INFECTIOUS ALLERGY

The allergic reactivity which accompanies various infectious diseases is different in certain fundamental principles from the allergic disease associated with hypersensitivity to such agents as pollens, dust, and foods. Allergic sensitivity associated with tuberculosis comes about because of the participation of a fatty fraction of the bacillus with another component of the bacterium which is acutally the sensitizing substance. The fatty fraction, if isolated from the bacillus, can act with various kinds of sensitizing substances that have nothing to do with tuberculosis to bring about the same kind of hypersensitivity that accompanies tuberculosis. Attempts are being made to learn more about the manner of action of this factor, and also to find out whether the organisms of other infectious diseases may have similar chemical constituents that cause allergic disease.     

Mycobacterium tuberculosis: just desserts for an ungrateful guest

Myobacterium tuberculosis is the most common infectious cause of death in the world, with up to one-third of the population infected. In industrial countries infection with M. tuberculosis and tuberculosis disease has been decreasing since the 19th century. Now, however, tuberculosis disease is on the increase again, with resistance of the bacillus to available drugs spreading rapidly. This resurgence can be seen from the ecological and evolutionary point of view, where human hosts are the niche of the tuberculosis bacillus.     

结核病动物模型研究进展

结核病是由结核分枝杆菌感染引起的传染病,是危害人类健康的主要传染病之一。动物模型已经成为研究人类传染病的标准化工具。虽然对于结核分枝杆菌而言并没有真正意义的动物资源,但由于不同种类的动物,对分枝杆菌的敏感性不一样,因此可以成为结核病研究的有利工具。结核病最常用的实验动物模型包括小鼠、兔和豚鼠。每种动物有其自身特点,但并不能完全模拟人类疾病。通过建立结核病的动物模型,可以大大增加我们对疾病的病因、毒力和发病机制的理解。除了这三种模型外,非人灵长类也常被用于结核病的研究。本文总结了这几种结核病模型的研究状况。     

Genome-wide association studies and susceptibility to infectious diseases

Progress in genomics and the associated technological, statistical and bioinformatics advances have facilitated the successful implementation of genome-wide association studies (GWAS) towards understanding the genetic basis of common diseases. Infectious diseases contribute significantly to the global burden of disease and there is robust epidemiological evidence that host genetic factors are important determinants of the outcome of interactions between host and pathogen. Indeed, infectious diseases have exerted profound selective pressure on human evolution. However, the application of GWAS to infectious diseases has been relatively limited compared with non-communicable diseases. Here we review GWAS findings for important infectious diseases, including malaria, tuberculosis and HIV. We highlight some of the pitfalls recognized more generally for GWAS, as well as issues specific to infection, including the role of the pathogen which also has a genome. We also discuss the challenges encountered when studying African populations which are genetically more ancient and more diverse that other populations and disproportionately bear the main global burden of serious infectious diseases.     

Systemic manifestations of erythema nodosum

The systemic manifestations accompanying erythema nodosum can be differentiated from those associated with the precipitating infectious process and from coincident disease processes. Erythema nodosum itself is characterized by (a) skin lesions at pressure sites, (b) malaise, fever and occasionally chills, (c) arthritis (70 per cent) and (d) over-reactivity of tissue. Tissue hypersensitivity is most pronounced at sites of trauma, at sites of specific skin testing, and in the lymphoid system draining infections in the pharynx and lung. Common infections of the respiratory tract most often antedate attacks of erythema nodosum. In New England, a beta-hemolytic streptococcus infection is a common causative factor, and tuberculosis is an unusual causative factor. In endemic areas, coccidioidomycosis is a common cause of erythema nodosum. The most important coincidental disease process is rheumatic heart disease. Rarely is it a sequel of erythema nodosum. Other "collagen diseases" may coexist with erythema nodosum. Erythema nodosum is its own most common complication. Follow-up studies indicate that over half of the patients have a subsequent attack, and a certain number have recurrent episodes for months to years. The management of erythema nodosum is expectant. In each case the cause should be found and treated. Steroid treatment is rarely justified, and should be used only after tuberculosis and other treatable entities have been ruled out.     

Cutting edge: persistence of increased mast cell numbers in tissues links dermatitis to enhanced airway disease in a mouse model of atopy

The development of chronic allergic dermatitis in early life has been associated with increased onset and severity of allergic asthma later in life. However, the mechanisms linking these two diseases are poorly understood. In this study, we report that the development of oxazolone-induced chronic allergic dermatitis, in a mouse model, caused enhanced OVA-induced allergic asthma after the resolution of the former disease. Our findings show that oxazolone-induced dermatitis caused a marked increase in tissue mast cells, which persisted long after the resolution of this disease. Subsequent OVA sensitization and airway challenge of mice that had recovered from dermatitis resulted in increased allergic airway hyperreactivity. The findings demonstrate that the accumulation of mast cells during dermatitis has the detrimental effect of increasing allergic airway hypersensitivity. Importantly, our findings also show that exposure to a given allergen can modify the immune response to an unrelated allergen.     

