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Background. The work environment presents major challenges for breastfeeding mothers through the physical separation of the mother and the baby post maternity leave. Objective. To explore the experiences of employed breastfeeding mothers from designated workplaces (with more than 50 employees) in Worcester, South Africa. Method. This qualitative study was conducted using focus group discussions (FDGs). Employed breastfeeding mothers from designated retail, manufacturing and public workplaces were recruited from local communities. Eligible participants were those who had exclusively or predominantly breastfed their children for up to 6 months and had given birth within the last 24 months. A community fieldworker recruited participants and coordinated scheduling for the FDGs. Results. Five FDGs (N=24) were conducted. The mothers described returning to work as emotionally and logistically challenging. Those who continued breastfeeding while working demonstrated a strong commitment to and belief in breastfeeding. Consistent enabling factors and main sources of support mentioned included immediate family members, such as grandmothers, siblings and spouses. The challenges identified were a lack of private spaces and time to express breastmilk at work, an unsupportive workplace culture and a lack of work-life balance. The support needs identified for a successful return to work while breastfeeding included flexible schedules, designated private spaces for expressing milk, supportive colleagues and managers and active engagement with senior management on breastfeeding support. Conclusion. There is a need for psychosocial support for breastfeeding mothers to manage the emotional demands of returning to work and logistical support, such as providing breastfeeding spaces and time for expressing breastmilk. Human resource managers, occupational health nurses and wellness officials should inform mothers about the recommendation to provide breastfeeding breaks at work. Engagement and advocacy efforts with workplaces and these stakeholders on the importance of breastfeeding support should be initiated. [ABSTRACT FROM AUTHOR]

Numerical simulations of relativistic plasmas have become more feasible, popular, and crucial for various astrophysical sources with the availability of computational resources. The necessity for high-accuracy particle dynamics is especially highlighted in pulsar modelling due to the extreme associated electromagnetic fields and particle Lorentz factors. Including the radiation-reaction force in the particle dynamics adds even more complexity to the problem, but is crucial for such extreme astrophysical sources. We have also realized the need for such modelling concerning magnetic mirroring and particle injection models proposed for AR Sco, the first white dwarf pulsar. This paper demonstrates the benefits of using higher-order explicit numerical integrators with adaptive time-step methods to solve the full particle dynamics with radiation-reaction forces included. We show that for standard test scenarios, namely various combinations of uniform E - and B -fields and a static dipole B -field, the schemes we use are equivalent to and in extreme field cases outperform standard symplectic integrators in accuracy. We show that the higher-order schemes have massive computational time improvements due to the adaptive time-steps we implement, especially in non-uniform field scenarios and included radiation reaction where the particle gyro-radius rapidly changes. When balancing accuracy and computational time, we identified the adaptive Dormand–Prince eighth-order scheme to be ideal for our use cases. The schemes we use maintain accuracy and stability in describing the particle dynamics and we indicate how a charged particle enters radiation-reaction equilibrium and conforms to the analytical Aristotelian Electrodynamics expectations. [ABSTRACT FROM AUTHOR]

Background. The positive deviance approach has been used to identify infant and young child feeding (IYCF) practices associated with a reduction in stunting, but this research is limited in South Africa (SA). Objective. To identify strategies among positive deviant (PD) caregivers of non-stunted children aged 6 - 18 months that influence infant and young child feeding (IYCF) practices and raise well-nourished children in two informal settlements in Harrismith. Methods. This study employed a mixed-method design using a PD approach. Demographic questionnaires were administered to 28 purposefully sampled caregiver-child pairs to determine caregiver, child and household characteristics. Socioeconomic scores were obtained from these interviews and used to select six PD and six non-positive deviant (NPD) caregivers for semi-structured qualitative interviews between March and June 2019. Results. Nutritional PD behaviours included consuming 'flesh foods' (meat) more often and practising responsive feeding and family eating. Non-nutritional PD behaviours included coping strategies involving health-seeking behaviour, financial strategy and social capital of caregivers. All caregivers displayed poor breastfeeding practices and an early introduction of solid foods. Primary healthcare nurses were reported to frequently provide breastfeeding advice from outdated prevention of mother-to-child transmission policy. Conclusions. Poor IYCF practices highlight the need for continued advocacy and promotion of IYCF in SA. Nutritional PD behaviours are key to health promotional messages relayed within the local community where the research was conducted. The presence of nutritional and non-nutritional PD behaviours highlights the need for a multi-sectoral response to addressing stunting and improving IYCF practices. [ABSTRACT FROM AUTHOR]

This article discusses strategic management resources for implementing a successful Technical and Vocational Education and Training (TVET) strategy in Lesotho. The Ministry of Education and Training (MOET) and TVET institutions use strategic management to achieve their strategic goals, but strategic resources are scarce. This hinders the expected development of human capital. Due to skills mismatches, TVET graduates leave institutions with irrelevant skills, causing unemployment, poverty and social inequality. TVET institutions lack strategic resources to implement TVET strategies. Pragmatism and a mixed-methods approach guided data collection, data analysis, and interpretation of the results of this study. MOET staff were interviewed to determine strategic management resources. TVET staff completed a questionnaire to assess access to the strategic resources needed to implement the strategy successfully. This study found that Lesotho's government and MOET do not comprehend TVET's strategic resources and do not support TVET institutions adequately. The study recommends revising public sector policies, stakeholders' collaboration, improvement of the robustness of TVET funding, enhanced leadership, and TVET corporate governance to support the successful implementation of the public sector TVET strategy. [ABSTRACT FROM AUTHOR]

