News highlights on health security threats and countermeasures curated by Global Biodefense
This week’s selections include reforming international legal frameworks for outbreak reporting; LRN monkeypox testing in the US; ISIS chemical weapons ambitions; and Chikungunya VLP vaccine development.
POLICY + GOVERNMENT
Increasing International Collaboration and Networking Among High-level Isolation Units and Programs
The global landscape of high-level isolation units (HLIUs), also referred to as special pathogens units or biocontainment patient care units, has evolved over the last several decades, in response to the increasing frequency of high-consequence infectious disease (HCID) outbreaks (eg, viral hemorrhagic fevers, monkeypox, Middle East respiratory syndrome). Increasingly, national health systems are recognizing the value of investing in such units for HCID preparedness and response, as evidenced by the establishment of additional HLIUs in the US, UK, Australia, and Malta, among others, in recent years. Health Security
Nominees to Lead PAHO Announced
The Pan American Health Organization (PAHO) will elect a new Director at the Pan American Sanitary Conference in late September. Speaking to The Lancet, the six nominees expressed a common desire for equitable access to health care, especially COVID-19 vaccines, action on the growing burden of non-communicable diseases, and a PAHO that is more attentive to the needs of smaller member states. By February 2022, Latin America accounted for 28% of globally registered deaths from COVID-19, despite being home to only 8.4% of the world’s population, according to WHO. The Lancet
Murky Data: Examining North Korea’s COVID-19 Reporting
After two years of claiming no confirmed COVID-19 cases, North Korea disclosed a nationwide outbreak on May 13 and began reporting detailed data on the scope and status of the outbreak. North Korea does not usually release much data on anything. The figures, especially the number of deaths reported, appear to run contrary to the global experience of COVID-19. The biggest mystery surrounds the announced number of reported deaths. As of June 21, that stood at 73 people, which is remarkably low for a COVID-19 outbreak that has hit 4.7 million people or roughly 18 percent of a completely unvaccinated population. At that level, the fatality rate is just 0.002 percent. 38 North
Russia Finds Another Stage for the Ukraine “Biolabs” Disinformation Show
Russia is building on its years-long misinformation campaign about a ‘US bioweapons program in Ukraine and other former Soviet republics’ to instigate a rarely used diplomatic procedure. The move to trigger Article V of the Biological Weapons Convention forces by accusing the US of having bioweapons labs on its borders is forces the treaty’s 184 member states to hold a special session this summer to hear the Russian allegations and the US response. Russia has already brought its assertions to the most prominent venue of international diplomacy, the United Nations Security Council. So far this year, the Council has met three times on supposed US bioweapons in formal and informal sessions. The UN, independent media, and outside experts have concluded that the Russian documentation of its claims carried no weight. Bulletin of the Atomic Scientists
International Law Reform for One Health Notifications
Epidemic risk assessment and response relies on rapid information sharing. Using examples from the past decade, experts here discuss the limitations of the present system for outbreak notifications, which suffers from ambiguous obligations, fragile incentives, and an overly narrow focus on human outbreaks. They examine existing international legal frameworks, and provide clarity on what a successful One Health approach to proposed international law reforms—including a pandemic treaty and amendments to the IHR—would require. The Lancet
Germany Prioritizes Biosecurity for Global Partnership
Germany plans to prioritize biological security during its year-long presidency of the Global Partnership Against the Proliferation of Weapons of Mass Destruction. He described an effort co-chaired by the United Kingdom and Canada that focuses on mitigating biological risks in Africa as a “key asset” that Germany will continue to prioritize, but also said that there is a need to “look at possible risks in other regions.” The Global Partnership is an initiative of the Group of Eight, now the Group of Seven (G7), industrialized nations. It was formed in 2002 to prevent terrorists from acquiring nuclear, chemical, and biological weapons. Arms Control Association
The COVID-19 Pandemic in Oceania: Health Policy Decisions Matter
This brief compares COVID-19 data across Pacific countries through the first week of June 2022. Data is drawn from regional reports from the World Health Organization (WHO), which has monitored the pandemic in Oceania since early March 2020, and situation reports on US-affiliated Pacific Islands compiled by the Pacific Islanders Health Organization Associations (PIHOA). These reports articulate a disparate range of pandemic experiences across Pacific Island countries and territories (PICTs), in terms of COVID 19 community transmission, cases, mortality, and vaccination rates.
