The global patent landscape of emerging infectious disease monkeypox.

BACKGROUND: Monkeypox is an emerging infectious disease with confirmed cases and deaths in several parts of the world. In light of this crisis, this study aims to analyze the global knowledge pattern of monkeypox-related patents and explore current trends and future technical directions in the medical development of monkeypox to inform research and policy. METHODS: A comprehensive study of 1,791 monkeypox-related patents worldwide was conducted using the Derwent patent database by descriptive statistics, social network method and linear regression analysis. RESULTS: Since the 21st century, the number of monkeypox-related patents has increased rapidly, accompanied by increases in collaboration between commercial and academic patentees. Enterprises contributed the most in patent quantity, whereas the initial milestone patent was filed by academia. The core developments of technology related to the monkeypox include biological and chemical medicine. The innovations of vaccines and virus testing lack sufficient patent support in portfolios. CONCLUSIONS: Monkeypox-related therapeutic innovation is geographically limited with strong international intellectual property right barriers though it has increased rapidly in recent years. The transparent licensing of patent knowledge is driven by the merger and acquisition model, and the venture capital, intellectual property and contract research organization model. Currently, the patent thicket phenomenon in the monkeypox field may slow the progress of efforts to combat monkeypox. Enterprises should pay more attention to the sharing of technical knowledge, make full use of drug repurposing strategies, and promote innovation of monkeypox-related technology in hotspots of antivirals (such as tecovirimat, cidofovir, brincidofovir), vaccines (JYNNEOS, ACAM2000), herbal medicine and gene therapy.

Model analysis and data validation of structured prevention and control interruptions of emerging infectious diseases.

The design of optimized non-pharmaceutical interventions (NPIs) is critical to the effective control of emergent outbreaks of infectious diseases such as SARS, A/H1N1 and COVID-19 and to ensure that numbers of hospitalized cases do not exceed the carrying capacity of medical resources. To address this issue, we formulated a classic SIR model to include a close contact tracing strategy and structured prevention and control interruptions (SPCIs). The impact of the timing of SPCIs on the maximum number of non-isolated infected individuals and on the duration of an infectious disease outside quarantined areas (i.e. implementing a dynamic zero-case policy) were analyzed numerically and theoretically. These analyses revealed that to minimize the maximum number of non-isolated infected individuals, the optimal time to initiate SPCIs is when they can control the peak value of a second rebound of the epidemic to be equal to the first peak value. More individuals may be infected at the peak of the second wave with a stronger intervention during SPCIs. The longer the duration of the intervention and the stronger the contact tracing intensity during SPCIs, the more effective they are in shortening the duration of an infectious disease outside quarantined areas. The dynamic evolution of the number of isolated and non-isolated individuals, including two peaks and long tail patterns, have been confirmed by various real data sets of multiple-wave COVID-19 epidemics in China. Our results provide important theoretical support for the adjustment of NPI strategies in relation to a given carrying capacity of medical resources.

Risk factors associated with severe COVID-19 outcomes in Jamaica: a cross-sectional study of national surveillance data / Factores de riesgo asociados a la COVID-19 grave en Jamaica: estudio transversal de datos nacionales de vigilancia / Fatores de risco associados a desfechos graves da COVID-19 na Jamaica: estudo transversal de dados de vigilância nacional

