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Nature Communications Jan 2023Transmission bottlenecks limit the spread of novel mutations and reduce the efficiency of selection along a transmission chain. While increased force of infection,...
Transmission bottlenecks limit the spread of novel mutations and reduce the efficiency of selection along a transmission chain. While increased force of infection, receptor binding, or immune evasion may influence bottleneck size, the relationship between transmissibility and the transmission bottleneck is unclear. Here we compare the transmission bottleneck of non-VOC SARS-CoV-2 lineages to those of Alpha, Delta, and Omicron. We sequenced viruses from 168 individuals in 65 households. Most virus populations had 0-1 single nucleotide variants (iSNV). From 64 transmission pairs with detectable iSNV, we identify a per clade bottleneck of 1 (95% CI 1-1) for Alpha, Delta, and Omicron and 2 (95% CI 2-2) for non-VOC. These tight bottlenecks reflect the low diversity at the time of transmission, which may be more pronounced in rapidly transmissible variants. Tight bottlenecks will limit the development of highly mutated VOC in transmission chains, adding to the evidence that selection over prolonged infections may drive their evolution.
Topics: Humans; COVID-19; SARS-CoV-2; Immune Evasion
PubMed: 36650162
DOI: 10.1038/s41467-023-36001-5 -
Molecular Neurobiology Aug 2019The large chronic wasting disease (CWD)-affected cervid population in the USA and Canada, and the risk of the disease being transmitted to humans through intermediate... (Review)
Review
The large chronic wasting disease (CWD)-affected cervid population in the USA and Canada, and the risk of the disease being transmitted to humans through intermediate species, is a highly worrying issue that is still poorly understood. In this case, recombinant protein misfolding cyclic amplification was used to determine, in vitro, the relevance of each individual amino acid on cross-species prion transmission. Others and we have found that the β2-α2 loop is a key modulator of transmission barriers between species and markedly influences infection by sheep scrapie, bovine spongiform encephalopathy (BSE), or elk CWD. Amino acids that differentiate ovine and deer normal host prion protein (PrP) and associated with structural rigidity of the loop β2-α2 (S173N, N177T) appear to confer resistance to some prion diseases. However, addition of methionine at codon 208 together with the previously described rigid loop substitutions seems to hide a key in this species barrier, as it makes sheep recombinant prion protein highly susceptible to CWD-induced misfolding. These studies indicate that interspecies prion transmission is not only governed just by the β2-α2 loop amino acid sequence but also by its interactions with the α3-helix as shown by substitution I208M. Transmissible spongiform encephalopathies, characterized by long incubation periods and spongiform changes associated with neuronal loss in the brain, have been described in several mammalian species appearing either naturally (scrapie in sheep and goats, bovine spongiform encephalopathy in cattle, chronic wasting disease in cervids, Creutzfeldt-Jakob disease in humans) or by experimental transmission studies (scrapie in mice and hamsters). Much of the pathogenesis of the prion diseases has been determined in the last 40 years, such as the etiological agent or the fact that prions occur as different strains that show distinct biological and physicochemical properties. However, there are many unanswered questions regarding the strain phenomenon and interspecies transmissibility. To assess the risk of interspecies transmission between scrapie and chronic wasting disease, an in vitro prion propagation method has been used. This technique allows to predict the amino acids preventing the transmission between sheep and deer prion diseases.
Topics: Amino Acid Sequence; Amino Acid Substitution; Animals; Chickens; Deer; Mice, Knockout; Prion Proteins; Protein Domains; Protein Folding; Protein Structure, Secondary; Recombinant Proteins; Sheep; Species Specificity
PubMed: 30592012
DOI: 10.1007/s12035-018-1443-8 -
Scientific Reports Aug 2021With an increasing body of evidence that SARS-CoV-2 is an airborne pathogen, droplet character formed during speech, coughs, and sneezes are important. Larger droplets...
