News highlights on health security threats and countermeasures curated by Global Biodefense
This week’s selections include DoD pharmaceutical supply chain risks, a prize challenge to advance patch-based vaccines, and delayed SARS-CoV-2 viral clearance with molnupiravir treatment.
POLICY + GOVERNMENT
A Proclamation on National Public Health Week, 2024
“In the last few years, we have made enormous progress in recovering from the pandemic, vaccinating 230 million Americans and getting kids back in school. None of that would have been possible without the courage and dedication of millions of first responders and social workers, doctors and nurses, and scientists and researchers…We owe them for carrying us through tough times and making our country healthier and more prosperous long-term. We have to help make their jobs easier by investing in the health of the American people.” The White House
EU Regulations for Maximum Containment Labs
In regions such as Europe, there are effective safety mechanisms in place that could serve as a model for maximum containment laboratories worldwide. The European Union is well prepared to lead and facilitate international laboratory safety policies. The European Research lnfrastructure on Highly Pathogenic Agents (ERINHA) currently federates facilities in 10 European countries. In tandem with its corporate partner, the European Biosafety Association, ERINHA offers expertise and applied biorisk management training to researchers throughout the world. Science
Promoting a Risk-Based Approach for Regulatory Oversight of Vaccines Used in Pandemics
During the 2009 H1N1 influenza pandemic, the deployment of pandemic influenza vaccines in importing countries was delayed or disrupted due to the lack of regulatory preparedness. This resulted in WHO developing guidelines for non-vaccine producing countries on the appropriate regulatory approaches to the marketing authorization and lot release of pandemic influenza vaccines in public health emergency conditions. However, subsequent public health emergencies such as the Ebola epidemic and COVID-19 pandemic further exposed gaps in regulatory preparedness for other types of pandemic vaccines. The role of national regulatory authorities was not acknowledged in national pandemic preparedness plans. World Health Organization
Joint Update by the Department of State and HHS on Negotiations Toward a Pandemic Accord
“We are taking steps to develop a more efficient and predictable process for financing global vaccines in the next pandemic, which will mean: leveraging pre-negotiated purchasing agreements to enable a more rapid start to donations of vaccines and other countermeasures when needed; negotiating more favorable pricing before and during the next pandemic; and benefitting American companies — by more clearly communicating demand for their products, companies will have more reliable order volume at the beginning of a pandemic emergency as well as access to new markets.” Department of Health and Human Services
MEDICAL COUNTERMEASURES
Innovation Challenge Announced for Patch-Based RNA Vaccines
Through the Patch Forward Prize, BARDA is incentivizing collaboration between vaccine and patch developers and providing resources to advance these combination products into Phase I clinical trials. A virtual Information Session on the Patch Forward Prize challenge will be held 18 April 2024. Global Biodefense
Surrogate Model for Human Ebola Virus Disease in BSL-2 Laboratory
The development of countermeasures against EBOV has been hindered by the lack of ideal animal models, as EBOV requires handling in biosafety level (BSL)-4 facilities. In this study, a recombinant vesicular stomatitis virus expressing Ebola virus glycoprotein (VSV-EBOV/GP) was constructed and applied as a surrogate virus, establishing a lethal infection in hamsters. Virological Sinica
ReAlta Development of RLS-0071 as Acute Radiation Syndrome Medical Countermeasure
Scientists at the Armed Forces Radiobiology Research Institute (AFRRI), with support from the Radiation and Nuclear Countermeasures Program (RNCP) at NIAID, will evaluate the ability of RLS-0071 to mitigate the gastrointestinal effects of ARS (GI-ARS) in a preclinical mouse model. Global Biodefense
BioFactura Triples Facility Space in Frederick for Smallpox Therapy Development
The facility is expected to open in the fall of 2024 and house more than 50 engineers, biologic manufacturing specialists, scientists, regulatory compliance and quality control, and clinical trial professionals. Frederick News-Post
Diazepam vs. Midazolam Following Seizures from Nerve Agent Exposure
Acute poisoning with organophosphorus cholinesterase inhibitors (OPs), such as OP nerve agents and pesticides, can cause life threatening cholinergic crisis and status epilepticus (SE). Survivors often experience significant morbidity, including brain injury, acquired epilepsy, and cognitive deficits. Current medical countermeasures for acute OP poisoning include a benzodiazepine to mitigate seizures. Diazepam was long the benzodiazepine included in autoinjectors used to treat OP-induced seizures, but it is now being replaced in many guidelines by midazolam, which terminates seizures more quickly, particularly when administered intramuscularly. Neuropharmacology
BIOSECURITY + BIOPREPAREDNESS
Report on the Department of Defense Pharmaceutical Supply Chain Risks
