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Using digital epidemiology methods to monitor influenza-like illness in the Netherlands in real-time: the 2017-2018 season

IntroductionDespite the early development of Google Flu Trends in 2009, digital epidemiology methods have not been adopted widely, with most research focusing on the USA. In this article we demonstrate the prediction of real-time trends in influenza-like illness (ILI) in the Netherlands using search engine query data.\n\nMethodsWe used flu-related search query data from Google Trends in combination with traditional surveillance data from 40 general sentinel practices to build our predictive models. We introduced an artificial 4-week delay in the use of GP data in the models, in order to test the predictive performance of the search engine data.\n\nSimulating the weekly use of a prediction model across the 2017/2018 flu season we used lasso regression to fit 52 prediction models (one for each week) for weekly ILI incidence. We used rolling forecast cross-validation for lambda optimization in each model, minimizing the maximum absolute error.\n\nResultsThe models accurately predicted the number of ILI cases during the 2017/18 ILI epidemic in real time with a mean absolute error of 1.40 (per 10,000 population) and a maximum absolute error of 6.36. The model would also have identified the onset, peak, and end of the epidemic with reasonable accuracy\n\nThe number of predictors that were retained in the prediction models was small, ranging from 3 to 5, with a single keyword ( Griep = Flu) having by far the most weight in all models.\n\nDiscussionThis study demonstrates the feasibility of accurate real-time ILI incidence predictions in the Netherlands using internet search query data. Digital ILI monitoring strategies may be useful in countries with poor surveillance systems, or for monitoring emergent diseases, including influenza pandemics. We hope that this transparent and accessible case study inspires and supports further developments in field of digital epidemiology in Europe and beyond.

epidemiology↗

The role of African buffalo in the epidemiology of foot-and-mouth disease in sympatric cattle and buffalo populations in Kenya

Transmission of pathogens at wildlife-livestock interfaces poses a substantial challenge to the control of infectious diseases, including for foot-and-mouth disease virus (FMDV) in African buffalo and cattle. The extent to which buffalo play a role in the epidemiology of this virus in livestock populations remains unresolved in East Africa. Here, we show that FMDV occurs at high seroprevalence (~77%) in Kenyan buffalo. In addition, we recovered 80 FMDV VP1 sequences from buffalo, all of which were serotype SAT1 and SAT2, and seventeen FMDV VP1 sequences from cattle, which included serotypes A, O, SAT1 and SAT2. Notably, six individual buffalo were co-infected with both SAT1 and SAT2 serotypes. Our results suggest that transmission of FMDV between sympatric cattle and buffalo is rare. However, viruses from FMDV outbreaks in cattle elsewhere in Kenya were caused by viruses closely related to SAT1 and SAT2 viruses found in buffalo. We also show that the circulation of FMDV in buffalo is influenced by fine-scale geographic features, such as rivers, and that social segregation amongst sympatric herds may limit between-herd transmission. Our results significantly advance knowledge of the ecology and molecular epidemiology of FMDV at wildlife-livestock interfaces in Eastern Africa, and will help to inform the design of control and surveillance strategies for this disease in the region.

epidemiology↗

The effect of pre-analytical conditions on blood metabolomics in epidemiological studies