[ABSTRACT]. Objectives. To describe the characteristics and outcomes of COVID-19 cases in Jamaica and to explore the risk factors associated with severe COVID-19 from 9 March to 31 December 2020. Methods. A cross-sectional analysis of national surveillance data was conducted using confirmed COVID-19 cases in Jamaica. Definitions of a confirmed case, disease severity, and death were based on World Health Organization guidelines. Chi-square and Fisher exact tests were used to determine association with outcomes. Logistic regression models were used to determine predictors of severe COVID-19. Results. This analysis included 12 169 cases of COVID-19 (median age, 36 years; 6 744 females [ 55.4%]) of which 512 cases (4.2%) presented with severe disease, and of those, 318 patients (62.1%) died (median age at death, 71.5 years). Severe disease was associated with being male (OR 1.4; 95% CI, 1.2-1.7) and 40 years or older (OR, 6.5; 95% CI, 5.1-8.2). COVID-19 death was also associated with being male (OR, 1.4; 95% CI, 1.1-1.7), age 40 years or older (OR, 17.9; 95% CI, 11.6-27.7), and in the Western versus South East Health Region (OR 1.7; 95% CI, 1.2-2.3). Conclusions. The findings of this cross-sectional analysis indicate that confirmed cases of COVID-19 in Jamaica were more likely to be female and younger individuals, whereas COVID-19 deaths occurred more frequently in males and older individuals. There is increased risk of poor COVID-19 outcomes beginning at age 40, with males disproportionately affected. COVID-19 death also varied by geographic region. This evidence could be useful to other countries with similar settings and to policymakers charged with managing outbreaks and health.

[RESUMEN]. Objetivos. Describir las características y los resultados de los casos de COVID-19 en Jamaica y explorar los factores de riesgo asociados a la COVID-19 grave desde el 9 de marzo hasta el 31 de diciembre del 2020. Métodos. Se realizó un análisis transversal de datos nacionales de vigilancia a partir de los casos confirma- dos de COVID-19 en Jamaica. Las definiciones de caso confirmado, gravedad de la enfermedad y muerte se basaron en las directrices de la Organización Mundial de la Salud. Para determinar la asociación con los criterios de valoración se utilizó la prueba de χ2 y la prueba exacta de Fisher. Se usaron modelos de regresión logística para determinar los factores predictivos de la COVID-19 grave. Resultados. Se incluyeron en el análisis 12 169 casos de COVID-19 (mediana de edad, 36 años; 6 744 mujeres [55,4%]), de los que 512 (4,2%) fueron de enfermedad grave. De estos pacientes, 318 (62,1%) fall- ecieron (mediana de edad al morir, 71,5 años). Se observó una asociación de la enfermedad grave con el sexo masculino (OR de 1,4; IC del 95 %, 1,2-1,7) y con la edad igual o superior a 40 años (OR de 6,5; IC del 95 %, 5,1-8,2). La muerte por COVID-19 también mostró una asociación con el sexo masculino (OR de 1,4; IC del 95%, 1,1-1,7), con la edad igual o superior a 40 años (OR de 17,9; IC del 95%, 11,6-27,7) y con la Región de Atención de Salud Occidental en comparación con la Sudoriental (OR de 1,7; IC del 95%, 1,2-2,3). Conclusiones. Los resultados de este análisis transversal indican que los casos confirmados de COVID-19 en Jamaica correspondieron una mayor probabilidad a mujeres y personas más jóvenes, mientras que las muertes por COVID-19 fueron más frecuentes en varones y personas de mayor edad. Hay un mayor riesgo de evolución desfavorable de la COVID-19 a partir de los 40 años, que afecta de manera desproporcionada a los varones. Las muertes por COVID-19 también variaron según la región geográfica. Esta evidencia podría ser de utilidad para otros países con entornos similares y para los responsables de la formulación de políticas en materia de gestión de brotes y salud.