Upgrading, maintenance and rehabilitation of road infrastructure is expensive, especially in view of the growing scarcity and cost of suitable road building materials. In areas with high mica content and secondary minerals such as smectite in the natural materials, stabilisation with cement is not viable. The Council for Scientific and Industrial Research of South Africa has embarked on a research programme to evaluate the performance of substandard materials improved with anionic nano-silane modified bitumen emulsions for use in base and subbase layers. This work comprises laboratory testing as well as Accelerated Pavement Testing using the Heavy Vehicle Simulator (HVS). The results of a full-scale HVS test on a light pavement as well as initial analysis on a medium traffic road are discussed. It has been shown that stabilisation of available substandard materials using an anionic nano-silane modified bitumen emulsion compared with the standard approach of importing high quality crushed aggregate can lead to savings as high as 40%–50% for equivalent performance. In addition, there was also a significant reduction in construction effort and time. [ABSTRACT FROM AUTHOR]

The aim of this article is to explore the untapped potential of the local informal waste economic sector in relation to solid waste management practices in local government. More specifically, it analyses the extent to which the informal waste economy is synchronised with municipal solid waste management policies and strategies. Waste pickers or recyclers play an important role in promoting local economic development. Consequently, waste pickers are not only responsible for recycling useful waste, but they also contribute significantly to the waste economy. The methodological approach of the article entails unobtrusive research methods (conceptual analysis and documentary analysis). It assessed authoritative documents such as official government policy documents, reports, the worldwide web, accredited academic journal articles and other relevant documents applicable to the informal waste economy and solid waste management in local government. The study found that the Mangaung Metropolitan Municipality has focused predominately on solid waste management, with the exclusion of the informal waste economy. This research offers recommendations on how the Mangaung Metropolitan Municipality can formalise the informal waste economy. This article provides a fresh perspective and highlights research gaps on the need to integrate the informal waste economy and municipal solid waste management policies, plans, projects and programmes in the Mangaung Metropolitan Municipality. [ABSTRACT FROM AUTHOR]

Background: Treponemal diseases are a significant global health risk, presenting challenges to public health and severe consequences to individuals if left untreated. Despite numerous genomic studies on Treponema pallidum and the known possible biases introduced by the choice of the reference genome used for mapping, few investigations have addressed how these biases affect phylogenetic and evolutionary analysis of these bacteria. In this study, we ascertain the importance of selecting an appropriate genomic reference on phylogenetic and evolutionary analyses of T. pallidum., Results: We designed a multiple-reference-based (MRB) mapping strategy using four different reference genomes and compared it to traditional single-reference mapping. To conduct this comparison, we created a genomic dataset comprising 77 modern and ancient genomes from the three subspecies of T. pallidum, including a newly sequenced seventeenth century genome (35X mean coverage) of a syphilis-causing strain (designated as W86). Our findings show that recombination detection was consistent across different references, but the choice of reference significantly affected ancient genome reconstruction and phylogenetic inferences. The high-coverage W86 genome introduced in this study also provided a new calibration point for Bayesian molecular clock dating, improving the reconstruction of the evolutionary history of treponemal diseases. Additionally, we identified novel recombination events, positive selection targets, and refined dating estimates for key events in the species' history., Conclusions: This study highlights the importance of considering methodological implications and reference genome bias in high-throughput sequencing-based whole-genome analysis of T. pallidum, especially of ancient or low-coverage samples, contributing to a deeper understanding of the treponemal pathogen and its subspecies., Competing Interests: Declarations. Ethics approval and consent to participate: The skeletal fragments used for invasive molecular studies and macroscopic anthropological studies from the early modern archaeological site of Ostrów Tumski in Wrocław belong to the bone collections of the Department of Anthropology at the University of Environmental and Life Sciences in Wrocław. The curator of the collections, Prof. Barbara Kwiatkowska, approved the usage of the bioarchaeological materials (ancient bone samples) in this study. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

East, South, and Southeast Asia (together referred to as Southeastern Asia hereafter) have been recognized as critical areas fuelling the global circulation of seasonal influenza. However, the seasonal influenza migration network within Southeastern Asia remains unclear, including how pandemic-related disruptions altered this network. We leveraged genetic, epidemiological, and airline travel data between 2007-2023 to characterise the dispersal patterns of influenza A/H3N2 and B/Victoria viruses both out of and within Southeastern Asia, including during perturbations by the 2009 A/H1N1 and COVID-19 pandemics. During the COVID-19 pandemic, consistent autumn-winter movement waves from Southeastern Asia to temperate regions were interrupted for both subtype/lineages, however the A/H1N1 pandemic only disrupted A/H3N2 spread. We find a higher persistence of A/H3N2 than B/Victoria circulation in Southeastern Asia and identify distinct pandemic-related disruptions in A/H3N2 antigenic evolution between two pandemics, compared to interpandemic levels; similar patterns are observed in B/Victoria using genetic distance. The internal movement structure within Southeastern Asia markedly diverged during the COVID-19 pandemic season, and to a lesser extent, during the 2009 A/H1N1 pandemic season. Our findings provide insights into the heterogeneous impact of two distinct pandemic-related disruptions on influenza circulation, which can help anticipate the effects of future pandemics and potential mitigation strategies on influenza dynamics., Competing Interests: Competing interests: H.Y. received research funding from Sanofi Pasteur, GlaxoSmithKline, Yichang HEC Changjiang, Shanghai Roche Pharmaceutical Company, and SINOVAC Biotech Ltd. None of these funds are related to this work. All other authors declare no competing interests., (© 2025. The Author(s).)