BackgroundSerum and plasma are commonly used biofluids for large-scale metabolomic-epidemiology studies. Their metabolomic profile is susceptible to changes due to variability in pre-analytical conditions and the impact of this is unclear.\n\nMethodsParticipant-matched EDTA-plasma and serum samples were collected from 37 non-fasting volunteers and profiled using a targeted nuclear magnetic resonance (NMR) metabolomics platform (N=151 traits). Metabolic concentrations were compared between reference (pre-storage: 4{degrees}C, 1.5h; post-storage: no sample preparation or NMR-analysis delays) and four, pre-storage, blood processing conditions, where samples were incubated at (i) 4{degrees}C, 24h; (ii) 4{degrees}C, 48h; (iii) 21{degrees}C, 24h; (iv) 21{degrees}C, 48h, before centrifugation; and two, post-storage, sample processing conditions in which samples (i) thawed overnight, then left for 24h before addition of sodium buffer followed by immediate NMR analysis; (ii) thawed overnight, addition of sodium buffer, then left for 24h before profiling. Linear regression models with random-intercepts were used to assess the impact of these six pre-analytical conditions on EDTA-plasma/serum metabolome.\n\nResultsFatty acids, beta-hydroxybutyrate, glycoprotein-acetyls and most lipid-related traits, in serum and plasma, were robust to the tested pre and post-storage conditions. Pre-storage conditions impacted concentrations of glycolysis metabolites, acetate, albumin and amino-acids by levels that could potentially bias research results (up to 1.4SD difference compared with reference). Post-storage conditions affected histidine, phenylalanine and LDL-particle-size, with differences up to 1.4SD.\n\nConclusionsMost metabolic traits are robust to the pre- and post-storage conditions tested here and that may commonly occur in large-scale cohorts. However, concentrations of glycolysis metabolites, and amino-acids may be compromised.\n\nKey messagesO_LIIn large scale epidemiological studies, blood processing delays, incubation at high temperature prior to long term storage, and NMR profiling delays after long term storage, may occur.\nC_LIO_LIConcentrations of fatty acids, beta-hydroxybutyrate, glycoprotein acetyls and most lipid-related traits are robust to variations in pre-storage temperature and duration of incubation (4{degrees}C or 21{degrees}C for up to 48h prior to centrifugation) and post-storage sample handling (24h delay in sample preparation or NMR profiling).\nC_LIO_LIGlycolytic metabolite concentrations are altered by pre-storage conditions and amino-acids, particularly histidine and phenylalanine, by both, pre and post-storage conditions.\nC_LI

epidemiology↗

Inquiry in Ridding the Democratic Republic of the Congo of sleeping sickness, a dream at our fingertips: comparing to the Epidemiology of human African trypanosomiasis in the Democratic Republic of the Congo 2002-2003

BackgroundIn the Democratic Republic of the Congo, the international support was suddenly withdrawn after the massacre of students at the Lubumbashi University in May 1990. The interruption of the international aid from 1990 to 1991 would undoubtedly have a long-lasting negative effect on case load. So, the National Sleeping Sickness Control Programme--NSSCP (Programme National de Lutte contre la Trypanosomiase Humaine Africaine) (PNLTHA) remains vulnerable without international aid. Currently, the number of reported new cases decreased. These achievements prove that the elimination of this neglected tropical disease is possible when there is a strong commitment of public authorities accompanied by scientific research centers, civil society and the private sector. Without international aid, sleeping sickness remains a formidable disease difficult to cure because it is depending on continued financial support and drug availability.\n\nObjectivesThe objectives of this work were: 1. to profile the incidence of new cases of human African trypanosomiasis in the Democratic Republic of the Congo from 2002 to 2003, depending on the stage of disease progression (stages 1 and 2); 2. Compare the evolution of this profile from one household to another; 3. Compare the rate of confirmed parasitological diagnosis with positive CATT; 4. Calculate the discrepancy rate between CATT+ and parasitological diagnosis. All the above objectives are aiming to sustain the efforts made for the adoption of the 2018 Francophonie resolution on the ridding of human African trypanosomiasis that may renewed donor interest, including the government of the Democratic Republic of the Congo because the control of HAT is completely dependent on international aid.\n\nMethodsResearch is necessary on how to rationalize control activities so that control programs can adopt the most effective and efficient strategies. To assess it, we analyzed epidemiologic data collected by PNLTHA from 2002 to 2003.\n\nResultsIn all endemic areas, 1,970,101 people were tested in 2002 and 2,311,507 people in 2003. The national average coverage of the total population tested (TPT) represents 16.20% of the exposed population among which 13,853 new cases were detected in 2002 and 11, 481 new cases detected in 2003 with the national average coverage of the population tested that represents 19.10 %.\n\nConclusionIn short, we said that the number of people already infected is probably higher than the new cases reported in 2003. We are still far from the situation of 1958/60 when there was 1 new case declared by 10,000 people tested (i.e. 1,100 new cases out of 13,000,000 people screen). Therefore, the Congolese government must make long-term financial commitments to ensure the continuity of HAT control activities.\n\nAuthor summaryFor the past three decades, the frequency of sleeping sickness tends to become a large in the Democratic Republic of the Congo. This paper reviews the status of sleeping sickness in DRC between 2002 and 2003, with a focus on stage patterns. Epidemiological trends at the national and provincial level are presented. Today, this deadly fly-borne disease threatens more than 65 million people worldwide and most of the reported cases (more than 8 out of 10) are in the Democratic Republic of the Congo. Fortunately, after decades of hard work, we have never been so close to eradicating sleeping sickness in the Democratic Republic of the Congo. In 2009, the number of reported cases fell below 10,000, the first in half a century. In 2015, only 2,804 cases had been listed. The Democratic Republic of the Congo is determined to eradicate the disease by 2020, paving the way for its global eradication. Thanks to these decades of work. I submit this inquiry to recognize also the work that my last mentor coauthor of this search did, he hold his doctorate on this disease. This submission is an appropriate way I found to honor and keep the memory of my supervisor who passed away! In advance, many thanks for your best understanding of this particular circumstance. From my last mentor work, we have never been so close to the definitive elimination of sleeping sickness. The number of reported new cases decreased from 26,318 in 1998 to 11,481 in 2003 and later to 2,804 in 2015. These achievements prove that the elimination of neglected tropical diseases is possible when there is a strong commitment of public authorities accompanied by scientific research centers, civil society and the private sector.

