Discussion on the problems of general epidemiology

The key problems of general epidemiology: the subject, method, causality in the epidemic process, the main categories and laws, the systematization of infectious pathology and epidemiological terminology are under discussion. It is at this stage when students should form valid notions, well grounded on scientific facts and practical experience, concerning the epidemiology of noninfectious diseases with due regard to the existing differences in the interpretation of the causes of the epidemic process in noninfectious diseases and to the characteristic distribution of noninfectious diseases among the population under the influence of environmental factors without any participation of parasitic systems. The review of the notion apparatus of the theoretical epidemiology and putting it in order in accordance with general biological concepts are proposed in connection with the necessity of differentiation between the epidemic process proper (in cases of anthroponosis) and the epidemic manifestations of epizoonotic and epiphytotic processes (in cases of zoonoses and sapronoses).     

Quantitative research on the cyclic fluctuations of the epidemic process in a number of infectious diseases in Bulgaria

The cyclic nature of the epidemic process in Bulgaria was studied by various methods (spectral analysis, etc.), forming a system. The morbidity dynamics in 10 infectious diseases (scarlet fever, rubella, measles, epidemic parotitis, whooping cough, diphtheria, typhoid fever, enterocolitis, bacterial dysentery, viral hepatitis) over the years of 1909-1983 were studied and cycles covering the periods of 3-4, 5-6, 10-11 and over 16 years were established. The data on the relative part of cyclic processes in the registered morbidity of infectious diseases, as well as information on the prognostication of the spread of infections in the absence of vaccinal prophylaxis, are presented.     

The system of the epidemic process

An original social-ecological concept of the epidemic process has been constructed on the basis of using social ecology, systemic approach and the basic principles of cybernetics. According to this concept, the epidemic process is regarded as a biosocial, hierarchic, integral system providing for the reproduction of the species of human parasites. At a higher level of organization, the epidemic process is an epidemiological social-ecological system consisting of two interacting subsystems: the biological (epidemiological ecosystem) and the social (social and economic conditions of life of the society) subsystems where the biological subsystem plays the role of the governed object and the social acts as the internal regulator of these interactions. On the basis of this concept a rational structure of the system of epidemiological surveillance over infectious diseases has been proposed according to which each level of the structure of the epidemic process should be subject to adequate monitoring.     

Manifestations of angina morbidity as a reflection of the self-regulation of the epidemic process in streptococcal infection

The data on the application of the principles of the self regulation of the epidemic process for understanding the annual dynamics of angina morbidity in organized groups of adults are presented. In this case the reservation of group A streptococci occurs in chronic (resident) carriers, whose proportion was found to be 15.8 +/- 2.6%. The epidemic manifestations of morbidity are regulated mainly by the concentration of newly arrived members in the groups, i. e. by the size of the stratum providing the optimum conditions for the parasitization of the streptococcal population. The annual morbidity levels depend essentially not only on the heterogeneity of the group members with respect to their susceptibility to streptococcal infection, but also on the conditions of their accommodation, affecting the transmission of droplet infection. The role of individual risk factors in the variation of the quantitative characteristics of the angina morbidity manifestations under study is calculated.     

The duality of the qualitative determinacy of the epidemic process in anthroponoses as the main trait distinguishing them from the epidemic manifestations of zoonotic diseases in man

The present article substantiates the necessity of defining more accurately the notion "epidemic process" and using this term only in reference to anthroponotic diseases. Proceeding from the philosophical concept of the qualitative definiteness of material objects and phenomena, the author proposes to distinguish the epidemic process in anthroponoses from mass spread of zoonotic diseases among humans on the basis of using the systemic qualities of the epidemic process, and in particular the principle of the dual character of the qualitative definiteness of objects and phenomena as the distinctive feature of the epidemic process of anthroponoses. Distinction, based on this principle, between anthroponotic diseases and zoonotic diseases in groups of humans must be reflected in the definitions of these phenomena. The application of the term "epidemic process" only in reference to anthroponotic diseases is proposed, while zoonotic diseases in groups of humans should be considered as epidemic manifestations of zoonotic infections.     