Introduction: Meaningful supervisor-resident relationships enhance feedback and learning, yet not all relationships reach this potential. While there is increasing interest in continuity of supervision (CoS) to build relationships that support feedback and promote learning, there remains a limited understanding of how relationships develop and influence assessment over time. The aim of this study was to explore how supervisors and learners in postgraduate medical education perceive CoS relationships and their impact on feedback and assessment., Methods: We used constructivist grounded theory informed by the educational alliance to develop insight into how supervisor and resident perceptions of episodic and continuous relationships impact feedback and assessment. We interviewed 22 participants, including 14 family medicine residents and eight faculty advisors. We iteratively analysed the data concurrently with data collection., Results: In episodic relationships, participants accepted superficiality for variety and diversity in feedback. In continuous relationships, we identified four sub-types. Our participants described how each of these relationships impacted their perceptions of the feedback and assessment information given or received and resulted in different steps taken in response to their perceptions: (i) Not developing-tolerate feedback and seek out additional assessors, (ii) deteriorating-avoid feedback and seek out alternative assessors, (iii) developing-value and tailor feedback and (iv) becoming a friendship-question bias in feedback and advocate for more assessors., Conclusions: Episodic and continuous relationships offered feedback and assessment value. However, deeper analysis of the continuous relationships revealed additional complexity. Understanding the nuances of CoS relationships is important for supporting successful relationships and improving feedback and assessment., (© 2024 The Author(s). Medical Education published by Association for the Study of Medical Education and John Wiley & Sons Ltd.)

Accurately estimating the effective reproduction number (Rt) of a circulating pathogen is a fundamental challenge in the study of infectious disease. The fields of epidemiology and pathogen phylodynamics both share this goal, but to date, methodologies and data employed by each remain largely distinct. Here we present EpiFusion: a joint approach that can be used to harness the complementary strengths of each field to improve estimation of outbreak dynamics for large and poorly sampled epidemics, such as arboviral or respiratory virus outbreaks, and validate it for retrospective analysis. We propose a model of Rt that estimates outbreak trajectories conditional upon both phylodynamic (time-scaled trees estimated from genetic sequences) and epidemiological (case incidence) data. We simulate stochastic outbreak trajectories that are weighted according to epidemiological and phylodynamic observation models and fit using particle Markov Chain Monte Carlo. To assess performance, we test EpiFusion on simulated outbreaks in which transmission and/or surveillance rapidly changes and find that using EpiFusion to combine epidemiological and phylodynamic data maintains accuracy and increases certainty in trajectory and Rt estimates, compared to when each data type is used alone. We benchmark EpiFusion's performance against existing methods to estimate Rt and demonstrate advances in speed and accuracy. Importantly, our approach scales efficiently with dataset size. Finally, we apply our model to estimate Rt during the 2014 Ebola outbreak in Sierra Leone. EpiFusion is designed to accommodate future extensions that will improve its utility, such as explicitly modelling population structure, accommodations for phylogenetic uncertainty, and the ability to weight the contributions of genomic or case incidence to the inference., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Judge et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The global dynamics of seasonal influenza viruses inform the design of surveillance, intervention, and vaccination strategies. The COVID-19 pandemic provided a singular opportunity to evaluate how influenza circulation worldwide was perturbed by human behavioral changes. We combine molecular, epidemiological, and international travel data and find that the pandemic's onset led to a shift in the intensity and structure of international influenza lineage movement. During the pandemic, South Asia played an important role as a phylogenetic trunk location of influenza A viruses, whereas West Asia maintained the circulation of influenza B/Victoria. We explore drivers of influenza lineage dynamics across the pandemic period and reasons for the possible extinction of the B/Yamagata lineage. After a period of 3 years, the intensity of among-region influenza lineage movements returned to pre-pandemic levels, with the exception of B/Yamagata, after the recovery of global air traffic, highlighting the robustness of global lineage dispersal patterns to substantial perturbation.