epidemiology↗

Epidemiological Analysis of Ear Diseases in 221 Dogs in Northwest of China

Ear disease is a relatively common disease in veterinary, and it will great effect on the pets life. This study mainly collected and collated the cases of Xian Teaching Hospital of Northwest A&F University from 2012 to 2016, and conducted an epidemiological analysis of the incidence of ear disease in dogs. In this study, the common ear diseases in dogs were divided into otitis externa, otitis media, otitis interna, and ear hematoma. The results showed that the total number of dog ear disease cases was 221, the highest incidence was otitis externa (84.62%), and the main cause of otitis externa was the bacterial infection (44.10%), which followed by fungal infection (32.31%). The ratio of male to female is 1:1.5. In terms of the dog species, the highest incidence was Teddy (18.55%), followed by the Golden Retriever (10.41%). The most common ear diseases in puppies was otitis externa, ear canal hyperplasia and ear canal tumors occur mainly in older dogs. Through the analysis of the 221 cases of ear diseases, we could better understand the development and epidemiology of dog ear diseases, and provide some reference for clinical diagnosis, treatment and prevention of dog ear diseases.

epidemiology↗

EMULSION: transparent and flexible multiscale stochastic models in epidemiology

Stochastic mechanistic models are essential to predictive epidemiology, to better explore biological assumptions and anticipate effects of control measures on pathogen spread. Their development is usually long and iterative, involving multi-disciplinary knowledge integration. However, knowledge often becomes lost in model code, hindering late changes in assumptions and often making models appearing as black boxes to end-users. We introduce here EMULSION, an artificial intelligence-based software intended to help modellers focus on model design rather than programming. EMULSION defines a domain-specific language to make all components of an epidemiological model (structure, processes, parameters...) explicit as a structured text file. This file is readable by scientists from other fields (epidemiologists, biologists, economists), who can contribute to validate or revise assumptions at any stage of model development. It is then automatically processed by EMULSION generic simulation engine, preventing any discrepancy between model description and implementation. The modelling language and simulation architecture both rely on the combination of advanced artificial intelligence methods (knowledge representation and multi-level agent-based simulation), allowing several modelling paradigms (from compartment- to individual-based models) at several scales (up to metapopulations). The flexibility of EMULSION and its capability to support iterative modelling are illustrated here through examples of progressive complexity, including late revisions of core model assumptions. EMULSION is also currently used to model the spread of several diseases in real pathosystems (zoonoses such as Q fever or the vector-borne Rift Valley fever; or bovine respiratory diseases, with a focus on detection and treatment protocols). EMULSION provides a command-line tool for checking models, producing model diagrams, running simulations, and plotting outputs. Implemented in Python 3, EMULSION runs on Linux, MacOS, and soon Windows. It is released under Apache-2.0 license. A comprehensive documentation with installation instructions, tutorial and examples is available from: https://sourcesup.renater.fr/emulsion-public.

