Streptococcus pneumoniae serotype 3 population structure in the era of conjugate vaccines, 2001-2018.

Background. Despite use of highly effective conjugate vaccines, invasive pneumococcal disease (IPD) remains a leading cause of morbidity and mortality and disproportionately affects Indigenous populations. Although included in the 13-valent pneumococcal conjugate vaccine (PCV13), which was introduced in 2010, serotype 3 continues to cause disease among Indigenous communities in the Southwest USA. In the Navajo Nation, serotype 3 IPD incidence increased among adults (3.8/100 000 in 2001-2009 and 6.2/100 000 in 2011-2019); in children the disease persisted although the rates dropped from 5.8/100 000 to 2.3/100 000.Methods. We analysed the genomic epidemiology of serotype 3 isolates collected from 129 adults and 63 children with pneumococcal carriage (n=61) or IPD (n=131) from 2001 to 2018 of the Navajo Nation. Using whole-genome sequencing data, we determined clade membership and assessed changes in serotype 3 population structure over time.Results. The serotype 3 population structure was characterized by three dominant subpopulations: clade II (n=90, 46.9 %) and clade Iα (n=59, 30.7 %), which fall into Clonal Complex (CC) 180, and a non-CC180 clade (n=43, 22.4 %). The proportion of clade II-associated IPD cases increased significantly from 2001 to 2010 to 2011-2018 among adults (23.1-71.8 %; P<0.001) but not in children (27.3-33.3 %; P=0.84). Over the same period, the proportion of clade II-associated carriage increased; this was statistically significant among children (23.3-52.6 %; P=0.04) but not adults (0-50.0 %, P=0.08).Conclusions. In this setting with persistent serotype 3 IPD and carriage, clade II has increased since 2010. Genomic changes may be contributing to the observed trends in serotype 3 carriage and disease over time.

Updated Insights into the Phylogenetics, Phylodynamics, and Genetic Diversity of Nipah Virus (NiV).

Nipah virus (NiV), a biosafety level 4 agent, was first identified in human clinical cases during an outbreak in 1998 in Malaysia and Singapore. While flying foxes are the primary host and viral vector, the infection is associated with a severe clinical presentation in humans, resulting in a high mortality rate. Therefore, NiV is considered a virus with an elevated epidemic potential which is further underscored by its recent emergence (September 2023) as an outbreak in India. Given the situation, it is paramount to understand the molecular dynamics of the virus to shed more light on its evolution and prevent potential future outbreaks. In this study, we conducted Bayesian phylogenetic analysis on all available NiV complete genomes, including partial N-gene NiV sequences (≥1000 bp) in public databases since the first human case, registered in 1998. We observed the distribution of genomes into three main clades corresponding to the genotypes Malaysia, Bangladesh and India, with the Malaysian clade being the oldest in evolutionary terms. The Bayesian skyline plot showed a recent increase in the viral population size since 2019. Protein analysis showed the presence of specific protein families (Hendra_C) in bats that might keep the infection in an asymptomatic state in bats, which also serve as viral vectors. Our results further indicate a shortage of complete NiV genomes, which would be instrumental in gaining a better understanding of NiV's molecular evolution and preventing future outbreaks. Our investigation also underscores the critical need to strengthen genomic surveillance based on complete NiV genomes that will aid thorough genetic characterization of the circulating NiV strains and the phylogenetic relationships between the henipaviruses. This approach will better prepare us to tackle the challenges posed by the NiV virus and other emerging viruses.

Environmental surface monitoring as a noninvasive method for SARS-CoV-2 surveillance in community settings: Lessons from a university campus study.

