How to make predictions about future infectious disease risks

Formal, quantitative approaches are now widely used to make predictions about the likelihood of an infectious disease outbreak, how the disease will spread, and how to control it. Several well-established methodologies are available, including risk factor analysis, risk modelling and dynamic modelling. Even so, predictive modelling is very much the 'art of the possible', which tends to drive research effort towards some areas and away from others which may be at least as important. Building on the undoubted success of quantitative modelling of the epidemiology and control of human and animal diseases such as AIDS, influenza, foot-and-mouth disease and BSE, attention needs to be paid to developing a more holistic framework that captures the role of the underlying drivers of disease risks, from demography and behaviour to land use and climate change. At the same time, there is still considerable room for improvement in how quantitative analyses and their outputs are communicated to policy makers and other stakeholders. A starting point would be generally accepted guidelines for 'good practice' for the development and the use of predictive models.     

Understanding the Development and Perception of Global Health for More Effective Student Education

The concept of “global health” that led to the establishment of the World Health Organization in the 1940s is still promoting a global health movement 70 years later. Today’s global health acts first as a guiding principle for our effort to improve people’s health across the globe. Furthermore, global health has become a branch of science, “global health science,” supporting institutionalized education. Lastly, as a discipline, global health should focus on medical and health issues that: 1) are determined primarily by factors with a cross-cultural, cross-national, cross-regional, or global scope; 2) are local but have global significance if not appropriately managed; and 3) can only be efficiently managed through international or global efforts. Therefore, effective global health education must train students 1) to understand global health status; 2) to investigate both global and local health issues with a global perspective; and 3) to devise interventions to deal with these issues.     

Ethical models underpinning responses to threats to public health: a comparison of approaches to communicable disease control in Europe

Increases in international travel and migratory flows have enabled infectious diseases to emerge and spread more rapidly than ever before. Hence, it is increasingly easy for local infectious diseases to become global infectious diseases (GIDs). National governments must be able to react quickly and effectively to GIDs, whether naturally occurring or intentionally instigated by bioterrorism. According to the World Health Organisation, global partnerships are necessary to gather the most up-to-date information and to mobilize resources to tackle GIDs when necessary. Communicable disease control also depends upon national public health laws and policies. The containment of an infectious disease typically involves detection, notification, quarantine and isolation of actual or suspected cases; the protection and monitoring of those not infected; and possibly even treatment. Some measures are clearly contentious and raise conflicts between individual and societal interests. In Europe national policies against infectious diseases are very heterogeneous. Some countries have a more communitarian approach to public health ethics, in which the interests of individual and society are more closely intertwined and interdependent, while others take a more liberal approach and give priority to individual freedoms in communicable disease control. This paper provides an overview of the different policies around communicable disease control that exist across a select number of countries across Europe. It then proposes ethical arguments to be considered in the making of public health laws, mostly concerning their effectiveness for public health protection.     

Global mapping of transposon location

Transposable genetic elements are ubiquitous, yet their presence or absence at any given position within a genome can vary between individual cells, tissues, or strains. Transposable elements have profound impacts on host genomes by altering gene expression, assisting in genomic rearrangements, causing insertional mutations, and serving as sources of phenotypic variation. Characterizing a genome's full complement of transposons requires whole genome sequencing, precluding simple studies of the impact of transposition on interindividual variation. Here, we describe a global mapping approach for identifying transposon locations in any genome, using a combination of transposon-specific DNA extraction and microarray-based comparative hybridization analysis. We use this approach to map the repertoire of endogenous transposons in different laboratory strains of Saccharomyces cerevisiae and demonstrate that transposons are a source of extensive genomic variation. We also apply this method to mapping bacterial transposon insertion sites in a yeast genomic library. This unique whole genome view of transposon location will facilitate our exploration of transposon dynamics, as well as defining bases for individual differences and adaptive potential.     

Global mapping of pharmacological space

We present the global mapping of pharmacological space by the integration of several vast sources of medicinal chemistry structure-activity relationships (SAR) data. Our comprehensive mapping of pharmacological space enables us to identify confidently the human targets for which chemical tools and drugs have been discovered to date. The integration of SAR data from diverse sources by unique canonical chemical structure, protein sequence and disease indication enables the construction of a ligand-target matrix to explore the global relationships between chemical structure and biological targets. Using the data matrix, we are able to catalog the links between proteins in chemical space as a polypharmacology interaction network. We demonstrate that probabilistic models can be used to predict pharmacology from a large knowledge base. The relationships between proteins, chemical structures and drug-like properties provide a framework for developing a probabilistic approach to drug discovery that can be exploited to increase research productivity.     