Purpose: Response assessment of classical Hodgkin lymphoma (cHL) with positron emission tomography-computerized tomography (PET-CT) is standard of care in well-resourced settings but unavailable in most African countries. We aimed to investigate correlations between changes in PET-CT findings at interim analysis with changes in blood test results in pediatric patients with cHL in 17 South African centers., Methods: Changes in ferritin, lactate dehydrogenase (LDH), erythrocyte sedimentation rate (ESR), albumin, total white cell count (TWC), absolute lymphocyte count (ALC), and absolute eosinophil count were compared with PET-CT Deauville scores (DS) after two cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine in 84 pediatric patients with cHL. DS 1-3 denoted rapid early response (RER) while DS 4-5 denoted slow early response (SER). Missing values were imputed using the k-nearest neighbor algorithm. Baseline and follow-up blood test values were combined into a single difference variable. Data were split into training and testing sets for analysis using Python scikit-learn 1.2.2 with logistic regression, random forests, naïve Bayes, and support vector machine classifiers., Results: Random forest analysis achieved the best validated test accuracy of 73% when predicting RER or SER from blood samples. When applied to the full data set, the optimal model had a predictive accuracy of 80% and a receiver operating characteristic AUC of 89%. The most predictive variable was the differences in ALC, contributing 21% to the model. Differences in ferritin, LDH, and TWC contributed 15%-16%. Differences in ESR, hemoglobin, and albumin contributed 11%-12%., Conclusion: Changes in low-cost, widely available blood tests may predict chemosensitivity for pediatric cHL without access to PET-CT, identifying patients who may not require radiotherapy. Changes in these nonspecific blood tests should be assessed in combination with clinical findings and available imaging to avoid undertreatment.

Vast amounts of pathogen genomic, demographic and spatial data are transforming our understanding of SARS-CoV-2 emergence and spread. We examined the drivers of molecular evolution and spread of 291,791 SARS-CoV-2 genomes from Denmark in 2021. With a sequencing rate consistently exceeding 60%, and up to 80% of PCR-positive samples between March and November, the viral genome set is broadly whole-epidemic representative. We identify a consistent rise in viral diversity over time, with notable spikes upon the importation of novel variants (e.g., Delta and Omicron). By linking genomic data with rich individual-level demographic data from national registers, we find that individuals aged  < 15 and  > 75 years had a lower contribution to molecular change (i.e., branch lengths) compared to other age groups, but similar molecular evolutionary rates, suggesting a lower likelihood of introducing novel variants. Similarly, we find greater molecular change among vaccinated individuals, suggestive of immune evasion. We also observe evidence of transmission in rural areas to follow predictable diffusion processes. Conversely, urban areas are expectedly more complex due to their high mobility, emphasising the role of population structure in driving virus spread. Our analyses highlight the added value of integrating genomic data with detailed demographic and spatial information, particularly in the absence of structured infection surveys., (© 2024. The Author(s).)

During the SARS-CoV-2 pandemic, many countries directed substantial resources toward genomic surveillance to detect and track viral variants. There is a debate over how much sequencing effort is necessary in national surveillance programs for SARS-CoV-2 and future pandemic threats. We aimed to investigate the effect of reduced sequencing on surveillance outcomes in a large genomic data set from Switzerland, comprising more than 143k sequences. We employed a uniform downsampling strategy using 100 iterations each to investigate the effects of fewer available sequences on the surveillance outcomes: (i) first detection of variants of concern (VOCs), (ii) speed of introduction of VOCs, (iii) diversity of lineages, (iv) first cluster detection of VOCs, (v) density of active clusters, and (vi) geographic spread of clusters. The impact of downsampling on VOC detection is disparate for the three VOC lineages, but many outcomes including introduction and cluster detection could be recapitulated even with only 35% of the original sequencing effort. The effect on the observed speed of introduction and first detection of clusters was more sensitive to reduced sequencing effort for some VOCs, in particular Omicron and Delta, respectively. A genomic surveillance program needs a balance between societal benefits and costs. While the overall national dynamics of the pandemic could be recapitulated by a reduced sequencing effort, the effect is strongly lineage-dependent-something that is unknown at the time of sequencing-and comes at the cost of accuracy, in particular for tracking the emergence of potential VOCs.IMPORTANCESwitzerland had one of the most comprehensive genomic surveillance systems during the COVID-19 pandemic. Such programs need to strike a balance between societal benefits and program costs. Our study aims to answer the question: How would surveillance outcomes have changed had we sequenced less? We find that some outcomes but also certain viral lineages are more affected than others by sequencing less. However, sequencing to around a third of the original effort still captured many important outcomes for the variants of concern such as their first detection but affected more strongly other measures like the detection of first transmission clusters for some lineages. Our work highlights the importance of setting predefined targets for a national genomic surveillance program based on which sequencing effort should be determined. Additionally, the use of a centralized surveillance platform facilitates aggregating data on a national level for rapid public health responses as well as post-analyses., Competing Interests: The authors declare no conflict of interest.

