News highlights on health security threats and countermeasures curated by Global Biodefense
This week’s selections include aircraft wastewater surveillance; organ-on-a-chip for medical countermeasure development; aerosolized COVID-19 vaccine Phase 3 trial in China; and the critical need for Congress to fund the Bio-Preparedness Workforce Pilot Program.
POLICY + GOVERNMENT
Infectious Diseases Specialists are Critical to the Health Preparedness Workforce But Need Support
Nearly 80% of U.S. counties don’t have a single ID physician, and the majority of communities, especially in rural areas, have little or no access to ID experts. The Bio-Preparedness Workforce Pilot Program was passed into law in 2022 as part of the PREVENT Pandemics Act, but still needs to be funded by the Senate and House Appropriations committees. The pilot will create a new loan repayment program for infectious diseases and emergency preparedness health care professionals who work in health professional shortage areas, medically underserved communities, federal health facilities (e.g., VA clinics or medical centers) or Ryan White-funded clinics. IDSA
USDA Provides Additional $502 Million For Highly Pathogenic Avian Influenza
The U.S. Department of Agriculture is providing $502 million under the Animal Health Protection Act to the Animal and Plant Health Inspection Service (APHIS) to prepare for potential additional detections of highly pathogenic avian influenza (HPAI) in the US. Previously, USDA has invested more than $793 million in emergency funding to respond to this outbreak by implementing quarantine restrictions, depopulating affected flocks, disposing of depopulated birds, cleaning and eliminating the virus from affected premises, and conducting surveillance in surrounding areas. APHIS
Global ‘Pandemic Treaty’: Nations Wrestle With How to Fairly Share Virus Data
Last week, negotiators met to discuss the latest draft of a ‘pandemic treaty’ — an agreement among countries worldwide about how to best respond to the next massive outbreak. One sticking point in the draft is how to fairly compensate countries for sharing viral-genome sequences. Researchers say a plan is needed to ensure countries aren’t being exploited, if the world is to prevent the next pandemic. Nature
House GOP Inquiry Over Gain-of-Function Research Targets a Scientific Giant
Last year, in an interview with Science, legacy NIAID scientist Bernie Moss said he planned to try to determine why one strain of mpox viruses, known as Clade 1, is so much more virulent than those in a second strain, Clade 2, by taking genes from the former and putting them into the latter. Clade 2 viruses are responsible for the ongoing mpox outbreak first detected in May 2022. Though the NIAID says Moss never actually conducted the work, his public expression of interest in research that might be seen as a so-called gain-of-function study appears to have been catnip to Republicans on the House Energy and Commerce Committee. STAT
U.S. Must Strengthen Biodefense, Reauthorize Laws
The Government Accountability Office published in March their snapshot report, “Biodefense: Actions Needed to Address Long Standing Challenges.” The GAO’s original report published in 2021 had 29 recommendations, but 21 remain unimplemented. The nation is still dragging its feet and — in some cases — reversing efforts already made to prepare for the next pandemic. National Defense
How the Pandemic Fund Can Strategically Invest in Pandemic Preparedness
The Pandemic Fund should strategically invest in pandemic preparedness, including for its first call for proposals for surveillance, laboratories, and human resources. This strategic approach should consider both ex ante and ex post considerations of investments for pandemic preparedness. Center for Global Development
Senate Committee Approves FY24 Agriculture Appropriations Bill
The U.S. Senate Committee on Appropriations on 22 June approved the FY2024 Agriculture, Rural Development, Food and Drug Administration, and Related Agencies Appropriations Act in a bipartisan vote of 28-0. The bill includes $ 1.171 billion for the USDA Animal and Plant Health Inspection Service (APHIS), an increase of more than $14 million above the FY23 enacted level. The funding will help protect the nation’s animal and plant resources from diseases and pests such as chronic wasting disease, African swine fever, and avian influenza. The USDA Food Safety and Inspection Service (FSIS) was allocated $1.205 billion for the safety and productivity of the nation’s $186 billion meat and poultry industry by supporting nearly 8,000 frontline inspection personnel for meat, poultry, and egg products at more than 6,800 facilities in the U.S. Senate Committee on Appropriations
Former Prime Minister Tells COVID Inquiry UK Erred in Focusing Too Much on Threat of a Flu Pandemic
Britain made a mistake in focusing too much on preparations for a flu pandemic rather than considering other types of pandemic in the years before the COVID-19 outbreak, former Prime Minister David Cameron told a public inquiry Monday. “So much time was spent on a pandemic influenza and that was seen as the greatest danger,” Cameron said. He said his government did look at other pandemics, including MERS and SARS. But he added: “I think the failing was not to ask more questions about asymptomatic transmission, highly infectious … what turned out to be the pandemic we had.” The official inquiry, led by a retired judge, is set to take three years to complete. Former Prime Minister Boris Johnson, who led the U.K. during the pandemic, agreed in late 2021 to hold the probe after heavy pressure from bereaved families. Many other senior politicians are expected to be called to face questions. Seattle Times
Republicans Rehash Vaccine Mandate Policies in NDAA Amendments