The DoD says it has a high dependence on foreign material and trade agreements to maintain current pharmaceutical capabilities. Approximately 54 percent of its pharmaceutical supply chain is considered either high or very high risk, with dependency on non-Trade Agreement Act compliant suppliers, sourcing from China and India, or unknown.” Five percent of essential drugs in its supply were made from active ingredients from China, while another 22 percent were made from ingredients from countries it couldn’t identify. Senate.gov
Biosecurity Assessments for Emerging Transdisciplinary Biotechnologies: Revisiting Biodefense in an Age of Synthetic Biology
The Synthetic Biology Assessment Framework is likely sufficient to assess new science and technology advances affecting conventional biological agents. However, the framework may have limited applicability for risk assessment of technologies that are not usable with conventional biological agents and result in economic or broader national security concerns. Applied Biosafety
How to Improve Preparedness for the Next Pandemic
Since the end of the COVID-19 pandemic, there has been an unfortunate decline in policy interest in preparations for the next one. Congress has not acted to renew the federal Pandemic and All Hazards Preparedness Act (PAHPA), which expired in September. This leaves federal programs to promote such preparedness on autopilot, without necessary reforms. Congress should additionally require that HHS adopt preparedness performance standards that allow a fair and full evaluation of the expected effectiveness and cost-effectiveness of preparedness programs. The Hill
Research Funding is Needed to Support an Effective, Equitable, and Sustainable Public Health System
As pandemic emergency funding is largely rescinded or spent, the nation will likely return to the boom-and-bust pattern of funding increases during public health emergencies followed by a return to chronic underfunding. Health Affairs
SELECT AGENTS + PRIORITY PATHOGENS
COGR Response to Proposed Rulemaking on Possession, Use, and Transfer of Select Agents and Toxins
COGR is an association of over 200 public and private U.S. research universities and affiliated academic medical centers and research institutes. Their letters here and here express support for the removal of Brucella abortus, Brucella melitensis, and Brucella suis from the select agent list. Additional comments raise concerns about regulatory phrasing that is impractically ambiguous, and about unnecessary reporting that imposes significant administrative burdens. Council on Governmental Relations
Thailand Steps Up Border Control of Livestock After Anthrax Outbreak is Reported in Neighboring Laos
Thailand’s government has ordered officials to closely monitor livestock along the border with Laos after more than 50 people were reported to have contracted anthrax in the neighboring country. Media in Laos earlier this month reported livestock deaths and cases of people contracting the disease in the southern province of Champasak. AP
In Bangladesh, Nipah Virus Keeps the Health System on its Toes
As many as 341 Nipah cases have been detected in Bangladesh, with 242 deaths, since the first recorded outbreak in 2001. It’s an uncommonly deadly illness, killing between 40% and 100% of people infected in outbreaks that have spanned Bangladesh, India, Malaysia and Singapore. Patients typically start displaying symptoms between 4 and 14 days after exposure – though incubation periods as long as 45 days have been observed. Gavi
Mpox Cases in the U.S. on the Rise as Vaccination Rates Lag and New Threats Loom
Mpox cases in the United States are twice as high as they were at this time last year, and experts are stressing the importance of improving vaccination coverage as transmission risks rise. There have been 511 cases reported this year through March 16, compared with fewer than 300 cases by late March 2023. CNN
AVIAN INFLUENZA
Upper Respiratory Tract Disease in a Dog Infected by a Highly Pathogenic Avian A/H5N1 Virus
In summer 2023, during an outbreak of highly pathogenic avian influenza (HPAI) in cats in Poland, a dog presented to a veterinary clinic with persistent, debilitating, dry cough, submandibular lymphadenomegaly, mild serous nasal discharge, and left apical heart murmur. A preliminary diagnosis of kennel cough was made and the treatment with amoxicillin/clavulanic acid and dexamethasone was initiated. Due to the lack of improvement within 2 days, a blood check-up, thoracic radiography and ultrasonography, and echocardiography were performed. A rapid test for orthomyxovirus type A antigen in a throat swab was carried out and proved positive. The result was verified using RT-qPCR, which yielded a positive result for A/H5N1 influenza virus and negative results for A/H1N1, A/H3N2, type B influenza, and SARS-CoV-2. This case indicates that HPAI should be considered as a differential diagnosis not only in cats, but also in dogs with upper respiratory tract disease, particularly in regions experiencing A/H5N1 avian influenza outbreaks. Microorganisms
For the First Time, U.S. Dairy Cows Have Tested Positive for Bird Flu
Livestock at multiple dairy farms across the U.S. have tested positive for bird flu — also known as highly pathogenic avian influenza, or HPAI — in an outbreak that’s likely spread to at least five states. It’s the first time the disease has been found in dairy cattle, according to the American Veterinary Medical Association. The cases come just days after a group of young goats contracted bird flu on a Minnesota farm. NPR
CHEMICAL + RADIOLOGICAL THREATS
Initial Characterization of Novichok A-Series Agent A-234
