Molecular Epidemiology Of Infectious Diseases Research Articles

Population Structure and Dynamics of Helminthic Infection: Schistosomiasis.

While disease and outbreaks are mainly clonal for bacteria and other asexually reproducing organisms, sexual reproduction in schistosomes and other helminths usually results in unique individuals. For sexually reproducing organisms, the traits conserved in clones will instead be conserved in the group of organisms that tends to breed together, the population. While the same tools are applied to characterize DNA, how results are interpreted can be quite different at times (see another article in this collection, http://www.asmscience.org/content/journal/microbiolspec/10.1128/microbiolspec.AME-0002-2018). It is difficult to know what the real effect any control program has on the parasite population without assessing the health of this population, how they respond to the control measure, and how they recover, if they do. This review, part of the Microbiology Spectrum Curated Collection: Advances in Molecular Epidemiology of Infectious Diseases, concentrates on one approach using pooled samples to study schistosome populations and shows how this and other approaches have contributed to our understanding of this parasite family's biology and epidemiology. *This article is part of a curated collection.

Differentiating Epidemic from Endemic or Sporadic Infectious Disease Occurrence.

One important scope of work of epidemiology is the investigation of infectious diseases that cluster in time and place. Clusters of infectious disease may represent outbreaks or epidemics in which the cases share in common a point source exposure or an infectious agent in a chain of transmission pathways. Investigations of outbreaks of an illness can facilitate identification of a source, risk, or cause of the illness. However, most infectious disease episodes occur not as part of any apparent outbreaks but as sporadic infections. Multiple sporadic infections that occur steadily in time and place are referred to as endemic disease. How does one investigate sources and risk factors for sporadic or endemic infections? As part of the Microbiology Spectrum Curated Collection: Advances in Molecular Epidemiology of Infectious Diseases, this review discusses limitations of traditional approaches and advantages of molecular epidemiology approaches to investigate sporadic and endemic infections. Using specific examples, the discussions show that most sporadic infections are actually part of unrecognized outbreaks and that what appears to be endemic disease occurrence is actually comprised of multiple small outbreaks. These molecular epidemiologic investigations have unmasked modes of transmission of infectious agents not known to cause outbreaks. They have also raised questions about the traditional ways to measure incidence and assess sources of drug-resistant infections in community settings. The discoveries made by the application of molecular microbiology methods in epidemiologic investigations have led to creation of new public health intervention strategies that have not been previously considered. *This article is part of a curated collection.

Phylogenetic Concepts and Tools Applied to Epidemiologic Investigations of Infectious Diseases.

In this review, which is a part of the Microbiology Spectrum Curated Collection: Advances in Molecular Epidemiology of Infectious Diseases, I present an overview of the principles used to classify organisms in the field of phylogenetics, highlight the methods used to infer the interrelationships of organisms, and summarize how these concepts are applied to molecular epidemiologic analyses. I present steps in analyses that come downstream of the assembly of a set of genomes or genes and the production of a multiple-sequence alignment or other matrices of putative orthologs for comparison. I focus on the history of the problem of phylogenetic reconstruction and debates within the field about the most appropriate methods. I illustrate methods that bridge the gap between molecular epidemiology and traditional epidemiology, including phylogenetic character evolution and geographic visualization. Finally, I provide practical advice on how to conduct an example analysis in the appendix. *This article is part of a curated collection.

Advances in Molecular Epidemiology of Infectious Diseases: Definitions, Approaches, and Scope of the Field.