Environmental testing of high-touch objects is a potential noninvasive approach for monitoring population-level trends of SARS-CoV-2 and other respiratory viruses within a defined setting. We aimed to determine the association between SARS-CoV-2 contamination on high-touch environmental surfaces, community level case incidence, and university student health data. Environmental swabs were collected from January 2022 to November 2022 from high-touch objects and surfaces from five locations on a large university campus in Florida, USA. RT-qPCR was used to detect and quantify viral RNA, and a subset of positive samples was analyzed by viral genome sequencing to identify circulating lineages. During the study period, we detected SARS-CoV-2 viral RNA on 90.7 % of 162 tested samples. Levels of environmental viral RNA correlated with trends in community-level activity and case reports from the student health center. A significant positive correlation was observed between the estimated viral gene copy number in environmental samples and the weekly confirmed cases at the university. Viral sequencing data from environmental samples identified lineages concurrently circulating in the local community and state based on genomic surveillance data. Further, we detected emerging variants in environmental samples prior to their identification by clinical genomic surveillance. Our results demonstrate the utility of viral monitoring on high-touch environmental surfaces for SARS-CoV-2 surveillance at a community level. In communities with delayed or limited testing facilities, immediate environmental surface testing may considerably inform epidemic dynamics.

Draft genome sequence of a highly proteolytic Staphylococcus aureus USA300 isolate from human urine.

The secreted proteases of Staphylococcus aureus have been shown to be critical during infection. Here, we present the draft genome sequence of S. aureus TGH337, a hyper-proteolytic USA300 strain isolated from human urine.

Genetic and structural analyses reveal the low potential of the SARS-CoV-2 EG.5 variant.

The severe acute respiratory syndrome coronavirus 2 EG.5 lineage is the latest variant under monitoring, and it is generating significant concern due to its recent upward trend in prevalence. Our aim was to gain insights into this emerging lineage and offer insights into its actual level of threat. Both genetic and structural data indicate that this novel variant presently lacks substantial evidence of having a high capacity for widespread transmission. Their viral population sizes expanded following a very mild curve and peaked several months after the earliest detected sample. Currently, neither the viral population size of EG.5 nor that of its first descendant is increasing. The genetic variability appear to be flattened, as evidenced by its relatively modest evolutionary rate (9.05 × 10-4 subs/site/year). As has been observed with numerous prior variants, attributes that might theoretically provide advantages seem to stem from genetic drift, enabling the virus to continually adjust to its host, albeit without a clear association with enhanced dangerousness. These findings further underscore the necessity for ongoing genome-based monitoring, ensuring preparedness and a well-documented understanding of the unfolding situation.

Integrative Genome-Based Survey of the SARS-CoV-2 Omicron XBB.1.16 Variant.

The XBB.1.16 SARS-CoV-2 variant, also known as Arcturus, is a recent descendant lineage of the recombinant XBB (nicknamed Gryphon). Compared to its direct progenitor, XBB.1, XBB.1.16 carries additional spike mutations in key antigenic sites, potentially conferring an ability to evade the immune response compared to other circulating lineages. In this context, we conducted a comprehensive genome-based survey to gain a detailed understanding of the evolution and potential dangers of the XBB.1.16 variant, which became dominant in late June. Genetic data indicates that the XBB.1.16 variant exhibits an evolutionary background with limited diversification, unlike dangerous lineages known for rapid changes. The evolutionary rate of XBB.1.16, which amounts to 3.95 × 10-4 subs/site/year, is slightly slower than that of its direct progenitors, XBB and XBB.1.5, which have been circulating for several months. A Bayesian Skyline Plot reconstruction suggests that the peak of genetic variability was reached in early May 2023, and currently, it is in a plateau phase with a viral population size similar to the levels observed in early March. Structural analyses indicate that, overall, the XBB.1.16 variant does not possess structural characteristics markedly different from those of the parent lineages, and the theoretical affinity for ACE2 does not seem to change among the compared variants. In conclusion, the genetic and structural analyses of SARS-CoV-2 XBB.1.16 do not provide evidence of its exceptional danger or high expansion capability. Detected differences with previous lineages are probably due to genetic drift, which allows the virus constant adaptability to the host, but they are not necessarily connected to a greater danger. Nevertheless, continuous genome-based monitoring is essential for a better understanding of its descendants and other lineages.

