Precognition of Known And Unknown Biothreats: A Risk-Based Approach.

Data mining and artificial intelligence algorithms can estimate the probability of future occurrences with defined precision. Yet, the prediction of infectious disease outbreaks remains a complex and difficult task. This is demonstrated by the limited accuracy and sensitivity of current models in predicting the emergence of previously unknown pathogens such as Zika, Chikungunya, and SARS-CoV-2, and the resurgence of Mpox, along with their impacts on global health, trade, and security. Comprehensive analysis of infectious disease risk profiles, vulnerabilities, and mitigation capacities, along with their spatiotemporal dynamics at the international level, is essential for preventing their transnational propagation. However, annual indexes about the impact of infectious diseases provide a low level of granularity to allow stakeholders to craft better mitigation strategies. A quantitative risk assessment by analytical platforms requires billions of near real-time data points from heterogeneous sources, integrating and analyzing univariable or multivariable data with different levels of complexity and latency that, in most cases, overwhelm human cognitive capabilities. Autonomous biosurveillance can open the possibility for near real-time, risk- and evidence-based policymaking and operational decision support.

Wake-Riding Effect-Inspired Opto-Hydrodynamic Diatombot for Non-Invasive Trapping and Removal of Nano-Biothreats.

Contamination of nano-biothreats, such as viruses, mycoplasmas, and pathogenic bacteria, is widespread in cell cultures and greatly threatens many cell-based bio-analysis and biomanufacturing. However, non-invasive trapping and removal of such biothreats during cell culturing, particularly many precious cells, is of great challenge. Here, inspired by the wake-riding effect, a biocompatible opto-hydrodynamic diatombot (OHD) based on optical trapping navigated rotational diatom (Phaeodactylum tricornutum Bohlin) for non-invasive trapping and removal of nano-biothreats is reported. Combining the opto-hydrodynamic effect and optical trapping, this rotational OHD enables the trapping of bio-targets down to sub-100 nm. Different nano-biothreats, such as adenoviruses, pathogenic bacteria, and mycoplasmas, are first demonstrated to be effectively trapped and removed by the OHD, without affecting culturing cells including precious cells such as hippocampal neurons. The removal efficiency is greatly enhanced via reconfigurable OHD array construction. Importantly, these OHDs show remarkable antibacterial capability, and further facilitate targeted gene delivery. This OHD serves as a smart micro-robotic platform for effective trapping and active removal of nano-biothreats in bio-microenvironments, and especially for cell culturing of many precious cells, with great promises for benefiting cell-based bio-analysis and biomanufacturing.

Development and application of DETECTR-based rapid detection for pathogenic Bacillusanthracis.

Bacillus anthracis (B. anthracis) is a gram-positive bacterium responsible for the acute disease anthrax. Rapid and reliable identification of pathogenic B. anthracis is important in the detection of natural infectious disease cases or bio-threats. Herein, a DNA endonuclease targeted CRISPR trans reporter (DETECTR) detection platform based on recombinase polymerase amplification (RPA) was studied. The DETECTR system targeted three sequences from B. anthracis (the BA_5345 chromosomal specific marker, the protective antigen gene pag A from pXO1 plasmid and the capsule-biosynthesis-related gene cap A from pXO2 plasmid). We developed a rapid (<40 min), easy-to-implement and accurate identification method for of B. anthracis nucleic acid with near two-copies sensitivity. The combination of tripartite primer sets is effective for the reliable identification of B. anthracis but also for fast screening of pathogenic strains. More importantly, DETECTR correctly detected simulated clinical blood samples and firstly detected positive samples collected from the location of world War-II site, preserved at north-east China (45°36'55.940″ N, 126°38'33.738″ E) with high sensitivity and specificity. Our study provides insight into the DETECTR-based detection of B. anthracis. We present a novel screening and diagnostic option for pathogenic B. anthracis that can be performed on a user-friendly portable device. Based on its proven reliability, sensitivity, specificity and simplicity, our proposed method can be readily adapted to detect pathogenic B. anthracis, anthrax and biothreats.

Efficacy of Treatment with the Antibiotic Novobiocin against Infection with Bacillus anthracis or Burkholderia pseudomallei.

