8.34 - Molecular Biomarkers

Streptococcus pyogenes, (colloquially named “group A streptococcus” (GAS)), is a pathogen of public health significance, infecting 18.1 million people worldwide and resulting in 500,000 deaths each year. This review identified published articles on the risk factors and public health prevention and control strategies for mitigating GAS diseases. The pathogen causing GAS diseases is commonly transmitted via respiratory droplets, touching skin sores caused by GAS or through contact with contaminated material or equipment. Foodborne transmission is also possible, although there is need for further research to quantify this route of infection. It was found that GAS diseases are highly prevalent in developing countries, and among indigenous populations and low socioeconomic areas in developed countries. Children, the immunocompromised and the elderly are at the greatest risk of S. pyogenes infections and the associated sequelae, with transmission rates being higher in schools, kindergartens, hospitals and residential care homes. This was attributed to overcrowding and the higher level of social contact in these settings. Prevention and control measures should target the improvement of living conditions, and personal and hand hygiene. Adherence to infection prevention and control practices should be emphasized in high-risk settings. Resource distribution by governments, especially in developed countries, should also be considered.

Diet and vitamin D as risk factors for lung impairment and COPD

The first children with HIV-1 infection were described in 1983. As of 1998, the global HIV epidemic is having a profound impact on the health and survival of children. Almost all HIV infections among young children are due to vertical transmission, and the intrapartum period appears to provide us with a crucial window of opportunity for prevention. Postnatal transmission through breastfeeding also contributes an estimated one third to one half of vertical transmission worldwide. Carefully conducted epidemiologic studies are elucidating the immunologic, virologic, and behavioral factors affecting the risk of HIV-1 transmission from mother to infant and the natural history of HIV disease in perinatally infected children. Transmission of HIV-1 is influenced by many factors, and a high maternal viral load is insufficient to fully explain vertical transmission of HIV-1. Pediatricians and other providers should counsel HIV-infected women about the means available to decrease the risk of HIV transmission to the infant. However, the majority of HIV-infected children are born in the developing world, and a crucial challenge is to identify safe and effective interventions that are feasible in those countries with the most significant HIV burden.

Efficient management of disasters has received increased attention globally. It has been realized by all countries in the world that no development is sustainable if human life is vulnerable to major Disaster risks. Disaster Preparedness and Response are the most important components of an effective Disaster Management strategy. The objective of Disaster Preparedness is to ensure that appropriate systems are in place and personnel are trained to provide immediate response to victims in the event of any Disaster. Medical response is one of the most critical, most important and of immediate requirement in any Disaster situation. The success or failure of any Disaster Management operations will depend to a great extent on the success achieved by the Medical and Health sector since most of the Deaths and illnesses caused by disasters are preventable health risks. Though Disaster Management is the responsibility of every organization and institution, the Health Sector has a key role to play, as it is the lead sector. Hence, health personnel play a very important role in reducing disaster risks. This paper briefly examines the role and responsibilities of Medical and Health personnel and provides an overview of Emergency medical preparedness for reducing disaster risks. The concept of Disaster Medicine in dealing with the public health management of Disasters and Emergency Medical Preparedness, including the Prevention, Response, Relief and Rescue operations of Health Management while addressing various issues like casualty area management and Hospital Management etc through various strategies and actions will also be discussed. The Impact of Disasters on Health and how they can be best managed to reduce the number of mortalities and morbidities resulting from Disasters will be examined. The need for ensuring Community Participation in Health Management and prevention of health risk through Immunization and vaccination, proper food & nutrition, maintenance of hygienic and sanitation, adequate system of garbage disposal, Vector control and Research and Epidemiological studies will also be discussed. Prof. Bhaskara Rao, Mulam, Specialist, Policy, Planning and Related Issues, SAARC Disaster Management Centre (SDMC), New Delhi

AGA Clinical Practice Update on Management of Inflammatory Bowel Disease in Elderly Patients: Expert Review