Global mapping of lymphatic filariasis

Disease maps are becoming increasingly important in infectious disease epidemiology and control. For lymphatic filariasis, the development of such maps has been hampered in the past by the lack of data on the geographical distribution of levels of infection or disease. Here, Edwin Michael and Don Bundy present an atlas for this parasitic disease derived from a recently compiled geographical database. Focusing on mapping and analysis of case prevalence data at the global and regional levels, the authors show how mapping the geographical distribution is integral not only to assessing spatial patterns in the infection and disease distribution but also to stratifying endemic areas by infection and/or disease rate.     

Prevalence of antibody to hantaviruses in humans and rodents in the Caribbean region of Colombia determined using Araraquara and Maciel virus antigens

We tested sera from 286 agricultural workers and 322 rodents in the department of Córdoba, northeastern Colombia, for antibodies against two hantaviruses. The sera were analysed by indirect ELISA using the lysate of Vero E6 cells infected with Maciel virus (MACV) or the N protein of Araraquara virus (ARAV) as antigens for the detection of antibodies against hantaviruses. Twenty-four human sera were IgG positive using one or both antigens. We detected anti-MACV IgG antibodies in 10 sera (3.5%) and anti-ARAV antibodies in 21 sera (7.34%). Of the 10 samples that were positive for MACV, seven (70%) were cross-reactive with ARAV; seven of the 21 ARAV-positive samples were cross-reactive with MACV. Using an ARAV IgM ELISA, two of the 24 human sera (8.4%) were positive. We captured 322 rodents, including 210 Cricetidae (181 Zygodontomys brevicauda, 28 Oligoryzomys fulvescens and 1 Oecomys trinitatis), six Heteromys anomalus (Heteromyidae), one Proechimys sp. (Echimyidae) and 105 Muridae (34 Rattus rattus and 71 Mus musculus). All rodent sera were negative for both antigens. The 8.4% detection rate of hantavirus antibodies in humans is much higher than previously found in serosurveys in North America, suggesting that rural agricultural workers in northeastern Colombia are frequently exposed to hantaviruses. Our results also indicate that tests conducted with South American hantavirus antigens could have predictive value and could represent a useful alternative for the diagnosis of hantavirus infection in Colombia.     

Environmental changes impacting Echinococcus transmission: research to support predictive surveillance and control

Echinococcosis, resulting from infection with tapeworms Echinococcus granulosus and E. multilocularis, has a global distribution with 2–3 million people affected and 200,000 new cases diagnosed annually. Costs of treatment for humans and economic losses to the livestock industry have been estimated to exceed $2 billion. These figures are likely to be an underestimation given the challenges with its early detection and the lack of mandatory official reporting policies in most countries. Despite this global burden, echinococcosis remains a neglected zoonosis. The importance of environmental factors in influencing the transmission intensity and distribution of Echinococcus spp. is increasingly being recognized. With the advent of climate change and the influence of global population expansion, food insecurity and land‐use changes, questions about the potential impact of changing temperature, rainfall patterns, increasing urbanization, deforestation, grassland degradation and overgrazing on zoonotic disease transmission are being raised. This study is the first to comprehensively review how climate change and anthropogenic environmental factors contribute to the transmission of echinococcosis mediated by changes in animal population dynamics, spatial overlap of competent hosts and the creation of improved conditions for egg survival. We advocate rigorous scientific research to establish the causal link between specific environmental variables and echinococcosis in humans and the incorporation of environmental, animal and human data collection within a sentinel site surveillance network that will complement satellite remote‐sensing information. Identifying the environmental determinants of transmission risk to humans will be vital for the design of more accurate predictive models to guide cost‐effective pre‐emptive public health action against echinococcosis.     

Temporal trends in the discovery of human viruses

On average, more than two new species of human virus are reported every year. We constructed the cumulative species discovery curve for human viruses going back to 1901. We fitted a statistical model to these data; the shape of the curve strongly suggests that the process of virus discovery is far from complete. We generated a 95% credible interval for the pool of as yet undiscovered virus species of 38-562. We extrapolated the curve and generated an estimate of 10-40 new species to be discovered by 2020. Although we cannot predict the level of health threat that these new viruses will present, we conclude that novel virus species must be anticipated in public health planning. More systematic virus discovery programmes, covering both humans and potential animal reservoirs of human viruses, should be considered.     

Application of Ethical Principles to Research using Public Health Data in The Global South: Perspectives from Africa

Existing ethics guidelines, influential literature and policies on ethical research generally focus on real‐time data collection from humans. They enforce individual rights and liberties, thereby lowering need for aggregate protections. Although dependable, emerging public health research paradigms like research using public health data (RUPD) raise new challenges to their application. Unlike traditional research, RUPD is population‐based, aligned to public health activities, and often reliant on pre‐collected longitudinal data. These characteristics, when considered in relation to the generally lower protective ethico‐legal frameworks of the Global South, including Africa, highlight ethical gaps. Health and demographic surveillance systems are examples of public health programs that accommodate RUPD in these contexts. We set out to explore the perspectives of professionals with a working knowledge of these systems to determine practical ways of appropriating the foundational principles of health research to advance the ever growing opportunities in RUPD. We present their perspectives and in relation to the literature and our ethical analysis, make context relevant recommendations. We further argue for the development of a framework founded on the discussions and recommendations as a minimum base for achieving optimal ethics for optimal RUPD in the Global South.     

