofluorene labeled IS 6110 as the probe gave satisfactory results, it is suggested that this non-radioactive probe can be used in hospitals and health centres for the epidemiological survey of M. tuberculosis infections.     

Genomic fluidity and pathogenic bacteria: applications in diagnostics, epidemiology and intervention

The increasing availability of DNA-sequence information for multiple pathogenic and non-pathogenic variants of individual bacterial species has indicated that both DNA acquisition and genome reduction have important roles in genome evolution. Such genomic fluidity, which is found in human pathogens such as Escherichia coli, Helicobacter pylori and Mycobacterium tuberculosis, has important consequences for the clinical management of the diseases that are caused by these pathogens and for the development of diagnostics and new molecular epidemiological methods.     

Genotyping of <Emphasis Type="Italic">Mycobacterium tuberculosis</Emphasis> using whole genome sequencing

Tuberculosis (TB) is considered one of the most serious infectious diseases worldwide. Effective control of tuberculosis infection involves multiple steps, such as reliable detection, treatment, an epidemiological control as a part of case management, and further surveillance and monitoring of TB spread in the human population. Due to the accelerating advances in molecular biology, especially in DNA sequencing, in the past decade, the application of these methods has become crucial for TB evolution studies, differentiation of Mycobacterium tuberculosis genotypes, and their distribution. Currently, several molecular genetic methods are available. The oldest typing methods (e.g., IS6110-RFLP, spoligotyping, and MIRU-VNTR) can discover the chain of transmission to the patient. Currently, whole genome sequencing facilitates is furthermore able to identify the source of infection, the transmission trays among individuals sharing the same isolate, as well as determination of the TB evolution and its resistance to antituberculotic agents. It is obvious that this technique will become a new gold standard in genotyping methods in tuberculosis molecular epidemiological studies. In this article, molecular genetic typing methods with a special focus on whole genome sequencing and data management are reviewed.     

Epidemiological patterns of tuberculosis in Croatia in the period 1996-2005

The last comprehensive publication on tuberculosis in Croatia and the earliest impact of war, besides the yearly routine reports, was done in 1996 in Croatian. We were, therefore, interested to explore incidence trends and to highlight the early post-war tuberculosis epidemiological patterns in the next ten years period (1996-2005). A retrospective analysis of epidemiological data on all registered tuberculosis cases in Croatia searching the databases of 21 Croatian Public Health Institutes and the National Tuberculosis Registry was made. During the study period, the total tuberculosis incidence rates in Croatia dropped from 45 to 25.8/100 000 inhabitants. The average highest age-specific rates were recorded in the age group > or = 65 years being in decrease in all age groups. Paediatric cases (0-14 years) represented 4.5% of all cases. Tuberculosis cases among males were recorded in 64% cases, and 83.6% were indigenous population. Tuberculosis was bacteriologically confirmed in 67.7% cases. A low proportion of drug resistance (3.3%) was recorded. During 1985-2005, 56 tuberculosis cases among 242 AIDS cases were reported. Tuberculosis mortality showed a decreasing trend (p < 0.001). However, tuberculosis has still had the highest mortality rates among infectious diseases in Croatia. Despite the War chain of events and tuberculosis programmatic changes, tuberculosis incidence rates in Croatia have been decreasing but they are still far away from national target, incidence rate of 10/100 000 declared in 1998 and much higher than in European Union and Western Europe. Tuberculosis among children, resistance to tuberculosis drugs and HIV prevalence, significant problems in many European countries, have not caused problems in tuberculosis control in Croatia. This favourable epidemiological situation must be kept and improved through strengthened tuberculosis control measures.     

eCOMPAGT – efficient Combination and Management of Phenotypes and Genotypes for Genetic Epidemiology

Background  

High-throughput genotyping and phenotyping projects of large epidemiological study populations require sophisticated laboratory information management systems. Most epidemiological studies include subject-related personal information, which needs to be handled with care by following data privacy protection guidelines. In addition, genotyping core facilities handling cooperative projects require a straightforward solution to monitor the status and financial resources of the different projects.     