[RESUMO]. Objetivos. Descrever as características e os desfechos dos casos de COVID-19 na Jamaica e explorar os fatores de risco associados à COVID-19 grave de 9 de março a 31 de dezembro de 2020. Métodos. Análise transversal de dados de vigilância nacional usando casos confirmados de COVID-19 na Jamaica. As definições de caso confirmado, gravidade da doença e morte foram baseadas nas recomendações da Organização Mundial da Saúde. Foram usados testes de qui-quadrado e exato de Fisher para determinar a associação com os desfechos. Modelos de regressão logística foram usados para deter- minar os preditores de COVID-19 grave. Resultados. Esta análise incluiu 12.169 casos de COVID-19 (idade mediana: 36 anos; 6 744 do sexo feminino [55,4%]), dos quais 512 casos (4,2%) apresentaram doença grave; desses, 318 pacientes (62,1%) morreram (idade mediana ao morrer: 71,5 anos). A doença grave estava associada a ser do sexo masculino (razão de chances [RC]: 1,4; intervalo de confiança de 95% [IC 95%]: 1,2–1,7) e ter 40 anos ou mais de idade (RC: 6,5; IC 95%: 5,1–8,2). A morte por COVID-19 também estava associada a ser sexo masculino (RC: 1,4; IC 95%: 1,1–1,7), ter 40 anos ou mais (RC: 17,9; IC 95%: 11,6–27,7) e estar na Região Sanitária Oeste em comparação com a Região Sanitária Sudeste (RC: 1,7; IC 95%: 1,2–2,3). Conclusões. Os achados desta análise transversal indicam que a probabilidade de casos confirmados de COVID-19 na Jamaica era maior em indivíduos do sexo feminino e mais jovens, ao passo que as mortes por COVID-19 ocorreram com mais frequência em indivíduos do sexo masculino e mais velhos. Há um risco maior de resultados desfavoráveis em relação à COVID-19 a partir dos 40 anos, e indivíduos do sexo masculino são desproporcionalmente mais afetados. A morte por COVID-19 também variou de acordo com a região geográ- fica. Essas evidências podem ser úteis para outros países com cenários semelhantes e para os formuladores de políticas encarregados de manejar surtos e gerenciar a saúde.

Reemergence of Bordetella parapertussis, United States, 2019-2023.

To determine changes in Bordetella pertussis and B. parapertussis detection rates, we analyzed 1.43 million respiratory multiplex PCR test results from US facilities from 2019 through mid-2023. From mid-2022 through mid-2023, Bordetella spp. detection increased 8.5-fold; 95% of detections were B. parapertussis. While B. parapertussis rates increased, B. pertussis rates decreased.

Modeling target-density-based cull strategies to contain foot-and-mouth disease outbreaks.

Total ring depopulation is sometimes used as a management strategy for emerging infectious diseases in livestock, which raises ethical concerns regarding the potential slaughter of large numbers of healthy animals. We evaluated a farm-density-based ring culling strategy to control foot-and-mouth disease (FMD) in the United Kingdom (UK), which may allow for some farms within rings around infected premises (IPs) to escape depopulation. We simulated this reduced farm density, or "target density", strategy using a spatially-explicit, stochastic, state-transition algorithm. We modeled FMD spread in four counties in the UK that have different farm demographics, using 740,000 simulations in a full-factorial analysis of epidemic impact measures (i.e., culled animals, culled farms, and epidemic length) and cull strategy parameters (i.e., target farm density, daily farm cull capacity, and cull radius). All of the cull strategy parameters listed above were drivers of epidemic impact. Our simulated target density strategy was usually more effective at combatting FMD compared with traditional total ring depopulation when considering mean culled animals and culled farms and was especially effective when daily farm cull capacity was low. The differences in epidemic impact measures among the counties are likely driven by farm demography, especially differences in cattle and farm density. To prevent over-culling and the associated economic, organizational, ethical, and psychological impacts, the target density strategy may be worth considering in decision-making processes for future control of FMD and other diseases.

Unveiling the Hidden Regulators: The Impact of lncRNAs on Zoonoses.