Comparing vaccination rates in the Northern Pacific, PICTs that have completed-vaccination rates of greater than 85%, are Guam, the Commonwealth of the Northern Mariana Islands, Palau, and American Samoa. These locations were still associated with significant COVID-19 community transmission rates and moderate mortality rates. East-West Center
MEDICAL COUNTERMEASURES
Emergent Inks Deal to Manufacture and Sell Ridgeback’s Ebola Drug in the US
A partnership between the U.S. government’s Biomedical Advanced Research and Development Authority (BARDA) and Ridgeback Biotherapeutics helped secure an FDA approval for Ebola treatment Ebanga back in December of 2020. Now, in an effort to expand access to the drug, Ridgeback and the government have turned to a familiar manufacturing partner—Emergent BioSolutions. Thursday, Emergent revealed that it will be responsible for the manufacture, sale and distribution of Ebanga in the U.S. and Canada. Fierce Pharma
Doctors are Clamoring for More Clarity on Paxlovid Prescribing Amid Covid-19 Rebound Concerns
Many providers and their colleagues aren’t on the same page about when to prescribe Paxlovid or the criteria that separates those who need it from those who do not. They also said it is unclear whether they can give a second course when patients test positive again after taking Paxlovid, a phenomenon known as a rebound. The pool of people who can prescribe Paxlovid is now even broader — on Wednesday, the FDA began allowing pharmacists to prescribe the drug. STAT
Identification of Potent Inhibitors of Arenavirus and SARS-Cov-2 Exoribonucleases by Fluorescence Polarization Assay
Researchers present a convenient method using fluorescence polarization (FP) to assess the ExoN activity and its inhibition in 384-well plates. The activity was used to screen a focused library of 113 metal chelators against SARS-CoV-2, Lymphocytic Choriomeningitis and Machupo viruses. Antiviral Research
Potential of Favipiravir as an Antiviral Against Junin Virus
Favipiravir is a nucleoside analogue that inhibits the replication and transcription of a broad spectrum of RNA viruses, including pathogenic arenaviruses. In this study, we isolated a favipiravir-resistant mutant of Junin virus (JUNV), which is the causative agent of Argentine hemorrhagic fever, and analyzed the antiviral mechanism of favipiravir against JUNV. Findings showed that treatment with a combination of favipiravir and either ribavirin or remdesivir inhibited JUNV replication in a synergistic manner, blocking the generation of the drug-resistant mutant — providing new insights for the clinical management and treatment of Argentine hemorrhagic fever. PLOS Pathogens
Safety And Immunogenicity of an Aluminium Hydroxide-Adjuvanted Chikungunya Virus-Like Particle Vaccine
This randomised, double-blind, parallel-group, phase 2 trial was conducted at three clinical trial centres in the USA. Eligible participants were healthy CHIKV-naïve adults aged 18–45 years. PXVX0317 was well tolerated and induced a robust and durable serum neutralising antibody immune response against CHIKV up to 2 years. A single 40 μg injection of adjuvanted PXVX0317 is being further investigated in phase 3 clinical trials. The Lancet Infectious Diseases
BIOSECURITY + BIOPREPAREDNESS
The Monkeypox Vaccine Underscores the Value of U.S. Investments in Preparedness
The U.S.’s investment in smallpox countermeasures, oft criticized, was prescient. Not only can the new vaccine be used to fight smallpox, but it also provides a platform for fighting other pathogens. Part of the technology behind Jynneos is a key component of a vaccine created to confront the Ebola crisis in 2014. And when the FDA approved this vaccine for use in the U.S., the approval included use against monkeypox. Jynneos is currently the only vaccine in the world approved for vaccination against monkeypox. Jynneos uses a live virus that Bavarian Nordic modified so it cannot replicate in the body. This means that it still produces a potent immune response but has a strong safety profile. Clinical trials and studies of the vaccine in the elderly, people with HIV, eczema, and other immunocompromised populations have all demonstrated the vaccine’s safety. STAT