全球抗病毒药物研发进展与展望

病毒是危害人体健康的主要病原体之一,病毒感染和传播造成的传染性疾病严重威胁人类健康。目前,艾滋病、病毒性肝炎等发病率高、治愈率低的病毒性疾病仍在全球蔓延,流感病毒、冠状病毒等呼吸道病毒不断发生变异,2019年以来,新冠病毒引起的全球疫情对世界各国产生巨大影响,疫情走向还存在很大不确定性,开发安全有效的抗病毒药物成为应对病毒性疾病的重要手段。拟在总结全球抗病毒药物研发整体现状的基础上,分析抗艾滋病病毒、肝炎病毒、新冠病毒等重点领域的新药研发进展,提出抗病毒药物的发展建议,为未来研发更加高效的抗病毒药物提供指引和参考。     

The manifestations of the epidemic process in shigellosis and their theoretical interpretation]

This work, based on the retrospective analysis of shigellosis morbidity among organized groups of adults, as well as the whole population of the city, demonstrates the manifestations of the epidemic process. Water supply was common in the city, while water consumption was autonomous. The organized groups of adults did not use the products of the local milk-processing factory. The following facts were established. The dynamics of morbidity in Flexner's dysentery showed the change of dominating variants of the infective agent, which reflected the action of internal mechanisms of the development of the epidemic process. The role of Sonne dysentery in the total structure of shigellosis morbidity did not correlate with the consumption of milk and milk products. The theory of the self-regulation of the parasitic system and the theory of correspondence served as the basis for the theoretical interpretation of the manifestations of the epidemic process of Shigella infections. To ascertain the real correspondence of individual Shigella species to concrete transmission factors, further investigation are necessary.     

Infectious disease in the Pleistocene: Old friends or old foes?

The impact of endemic and epidemic disease on humans has traditionally been seen as a comparatively recent historical phenomenon associated with the Neolithisation of human groups, an increase in population size led by sedentarism, and increasing contact with domesticated animals as well as species occupying opportunistic symbiotic and ectosymbiotic relationships with humans. The orthodox approach is that Neolithisation created the conditions for increasing population size able to support a reservoir of infectious disease sufficient to act as selective pressure. This orthodoxy is the result of an overly simplistic reliance on skeletal data assuming that no skeletal lesions equated to a healthy individual, underpinned by the assumption that hunter-gatherer groups were inherently healthy while agricultural groups acted as infectious disease reservoirs. The work of van Blerkom, Am. J. Phys. Anthropol., vol. suppl 37 (2003), Wolfe et al., Nature, vol. 447 (2007) and Houldcroft and Underdown, Am. J. Phys. Anthropol., vol. 160, (2016) has changed this landscape by arguing that humans and pathogens have long been fellow travelers. The package of infectious diseases experienced by our ancient ancestors may not be as dissimilar to modern infectious diseases as was once believed. The importance of DNA, from ancient and modern sources, to the study of the antiquity of infectious disease, and its role as a selective pressure cannot be overstated. Here we consider evidence of ancient epidemic and endemic infectious diseases with inferences from modern and ancient human and hominin DNA, and from circulating and extinct pathogen genomes. We argue that the pandemics of the past are a vital tool to unlock the weapons needed to fight pandemics of the future.     

The uses of epidemic models.

This paper is concerned with models formulated to describe the spread of infectious diseases through a community. Some standard epidemic models are introduced and an overview of their uses is provided. The paper includes a discussion of the advantages of simple models over complex ones and the advantages of stochastic models over deterministic ones. The role that epidemic models can play in helping us to understand the spread of diseases and to plan control policies for diseases is explained. The paper also contains a review of some major insights gained from a study of epidemic models and from statistical analyses of disease data using epidemic models. Some explicit suggestions for future research projects are made.     

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 Modeling of Global Epidemics: Stochastic Dynamics and Predictability

The global spread of emergent diseases is inevitably entangled with the structure of the population flows among different geographical regions. The airline transportation network in particular shrinks the geographical space by reducing travel time between the world's most populated areas and defines the main channels along which emergent diseases will spread. In this paper, we investigate the role of the large-scale properties of the airline transportation network in determining the global propagation pattern of emerging diseases. We put forward a stochastic computational framework for the modeling of the global spreading of infectious diseases that takes advantage of the complete International Air Transport Association 2002 database complemented with census population data. The model is analyzed by using for the first time an information theory approach that allows the quantitative characterization of the heterogeneity level and the predictability of the spreading pattern in presence of stochastic fluctuations. In particular we are able to assess the reliability of numerical forecast with respect to the intrinsic stochastic nature of the disease transmission and travel flows. The epidemic pattern predictability is quantitatively determined and traced back to the occurrence of epidemic pathways defining a backbone of dominant connections for the disease spreading. The presented results provide a general computational framework for the analysis of containment policies and risk forecast of global epidemic outbreaks. On leave from CEA-Centre d'Etudes de Bruyères-Le-Chatel, France.     