Molecular epidemiology is a discipline that uses molecular microbiology tools to study the distribution and determinants of diseases in human populations and veterinary animals. Our understanding of epidemiology of infectious diseases has evolved with technological advancements made in molecular biology that refine our perception of the identity and dynamics of microorganisms. This review is an introduction to the Microbiology Spectrum Curated Collection: Advances in Molecular Epidemiology of Infectious Diseases that will discuss how these advancements have contributed to investigations of infectious disease outbreaks/epidemics, surveillance, transmission dynamics, risk factor identification, pathogenesis, and etiologic attribution of bacterial, viral, protozoan, and helminthic pathogens to a disease. Here we define "molecular epidemiology" and distinguish it from other disciplines that use many of the same molecular biology tools-taxonomy, phylogenetics, and molecular evolution of microorganisms. The Curated Collection will be spread throughout multiple issues of Microbiology Spectrum and will be divided into four general sections: (i) laboratory methods used to strain type microbial pathogens, (ii) methods used to analyze genotyping data, (iii) examples of molecular epidemiologic investigations of bacterial, viral, and parasitic diseases, and (iv) applications of molecular epidemiology to address new research questions in communicable and noncommunicable diseases. The major theme of this Curated Collection is to address the following question frequently asked by clinicians, clinical microbiologists, and public health professionals: what is the advantage or unique contribution of molecular epidemiology in solving infectious disease problems in the clinical and public health arenas? *This article is part of a curated collection.

Laboratory Methods in Molecular Epidemiology: Viral Infections.

Viruses, which are the most abundant biological entities on the planet, have been regarded as the "dark matter" of biology in the sense that despite their ubiquity and frequent presence in large numbers, their detection and analysis are not always straightforward. The majority of them are very small (falling under the limit of 0.5 μm), and collectively, they are extraordinarily diverse. In fact, the majority of the genetic diversity on the planet is found in the so-called virosphere, or the world of viruses. Furthermore, the most frequent viral agents of disease in humans display an RNA genome, and frequently evolve very fast, due to the fact that most of their polymerases are devoid of proofreading activity. Therefore, their detection, genetic characterization, and epidemiological surveillance are rather challenging. This review (part of the Curated Collection on Advances in Molecular Epidemiology of Infectious Diseases) describes many of the methods that, throughout the last few decades, have been used for viral detection and analysis. Despite the challenge of having to deal with high genetic diversity, the majority of these methods still depend on the amplification of viral genomic sequences, using sequence-specific or sequence-independent approaches, exploring thermal profiles or a single nucleic acid amplification temperature. Furthermore, viral populations, and especially those with RNA genomes, are not usually genetically uniform but encompass swarms of genetically related, though distinct, viral genomes known as viral quasispecies. Therefore, sequence analysis of viral amplicons needs to take this fact into consideration, as it constitutes a potential analytic problem. Possible technical approaches to deal with it are also described here. *This article is part of a curated collection.

Laboratory Methods in Molecular Epidemiology: Bacterial Infections.

In infectious disease epidemiology, the laboratory plays a critical role in diagnosis, outbreak investigations, surveillance, and characterizing biologic properties of microbes associated with their transmissibility, resistance to anti-infectives, and pathogenesis. The laboratory can inform and refine epidemiologic study design and data analyses. In public health, the laboratory functions to assess effect of an intervention. In addition to research laboratories, the new-generation molecular microbiology technology has been adapted into clinical and public health laboratories to simplify, accelerate, and make precise detection and identification of infectious disease pathogens. This technology is also being applied to subtype microbes to conduct investigations that advance our knowledge of epidemiology of old and emerging infectious diseases. Because of the recent explosive progress in molecular microbiology technology and the vast amount of data generated from the applications of this technology, this Microbiology Spectrum Curated Collection: Advances in Molecular Epidemiology of Infectious Diseases describes these methods separately for bacteria, viruses, and parasites. This review discusses past and current advancements made in laboratory methods used to conduct epidemiologic studies of bacterial infections. It describes methods used to subtype bacterial organisms based on molecular microbiology techniques, following a discussion on what is meant by bacterial "species" and "clones." Discussions on past and new genotyping tests applied to epidemiologic investigations focus on tests that compare electrophoretic band patterns, hybridization matrices, and nucleic acid sequences. Applications of these genotyping tests to address epidemiologic issues are detailed elsewhere in other reviews of this series. *This article is part of a curated collection.

