This week’s selections include investigation of the bifurcated needle for mpox vaccination, new tariffs to hit the PPE supply chain, a framework to prevent an AMR pandemic, and a new CDC health alert for mpox prevention.
FEATURED
Bifurcated Needles Could be the Key to Mpox Vaccination
As experts work to contain the mpox outbreak, PATH investigates whether the tool that helped eradicate smallpox could expedite lifesaving immunization. Two-prong, bifurcated needles administer a small droplet of vaccine held between the prongs by piercing only the top-most layer of the skin. Bifurcated needles were widely used decades ago in WHO smallpox vaccine campaigns, as they were a low-cost and effective means of administering millions of smallpox vaccines. PATH is providing technical assistance to UNICEF to support device procurement for mpox vaccines. As part of this support, they are conducting testing of bifurcated needles to determine whether devices meet the required specifications for mpox vaccine delivery. PATH
USTR Tariff Increases on PPE: What It Means for the Healthcare Supply Chain
The U.S. Trade Representative announced significant tariff increases on electric vehicles, semiconductors, solar cells and key medical goods to counter China’s trade practices and support U.S. industries. The tariff hikes, which are set to be implemented gradually over the next few years, target various types of PPE including facemasks and respirators (tariffs will rise to 25% in 2024, with a further increase to 50% by 2026); medical and surgical gloves (starting in 2025, tariffs will increase to 50%, rising to 100% by 2026); and syringes and needles used in medical, surgical, dental, and veterinary sciences (increase to 100% in 2024). USTR, JD Supra, Faegre Drinker
How to Prevent the ‘Grand Pandemic’
In a new report entitled Stopping the Grand Pandemic: A Framework for Action, the World Bank argues that addressing AMR must become a critical priority for governments and their development- and private-sector partners. Left unchecked, AMR could cause 10 million deaths per year by 2050. The report estimates it could push 28 million people into poverty, and wipe 3.8% off the global annual gross domestic product. Devex
CDC Health Alert: Prevention Strategies for Mpox
Although the United States continues to be affected by an ongoing global outbreak of clade II mpox that began in 2022, no domestic cases of clade I mpox have been identified in the U.S. at this time. CDC advises travelers to DRC or other countries where clade I MPXV is spreading regardless of sexual orientation or gender identity, should be made aware of activities associated with cases and should be vaccinated with two doses of JYNNEOS if they anticipate certain sexual exposures while traveling. CDC HAN
Apathy and Ignorance Towards Bird Flu and Mpox Prove We Learnt Nothing From Covid, Say Virologists
Dozens of leading virologists recently gathered in Durban, South Africa, at the annual meeting of the Global Virus Network (GVN). The US government’s failure to give flu jabs to farm workers in areas where H5N1 flu is spreading through cattle, and nations hoarding mpox vaccines even as the virus ravages parts of Africa are both examples of failing to learn lessons, they said. The Telegraph
POLICY + GOVERNMENT
Governments Progress on Negotiations for a Pandemic Agreement to Boost Global Preparedness for Future Emergencies
Substantive progress on the draft agreement, increased involvement of civil society and non-State actors, and a commitment by all parties to sustain momentum towards a pandemic agreement were hallmarks of the 11th meeting of the Intergovernmental Negotiating Body (INB), which comprises the 194 member governments of WHO, and ran from 9-20 September in Geneva. Negotiators will resume discussions, at a 12th round, from 4-15 November. World Health Organization
‘Not Enough Progress’ Made at 11th Round of Pandemic Agreement Talks
According to the latest draft of the pandemic agreement, the most controversial part of the agreement – developing a pathogen access and benefit-sharing (PABS) system (Article 12) – will now be addressed via a separate “instrument”. The provisions governing the PABS system will be developed by the Conference of the Parties (COP). This COP will be set up after the World Health Assembly has adopted the pandemic agreement. Health Policy Watch
Republican Governors on International Pandemic Plan: We Will Not Comply
In yet another example of how all things related to the pandemic have become political, nearly all of the country’s Republican governors have expressed their staunch opposition to a World Health Organization agreement about how nations should collectively prevent, prepare and respond to future global public health emergencies. “The World Health Organization is attempting one world control over health policy with their new ‘Pandemic Agreement,’” said 24 Republican governors in a joint statement late last month. “Put simply, Republican Governors will not comply.” Route Fifty