The poisoning of a former Russian spy Sergei Skripal and his daughter in Salisbury, England, in March 2018 led to the inclusion of A-234 and other A-series agents into the Chemical Weapons Convention. Even though five years have already passed, there is still very little information on its chemical properties, biological activities, and treatment options with established antidotes. Archives of Toxicology
DEARE Characteristics, Mechanisms, Animal Models, and Promising Medical Countermeasures
Although relevant animal models have been developed in several species and four MCM for treatment of the acute radiation syndrome are now FDA-approved, animal models for the delayed effects of acute radiation exposure (DEARE) have only recently been developed, and there are no licensed MCM for DEARE. International Journal of Radiation Biology
Russian Chemical and Biological Weapons: Limiting the Effects of Russian CBW Programs on NATO Security Through 2035
This thesis demonstrates that Russian chemical and biological weapons programs have remained consistently in violation of international arms control agreements since the fall of the Soviet Union, that they hold the potential to cause damage to NATO member states, and that they are used in ways that affect both civil society and military formations. Missouri State
Keeping Soft Targets and Crowded Places Safe from Mass-Casualty Attacks
Soft targets and crowded places (ST-CPs) are easily accessible to large numbers of people and have limited security or protective measures in place, making them vulnerable to attack. Examples include sports arenas, shopping centers, schools, transportation systems, and houses of worship. Although attacks on them are relatively rare, they result in significant loss of life and contribute to an atmosphere of fear throughout society. Layered security strategies, in which measures work together, improve the chance that an attack will be prevented, halted, or mitigated. Tips from the public have prevented attacks. Funding for enhanced public education on what to report and how, and support for threat assessment teams are recommended. RAND
CBRN Threats – Advancing National Security Through Interdisciplinary Innovations
This article examines the effectiveness of radiological and nuclear (R&N) threat detection technologies. It assesses current methodologies, interdisciplinary approaches and their impact on national security. Zeszyty Naukowe SGSP
ONE HEALTH
Protect Habitat to Prevent Pandemics
Pandemics begin when disease-harboring animals, such as bats, come in close proximity with people, livestock or other animals and pass on new pathogens. An international team of 25 scientists led by a Cornell expert has proposed a roadmap for how to prevent the next pandemic by conserving natural areas and promoting biodiversity, thereby providing animals with enough food, safe havens and distance to limit contact and transfer of pathogens to humans. Cornell Chronicle
COVID-19 PANDEMIC
Trial Shows Increased SARS-CoV-2 Mutations, Delayed Viral Clearance with Molnupiravir Treatment
Molnupiravir is an EUA antiviral to treat mild-to-moderate COVID-19 in high-risk persons. Molnupiravir uses a mechanism commonly referred to as “error catastrophe” or “lethal mutagenesis,” an accumulation of mutations in the virus that eventually results in an inability to replicate; this differs from other drugs such as remdesivir or Paxlovid, which rapidly shut down RNA or protein synthesis to cease viral replication. Molnupiravir’s mutagenesis mechanism, coupled with lower effectiveness against severe disease outcomes in clinical trials data, has raised concerns about the drug’s potential to contribute to viral evolution during infection and hypothetical onward transmission of novel variants. COVID-19 Real-Time Learning Network
COVID-19 Vaccine Protects Against Multisystem Inflammatory Syndrome in Children
Although the incidence of MIS-C has decreased significantly since its initial recognition, the children most at risk for this serious, sometimes deadly, condition are those who have not received a COVID-19 vaccine. NEJM Journal Watch
HISTORICAL REFLECTIONS
How Bad Was the World’s First Pandemic?
Elites of the Pax Romana—the Roman Empire’s political and economic apex—had little reason to fear for the future of their world order. Rome of the mid-second century AD was a cosmopolis of over 1,000,000 souls, and capital of consumption. The end of this era, therefore, came as a shock to those who witnessed the Pax Romana’s sudden ruination. What exogenous shock knocked the Empire from its prosperous and peaceful pinnacle? In recent years, historians have zeroed in on an infectious outbreak known as the Antonine plague—an apparent pox-like disease that ravaged not just Rome, but several Roman cities during Marcus’ reign. Princeton University Press
SPECIAL INTEREST
Wanted: Your Input for the NIAID 2025-2029 Strategic Plan
The National Institute of Allergy and Infectious Diseases (NIAID) is updating its Strategic Plan, which will guide NIAID’s priorities over the next five years. Public comments are sought on a new Request for Information available for comment through May 27, 2024. Grants.gov
ALSO READING
Frontiers’ journals saw large scale retractions—where does that leave the publisher’s reputation with researchers? The BMJ
A dynamic ensemble model for short-term forecasting in pandemic situations. MedRxiv
What Is Former CDC Director Rochelle Walensky Doing Now? MedPage Today
Lipid nanoparticle-based inhibitors for sars-cov-2 host cell infection. International Journal of Nanomedicine
Tackling the outbreak of Nipah virus in Bangladesh amidst COVID-19. Health Science Reports
Rapid development of double-hit mRNA antibody cocktail against orthopoxviruses. Signal Transduction and Targeted Therapy