With an increasing body of evidence that SARS-CoV-2 is an airborne pathogen, droplet character formed during speech, coughs, and sneezes are important. Larger droplets tend to fall faster and are less prone to drive the airborne transmission pathway. Alternatively, small droplets (aerosols) can remain suspended for long time periods. The small size of SARS-CoV-2 enables it to be encapsulated in these aerosols, thereby increasing the pathogen's ability to be transmitted via airborne paths. Droplet formation during human respiratory events relates to airspeed (speech, cough, sneeze), fluid properties of the saliva/mucus, and the fluid content itself. In this work, we study the fluidic drivers (fluid properties and content) and their influence on factors relating to transmissibility. We explore the relationship between saliva fluid properties and droplet airborne transmission paths. Interestingly, the natural human response appears to potentially work with these drivers to mitigate pathogen transmission. In this work, the saliva is varied using two approaches: (1) modifying the saliva with colloids that increase the viscosity/surface tension, and (2) stimulating the saliva content to increased/decreased levels. Through modern experimental and numerical flow diagnostic methods, the character, content, and exposure to droplets and aerosols are all evaluated. The results indicate that altering the saliva properties can significantly impact the droplet size distribution, the formation of aerosols, the trajectory of the bulk of the droplet plume, and the exposure (or transmissibility) to droplets. High-fidelity numerical methods used and verify that increased droplet size character enhances droplet fallout. In the context of natural saliva response, we find previous studies indicating natural human responses of increased saliva viscosity from stress and reduced saliva content from either stress or illness. These responses both favorably correspond to reduced transmissibility. Such a finding also relates to potential control methods, hence, we compared results to a surgical mask. In general, we find that saliva alteration can produce fewer and larger droplets with less content and aerosols. Such results indicate a novel approach to alter SARS-CoV-2's transmission path and may act as a way to control the COVID-19 pandemic, as well as influenza and the common cold.
Topics: Aerosols; Air Microbiology; COVID-19; Colloids; Cough; Humans; Pandemics; SARS-CoV-2; Saliva; Sneezing; Viscosity
PubMed: 34362974
DOI: 10.1038/s41598-021-95559-6 -
Epidemics Jun 2017The recent global dissemination of Chikungunya and Zika has fostered public health concern worldwide. To better understand the drivers of transmission of these two... (Comparative Study)
Comparative Study
The recent global dissemination of Chikungunya and Zika has fostered public health concern worldwide. To better understand the drivers of transmission of these two arboviral diseases, we propose a joint analysis of Chikungunya and Zika epidemics in the same territories, taking into account the common epidemiological features of the epidemics: transmitted by the same vector, in the same environments, and observed by the same surveillance systems. We analyse eighteen outbreaks in French Polynesia and the French West Indies using a hierarchical time-dependent SIR model accounting for the effect of virus, location and weather on transmission, and based on a disease specific serial interval. We show that Chikungunya and Zika have similar transmission potential in the same territories (transmissibility ratio between Zika and Chikungunya of 1.04 [95% credible interval: 0.97; 1.13]), but that detection and reporting rates were different (around 19% for Zika and 40% for Chikungunya). Temperature variations between 22°C and 29°C did not alter transmission, but increased precipitation showed a dual effect, first reducing transmission after a two-week delay, then increasing it around five weeks later. The present study provides valuable information for risk assessment and introduces a modelling framework for the comparative analysis of arboviral infections that can be extended to other viruses and territories.
Topics: Chikungunya Fever; Epidemics; Humans; Polynesia; West Indies; Zika Virus; Zika Virus Infection
PubMed: 28139388
DOI: 10.1016/j.epidem.2017.01.001 -
Virus Research Dec 2013Highly pathogenic avian H5N1 influenza A viruses occasionally infect humans and cause severe respiratory disease and fatalities. Currently, these viruses are not... (Review)
Review
Highly pathogenic avian H5N1 influenza A viruses occasionally infect humans and cause severe respiratory disease and fatalities. Currently, these viruses are not efficiently transmitted from person to person, although limited human-to-human transmission may have occurred. Nevertheless, further adaptation of avian H5N1 influenza A viruses to humans and/or reassortment with human influenza A viruses may result in aerosol transmissible viruses with pandemic potential. Although the full range of factors that modulate the transmission and replication of influenza A viruses in humans are not yet known, we are beginning to understand some of the molecular changes that may allow H5N1 influenza A viruses to transmit via aerosols or respiratory droplets among mammals. A better understanding of the biological basis and genetic determinants that confer transmissibility to H5N1 influenza A viruses in mammals is important to enhance our pandemic preparedness.
