Rapid clade divergence and phyletic gradualism in an interacting particle model of sympatric speciation.

The coexistence of cladogenesis, i.e., the branching of lineages along an evolutionary tree as observed in the fossil record, and anagenesis, which is the progressive evolution within populations, lacks a clear explanation. In this study, we examine a simple model that simulates the evolutionary changes occurring within populations inhabiting the same environment in sympatry, and driven by ecological competition. Our model characterizes populations through a set of evolving morphological traits represented by mathematical points within a two-dimensional morphospace. Such points may reproduce or die due to overcrowding, implying competition in morphospace as suggested by the ecological phenomenon of character displacement. By focusing on the morphospace rather than physical space, the model effectively captures the simultaneous evolution of coexisting populations. Central to the model is the delicate balance between the range of competition and the range of reproduction within the morphospace. Interesting patterns emerge when the ratio between the competition to reproducetion ranges, referred to as CR ratio, changes from values slightly smaller to significantly larger than unity. When competition acts over short distances relative to the reproduction range (low CR), the phylogenetic tree takes on a nearly uniform appearance, gradually transforming into a more bush-like structure for slightly higher CR values. With further increases in CR, evolutionary lineages become more discernible, and the morphogenetic pattern shifts from a bush-like shape to a more tree-like arrangement and few branches for very large CRs. At specific time sections, the synthetic phylogenetic tree appears as an assembly of clusters of individuals within the morphospace. These clusters, interpretable as simulated models of species, exhibit distinct separation within the morphospace and are subject to dynamic inter-cluster repulsion. Notably, clusters tend to be resistant to change. They maintain relatively constant abundances while gradually shifting their positions within the morphospace-a phase that aligns with the concept of phyletic gradualism. However, this predictable pattern is occasionally upset by the abrupt divisions into multiple groups, interpreted as cladogenesis events. The intricacies of the splitting process are explored, revealing that in scenarios with large CR values, the splitting can emerge much more rapidly than phyletic changes. This accelerated process of splitting is initiated by one or few individuals at the fringes of a cluster, where competition is minimal. The newly generated cluster then undergoes deformation, swiftly followed by divergence and splitting (seen as branching in the synthetic phylogenetic tree), as if an inherent "repulsion" triggered the division between species. The simple rules implied in the interacting-particle model may provide insight into the coexistence of gradualism and cladogenesis along lineages, illustrating the capacity for rapid shifts during cladogenesis and the more gradual process of anagenesis.

Short-term association between air temperature and mortality in seven cities in Norway: A time series analysis.

BACKGROUND: The association between ambient air temperature and mortality has not been assessed in Norway. This study aimed to quantify for seven Norwegian cities (Oslo, Bergen, Stavanger, Drammen, Fredrikstad, Trondheim and Tromsø) the non-accidental, cardiovascular and respiratory diseases mortality burden due to non-optimal ambient temperatures. METHODS: We used a historical daily dataset (1996-2018) to perform city-specific analyses with a distributed lag non-linear model with 14 days of lag, and pooled results in a multivariate meta-regression. We calculated attributable deaths for heat and cold, defined as days with temperatures above and below the city-specific optimum temperature. We further divided temperatures into moderate and extreme using cut-offs at the 1st and 99th percentiles. RESULTS: We observed that 5.3% (95% confidence interval (CI) 2.0-8.3) of the non-accidental related deaths, 11.8% (95% CI 6.4-16.4) of the cardiovascular and 5.9% (95% CI -4.0 to 14.3) of the respiratory were attributable to non-optimal temperatures. Notable variations were found between cities and subgroups stratified by sex and age. The mortality burden related to cold dominated in all three health outcomes (5.1%, 2.0-8.1, 11.4%, 6.0-15.4, and 5.1%, -5.5 to 13.8 respectively). Heat had a more pronounced effect on the burden of respiratory deaths (0.9%, 0.2-1.0). Extreme cold accounted for 0.2% of non-accidental deaths and 0.3% of cardiovascular and respiratory deaths, while extreme heat contributed to 0.2% of non-accidental and to 0.3% of respiratory deaths. CONCLUSIONS: Most of the burden could be attributed to the contribution of moderate cold. This evidence has significant implications for enhancing public-health policies to better address health consequences in the Norwegian setting.

Pertussis epidemiology including direct and indirect effects of the childhood pertussis booster vaccinations, Norway, 1998-2019.

