scholarly journals Reply to the Commentary on population matched (pm) germline allelic variants of immunoglobulin (IG) loci: relevance in infectious diseases and vaccination studies in human populations

2021 ◽  
Author(s):  
Indu Khatri ◽  
Magdalena A. Berkowska ◽  
Erik B. van den Akker ◽  
Cristina Teodosio ◽  
Marcel J. T. Reinders ◽  
...  
Keyword(s):  
Infectious Diseases ◽  
Human Populations ◽  
Allelic Variants

scholarly journals Population matched (pm) germline allelic variants of immunoglobulin (IG) loci: Relevance in infectious diseases and vaccination studies in human populations

2021 ◽  
Author(s):  
Indu Khatri ◽  
Magdalena A. Berkowska ◽  
Erik B. van den Akker ◽  
Cristina Teodosio ◽  
Marcel J. T. Reinders ◽  
...  
Keyword(s):  
Infectious Diseases ◽  
Immune Responses ◽  
B Cell ◽  
Association Studies ◽  
Cell Receptor ◽  
Human Populations ◽  
Allelic Variants ◽  
Evolutionary Selection ◽  
Selection Processes ◽  
Novel Alleles

AbstractImmunoglobulin (IG) loci harbor inter-individual allelic variants in many different germline IG variable, diversity and joining genes of the IG heavy (IGH), kappa (IGK) and lambda (IGL) loci, which together form the genetic basis of the highly diverse antigen-specific B-cell receptors. These allelic variants can be shared between or be specific to human populations. The current immunogenetics resources gather the germline alleles, however, lack the population specificity of the alleles which poses limitations for disease-association studies related to immune responses in different human populations. Therefore, we systematically identified germline alleles from 26 different human populations around the world, profiled by “1000 Genomes” data. We identified 409 IGHV, 179 IGKV, and 199 IGLV germline alleles supported by at least seven haplotypes. The diversity of germline alleles is the highest in Africans. Remarkably, the variants in the identified novel alleles show strikingly conserved patterns, the same as found in other IG databases, suggesting over-time evolutionary selection processes. We could relate the genetic variants to population-specific immune responses, e.g. IGHV1-69 for flu in Africans. The population matched IG (pmIG) resource will enhance our understanding of the SHM-related B-cell receptor selection processes in (infectious) diseases and vaccination within and between different human populations.

scholarly journals Patterns of smallpox mortality in London, England, over three centuries

PLoS Biology ◽  
2020 ◽  
Vol 18 (12) ◽  
pp. e3000506
Author(s):  
Olga Krylova ◽  
David J. D. Earn
Keyword(s):  
Public Health ◽  
Infectious Disease ◽  
Time Series ◽  
Spectral Analysis ◽  
Infectious Diseases ◽  
Health Policies ◽  
Human Populations ◽  
Public Health Policies ◽  
History Of ◽  
History Of Control

Smallpox is unique among infectious diseases in the degree to which it devastated human populations, its long history of control interventions, and the fact that it has been successfully eradicated. Mortality from smallpox in London, England was carefully documented, weekly, for nearly 300 years, providing a rare and valuable source for the study of ecology and evolution of infectious disease. We describe and analyze smallpox mortality in London from 1664 to 1930. We digitized the weekly records published in the London Bills of Mortality (LBoM) and the Registrar General’s Weekly Returns (RGWRs). We annotated the resulting time series with a sequence of historical events that might have influenced smallpox dynamics in London. We present a spectral analysis that reveals how periodicities in reported smallpox mortality changed over decades and centuries; many of these changes in epidemic patterns are correlated with changes in control interventions and public health policies. We also examine how the seasonality of reported smallpox mortality changed from the 17th to 20th centuries in London.

scholarly journals Population matched (PM) germline allelic variants of immunoglobulin (IG) loci: New pmIG database to better understand IG repertoire and selection processes in disease and vaccination

2020 ◽  
Author(s):  
Indu Khatri ◽  
Magdalena A. Berkowska ◽  
Erik B. van den Akker ◽  
Cristina Teodosio ◽  
Marcel J.T. Reinders ◽  
...  
Keyword(s):  
B Cell ◽  
Human Populations ◽  
Signal Sequences ◽  
Allelic Variants ◽  
Recombination Signal ◽  
Evolutionary Selection ◽  
1000 Genomes ◽  
Recombination Signal Sequences ◽  
Selection Processes ◽  
Over Time