The U.S. May Be Losing the Fight Against Monkeypox, Scientists Say
The first cases of monkeypox were reported in May, but tests will not be readily available until sometime this month. Vaccines will be in short supply for months longer. There are already at least 700 cases in the United States, but experts say the real number is likely to be much higher. Surveillance is spotty at best. State and county-level health departments often set their own rules and priorities, sometimes at odds with federal guidance. “The machine is just so ossified,” said Gregg Gonsalves, an activist and epidemiologist at the Yale School of Public Health. The “house is on fire, and it’s like everything is moving at sort of normal speed.” Many confirmed patients cannot identify the source of their infections, suggesting that there is significant community transmission. New York Times
Survey Results Highlight Veterinary Vaccinology Gaps, Priorities and Barriers
UKRI-BBSRC surveyed the veterinary vaccinology community to rate the importance of research and innovation gaps within different fields of veterinary vaccinology. Gaps identified included the need to discover and validate new adjuvants, and to incorporate tools such as bioinformatics with wet lab work to assist in veterinary vaccine research and development. The report highlighted the importance of partnering with industry as well as maintaining sustainable and open access to immunological tools and associated databases. International Veterinary Vaccinology
The Evolution of the National Special Pathogen System of Care
Through the Hospital Preparedness Program, within the HHS/ASPR, a nationwide Regional Ebola Treatment Network (RETN) was developed, building upon a state- and jurisdiction-based tiered hospital approach. This network, spearheaded by the National Emerging Special Pathogens Training and Education Center, developed a conceptual framework and plan for the evolution of the RETN into the National Special Pathogen System of Care (NSPS). The NSPS is an ambitious but critical effort that will have impacts for years to come. Special pathogens will continue to emerge, and new infrastructure and treatments will be needed to mitigate their impact. As such, mitigation efforts will not be possible without a coordinated plan that addresses healthcare system needs, gaps, and capabilities and carefully considers how public and private stakeholders can collaborate and maximize resources to ensure an effective and equitable system of care. Health Security
SELECT AGENTS + PRIORITY PATHOGENS
Rapid Diagnostic Testing for Response to the Monkeypox Outbreak — Laboratory Response Network, United States, May 17–June 30, 2022
To effectively respond to a potential Orthopoxvirus outbreak, CDC and the Laboratory Response Network (LRN) worked to design, develop, and validate an assay to detect non-variola Orthopoxviruses (NVOs), such as Vaccinia, Cowpox, Monkeypox, and Ectromelia viruses. The NVO assay first received 510(k) clearance by FDA in 2005 and was cleared again in 2018 to update the labeling and use of reagents. The NVO assay does not differentiate Monkeypox virus from other Orthopoxviruses. Prior to the current monkeypox outbreak, the NVO assay has been used to detect cases of Vaccinia virus infection associated with vaccination and two imported cases of monkeypox from travelers in 2021.
Nationwide, 68 LRN laboratories had capacity to test approximately 8,000 NVO tests per week during June. During May 17–June 30, LRN laboratories tested 2,009 specimens from suspected monkeypox cases. Among those, 730 (36.3%) specimens from 395 patients were positive for NVO. NVO-positive specimens from 159 persons were confirmed by CDC to be monkeypox; final characterization is pending for 236.
CDC and LRN are supporting five large commercial laboratories with a national footprint (Aegis Science, LabCorp, Mayo Clinic Laboratories, Quest Diagnostics, and Sonic Healthcare) to establish NVO testing capacity of 10,000 specimens per week per laboratory. On July 6, 2022, the first commercial laboratory began accepting specimens for NVO testing based on clinician orders.