Population Genetics and Molecular Epidemiology of Eukaryotes.

Molecular epidemiology uses the distribution and organization of a pathogen's DNA to understand the distribution and determinants of disease. Since the biology of DNA for eukaryotic pathogens differs substantially from that of bacteria, the analytic approach to their molecular epidemiology can also differ. While many of the genotyping techniques presented earlier in this series, "Advances in Molecular Epidemiology of Infectious Diseases," can be applied to eukaryotes, the output must be interpreted in the light of how DNA is distributed from one generation to the next. In some cases, parasite populations can be evaluated in ways reminiscent of bacteria. They differ, however, when analyzed as sexually reproducing organisms, where all individuals are unique but the genetic composition of the population does not change unless a limited set of events occurs. It is these events (migration, mutation, nonrandom mating, selection, and genetic drift) that are of interest. At a given time, not all of them are likely to be equally important, so the list can easily be narrowed down to understand the driving forces behind the population as it is now and even what it will look like in the future. The main population characteristics measured to assess these events are differentiation and diversity, interpreted in the light of what is known about the population from observation. The population genetics of eukaryotes is important for planning and evaluation of control measures, surveillance, outbreak investigation, and monitoring of the development and spread of drug resistance. *This article is part of a curated collection.

Survey on the Use of Whole-Genome Sequencing for Infectious Diseases Surveillance: Rapid Expansion of European National Capacities, 2015-2016.

Whole-genome sequencing (WGS) has become an essential tool for public health surveillance and molecular epidemiology of infectious diseases and antimicrobial drug resistance. It provides precise geographical delineation of spread and enables incidence monitoring of pathogens at genotype level. Coupled with epidemiological and environmental investigations, it delivers ultimate resolution for tracing sources of epidemic infections. To ascertain the level of implementation of WGS-based typing for national public health surveillance and investigation of prioritized diseases in the European Union (EU)/European Economic Area (EEA), two surveys were conducted in 2015 and 2016. The surveys were designed to determine the national public health reference laboratories’ access to WGS and operational WGS-based typing capacity for national surveillance of selected foodborne pathogens, antimicrobial-resistant pathogens, and vaccine-preventable diseases identified as priorities for European genomic surveillance. Twenty-eight and twenty-nine out of the 30 EU/EEA countries participated in the survey in 2015 and 2016, respectively. National public health reference laboratories in 22 and 25 countries had access to WGS-based typing for public health applications in 2015 and 2016, respectively. Reported reasons for limited or no access were lack of funding, staff, and expertise. Illumina technology was the most frequently used followed by Ion Torrent technology. The access to bioinformatics expertise and competence for routine WGS data analysis was limited. By mid-2016, half of the EU/EEA countries were using WGS analysis either as first- or second-line typing method for surveillance of the pathogens and antibiotic resistance issues identified as EU priorities. The sampling frame as well as bioinformatics analysis varied by pathogen/resistance issue and country. Core genome multilocus allelic profiling, also called cgMLST, was the most frequently used annotation approach for typing bacterial genomes suggesting potential bioinformatics pipeline compatibility. Further capacity development for WGS-based typing is ongoing in many countries and upon consolidation and harmonization of methods should enable pan-EU data exchange for genomic surveillance in the medium-term subject to the development of suitable data management systems and appropriate agreements for data sharing.

Molecular epidemiology of infectious diseases.

Molecular epidemiology (ME) is a branch of epidemiology developed by merging molecular biology into epidemiological studies. In this paper, the authors try to discuss the ways that molecular epidemiology studies identify infectious diseases’ causation and pathogenesis, and unravel infectious agents’ sources, reservoirs, circulation pattern, transmission pattern, transmission probability, and transmission order. They bring real-world examples of research works in each area to make each study design more understandable. They also address some research areas and study design aspects that need further attention in future. They close with some thoughts about future directions in this field and emphasize on the need for training competent molecular epidemiology specialists that are capable of dealing with rapid advances in the field.

