News highlights on health security threats and countermeasures curated by Global Biodefense
This week’s selections include increasing dual-use research oversight; progress on a Chikungunya vaccine; detection technologies for African Swine Fever; and the security vulnerabilities of chemical facilities in the U.S.
POLICY + GOVERNMENT
Biotech Promises Miracles. But The Risks Call for More Oversight
Despite the dramatic pace of discoveries in the life sciences, the regulatory systems established for other dual-use risk domains, such as chemical and nuclear research, remain far more mature than those for oversight of the bioeconomy. Even if existing biosafety and biosecurity regulations were expanded to include the private sector (not just federally funded research), which government agencies would have lead responsibilities for oversight of different types of biorisk remains ill-defined. Similarly, without international harmonization of dual-use guidelines, the prognosis for orderly and responsible global development of these technologies will remain problematic. Bulletin of the Atomic Scientists
We Cannot Give Up on the Global Pandemic Treaty
“As the Covid-19 pandemic waned, our elected leaders lost focus on their responsibility to prevent another such event. Nearly two years after countries agreed to develop a new pandemic treaty, the prospect of achieving a bold new global agreement to prepare and respond to future disease threats is slipping away. The sense of urgency that gripped nations to be better prepared in future has been replaced by complacency… Simply heaping more responsibility on the WHO to work things out as they go would leave us where we started. Yet that is where the process is headed. The most recent round of treaty talks failed to bring a breakthrough in any of the areas of disagreement, signalling serious trouble ahead. While there is still time to turn things around, that time is short.” Financial Times
White House Seeks Input on Tightening Rules for Risky Pathogen Research
A panel’s recommendations earlier this year to tighten U.S. rules for funding research on dangerous pathogens sparked concerns that some of the changes would hamper routine studies important to public health. Now, the White House is looking at ways to narrow the swath of federally funded research that would undergo the heightened reviews proposed by the National Science Advisory Board for Biosecurity (NSABB). Science
Public Health Position Available: Low Pay. Promise of Burnout and Harassment. Master’s Preferred.
One weakness of the National Biodefense Strategy is that it doesn’t adequately describe the gutted state of the public health workforce. The state and local health departments responsible for disease surveillance, vaccination campaigns, and assistance in natural disasters like wildfires or hurricanes are hemorrhaging workers, with an additional 130,000 at risk of leaving the profession by 2025. Unless something changes soon, there will be too few new employees to backfill empty positions—or to make up for the loss of invaluable institutional knowledge. Many workers left these jobs in recent years after experiencing burnout or aggressive harassment during the pandemic. Bulletin of the Atomic Scientists
How and Why DoD Has Updated Its Readiness Plan for Biodefense
Transcript of interview with Principal Deputy Assistant Secretary of Defense for Nuclear, Chemical and Biological Defense Programs, Brandi Vann. “So I think the thing that we recognized in the Biodefense Review was that, again, the complexity of the threats and the sheer number of threats that we potentially face in the department and as a nation for national security is so large that it takes us actually relooking at how we structure our preparedness and response activities.” Federal News Network
MEDICAL COUNTERMEASURES
Disease X: CEPI and University of Oxford Collaborate on Rapid Response Vaccine Technology
CEPI commits up to $80 million to support design, manufacture and vaccination strategies for globally accessible vaccines against outbreak pathogens. ChAdOx is one of a handful of rapid response vaccine technologies they will work from with proven capability as a platform on which safe and effective vaccines can be quickly developed and manufactured at scale and low cost. The ChAdOx platform was the basis for Oxford’s COVID-19 vaccine which became one of the most widely used COVID-19 vaccines in the world. Global Biodefense
Engineering the Live-Attenuated Polio Vaccine to Prevent Reversion to Virulence
The live-attenuated oral poliovirus vaccine (OPV or Sabin vaccine) replicates in gut-associated tissues, eliciting mucosa and systemic immunity. The ability of OPV to regain replication fitness and establish new epidemics represents a significant risk of polio re-emergence should immunization cease. This report is on the development of a poliovirus type 2 vaccine strain (nOPV2) that is genetically more stable and less likely to regain virulence than the original Sabin2 strain. Cell Host & Microbe