AbstractAt the population level, immunoglobulin (IG) loci harbor inter-individual allelic variants in the many different germline IG variable (V), Diversity (D) and Joining (J) genes of the IG heavy (IGH), IG kappa (IGK) and IG lambda (IGL) loci, which together form the genetic basis of the highly diverse antigen-specific B-cell receptors. These inter-individual allelic variants can be shared between or be specific to human populations. The current IG databases IMGT, VBASE2 and IgPdb hold information about germline alleles, most of which are partial sequences, obtained from a mixture of human (B-cell) samples, many with sequence errors and/or acquired (non-germline) IG variations, induced by somatic hypermutation (SHM) during antigen-specific B-cell responses. We systematically identified true germline alleles (without SHM) from 26 different human populations around the world, profiled by the “1000 Genomes data”. Our resource is uniquely enriched with complete IG allele sequences and their frequencies across human populations. We identified 409 IGHV, 179 IGKV, and 199 IGLV germline alleles supported by at least seven haplotypes (= minimum of four individuals), after removal of potential false-positives, based on using other genomic databases, i.e. ENSEMBL, TopMed, ExAC, ProjectMine. Remarkably, the positions of the identified variant nucleotides of the different alleles are not at random (as observed in case of SHM), but show striking patterns, restricted to limited nucleotide positions, the same as found in other IG data bases, suggesting over-time evolutionary selection processes. The identification of these specific patterns provides extra evidence that the identified variant nucleotides are not sequencing errors, but genuine allelic variants. The diversity of germline allelic variants in IGH and IGL loci is the highest in Africans, while the IGK locus is most diverse in Europeans. We also report on the presence of recombination signal sequences (RSS) in V pseudogenes, explaining their usage in V(D)J rearrangements. We propose that this new set of genuine germline IG sequences can serve as a new population-matched IG (pmIG) database for better understanding B-cell repertoire and B-cell receptor selection processes in disease and vaccination within and between different human populations. The database in format of fasta is available via GitHub (https://github.com/InduKhatri/pmIG).Contribution to the Field StatementWe present a catalogue of immunoglobulin (IG) germline-alleles of unprecedented completeness and accuracy from 26 different human populations belonging to five different large ethnicities (Source: 1000 Genomes). We identified the population distribution of several known germline alleles and identified multiple new alleles, especially in African populations, indicative of high allelic diversity of IG genes in Africa. Strikingly, the identified variant nucleotides of the different alleles are not at random, but show striking patterns, restricted to limited nucleotide positions, the same as found in other IG databases, suggesting over-time evolutionary selection processes. Furthermore, we identified recombination signal sequences in pseudogenes (previously not known). We provide an overview of IG germline alleles shared with and between known databases and also point to potential sources of non-germline variation and incompleteness of the existing IG databases. More importantly, we believe that this information can serve as a novel population-matched IG (pmIG) database, highly valuable for the research community in supporting the dissection and understanding of differences in effectiveness of antibody-based immune responses in infectious diseases, other (immune) diseases and vaccination within and between human populations. Such knowledge might be used in developing population-specific vaccination strategies e.g. for currently ongoing SARS-CoV2 pandemic.

scholarly journals pmTR database: population matched (PM) germline allelic variants of T-cell receptor (TR) loci

2020 ◽  
Author(s):  
Julian Dekker ◽  
Jacques J.M. van Dongen ◽  
Marcel J.T. Reinders ◽  
Indu Khatri
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
T Cell Receptor ◽  
Genetic Basis ◽  
Cell Receptor ◽  
Human Populations ◽  
Allelic Variants ◽  
Asian Populations ◽  
African Populations ◽  
Source Of Information

AbstractT-cell receptor (TR) germline alleles are arranged, organized and made available to the research community by the IMGT database. This state-of-the-art database, however, does not provide information regarding population specificity and allelic frequencies of the genes all four human TR loci (TRA, TRB, TRG and TRD). The specificity of allelic variants to different human populations can, however, be a rich source of information when studying the genetic basis of population-specific immune responses in vaccination and disease. To make TR germline alleles available for such population-specific studies, we meticulously identified true germline alleles enriched with complete TR allele sequences and their frequencies across 26 different human populations, profiled by “1,000 Genomes data”. We identified 205 TRAV, 249 TRBV, 16 TRGV and 5 TRDV germline alleles supported by at least four haplotypes (= minimum of two individuals). The diversity of germline allelic variants in the TR loci is highest in Africans followed by Non-African populations. A majority of the Non-African alleles are specific to the Asian populations, suggesting a diverse profile of TR germline alleles in different human populations. Interestingly, the alleles known in the IMGT database are frequent and common across all the superpopulations. We believe that this new set of genuine germline TR sequences represents a valuable new resource which we have made available through the new population-matched TR (pmTR) database, accessible via https://pmtrig.lumc.nl/.

scholarly journals Mathematical Epidemiological Model of the Propagation and Prevention of Infectious Diseases Considering COVID-19 Vaccination

2021 ◽  
Author(s):  
Kazumi Omata ◽  
Hiroaki Mitsuya
Keyword(s):  
Infectious Diseases ◽  
Time Scale ◽  
Reproduction Number ◽  
Herd Immunity ◽  
Epidemiological Studies ◽  
Human Populations ◽  
Future Scenarios ◽  
Vaccination Programs ◽  
Asymptotic Nature ◽  
Alternative Approach