The microbial pathogens Burkholderia pseudomallei and Bacillus anthracis are unrelated bacteria, yet both are the etiologic agents of naturally occurring diseases in animals and humans and are classified as Tier 1 potential biothreat agents. B. pseudomallei is the gram-negative bacterial agent of melioidosis, a major cause of sepsis and mortality globally in endemic tropical and subtropical regions. B. anthracis is the gram-positive spore-forming bacterium that causes anthrax. Infections acquired by inhalation of these pathogens are challenging to detect early while the prognosis is best; and they possess innate multiple antibiotic resistance or are amenable to engineered resistance. Previous studies showed that the early generation, rarely used aminocoumarin novobiocin was very effective in vitro against a range of highly disparate biothreat agents. The objective of the current research was to begin to characterize the therapeutic efficacy of novobiocin in mouse models of anthrax and melioidosis. The antibiotic was highly efficacious against infections by both pathogens, especially B. pseudomallei. Our results supported the concept that specific older generation antimicrobials can be effective countermeasures against infection by bacterial biothreat agents. Finally, novobiocin was shown to be a potential candidate for inclusion in a combined pre-exposure vaccination and post-exposure treatment strategy designed to target bacterial pathogens refractory to a single medical countermeasure.

Improving Pandemic Response With Military Tools: Using Enhanced Intelligence, Surveillance, and Reconnaissance.

The coronavirus disease 2019 (COVID-19) pandemic rocked the world, spurring the collapse of national commerce, international trade, education, air travel, and tourism. The global economy has been brought to its knees by the rapid spread of infection, resulting in widespread illness and many deaths. The rise in nationalism and isolationism, ethnic strife, disingenuous governmental reporting, lockdowns, travel restrictions, and vaccination misinformation have caused further problems. This has brought into stark relief the need for improved disease surveillance and health protection measures. National and international agencies that should have provided earlier warning in fact failed to do so. A robust global health network that includes enhanced cooperation with Military Intelligence, Surveillance, and Reconnaissance (ISR) assets in conjunction with the existing international, governmental, and nongovernment medical intelligence networks and allies and partners would provide exceptional forward-looking and early-warning and is a proactive step toward making our future safe. This will be achieved both by surveilling populations for new biothreats, fusing and disseminating data, and then reaching out to target assistance to reduce disease spread in unprotected populations.

The role of mobile phones as a possible pathway for pathogen movement, a cross-sectional microbial analysis.

INTRODUCTION: Mobile phones are used the world over, including in healthcare settings. This study aimed to investigate the viable microbial colonisation of mobile phones used by healthcare personnel. METHODS: Swabs collected on the same day from 30 mobile phones belonging to healthcare workers from three separate paediatric wards of an Australian hospital were cultured on five types of agar plate, then colonies from each phone were pooled, extracted and sequenced by shotgun metagenomics. Questionnaires completed by staff whose phones were sampled assisted in the analysis and interpretation of results. RESULTS AND DISCUSSION: All phones sampled cultured viable bacteria. Overall, 399 bacterial operational taxonomic units were identified from 30 phones, with 1432 cumulative hits. Among these were 58 recognised human pathogenic and commensal bacteria (37 Gram-negative, 21 Gram-positive). The total number of virulence factor genes detected was 347, with 1258 cumulative hits. Antibiotic resistance genes (ARGs) were detected on all sampled phones and overall, 133 ARGs were detected with 520 cumulative hits. The most important classes of ARGs detected encoded resistance to beta-lactam, aminoglycoside and macrolide antibiotics and efflux pump mediated resistance mechanisms. CONCLUSION: Mobile phones carry viable bacterial pathogens and may act as fomites by contaminating the hands of their users and indirectly providing a transmission pathway for hospital-acquired infections and dissemination of antibiotic resistance. Further research is needed, but meanwhile adding touching mobile phones to the five moments of hand hygiene is a simple infection control strategy worth considering in hospital and community settings. Additionally, the implementation of practical and effective guidelines to decontaminate mobile phone devices would likely be beneficial to the hospital population and community at large.

Adult COVID-19 Patients Cared for in a Pediatric ICU Embedded in a Regional Biothreat Center: Disease Severity and Outcomes.