Modulation of gene expression is influenced by environmental exposures, genetic variation and stochastic processes. Epigenetic biomarkers that signal the outcome of their combined impact could be important early predictors of susceptibility to chronic noncommunicable diseases. Can epigenetic epidemiology shed light on causality and mechanism? Common complex traits arise over time and are the end result of lifestyle choices and a combination of environmental exposures during periods of developmental vulnerability and epigenetic plasticity in the presence of a combination of susceptible genetic variants. Genome-wide association studies to identify the genetic contributions to complex traits have identified many high probability allelic associations, but almost invariably each with a small effect, explaining only a modest percentage of the heritability of the trait. Notably, many estimates of heritability are inflated and do not adequately take into account-shared environment and other familial factors. It is not new to suggest that tissue-specific epigenetic modulation plays a major role in the development of complex traits, yet few have managed to support this using a robust experimental approach. Whereas the genome remains constant, gene expression is labile, demonstrates cell type and developmental specificity, age and sex differences, and is variably responsive to changes in the environment. What are the relationships between genetic variation and different environments that influence epigenetic responses? How do we begin to understand causal relationships that influence gene expression? From an experimental perspective, it is challenging to design studies that can address these questions, yet present a feasible and affordable approach. Large international and interdisciplinary studies are beginning to provide a good framework to better understand gene expression regulation in humans. Though open to criticism, their value should not be underestimated. They include ENCODE that examined 147 cell lines to search for functional elements in the genome [1]; the Epigenomics Roadmap [2] that examined 127 tissue biopsies from embryos and adults, both diseased and healthy, with a focus on identifying functional regulatory elements; the International Human Epigenome Consortium [3]; and the Genome Tissue Expression project (GTEx) that explores the relationship between genetic variation and tissue-specific gene expression and alternate splicing by sequencing whole genomes and examining gene expression in over 20,000 tissue samples from 900 individuals [4]. These data are beginning to give insight into cell specific, developmental stage, sex, age and ethnicity influenced, and stochastic gene expression differences at an individual and population level. The layered annotations in genome browsers highlight the importance of integrating transcriptome data (mRNA, miRNA and lncRNA) with DNA methylation, histone modification and chromatin interaction data to more fully understand function. Epigenome-wide association studies (EWASs) to identify regulatory mechanisms Epigenetic epidemiology: is there cause for optimism?

Traditional environmental epidemiology has relied on assessing individual exposures and their effects. Exposure science methods provides opportunities to advance epidemiological studies considering multiple and consequent exposures and over extended periods of time. Materializing the exposome concept requires methods to collect, integrate and assimilate data from multiple exposures including at personal levels, genomics, personal activities, locations, socio-behaviors, biomarkers of exposures, physiological effects, and health outcomes - all with appropriate spatiotemporal descriptions and associated uncertainties in measurements. Such an exposome requires integration of data from wearable and stationary sensors, environmental monitors, physiology, medication use and other clinical data. In addition, such an integration needs to have a high spatial-temporal resolution for correlating times and location of exposures to occurrences of conditions and their severities. This would require filling any gaps in the measured data with modeled data along with characterization of any uncertainties. Informatics is the scientific field that deals with biomedical information, data, and knowledge - their storage, retrieval, and optimal use for problem solving and decision-making. Recently, informatics methods are being developed, evaluated and utilized in sphere of environmental epidemiological and the exposome. In this symposium, we define the novel informatics sub-field, Exposure Health Informatics, and discuss challenges that require development of informatics methods. We then formally describe informatics methods that address these challenges, and their implementation as a scalable computation infrastructure, the Exposure Health Informatics Ecosystem (EHIE). EHIE is a comprehensive, standards-based, open-source informatics platform that provides semantically consistent, metadata-driven, event-based management of exposomic data consisting of sensor data acquisition pipelines, participant and researcher facing tools, computational modeling, and big data integration platform. Finally, with PRISMS pediatric asthma, Environmental Children’s Health Outcomes, diabetes and molecular epidemiological studies as exemplars, we discuss the generalizability of these multi-scale and multi-omics informatics methods for providing epidemiological researchers with robust reproducible pipelines.