MEDICAL COUNTERMEASURES
Virology—The Next Fifty Years
“If virology is not nurtured, we cannot hope to detect or respond to threats effectively without the arsenal of knowledge built through steady research and scientific discovery: we are effectively disarming our best defense. The current political environment and the anti-science sentiment it has nourished means that we are arguably less well prepared for a pandemic than we were in January 2020. To compound this issue, the assault on virology will deter the next generation of scientists from entering fields driving the science critical to pandemic response.” Cell
Novel Platform for Engineering Stable and Effective Vaccines Against Botulinum Neurotoxins A, B and E
Given the threat of BoNTs as bioterrorism agents, there is an urgent need for diverse vaccine platforms and delivery systems that are safer, more effective, and more stable. This study describes a novel, stable tetrameric antigen, EBA, which incorporates functional neutralising epitopes from BoNT/A, BoNT/B, and BoNT/E in a mouse model. Frontiers in Immunology
Combating Biothreat Pathogens: Ongoing Efforts for Countermeasure Development and Unique Challenges
A comprehensive tabular review of current in vitro, in vivo, pharmacokinetic and efficacy datasets for finding new antibodies, antibiotics, and antiviral molecules for pathogens of biothreat concern. Drug Discovery Targeting Drug-Resistant Bacteria
A Bacteriophage Cocktail Targeting Yersinia pestis Provides Strong Post-Exposure Protection in a Rat Pneumonic Plague Model
This study examined post-exposure efficacy of a bacteriophage cocktail, YPP-401, to combat pneumonic plague caused by Y. pestis CO92. YPP-401 is a four-phage preparation effective against a panel of at least 68 genetically diverse Y. pestis strains. Microbiology Spectrum
Building Resilience in the UK: Localized mRNA Manufacturing for Enhanced Pandemic Preparedness
Under construction near Oxford, the Moderna Innovation and Technology Centre (MITC) will feature state-of-the-art manufacturing and clinical laboratory capabilities. The MITC is part of a 10-year strategic partnership with the U.K. government, which includes working with academic and NHS partners to invest in mRNA research and grow our clinical trials footprint across the U.K. Moderna
Research Project: Nipah VLP Vaccine for Pandemic Preparedness
Well established platforms are pivotal to pandemic preparedness for Nipah disease outbreaks of human disease that might emerge in the future. This project hypothesizes that an efficacious plant produced NiV VLP, antigenically matched to a strain of concern will elicit the known correlates of protection in pigs. USDA ARS
A Chimeric mRNA Vaccine Conferring Broad Protection Against Influenza and COVID-19 Variants
This vaccine effectively afforded complete protection to mice against H1N1 or heterosubtypic H5N8 subtypes, as well as the SARS-CoV-2 Delta and Omicron BA.2 variants. Additionally, the mRNA vaccine design can be easily adapted from Delta RBD to Omicron RBD antigens, providing protection against emerging variants. PLOS Pathogens
Reactogenicity and Immunogenicity of Intradermal Administration of Modified Vaccinia Ankara Compared to Standard Subcutaneous Route
Study found that the intradermal route elicited slightly higher titers of MPXV-specific IgG and nAbs than the subcutaneous one. MVA-BN was globally well tolerated despite higher reactogenicity for the intradermal than the subcutaneous route, especially for the reactions at the local injection site. The intradermal dose-sparing strategy was proven safe and immunogenic and would make vaccination available to more people. MedRxiv
BIOSECURITY + BIOPREPAREDNESS
Widening the Lens for Pandemic Preparedness: Children Must Be Seen and Heard
New diseases with pandemic potential are emerging at an alarming rate given the cumulative impacts of climate change and an expanding global population. Child health professionals have major concerns about the profound effect that pandemic disruption has had on children during crucial formative years. Children of this generation and future generations will likely endure further pandemics over their lifetimes. Widening the lens for pandemic preparedness to better incorporate the needs and voices of children is essential to avert potential lifelong consequences and social harm that has occurred with the COVID-19 pandemic. The Lancet Regional Health
Logistics for Rapid Isolation of Viruses From Humans
An important aspect of microbiological surveillance is the ability to access to live viruses for microneutralization assays, which enables the study of viral characteristics and mechanisms in vitro and production of positive controls for diagnostic methods. During the COVID-19 pandemic, the Public Health Agency of Sweden established a protocol for the rapid collection of clinical samples and subsequent isolation of novel virus variants. Health Security