对研发新型结核病疫苗的分析和展望

结核病是公共卫生当前面临的重要问题。由于BCG预防效果不佳,研究和开发新型结核病疫苗显得必须且急迫。新型结核病疫苗的研究开发路径和观念也经历了变迁,当前主流的研发路径有重组BCG或重组结核菌、重组痘病毒或重组腺病毒载体疫苗、蛋白质亚单位或重组融合蛋白质亚单位疫苗三类,它们在疫苗效力前景,抗原选型、配方、剂型,免疫应答,疫苗生产,疫苗质量控制,临床前研究动物试验,临床试验和使用,对结核病公共卫生政策的影响等方面各有优劣。新型结核病疫苗的成功研发,还需要病原学、发病机制、免疫学和疫苗研发科学的进一步努力。     

Consumption, silicosis, and the social construction of industrial disease.

In the wake of the bacterial revolution after Robert Koch identified the tuberculosis bacillus, medical and public health professionals classified the various forms of consumption and phthisis as a single disease--tuberculosis. In large measure, historians have adopted that perspective. While there is undoubtedly a great deal of truth in this conceptualization, we argue that it obscures almost as much as it illuminates. By collapsing the nineteenth-century terms phthisis and consumption into tuberculosis, we maintain that historians have not understood the effect of non-bacterial consumption on working-class populations who suffered from the symptoms of coughing, wasting away, and losing weight. In this essay, we explore how, in the nineteenth century, what we now recognize as silicosis was referred to as miners' "con," stonecutters' phthisis, and other industry-specific forms of phthisis and consumption. We examine how the later and narrower view of the bacterial origins of tuberculosis limited the medical professions' ability to diagnose and understand diseases caused by industrial dust. This paper explores the contention that developed at the turn of the century over occupational lung disease and tuberculosis and the circumstances that led to the unmasking of silicosis as a disease category.     

Il-4 influences apoptosis of mycobacterium-reactive lymphocytes in the presence of TNF-alpha

T cell apoptosis is associated with defective cell-mediated effector functions in several infectious diseases. In tuberculosis, there is evidence that T cell apoptosis may be cytokine mediated, but the mechanisms are not clearly understood. Type 2 cytokines have recently been associated with disease extent in human tuberculosis, but they have not previously been linked to apoptosis in mycobacterium-reactive T cells. This study presents evidence that PBLs from healthy donors respond to sonicated Mycobacterium tuberculosis Ags with increased IL-4 gene activation, CD30 expression, and apoptosis. The changes were significantly greater than those observed when cells were stimulated with Ags from nonpathogenic Mycobacterium vaccae. A hypothesis linking these observations was tested. CD30 expression and TNF-alpha-mediated lymphocyte apoptosis were both down-regulated by inhibiting IL-4 in this model. TNFR-associated factor 2 (TRAF2) expression was down-regulated in CD30(+) cells, and addition of anti-TNF-alpha Ab significantly reduced apoptosis in the CD30(+) but not the CD30(-) population. These observations support the hypothesis that increased IL-4 expression in M. tuberculosis-activated lymphocytes promotes CD30 expression, which sensitizes the lymphocytes to TNF-alpha-mediated apoptosis via TRAF2 depletion. This may be one mechanism by which IL-4 is associated with immunopathological consequences in human tuberculosis.     

Historical perspectives on the etiology of tuberculosis

Robert Koch's 1882 demonstration that the tubercle bacillus was the true cause of tuberculosis established a new understanding of causation in medicine. This scientific breakthrough set in motion an etiological revolution with vast implications for the control of infectious disease, and its ramifications are still being felt today.     

Trends in population-based studies of human genetics in infectious diseases

Pathogen genetics is already a mainstay of public health investigation and control efforts; now advances in technology make it possible to investigate the role of human genetic variation in the epidemiology of infectious diseases. To describe trends in this field, we analyzed articles that were published from 2001 through 2010 and indexed by the HuGE Navigator, a curated online database of PubMed abstracts in human genome epidemiology. We extracted the principal findings from all meta-analyses and genome-wide association studies (GWAS) with an infectious disease-related outcome. Finally, we compared the representation of diseases in HuGE Navigator with their contributions to morbidity worldwide. We identified 3,730 articles on infectious diseases, including 27 meta-analyses and 23 GWAS. The number published each year increased from 148 in 2001 to 543 in 2010 but remained a small fraction (about 7%) of all studies in human genome epidemiology. Most articles were by authors from developed countries, but the percentage by authors from resource-limited countries increased from 9% to 25% during the period studied. The most commonly studied diseases were HIV/AIDS, tuberculosis, hepatitis B infection, hepatitis C infection, sepsis, and malaria. As genomic research methods become more affordable and accessible, population-based research on infectious diseases will be able to examine the role of variation in human as well as pathogen genomes. This approach offers new opportunities for understanding infectious disease susceptibility, severity, treatment, control, and prevention.     