A survey of tools for analysing DNA fingerprints.

DNA fingerprinting is a genetic typing technique that allows the analysis of the genomic relatedness between samples, and the comparison of DNA patterns. This technique has multiple applications in different fields (medical diagnosis, forensic science, parentage testing, food industry, agriculture and many others). An important task in molecular epidemiology of infectious diseases is the analysis and comparison of pulsed-field gel electrophoresis (PFGE) patterns. This is applied to determine the clonal diversity of bacteria in the follow-up of outbreaks or for tracking specific clones of special relevance. The resulting images produced by DNA fingerprinting are sometimes difficult to interpret, and multiple tools have been developed to simplify this task. In this article, we present a survey of tools for analysing DNA fingerprints. In particular, we compare 33 tools using a set of predefined criteria. The comparison was carried out by hands-on experiences-whenever possible-and inspecting the documentation of the tools. As no system is preferred in all the possible scenarios, we have created a spreadsheet that can be customized by researchers to determine the best system for their needs.

Molecular epidemiology of infectious diseases: analytical methods and results interpretation

Molecular typing and fingerprinting of microbial pathogens represent an essential tool for the epidemiological surveillance, outbreak detection and control of infectious diseases. Indeed, epidemiological investigation without genotyping data may not provide comprehensive information to allow the most appropriate interventions; despite this consideration, some barriers still hamper the routine application and interpretation of molecular typing data. In this paper, the most important methods currently used for characterization of pathogenic microorganisms for microbial source tracking and for the identification of clonal relationships among different isolates, are described according to their principles, advantages and limitations. Criteria for their evaluation and guidelines for the correct interpretation of results are also proposed. Molecular typing methods can be grouped into four categories based on different methodological principles, which include the characterization of restriction sites in genomic or plasmid DNA; the amplification of specific genetic targets; the restriction enzyme digestion and the subsequent amplification; sequence analysis. Although the development and the extensive use of molecular typing systems have greatly improved the understanding of the infectious diseases epidemiology, the rapid diversification, partial evaluation and lack of comparative data on the methods have raised significant questions about the selection of the most appropriate typing method, as well as difficulties for the lack of consensus about the interpretation of the results and nomenclature used for interpretation. Several criteria should be considered in order to evaluate the intrinsic performance and practical advantages of a typing system. However none of the available genotyping methods fully meets all these requirements. Therefore, the combined use of different approaches may lead to a more precise characterization and discrimination of isolates than a single method, especially if used in a hierarchical manner. The interpretation of the molecular results differs according to the typing system's characteristics: for example in the restriction fragments-based analysis, the divergences or the similarity percentages among the profiles are evaluated, whilst the differences in terms of number and intensity of bands are analyzed in the amplification-based approaches. Moreover, a correct interpretation of molecular results significantly depends by other critical factors, such as the comprehension of the typing system and data quality, the microbial diversity, and the epidemiological context in which the method is used. The analysis of PFGE data, considered as the "gold standard", is based on the differences of the number and position of bands patterns, although recent recommendations are now available from the Centers for Diseases Control and Prevention (CDC) for a more accurate interpretation, which also include the evaluation of the gel quality, the genetic diversity of the microorganism, the time and geographical scale of an epidemic event. Future advances in the molecular typing technologies indeed will provide rapid methodological improvements, such as a greater degree of automation, better resolution, higher throughput, and a greater availability of dedicated bioinformatics tools. These factors will all contribute to an increasing application of genotyping methods to better understand the epidemiology of infectious diseases, and to implement, along with the strengthened international and interdisciplinary partnerships, more effective control and prevention strategies for Public Health improvements.