Joining Forces against Antibiotic Resistance: The One Health Solution.

Antibiotic resistance is a significant global health concern that affects both human and animal populations. The One Health approach acknowledges the interconnectedness of human health, animal health, and the environment. It emphasizes the importance of collaboration and coordination across these sectors to tackle complex health challenges such as antibiotic resistance. In the context of One Health, antibiotic resistance refers to the ability of bacteria to withstand the efficacy of antibiotics, rendering them less effective or completely ineffective in treating infections. The emergence and spread of antibiotic-resistant bacteria pose a threat to human and animal health, as well as to the effectiveness of medical treatments and veterinary interventions. In particular, One Health recognizes that antibiotic use in human medicine, animal agriculture, and the environment are interconnected factors contributing to the development and spread of antibiotic resistance. For example, the misuse and overuse of antibiotics in human healthcare, including inappropriate prescribing and patient non-compliance, can contribute to the selection and spread of resistant bacteria. Similarly, the use of antibiotics in livestock production for growth promotion and disease prevention can contribute to the development of antibiotic resistance in animals and subsequent transmission to humans through the food chain. Addressing antibiotic resistance requires a collaborative One Health approach that involves multiple participants, including healthcare professionals, veterinarians, researchers, and policymakers.

Monitoring Monkeypox: Safeguarding Global Health through Rapid Response and Global Surveillance.

Monkeypox, a viral zoonotic disease, has emerged as a significant global threat in recent years. This review focuses on the importance of global monitoring and rapid response to monkeypox outbreaks. The unpredictable nature of monkeypox transmissions, its potential for human-to-human spread, and its high morbidity rate underscore the necessity for proactive surveillance systems. By analyzing the existing literature, including recent outbreaks, this review highlights the critical role of global surveillance in detecting, containing, and preventing the further spread of monkeypox. It also emphasizes the need for enhanced international collaboration, data sharing, and real-time information exchange to effectively respond to monkeypox outbreaks as a global health concern. Furthermore, this review discusses the challenges and opportunities of implementing robust surveillance strategies, including the use of advanced diagnostic tools and technologies. Ultimately, these findings underscore the urgency of establishing a comprehensive global monitoring framework for monkeypox, enabling early detection, prompt response, and effective control measures to protect public health worldwide.

Genomic Epidemiology and Lineage Dynamics of SARS-CoV-2 in Bulgaria: Insights from a Three-Year Pandemic Analysis.

The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has brought about significant challenges worldwide. In this study, we present a comprehensive analysis of the genomic epidemiology and lineage dynamics of SARS-CoV-2 in Bulgaria over a three-year period. Through extensive genomic sequencing and data analysis, we investigated the evolution of the virus, the emergence of variants of concern (VOCs), and their impact on the country's pandemic trajectory. We also assessed the relationship between viral diversity and COVID-19 morbidity and mortality in Bulgaria. Our findings shed light on the temporal and spatial distribution of SARS-CoV-2 lineages and provide crucial insights into the dynamics of the pandemic in the country. The interplay between international travel and viral transmission plays a significant role in the emergence and dissemination of different SARS-CoV-2 variants. The observed proportions of exportation to various continents provide insights into the potential pathways through which these lineages spread globally. Understanding the genomic epidemiology of SARS-CoV-2 in Bulgaria is essential for formulating targeted public health strategies, enhancing vaccination efforts, and effectively managing future outbreaks.

Early Detection of the Recombinant SARS-CoV-2 XAN Variant in Bulgaria: Initial Genomic Insights into Yet Another Piece of the Growing Puzzle of Recombinant Clades.

The first recombinant SARS-CoV-2 variants were identified in 2022, causing public health concerns. The importance of recombinant variants has increased especially since the WHO designated the recombinant variant XBB and its lineages as subvariants that require monitoring on 20 November 2022. In this study, we provide the first insights into the new SARS-CoV-2 variant named XAN, a recombinant composed of Omicron sub-lineages BA.2 and BA.5. To our knowledge, this is the first report on the recombinant SARS-CoV-2 XAN variant identified in Bulgaria.