epidemiology↗

Compartmental Modeling Software: a fast, discrete stochastic framework for biochemical and epidemiological simulation

The compartmental modeling software (CMS) is an open source computational framework that can simulate discrete, stochastic reaction models which are often utilized to describe complex systems from epidemiology and systems biology. In this article, we report the computational requirements, the novel input model language, the available numerical solvers, and the output file format for CMS. In addition, the CMS code repository also includes a library of example model files, unit and regression tests, and documentation. Two examples, one from systems biology and the other from computational epidemiology, are included that highlight the functionality of CMS. We believe the creation of computational frameworks such as CMS will advance our scientific understanding of complex systems as well as encourage collaborative efforts for code development and knowledge sharing.

epidemiology↗

Spatial and epidemiologic features of dengue in Sabah, Malaysia

In South East Asia, dengue epidemics have increased in size and geographical distribution in recent years. Most studies investigating dengue transmission and control have had an urban focus, while less consideration is currently given to rural settings, or where urban and rural areas overlap. We examined the spatiotemporal distribution and epidemiological characteristics of reported dengue cases in the predominantly rural state of Sabah, in Malaysian Borneo - an area where sylvatic and urban circulation of pathogens are known to intersect. We found that annual dengue incidence rates were spatially variable over the 7-year study period from 2010-2016 (state-wide mean annual incidence of 21 cases/100,000 people; range 5-42/100,000), but were highest in rural localities in the western districts of the state (Kuala Penyu, Nabawan, Tenom and Kota Marudu). The eastern districts exhibited lower overall dengue rates; however, we noted a concentration of severe (haemorrhagic) dengue cases (44%) in Sandakan and Tawau districts. Dengue incidence was slightly higher for males than females, and was significantly higher for both genders aged between 10 and 29 years (24/100,000; p=0.029). The largest ever recorded outbreaks occurred during 2015-2016, with the vector Aedes albopictus found to be most prevalent in both urban and rural households (House Index of 64%), compared with Ae. Aegypti (15%). These findings suggest that dengue outbreaks in Sabah are driven by the sporadic expansion of dengue virus in both urban and rural settings. This may require tailoring of preventative strategies to suit different transmission ecologies across Sabah. Further studies to better understand the drivers of dengue in Sabah may aid dengue control efforts in Malaysia, and more broadly in South East Asia.\n\nAuthor summaryIn order to combat the rising regional incidence of dengue in South East Asia, the drivers of transmission must be better characterised across different environmental settings. We conducted the first retrospective analysis of dengue epidemiology in the predominantly rural state of Sabah, Malaysia, where both urban and sylvatic transmission cycles exist. Human notification data over a 7-year period were reviewed and spatiotemporal and demographic risk factors identified. We found: O_LIUrban habitats and population density are not the only determinants mediating the spread of epidemic dengue in Sabah. Case from both urban and rural localities contributed equally to dengue outbreaks.\nC_LIO_LIHuman demographic risk factors included being aged between 10 and 29 years, and being male.\nC_LIO_LIHigh incidence areas for dengue do not predict the occurrence of severe dengue. Severe dengue was largely localised to lower incidence districts in the east of the state.\nC_LIO_LIThe sole presence of Aedes albopictus in and around the majority of urban and rural case households suggests that this vector may play a major role in facilitating outbreaks.\nC_LI\n\nA complex interplay of risk factors likely mediates dengue transmission in Sabah, influenced by both regional climate trends and localised human and ecological influences. This study emphasises that the increasing spread of dengue in urban South East Asia is also mirrored in more rural areas, and suggests a need for control strategies that address both urban and rural dengue risk.