Tuberculosis y hacinamiento carcelario desde la perspectiva de las inequidades sociales en salud en Colombia, 2018

Introduction:

Prison population is affected by tuberculosis (TB) due to prison overcrowding. This situation reflects an inequity in health, understood as an unfair and avoidable difference between individuals and populations.

Objective:

To estimate the conditions of prison overcrowding as health inequity in prison population suffering from TB in Colombia during 2018.

Materials and methods:

This is an ecological study to estimate inequities at the national level in prison population through the use of the World Health Organization methodology for the measurement of inequalities. Based on data from the public health surveillance system, the incidence of TB was taken as an indicator and the percentage of overcrowding as an equity stratifier. Simple and complex measures of inequality were calculated.

Results:

The relative inequality between the lowest and highest quintiles of crowding showed that TB incidence among prison population with the highest crowding was 1.92 times that of the group with the lowest crowding. The inequality index identified an excess of 724 TB cases per 100,000 among those with the highest concentration of overcrowding. The health concentration index was -0.121, which shows that the incidence was concentrated in the group with the most overpopulation.

Conclusion:

In Colombia, prison population in overcrowded conditions and suffering from TB has to face unfair and avoidable inequalities as compared with those not living in these conditions. Policies are required to reduce overcrowding and improve living conditions in prisons.     

大比例尺土壤保持服务制图分级方法研究

科学地编制生态系统服务空间分布图,有助于识别生态系统优先保护热点及空缺,能够为国土安全规划提供基础信息。但由于缺乏统一科学的生态系统服务分级方法,生态系统服务分布图的展示效果和制图效率都受到限制。不恰当的分级制图会误导决策者对生态系统服务空间分布特征的判断,增加生态保护决策的不确定性。以构建生态服务制图分级标准为目标,对我国6个典型县区的土壤保持服务数据展开1：25万比例尺制图分级案例研究。采用分级精度、面积均衡性、极差一致性、空间自相关一致性4个分级质量评价指标评价并比较了目前地图编制中常用的自然断点法、几何间隔法、累积比例法、等差法、分位数法5种分级算法的分级制图效果。结果表明,6个县区有相似的土壤保持服务分布特征：低值区覆盖面积大,高值区覆盖面积小。各县区土壤保持服务制图最优分级方法有差异：延庆区、丰满区最优分级方法为自然断点法;永靖县、天山区、安宁市最优分级方法为累积比例法;富阳区最优分级方法为几何间隔法。各分级方法中,累积比例法在6个县区综合制图效果最优或接近最优,适用性最好,能够较好的刻画各县区的土壤保持服务空间分布特征。本文提出的分级评价方法及其结果,可为生态系统土壤保持服务制图规范化和自动化提供科学依据。     

Global distribution of outbreaks of water-associated infectious diseases

Background

Water plays an important role in the transmission of many infectious diseases, which pose a great burden on global public health. However, the global distribution of these water-associated infectious diseases and underlying factors remain largely unexplored.

Methods and Findings

Based on the Global Infectious Disease and Epidemiology Network (GIDEON), a global database including water-associated pathogens and diseases was developed. In this study, reported outbreak events associated with corresponding water-associated infectious diseases from 1991 to 2008 were extracted from the database. The location of each reported outbreak event was identified and geocoded into a GIS database. Also collected in the GIS database included geo-referenced socio-environmental information including population density (2000), annual accumulated temperature, surface water area, and average annual precipitation. Poisson models with Bayesian inference were developed to explore the association between these socio-environmental factors and distribution of the reported outbreak events. Based on model predictions a global relative risk map was generated. A total of 1,428 reported outbreak events were retrieved from the database. The analysis suggested that outbreaks of water-associated diseases are significantly correlated with socio-environmental factors. Population density is a significant risk factor for all categories of reported outbreaks of water-associated diseases; water-related diseases (e.g., vector-borne diseases) are associated with accumulated temperature; water-washed diseases (e.g., conjunctivitis) are inversely related to surface water area; both water-borne and water-related diseases are inversely related to average annual rainfall. Based on the model predictions, “hotspots” of risks for all categories of water-associated diseases were explored.

Conclusions

At the global scale, water-associated infectious diseases are significantly correlated with socio-environmental factors, impacting all regions which are affected disproportionately by different categories of water-associated infectious diseases.     