Zoonoses are diseases and infections naturally transmitted between humans and vertebrate animals. They form the dominant group of diseases among emerging infectious diseases and represent critical threats to global health security. This dilemma is largely attributed to our insufficient knowledge of the pathogenesis regarding zoonotic spillover. Long non-coding RNAs (lncRNAs) are transcripts with limited coding capacity. Recent technological advancements have enabled the identification of numerous lncRNAs in humans, animals, and even pathogens. An increasing body of literature suggests that lncRNAs function as key regulators in zoonotic infection. They regulate immune-related epigenetic, transcriptional, and post-transcriptional events across a broad range of organisms. In this review, we discuss the recent research progress on the roles of lncRNAs in zoonoses. We address the classification and regulatory mechanisms of lncRNAs in the interaction between host and zoonotic pathogens. Additionally, we explore the surprising function of pathogen-derived lncRNAs in mediating the pathogenicity and life cycle of zoonotic bacteria, viruses, and parasites. Understanding how these lncRNAs influence the zoonotic pathogenesis will provide important therapeutic insights to the prevention and control of zoonoses.

Central nervous system infections in the tropics.

PURPOSE OF REVIEW: Emerging and re-emerging central nervous system (CNS) infections are a major public health concern in the tropics. The reasons for this are myriad; climate change, rainfall, deforestation, increased vector density combined with poverty, poor sanitation and hygiene. This review focuses on pathogens, which have emerged and re-emerged, with the potential for significant morbidity and mortality. RECENT FINDINGS: In recent years, multiple acute encephalitis outbreaks have been caused by Nipah virus, which carries a high case fatality. Arboviral infections, predominantly dengue, chikungunya and Zika are re-emerging increasingly especially in urban areas due to changing human habitats, vector behaviour and viral evolution. Scrub typhus, another vector borne disease caused by the bacterium Orientia tsutsugamushi , is being established as a leading cause of CNS infections in the tropics. SUMMARY: A syndromic and epidemiological approach to CNS infections in the tropics is essential to plan appropriate diagnostic tests and management. Rapid diagnostic tests facilitate early diagnosis and thus help prompt initiation and focusing of therapy to prevent adverse outcomes. Vector control, cautious urbanization and deforestation, and reducing disturbance of ecosystems can help prevent spread of vector-borne diseases. Regional diagnostic and treatment approaches and specific vaccines are required to avert morbidity and mortality.

Underdetected dispersal and extensive local transmission drove the 2022 mpox epidemic.

The World Health Organization declared mpox a public health emergency of international concern in July 2022. To investigate global mpox transmission and population-level changes associated with controlling spread, we built phylogeographic and phylodynamic models to analyze MPXV genomes from five global regions together with air traffic and epidemiological data. Our models reveal community transmission prior to detection, changes in case reporting throughout the epidemic, and a large degree of transmission heterogeneity. We find that viral introductions played a limited role in prolonging spread after initial dissemination, suggesting that travel bans would have had only a minor impact. We find that mpox transmission in North America began declining before more than 10% of high-risk individuals in the USA had vaccine-induced immunity. Our findings highlight the importance of broader routine specimen screening surveillance for emerging infectious diseases and of joint integration of genomic and epidemiological information for early outbreak control.

Vigilance in infectious disease emergencies: Expanding the concept.

In their 2010 book, Lorna Weir and Eric Mykhalovskiy conceptualised the role of vigilance in unknown and emerging infectious disease threats. Theirs is a macro-level account which draws on empirical data to describe vigilance as a set of technical and political arrangements that govern collection, analysis, interpretation and communication of data as it pertains to unknown threats. In this paper we expand their work to detail a conceptual analysis of the role of vigilance at the micro-level during periods of high infectious disease threat. Our data are daily press conferences and associated non-discursive tools in New South Wales (NSW), Australia during times of heightened COVID-19 risk. This paper is a conceptual analysis that draws on theories of vigilance and related concepts to show how a key aspect of vigilance is making previously unseen threats visible or present. Communications formulated and encouraged three types of vigilance as a set of governing relations: institutional or authority-based; individual outward-facing; and individual inward-facing. We also describe the relationship between vigilance and related concepts that are used in response to anticipated public threats. Authority based vigilance involved contact tracing and policing of movement and behaviours. In individual outward facing vigilance people were asked to be alert to, analyse, and react to risk in their immediate environment. Inward facing vigilance required people to gather and react to information about their own behaviours and within their own bodies. There was a relationship between different types of vigilance; as risk increased and authority-based vigilance was less successful in containing the spread of infection, individual vigilance had a stronger role to play. This extension of vigilance at the micro-level sees some of the same unintended consequences as Weir and Mykhalovskiy describe at the global level, particularly in how burdens are inequitably distributed and experienced.