Epidemiological models of Mycobacterium tuberculosis complex infections

The resurgence of tuberculosis in the 1990s and the emergence of drug-resistant tuberculosis in the first decade of the 21st century increased the importance of epidemiological models for the disease. Due to slow progression of tuberculosis, the transmission dynamics and its long-term effects can often be better observed and predicted using simulations of epidemiological models. This study provides a review of earlier study on modeling different aspects of tuberculosis dynamics. The models simulate tuberculosis transmission dynamics, treatment, drug resistance, control strategies for increasing compliance to treatment, HIV/TB co-infection, and patient groups. The models are based on various mathematical systems, such as systems of ordinary differential equations, simulation models, and Markov Chain Monte Carlo methods. The inferences from the models are justified by case studies and statistical analysis of TB patient datasets.     

Epidemiological characteristics of Angola

The epidemiological analysis of infectious morbidity for recent years has been made and the main nosological forms existing in Angola (malaria, tuberculosis, lepra, African trypanosomiasis, plague, intestinal diseases, etc.) have been briefly characterized on the basis of primary medical reports and the data provided by the literature and experimental work. This analysis creates the necessary prerequisites which enable the local public health organs to determine the regularities of the epidemic process, thus making it possible to take rational prophylactic measures and to organize proper epidemiological supervision.     

The epidemiological consequences of leprosy-tuberculosis co-infection

While in antiquity both leprosy and tuberculosis were prevalent in Europe, leprosy declined thereafter and, simultaneously, tuberculosis prevalence increased. Since both diseases are caused by mycobacterial infections, it has been suggested that there might be a causal relationship between both epidemics.Chaussinand observed the inverse prevalence of leprosy and tuberculosis and suggested that individuals with a latent tuberculosis infection are protected from acquiring leprosy. His cross-immunity hypothesis has been countered more recently by a co-infection hypothesis. The latter suggestion, proposed by Donoghue, states that people being infected with multi-bacillary leprosy are more susceptible to tuberculosis, which leads to increased mortality from the disease.This study utilizes mathematical modeling to explore the epidemiological consequences of the co-infection hypothesis for realistically confined parameter values. While the co-infection hypothesis appears plausible at first glance, a second thought reveals that it comprises also substantial consequences for tuberculosis epidemics: if co-infection raises the mortality rate above that of purely tuberculosis infected persons, then tuberculosis might as well be eradicated by leprosy. It is the specific interplay of both increased susceptibility towards tuberculosis and increased death rate when co-infected that determines the epidemiological fate.As a result of this analysis, it is shown that there is a large parameter region where the eventual disappearance of leprosy could indeed be explained by co-infection. This parameter region is considerably larger than that predicted by the cross-immunity hypothesis. This shows that the co-infection hypothesis should be considered a significant alternative to the cross-immunity hypothesis. The time scales at which the effects of co-infection are observed depend critically on the spatial distribution of the individuals but reach epidemiologically realistic values for rather immobile individuals with local interaction.     

Mycobacterium tuberculosis complex differentiation using gyrB-restriction fragment length polymorphism analysis

Mycobacterium tuberculosis complex (MTBC) members are causative agents of human and animal tuberculosis. Differentiation of MTBC members is required for appropriate treatment of individual patients and for epidemiological purposes. Strains from six MTBC species -- M. tuberculosis, M. bovis subsp. bovis, M. bovis BCG, M. africanum, M. pinnipedii, and "M. canetti" -- were studied using gyrB-restriction fragment length polymorphism (gyrB-RFLP) analysis. A table was elaborated, based on observed restriction patterns and published gyrB sequences. To evaluate applicability of gyrB-RFLP at Instituto Adolfo Lutz, Sao Paulo, Mycobacterial Reference Laboratory, 311 MTBC clinical isolates, previously identified using traditional methods as M. tuberculosis (306), M. bovis (3), and M. bovis BCG (2), were analyzed by gyrB-RFLP. All isolates were correctly identified by the molecular method, but no distinction between M. bovis and M. bovis BCG was obtained. Differentiation of M. tuberculosis and M. bovis is of utmost importance, because they require different treatment schedules. In conclusion, gyrB-RFLP is accurate and easy-to-perform, with potential to reduce time needed for conventional differentiation methods. However, application for epidemiological studies remains limited, because it cannot differentiate M. tuberculosis from M. africanum subtype II, and "M. canetti", M. africanum subtype I from M. pinnipedii, and. M. bovis from M. bovis BCG.     