epidemiology↗

Neanderthal Genomics Suggests a Pleistocene Time Frame for the First Epidemiologic Transition

High quality Altai Neanderthal and Denisovan genomes are revealing which regions of archaic hominin DNA have persisted in the modern human genome. A number of these regions are associated with response to infection and immunity, with a suggestion that derived Neanderthal alleles found in modern Europeans and East Asians may be associated with autoimmunity. Independent sources of DNA-based evidence allow a re-evaluation of the nature and timing of the first epidemiologic transition. By combining skeletal, archaeological and genetic evidence we question whether the first epidemiologic transition in Eurasia was as tightly tied to the onset of the Holocene as has previously been assumed. There clear evidence to suggest that this transition began before the appearance of agriculture and occurred over a timescale of tens of thousands of years. The transfer of pathogens between human species may also have played a role in the extinction of the Neanderthals.

Genetics↗

Epidemiological and ecological modelling reveal diversity in microbial population structures from a cross-sectional community swabbing study

Respiratory tract infections (RTI) are responsible for over 4 million deaths per year worldwide with pathobiont carriage a required precursor to infection. Through a cross-sectional community-based nasal self-swabbing study we sought to determine carriage epidemiology for respiratory pathogens amongst bacteria (Streptococcus pneumoniae, Haemophilus influenza, Moraxella catarrhalis, Staphylococcus aureus, Pseudomonas aeruginosa and Neisseria meningitidis) and viruses (RSV, Influenza viruses A and B, Rhinovirus/Enterovirus, Coronavirus, Parainfluenza viruses 1-3 and Adenovirus (ADV)). Carriage of bacterial and viral species was shown to vary with participant age, recent RTI and the presence of other species. The spatial structure of microbial respiratory communities was less nested (more disordered) in the young (0-4 years) and those with recent RTI. Species frequency distributions were flatter than random expectation in young individuals (X2 = 20.42, p = 0.002), indicating spatial clumping of species consistent with facilitative relationships amongst them. Deviations from a neutral model of ecological niches were observed for samples collected in the summer and from older individuals (those aged 5-17, 18-64 and [≥]65 years) but not in samples collected from winter, younger individuals (those aged 0-4 years), individuals with recent RTI and individuals without recent RTI, demonstrating the importance of both neutral and niche processes in respiratory community assembly. The application of epidemiological methods and ecological theory to sets of respiratory tract samples has yielded novel insights into the factors that drive microbial community composition, such as seasonality and age, as well as species patterns and interactions within the nose.

microbiology↗

A Vibrio Cholerae Core Genome Multilocus Sequence Typing Scheme to Facilitate the Epidemiological Study of Cholera

Core genome multilocus sequence typing (cgMLST) has gained popularity in recent years in epidemiological research and subspecies level classification. cgMLST retains the intuitive nature of traditional MLST but offers much greater resolution by utilizing significantly larger portions of the genome. Here, we introduce a cgMLST scheme for Vibrio cholerae, a bacterium abundant in marine and freshwater environments and the etiologic agent of cholera. A set of 2,443 core genes ubiquitous in V. cholerae were used to analyze a comprehensive dataset of 1,262 clinical and environmental strains collected from 52 countries, including 65 newly sequenced genomes in this study. We established a sublineage threshold based on 133 allelic differences that creates clusters nearly identical to traditional MLST types, providing backwards compatibility to new cgMLST classifications. We also defined an outbreak threshold based on seven allelic differences that is capable of identifying strains from the same outbreak and closely related isolates which could give clues on outbreak origin. Using cgMLST, we confirmed the South Asian origin of modern epidemics and identified clustering affinity among sublineages of environmental isolates from the same geographic origin. Advantages of this method are highlighted by direct comparison with existing classification methods, such as MLST and single nucleotide polymorphism-based methods. cgMLST outperforms all existing methods in terms of resolution, standardization, and ease-of-use. We anticipate this scheme will serve as a basis for a universally applicable and standardized classification system for V. cholerae research and epidemiological surveillance in the future. This cgMLST scheme is publicly available on PubMLST (https://pubmlst.org/vcholerae/). IMPORTANCEToxigenic Vibrio cholerae of the O1 and O139 serogroups are the causative agent of cholera, an acute diarrheal disease that plagued the world for centuries, if not millennia. Here, we introduce a core genome multilocus sequence typing (cgMLST) scheme for V. cholerae. Using cgMLST, we established an outbreak threshold that can efficiently identify outbreak related strains and potential sources of introduction. We also defined a sublineage threshold that is similar to traditional MLST sequence type which will provide context to this new typing method by relating it to previous MLST results. cgMLST outperforms all existing methods in terms of resolution, standardization, and ease-of-use, making this scheme the most suitable method for V. cholerae typing and surveillance worldwide.