The origins of treponemal diseases have long remained unknown, especially considering the sudden onset of the first syphilis epidemic in the late 15th century in Europe and its hypothesized arrival from the Americas with Columbus' expeditions 1,2 . Recently, ancient DNA evidence has revealed various treponemal infections circulating in early modern Europe and colonial-era Mexico 3-6 . However, there has been to our knowledge no genomic evidence of treponematosis recovered from either the Americas or the Old World that can be reliably dated to the time before the first trans-Atlantic contacts. Here, we present treponemal genomes from nearly 2,000-year-old human remains from Brazil. We reconstruct four ancient genomes of a prehistoric treponemal pathogen, most closely related to the bejel-causing agent Treponema pallidum endemicum. Contradicting the modern day geographical niche of bejel in the arid regions of the world, the results call into question the previous palaeopathological characterization of treponeme subspecies and showcase their adaptive potential. A high-coverage genome is used to improve molecular clock date estimations, placing the divergence of modern T. pallidum subspecies firmly in pre-Columbian times. Overall, our study demonstrates the opportunities within archaeogenetics to uncover key events in pathogen evolution and emergence, paving the way to new hypotheses on the origin and spread of treponematoses., (© 2024. The Author(s).)

The large amount and diversity of viral genomic datasets generated by next-generation sequencing technologies poses a set of challenges for computational data analysis workflows, including rigorous quality control, scaling to large sample sizes, and tailored steps for specific applications. Here, we present V-pipe 3.0, a computational pipeline designed for analyzing next-generation sequencing data of short viral genomes. It is developed to enable reproducible, scalable, adaptable, and transparent inference of genetic diversity of viral samples. By presenting 2 large-scale data analysis projects, we demonstrate the effectiveness of V-pipe 3.0 in supporting sustainable viral genomic data science., (© The Author(s) 2024. Published by Oxford University Press on behalf of GigaScience.)

Background: Historic South African 5-year overall survival (OS) rates for Hodgkin lymphoma (HL) from 2000 to 2010 were 46% and 84% for human immunodeficiency virus (HIV)-positive and HIV-negative children, respectively. We investigated whether a harmonised treatment protocol using risk stratification and response-adapted therapy could increase the OS of childhood and adolescent HL., Methods: Seventeen units prospectively enrolled patients less than 18 years, newly diagnosed with classical HL onto a risk-stratified, response-adapted treatment protocol from July 2016 to December 2022. Low- and intermediate-risk patients received four and six courses of adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD), respectively. High-risk patients received two courses of ABVD, followed by four courses of cyclophosphamide, vincristine, prednisone, and dacarbazine (COPDac). Those with a slow early response and bulky disease received consolidation radiotherapy. HIV-positive patients could receive granulocyte colony-stimulating factor and less intensive therapy if stratified as high risk, at the treating clinician's discretion. Kaplan-Meier survival analysis was performed to determine 2-year OS and Cox regression to elucidate prognostic factors., Results: The cohort comprised 132 patients (19 HIV-positive, 113 HIV-negative), median age of 9.7 years, with a median follow-up of 2.2 years. Risk grouping comprised nine (7%) low risk, 36 (27%) intermediate risk and 87 (66%) high risk, with 71 (54%) rapid early responders and 45 (34%) slow early responders, and 16 (12%) undocumented. Two-year OS was 100% for low-risk, 93% for intermediate-risk, and 91% for high-risk patients. OS for HIV-negative (93%) and HIV-positive (89%) patients were similar (p = .53). Absolute lymphocyte count greater than 0.6 × 10 9 predicted survival (94% vs. 83%, p = .02)., Conclusion: In the first South African harmonised HL treatment protocol, risk stratification correlated with prognosis. Two-year OS of HIV-positive and HIV-negative patients improved since 2010, partially ascribed to standardised treatment and increased supportive care. This improved survival strengthens the harmonisation movement and gives hope that South Africa will achieve the WHO Global Initiative for Childhood Cancer goals., (© 2023 The Authors. Pediatric Blood & Cancer published by Wiley Periodicals LLC.)

The pronounced growth in livestock populations since the 1950s has altered the epidemiological and evolutionary trajectory of their associated pathogens. For example, Marek's disease virus (MDV), which causes lymphoid tumors in chickens, has experienced a marked increase in virulence over the past century. Today, MDV infections kill >90% of unvaccinated birds, and controlling it costs more than US$1 billion annually. By sequencing MDV genomes derived from archeological chickens, we demonstrate that it has been circulating for at least 1000 years. We functionally tested the Meq oncogene, one of 49 viral genes positively selected in modern strains, demonstrating that ancient MDV was likely incapable of driving tumor formation. Our results demonstrate the power of ancient DNA approaches to trace the molecular basis of virulence in economically relevant pathogens.

Bovine tuberculosis (bTB) is a costly, epidemiologically complex, multi-host, endemic disease. Lack of understanding of transmission dynamics may undermine eradication efforts. Pathogen whole-genome sequencing improves epidemiological inferences, providing a means to determine the relative importance of inter- and intra-species host transmission for disease persistence. We sequenced an exceptional data set of 619 Mycobacterium bovis isolates from badgers and cattle in a 100 km 2 bTB 'hotspot' in Northern Ireland. Historical molecular subtyping data permitted the targeting of an endemic pathogen lineage, whose long-term persistence provided a unique opportunity to study disease transmission dynamics in unparalleled detail. Additionally, to assess whether badger population genetic structure was associated with the spatial distribution of pathogen genetic diversity, we microsatellite genotyped hair samples from 769 badgers trapped in this area. Birth death models and TransPhylo analyses indicated that cattle were likely driving the local epidemic, with transmission from cattle to badgers being more common than badger to cattle. Furthermore, the presence of significant badger population genetic structure in the landscape was not associated with the spatial distribution of M. bovis genetic diversity, suggesting that badger-to-badger transmission is not playing a major role in transmission dynamics. Our data were consistent with badgers playing a smaller role in transmission of M. bovis infection in this study site, compared to cattle. We hypothesize, however, that this minor role may still be important for persistence. Comparison to other areas suggests that M. bovis transmission dynamics are likely to be context dependent, with the role of wildlife being difficult to generalize.