Several Republican House lawmakers are trying to force the Pentagon to allow troops who were separated for refusing the COVID-19 vaccine to rejoin the service, get back pay, and avoid other usual consequences of refusing a lawful order. During the House Armed Services Committee markup for the 2024 NDAA, a handful of Republican lawmakers introduced several COVID-19 vaccine-related amendments, hammering home the Republican position that the vaccine should have been a choice, and the DOD’s mandate hurt troops who had religious or moral reasons for refusing the vaccine. Rep. Adam Smith, D-Wash. the ranking member of the House Armed Services Committee, objected to an amendment disallowing any form adverse actions for those who refused the vaccine, saying it and others like it set a “really dangerous precedent” for the committee, because they tell troops they have the option to refuse a lawful order. “Also, now that we have lifted that requirement as the pandemic has passed, the secretary of defense and the Department of Defense is going through a process of reinstating some of these members. I don’t think we should be dictating what that process is.” Defense One
U.S. Intelligence Report Finds No Clear Evidence of Covid Origins in Wuhan Lab
The Office of the Director of National Intelligence released a long-awaited declassified report, which included spy agencies’ findings on the so-called lab leak theory, but the material is unlikely to satisfy many people who have been wrestling with the unanswered questions on the origins of the Covid outbreak. “The I.C. has no information, however, indicating that any W.I.V. genetic engineering work has involved SARS-CoV-2, a close progenitor, or a backbone virus that is closely related enough to have been the source of the pandemic.” New York Times
‘Ridiculous,’ Says Chinese Scientist Accused of Being Pandemic’s Patient Zero
“The recent news about so-called ‘patient zero’ in WIV are absolutely rumors and ridiculous,” Ben Hu emailed Science in his first public response to the charges, which have been attributed to anonymous former and current U.S. Department of State officials. A WIV colleague who has also been named as one of the first COVID-19 cases denies the accusation as well. She wrote in an email that Hu, Yu, and Zhu “worked on genome sequencing based on extract RNA and never worked on live virus.” She also said that everyone in the lab received a COVID-19 antibody test on 3 March 2020 and no one had evidence of having been infected. “All the allegations about the lab-associated accident of COVID-19 are wrong…The prevalence of lab-leak conspiracy is harmful for us to get further funding to continue our research on zoonosis, which is the major threat to the public health in the future.” Science
MEDICAL COUNTERMEASURES
Developing Vaccines to Improve Preparedness for Filovirus Outbreaks: The Perspective of BARDA
Outbreaks of viral hemorrhagic fever caused by filoviruses have become more prevalent in recent years, with outbreaks of Ebola virus (EBOV), Sudan virus (SUDV), and Marburg virus (MARV) all occurring in 2022 and 2023. While licensed vaccines are now available for EBOV, vaccine candidates for SUDV and MARV are all in preclinical or early clinical development phases. During the recent outbreak of SUDV virus disease, the Biomedical Advanced Research and Development Authority (BARDA), as part of the Administration for Strategic Preparedness and Response within the U.S. Department of Health and Human Services, implemented key actions with our existing partners to advance preparedness and enable rapid response to the outbreak, while also aligning with global partners involved in the implementation of clinical trials in an outbreak setting. Partnerships among government investors and subject-matter experts, global stakeholders, and product sponsors will be essential to advance SUDV and MARV vaccines to licensure. Vaccines
Pulmonary Expression of Interleukin-17 Contributes to Neutrophil Infiltration Into the Lungs During Pneumonic Plague
Inhalation of respiratory droplets infected with Yersinia pestis results in a rapidly progressing and lethal necrotic pneumonia called primary pneumonic plague. This work indicates that IL-17 is a critical cytokine, the expression of which contributes to the biphasic progression of pneumonic plague. Targeting IL-17 in tandem with antibiotic therapy may aid in treating late-stage pneumonic plague or pneumonia caused by other agents in which IL-17-driven neutrophil infiltration in the airways contributes to pathogenesis. Infection and Immunity
Soldier-on-a-Chip: Interrogating Effects of Chemical and Biological Threat Agent Exposure Using a Multi-Organ Microphysiological System
Micro-physiological systems (MPS) technology offers a high throughput process that overcomes the drawbacks to both conventional in vitro and animal modeling by supplying cutting edge Organs-on-a-chip (OOC) that imitate human tissue-tissue interfaces, chemical and mechanical microenvironments specific to living human organs. This is a slide deck from the U.S. Army DEVCOM Chemical Biological Center. NIEHS
MERS-CoV RBD-mRNA Vaccine Induces Potent and Broadly Neutralizing Antibodies
Middle East respiratory syndrome coronavirus (MERS-CoV) continues to post a threat to human health. Most of the current vaccines for MERS are in preclinical development, and are based on recombinant proteins, nanoparticles, DNA, or viral vectors. Here researchers designed an effective mRNA vaccine encoding the RBD of MERS-CoV S protein (RBD-mRNA) and evaluated its immunogenicity and protective efficacy in a mouse model. Virus Research
Quadrivalent mRNA Seasonal Influenza Vaccine Safety and Immunogenicity Phase 1/2 Clinical Trial