microbiology↗

Clinical Epidemiology of congenital heart diseases in dogs: prevalence, popularity and volatility throughout twenty years of clinical practice

The epidemiology of Congenital Heart Diseases (CHDs) has changed over the past twenty years. We evaluated the prevalence of CHDs in the population of dogs recruited in a single referral center (RC); compared the epidemiological features of CHDs in screened breeds (Boxers) versus nonscreened (French and English Bulldogs and German Shepherds), investigated the association of breeds with the prevalence of CHDs, determined the popularity and volatility of breeds over a 20-year period; and analysed the trends of the most popular breeds in the overall population of new-born dogs registered in the Italian Kennel Club from 1st January 1997 to 31st December 2017. This was a retrospective observational study, the cardiological database of the RC was analysed, and 1,779 clinical records fulfilled the inclusion criteria. Descriptive statistics and frequencies regarding the most representative breeds and CHDs were generated. A logistic regression model was used to analyse the trends of the most common CHDs found in single breeds (French Bulldog, English Bulldog, Boxer, and German Shepherd), and in groups of breeds (brachycephalic breeds and the most represented large breeds). The relationships between the breed popularity and the presence of CHDs was studied. The most common CHDs were Pulmonic Stenosis (34,1%), Patent Ductus Arteriosus (26,4%), Subaortic Stenosis (14,6%), Ventricular Septal Defect (4,8%), Aortic Stenosis (4,7%), Tricuspid Dysplasia (3,4%), Atrial Septal Defect (1,9%), Double Chamber Right ventricle (1,8%), Mitral Dysplasia (1,6%), and reverse Patent Ductus Arteriosus (0,7%). The most represented pure breeds were Boxer (19,4%), German Shepherd (9,4%), French Bulldog (6,2%), English Bulldog (4,9%), Maltese (3,7%), Newfoundland (3,1%), Rottweiler (3,1%), Golden Retriever (3,0%), Chihuahua (2,8%), Poodle (2,5%), Cavalier King Charles Spaniel (2,2%), American Staffordshire Terrier (2,1%), Labrador Retriever (2,3%), Dobermann (2,1%), Miniature Pinscher (2,0%), Cocker Spaniel (2,0%), Yorkshire Terrier (1,7%), Dogue de Bordeaux (1,6%), Dachshund (1,6%), and Bull Terrier (1,5%). Chihuahuas, American Staffordshire Terriers, Border Collies, French Bulldogs, and Cavalier King Charles Spaniel were the most appreciated small and medium breeds, all of which showed a high value of volatility. In conclusion, this study found evidence for the value of the screening program implemented in Boxers, which decreased the prevalence of Subaortic Stenosis and Pulmonic Stenosis. However, fashions and trends influence dog owners choices more than the worries of health problems frequently found in a breed. Effective breeding programs are needed in order to control the diffusion of CHDs without impoverishing the genetic pool; in addition, dog owners should be educated, and the breeders supported by a network of veterinary cardiology centers.