Introduction: Collaborative studies have contributed to improved survival of pediatric Hodgkin lymphoma in well-resourced settings, but few are documented in resource-constrained countries. The South Africa Children's Cancer Study Group initiated harmonization of management protocols in 2015. This article analyzes barriers and enablers of the process. Methods: Clinician-researchers at 11 state-funded pediatric oncology units completed preparatory questionnaires in June 2018. Parameters included infrastructure, access to therapeutic modalities and clinician numbers. A reassessment of 13 sites (two new pediatric oncology unit) in February 2021 ascertained changes in resources and identified challenges to full participation. Questions investigated the presence and quality of diagnostic radiology, availability of surgeons, cytology/pathology options and hematology laboratory facilities. Results: The response rate was 11/11 to survey 1 and 13/13 to survey 2. The anticipated pre-study barriers to participation of pediatric oncology units included time constraints and understaffing. PET-CT was unavailable to two centers. The majority of pediatric oncology units met the minimum criteria to participate. The interim survey confirmed chemotherapy and radiotherapy availability nearly 100% of the time. One site reported improved access to radiotherapy while another reported improved access to PET-CT. Barriers to participation included excessive times to obtain regulatory approvals, time constraints and lack of dedicated research staff. Enablers include the simple management algorithm and communication tools. Conclusion: This study demonstrates that multicenter collaboration and harmonization of management protocols are achievable in a middle-income setting. Minimal funding is required but full participation to run high-quality studies requires more financial investment. Focused funding and increased prioritization of research may address systemic barriers to full participation.

Genome sequences from evolving infectious pathogens allow quantification of case introductions and local transmission dynamics. We sequenced 11,357 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomes from Switzerland in 2020-the sixth largest effort globally. Using a representative subset of these data, we estimated viral introductions to Switzerland and their persistence over the course of 2020. We contrasted these estimates with simple null models representing the absence of certain public health measures. We show that Switzerland's border closures decoupled case introductions from incidence in neighboring countries. Under a simple model, we estimate an 86 to 98% reduction in introductions during Switzerland's strictest border closures. Furthermore, the Swiss 2020 partial lockdown roughly halved the time for sampled introductions to die out. Last, we quantified local transmission dynamics once introductions into Switzerland occurred using a phylodynamic model. We found that transmission slowed 35 to 63% upon outbreak detection in summer 2020 but not in fall. This finding may indicate successful contact tracing over summer before overburdening in fall. The study highlights the added value of genome sequencing data for understanding transmission dynamics.

The SARS-CoV-2 Delta (Pango lineage B.1.617.2) variant of concern spread globally, causing resurgences of COVID-19 worldwide 1,2 . The emergence of the Delta variant in the UK occurred on the background of a heterogeneous landscape of immunity and relaxation of non-pharmaceutical interventions. Here we analyse 52,992 SARS-CoV-2 genomes from England together with 93,649 genomes from the rest of the world to reconstruct the emergence of Delta and quantify its introduction to and regional dissemination across England in the context of changing travel and social restrictions. Using analysis of human movement, contact tracing and virus genomic data, we find that the geographic focus of the expansion of Delta shifted from India to a more global pattern in early May 2021. In England, Delta lineages were introduced more than 1,000 times and spread nationally as non-pharmaceutical interventions were relaxed. We find that hotel quarantine for travellers reduced onward transmission from importations; however, the transmission chains that later dominated the Delta wave in England were seeded before travel restrictions were introduced. Increasing inter-regional travel within England drove the nationwide dissemination of Delta, with some cities receiving more than 2,000 observable lineage introductions from elsewhere. Subsequently, increased levels of local population mixing-and not the number of importations-were associated with the faster relative spread of Delta. The invasion dynamics of Delta depended on spatial heterogeneity in contact patterns, and our findings will inform optimal spatial interventions to reduce the transmission of current and future variants of concern, such as Omicron (Pango lineage B.1.1.529)., (© 2022. The Author(s).)