Chikungunya Vaccine: Health Canada Moves Forward with Valneva Review
Health Canada has completed screening validation of the company’s regulatory application for marketing approval of its single-shot chikungunya vaccine candidate VLA1553 in persons aged 18 years and above. Valneva estimates regulatory review could be completed by mid-2024. The vaccine candidate in also currently under priority review by the US FDA. Global Biodefense
Development of an AP-1 Gene Reporter Potency Assay for Anti-Anthrax Toxin Therapeutics
Report on the development of a new cell-based AP-1 reporter potency assay for anti-anthrax toxin therapeutic antibodies, based on their neutralizing activity on a specific effect of anthrax toxin conserved among mammalian cell targets. The new high-performing AP-1 reporter assay may be used for evaluation of the potency of a variety of therapeutics targeting PA, including other licensed mAbs (e.g., obiltoxaximab) or Anthrax Immunoglobulin Intravenous (AIGIV). It may also warrant investigation for use in evaluation of the immunogenicity of anthrax vaccines by measuring the anti-PA titers in humans following vaccination of BioThrax AVA and other recombinant PA vaccines, once validated for use in a serum matrix. Toxins
CSL Seqirus Awarded Contract for Influenza A(H5N8) Candidate Vaccine
CSL Seqirus will provide a bulk lot of H5N8 A/Astrakhan antigen for BARDA’s stockpile of vaccine materials to support rapid response in an associated influenza pandemic. This is the third flu pandemic preparedness contract awarded to the company by HHS in the last two years. Global Biodefense
BIOSECURITY + BIOPREPAREDNESS
From Private Incentives to Public Health Need: Rethinking Research and Development for Pandemic Preparedness
Current approaches to pharmaceutical innovation mainly rely on market dynamics to drive product development, manufacturing, and distribution, even for epidemics that are threats of international concern. Governments have used a range of push and pull mechanisms to attract R&D investment in areas of public health need and uncertain market return, including research subsidies, tax credits, regulatory incentives, and advance purchase agreements. Although these are designed to accelerate commercial product development, they often do not translate into products optimized for use by public health systems especially in low-resource environments, or to equitable access to products or technologies. The Lancet Health Policy
Biosecurity, Biosafety and Dual Use: Will Humanity Minimize Potential Harms in the Age of Biotechnology?
Despite the inevitability of the dual-purpose nature of research, including a multi-billion-dollar increase in biodefence research funding in the United States after 2001, surprisingly little research is censored or held to be a risk. One approach to dual-use governance is to recognize that all life sciences research and technology has the potential to be misused, and that dual-use concerns lie along a spectrum of potential hazards. “When a potentially calamitous downside is conceivable—not just in accelerator experiments, but in genetics, robotics, and nanotechnology—can scientists provide the ultraconfident assurance that the public may demand? What should be the guidelines for such experiments, and who should formulate them? Above all, even if guidelines are agreed upon, how can they be enforced? As the power of science grows, such risks will, I believe, become more varied and widely diffused. Even if each risk is small, they could mount up to a substantial cumulative danger.” OAPEN
U.S. Army Laboratory Technicians Train with Romanian Troops at Bucharest Biological Research Facility
Members of the specialized 1st Area Medical Laboratory recently visited Bucharest to teach mobile PCR biothreat identification techniques and exchange knowledge for threat response with Romanian Army CBRN and scientific counterparts. Global Biodefense
SELECT AGENTS + PRIORITY PATHOGENS
WHO Reports 3 More MERS Cases from Saudi Arabia
Since September 2022, Saudi Arabia has reported three more Middle East respiratory syndrome coronavirus (MERS-CoV) cases, two of them fatal, all involving men who had contact with camels or had consumed raw camel milk before they got sick. No secondary cases were identified. CIDRAP
The Lifespan of Bacillus anthracis Spores in Environmental Reservoirs
Spores of B. anthracis are highly resistant to adverse environmental conditions and can withstand a variety of stressors such as heat and ultraviolet (UV) radiation. Fundamental questions surrounding the environmental reservoir of B. anthracis remain unanswered, including what factors affect spore concentrations at pathogen reservoir sites (i.e., anthrax carcass sites) and how long these sites remain infectious. Research in Microbiology
Analysis of Bacillus cereus Biovar anthracis Isolated from Archival Bone Samples