Interim analysis findings from 2 parts of a phase 1/2, first-in-human clinical trial on the safety and immunogenicity of an investigational mRNA-based quadrivalent vaccine against seasonal influenza (mRNA-1010) in healthy adults ≥18 years. The placebo-controlled Part 1 of this study showed that a single dose of mRNA-1010 (50 µg, 100 µg, or 200 µg) elicited HAI antibodies against vaccine-matched strains at 28 days after vaccination in both younger and older healthy adults. Based on the comparable immunogenicity across the mRNA-1010 dose levels in Part 1, a lower dose level range of mRNA-1010 (25 µg, 50 µg, or 100 µg) was evaluated in a larger number of participants in Part 2. Findings in Part 2 suggest that mRNA-1010 could elicit higher immunogenicity than a standard-dose influenza vaccine for influenza A strains and comparable immunogenicity for influenza B strains in medically stable adults. Higher responses for influenza A strains remain important, as the A/H3N2 strain in particular causes a larger burden of severe outcomes in older adults, thus raising the potential for mRNA-1010 to further address this burden in vulnerable age groups. In both parts of the trial, no treatment-related SAEs were reported, nor any safety concerns identified. Nature Communications
Chimeric Vaccine Design Against Langya Henipavirus Using Immunoinformatics and Validation Via Immune Simulation Approaches
In July 2022, a new virus called Langya virus (LayV) was discovered in China in patients who had a fever. This Henipavirus (HNV) is closely linked to Hendra and Nipah viruses and is considered a potential threat as it could spread from animals to humans. This study employs various immunoinformatics methods to predict B cell, HTL and T cell epitopes from the LayV proteome in order to find the most promising candidate for a LayV vaccine. Heliyon
Identification of Tecovirimat Resistance-Associated Mutations in Human Monkeypox Virus
Tecovirimat (also known as TPOXX) is a drug available for the treatment of mpox through the CDC’s Expanded Access Investigational New Drug “compassionate use” protocol. In Los Angeles County, a fatal case of mpox with tecovirimat resistance was previously reported. Epidemiological surveillance in LA County has since identified additional cases of severe mpox that did not improve after multiple rounds of tecovirimat treatment, including one involving a person who succumbed to infection. The identified cases involved host immunodeficiency due to advanced HIV infection. Antimicrobial Agents and Chemotherapy
Newly Designed Poxviral Promoters to Improve Immunogenicity and Efficacy of MVA-NP Candidate Vaccines against Lethal Influenza Virus Infection in Mice
Here researchers generated and characterized recombinant Modified Vaccinia virus Ankara (MVA) candidate vaccines that deliver the highly conserved internal nucleoprotein (NP) of Influenza A viruses (IAV) under the transcriptional control of five newly designed chimeric poxviral promoters to further increase the immunogenic properties of the recombinant viruses (MVA-NP). Infections of avian cell cultures with the recombinant MVA-NPs demonstrated efficient synthesis of the IAV-NP which was expressed under the control of the five new promoters. Further studies are warranted to evaluate the immunogenicity and efficacy of these recombinant MVA-NP vaccines in other IAV challenge models in more detail. Pathogens
Potential Cross-Species Transmission of HPAI H5 Viruses to Humans Calls
Recently, Highly Pathogenic Avian Influenza H5 Subtype (HPAI H5) has caused more sporadic cases, or even outbreaks, in mammals, including minks, otters, foxes, and sea lions. With possible further mutations in avian and mammalian species, HPAI H5 has a strong potential to cause human infection and trigger a global pandemic. Therefore, it is essential to develop an H5-specific vaccine, as well as a universal influenza vaccine, to fully cover a broad range of influenza strains. Cell Discovery
BIOSECURITY + BIOPREPAREDNESS
Are Public Health Agencies Ready, or Just Prepared?
Perhaps it is time to retire the term. As the COVID-19 pandemic emergency declaration sunsets and officials review their various public health actions, it may be time to collectively take the initiative to retire the term ‘public health preparedness’ and replace it with ‘public health readiness’. Readiness takes into account all of the previous elements that the preparedness grants encompassed but also includes other areas that COVID-19 has shown to be lacking, including supply chain management, a stronger relationship with emergency management, and an organization-wide commitment to public health emergency response. The CDC is thinking along these lines as an element of the next five-year cooperative agreement cycle with state health departments. Domestic Preparedness
The Livestock Veterinarian Shortage: Implications for Food Safety and Security
Veterinarians involved in food supply veterinary medicine serve on the frontlines for infectious disease surveillance, including for emerging zoonotic diseases, and through this, contribute to national and global health security. Over the last several decades, the number of food animal veterinarians has decreased
dramatically in the United States. This trend endangers public health by increasing our vulnerability to zoonoses, compromising food safety, and threatening food security. Poor preventive care and infection control in livestock also leads to the misuse and overuse of antibiotics. The problem is projected to worsen in the coming years, especially in rural communities. Johns Hopkins Center for a Livable Future
The Role of Reusable Respiratory Protection Among Ambulance Companies
This case report highlights a full-service ambulance company’s experience with procuring and implementing NIOSH approved elastomeric half-mask respirators (EHMRs) at its Michigan headquarters location. After management discussed the decision to fit test first responders to EHMRs, the company decided to share feedback on how the company managed to maintain its EHMR program after N95 FFR supplies stabilized, and other lessons learned for those considering reusable respirators at their workplace. JEMS
SELECT AGENTS + PRIORITY PATHOGENS
Will ‘Langya’ Cause the Next Pandemic?