Animal models for protein respiratory sensitizers

Protein induced respiratory hypersensitivity, particularly atopic disease in general, and allergic asthma in particular, has increased dramatically over the last several decades in the US and other industrialized nations as a result of ill-defined changes in living conditions in modern western society. In addition, work-related asthma has become the most frequently diagnosed occupational respiratory illness. Animal models have demonstrated great utility in developing an understanding of the etiology and mechanisms of many diseases. A few models been developed as predictive models to identify a protein as an allergen or to characterize its potency. Here we describe animal models that have been used to investigate and identify protein respiratory sensitizers. In addition to prototypical experimental design, methods for exposure route, sample collection, and endpoint assessment are described. Some of the most relevant endpoints in assessing the potential for a given protein to induce atopic or allergic asthma respiratory hypersensitivity are the development of cytotropic antibodies (IgE, IgG1), eosinophil influx into the lung, and airway hyperresponsiveness to the sensitizing protein and/or to non-antigenic stimuli (Mch). The utility of technologies such as PCR and multiplexing assay systems is also described. These models and methods have been used to elucidate the potential for protein sources to induce allergy, identify environmental conditions (pollutants) to impact allergy responsiveness, and establish safe exposure limits. As an example, data are presented from an experiment designed to compare the allergenicity of a fungal biopesticide Metarhizium anisopliae (MACA) crude extract with the one of its components, conidia (CON) extract.     

Toll-like receptors: function and roles in lung disease

Toll-like receptor (TLR) proteins have been shown to play a pivotal role in both innate and adaptive immune responses in higher vertebrates. TLR proteins enable the host to recognize a large number of pathogen-associated molecular patterns such as bacterial lipopolysaccharides, viral RNA, CpG-containing DNA, and flagellin, among others. Engagement of TLR proteins leads to the upregulation of costimulatory molecules and proinflammatory cytokines, as well as reactive nitrogen and oxygen products. The role of TLR proteins in lung-associated pathologies such as airway hyperreactivity, allergic asthma, and tuberculosis is being intensively studied. This review summarizes many of the findings made to date on the roles of TLR proteins in a variety of lung diseases. Generally, TLR proteins serve a protective role in infectious diseases, such as tuberculosis. The progression of chronic inflammatory lung diseases, such as allergic asthma, can also be influenced by TLR-dependent responses.     

剑阁县2001-2010年法定传染病流行特征及防治对策分析

目的：通过分析10年法定传染病疫情的流行趋势和三间分布特征,为制定传染病预防控制策略和措施提供依据。方法：采用描述性流行病学方法分析疫情趋势和三间分布情况,数据资料用SPSS10．0和Excel2003进行统计分析。结果：2001～2010年共报告乙、丙类传染病25种26129例,年均发病率386．89／10万,年均死亡率0．15／10万,10年间报告法定传染病以血源及性传播传染病和呼吸道传染病为主,居第1位的是血源及性传播传染病,共报告5种12453例,占53．03％;其次是呼吸道传染病,共报告5种9828例,占41．85％,近3年发病居于各类传染病首位;第三位的是肠道传染病,共报5种1149例,占4．89％。发病居前5位的传染为乙肝、肺结核、流行性腮腺炎、痢疾、麻疹,主要传染病以乙肝、肺结核为主,近年性传播疾病呈快速增长趋势。结论：血源及性传播传染病和呼吸道传染病是今后重点防控传染病。     

剑阁县2001～2010 年法定传染病流行特征及防治对策分析

目的:通过分析10年法定传染病疲情的流行趋势和三间分布特征,为制定传染病预防控制策略和措施提供依据.方法:采用描述性流行病学方法分析疫情趋势和三间分布情况,数据资料用SPSS10.0和Excel 2003进行统计分析.结果:2001～2010年共报告乙、丙类传染病25种26 129例,年均发病率386.89/10万,年均死亡率0.15/10万,10年间报告法定传染病以血源及性传播传染病和呼吸道传染病为主,居第1位的是血源及性传播传染病,共报告5种12 453例,占53.03％;其次是呼吸道传染病,共报告5种9828例,占41.85％,近3年发病居于各类传染病首位;第三位的是肠道传染病,共报5种1149例,占4.89％.发病居前5位的传染为乙肝、肺结核、流行性腮腺炎、痢疾、麻疹,主要传染病以乙肝、肺结核为主,近年性传播疾病呈快速增长趋势.结论:血源及性传播传染病和呼吸道传染病是今后重点防控传染病.     