Bacillus cereus biovar anthracis (Bcbva) was the causative agent of an anthrax-like fatal disease among wild chimpanzees in 2001 in Côte d’Ivoire. Before this, there had not been any description of an anthrax-like disease caused by typically avirulent Bacillus cereus. Genetic analysis found that B. cereus had acquired two anthrax-like plasmids in the wild. In this work, archival non-human primate bone samples from the endemic forest anthrax zone were analyzed for the presence of Bcbva. Study results shows that Bcbva spores can survive decades and remain infectious in animal material. Future work focusing on the differences in ecology of Bcbva-caused anthrax and classical B. anthracis anthrax is warranted given how little is known and their overlapping geographies in Western and Central Africa. Pathogens
Mpox in Pregnancy: Viral Clade Differences and Their Associations with Varying Obstetrical and Fetal Outcomes
There have been at least 58 cases of mpox infection occurring in pregnant women during the 2022–2023 outbreak. No confirmed cases of adverse perinatal outcome, including stillbirth, have been reported. The absence of perinatal morbidity and mortality from Clade IIb corresponds to the overall case fatality rate among non-pregnant women of <0.1%, as this clade has been demonstrated to produce a less-severe disease than the mpox Clade I or IIa variants. Prior to the 2022–2023 global outbreak, mpox infections among pregnant women caused by Clade I were reported to have a 75% perinatal case fatality rate in the Democratic Republic of Congo, including the only documented case of placental infection and stillbirth from the Congenital Mpox Syndrome, and the Clade IIa mpox infection was associated with stillbirths in Nigeria. Viruses
Microbe of the Month: Burkholderia pseudomallei
Local regulatory guidelines for B. pseudomallei vary across the globe. The US categorizes the organism as a biosafety level 3 (BSL-3) pathogen and select agent. Comprehensive global modeling estimated that there were 165,000 melioidosis cases in 2015, resulting in 89,000 deaths worldwide (estimated 54% mortality rate). Environmental factors, such as soil type, temperature, moisture, pH, salinity, and nutrient levels influence B. pseudomallei prevalence in the soil. B. pseudomallei is intrinsically resistant to multiple classes of antibiotics, including aminoglycosides, rifamycins, penicillins, cephalosporins, and cationic peptides. Human-to-human transmission is rare, and infections are primarily due to environmental exposure to contaminated soil or water. Trends in Microbiology
AVIAN INFLUENZA
A Comprehensive Review of Highly Pathogenic Avian Influenza (HPAI) H5N1: An Imminent Threat at Doorstep
The origin and evaluation of HPAI H5N1 are examined, shedding light on its emergence, and spread across different geographic regions. The genome organization and structural biology of the H5N1 virus are explored, providing insights into its molecular composition and key structural features. Diagnostic tools and preventive and therapeutic strategies are also discussed, highlighting the current approaches and potential future directions for better management of the potential pandemic. Travel Medicine and Infectious Disease
Asymptomatic Infection with Clade 2.3.4.4b Highly Pathogenic Avian Influenza A(H5N1) in Pets
Report of the serological evidence of HPAI H5N1 virus infection in five dogs and one cat on a rural farm in Italy. The recent cases of H5N1 virus infections in domestic cats in France and Poland and in farmed fur animals across Finland were initially detected because of their overt clinical manifestations. In contrast, the affected pets in this report were completely asymptomatic, raising concerns over the possibility of subclinical infections with zoonotic viruses in animals in close contact with humans. Eurosurveillance
Detection of Avian Influenza A Virus in Respiratory Specimens Collected from Live Bird Market Workers
Study investigated molecular detections of avian influenza A virus (AIV) RNA with serology. AIV RNA detections in contaminated settings may suggest environmental contamination. Influenza-like illness symptom frequency was similar between live bird market workers with and without AIV RNA. Symptomatic and asymptomatic workers exhibited comparable AIV RNA detection patterns. Relying on rRT-PCR detections can overestimate AIV infections. International Journal of Infectious Diseases
CHEMICAL + RADIOLOGICAL THREATS
America’s Fight Against Chemical Terrorism is at Risk
For more than 15 years, the Cybersecurity and Infrastructure Security Agency (CISA) and its predecessor organization have helped keep communities safe through the Chemical Facility Anti-Terrorism Standards (CFATS) program. The statutory authority for CFATS expired on July 28, despite strong support from industry and overwhelming bipartisan backing in both the House and the Senate. Members of Congress adjourned for August recess on July 27 – a day earlier than expected, and leaving a lot of work undone. Until Congress reauthorizes the program, CISA can no longer inspect more than 3,200 high-risk sites, enforce implementation of security measures, vet individuals seeking access to dangerous chemicals or identify new facilities that possess high-risk chemicals. Washington Post