The first SARS-CoV-2 variant of concern (VOC) to be designated was lineage B.1.1.7, later labelled by the World Health Organization as Alpha. Originating in early autumn but discovered in December 2020, it spread rapidly and caused large waves of infections worldwide. The Alpha variant is notable for being defined by a long ancestral phylogenetic branch with an increased evolutionary rate, along which only two sequences have been sampled. Alpha genomes comprise a well-supported monophyletic clade within which the evolutionary rate is typical of SARS-CoV-2. The Alpha epidemic continued to grow despite the continued restrictions on social mixing across the UK and the imposition of new restrictions, in particular, the English national lockdown in November 2020. While these interventions succeeded in reducing the absolute number of cases, the impact of these non-pharmaceutical interventions was predominantly to drive the decline of the SARS-CoV-2 lineages that preceded Alpha. We investigate the only two sampled sequences that fall on the branch ancestral to Alpha. We find that one is likely to be a true intermediate sequence, providing information about the order of mutational events that led to Alpha. We explore alternate hypotheses that can explain how Alpha acquired a large number of mutations yet remained largely unobserved in a region of high genomic surveillance: an under-sampled geographical location, a non-human animal population, or a chronically infected individual. We conclude that the latter provides the best explanation of the observed behaviour and dynamics of the variant, although the individual need not be immunocompromised, as persistently infected immunocompetent hosts also display a higher within-host rate of evolution. Finally, we compare the ancestral branches and mutation profiles of other VOCs and find that Delta appears to be an outlier both in terms of the genomic locations of its defining mutations and a lack of the rapid evolutionary rate on its ancestral branch. As new variants, such as Omicron, continue to evolve (potentially through similar mechanisms), it remains important to investigate the origins of other variants to identify ways to potentially disrupt their evolution and emergence., (© The Author(s) 2022. Published by Oxford University Press.)

Next generation vaccines have the capability to contribute to and revolutionise the veterinary vaccine industry. African horse sickness (AHS) is caused by an arbovirus infection and is characterised by respiratory distress and/or cardiovascular failure and is lethal to horses. Mandatory annual vaccination in endemic areas curtails disease occurrence and severity. However, development of a next generation AHSV vaccine, which is both safe and efficacious, has been an objective globally for years. In this study, both AHSV serotype 5 chimaeric virus-like particles (VLPs) and soluble viral protein 2 (VP2) were successfully produced in Nicotiana benthamiana ΔXT/FT plants, partially purified and validated by gel electrophoresis, transmission electron microscopy and liquid chromatography-mass spectrometry (LC-MS/MS) based peptide sequencing before vaccine formulation. IFNAR -/- mice vaccinated with the adjuvanted VLPs or VP2 antigens in a 10 µg prime-boost regime resulted in high titres of antibodies confirmed by both serum neutralising tests (SNTs) and enzyme-linked immunosorbent assays (ELISA). Although previous studies reported high titres of antibodies in horses when vaccinated with plant-produced AHS homogenous VLPs, this is the first study demonstrating the protective efficacy of both AHSV serotype 5 chimaeric VLPs and soluble AHSV-5 VP2 as vaccine candidates. Complementary to this, coating ELISA plates with the soluble VP2 has the potential to underpin serotype-specific serological assays., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: ‘Plant-produced chimaeric Orbivirus VLPs underpinning the development of the VLP vaccine was patented (PCT/IB2017/052236, PCT publication number WO2017/182958, US 11,053,509 B2, 2021 granted) with co-inventors from CSIR (Dr Rutkowska, Dr Stark and Dr O’Kennedy), OBP (Dr Mokoena) and inventors from the University of Cape Town whilst the design of the plant-produced soluble VP2 is proprietary to CSIR. A provisional patent protecting the design of the plant-produced AHS VP2 fusion protein and uses thereof, filed (Inventors: MM O’Kennedy and Y Lemmer)., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The effects of the GnRH vaccine Improvac ® on testicular and epididymal morphometrics, histology and spermatogenesis were measured in 19 young (15-20 months) colts randomly assigned to one control (saline, castration at 57 days, n = 6) or either of two GnRH vaccine-treatment groups, T-57 (castration at 57 days, n = 7) or T-100 (castration at 100 days, n = 6), respectively. All were immunized on Day 0 with a single booster on Day 28. Excised testes and epididymides were weighed and processed for histology to measure tubule, epithelial and muscle dimensions, the ratio of interstitial tissue to seminiferous tubules and determine the stage of spermatogenesis. Testis volume, unchanged within controls, decreased in T-57 and T-100 groups by 50% and 70%, respectively. Treated colts' testes were significantly lighter than controls (64% relative difference); however, epididymal mass showed no significant differences between groups. Proportionally less seminiferous tubule relative to interstitial tissue was observed in both treatment groups (5%) versus controls (22%) with a mean tubule size 28% smaller than controls. Controls exhibited a high proportion of seminiferous tubules with advanced stages of spermatogenesis, whereas treated colts showed a high proportion of tubules in the early stages of spermatogenesis. In conclusion, immunization against GnRH in prepubertal colts was effective at reducing the development of their intra-scrotal reproductive organs and preventing normal spermatogenesis. GnRH vaccination of young colts effectively and consistently reduced testis mass, tubule size and relative proportion of seminiferous tubule tissue while retarding spermatogenesis. The epididymis showed changes with a smaller tubule diameter, lower epithelial height and thicker muscle layer recorded in treated compared to control colts., (© 2022 The Authors. Reproduction in Domestic Animals published by Wiley-VCH GmbH.)