Primary and Secondary Antifungal Prophylaxis in the Immunocompromised Child: Where do we Stand?

Invasive opportunistic fungal infections are important causes of morbidity and mortality in immunocompromised children undergoing chemotherapy or haematopoietic stem cell transplantation (HSCT). Primary and secondary chemoprophylaxis of invasive fungal infections targets high risk disease-related patients with acute myeloid leukaemia, high risk acute lymphoblastic leukaemias, recurrent leukaemias and those following allogeneic HSCT. The rationale for antifungal prophylaxis in high risk patients comes from two different aspects. On the one hand, is the difficulty of instant diagnosis and, on the other hand, the consequences of morbidity and mortality by invasive infectious diseases. Although we have limited pediatric data concerning antifungal prophylaxis, it has become part of infectious disease supportive care schemes in most of paediatric leukaemia and HSCT centres. This review has insights on the evidence concerning primary and secondary antifungal prophylaxis in immunocompromised children. Although our knowledge comes from large adult studies concerning antifungal agents, there is a great need for evidence of primary or secondary antifungal prophylaxis in large pediatric clinical trials in order to have a consensus in primary and secondary antifungal prophylaxis in immunocompromised children.     

The general characteristics of the epidemic process and of the circulating streptococcal strains during an upsurge in scarlatina morbidity in Leningrad

The dynamics of scarlet fever morbidity in Leningrad for many years was studied and the absence of any effect produced by the existing system of preventive measures against this disease for the last 30 years was shown. On the basis of epidemiological and bacteriological data the authors came to the conclusion on the unity of the epidemic process of scarlet fever in the whole city and the relatively autonomous character of the process in individual districts. The necessity of the realization of epidemiological surveillance on streptococcal infection, with special emphasis on the multilevel social structure of the city and the wide use of the bacteriological diagnosis of streptococcal diseases, is substantiated.     

Determining travel fluxes in epidemic areas

Infectious diseases attack humans from time to time and threaten the lives and survival of people all around the world. An important strategy to prevent the spatial spread of infectious diseases is to restrict population travel. With the reduction of the epidemic situation, when and where travel restrictions can be lifted, and how to organize orderly movement patterns become critical and fall within the scope of this study. We define a novel diffusion distance derived from the estimated mobility network, based on which we provide a general model to describe the spatiotemporal spread of infectious diseases with a random diffusion process and a deterministic drift process of the population. We consequently develop a multi-source data fusion method to determine the population flow in epidemic areas. In this method, we first select available subregions in epidemic areas, and then provide solutions to initiate new travel flux among these subregions. To verify our model and method, we analyze the multi-source data from mainland China and obtain a new travel flux triggering scheme in the selected 29 cities with the most active population movements in mainland China. The testable predictions in these selected cities show that reopening the borders in accordance with our proposed travel flux will not cause a second outbreak of COVID-19 in these cities. The finding provides a methodology of re-triggering travel flux during the weakening spread stage of the epidemic.     

Nutrition and infectious diseases in developing countries and problems of acquired immunodeficiency syndrome

Infectious diseases are the major causes of death and morbidity in underdeveloped countries, particularly in children. Increasing evidence suggests that malnutrition-both Protein-Energy type Malnutrition (PEM) and essential micronutrient (vitamins, trace minerals, essential amino acids, polyunsaturated fatty acids) type-is the underlying reason for increased susceptibility to infections. On the other hand, certain infectious diseases also cause malnutrition, which results in a vicious cycle. Before its viral origin was known, acquired immunodeficiency syndrome (AIDS) had been termed the thin disease because cachexia was AIDS' main clinical manifestation. The relationship between infection and malnutrition is well documented in the literature. Our experience supports this. Preventive and therapeutic measures are suggested.     

Significance of the heterogeneity of respiratory syncytial viral populations in the development of the epidemic process

The manifestations of the epidemic process in respiratory syncytial (RS) virus infection induced by the strains of the infective agent, differing in their capacity for reproduction at 39 degrees and 37 degrees C and in their sensitivity to antibodies, were compared. The observation of children in a group (about 80 children simultaneously) with the systematic serological and virological examination of sick and healthy children was the main method in this investigation. The circulation of RS viruses with greater capacity for reproduction at 39 degrees and 37 degrees C and lesser sensitivity to antibodies, i.e. viruses with greater virulence, was accompanied by the increased intensity of manifestations of the epidemic process. An increase in the heterogeneity of RS virus populations isolated at the same period of observation was accompanied by the intensification of the epidemic process, which was manifested by increased morbidity rate and a higher level of contamination in children, an increase in the incidence of outbreaks and in the frequency of RS virus reinfection.     