Langya is most closely related to the Mòjiāng virus, which presents with symptoms startlingly similar to those of the initial COVID-19, according to the authors. Langya and Mòjiāng are known to cause severe pneumonia. And Mòjiāng tends to cause ground-glass opacities on lung X-ray in those infected, as well as the often-fatal severe acute respiratory distress syndrome (ARDS). The Mòjiāng virus was discovered in 2012, when it reportedly sickened six miners and killed three who had contact with bats in the Tongguan mineshaft in Mòjiāng, China. Fortune
Ebola Outbreak Detection and Response Since 2013
Since 2013, 12 outbreaks caused by an Ebola virus have been reported. Collectively, these 12 outbreaks have shown that along with rapid outbreak detection, early containment of Ebola virus outbreaks depends on successful and rapid identification, isolation, and treatment of cases, contact tracing, implementation of appropriate infection prevention-and-control measures in health facilities, safe and dignified burials, engagement with affected communities, and, when possible, timely use of vaccines. All of these elements are crucial for ending an Ebola virus outbreak. The Lancet Microbe
Brazil Reports Fatal H1N1v Flu Case
Brazilian health officials have reported a fatal swine-origin variant H1N1 (H1N1v) case to the World Health Organization (WHO), which the group says is part of a sporadic pattern with the virus in the country, with no evidence of human-to-human spread. The patient is a 42-year-old woman with underlying health conditions died from her infection on May 5. Investigators found that the woman lived near a swine farm, though she had no direct contact with the animals. CIDRAP
What Providers Need to Know About Zoonotic Influenza
The CDC’s Clinician Outreach and Communication Activity (COCA) video webinar on What Providers Need to Know about Zoonotic Influenza is now online. The accompanying 78-page slide show nicely outlines avian and swine virology, surveillance strategies and risk assessment tools – and is worth downloading as a reference. (h/t Avian Flu Diary). CDC
Comparative Characterization of Crimean-Congo Hemorrhagic Fever Virus Cell Culture Systems
Crimean-Congo hemorrhagic fever orthonairovirus (CCHFV) is a biosafety level 4 and World Health Organization top priority pathogen. Despite the severity of disease and the potential of CCHFV geographic expansion to cause widespread outbreaks, no approved vaccine or treatment is currently available. Critical for basic research and the development of diagnostics or medical countermeasures, CCHFV viral stocks are commonly produced in Vero E6 and SW-13 cell lines. While a variety of in-house methods are being used across different laboratories, there has been no clear, specific consensus on a standard, optimal system for CCHFV growth and titration. Data presented here may serve as a basis for a reproducible, standardized and user-friendly platform for CCHFV propagation and titration. Virology Journal
We Need to Development Preventive Measures and Treatment Strategies Against Nipah Virus
NiV has numerous characteristics that highlight its potential as a pandemic danger, such as its human-to-human transmission capability and its propensity to infect humans directly from natural reservoirs and/or from other animals. Since there are no approved vaccines or medications available to treat NiV-infection, patients can only be managed with supportive and preventative care. Maintaining prophylaxis of venous thrombosis, fluid and electrolyte balance, airway patency, mechanical ventilation are fundamental clinical practices. Additionally, broad-spectrum antibiotics are administered to NiV-infected individuals. It is questionable whether the ribavirin given during the epidemic in Malaysia and the acyclovir given in Singapore were effective. Chloroquine showed efficiency in suppressing Nipah virus in cell cultures, however this result could not be verified in animal models. Clinical Pathology
Phenotypic and Genotypic Discrimination of Francisella tularensis ssp. holarctica Clades
Results indicate that there may be differences in the fitness of F. tularensis ssp. holarctica (Fth) strains belonging to the different clades. As previously published, B.12 and B.6 clades may display differences in pathogenicity. Further experimental data is needed to confirm reports about differences in virulence between strains of basal clades B.12 and B.6. Fth isolates can be distinguished by phylogenetic tree analysis (genome based) and it even seems possible to discriminate Fth strains of basal clades B.12 and B.6 by mass spec proteomic profiling. This study corroborates these findings also for strains of the new clades B.71 and B.72 of clade B.12, and this differentiation also seems to correlate with the backscatter light intensity curves of the respective isolates. International Journal of Medical Microbiology
Novel Evidence on Sepsis-Inducing Pathogens: From Laboratory to Bedside
Among the leading causative agents of sepsis are bacterial pathogens Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus, Pseudomonas aeruginosa, and Streptococcus pyogenes, along with fungal pathogens of the Candida species. A list of curated novel host and pathogen factors, diagnostic and prognostic markers, and potential therapeutical targets to tackle sepsis from the research laboratory is presented. Frontiers in Microbiology
Middle East Respiratory Syndrome (MERS-CoV) Risk Assessment
As of June 2023, over 2,600 cases of Middle East Respiratory Syndrome (MERS-CoV) have been reported by the WHO. The majority of MERS-CoV cases have been reported from the Arabian Peninsula, with one large outbreak outside this region involving 186 cases in the Republic of Korea (RoK) in 2015. The majority of outbreaks of MERS-CoV in the Middle East have been linked to healthcare settings. Gov.UK
CHEMICAL + RADIOLOGICAL THREATS
Have Chemical Weapons been Used in Ukraine?