BACKGROUND: The acellular pertussis vaccine has been used in the Norwegian national immunisation program since 1998. Following an increase in pertussis incidence in all age groups, booster doses were introduced for 7-8-year-olds in 2006, and for 15-16-year-olds in 2013. We assessed the effects of the booster doses on pertussis incidence in different age groups to inform potential changes in vaccination policy. METHODS: We included all pertussis cases notified to the Norwegian Surveillance System for Communicable Diseases in 1998-2019. We calculated annual incidence rates (IR, per 100,000 inhabitants) by age group. We estimated average annual changes in IRs (incidence rate ratios, IRR) for each age group for 2006-2012 and 2013-2019 using Poisson regression. RESULTS: In 1998-2019, 74,675 cases of pertussis were notified. Coinciding with booster introduction, between 2006 and 2012 the IR decreased among 8-15-year-olds (from 433 to 199/100,000, IRR 0.89 [95% confidence interval 0.88-0.90]). A similar decrease was seen between 2013 and 2019 among 16-19-year-olds (from 171 to 77/100,000, IRR 0.84 [0.82-0.86]). There was no significant change in IRs among children < 1 year of age between 2006 and 2012 (IRR 0.99 [0.95-1.04]) or 2013-2019 (IRR 0.96 [0.91-1.02]). The IR decreased in both periods among adults aged 20-39 and 40+ (IRR 0.94 [0.93-0.95] and 0.92 [0.91-0.92] in 2006-2012; IRR 0.97 [0.96-0.99] and 0.97 [0.96-0.99] in 2013-2019, respectively). Despite steady, high vaccination coverage, in 2013-2019, there was an increase in the IR among children aged 1-7 (63 to 86/100,000, IRR 1.05 [1.03-1.07]) and 8-15 years (88 to 122/100,000, IRR 1.08 [1.06-1.10]). CONCLUSIONS: Pertussis booster doses have offered direct protection in the targeted age groups. Our findings suggest indirect protection in adults, while the incidence in infants hasn't changed. The recent increase in IRs among 1-15-year-olds warrants close monitoring and further evaluation of the vaccination schedule.

Assessment of Coronavirus Disease 2019 Intervention Strategies in the Nordic Countries Using Genomic Epidemiology.

We explored how the duration, size, and number of virus transmission clusters, defined as country-specific monophyletic groups in a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) phylogenetic tree, differed among the Nordic countries of Norway, Sweden, Denmark, Finland, and Iceland. Our results suggest that although geographical connectivity, population density, and openness influence the spread and the size of SARS-CoV-2 transmission clusters, the different country-specific intervention strategies had the largest impact. We also found a significant positive association between the size and duration of transmission clusters in the Nordic countries, suggesting that the rapid deployment of contact tracing is a key response measure in reducing virus transmission.

The impact of public health interventions in the Nordic countries during the first year of SARS-CoV-2 transmission and evolution.

BackgroundMany countries have attempted to mitigate and control COVID-19 through non-pharmaceutical interventions, particularly with the aim of reducing population movement and contact. However, it remains unclear how the different control strategies impacted the local phylodynamics of the causative SARS-CoV-2 virus.AimWe aimed to assess the duration of chains of virus transmission within individual countries and the extent to which countries exported viruses to their geographical neighbours.MethodsWe analysed complete SARS-CoV-2 genomes to infer the relative frequencies of virus importation and exportation, as well as virus transmission dynamics, in countries of northern Europe. We examined virus evolution and phylodynamics in Denmark, Finland, Iceland, Norway and Sweden during the first year of the COVID-19 pandemic.ResultsThe Nordic countries differed markedly in the invasiveness of control strategies, which we found reflected in transmission chain dynamics. For example, Sweden, which compared with the other Nordic countries relied more on recommendation-based rather than legislation-based mitigation interventions, had transmission chains that were more numerous and tended to have more cases. This trend increased over the first 8 months of 2020. Together with Denmark, Sweden was a net exporter of SARS-CoV-2. Norway and Finland implemented legislation-based interventions; their transmission chain dynamics were in stark contrast to their neighbouring country Sweden.ConclusionSweden constituted an epidemiological and evolutionary refugium that enabled the virus to maintain active transmission and spread to other geographical locations. Our analysis reveals the utility of genomic surveillance where monitoring of active transmission chains is a key metric.

Poor self-reported adherence to COVID-19-related quarantine/isolation requests, Norway, April to July 2020.

To limit SARS-CoV-2 spread, quarantine and isolation are obligatory in several situations in Norway. We found low self-reported adherence to requested measures among 1,704 individuals (42%; 95% confidence interval: 37-48). Adherence was lower in May-June-July (33-38%) compared with April (66%), and higher among those experiencing COVID-19-compatible symptoms (71%) compared with those without (28%). These findings suggest that consideration is required of strategies to improve people's adherence to quarantine and isolation.