The CDC Monkeypox virus testing algorithm includes NVO testing, and if results are positive for Orthopoxvirus, further characterization testing at CDC. A subset of specimens was characterized at CDC by a Monkeypox virus specific real-time PCR assay and genetic sequencing. Because monkeypox disease has been rare in the United States, CDC’s NVO assay is the only FDA 510(k)–cleared assay to detect NVO; at the onset of this outbreak, use of the assay was limited to LRN laboratories. MMWR
Ghana Prepares for Possible First-Ever Marburg Virus Outbreak
Preliminary findings of two Marburg virus cases (both of which have died) have prompted Ghana to prepare for a potential outbreak of the disease. If confirmed, these would the first such infections recorded in the country, and only the second in West Africa. Marburg is a highly infectious viral haemorrhagic fever in the same family as the more well-known Ebola virus disease. UN News
Has Epizootic Become Enzootic? Evidence for a Fundamental Change in the Infection Dynamics of Highly Pathogenic Avian Influenza in Europe
Phylogenetic evidence from the recent resurgence of high-pathogenicity avian influenza (HPAI) virus subtype H5N1, clade 2.3.4.4b, observed in European wild birds and poultry since October 2021, suggests at least two different and distinct reservoirs. We propose contrasting hypotheses for this emergence: (i) resident viruses have been maintained, presumably in wild birds, in northern Europe throughout the summer of 2021 to cause some of the outbreaks that are part of the most recent autumn/winter 2021 epizootic, or (ii) further virus variants were reintroduced by migratory birds, and these two sources of reintroduction have driven the HPAI resurgence. The evidence of enzootic HPAI virus circulation during the summer of 2021 indicates a possible paradigm shift in the epidemiology of HPAI in Europe. mBio
Lassa Virus Infection: A Summary for Clinicians
This summary on Lassa virus (LASV) infection was developed to provide clinicians with a condensed, accessible understanding of the current literature. The information provided highlights pathogenesis, clinical features, and diagnostics emphasizing therapies and vaccines that have demonstrated potential value for use in clinical or research environments. Two antiviral medications with potential benefit for the treatment of LASV infection and 1 for post-exposure prophylaxis were identified, although a larger number of therapeutic candidates are currently being evaluated. Multiple vaccine platforms are in pre-clinical development for LASV prevention. International Journal of Infectious Diseases
Understanding Sabiá Virus Infections (Brazilian mammarenavirus)
Although exceedingly rare, Brazilian mammarenavirus infection is an etiology for acute hemorrhagic fever syndrome. The two fatal cases here had peculiar histopathological findings not previously described. Patients presented with hepatitis, bleeding and neurological alterations. Both patients died. Autopsies uncovered unique features on electron microscopy, such as hepatocyte “pinewood knot” lesions. Contact tracing was conducted for twenty-nine hospital contacts which were evaluated clinically and by RT-PCR and neutralizing antibodies. Although previous reports with similar New-World arenavirus had nosocomial transmission, none were identified here by contact tracing. Travel Medicine and Infectious Diseases
Crimean-Congo Haemorrhagic Fever During the COVID-19 Pandemic in Africa: Efforts, Recommendations and Challenges at Hand
CCHF is endemic in Africa with a 40% case fatality rate. Since the start of the COVID-19 pandemic, CCHF is on the long list of other diseases that have been neglected. CCHF has many unique symptoms that can help clinically differentiate between a COVID-19 infection. Employment history plays a major factor as well with people working in the cattle sector, such as agricultural laborers, slaughterhouse employees, and veterinarians, at a higher risk of contracting CCHF. A week after initial symptoms, the clinical difference becomes much clearer with the increased risk of bleeding in patients with CCHF infections which does not occur in COVID-19 infections. African Journal of Emergency Medicine
CHEMICAL + RADIOLOGICAL THREATS
Adding Novichok Nerve Agents to the CWC Annex on Chemicals: A Technical Fix and Its Implications for the Chemical Weapons Prohibition Regime