From molecular to genomic epidemiology: transforming surveillance and control of infectious diseases

The use of increasingly powerful genotyping tools for the characterisation of pathogens has become a standard component of infectious disease surveillance and outbreak investigations. This thematic issue of Eurosurveillance, published in two parts, provides a series of review and original research articles that gauge progress in molecular epidemiology strategies and tools, and illustrate their applications in public health. Molecular epidemiology of infectious diseases combines traditional epidemiological methods with analysis of genome polymorphisms of pathogens over time, place and person across human populations and relevant reservoirs, to study host–pathogen interactions and infer hypotheses about host-to-host or source-to-host transmission [1-3]. Based on discriminant genotyping of human pathogens, clonally derived strains can be identified as likely links in a chain of transmission [1-3]. In this two-part issue of Eurosurveillance, Goering et al. explain that such biological evidence of clonal linkage complements but does not replace epidemiological evidence of personto-person contact or common exposure to a potential source [3]. Muellner et al. provide clear examples how prediction about infectious disease outcome and transmission risks can be enhanced through integration of pathogen genetic information and epidemiological modelling to inform public health decisions about food-borne disease prevention [4].

National Reference Centre for Genomics and Proteomics — Macprogen

The “National Reference Centre for Genomics and Proteomics” (MACPROGEN) was financed by the European Commission within the FP7 Capacities Work Program for a period of 3 years, starting April 1 2009. The MACPROGEN project aimed at upgrading and improving the capacity of the Research Centre for Genetic Engineering and Biotechnology (RCGEB) “Georgi D. Efremov,” Macedonian Academy of Sciences and Arts (MASA), Skopje, Republic of Macedonia, for research and education in the fields of genomics and proteomics. The main objectives of the project were to establish a technological platform for high throughput genomics and proteomics research, networking with European Union (EU) research institutions in order to foster collaborative activities, disseminating knowledge and expertise and ultimately building an interactive and competitive research environment. Altogether, the realization of MACPROGEN objectives was contributing to the strengthening of Macedonian research, technology and development capacities and enhancing career opportunities for Macedonian scientists. The RCGEB is one of the few institutions from the Republic of Macedonia that met the criteria for a center of excellence due to its esteemed scientific and educational record in life sciences. The RCGEB was founded in 1987 as a research unit of MASA with the main goal of advancing scientific knowledge in the field of protein chemistry, molecular biology, genetic engineering and biotechnology through research, practical training of scientists and postgraduate studies. Under the guidance of the late Academician Georgi D. Efremov, the founder and Director of RCGEB until his death in May 2011, the RCGEB became a hub for research in the field of biomolecular sciences in the Republic of Macedonia. It was one of the first institutions in the region that applied these new technologies in molecular diagnostics of human diseases and became an international center for training in basic and advanced methods in these sciences. Immediately after his death, the Presidency of MASA renamed the center in his honor, as the Research Centre for Genetic Engineering and Biotechnology “Georgi D. Efremov.” In the past 25 years, the RCGEB scientists have published over 150 papers in international and national journals, as well as several chapters in books and monographs. The RCGEB collaborates with numerous institutions from the Republic of Macedonia, medical institutions from neighboring countries and many academic institutions from different countries worldwide. The main research interest at the RCGEB during the past 25 years has been molecular characterization of the most common monogenic diseases, with a special emphasis on hemoglobinopathies, as well as some aspects of the molecular epidemiology of infectious diseases, genetics of the most common malignancies and DNA markers for human identification. The upgrading of the RCGEB infrastructure by MACPROGEN funds has enabled widening of the research objectives toward larger scale investigations of monogenic diseases and also shifting our research interest toward comprehensive studies of some common complex diseases such as cancers, infertility, mental retardation and deafness by high throughput genomic and proteomic technologies.