Quantifying the transmission dynamics of MRSA in the community and healthcare settings in a low-prevalence country.

Methicillin-resistant Staphylococcus aureus (MRSA) is a primarily nosocomial pathogen that, in recent years, has increasingly spread to the general population. The rising prevalence of MRSA in the community implies more frequent introductions in healthcare settings that could jeopardize the effectiveness of infection-control procedures. To investigate the epidemiological dynamics of MRSA in a low-prevalence country, we developed an individual-based model (IBM) reproducing the population's sociodemography, explicitly representing households, hospitals, and nursing homes. The model was calibrated to surveillance data from the Norwegian national registry (2008-2015) and to published household prevalence data. We estimated an effective reproductive number of 0.68 (95% CI 0.47-0.90), suggesting that the observed rise in MRSA infections is not due to an ongoing epidemic but driven by more frequent acquisitions abroad. As a result of MRSA importations, an almost twofold increase in the prevalence of carriage was estimated over the study period, in 2015 reaching a value of 0.37% (0.25-0.54%) in the community and 1.11% (0.79-1.59%) in hospitalized patients. Household transmission accounted for half of new MRSA acquisitions, indicating this setting as a potential target for preventive strategies. However, nosocomial acquisition was still the primary source of symptomatic disease, which reinforces the importance of hospital-based transmission control. Although our results indicate little reason for concern about MRSA transmission in low-prevalence settings in the immediate future, the increases in importation and global circulation highlight the need for coordinated initiatives to reduce the spread of antibiotic resistance worldwide.

A theoretical single-parameter model for urbanisation to study infectious disease spread and interventions.

The world is continuously urbanising, resulting in clusters of densely populated urban areas and more sparsely populated rural areas. We propose a method for generating spatial fields with controllable levels of clustering of the population. We build a synthetic country, and use this method to generate versions of the country with different clustering levels. Combined with a metapopulation model for infectious disease spread, this allows us to in silico explore how urbanisation affects infectious disease spread. In a baseline scenario with no interventions, the underlying population clustering seems to have little effect on the final size and timing of the epidemic. Under within-country restrictions on non-commuting travel, the final size decreases with increased population clustering. The effect of travel restrictions on reducing the final size is larger with higher clustering. The reduction is larger in the more rural areas. Within-country travel restrictions delay the epidemic, and the delay is largest for lower clustering levels. We implemented three different vaccination strategies-uniform vaccination (in space), preferentially vaccinating urban locations and preferentially vaccinating rural locations. The urban and uniform vaccination strategies were most effective in reducing the final size, while the rural vaccination strategy was clearly inferior. Visual inspection of some European countries shows that many countries already have high population clustering. In the future, they will likely become even more clustered. Hence, according to our model, within-country travel restrictions are likely to be less and less effective in delaying epidemics, while they will be more effective in decreasing final sizes. In addition, to minimise final sizes, it is important not to neglect urban locations when distributing vaccines. To our knowledge, this is the first study to systematically investigate the effect of urbanisation on infectious disease spread and in particular, to examine effectiveness of prevention measures as a function of urbanisation.

The Role of Polymorphonuclear Leukocyte Counts from Urethra, Cervix, and Vaginal Wet Mount in Diagnosis of Nongonococcal Lower Genital Tract Infection.

Objective: The aim of this study was to evaluate whether the polymorphonuclear leukocyte (PMNL) inflammatory response in women with nongonococcal lower genital tract infection (LGTI) can be used to optimize criteria for syndromic treatment. Methods: A cross-sectional study of 375 women attending the STI clinic in Oslo. Urethral, cervical, and vaginal specimens underwent microscopy for PMNLs. Chlamydia trachomatis (Ct) and other STIs were detected in the cervical/vaginal swabs and urine, using nucleic acid amplification test (NAAT). After excluding vulvovaginal candidiasis, genital herpes, and trichomoniasis, we correlated clinical and microscopic signs of inflammation with positive NAAT for Ct, mycoplasma genitalium (Mg), and Ureaplasma urealyticum (Uu) in a subgroup of 293 women. Results: To predict a positive Ct, the combination of high cut-off urethritis (≥10 PMNLs/HPF) and microscopic cervicitis had a high specificity of 0.93, a PPV of 0.37, and a sensitivity of 0.35. LGTI criteria had low predicting values for Mg and Uu. Conclusion: Including microscopic criteria for the diagnosis of LGTI gives better indication for presumptive antibiotic treatment than anamnestic and clinical diagnosis alone.