US Safety Board Warns of Hurricane Threat to Chemical Facilities
Steve Owens, the chairman of the US Chemical Safety Board (CSB), has warned that hurricanes and high winds could ‘significantly impact’ the US bulk-power system and trigger the release of hazardous chemicals if facilities lose power. It’s not a theoretical risk. CSB has in recent years investigated two serious chemical releases that were caused or made worse by loss of power during hurricanes. After hurricane Harvey in 2017, significant flooding knocked out power to the Arkema chemical plant in Crosby, Texas. Stored organic peroxides ignited after refrigerators, generators and backup cooling methods failed. 200 residents were forced to evacuate and more than twenty first responders were hospitalized due to exposure to the resulting fumes. Chemistry World
Development of Radiation Countermeasure Agents for Acute Radiation Syndromes
Review of the World Health Organization’s updated list of essential medicines for 2023 for the proper management of national stockpiles and the treatment of radiological emergencies. This review also discusses the types of radiation-induced health injuries and the related mechanisms, as well as the development of various radioprotective agents for which significant survival benefits have been demonstrated in animal models of acute radiation syndrome. Animal Models and Experimental Medicine
SURVEILLANCE + DETECTION
Ambient Ionization Mass Spectrometry for Rapid Detection of Biological Warfare Agents and Their Simulants
The rapid advancement of ambient ionization mass spectrometry (AIMS) provides promising opportunities for rapid, real-time, and accurate analysis of trace emerging pathogenic microorganisms and toxins. In most MS analyses, samples typically undergo purification and separation procedures prior to introduction into mass spectrometers. However, ambient ionization mass spectrometry (AIMS) is ideal for in-situ analysis. This review article provides an overview of several exemplary applications of AIMS in biodefense for the rapid detection and identification of biological weapons. Microchemical Journal
Online Acid Cleavage of Proteins for LC-MS Bottom-Up Protein Analysis ─ Application for Ricin Detection
Report on a fast online method for postinjection acid cleavage of proteins directly in the mobile phase typically used for LC-MS analyses in proteomics. The procedure requires only one manual step, significantly decreasing sample transfer losses. The method was demonstrated with rapid detection of ricin, unambiguously identified from an injection of 10 ng, with results obtained within 7–8 min after ‘suspicious sample’ receipt. Analytical Chemistry
Dual-Antigen Indirect ELISA to Detect Antibodies against African Swine Fever Virus
Researchers chose an early antigen and a late-expressed antigen to co-detect the target antibody, which not only helps in early detection but also improves accuracy and sensitivity. The detection method provides a new low cost, streamlined method for the serological diagnosis of ASF. Viruses
Accelerometer-Based Detection of African Swine Fever Infection
Although animal tracking technologies are used to discern behavioral changes, they are rarely used to monitor wildlife diseases. Common disease-induced behavioral changes include reduced activity and lethargy (‘sickness behavior’). Researchers investigated whether accelerometer sensors could detect the onset of African swine fever (ASF), a viral infection that induces high mortality in suids for which no vaccine is currently available. The scientists equipped 12 wild boars with an accelerometer tag and quantified how ASF affects their activity pattern and behavioral fingerprint, using overall dynamic body acceleration. Proceedings of the Royal B Society
Identification of Novel Animal Pathogen Trueperella pecoris by LAMP Diagnostics
Trueperella pecoris was described as a new species of the genus Trueperella in 2021 and might be pathogenic to various animal species. However, the lack of a suitable diagnostic test system stands in the way of epidemiological surveys to clarify possible causalities. In this study, a Loop-mediated Isothermal Amplification (LAMP) assay was developed and validated, showing the test that was highly specific for T. pecoris. Scientific Reports
Estimating the Effectiveness of Control Actions on African Swine Fever Transmission in Commercial Swine Populations
This study extends the previously developed farm-level stochastic transmission model PigSpread to simulate ASF dissemination within the domestic swine population of the southeastern U.S. This is the first published study to estimate the dissemination of ASF among a commercial swine population in the U.S. using real population and multiple contact networks, incorporating most of the known direct and indirect transmission routes for the virus. Preventive Veterinary Medicine
INFECTIOUS DISEASES
A Deadly Tick-Borne Epidemic is Raging. Dogs are Key to Ending It.