Metagenomics for Pathogen Detection During a Mass Mortality Event in Songbirds.

Mass mortality events in wildlife can be indications of an emerging infectious disease. During the spring and summer of 2021, hundreds of dead passerines were reported across the eastern US. Birds exhibited a range of clinical signs including swollen conjunctiva, ocular discharge, ataxia, and nystagmus. As part of the diagnostic investigation, high-throughput metagenomic next-generation sequencing was performed across three molecular laboratories on samples from affected birds. Many potentially pathogenic microbes were detected, with bacteria forming the largest proportion; however, no singular agent was consistently identified, with many of the detected microbes also found in unaffected (control) birds and thus considered to be subclinical infections. Congruent results across laboratories have helped drive further investigation into alternative causes, including environmental contaminants and nutritional deficiencies. This work highlights the utility of metagenomic approaches in investigations of emerging diseases and provides a framework for future wildlife mortality events.

Six dilemmas for stakeholders inherently affecting data sharing during a zoonotic (re-)emerging infectious disease outbreak response.

BACKGROUND: Timely access to outbreak related data, particularly in the early events of a spillover, is important to support evidence based control measures in response to outbreaks of zoonotic Emerging Infectious Diseases (EID). Yet, this is impeded by several barriers that need to be understood to promote timely sharing of data. Using the MERS epidemic as a model for a zoonotic EID outbreak, this study sought to provide an in-depth understanding of data sharing practices. METHODS: Semi-structured interviews with 25 experts were conducted, along with Focus Group Discussions with 15 additional experts. A root-cause analysis was performed to examine the causal relationships between barriers. Enablers were mapped to the root-cause analysis to understand their influence on the barriers. Finally, root causes were placed in context of core dilemmas identified from the qualitative analysis. FINDINGS: Eight barriers to data sharing were identified, related to collaboration, technical preparedness, regulations, and (conflict of) interests, and placed in the context of six dilemmas inherent to the multi-stakeholder collaboration required for a zoonotic outbreak response. Fourteen identified enablers showed the willingness of stakeholders to overcome or circumvent these barriers, but also indicated the inherent trial and error nature of implementing such enablers. INTERPRETATION: Addressing the barriers requires solutions that must consider the complexity and interconnectedness of the root causes underlying them, and should consider the distinct scopes and interests of the different stakeholders. Insights provided by this study can be used to encourage data sharing practices for future outbreaks FUNDING: Wellcome Trust and UK Aid; EU-H2020 Societal Challenges (grant agreement no. 643476), Nederlandse Organisatie voor Wetenschappelijk Onderzoek (VI.Veni.201S.044).

Vaccination against emerging and reemerging infectious diseases in places of detention: a global multistage scoping review.

Background: Despite the elevated risks of infection transmission, people in prisons frequently encounter significant barriers in accessing essential healthcare services in many countries. The present scoping review aimed to evaluate the state of availability and model of delivery of vaccination services within correctional facilities across the globe. Methods: Following the methodological framework for scoping reviews and adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) extension for scoping reviews criteria, we conducted a systematic search across four peer-reviewed literature databases (Medline via PubMed, Web of Science, the Cochrane Library, Science Direct, and EBSCO), as well as 14 sources of grey literature. Two researchers meticulously examined the identified papers independently to extract pertinent data published between 2012 and 2022. The quality of the selected publications was assessed using established quality assessment tools. Results: Of the 11,281 identified papers 52 met the inclusion criteria. With the exception of one, all the included publications presented data from high-income countries, predominantly originating from the United States. Across the world, the most prevalent vaccines available in prison settings were COVID-19 and HBV vaccines, typically distributed in response to health crises such as pandemics, epidemics, and local outbreaks. Vaccine coverage and uptake rates within correctional facilities displayed noteworthy disparities among various countries and regions. Besides, individual and organizational barriers and facilitating factors of vaccination in prison settings emerged and discussed in the text. Discussion: The lack of vaccination services combined with low rates of vaccination coverage and uptake among people living and working in correctional facilities represents a cause for concern. Prisons are not isolated from the broader community, therefore, efforts to increase vaccine uptake among people who live and work in prisons will yield broader public health benefits.