Analysis of multi-level spatial data reveals strong synchrony in seasonal influenza epidemics across Norway, Sweden, and Denmark.

Population structure, spatial diffusion, and climatic conditions mediate the spatiotemporal spread of seasonal influenza in temperate regions. However, much of our knowledge of these dynamics stems from a few well-studied countries, such as the United States (US), and the extent to which this applies in different demographic and climatic environments is not fully understood. Using novel data from Norway, Sweden, and Denmark, we applied wavelet analysis and non-parametric spatial statistics to explore the spatiotemporal dynamics of influenza transmission at regional and international scales. We found the timing and amplitude of epidemics were highly synchronized both within and between countries, despite the geographical isolation of many areas in our study. Within Norway, this synchrony was most strongly modulated by population size, confirming previous findings that hierarchical spread between larger populations underlies seasonal influenza dynamics at regional levels. However, we found no such association when comparing across countries, suggesting that other factors become important at the international scale. Finally, to frame our results within a wider global context, we compared our findings from Norway to those from the US. After correcting for differences in geographic scale, we unexpectedly found higher levels of synchrony in Norway, despite its smaller population size. We hypothesize that this greater synchrony may be driven by more favorable and spatially uniform climatic conditions, although there are other likely factors we were unable to consider (such as reduced variation in school term times and differences in population movements). Overall, our results highlight the importance of comparing influenza spread at different spatial scales and across diverse geographic regions in order to better understand the complex mechanisms underlying disease dynamics.

The natural history of varicella zoster virus infection in Norway: Further insights on exogenous boosting and progressive immunity to herpes zoster.

We use age-structured models for VZV transmission and reactivation to reconstruct the natural history of VZV in Norway based on available pre-vaccination serological data, contact matrices, and herpes zoster incidence data. Depending on the hypotheses on contact and transmission patterns, the basic reproduction number of varicella in Norway ranges between 3.7 and 5.0, implying a vaccine coverage between 73 and 80% to effectively interrupt transmission with a 100% vaccine efficacy against infection. The varicella force of infection peaks during early childhood (3-5 yrs) and shows a prolonged phase of higher risk during the childbearing period, though quantitative variations can occur depending on contact patterns. By expressing the magnitude of exogenous boosting as a proportion of the force of infection, it is shown that reactivation is well described by a progressive immunity mechanism sustained by a large, though possibly below 100%, degree of exogenous boosting, in agreement with findings from other Nordic countries, implying large reproduction numbers of boosting. Moreover, magnitudes of exogenous boosting below 40% are robustly disconfirmed by data. These results bring further insight on the magnitude of immunity boosting and its relationship with reactivation.

Estimating Age-Specific Immunity and Force of Infection of Varicella Zoster Virus in Norway Using Mixture Models.

This study applies mixture modelling to examine age-specific immunity to varicella zoster virus (VZV) infection in Norway based on the first large-scale serological study in the general population. We estimated the seropositive proportions at different ages and calculated the underlying force of infection by using a sample of 2103 residual sera obtained from patients seeking primary and hospital care. A rapid increase in the VZV-associated immunity is observed in the first years of life with 63% of children being immune by age 5. The increase in the immunity levels slows down thereafter, with a large proportion of adults still susceptible by age 20 (around 14.5%), thus at risk of serious sequelae of varicella infection. The corresponding force of infection peaks during the preschool period, subsequently declines to a minimum between ages 10 and 20 years, and afterwards moderately increases to reach a plateau lasting throughout the childbearing period. In comparison with the traditional cut-off approach, mixture modelling used the whole data without producing any inconclusive cases, led to an unbiased classification of individuals between susceptible and immune, and provided a smoother immune profile by age. These findings represent an important step towards any decision about the introduction of varicella vaccination in Norway, as they are a primary input for mathematical transmission models aimed at evaluating potential vaccination scenarios.

Dynamic modeling of cost-effectiveness of rotavirus vaccination, Kazakhstan.

The government of Kazakhstan, a middle-income country in Central Asia, is considering the introduction of rotavirus vaccination into its national immunization program. We performed a cost-effectiveness analysis of rotavirus vaccination spanning 20 years by using a synthesis of dynamic transmission models accounting for herd protection. We found that a vaccination program with 90% coverage would prevent ≈880 rotavirus deaths and save an average of 54,784 life-years for children <5 years of age. Indirect protection accounted for 40% and 60% reduction in severe and mild rotavirus gastroenteritis, respectively. Cost per life year gained was US $18,044 from a societal perspective and US $23,892 from a health care perspective. Comparing the 2 key parameters of cost-effectiveness, mortality rates and vaccine cost at