Recognizing the increasing cancer burden worldwide, Nasca & Pastides provide a basic understanding of cancer epidemiology, with a particular focus on cancer biology, gene–environment associations in the cancer etiology and major risk factors for cancer. The intended readers are students in public health schools and related medical and para-medical fields as well as those working in cancer control on a regional, national and international level. Since, according to the authors, there is no textbook dealing with cancer epidemiology for first-time students, this book aims to be such a textbook for those with basic knowledge in epidemiology. Nasca & Pastides begin by emphasizing the importance of describing the cancer burden and trends using appropriate measures. Then they explain what cancer is and how it can be diagnosed and categorized using different cancer classification schemes (e.g staging, coding). Chapters 3–7 contribute to the methodological and technical knowledge on cell biology and on study types, which are of particular relevance for investigating carcinogenicity, biomarkers and genetic risk factors. Among them are experimental studies, molecular–epidemiological studies, studies on gene–environment interactions and genetic epidemiology studies. The subsequent chapters (8–16) describe risk factors for cancer in a detailed and comprehensive way. Not only are classic lifestyle and well known risk factors such as tobacco, alcohol, diet and occupational hazards considered but also genetic factors, ionization and radiation, infections, immunological factors and hormones. Possible dose–response relationships are addressed and figures and illustrations help to understand the etiology and terminology. The chapters on risk factors are internally structured in different ways, some by cancer sites, others by the particular factors associated with the increased risks, taking into account the different study types that address these associations. One whole chapter is dedicated to the risk factors for and occurrence of childhood cancers and points out the need for the life–course perspective in cancer research. This chapter was newly added into this second edition. The last section gives an introduction to cancer screening as a method for early detection using certain cancers as examples to demonstrate different screening concepts. Although the chapter on infectious agents and occupational carcinogens addresses the disproportionate geographical burden between high- and low-income countries, not much information in general is provided on geographical differences in cancer burden and survival. Using “descriptive epidemiology” as a chapter heading, one would expect more technical information on what this is. The book makes us aware of the need to take care in interpreting comparisons, trends and data on cancer occurrence; however, it does not state how to carefully interpret these statistics. The authors use tables and figures that aid in understanding the burden of cancer and distribution of cancer sites as well as the categorization within different cancer classification schemes. Several illustrations are used to make etiology and biology of cancer understandable also to non-medical professionals. The appendix provides a detailed glossary with a particular focus on biological and medical terminology, a feature that is usually available in reference books used by medical students. Appendix B lists web sites without indicating the kind of information they could provide to the reader. A more helpful table for major cancer web resources is available on page 3. Every chapter ends with a summary and discussion questions. However, it would be helpful to provide specific answers to these questions in the appendix, which would make an improvement to the relatively ineffectual appendices. The book is an important reference book for students, whether beginners or post-graduate students. It is written in a clear language, is well ordered and accurate. Nevertheless, several cancer epidemiology textbooks are already available from IARC (International Agency for Research on Cancer). Thus the main strength of this book is its strong biological and medical basis as well as the up-to-date reference to the continuum of genetics and biomarkers in cancer epidemiology. Although health policy-makers are not the priority audience, and few words are said on cancer control activities, an introduction in this field would significantly add to Fundamentals of cancer epidemiology. ■

Methodological issues in pooled analysis of biomarker studies.

ObjectivesIn this cross-sectional epidemiological study we aimed to identify molecular profiles for Trichomonas vaginalis and to determine how these molecular profiles were related to patient demographic and clinical characteristics.SettingMolecular typing...