S3QL: A distributed domain specific language for controlled semantic integration of life sciences data

BackgroundThe value and usefulness of data increases when it is explicitly interlinked with related data. This is the core principle of Linked Data. For life sciences researchers, harnessing the power of Linked Data to improve biological discovery is still challenged by a need to keep pace with rapidly evolving domains and requirements for collaboration and control as well as with the reference semantic web ontologies and standards. Knowledge organization systems (KOSs) can provide an abstraction for publishing biological discoveries as Linked Data without complicating transactions with contextual minutia such as provenance and access control.We have previously described the Simple Sloppy Semantic Database (S3DB) as an efficient model for creating knowledge organization systems using Linked Data best practices with explicit distinction between domain and instantiation and support for a permission control mechanism that automatically migrates between the two. In this report we present a domain specific language, the S3DB query language (S3QL), to operate on its underlying core model and facilitate management of Linked Data.ResultsReflecting the data driven nature of our approach, S3QL has been implemented as an application programming interface for S3DB systems hosting biomedical data, and its syntax was subsequently generalized beyond the S3DB core model. This achievement is illustrated with the assembly of an S3QL query to manage entities from the Simple Knowledge Organization System. The illustrative use cases include gastrointestinal clinical trials, genomic characterization of cancer by The Cancer Genome Atlas (TCGA) and molecular epidemiology of infectious diseases.ConclusionsS3QL was found to provide a convenient mechanism to represent context for interoperation between public and private datasets hosted at biomedical research institutions and linked data formalisms.

Contributions of Molecular Epidemiology to the Understanding of Infectious Disease Transmission, Pathogenesis, and Evolution

Describe the contributions of molecular genetics to our understanding of the molecular epidemiology of infectious diseases caused by bacteria. Synthesize the literature, highlighting work on Escherichia coli and Group B streptococcus. 1) Commensal bacteria are genetically and phenotypically diverse. 2) Disease-causing strains of commensal bacteria often have special characteristics than allow them to be distinguished from common inhabitants. 3) Colonization by commensal bacteria is dynamic. 4) Commensal bacteria are transmitted between individuals. Applications of epidemiologic principles to bacterial populations gives insight into the natural history of colonization and transmission in the human host.

Phylogenetic Analysis as a Tool in Molecular Epidemiology of Infectious Diseases

Phylogenetics is a powerful tool for microbial epidemiology, but it is a tool that is often misused and misinterpreted by the field. Microbial epidemiologists are cautioned that in order to draw any inferences about the order of descent from a common ancestor it is necessary to correctly root a phylogenetic tree. Epidemiological samples of microbial populations typically include both ancestors and their descendants. In order to illustrate the relationships of those isolates, the phylogenetic method used must be able to detect zero-length branches. Unweighted Pair-Group Method (UPGMA) is the phylogenetic method that is most widely used in microbial epidemiology. Because UPGMA cannot detect zero length branches, and because it places the root of the tree based on a usually-false assumption, UPGMA is the worst possible choice among the several phylogenetic methods available. Because microbial epidemiology deals with relationships among strains within a species, rather than with relationships among species, recombination within those species can render phylogenetic trees meaningless and positively misleading. When there is evidence of significant recombination within the species of interest phylogenetic trees should not be used at all. Instead, alternative tools such as eBURST should be used to understand relationships among isolates.

Molecular Epidemiology of Infectious Diseases - Edited by R. C. Andrew Thompson

Molecular Epidemiology of Infectious Diseases - Edited by R. C. Andrew Thompson

HIV type 1 tat gene heteroduplex mobility assay as a tool to establish epidemiologic relationships among HIV type 1-infected individuals.

Molecular biology techniques are increasingly used to study the molecular epidemiology of infectious diseases. Most of these methods are expensive and labor-intensive. The human immunodeficiency virus (HIV) has substantial genomic variation, such that HIVs from different individuals are genetically diverse, although mutation rates differ for distinct regions of the genome. Most studies of HIV linkage and molecular evolution have focused on env or gag regions. We show that heteroduplex mobility analysis of the first exon of the HIV tat gene provides a simple, rapid, inexpensive, and reliable discriminatory tool for the molecular differentiation of shared versus distinct HIV-1 quasispecies when epidemiologic relations need to be defined. tat, as a relatively conserved region, appears to be a better region than the more variable env region to establish HIV-1 epidemiological linkages.