Against the background of the cases where nerve agents have been used for political assassination, the report concludes with a discussion of implications of the schedule amendments for compliance with, and implementation of, the chemical weapons prohibition regime. In particular, it highlights the limitations inherent in list-based approaches for the operationalisation of a generic prohibition, such as the one contained in the CWC. The report also recommends that CWC states parties consider a re-affirmation and clarification of the CWC’s general-purpose criterion in the context of the Fifth CWC Review Conference in May 2023. UNIDIR
ISIS Planned Chemical Attacks in Europe, New Details on Weapons Program Reveal
That the Islamic State had manufactured small quantities of chemical weapons has been previously reported. The terrorist group used chlorine and mustard gas against Kurdish and Iraqi forces nearly two dozen times, from early 2015 until the liberation of the Iraqi city of Mosul two years later. But new insights are emerging on a concerted effort by Islamic State actors aimed at building the biggest arsenal of chemical and, potentially, biological weapons ever assembled by a terrorist group. Several current and former U.S. officials in interviews with The Post spoke for the first time in detail about an urgently planned military operation, conducted in 2015 by U.S. Special Operations forces with assistance from Kurdish Peshmerga operatives, to kill Salih al-Sabawi (a Russian-trained engineer who had once helped Saddam Hussein build an extensive arsenal of chemical weapons) and crush the weapons program before it reached maturity. Washington Post
SURVEILLANCE + DETECTION
Wastewater-Based Detection of Two Influenza Outbreaks
Here researchers quantified influenza A virus (IAV) RNA in wastewater during two active outbreaks on university campuses (University of Michigan and Stanford) during different times of year using case data from an outbreak investigation and high-quality surveillance data from student athletes. In both cases, the IAV RNA concentrations were strongly associated with reported IAV incidence rates. Furthermore, the RNA concentrations reflected outbreak patterns and magnitudes. The results demonstrate that wastewater surveillance can effectively detect influenza outbreaks and will therefore be a valuable supplement to traditional forms of influenza surveillance. Environmental Science & Technology Letters
WildHealthNet: Supporting the Development of Sustainable Wildlife Health Surveillance Networks in Southeast Asia
Wildlife and wildlife interfaces with people and livestock are essential surveillance targets to monitor emergent or endemic pathogens or new threats affecting wildlife, livestock, and human health. However, limitations of previous investments have resulted in a neglect of wildlife health surveillance (WHS) systems at national and global scales, particularly in lower and middle income countries (LMICs). Here researchers demonstrate the implementation of a locally-driven multi-pronged One Health approach to establishing wildlife health surveillance in Cambodia, Lao PDR and Viet Nam under the WildHealthNet initiative. Surveillance activities detected outbreaks of H5N1 highly pathogenic avian influenza in wild birds, African swine fever in wild boar, Lumpy skin disease in banteng, and other endemic zoonotic pathogens identified as surveillance priorities by local stakeholders. SSRN pre-print
Impact of African Swine Fever Virus Detergent Inactivation on Biomarkers in Serum and Saliva Samples
As reliable protocols are often established in laboratories with lower biosafety, the reliable inactivation of ASFV samples which preserve biomarkers for downstream analysis is crucial. Three different inactivation protocols were employed (NP-40, Triton-X-100 and 95C heating). All samples treated with 0.5% (v/v) concentration of both detergents showed an absence of virus infectivity. The same was true for heated samples. However, heated serum was not suitable for analyses. While all protocols had an impact on the detection of biomarkers, correlation was retained. In particular, NP-40 may be the desired detergent for more accurate measurements while achieving efficient virus inactivation. Pathogens
Development of a Duplex Insulated Isothermal PCR Assay for Rapid On-Site Detection and Differentiation of Genotypes 1 and 2 of African Swine Fever Virus
Genotype II African swine fever virus (ASFV) has been plaguing Asian pig industry since 2018. Recently, genotype I ASFV was reported for the first time in China. Since there is no commercial vaccine available against ASFV, early onsite detection and quick culling procedures are commonly used by many countries all over the world. It is important that the above two genotypes of ASFV could be quickly differentiated during onsite detection at the same time. this study, we established a sensitive and simple Fluorescent Probe Hydrolysis-Insulated isothermal PCR (iiPCR) that can detect and differentiate two genotypes of ASFV within 40 minutes. Frontiers in Cellular and Infection Microbiology