Limited genomic sampling in many high-incidence countries has impeded studies of severe respiratory syndrome coronavirus 2 (SARS-CoV-2) genomic epidemiology. Consequently, critical questions remain about the generation and global distribution of virus genetic diversity. We investigated SARS-CoV-2 transmission dynamics in Gujarat, India, during the state's first epidemic wave to shed light on spread of the virus in one of the regions hardest hit by the pandemic. By integrating case data and 434 whole-genome sequences sampled across 20 districts, we reconstructed the epidemic dynamics and spatial spread of SARS-CoV-2 in Gujarat. Our findings indicate global and regional connectivity and population density were major drivers of the Gujarat outbreak. We detected >100 virus lineage introductions, most of which appear to be associated with international travel. Within Gujarat, virus dissemination occurred predominantly from densely populated regions to geographically proximate locations that had low population density, suggesting that urban centers contributed disproportionately to virus spread.

The SARS-CoV-2 epidemic in southern Africa has been characterized by three distinct waves. The first was associated with a mix of SARS-CoV-2 lineages, while the second and third waves were driven by the Beta (B.1.351) and Delta (B.1.617.2) variants, respectively 1-3 . In November 2021, genomic surveillance teams in South Africa and Botswana detected a new SARS-CoV-2 variant associated with a rapid resurgence of infections in Gauteng province, South Africa. Within three days of the first genome being uploaded, it was designated a variant of concern (Omicron, B.1.1.529) by the World Health Organization and, within three weeks, had been identified in 87 countries. The Omicron variant is exceptional for carrying over 30 mutations in the spike glycoprotein, which are predicted to influence antibody neutralization and spike function 4 . Here we describe the genomic profile and early transmission dynamics of Omicron, highlighting the rapid spread in regions with high levels of population immunity., (© 2022. The Author(s).)

Inferring the dynamics of pathogen transmission during an outbreak is an important problem in infectious disease epidemiology. In mathematical epidemiology, estimates are often informed by time series of confirmed cases, while in phylodynamics genetic sequences of the pathogen, sampled through time, are the primary data source. Each type of data provides different, and potentially complementary, insight. Recent studies have recognised that combining data sources can improve estimates of the transmission rate and the number of infected individuals. However, inference methods are typically highly specialised and field-specific and are either computationally prohibitive or require intensive simulation, limiting their real-time utility. We present a novel birth-death phylogenetic model and derive a tractable analytic approximation of its likelihood, the computational complexity of which is linear in the size of the dataset. This approach combines epidemiological and phylodynamic data to produce estimates of key parameters of transmission dynamics and the unobserved prevalence. Using simulated data, we show (a) that the approximation agrees well with existing methods, (b) validate the claim of linear complexity and (c) explore robustness to model misspecification. This approximation facilitates inference on large datasets, which is increasingly important as large genomic sequence datasets become commonplace., Competing Interests: The authors have declared that no competing interests exist.

Understanding SARS-CoV-2 transmission in higher education settings is important to limit spread between students, and into at-risk populations. In this study, we sequenced 482 SARS-CoV-2 isolates from the University of Cambridge from 5 October to 6 December 2020. We perform a detailed phylogenetic comparison with 972 isolates from the surrounding community, complemented with epidemiological and contact tracing data, to determine transmission dynamics. We observe limited viral introductions into the university; the majority of student cases were linked to a single genetic cluster, likely following social gatherings at a venue outside the university. We identify considerable onward transmission associated with student accommodation and courses; this was effectively contained using local infection control measures and following a national lockdown. Transmission clusters were largely segregated within the university or the community. Our study highlights key determinants of SARS-CoV-2 transmission and effective interventions in a higher education setting that will inform public health policy during pandemics., (© 2022. The Author(s).)

High-throughput sequencing enables rapid genome sequencing during infectious disease outbreaks and provides an opportunity to quantify the evolutionary dynamics of pathogens in near real-time. One difficulty of undertaking evolutionary analyses over short timescales is the dependency of the inferred evolutionary parameters on the timespan of observation. Crucially, there are an increasing number of molecular clock analyses using external evolutionary rate priors to infer evolutionary parameters. However, it is not clear which rate prior is appropriate for a given time window of observation due to the time-dependent nature of evolutionary rate estimates. Here, we characterize the molecular evolutionary dynamics of SARS-CoV-2 and 2009 pandemic H1N1 (pH1N1) influenza during the first 12 months of their respective pandemics. We use Bayesian phylogenetic methods to estimate the dates of emergence, evolutionary rates, and growth rates of SARS-CoV-2 and pH1N1 over time and investigate how varying sampling window and data set sizes affect the accuracy of parameter estimation. We further use a generalized McDonald-Kreitman test to estimate the number of segregating nonneutral sites over time. We find that the inferred evolutionary parameters for both pandemics are time dependent, and that the inferred rates of SARS-CoV-2 and pH1N1 decline by ∼50% and ∼100%, respectively, over the course of 1 year. After at least 4 months since the start of sequence sampling, inferred growth rates and emergence dates remain relatively stable and can be inferred reliably using a logistic growth coalescent model. We show that the time dependency of the mean substitution rate is due to elevated substitution rates at terminal branches which are 2-4 times higher than those of internal branches for both viruses. The elevated rate at terminal branches is strongly correlated with an increasing number of segregating nonneutral sites, demonstrating the role of purifying selection in generating the time dependency of evolutionary parameters during pandemics., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.)

Competing Interests: Competing interests: None declared.