Development of a reverse transcriptase digital droplet polymerase chain reaction-based approach for SARS-CoV-2 variant surveillance in wastewater.

An urgent need for effective surveillance strategies arose due to the global emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although vaccines and antivirals are available, concerns persist about the evolution of new variants with potentially increased infectivity, transmissibility, and immune evasion. Therefore, variant monitoring is crucial for public health decision-making. Wastewater-based surveillance has proven to be an effective tool to monitor SARS-CoV-2 variants within populations. Specific SARS-CoV-2 variants are detected and quantified in wastewater in this study using a reverse transcriptase digital droplet polymerase chain reaction (RT-ddPCR) approach. The 11 designed assays were first validated in silico using a substantial dataset of high-quality SARS-CoV-2 genomes to ensure comprehensive variant coverage. The assessment of the sensitivity and specificity with reference material showed the capability of the developed assays to reliably identify target mutations while minimizing false positives and false negatives. The applicability of the assays was evaluated using wastewater samples from a wastewater treatment plant in Ghent, Belgium. The quantification of the specific mutations linked to the variants of concern present in these samples was calculated using these assays based on the detection of single mutations, which confirms their use for real-world variant surveillance. In conclusion, this study provides an adaptable protocol to monitor SARS-CoV-2 variants in wastewater with high sensitivity and specificity. Its potential for broader application in other viral surveillance contexts highlights its added value for rapid response to emerging infectious diseases. PRACTITIONER POINTS: Robust RT-ddPCR methodology for specific SARS-CoV-2 variants of concern detection in wastewater. Rigorous validation that demonstrates high sensitivity and specificity. Demonstration of real-world applicability using wastewater samples. Valuable tool for rapid response to emerging infectious diseases.

"Smart markets": harnessing the potential of new technologies for endemic and emerging infectious disease surveillance in traditional food markets.

Emerging and endemic zoonotic diseases continue to threaten human and animal health, our social fabric, and the global economy. Zoonoses frequently emerge from congregate interfaces where multiple animal species and humans coexist, including farms and markets. Traditional food markets are widespread across the globe and create an interface where domestic and wild animals interact among themselves and with humans, increasing the risk of pathogen spillover. Despite decades of evidence linking markets to disease outbreaks across the world, there remains a striking lack of pathogen surveillance programs that can relay timely, cost-effective, and actionable information to decision-makers to protect human and animal health. However, the strategic incorporation of environmental surveillance systems in markets coupled with novel pathogen detection strategies can create an early warning system capable of alerting us to the risk of outbreaks before they happen. Here, we explore the concept of "smart" markets that utilize continuous surveillance systems to monitor the emergence of zoonotic pathogens with spillover potential.IMPORTANCEFast detection and rapid intervention are crucial to mitigate risks of pathogen emergence, spillover and spread-every second counts. However, comprehensive, active, longitudinal surveillance systems at high-risk interfaces that provide real-time data for action remain lacking. This paper proposes "smart market" systems harnessing cutting-edge tools and a range of sampling techniques, including wastewater and air collection, multiplex assays, and metagenomic sequencing. Coupled with robust response pathways, these systems could better enable Early Warning and bolster prevention efforts.