Recent reports suggest that Russia has made limited use of riot control agent as a weapon during its war against Ukraine. If true, what might explain this particular use – and what are the prospects of more widescale deployment of chemical weapons by Moscow? Is this the thin end of a wedge, or does it merely represent localized attempts to break a stalemate? Footage shown on state-controlled media showed village of Spirne. Russian leadership claiming to have used drones to drop K-51 grenades containing cheryomukha onto Ukrainian positions. He referred to the chemical as tear gas, saying it was used to ‘smoke out’ the Ukrainians, who tried to use gas masks to protect themselves but to no avail. It is difficult to ascertain whether or not gas masks were in fact worn, whether they afforded any protection, and whether or not this use of a riot-control agent (RCA) as a method of warfare helped at all in the battle for Spirne. From a technical perspective, RCAs are very simple to protect against, and most modern CBRN gas masks will provide more than adequate protection against such incapacitants. However, what this case does show is that not only has the Russian military contravened the CWC, but it has announced this on state-controlled media. RUSI
Zelensky Accuses Russia of Plotting ‘Radiation Leak’ Attack at Zaporizhzhia Nuclear Plant
Ukraine has new evidence Russia is plotting a “terrorist” attack on the Zaporizhzhia power plant that will result in a radiation leak, President Volodymyr Zelensky has warned. The Kremlin dismissed the allegation as “another lie”, and said a team of United Nations nuclear inspectors had visited the plant. The two sides have accused each other of shelling the vast facility, and international efforts to establish a demilitarized zone around it have failed so far. The Independent
The OPCW’s Never-Ending Fight to Eliminate Chemical Weapons
The OPCW is approaching a new milestone: the destruction of all declared stockpiles of chemical weapons by its 193 member states. (Only four countries—Egypt, Israel, North Korea, and South Sudan—aren’t members.) In a few weeks, the destruction of the remaining stockpiles by the US will be completed. Now that its original mandate is largely complete, the OPCW can shift its focus to monitoring new and emerging threats and preventing the reemergence of destroyed chemical weapons. To support these efforts, the OPCW inaugurated the Centre for Chemistry and Technology in May, located near its headquarters in The Hague. C&EN
CBRN Disaster Hospital Response and Preparedness. An Italian Civilian Military Cooperation Teaching Model
Preparing to evaluate and manage victims from CBRN exposure events in one aspect of hospital preparedness, is often underestimated. Specific skills and capabilities are required to manage these events. A drill exercise was performed on a radiological fall-out incident to test the hospital’s emergency response staff preparedness. Hospital management and decontamination procedures were analyzed to treat victims as well as first responders and to train hospital staff with few resources available. Prehospital and Disaster Medicine
SURVEILLANCE + DETECTION
Strengthening Existing Surveillance Platforms to Monitor Pandemic-Prone Pathogens
To achieve more integrated surveillance systems for influenza, an integration of a range of other respiratory viruses with epidemic or pandemic potential into existing influenza surveillance infrastructure is required. This integration might involve exhaustive data collection and management and the development, evaluation, and validation of multiplex or combination assays to test samples for influenza and other epidemic-prone or pandemic-prone respiratory viruses simultaneously. The Lancet Global Health
Rapid and Stain-Free Quantification of Viral Plaque Via Lens-Free Holography and Deep Learning
A plaque assay—the gold-standard method for measuring the concentration of replication-competent lytic virions—requires staining and usually more than 48 h of runtime. Here researchers show that lens-free holographic imaging and deep learning can be combined to expedite and automate the assay. Nature Biomedical Engineering
Advancing the Central Role of Non-Model Biorepositories in Predictive Modeling of Emerging Pathogens