Update on the Phylodynamic and Genetic Variability of Marburg Virus.

The COVID-19 pandemic has not only strained healthcare systems in Africa but has also intensified the impact of emerging and re-emerging diseases. Specifically in Equatorial Guinea, mirroring the situation in other African countries, unique zoonotic outbreaks have occurred during this challenging period. One notable resurgence is Marburg virus disease (MVD), which has further burdened the already fragile healthcare system. The re-emergence of the Marburg virus amid the COVID-19 pandemic is believed to stem from a probable zoonotic spill-over, although the precise transmission routes remain uncertain. Given the gravity of the situation, addressing the existing challenges is paramount. Though the genome sequences from the current outbreak were not available for this study, we analyzed all the available whole genome sequences of this re-emerging pathogen to advocate for a shift towards active surveillance. This is essential to ensure the successful containment of any potential Marburg virus outbreak in Equatorial Guinea and the wider African context. This study, which presents an update on the phylodynamics and the genetic variability of MARV, further confirmed the existence of at least two distinct patterns of viral spread. One pattern demonstrates a slower but continuous and recurring virus circulation, while the other exhibits a faster yet limited and episodic spread. These results highlight the critical need to strengthen genomic surveillance in the region to effectively curb the pathogen's dissemination. Moreover, the study emphasizes the importance of prompt alert management, comprehensive case investigation and analysis, contact tracing, and active case searching. These steps are vital to support the healthcare system's response to this emerging health crisis. By implementing these strategies, we can better arm ourselves against the challenges posed by the resurgence of the Marburg virus and other infectious diseases.

Epidemic history and evolution of an emerging threat of international concern, the severe acute respiratory syndrome coronavirus 2.

This comprehensive review focuses on the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its impact as the cause of the COVID-19 pandemic. Its objective is to provide a cohesive overview of the epidemic history and evolutionary aspects of the virus, with a particular emphasis on its emergence, global spread, and implications for public health. The review delves into the timelines and key milestones of SARS-CoV-2's epidemiological progression, shedding light on the challenges encountered during early containment efforts and subsequent waves of transmission. Understanding the evolutionary dynamics of the virus is crucial in monitoring its potential for adaptation and future outbreaks. Genetic characterization of SARS-CoV-2 is discussed, with a focus on the emergence of new variants and their implications for transmissibility, severity, and immune evasion. The review highlights the important role of genomic surveillance in tracking viral mutations linked to establishing public health interventions. By analyzing the origins, global spread, and genetic evolution of SARS-CoV-2, valuable insights can be gained for the development of effective control measures, improvement of pandemic preparedness, and addressing future emerging infectious diseases of international concern.

Antigen test swabs are comparable to nasopharyngeal swabs for sequencing of SARS-CoV-2.

Viral genomic surveillance has been integral in the global response to the SARS-CoV-2 pandemic. Surveillance efforts rely on the availability of representative clinical specimens from ongoing testing activities. However, testing practices have recently shifted due to the widespread availability and use of rapid antigen tests, which could lead to gaps in future monitoring efforts. As such, genomic surveillance strategies must adapt to include laboratory workflows that are robust to sample type. To that end, we compare the results of RT-qPCR and viral genome sequencing using samples from positive BinaxNOW COVID-19 Antigen Card swabs (N = 555) to those obtained from nasopharyngeal (NP) swabs used for nucleic acid amplification testing (N = 135). We show that swabs obtained from antigen cards are comparable in performance to samples from NP swabs, providing a viable alternative and allowing for the potential expansion of viral genomic surveillance to outpatient clinic as well as other settings where rapid antigen tests are often used.

A collaborative approach to improving representation in viral genomic surveillance.