The long-run heterogeneous effects of a cholera pandemic on stature: Evidence from industrializing Japan

The recent COVID-19 pandemic poses the general question on how infectious diseases can persistently affect human health. A growing body of literature has found a significant amount of evidence on the long-term adverse effects of infectious diseases, such as influenza, typhoid fever, and yellow fever. However, we must be careful about the fact that little is known about the long-term consequences of the acute diarrheal disease pandemic cholera – Vibrio cholerae bacillus – which still threatens the health of the population in many developing countries. To bridge this gap in the body of knowledge, we utilized unique census-based data on army height at age 20 in early 20th-century Japan, with a difference-in-differences estimation strategy using regional variation in the intensity of cholera pandemics. We found that early-life exposure to a cholera pandemic had heterogeneous stunting effects on the final height of men; the magnitude of the stunting effects increased as the intensity of exposure increased.     

药物作用靶点研究最新进展

通过对我国学者近2年在国内外发表的相关论文进行检索和整理,分类综述针对神经退行性疾病（如阿尔茨海默病、帕金森病等）、心血管疾病（如高血压、心律失常、心衰、冠心病、心肌梗死、动脉粥样硬化等）、脑血管疾病、代谢类疾病（如肥胖症、血脂异常、脂肪肝、糖尿病等）、感染性疾病（如艾滋病、流感、结核病等）、恶性肿瘤、自身免疫性疾病等多种疾病的药物作用靶点研究最新进展。     

Evaluating Spatial Overlap and Relatedness of White-tailed Deer in a Chronic Wasting Disease Management Zone

Wildlife disease transmission, at a local scale, can occur from interactions between infected and susceptible conspecifics or from a contaminated environment. Thus, the degree of spatial overlap and rate of contact among deer is likely to impact both direct and indirect transmission of infectious diseases such chronic wasting disease (CWD) or bovine tuberculosis. We identified a strong relationship between degree of spatial overlap (volume of intersection) and genetic relatedness for female white-tailed deer in Wisconsin’s area of highest CWD prevalence. We used volume of intersection as a surrogate for contact rates between deer and concluded that related deer are more likely to have contact, which may drive disease transmission dynamics. In addition, we found that age of deer influences overlap, with fawns exhibiting the highest degree of overlap with other deer. Our results further support the finding that female social groups have higher contact among related deer which can result in transmission of infectious diseases. We suggest that control of large social groups comprised of closely related deer may be an effective strategy in slowing the transmission of infectious pathogens, and CWD in particular.     

The paradoxical effects of vitamin D on type 1 mediated immunity

Low vitamin D status is associated with an increased risk of Th1 mediated autoimmune diseases like inflammatory bowel disease. 1,25(OH)(2)D(3) treatments have been shown to suppress Th1 mediated immunity and protect animals from experimental autoimmunity. Th1 mediated immunity is important for clearance of a number of different infectious diseases. For tuberculosis 1,25(OH)(2)D(3) treatment is associated with decreased Th1 mediated immunity but increased bactericidal activity. Systemic candidiasis is unaffected by 1,25(OH)(2)D(3) treatment. The seemingly paradoxical effects of 1,25(OH)(2)D(3) and vitamin D on Th1 mediated autoimmunity versus infectious immunity point to a broad array of vitamin D targets in the immune system. The interplay of these vitamin D targets and their impact on the host-immune response then dictate the outcome.     

Evolution, revolution and heresy in the genetics of infectious disease susceptibility

Infectious pathogens have long been recognized as potentially powerful agents impacting on the evolution of human genetic diversity. Analysis of large-scale case-control studies provides one of the most direct means of identifying human genetic variants that currently impact on susceptibility to particular infectious diseases. For over 50 years candidate gene studies have been used to identify loci for many major causes of human infectious mortality, including malaria, tuberculosis, human immunodeficiency virus/acquired immunodeficiency syndrome, bacterial pneumonia and hepatitis. But with the advent of genome-wide approaches, many new loci have been identified in diverse populations. Genome-wide linkage studies identified a few loci, but genome-wide association studies are proving more successful, and both exome and whole-genome sequencing now offer a revolutionary increase in power. Opinions differ on the extent to which the genetic component to common disease susceptibility is encoded by multiple high frequency or rare variants, and the heretical view that most infectious diseases might even be monogenic has been advocated recently. Review of findings to date suggests that the genetic architecture of infectious disease susceptibility may be importantly different from that of non-infectious diseases, and it is suggested that natural selection may be the driving force underlying this difference.