Are there Characteristics of Infectious Diseases that Raise Special Ethical Issues?1

This paper examines the characteristics of infectious diseases that raise special medical and social ethical issues, and explores ways of integrating both current bioethical and classical public health ethics concerns. Many of the ethical issues raised by infectious diseases are related to these diseases' powerful ability to engender fear in individuals and panic in populations. We address the association of some infectious diseases with high morbidity and mortality rates, the sense that infectious diseases are caused by invasion or attack on humans by foreign micro-organisms, the acute onset and rapid course of many infectious diseases, and, in particular, the communicability of infectious diseases. The individual fear and community panic associated with infectious diseases often leads to rapid, emotionally driven decision making about public health policies needed to protect the community that may be in conflict with current bioethical principles regarding the care of individual patients. The discussion includes recent examples where dialogue between public health practitioners and medical-ethicists has helped resolve ethical issues that require us to consider the infected patient as both a victim with individual needs and rights and as a potential vector of disease that is of concern to the community.     

The evolutionary economics of immunity

How much of its resources should an individual invest in a costly immune system? In this article, we apply an evolutionarily stable strategy analysis to an epidemic model to answer this question. On the one hand, an investment in immune function confers protection to infectious agents by reducing host susceptibility, pathogen virulence, or the length of the infectious period. On the other hand, an immune system is costly since it absorbs resources that otherwise might be invested in increasing the host's fertility or longevity. In addition, an active immune system may be able to clear pathogens efficiently but at the same time may result in immunopathology. By means of a reproductive value approach, we show how to compare the costs and benefits of an immune system systematically and how to derive the evolutionarily stable level of immune function. We then apply these methods to various plausible scenarios. The analysis reveals that the relationship between the life span of an organism and the optimal level of investment in immune function is less straightforward than one might expect. First, the prevalence of infection is reduced to the lowest possible level only under special circumstances. Second, members of a long-lived species do not necessarily have to invest more in immune function than those of a short-lived species. In fact, the opposite may be true. Third, the outcome of evolution can be contingent on the initial conditions. Depending on its initial investment strategy, a population may evolve to a state where very much or almost nothing is invested in a costly immune system.     

Epidemic enhancement in partially immune populations

We observe that a pathogen introduced into a population containing individuals with acquired immunity can result in an epidemic longer in duration and/or larger in size than if the pathogen were introduced into a naive population. We call this phenomenon "epidemic enhancement," and use simple dynamical models to show that it is a realistic scenario within the parameter ranges of many common infectious diseases. This finding implies that repeated pathogen introduction or intermediate levels of vaccine coverage can lead to pathogen persistence in populations where extinction would otherwise be expected.     

Edge-Based Compartmental Modelling of an SIR Epidemic on a Dual-Layer Static–Dynamic Multiplex Network with Tunable Clustering

The duration, type and structure of connections between individuals in real-world populations play a crucial role in how diseases invade and spread. Here, we incorporate the aforementioned heterogeneities into a model by considering a dual-layer static–dynamic multiplex network. The static network layer affords tunable clustering and describes an individual’s permanent community structure. The dynamic network layer describes the transient connections an individual makes with members of the wider population by imposing constant edge rewiring. We follow the edge-based compartmental modelling approach to derive equations describing the evolution of a susceptible–infected–recovered epidemic spreading through this multiplex network of individuals. We derive the basic reproduction number, measuring the expected number of new infectious cases caused by a single infectious individual in an otherwise susceptible population. We validate model equations by showing convergence to pre-existing edge-based compartmental model equations in limiting cases and by comparison with stochastically simulated epidemics. We explore the effects of altering model parameters and multiplex network attributes on resultant epidemic dynamics. We validate the basic reproduction number by plotting its value against associated final epidemic sizes measured from simulation and predicted by model equations for a number of set-ups. Further, we explore the effect of varying individual model parameters on the basic reproduction number. We conclude with a discussion of the significance and interpretation of the model and its relation to existing research literature. We highlight intrinsic limitations and potential extensions of the present model and outline future research considerations, both experimental and theoretical.