pathology↗

Molecular epidemiology of mumps viruses detected in the Netherlands, 2017-2019

Mumps cases continue to occur, also in countries with a relatively high vaccination rate. The last major outbreaks of mumps in the Netherlands were from 2009-2012 and thereafter, only small clusters and single cases were reported. Molecular epidemiology can provide insights in the circulation of mumps viruses. The aims of the present study were to analyze the molecular epidemiology of mumps viruses in the Netherlands in 2017-2019 and to elucidate whether complete genome sequencing adds to the molecular resolution of mumps viruses when compared to sequencing of the mumps SH gene and non-coding regions (SH+NCRs). To this end, Sanger sequence data from the SH+NCRs were analyzed from 82 mumps genotype G viruses. In addition, the complete genomes were obtained from 10 mumps virus isolates using next-generation sequencing. Analysis of SH+NCRs of mumps viruses revealed the presence of two major lineages in the Netherlands, which was confirmed by analysis of complete genomes. Comparison of molecular resolution obtained with SH+NCRs and complete genomes clearly indicated that additional molecular resolution can be obtained by analyzing complete genomes. In conclusion, analysis of SH + NCRs sequence data from recent mumps genotype G viruses indicate that mumps viruses continue to circulate in the Netherlands and surrounding countries. However, to understand exact transmission trees and to compare mumps viruses on a large geographic scale, analysis of complete genomes is a very useful approach.

microbiology↗

How bank vole-PUUV interactions influence the eco-evolutionary processes driving nephropathia epidemica epidemiology: An experimental and genomic approach.

In Europe, Puumala virus (PUUV) is responsible for nephropathia epidemica (NE), a mild form of haemorrhagic fever with renal syndrome (HFSR). Despite the presence of its reservoir, the bank vole, on most of French territory, the geographic distribution of NE cases is heterogeneous and NE endemic and non-endemic areas have been reported. In this study we analyzed whether bank vole-PUUV interactions could partly shape these epidemiological differences. We performed crossed-experimental infections using wild bank voles from French endemic (Ardennes) and non-endemic (Loiret) areas, and two French PUUV strains isolated from these areas. The serological response and dynamics of PUUV infection were compared between the four cross-infection combinations. We showed that the serological response and the presence of PUUV in excretory organs were more important in bank voles infected with the PUUV endemic strain. Moreover, the within-host viral diversity in excretory organs was higher than in other non-excretory organs for the NE endemic cross-infection, but not for the NE non-endemic cross-infection. Altogether, our results showed that genetically different PUUV strains, and in a lesser extent their interaction with sympatric bank voles, could affect virus replication and diversity. This could impact PUUV excretion/transmission between rodents and to humans, and in turn at least partly shape NE epidemiology in France.

evolutionary biology↗

A General Birth-Death-Sampling Model for Epidemiology and Macroevolution

Birth-death stochastic processes are the foundation of many phylogenetic models and are widely used to make inferences about epidemiological and macroevolutionary dynamics. There are a large number of birth-death model variants that have been developed; these impose different assumptions about the temporal dynamics of the parameters and about the sampling process. As each of these variants was individually derived, it has been difficult to understand the relationships between them as well as their precise biological and mathematical assumptions. Without a common mathematical foundation, deriving new models is non-trivial. Here we unify these models into a single framework, prove that many previously developed epidemiological and macroevolutionary models are all special cases of a more general model, and illustrate the connections between these variants. This framework centers around a technique for deriving likelihood functions for arbitrarily complex birth-death(-sampling) models that will allow researchers to explore a wider array of scenarios than was previously possible. We then use this frame-work to derive general model likelihoods for both the "single-type" case in which all lineages diversify according to the same process and the "multi-type" case, where there is variation in the process among lineages. By re-deriving existing single-type birth-death sampling models we clarify and synthesize the range of explicit and implicit assumptions made by these models.