The boy came home from school weakened by fever, his ears burning-hot. Over the next few days, the 7-year-old got sicker — vomiting and complaining of abdominal pain, his mother recalled. Then, the telltale red spots appeared on his hands. But none of the doctors in this rural community along Mexico’s Pacific coast recognized the warning sign for one of the most lethal infectious diseases in the Americas — Rocky Mountain spotted fever. A week later, the boy was dead. The disease, spread through the bite of an infected tick that lives primarily on dogs, is rare, but its incidence is rising. It has reemerged at epidemic levels in northern Mexico, where more than 2,000 cases, resulting in hundreds of deaths Washington Post
With Mississippi Declared Endemic Area for Melioidosis Pathogen – Public Health Needs Support to Respond
Burkholderia pseudomallei is a gram-negative bacterium and Tier 1 Select Agent that typically lives in soil and water in regions with tropical and subtropical climates around the world, such as South and Southeast Asia, northern Australia, parts of Central and South America, the U.S. Virgin Islands, and Puerto Rico. The U.S. state of Mississippi recently joined the list of endemic areas. Finding human cases of melioidosis in the Gulf Coast region calls for increased education, diagnostics, research and development in neglected areas of public health. Global Biodefense
Grave Health Crisis as Measles Cases Surge in Yemen
In the first half of 2023, the number of measles patients received in MSF-supported facilities in Yemen has nearly tripled, at almost 4,000, compared to the whole of 2022. Considering the impact of almost nine years of conflict, and the economic hardship wracking the country, what they’re seeing is likely the tip of the iceberg. Measles is a highly contagious viral infection that can easily spread in densely populated communities. It predominantly affects children under five and is particularly dangerous for those with underlying conditions or complications. Médecins Sans Frontières
Ongoing Measles Outbreaks in Romania, March 2023 to August 2023
Following a 2-year period with zero indigenous measles cases, the disease reappeared in late 2022. Outbreaks of measles occurred in March 2023 in the northern part of Romania and by August 2023, 460 of 580 possible measles cases were confirmed in 17 of the 41 Romanian counties. Most cases were registered among unvaccinated children. No measles-related deaths have so far been notified. Eurosurveillance
ANTIMICROBIAL RESISTANCE CRISIS
Novel Combinations with Last-Line Antibiotics against Klebsiella pneumoniae
This study aimed to identify partners that could potentiate the activity of tigecycline, colistin and fosfomycin, three last-line antibiotics currently used to treat infections caused by multi-drug resistant K. pneumoniae. Synergistic and killing effects were evaluated at different time points to obtain a priority list of combinations. Among them, zidovudine and azithromycin resulted in the most potent synergistic partners of the three antimicrobials with the highest potential for clinical translation. Scientific Reports
Plasmodium falciparum Resistant to Artemisinin and Diagnostics Have Emerged in Ethiopia
Monitoring emergence, evolution and spread of drug- and diagnostics-resistant parasites are required for effective malaria control. This genetic analyses confirms that the WHO candidate artemisinin partial-resistance kelch 622I mutation is common in three regions of Ethiopia and suggests recent clonal spread of this mutation. Continued use of artemisinin-combination therapies (ACTs) and other antimalarials puts pressure on the P. falciparum population and could be one factor driving the emergence of antimalarial drug resistance. ACTs have been the first-line treatment for uncomplicated falciparum malaria in Ethiopia for nearly two decades. Reports of 622I at high prevalence in neighboring Eritrea (16.7% in 2016) and association with 6.3% delayed clearance on day 3 of artemether-lumefantrine treatment raise further concern about this mutation. Nature Microbiology
COVID-19 PANDEMIC
Not Over Yet: Late-Summer Covid Wave Brings Warning of More to Come