Clinical Evaluation of the Biofire Global Fever Panel for Identification of Malaria, Leptospirosis, Chikungunya, and Dengue from Whole Blood
Assays that can diagnose a variety of common pathogens in blood could help to establish a diagnosis for targeted disease management. This paper evaluates the performance of the BioFire Global Fever Panel (GF Panel), a multiplex nucleic acid amplification test performed on whole blood specimens in the diagnosis of several pathogens that cause acute febrile illness. The Lancet Infectious Diseases
Before You Go: A Packing List for Portable DNA Sequencing of Microbiomes and Metagenomes
A field lab will rarely match the standards of a clean lab. However, some basic precautions can reduce the impact of contamination. As standard, aerosol-resistant filter tips and gloves should be used, and with good aseptic technique. Working into a fresh breeze outdoors can reduce the likelihood of airborne contaminants for sensitive steps. Sample bags can provide a sterile working surface if cut open, and household bleach can be diluted to provide a decontamination solution. Chlorine-based water disinfection tablets provide a travel-friendly way to prepare a decontamination solution once at the destination. Site-specific consideration needs to be given for the safe storage, transport, or disposal of waste reagents and plasticware. Given the ad hoc nature of these measures, the normal emphasis on sequencing negative controls to detect contaminants is reinforced. Microbiology Research
COVID-19 Public Transportation Air Circulation and Virus Mitigation Study
Various technologies (including positive pressure environment inside the cabin, HEPA filters with different MERV ratings, concentrated UV exposure with charged carbon filters in the HVAC systems, center point photocatalytic oxidation technology, ionization, and surface antiviral agents) were tested to evaluate the potential of mitigating COVID-19 infections via air and surfaces in public transportation. The effectiveness of these technologies on three live viruses was tested in both the lab and in buses in the field. Mineta Transportation Institute
Community Acceptability of Dengue Fever Surveillance Using Unmanned Aerial Vehicles
A cross-sectional study was conducted in Malaysia, Mexico, and Turkey to assess knowledge of diseases caused by Aedes mosquitoes, perceptions about drone use for data collection, and acceptance of drones for Aedes mosquito surveillance around homes. Compared with people living in Turkey, Mexicans had 14.3 (p < 0.0001) times higher odds and Malaysians had 4.0 (p = 0.7030) times the odds of being willing to download a mosquito surveillance app. Compared to urban dwellers, rural dwellers had 1.56 times the odds of being willing to be trained. The authors conclude there is widespread community support for drone use in mosquito surveillance and this community buy-in suggests a potential for success in mosquito surveillance using drones. Travel Medicine and Infectious Disease
Also Reading:
WHO BioHub System Biosafety and Biosecurity: Criteria and Operational Modalities World Health Organization
Phylogenomic Characterization of Historic Lumpy Skin Disease Virus Isolates from South Africa. Archives of Virology
Implementation of a Comprehensive Testing Protocol for a Rapidly Manufactured Mechanical Ventilator. Open Respiratory Archives
Susceptibility of Domestic Pigs to Experimental Infection with Ebolaviruses. ProQuest
Highly Pathogenic Avian Influenza (HPAI H5Nx, Clade 2.3.4.4.b) in Poultry and Wild Birds in Sweden: Synopsis of the 2020–2021 Season. Veterinary Sciences
AuNP-based biosensors for the diagnosis of pathogenic human coronaviruses: COVID-19 pandemic developments. Analytical and Bioanalytical Chemistry
An experimental approach of an in vivo pathogen genome targeting strategy to generate African swine fever resistant pigs. University of Veterinary Medicine Hannover
In Silico Analyses of the Role of Codon Usage at the Hemagglutinin Cleavage Site in Highly Pathogenic Avian Influenza Genesis. Viruses
Harmonizing the COVID-19 sample biobanks: Barriers and opportunities for standards, best practices and networks. Biosafety and Health
Are pigs overestimated as a source of zoonotic influenza viruses? Porcine Health Management
Addressing biohazards to food security in primary production. Food Security