Exploring vulnerability of listed Mediterranean plants in relation to risks of population loss

In this paper, we propose a method to assess population numbers and quantify their vulnerability for listed plant species. For six study species, the spatial aggregation of point data allowed us to identify the numbers of populations for each species and thus how they differ in regional abundance. We assessed vulnerability by according a score to each population in relation to three criteria: (i) land-use (urbanisation, agriculture and natural areas), (ii) fragmentation of populations by infrastructures and (iii) protected status of populations. As a result of the combination and scoring of populations across the three criteria, only 9% have a low extinction risk and 73% are in one of the three classes of high vulnerability with 16% in the highest category. Finally, 29 of 32 populations monitored in a separate study are in one of the three highest categories of vulnerability. This study illustrates how information on population numbers of listed species at the regional scale brings to the fore their generalised vulnerability to threats in the Mediterranean landscape. This information is vital for conservation management staff to develop a strategy and appropriate actions for listed species’ protection.     

On the epidemiological situation in quarantine, natural focal and other infections on the territory of the Southern Federal District

The data on the sanitary and epidemiological situation in the Southern Federal District are presented. The analysis of morbidity in tuberculosis, measles, HIV infection, viral hepatitis A, typhoid fever, cholera and quarantine infections, Crimean hemorrhagic fever, West Nile fever, rabies, malaria has been carried out. Special attention has been given to "new and newly returning infections", and among them to the spread of SARS ("atypical pneumonia"). The role of regional epidemiological safety programs, in particular such program as "The prophylaxis of quarantine and natural focal infections and the sanitary protection of the territory of the Southern Federal District of the Russian Federation from the import and spread infectious diseases in 2003-2005", has been substantiated.     

Analysis of sequence diversity among IS6110 sequence of Mycobacterium tuberculosis: possible implications for PCR based detection

The IS6110 belongs to the family of insertion sequences (IS) of the IS3 category. This insertion sequence was reported to be specific for Mycobacterium tuberculosis complex and hence is extensively exploited for laboratory detection of the agent of tuberculosis and for epidemiological investigations based on polymerase chain reaction. IS6110 is 1361-bp long and within this sequence different regions have been utilized as targets in the identification of M. tuberculosis by PCR. However, the results are not always consistent, specific and sensitive. In recent years, a few clinical investigations raised concerns over IS6110 specificity and sensitivity in the diagnosis of tuberculosis due to false-positive (homology with other target DNA besides M. tuberculosis) or false negative (due to absence of copies of IS6110) results with IS6110 specific primers. To unravel the variations in IS6110 sequences, an insilico analysis of IS6110 sequence of different strains of M. tuberculosis was carried out. Our results of comparative analysis of IS6110 insertion sequences of M. tuberculosis complex suggests that, IS6110 insertion sequences harbored variations in its sequence, which is evident from the phylogenetic analysis. Importantly, IS6110 sequence has divergence within the copies of same strain and formed different clusters. A list of IS6110 specific primers used in various clinical investigation of tuberculosis was obtained from the literature and their performance scrutinized. Our study emphasizes the need to develop PCR assays (multiplex format) targeting more than one region of the genome of M. tuberculosis.     

全球结核病疫苗研究进展

本文旨在对全球结核病疫苗研究进展进行系统综述,描述国际上目前进入临床试验不同阶段的新型疫苗,包括重组卡介苗、亚单位疫苗、治疗性疫苗等,分析我国结核病疫苗研究现状,介绍国际研究发展趋势,如人类疫苗计划、全细胞疫苗、多阶段疫苗等,并对存在的问题和挑战进行讨论,展望未来发展趋势。     

Forme pseudo-tuberculeuse d’un carcinome épidermoïde du poumon exploré par TEP/TDM

In Oncology, PET/CT images interpretation can prove tricky due to the lack of specific radiolabelled tracers. We present a tobacco addict 58 years old man with lung squamous cell carcinoma mimicking evolutive tuberculosis on radiological imaging. In this patient, a negative sputum analysis of mycobaterium tuberculosis and scanty radiologic data triggered a PET/CT exam. Eventually, biopsy conveyed the proper diagnosis of lung squamous cell carcinoma. Ordering a PET/CT examen must take into account good analysis of radiologic imaging and endoscopic data susceptible to bring essential information in lung tumours related clinical conditions; allowing to streamline the diagnostic work-up.     