Researchers here focus on the enormous but relatively untapped potential of non-model host biorepositories and their associated databases to fuel predictive modeling of host–pathogen interactions, emergence risk, and pandemic potential across human–animal–environment interfaces. Non-model biorepositories, in this context, including natural history, agricultural, and other biodiversity collections that preserve biological materials (i.e., samples, specimens) in perpetuity. The metadata associated with the specimens warehoused in non-model biorepositories are served publicly online. Through the newly established PICANTE (Pathogen Informatics Center: Analysis, Networking, Translation, and Education) initiative, they advocate for a multidisciplinary and proactive approach to pandemic prediction and prevention that emphasizes strategic expansion of non-model biorepositories, particularly in biodiverse countries, to stimulate and refine predictive modeling of emerging diseases. PLOS Pathogens
Mpox: Evidence for Strengthening and Sustaining Global Surveillance
This study is the first global description of the 2022 mpox outbreak and confirms the observations of individual national and regional studies. Clear evidence of sustained, multi-country transmission of mpox is provided. This finding is contrary to our previous understanding of the disease whereby transmission was thought to be primarily zoonotic with only short onward human to human transmission chains. By enabling comparison of country level data with the global picture, standardised reporting on this scale allows international consensus on the risk factors and groups most at risk in order to prioritise public health interventions. The Lancet Global Health
Evaluating Theoretical Performance of Aircraft Wastewater Monitoring as Tool for SARS-Cov-2 Surveillance
Assessment of the theoretical limits of aircraft wastewater monitoring and comparison of its performance to post-arrival border screening approaches. Using an infectious disease model, researchers simulate an unmitigated SARS-CoV-2 epidemic originating in a seed country and spreading to the United Kingdom through daily flights. Comparisons to respiratory swab screening suggest that aircraft wastewater monitoring is as effective as random screening of 20% of passengers at the border, using a test with 95% sensitivity. For testing regimes with sensitivity of 85% or less, the required coverage to outperform wastewater monitoring increases to 30%. PLOS Global Public Health
A Three-Level Model for Therapeutic Drug Monitoring of Antimicrobials at the Site of Infection
Antibiotic tissue penetration can vary in patients who are critically or chronically ill and can potentially lead to treatment failure. Antibiotics such as β-lactams and glycopeptides are detectable in non-invasively collectable biofluids, such as sweat and exhaled breath. The emergence of wearable sensors enables easy access to these non-invasive biofluids, and thus a laboratory-independent analysis of various disease-associated biomarkers and drugs. Here researchers introduce a three-level model for therapeutic drug monitoring (TDM) of antibiotics to describe concentrations at the site of infection (SOI) by use of wearable sensors. The Lancet Infectious Diseases
ENVIRONMENTAL FLUX
3 People Have Acquired Malaria in the US. They’re The First in 20 Years.
In late May, Sarasota County, Florida, health officials confirmed they had identified a case of locally transmitted malaria. In mid-June, they confirmed the second. On June 23, Texas joined in: its state health department announced it had confirmed a case of local malaria transmission in Cameron County. Malaria was a huge problem in the US until it was eradicated in the 1950s, largely by spraying the insecticide DDT in homes and environmental areas to kill the mosquitoes that spread it. Vox
Mosquito-Borne Diseases Becoming Increasing Risk in Europe
Mosquitoes that carry viruses like dengue and chikungunya have moved into new parts of Europe, increasing the risk of illness, top experts warn. European scientists say more frequent heatwaves and flooding, and longer, warmer summers, have created more favorable conditions for the bugs. The report, by the European Centre for Disease Prevention and Control (ECDC), tracks the spread of different species of mosquitoes that can carry and transmit a number different of viruses (such as dengue and Zika) to humans. BBC
Peru is Reeling From Record Case Counts of Dengue Fever. What’s Driving the Outbreak?