The lack of routine viral genomic surveillance delayed the initial detection of SARS-CoV-2, allowing the virus to spread unfettered at the outset of the U.S. epidemic. Over subsequent months, poor surveillance enabled variants to emerge unnoticed. Against this backdrop, long-standing social and racial inequities have contributed to a greater burden of cases and deaths among minority groups. To begin to address these problems, we developed a new variant surveillance model geared toward building 'next generation' genome sequencing capacity at universities in or near rural areas and engaging the participation of their local communities. The resulting genomic surveillance network has generated more than 1,000 SARS-CoV-2 genomes to date, including the first confirmed case in northeast Louisiana of Omicron, and the first and sixth confirmed cases in Georgia of the emergent BA.2.75 and BQ.1.1 variants, respectively. In agreement with other studies, significantly higher viral gene copy numbers were observed in Delta variant samples compared to those from Omicron BA.1 variant infections, and lower copy numbers were seen in asymptomatic infections relative to symptomatic ones. Collectively, the results and outcomes from our collaborative work demonstrate that establishing genomic surveillance capacity at smaller academic institutions in rural areas and fostering relationships between academic teams and local health clinics represent a robust pathway to improve pandemic readiness.

Favipiravir Suppresses Zika Virus (ZIKV) through Activity as a Mutagen.

In a companion paper, we demonstrated that the nucleoside analogue favipiravir (FAV) suppressed Zika virus (ZIKV) replication in three human-derived cell lines-HeLa, SK-N-MC, and HUH-7. Our results revealed that FAV's effect was most pronounced in HeLa cells. In this work, we aimed to explain variation in FAV activity, investigating its mechanism of action and characterizing host cell factors relevant to tissue-specific differences in drug effect. Using viral genome sequencing, we show that FAV therapy was associated with an increase in the number of mutations and promoted the production of defective viral particles in all three cell lines. Our findings demonstrate that defective viral particles made up a larger portion of the viral population released from HeLa cells both at increasing FAV concentrations and at increasing exposure times. Taken together, our companion papers show that FAV acts via lethal mutagenesis against ZIKV and highlight the host cell's influence on the activation and antiviral activity of nucleoside analogues. Furthermore, the information gleaned from these companion papers can be applied to gain a more comprehensive understanding of the activity of nucleoside analogues and the impact of host cell factors against other viral infections for which we currently have no approved antiviral therapies.

SARS-CoV CH.1.1 Variant: Genomic and Structural Insight.

In early February 2023, the Omicron subvariant XBB.1.5, also known as "Kraken", accounted for more than 44% of new COVID-19 cases worldwide, whereas a relatively new Omicron subvariant named CH.1.1, deemed "Orthrus", accounted for less than 6% of new COVID-19 cases during the subsequent weeks. This emerging variant carries a mutation, L452R, previously observed in the highly pathogenic Delta and the highly transmissible BA.4 and BA.5 variants, necessitating a shift to active surveillance to assure adequate preparedness for likely future epidemic peaks. We provide a preliminary understanding of the global distribution of this emerging SARS-CoV-2 variant by combining genomic data with structural molecular modeling. In addition, we shield light on the number of specific point mutations in this lineage that may have functional significance, thereby increasing the risk of disease severity, vaccine resistance, and increased transmission. This variant shared about 73% of the mutations with Omicron-like strains. Our homology modeling analysis revealed that CH.1.1 may have a weakened interaction with ACE2 and that its electrostatic potential surface appears to be more positive than that of the reference ancestral virus. Finally, our phylogenetic analysis revealed that this likely-emerging variant was already cryptically circulating in European countries prior to its first detection, highlighting the importance of having access to whole genome sequences for detecting and controlling emerging viral strains.

Global SARS-CoV-2 genomic surveillance: What we have learned (so far).