Skeletal evidence for the emergence of infectious disease in bronze and iron age northern Vietnam

Human skeletal evidence for the emergence of chronic infectious disease in northern Vietnam is examined. The sample includes the remains of 192 individuals representing the Mid-Holocene and Bronze to Iron Ages. The objective is to see if the transition from sedentary, foraging, coastally oriented economies to centralized chiefdoms with attendant development and intensification of agriculture, trade, metal technologies, warfare, and population increase was accompanied by an emergence of and/or increase in infectious disease. It was found that skeletal evidence for infectious disease was absent in the Mid-Holocene, while over 10% of the Metal period sample exhibited lesions consistent with either infectious disease or immune system disorders. Factors potentially contributing to the emergence of infectious disease in northern Vietnam in the Metal period include: increased contact with bacterial or fungal pathogens either directly or by way of vertebrate and/or arthropod vectors; higher levels of debilitation and/or decreased levels of immunocompetence in the Metal period; and evolution of pathogens present in Mid-Holocene human hosts into more virulent forms in the Metal period. The first two factors may be related to historically and archaeologically documented major demographic (Han colonizing efforts) and economic (agricultural intensification) changes in the region during the Metal period.     

Global leaf-trait mapping based on optimality theory

Aim

Leaf traits are central to plant function, and key variables in ecosystem models. However recently published global trait maps, made by applying statistical or machine-learning techniques to large compilations of trait and environmental data, differ substantially from one another. This paper aims to demonstrate the potential of an alternative approach, based on eco-evolutionary optimality theory, to yield predictions of spatio-temporal patterns in leaf traits that can be independently evaluated.

Innovation

Global patterns of community-mean specific leaf area (SLA) and photosynthetic capacity (V_cmax) are predicted from climate via existing optimality models. Then leaf nitrogen per unit area (N_area) and mass (N_mass) are inferred using their (previously derived) empirical relationships to SLA and V_cmax. Trait data are thus reserved for testing model predictions across sites. Temporal trends can also be predicted, as consequences of environmental change, and compared to those inferred from leaf-level measurements and/or remote-sensing methods, which are an increasingly important source of information on spatio-temporal variation in plant traits.

Main conclusions

Model predictions evaluated against site-mean trait data from > 2,000 sites in the Plant Trait database yielded R² = 73% for SLA, 38% for N_mass and 28% for N_area. Declining species-level N_mass, and increasing community-level SLA, have both been recently reported and were both correctly predicted. Leaf-trait mapping via optimality theory holds promise for macroecological applications, including an improved understanding of community leaf-trait responses to environmental change.     

Transgenic plants for animal health: plant-made vaccine antigens for animal infectious disease control

A variety of plant species have been genetically modified to accumulate vaccine antigens for human and animal health and the first vaccine candidates are approaching the market. The regulatory burden for animal vaccines is less than that for human use and this has attracted the attention of researchers and companies, and investment in plant-made vaccines for animal infectious disease control is increasing. The dosage cost of vaccines for animal infectious diseases must be kept to a minimum, especially for non-lethal diseases that diminish animal welfare and growth, so efficient and economic production, storage and delivery are critical for commercialization. It has become clear that transgenic plants are an economic and efficient alternative to fermentation for large-scale production of vaccine antigens. The oral delivery of plant-made vaccines is particularly attractive since the expensive purification step can be avoided further reducing the cost per dose. This review covers the current status of plant-produced vaccines for the prevention of disease in animals and focuses on barriers to the development of such products and methods to overcome them.     

Surveillance and control of asymptomatic carriers of drug‐resistant bacteria

Drug‐resistant bacterial infections constitute a major threat to global public health. Several key bacteria that are becoming increasingly resistant are among those that are ubiquitously carried by human beings and usually cause no symptoms (i.e. individuals are asymptomatic carriers) until and/or unless a precipitating event leads to symptomatic infection (and thus disease). Carriers of drug‐resistant bacteria can also transmit resistant pathogens to others, thus putting the latter at risk of resistant infections. Accumulating evidence suggests that such transmission occurs not only in hospital settings but also in the general community, although considerably more data are needed to assess the extent of this problem. Asymptomatic carriage of drug‐resistant bacteria raises important ethical questions regarding the appropriate public health response, including the degree to which it would be justified to impose burdens on asymptomatic carriers (and others) in order to prevent transmission. In this paper, we (i) summarize current evidence regarding the carriage of key drug‐resistant bacteria, noting important knowledge gaps; and (ii) explore the particular implications of existing public health ethics frameworks for policy‐making regarding asymptomatic carriers. Inter alia, we argue that the relative burdens imposed by public health measures on healthy carriers (as opposed to sick individuals) warrant careful consideration and should be proportionate to the expected public health benefits in terms of risks averted. We conclude that more surveillance and research regarding community transmission will be needed in order to clarify relevant risks and design proportionate policies, although extensive community surveillance itself would also require careful ethical consideration.