Abstract The duration of the necessity of current restrictions and preventive countermeasures against the COVID-19 pandemic is of great concern. While several previous epidemiological studies have discussed controlling the course of the epidemic with regard to social distancing, vaccination, care capacities, and future scenarios, we adopt an alternative approach to provide insights into the time scale of epidemic propagation in human populations. We show that the reproduction number modified by preventive countermeasures Rm implies a threshold R~m to reach the herd immunity level at time Th. While Th varies moderately for large Rm, it increases sharply around Rm=R~m, and Th is infinite below Rm=R~m. The transition region for this increase is minute, demonstrating that prevention of infectious diseases must consider the relatively asymptotic nature of their propagation, which varies unpredictably between steady transmission and explosive outbreaks. These results suggest the continuation of preventive countermeasures to suppress the transmission of COVID-19 for many years; if they were discontinued or reduced such that Rm exceeded R~m, the disease would be transmitted throughout the considered community, and the required herd immunity level would be reached within 250 days if Rm > 1.6. However, the implementation of vaccination programs could drastically alter this dynamic.

scholarly journals Red fox viromes across an urban-rural gradient

2020 ◽  
Author(s):  
Sarah J Campbell ◽  
Wilbur Ashley ◽  
Margarita Gil-Fernandez ◽  
Thomas M. Newsome ◽  
Francesca Di Giallonardo ◽  
...  
Keyword(s):  
Infectious Diseases ◽  
Urban Areas ◽  
Red Fox ◽  
Disease Risk ◽  
Close Contact ◽  
Food Resources ◽  
Human Populations ◽  
Red Foxes ◽  
Domestic Species ◽  
Rabbit Haemorrhagic Disease

AbstractThe Red fox (Vulpes vulpes) has established large populations in Australia’s urban and rural areas since its introduction following European settlement. Foxes’ cryptic and highly adaptable nature allows them to invade cities and live among humans while remaining largely unnoticed. Urban living and access to anthropogenic food resources also influences fox ecology. Urban foxes grow larger, live at higher densities and are more social than their rural counterparts. These ecological changes in urban red foxes are likely to impact the pathogens that they harbour, and foxes could pose a disease risk to humans and other species that share these urban spaces. To assess this possibility, we used a meta-transcriptomic approach to characterise the viromes of urban and rural foxes across the Greater Sydney region in Australia. Urban and rural foxes differed significantly in virome composition, with rural foxes harbouring a greater abundance of viruses compared to their urban counterparts. In contrast, urban fox viromes comprised a greater diversity of viruses compared to rural foxes. We identified nine potentially novel vertebrate-associated viruses in both urban and rural foxes, some of which are related to viruses associated with disease in domestic species and humans. These included members of the Astroviridae, Picobirnaviridae, Hepeviridae and Picornaviridae as well as rabbit haemorrhagic disease virus-2 (RHDV2). This study sheds light on the viruses carried by urban and rural foxes and emphasises the need for greater genomic surveillance of foxes and other invasive species at the human-wildlife interface.ImportanceUrbanisation of wild environments is increasing as human populations continue to expand. Remnant pockets of natural environments and other green spaces in urban landscapes provide invasive wildlife such as red foxes with refuges within urban areas, where they thrive on the food resources provisioned by humans. Close contact between humans, domestic species and foxes likely increases the risk of novel pathogen emergence. Indeed, the vast majority of emerging infectious diseases in humans originate in wild animals. Here, we explored potential differences in viromes between urban fox invaders and their rural counterparts. Viromes of foxes and their ectoparasites comprise a diversity of viruses including those from the Astroviridae, Picobirnaviridae, Hepeviridae, Caliciviridae and Picornaviridae. Microbial surveillance in foxes and other urban wildlife is vital for monitoring viral emergence and for the prevention of infectious diseases.

Infectious diseases in low-income countries: where are we now?

2018 ◽  
Author(s):  
Benjamin Roche ◽  
Thierry Baldet ◽  
Simard Frédéric
Keyword(s):  
Infectious Diseases ◽  
Low Income ◽  
Control Strategies ◽  
Low Income Countries ◽  
Western World ◽  
Human Populations ◽  
Health Campaigns ◽  
Human Pathogens ◽  
Public Health Campaigns ◽  
Made In

It is widely documented that infectious diseases have a very deep impact on numerous human populations. While public health campaigns have achieved spectacular successes, they do not appear to be evenly distributed throughout the world. Indeed, although many infectious diseases have been eliminated in the Western world, deadly pathogens are still spreading in many low-income countries. This chapter aims to describe the current epidemiological situations, reviewing control strategies and the progress that has been made in the fight against major human pathogens with the strongest impact in low-income countries. This chapter, therefore, introduces most of the pathogens that will be discussed in the book, and it describes why some epidemiological situations improved for some diseases more than for others.

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