Unmanned Aircraft Systems for Studying Spatial Abundance of Ungulates: Relevance to Spatial Epidemiology

Complex ecological and epidemiological systems require multidisciplinary and innovative research. Low cost unmanned aircraft systems (UAS) can provide information on the spatial pattern of hosts’ distribution and abundance, which is crucial as regards modelling the determinants of disease transmission and persistence on a fine spatial scale. In this context we have studied the spatial epidemiology of tuberculosis (TB) in the ungulate community of Doñana National Park (South-western Spain) by modelling species host (red deer, fallow deer and cattle) abundance at fine spatial scale. The use of UAS high-resolution images has allowed us to collect data to model the environmental determinants of host abundance, and in a further step to evaluate their relationships with the spatial risk of TB throughout the ungulate community. We discuss the ecological, epidemiological and logistic conditions under which UAS may contribute to study the wildlife/livestock sanitary interface, where the spatial aggregation of hosts becomes crucial. These findings are relevant for planning and implementing research, fundamentally when managing disease in multi-host systems, and focusing on risky areas. Therefore, managers should prioritize the implementation of control strategies to reduce disease of conservation, economic and social relevance.     

结核分枝杆菌中插入序列的研究

用人型复合分枝杆菌的特异插入序列IS6110和IS1081制 备探针,对5种限制性内切酶消化的结核分枝杆菌DNA进行杂交。结果表明,经PvuⅡ酶消化 的结核分枝杆菌DNA,用IS6110制备的探针进行杂交呈现高度多态性,说明IS6110对于人型 复合分枝杆菌分型研究和结核病流行病学研究具有很大价值。用IS6110制备的317bp探针对4 6株人结核分枝杆菌分离株多态性分析研究证实,这些菌株呈现高度DNA多态性,而且所含拷 贝数也极为不同,一般含7～18个拷贝。     

基于数据挖掘的门诊信息资源分析

目的：随着各级医院信息化建设的不断加强,医院的信息化水平也日益提高。目前各医院都有自己完善的信息化系统,在日常的门诊中,信息化系统积累了大量的门诊就诊数据,但长久以来这部分数据只是处于低层次的应用。对数据的深层次分析、加工以及对医院管理层的决策支持能力较弱。面对着这些宝贵的数据,医院迫切需要数据挖掘和分析工具从积累的就诊数据中分析出更深层次的、高价值的信息,从而为医院的管理决策提供高价值的决策信息。方法：以聚类算法进行数据挖掘建模,对某院门诊信息资源中有用字段进行挖掘分析。结果：根据数据挖掘模型进行挖掘分析,对有价值字段进行聚类分析,得到相关字段数据挖掘结果。结论：将得到相关字段数据挖掘结果进行分析,并将所分析的结果在医院管理决策和医疗质量管理等方面的应用进行探讨。     

At Baltic crossroads: a molecular snapshot of Mycobacterium tuberculosis population diversity in Kaliningrad, Russia

The Kaliningrad region is the westernmost part of the Russian Federation; it includes an enclave on the Baltic Sea inside the European Union separated from mainland Russia by Lithuania and Poland. The incidence of tuberculosis in Kaliningrad has shown a steady and dramatic increase from 83/100 000 in 2000 to 134/100 000 in 2006; the rate of multidrug-resistant tuberculosis (MDR-tuberculosis) in the Kaliningrad region was reported to be 30.5% among newly diagnosed tuberculosis patients. This study presents a first molecular snapshot of the population diversity of Mycobacterium tuberculosis in this region. A total of 90 drug-resistant and susceptible M. tuberculosis strains from Kaliningrad were subjected to spoligotyping, 12-locus MIRU typing and mutation analysis of the drug resistance genes rpoB and katG . A comparison with international databases showed that the M. tuberculosis population in this region shares a joint pool of strains with the European part of Russia, and also exhibits a certain affinity with those of its northern European neighbours, such as Poland and Germany. Comparison of the genotyping and drug resistance data emphasized that the high prevalence of the MDR Beijing genotype strains is a major cause of the adverse epidemiological situation of MDR-tuberculosis in the Kaliningrad region.