Topics: Animals; Humans; Influenza A Virus, H5N1 Subtype; Influenza, Human; Mammals; Orthomyxoviridae Infections
PubMed: 23954580
DOI: 10.1016/j.virusres.2013.07.017 -
Methods in Molecular Biology (Clifton,... 2017Prions represent a new paradigm of protein-mediated information transfer. In the case of mammals, prions are the cause of fatal, transmissible neurodegenerative... (Review)
Review
Prions represent a new paradigm of protein-mediated information transfer. In the case of mammals, prions are the cause of fatal, transmissible neurodegenerative diseases, sometimes referred to as transmissible spongiform encephalopathies (TSEs), which frequently occur as epidemics. An increasing body of evidence indicates that the canonical mechanism of conformational corruption of cellular prion protein (PrP) by the pathogenic isoform (PrP) that is the basis of prion formation in TSEs is common to a spectrum of proteins associated with various additional human neurodegenerative disorders, including the more common Alzheimer's and Parkinson's diseases. The peerless infectious properties of TSE prions, and the unparalleled tools for their study, therefore enable elucidation of mechanisms of template-mediated conformational propagation that are generally applicable to these related disease states. Many unresolved issues remain including the exact molecular nature of the prion, the detailed cellular and molecular mechanisms of prion propagation, and the means by which prion diseases can be both genetic and infectious. In addition, we know little about the mechanism by which neurons degenerate during prion diseases. Tied to this, the physiological role of the normal form of the prion protein remains unclear and it is uncertain whether or not loss of this function contributes to prion pathogenesis. The factors governing the transmission of prions between species remain unclear, in particular the means by which prion strains and PrP primary structure interact to affect interspecies prion transmission. Despite all these unknowns, advances in our understanding of prions have occurred because of their transmissibility to experimental animals, and the development of transgenic (Tg) mouse models has done much to further our understanding about various aspects of prion biology. In this review, we will focus on advances in our understanding of prion biology that occurred in the past 8 years since our last review of this topic.
Topics: Animals; Brain; Cattle; Creutzfeldt-Jakob Syndrome; Disease Models, Animal; Encephalopathy, Bovine Spongiform; Gene Expression; Humans; Mice; Mice, Transgenic; PrPC Proteins; PrPSc Proteins; Protein Conformation, beta-Strand; Protein Folding; Scrapie; Wasting Disease, Chronic
PubMed: 28861793
DOI: 10.1007/978-1-4939-7244-9_16 -
Epidemiology and Infection Sep 2022Coronavirus disease 2019 (COVID-19) asymptomatic cases are hard to identify, impeding transmissibility estimation. The value of COVID-19 transmissibility is worth...
Coronavirus disease 2019 (COVID-19) asymptomatic cases are hard to identify, impeding transmissibility estimation. The value of COVID-19 transmissibility is worth further elucidation for key assumptions in further modelling studies. Through a population-based surveillance network, we collected data on 1342 confirmed cases with a 90-days follow-up for all asymptomatic cases. An age-stratified compartmental model containing contact information was built to estimate the transmissibility of symptomatic and asymptomatic COVID-19 cases. The difference in transmissibility of a symptomatic and asymptomatic case depended on age and was most distinct for the middle-age groups. The asymptomatic cases had a 66.7% lower transmissibility rate than symptomatic cases, and 74.1% (95% CI 65.9-80.7) of all asymptomatic cases were missed in detection. The average proportion of asymptomatic cases was 28.2% (95% CI 23.0-34.6). Simulation demonstrated that the burden of asymptomatic transmission increased as the epidemic continued and could potentially dominate total transmission. The transmissibility of asymptomatic COVID-19 cases is high and asymptomatic COVID-19 cases play a significant role in outbreaks.
Topics: Humans; Middle Aged; Computer Simulation; COVID-19; Disease Outbreaks; Epidemics; SARS-CoV-2; Asymptomatic Infections
PubMed: 36263615
DOI: 10.1017/S0950268822001467 -
BMC Infectious Diseases May 2021After relaxing social distancing measures, South Korea experienced a resurgent second epidemic wave of coronavirus disease 2019 (COVID-19). In this study, we aimed to...
BACKGROUND
After relaxing social distancing measures, South Korea experienced a resurgent second epidemic wave of coronavirus disease 2019 (COVID-19). In this study, we aimed to identify the transmission dynamics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and assess the impact of COVID-19 case finding and contact tracing in each epidemic wave.