The COVID-19 pandemic has brought significant challenges for genomic surveillance strategies in public health systems worldwide. During the past thirty-four months, many countries faced several epidemic waves of SARS-CoV-2 infections, driven mainly by the emergence and spread of novel variants. In that line, genomic surveillance has been a crucial toolkit to study the real-time SARS-CoV-2 evolution, for the assessment and optimization of novel diagnostic assays, and to improve the efficacy of existing vaccines. During the pandemic, the identification of emerging lineages carrying lineage-specific mutations (particularly those in the Receptor Binding domain) showed how these mutations might significantly impact viral transmissibility, protection from reinfection and vaccination. So far, an unprecedented number of SARS-CoV-2 viral genomes has been released in public databases (i.e., GISAID, and NCBI), achieving 14 million genome sequences available as of early-November 2022. In the present review, we summarise the global landscape of SARS-CoV-2 during the first thirty-four months of viral circulation and evolution. It demonstrates the urgency and importance of sustained investment in genomic surveillance strategies to timely identify the emergence of any potential viral pathogen or associated variants, which in turn is key to epidemic and pandemic preparedness.

Assessment of the Stability of Midregional Proadrenomedullin in Different Biological Matrices.

Midregional proadrenomedullin (MR-proADM) has been shown to play a key role in endothelial dysfunction, with increased levels helping to prevent early stages of organ dysfunction. Recent clinical evidence has demonstrated MR-proADM to be a helpful biomarker to identify disease severity in patients with sepsis as well as pneumonia. This biomarker is helpful at triage in emergency departments to assess risk level of patients. The aim of this study is to evaluate the stability of MR-proADM in different biological matrices. The results, obtained by Bland-Altman and scatter plot analyses, demonstrate that deviation of MR-proADM concentration in serum compared to EDTA plasma unequivocally shows that serum should not be used as a sample matrix. Instead, the excellent correlation of heparin plasma vs EDTA plasma samples shows that heparin plasma can be used without reservation in clinical routine and emergency samples.

Monitoring monkeypox: safeguarding global health through rapid response and global surveillance

Monkeypox, a viral zoonotic disease, has emerged as a significant global threat in recent years. This review focuses on the importance of global monitoring and rapid response to monkeypox outbreaks. The unpredictable nature of monkeypox transmissions, its potential for human-to-human spread, and its high morbidity rate underscore the necessity for proactive surveillance systems. By analyzing the existing literature, including recent outbreaks, this review highlights the critical role of global surveillance in detecting, containing, and preventing the further spread of monkeypox. It also emphasizes the need for enhanced international collaboration, data sharing, and real-time information exchange to effectively respond to monkeypox outbreaks as a global health concern. Furthermore, this review discusses the challenges and opportunities of implementing robust surveillance strategies, including the use of advanced diagnostic tools and technologies. Ultimately, these findings underscore the urgency of establishing a comprehensive global monitoring framework for monkeypox, enabling early detection, prompt response, and effective control measures to protect public health worldwide

Genomic epidemiology and lineage dynamics of SARS-CoV-2 in Bulgaria: insights from a three-year pandemic analysis

The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has brought about significant challenges worldwide. In this study, we present a comprehensive analysis of the genomic epidemiology and lineage dynamics of SARS-CoV-2 in Bulgaria over a three-year period. Through extensive genomic sequencing and data analysis, we investigated the evolution of the virus, the emergence of variants of concern (VOCs), and their impact on the country’s pandemic trajectory. We also assessed the relationship between viral diversity and COVID-19 morbidity and mortality in Bulgaria. Our findings shed light on the temporal and spatial distribution of SARS-CoV-2 lineages and provide crucial insights into the dynamics of the pandemic in the country. The interplay between international travel and viral transmission plays a significant role in the emergence and dissemination of different SARS-CoV-2 variants. The observed proportions of exportation to various continents provide insights into the potential pathways through which these lineages spread globally. Understanding the genomic epidemiology of SARS-CoV-2 in Bulgaria is essential for formulating targeted public health strategies, enhancing vaccination efforts, and effectively managing future outbreaks.