The epidemiology of tuberculosis (TB) in high-income countries is increasingly dictated by immigration. The influence of this trend on paediatric TB and TB elimination are not well defined.We undertook a 25-year conventional and molecular epidemiologic study of paediatric TB in Alberta, one of four major immigrant-receiving provinces in Canada. All isolates of Mycobacterium tuberculosis were DNA fingerprinted using standard methodology.Between 1990 and 2014, 176 children aged 0–14 years were diagnosed with TB. Foreign-born children or Canadian-born children of foreign-born parents accounted for an increasingly large proportion of total cases during the study period (from 32.1% to 89.5%). Of the 78 culture-positive cases, 35 (44.9%) had a putative source case identified by conventional epidemiology, with 34 (97.1%) having a concordant molecular profile. Of the remaining 43 culture-positive cases, molecular profiling identified spatially and temporally related sources in six cases (14.0%). These six children, along with four other children whose source cases were discovered through reverse-contact tracing, had a high morbidity and mortality.The increasing burden of paediatric TB in both foreign-born children and Canadian-born children of foreign-born parents calls for more timely diagnosis of source cases and more targeted screening for latent TB infection.

To investigate whether Hantavirus (HV) and Orientia tsutsugamushi ( OT) can naturally infect and coexist in their host and role. By field epidemiological study, Leptotrombidium scutellare (3829) was collected and separated from mice(166) in epidemic areas. The cells of mites separated from their host and role were cultured. PCR was used to detect HV-RNA and OT-DNA in the cell culture. In 105 Apodemus agrarius, 3 HV-RNA positive, 2 OT-DNA positive and 2 coinfection with HV and OT were detected;in 41 Brown rattus, 2 HV-RNA positive, 1 OT-DNA positive and 1 co-infection with HV and OT were detected. From 15 mites co-infected with HV and OT, 2 strains of HV pathogen, 2 strains of OT pathogen were separated and 1 HV and OT pathogen in the same mite were separate. The study demonstrates that co-infection of HV and OT did simultaneously exist in wild Leptotrombidium scutellare. This theory has some significance to the epidemic and precaution of HV and OT.

The development of effective disease prevention and treatment programs depends on an understanding of the natural history of disease. A conceptual framework is presented for disease natural history and consists of an asymptomatic period of disease followed by a period of symptomatic disease. The focus is on epidemiologic studies for identifying risk factors of the onset of asymptomatic disease, for identifying cofactors of progression to symptomatic disease, and for estimating the duration of the asymptomatic period. The strengths and limitations of various epidemiologic study designs and sources of epidemiologic data are considered for characterizing disease natural history. Issues in the interpretation and analysis of natural history parameters of disease estimated from cross-sectional, prevalent cohort, cohort, and matched case-control studies are considered. The issues and analytic methods are illustrated with studies of the acquired immunodeficiency syndrome (AIDS) and cervical cancer. Based on these analytic methods, an estimate of the incubation period distribution of AIDS is given.

Haemophilus parasuis: new trends on diagnosis, epidemiology and control

The genetic variations in internal transcribed spacers (ITS) spanning ITS-1, 5.8S and ITS-2 rDNA of Dicrocoelium dendriticum, isolated from sheep and goats in four geographical regions in Shaanxi province, were examined. The lengths of ITS-1, 5.8S and ITS-2 rDNA sequences for D. dendriticum were 749bp, 161bp and 234bp, respectively. Intra-specific sequence variations of D. dendriticum were 0-0.5% for ITS-1 and 0-1.3% for ITS-2 rDNA, while the inter-specific variations among species in genus Dicrocoelium in ITS-2 rDNA were 3.4-12.3%. Phylogenetic analysis based on sequences of ITS-2 rDNA showed that all D. dendriticum isolates in the present study were grouped with reference D. dendriticum isolates from sheep and goats, and D. dendriticum isolates from cattle and Japanese serow were clustered in a sister clade. However, the phylogenetic tree could not reveal geographically genetic relationships of D. dendriticum isolates in different origins and hosts. These findings provided basic information for further study of molecular epidemiology and control of D. dendriticum infection in Shaanxi province as well as in the world.