The objective of this study was to describe the clinical characteristics and outcomes of adult coronavirus disease 2019 (COVID-19) patients admitted to a pediatric intensive care unit (PICU), with assessment of respiratory clinical severity and outcomes when cared for by pediatric intensivists utilizing specific care processes. We conducted a retrospective cohort study of adult patients admitted to the 14-bed PICU of a quaternary referral center during the COVID-19 surge in Boston between April and June 2020. A total of 37 adults were admitted: 28 tested COVID-19 positive and 9 tested COVID-19 negative. Of the COVID-19-positive patients, 21 (75%), were male and 12 (60.7%) identified as Hispanic/Latino. Comorbidities in the patients included diabetes mellitus (39.3%), hyperlipidemia (39.3%), and hypertension (32.1%). Twenty-four (85.7%) required mechanical ventilation, in whom the lowest median ratio of arterial oxygen partial pressure to fractional inspired pressure was 161.5 (141.0 to 184.5), the median peak positive end-expiratory pressure (PEEP) was 14 (12.0 to 15.8) cmH2O and 15 (62.5%) underwent an optimal PEEP maneuver. Twelve (50%) patients were proned for a median of 3.0 (3.0 to 4.8) days. Of the 15 patients who were extubated, 3 (20%) required reintubation. Tracheostomy was performed in 10 patients: 3 after extubation failure and 7 for prolonged mechanical ventilation and weakness. Renal replacement therapy was required by 4 (14.3%) patients. There were 2 (7.1%) mortalities. We report detailed clinical outcomes of adult patients when cared for by intact pediatric critical care teams during the COVID-19 pandemic. Good clinical outcomes, when supported by adult critical care colleagues and dedicated operational processes are possible.

Dangerous Pathogens as a Potential Problem for Public Health.

Pathogens are various organisms, such as viruses, bacteria, fungi, and protozoa, which can cause severe illnesses to their hosts. Throughout history, pathogens have accompanied human populations and caused various epidemics. One of the most significant outbreaks was the Black Death, which occurred in the 14th century and caused the death of one-third of Europe's population. Pathogens have also been studied for their use as biological warfare agents by the former Soviet Union, Japan, and the USA. Among bacteria and viruses, there are high priority agents that have a significant impact on public health. Bacillus anthracis, Francisella tularensis, Yersinia pestis, Variola virus, Filoviruses (Ebola, Marburg), Arenoviruses (Lassa), and influenza viruses are included in this group of agents. Outbreaks and infections caused by them might result in social disruption and panic, which is why special operations are needed for public health preparedness. Antibiotic-resistant bacteria that significantly impede treatment and recovery of patients are also valid threats. Furthermore, recent events related to the massive spread of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are an example of how virus-induced diseases cannot be ignored. The impact of outbreaks, such as SARS-CoV-2, have had far-reaching consequences beyond public health. The economic losses due to lockdowns are difficult to estimate, but it would take years to restore countries to pre-outbreak status. For countries affected by the 2019 coronavirus disease (COVID-19), their health systems have been overwhelmed, resulting in an increase in the mortality rate caused by diseases or injuries. Furthermore, outbreaks, such as SARS-CoV-2, will induce serious, wide-ranging (and possibly long-lasting) psychological problems among, not only health workers, but ordinary citizens (this is due to isolation, quarantine, etc.). The aim of this paper is to present the most dangerous pathogens, as well as general characterizations, mechanisms of action, and treatments.

Monoclonal antibodies as anti-infective products: a promising future?

BACKGROUND: The paucity of licensed monoclonal antibodies (mAbs) in the infectious diseases arena strongly contrasts with the ready availability of these therapeutics for use in other conditions. AIMS: This narrative review aims to assess the potential of monoclonal antibody-based interventions for infectious diseases. SOURCES: A review of the literature via the Medline database was performed and complemented by published official documents on licensed anti-infective mAbs. In addition, ongoing trials were identified through a search of the clinical trial registration platform ClinicalTrials.gov. CONTENT: We identified the few infections for which mAbs have been added to the therapeutic armamentarium and stressed their potential in representing a readily available protection tool against biothreats and newly emerging and reemerging infectious agents. In reviewing the historical context and main features of mAbs, we assert a potentially wider applicability and cite relevant examples of ongoing therapeutic developments. Factors hindering successful introduction of mAbs on a larger scale are outlined and thoughts are offered on how to possibly address some of these limitations. IMPLICATIONS: mAbs may represent important tools in treating or preventing infections occurring with reasonably sufficient prevalence to justify demand and for which existing alternatives are not deemed fully adequate. Future initiatives need to address the prohibitive costs encountered in the development process. The feasibility of more large-scale administration of alternative modalities merits further exploration. In order to ensure optimal prospect of regulatory success, an early dialogue with competent authorities is encouraged.