Hospitalizations have increased 24 percent in a two-week period ending Aug. 12, according to the most recent data from the Centers for Disease Control and Prevention. Wastewater monitoring suggests a recent rise in Covid infections in the West and Northeast. Public health officials said that the latest increase in Covid hospitalizations is still relatively small and that the vast majority of the sick are experiencing mild symptoms comparable to a cold or the flu. New York Times
UK Decides on Earlier Fall Push for Flu Vaccines, COVID Boosters
The UK Department of Health and Social Care (DHSC) announced that this year’s autumn flu and COVID-19 vaccine program will start a month earlier than planned in England as a precautionary measure following the identification of a new SARS-CoV-2 variant (BA.2.86). Their operating principle for fall is whenever possible, flu and COVID-19 vaccines should be administered at the same time to increase reach. Global Biodefense
Accelerated Evolution of SARS-CoV-2 in Free-Ranging White-Tailed Deer
Newly developed phylogenetic methods quantified how SARS-CoV-2 evolution is not only three-times faster in white-tailed deer compared to the rate observed in humans but also driven by different mutational biases and selection pressures. The long-term effect of this accelerated evolutionary rate remains to be seen. Still, SARS-CoV-2 has transmitted in white-tailed deer populations for a relatively short duration, and the risk of future changes may have serious consequences for humans and livestock. Nature Communications
Antibody Response in Elderly Vaccinated Four Times with an mRNA COVID-19 Vaccine
This study addresses the immune response to the third and fourth doses of a COVID-19 mRNA vaccine in an elderly population residing in an assisted living facility, where COVID-19 cases were not reported among residents until January 1st 2022. The present study shows that in the Elderly (85 years median), a fourth dose maintains and even expands the functional antibodies against the ancestral Wuhan strain and the BA.1 Omicron variant. This correlates well with vaccine efficacy (VE) studies showing that the fourth dose recipients seemed to benefit an equal or even better VE when compared to third-dose recipients. As the Elderly are the most at-risk population, their ability to respond to four vaccine doses delivered within a year speaks to a robustness of immune response, rather than exhaustion. Scientific Reports
Comparison of Bivalent and Monovalent SARS-CoV-2 Variant Vaccines
In a phase 2, open-label, randomized clinical trial (COVAIL) with sequentially enrolled stages at 22 US sites, researchers assessed safety and immunogenicity of a second boost with monovalent or bivalent variant vaccines from mRNA and protein-based platforms targeting wild-type, Beta, Delta and Omicron BA.1 spike antigens. Results indicate updated vaccines targeting Beta or Omicron BA.1 provide broadly crossprotective neutralizing antibody responses against diverse SARS-CoV-2 variants without sacrificing immunity to the ancestral strain. Nature Medicine
ALSO READING
ProMED issues ultimatum to striking moderators, as questions about site’s future persist. STAT
VP24 matrix proteins of eight filoviruses downregulate innate immune response by inhibiting the interferon-induced pathway. Journal of General Virology
TRIM5alpha restricts poxviruses and is antagonized by CypA and the viral protein C6. Nature
Early transcriptomic host response signatures in the serum of dengue patients provides insights into clinical pathogenesis and disease severity. Scientific Reports
Smallpox, an ancient term for various infectious diseases. JPMH
Biological threats have evolved for the worse, and we are not prepared. Center for Arms Control and Non-Proliferation
Cell–Cell Fusion Assays to Study Henipavirus Entry and Evaluate Therapeutics. Nipah Virus
Inactivation of Bacteriophage ɸ6 and SARS-CoV-2 in Antimicrobial Surface Tests. Viruses
Real-Time Radiation Detection within the Gastrointestinal Tract. MIT Libraries
Experimental Study on Key Effectiveness of Bioaerosol Alarm. Research Square
Chemical Agents Enhancing Resistance to Sulphur Mustard Injury: Developing a Model to Explore Pre-Exposure Strategies. JMVH