evolutionary biology↗

The genomic epidemiology of SARS-CoV-2 in Palestine

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the novel coronavirus responsible for the COVID-19 pandemic, continues to cause significant public health burden and disruption globally. Genomic epidemiology approaches point to most countries in the world having experienced many independent introductions of SARS-CoV-2 during the early stages of the pandemic. However, this situation may change with local lockdown policies and restrictions on travel leading to the emergence of more geographically structured viral populations and lineages transmitting locally. Here, we report the first SARS-CoV-2 genomes from Palestine sampled from early March, when the first cases were observed, through to August of 2020. SARS-CoV-2 genomes from Palestine fall across the diversity of the global phylogeny, consistent with at least nine independent introductions into the region. We identify one locally predominant lineage in circulation represented by 50 Palestinian SARS-CoV-2, grouping with isolated viral samples from patients in Israel and the UK. We estimate the age of introduction of this lineage to 05/02/2020 (16/01/2020 - 19/02/2020), suggesting SARS-CoV-2 was already in circulation in Palestine predating its first detection in Bethlehem in early March. Our work highlights the value of ongoing genomic surveillance and monitoring to reconstruct the epidemiology of COVID-19 at both local and global scales.

genomics↗

Epidemiological transcriptomic data supports BCG protection in viral diseases including COVID-19

Epidemiological and clinical evidence suggests that Bacille Calmette-Guerin (BCG) vaccine induced trained immunity protects against non-specific infections. Multiple clinical trials are currently underway to assess effectiveness of the vaccine in the coronavirus disease 2019 (COVID-19). However, the durability and mechanism of BCG trained immunity remain unclear. Here, an integrative analysis of available epidemiological transcriptomic data related to BCG vaccination and respiratory tract viral infections, and transcriptomic alterations reported in COVID-19 is presented toward addressing this gap. Results suggest that the vaccine induces very long-lasting transcriptomic changes that, unsurprisingly, mimic viral infections by upregulated antiviral defense response, and, counterintuitively. oppose viral infections by downregulated myeloid cell activation. These durability and mechanistic insights have immediate implications in fight against the COVID-19 pandemic.

genomics↗

The genomic epidemiology of multi-drug resistant nontyphoidal Salmonella causing invasive disease in sub-Saharan Africa

BackgroundInvasive nontyphoidal Salmonella (iNTS) is one of the leading causes of bacteraemia in sub-Saharan Africa. Multi-drug resistance (MDR) and further resistance to third generation cephalosporins and fluoroquinolones have emerged in multiple iNTS serotypes. Molecular epidemiological investigations of nontyphoidal Salmonella are needed to better understand the genetic characteristics and transmission dynamics associated with major MDR iNTS serotypes across the continent. MethodsA total of 166 nontyphoidal Salmonella isolates causing invasive disease were collected from a multi-centre study in eight African countries between 2010 and 2014, and whole-genome sequenced to investigate the geographical distribution, antimicrobial genetic determinants and population structure of iNTS serotypes-genotypes. Phylogeographical reconstruction was further conducted in context of the existing genomic framework of iNTS serotypes Typhimurium and Enteritidis. Population-based incidence of MDR-iNTS disease was also estimated. ResultsSalmonella enterica subsp. Enterica serotype Typhimurium (S. Typhimurium) sequence-type (ST) 313 and Salmonella enterica subsp. Enterica serotype Enteritidis (S. Enteritidis) ST11 were predominant, and both exhibited high frequencies of MDR. Salmonella enterica subsp. Enterica serotype Dublin (S. Dublin) ST10 emerged in West Africa. Mutations in the gyrA gene were identified in S. Enteritidis and S. Typhimurium in Ghana; and ST313 carrying blaCTX-M-15 was found in Kenya. Inter-country transmission of MDR ST313 lineage II and the West African Clade of MDR ST11 between Ghana and neighbouring countries including Mali, Burkina Faso, and Nigeria were evident. The incidence of MDR-iNTS disease exceeded 100/100,000-person years-of-observation (PYO) in children aged <5 years in several West African countries. ConclusionsMultiple MDR iNTS serotypes-sequence types, predominantly S. Typhimurium ST313 and S. Enteritidis ST11, are co-circulating in sub-Saharan Africa with evidence of transmission between West African countries. The development of safe and effective iNTS vaccines coupled with appropriate antimicrobial stewardship and adequate epidemiological monitoring are essential to limit the impact of these pathogens in Africa.

genomics↗