The Andean nation is not alone. The disease is on the rise around the globe. The WHO says reported cases jumped from 505,430 in 2000 to 5.2 million in 2019. Most cases are asymptomatic or result in only mild sickness. But a number of patients do go on to develop severe dengue, which can be fatal in up to 13% of untreated patients. Peru’s unprecedented outbreak has been driven by unusually warm and rainy conditions, first triggered by Yaku, a tropical cyclone not normally seen in this part of the Pacific, and then a localized “coastal” El Niño effect of warmer ocean waters which allowed the Aedes aegypti mosquito to breed in large numbers. NPR
ANTIMICROBIAL RESISTANCE CRISIS
Will Invasive Fungal Infections Be The Last Of Us? The Importance of Surveillance, Public-Health Interventions, and Antifungal Stewardship
The video game-turned-HBO show ‘The Last of Us’ is a fanciful representation of a zombie apocalypse caused by a fungal infection. Although Ophiocordyceps, the ‘zombie fungi’ featured in the show, do not infect vertebrates, the show serves as a reminder that many fungi can cause life-threatening invasive fungal infections (IFIs). Each year, IFIs are responsible for over 1.5 million deaths globally and, in the United States alone, impose health-care costs ranging from five to seven billion dollars. IFIs are a growing threat to public health, and the lack of emphasis given to these pathogens has led to improper diagnosis, inadequate treatment, limited surveillance, and increased antifungal resistance. Enhancement of laboratory capacity around the world is critical to prevent disease and deaths caused by fungal infections. The development of quicker and more reliable diagnostic tools, expansion of training programs, and adequate funding could help achieve this goal. Expert Review of Anti-Infective Therapy
Zoonotic Sources and the Spread of Antimicrobial Resistance from the LMIC Perspective
Overview on the zoonotic sources of AMR, associated challenges and relevance to low- and middle-income countries (LMIC). Livestock farming accounts for substantial AMU in both high- and low-income settings. While regulations to control and restrict excessive use of antimicrobials have been implemented in high-resource settings, efforts should be made to support LMIC in developing strategies to better monitor and optimize antimicrobial use. Furthermore, bushmeat and aquaculture are relevant sources of animal meat in LMIC and should be targeted for AMR surveillance and research. Infectious Diseases of Poverty
Launch of Global Summit to Preserve Antimicrobials
More than 200 representatives from drug regulatory bodies and health agencies recently gathered for the 1st Global Joint Summit of Human and Veterinary Medicines Regulatory Authorities to Preserve Antimicrobials. It was clear that antibiotic seeking behavior and regulation differed between countries. Although the first iteration of this Summit presented more challenges than solutions to mitigating AMR, it was an opportunity for countries to share their varied experiences. The success stories that were shared involved multidisciplinary efforts that spanned several years or decades. The Lancet Microbe
Treatment of Critically Ill Patients with Cefiderocol for Infections Caused by Multidrug-Resistant Pathogens: Review of the Evidence
Several new antibiotics have shown in vitro activity against carbapenem-resistant Enterobacterales (CRE) and difficult-to-treat resistant Pseudomonas aeruginosa. Cefiderocol is the first approved siderophore beta-lactam antibiotic with potent activity against multidrug-resistant, carbapenem-resistant, difficult-to-treat or extensively drug-resistant Gram-negative pathogens, which have limited treatment options. The spectrum of activity of cefiderocol includes drug-resistant strains of Acinetobacter baumannii, P. aeruginosa, Stenotrophomonas maltophilia, Achromobacter spp. and Burkholderia spp. and CRE that produce serine- and/or metallo-carbapenemases. Annals of Intensive Care
Tackling Antimicrobial Resistance: Council Adopts Recommendation
The proposed measures to step up EU action to combat antimicrobial resistance include: concrete targets to reduce antimicrobial use by 2030, including a 20% reduction in total human consumption of antibiotics and a 50% reduction in overall EU sales of antimicrobials used for farm animals and aquaculture; strengthening of national action plans to help implement these targets and monitor the use of antibiotics at national level, including indicators to assess progress; better surveillance of AMR and antimicrobial consumption at all levels, including hospitals and long-term care facilities; and efforts to improve the health and welfare of food-producing animals to decrease the spread of infectious diseases in farming. European Council of the European Union
COVID-19 PANDEMIC
COVID-19 Mortality in the US: Nearly 1.2 Million Excess Deaths in First 2 Years of COVID Pandemic
A University of Pennsylvania-led study estimates that 1,179,024 excess US deaths occurred in the first 2 years of the COVID-19 pandemic, with excess mortality declining in metropolitan counties and rising in nonmetropolitan counties over the period. “Estimates of excess mortality, which compare observed deaths to those expected in the absence of the pandemic, suggest that the true death toll of the pandemic is much larger than indicated by official COVID-19 deaths alone. Excess mortality is likely to provide a more accurate measure of the pandemic’s impact for purposes of resource allocation and evaluating health disparities.” CIDRAP
Probable Transmission of SARS-CoV-2 from African Lion to Zoo Employees
Researchers describe animal-to-human transmission of SARS-CoV-2 in a zoo setting in Indiana, USA. This multispecies cluster of SARS-CoV-2 included 3 confirmed cases (2 human, 1 felid) and 1 probable case (human). The investigation strongly suggests that lion-to-human transmission took place in 2, and possibly 3, instances, which is important for at least 2 reasons. First, animal-to-person transmission of SARS-CoV-2 is an occupational health risk for veterinary and animal care staff that interact closely with susceptible animals. Second, transmission occurred despite an up-to-date SARS-CoV-2 vaccination history in every person involved, including the person or persons who likely transmitted the virus to the lion, the lion, and the person or persons who likely became infected from the lion. Emerging Infectious Diseases