Current progress and future opportunities in applications of bioinformatics for biodefense and pathogen detection: report from the Winter Mid-Atlantic Microbiome Meet-up, College Park, MD, January 10, 2018.

The Mid-Atlantic Microbiome Meet-up (M3) organization brings together academic, government, and industry groups to share ideas and develop best practices for microbiome research. In January of 2018, M3 held its fourth meeting, which focused on recent advances in biodefense, specifically those relating to infectious disease, and the use of metagenomic methods for pathogen detection. Presentations highlighted the utility of next-generation sequencing technologies for identifying and tracking microbial community members across space and time. However, they also stressed the current limitations of genomic approaches for biodefense, including insufficient sensitivity to detect low-abundance pathogens and the inability to quantify viable organisms. Participants discussed ways in which the community can improve software usability and shared new computational tools for metagenomic processing, assembly, annotation, and visualization. Looking to the future, they identified the need for better bioinformatics toolkits for longitudinal analyses, improved sample processing approaches for characterizing viruses and fungi, and more consistent maintenance of database resources. Finally, they addressed the necessity of improving data standards to incentivize data sharing. Here, we summarize the presentations and discussions from the meeting, identifying the areas where microbiome analyses have improved our ability to detect and manage biological threats and infectious disease, as well as gaps of knowledge in the field that require future funding and focus.

Biothreat Agents and Emerging Infectious Disease in the Emergency Department.

The challenges faced by the emergency physician with recognizing and treating category A biothreat agents and emerging infectious disease are summarized and reviewed.

Biothreat Reduction and Economic Development: The Case of Animal Husbandry in Central Asia.

Improving human welfare is a critical global concern, but not always easy to achieve. Complications in this regard have been faced by the states of the Former Soviet Union, where socialist-style economic institutions have disappeared, and the transition to a market economy has been slow in coming. Lack of capital, ethnic conflict, and political instability have at times undermined the institutional reform that would be necessary to enable economic efficiency and development. Nowhere are such challenges more pronounced than in the new nation states of central Asia, including Kazakhstan, Kyrgyzstan, Tajikistan, Turkmenistan, and Uzbekistan. Here, a severe climate limits agriculture, and industrialization has been inhibited by lack of infrastructure, low levels of human capital, and a scarcity of financial resources. These conditions are aggravated by the fact that the central Asian states are landlocked, far from centers of market demand and capital availability. Despite these daunting barriers, development potential does exist, and the goal of the paper is to consider central Asia's pastoral economy, with a focus on Kazakhstan, which stands poised to become a regional growth pole. The article pursues its goal as follows. It first addresses the biothreat situation to central Asian livestock herds, the most significant existing impediment to realizing the full market potential of the region's animal products. Next, it provides an outline of interventions that can reduce risk levels for key biothreats impacting central Asia, namely foot and mouth disease (FMD), which greatly impacts livestock and prohibits export, and Brucellosis, a bacterial zoonosis with high incidence in both humans and livestock in the region. Included is an important success story involving the FMD eradication programs in Brazil, which enabled an export boom in beef. After this comes a description of the epidemiological situation in Kazakhstan; here, the article considers the role of wildlife in acting as a possible disease reservoir, which presents a conservation issue for the Kazakhstani case. This is followed by a discussion of the role of science in threat reduction, particularly with respect to the potential offered by geospatial technologies to improve our epidemiological knowledge base. The article concludes with an assessment of the research that would be necessary to identify feasible pathways to develop the economic potential of central Asian livestock production as changes in policy are implemented and livestock health improves.