METHODS
We collected data on COVID-19 cases published by local public health authorities in South Korea and divided the study into two epidemic periods (19 January-19 April 2020 for the first epidemic wave and 20 April-11 August 2020 for the second epidemic wave). To identify changes in the transmissibility of SARS-CoV-2, the daily effective reproductive number (R) was estimated using the illness onset of the cases. Furthermore, to identify the characteristics of each epidemic wave, frequencies of cluster types were measured, and age-specific transmission probability matrices and serial intervals were estimated. The proportion of asymptomatic cases and cases with unknown sources of infection were also estimated to assess the changes of infections identified as cases in each wave.
RESULTS
In early May 2020, within 2-weeks of a relaxation in strict social distancing measures, R increased rapidly from 0.2 to 1.8 within a week and was around 1 until early July 2020. In both epidemic waves, the most frequent cluster types were religious-related activities and transmissions among the same age were more common. Furthermore, children were rarely infectors or infectees, and the mean serial intervals were similar (~ 3 days) in both waves. The proportion of asymptomatic cases at presentation increased from 22% (in the first wave) to 27% (in the second wave), while the cases with unknown sources of infection were similar in both waves (22 and 24%, respectively).
CONCLUSIONS
Our study shows that relaxing social distancing measures was associated with increased SARS-CoV-2 transmission despite rigorous case findings in South Korea. Along with social distancing measures, the enhanced contact tracing including asymptomatic cases could be an efficient approach to control further epidemic waves.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Basic Reproduction Number; COVID-19; Child; Cluster Analysis; Communicable Disease Control; Epidemics; Female; Humans; Male; Middle Aged; Republic of Korea; SARS-CoV-2; Young Adult
PubMed: 34039296
DOI: 10.1186/s12879-021-06204-6 -
Viruses Jun 2021The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is genetically variable, allowing it to adapt to various hosts including humans. Indeed, SARS-CoV-2 has... (Review)
Review
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is genetically variable, allowing it to adapt to various hosts including humans. Indeed, SARS-CoV-2 has accumulated around two mutations per genome each month. The first relevant event in this context was the occurrence of the mutant D614G in the Spike gene. Moreover, several variants have emerged, including the well-characterized 20I/501Y.V1, 20H/501Y.V2, and 20J/501Y.V3 strains, in addition to those that have been detected within clusters, such as 19B/501Y or 20C/655Y in France. Mutants have also emerged in animals, including a variant transmitted to humans, namely, the Mink variant detected in Denmark. The emergence of these variants has affected the transmissibility of the virus (for example, 20I/501Y.V1, which was up to 82% more transmissible than other preexisting variants), its severity, and its ability to escape natural, adaptive, vaccine, and therapeutic immunity. In this respect, we review the literature on variants that have currently emerged, and their effect on vaccines and therapies, and, in particular, monoclonal antibodies (mAbs). The emergence of SARS-CoV-2 variants must be examined to allow effective preventive and curative control strategies to be developed.
Topics: Antibodies, Monoclonal; Antibodies, Neutralizing; Antibodies, Viral; COVID-19; COVID-19 Vaccines; Humans; Mutation; SARS-CoV-2
PubMed: 34207378
DOI: 10.3390/v13061171 -
Emerging Infectious Diseases 1998Since blood is a biologic product, it is unlikely that the risk for transfusion-transmitted infection will ever be reduced to zero. The approach to emerging infections...
Since blood is a biologic product, it is unlikely that the risk for transfusion-transmitted infection will ever be reduced to zero. The approach to emerging infections associated with transfusion of blood and blood products includes assessing the transmissibility of the agent by this route; developing effective prevention strategies, including screening tests and donor deferral policies; improving viral and bacterial inactivation procedures; and surveillance for known, as well as emerging and poorly characterized, transfusion-transmitted agents. Vigilance is needed to help ensure proper balance between safety and the availability of blood. Finally, vigilance needs to extend to the developing world, where the basic elements to reduce transfusion-transmitted infections and systems of disease surveillance are often not available.
Topics: Biological Products; Blood Banks; Blood Transfusion; Blood-Borne Pathogens; Communicable Diseases; Humans; Safety
PubMed: 9716958
DOI: 10.3201/eid0403.980317