Safety, Immunogenicity And Protection of Heterologous Boost with an Aerosolized Ad5-nCoV
Aerosolised Ad5-nCoV is one of the first licensed mucosal respiratory vaccine against SARS-CoV-2 in the world; however, the safety profile of this vaccine has not been reported in a large population yet. This multicenter, open-label phase 3 trial, done in 15 centers in six provinces in China, evaluated the safety and immunogenicity of aerosolized Ad5-nCoV in healthy adults. Participants in the aerosolized Ad5-nCoV group had a significantly higher level of the neutralizing antibodies against omicron BA.4/5 than did those in the inactivated vaccine group at day 28. The Lancet Infectious Diseases
Serological Response Following COVID-19 Vaccines in Patients Living with HIV
This study demonstrated that only 75.0% patients living with HIV achieved a seroconversion after uncomplete vaccination, which improved to 89.3% after complete vaccination, and 98.4% after booster vaccination. The seroconversion rates were significantly lower compared to controls at all the stages, while the risk ratios for uncomplete, complete, and booster vaccination were 0.87, 0.95, and 0.97, respectively, suggesting the urgent need for booster vaccination in patients living with HIV. Scientific Reports
Genomic Surveillance for SARS-CoV-2 Variants: Circulation of Omicron Lineages
Weekly estimates of variant proportions during January 2, 2022–May 13, 2023, identified the emergence and subsequent predominance of multiple Omicron lineages in the United States, including BA.2, BA.2.12.1, BA.5, and XBB.1.5. Repeated independent substitutions in the spike protein suggested convergent evolution related to immune evasion. Analytic methods for variant proportion estimation have been updated as numbers of cases and sequenced specimens have declined. MMWR
Adapted Vaccine Strategy: Facing the Persistent Challenges of COVID-19
There is a deficiency of large-scale population-based effectiveness data on head-to-head comparison of omicron-containing vaccines and ancestral monovalent vaccines, which warrants research. In addition to the composition of the vaccines, the time required for vaccine development and the speed of clinical availability are also crucial when facing the rapidly mutating omicron variants. The method of predicting circulating strains and updating components of vaccines annually without repeating clinical trials has been successful in influenza vaccines. Regulating agencies need to formulate an approval framework that harmonizes safety, effectiveness, and speed. The Lancet Infectious Diseases
A Respiratory Sounds and Symptoms Dataset for Remote Screening of SARS-Cov-2 Infection
Listening to respiratory sounds, such as deep breathing, with a stethoscope has served as a useful methodology to screen respiratory ailments. Utilizing digital technologies, respiratory sound samples can be collected via internet connected devices. Here researchers created a respiratory sound and symptom dataset named Coswara, composed of breathing, cough, and speech sounds along with the health related symptoms, recorded from individuals with, without, and recovered from SARS-CoV-2 infection. Scientific Data
Trends in Laboratory-Confirmed SARS-CoV-2 Reinfections and Associated Hospitalizations
During September 2021–December 2022, the percentages of reinfections among all COVID-19 cases, hospitalizations, and deaths reported by 18 U.S. jurisdictions increased substantially as new Omicron lineages became predominant. Higher percentages of reinfections among COVID-19 cases and associated hospitalizations and deaths were observed among younger adults compared with older adults, particularly in late 2022. The higher percentages in younger age groups might be attributable to multiple factors, including higher cumulative incidence of first infections, later eligibility for vaccination, lower vaccination coverage, increased exposure risk, and a possible survival bias because of less severe initial infections. MMWR
Bivalent COVID-19 mRNA Vaccine Against Omicron Subvariants in Immunocompromised Patients
SARS-CoV-2 infection continues to result in moderate to severe disease in immunocompromised patients. This study suggests that, while bivalent vaccination increases BA.4/5-directed neutralizing antibody in immunocompromised people, it only modestly impacts BQ.1.1 and XBB.1.5 neutralization. By contrast, substantial cross-protective neutralizing antibody is observed following previous Omicron infection. T-cell responses are more readily detectable and conserved across BA.4/5, BQ.1.1, and XBB.1.5 variants, thereby possibly providing some cross-variant protection. However, no additional boosting of T-cell response was evident following bivalent vaccine. These results suggest that, although vaccination is important, additional strategies such as the ongoing development of prophylactic monoclonal antibodies and use of early COVID-19 therapies are crucial for immunocompromised patients. The Lancet Infectious Diseases
SPECIAL INTEREST
Eddie Holmes on SARS-CoV-2 Origins
Podcast guest is virologist Eddie Holmes discussing the evidence for SARS-CoV-2 spillover into humans in the Huanan Market in Wuhan, absence of evidence for other origins, and his work on the virosphere. TWiV
Loud-Mouthed Personality Wants a “Debate” on Vaccines with Respected Scientist. Don’t Give it to Him.
Here’s why debates are actually a bad forum for discussing contentious scientific issues — and what works better. A debate about a scientific issue implies there is scientific disagreement about that issue. You’re “giving individuals a platform to really promote something that goes against scientific consensus.” That creates a sense of false equivalence. It’s not just vaccine science: Many areas of science really don’t benefit from “debate.” A debate’s performative aspect means its participants are rewarded for doing what best preserves their public image. For people whose public identity is strongly tied to holding specific beliefs, that means standing their ground — not learning something new, which they may see as signaling to their audience that their identity is on shaky ground. With a Q&A at least, even when the parties come with less than altruistic intentions, the premise is more learning and less “winning”. Vox
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