Understanding Responses and Developing Pandemic Preparedness in Alaska
In 2023, the National Science Foundation funded a conference of circumpolar researchers and Indigenous partners to reflect on COVID-19-related research. This paper builds on these findings to identify potential areas of future pandemic-related research in Alaska, and pose new preparedness research questions that elevate the needs of Alaska and its people. International Journal of Circumpolar Health
The Global Pandemic Preparedness Summit 2024: Outcomes Report
The new report aims to inform global leaders’ decision-making around international pandemic preparedness efforts by presenting outcomes and recommendations from the Summit. CEPI
The Frontline Responders in Health Emergencies
Lieutenant Colonel Emmanuel Chapeau, the National Emergency Medical Team Focal Point for France, discusses the vital role of these teams, their operations and the future of emergency medical response in the country. World Health Organization
Hospital Emergency Response Checklist
Limited resources, a surge in demand for medical services, and the disruption of communication and supply lines create a significant barrier to the provision of health care. This document provides an all-hazards list of key actions to be considered by hospitals in responding to any disaster event. World Health Organization
SELECT AGENTS + PRIORITY PATHOGENS
Mpox Control Strategies: Using Behaviour Change to Complement, Not Replace, Vaccination
Although risk communication and community engagement proved effective in reducing transmission in specific groups during the global 2022–23 outbreak, such strategies alone might not be applicable to, or sufficient in, the African context. However, these strategies could become useful again if future outbreaks more widely affect MSM populations, as occurred in 2022. Addressing the mpox crisis will require a multifaceted approach that ensures equitable access to vaccines and health-care services, enhances surveillance and diagnostic capacities, and increases investment in research to enhance our understanding of viral evolution and its effect on the shifting epidemiology of mpox. The Lancet Infectious Diseases
India Reports First Case of Mpox from Fast-Spreading Clade 1b Variety
India said on Monday that an mpox case involving a man in the southern state of Kerala was from the fast-spreading clade 1b variety, marking South Asia’s first recorded case from the new strain. The patient is a 38-year-old man who had travelled from the United Arab Emirates. About 29 friends and family members of the patient along with 37 passengers on his flight are being monitored at home. Reuters
Nipah Virus: Kerala Reports Second Death in Four Months
A 24 year old student who was visiting his hometown of Malappuram, in the southern Indian state of Kerala, has become the second person to die from Nipah virus infection in the state this year, the country’s national laboratory confirmed on 15 September. The first was a 14 year old boy who died in June within days of testing positive for Nipah. The BMJ, CIDRAP
Eco-Thrax: Anthrax Narratives and Unstable Ground
The threat of anthrax has shifted in light of the environmental realities of a warming planet. The threat of anthrax has instead transformed into an activated harm emerging from once-stable layers of permafrost. The narratives told around microbial harm necessitate new ways of thinking about human–ecological and human–microbial relationships. Open Cultural Studies
The Dangerous Biology of Pathogenic Germs
Advances in biotechnology are ushering in a new era, one of unprecedented scientific progress in our knowledge of living organisms, but also one of dangerous biology, for which we must be extremely vigilant. One can now easily modify the genome of microorganisms (loss or gain-of-function) and synthesize gene sequences and even entire microorganisms (bacteria and viruses), enabling major advances in many areas of science. All these manipulations can be aided by the use of AI to design de novo manipulations and genome syntheses. These include a better understanding of the evolution and properties of dangerous pathogens. However, this has also implications in terms of dual use and availability of highly dangerous germs that can be synthesised from in silico sequences available from databases. Biologies
AVIAN INFLUENZA
Serologic Testing of Missouri H5 Cases Underway
The Missouri Department of Health and Senior Services collected blood samples from the person who tested positive for H5N1 in Missouri and a household contact who became ill on the same day and was not tested. Both persons have since recovered. The samples are being sent to CDC for serologic testing to look for antibodies to avian influenza A(H5) virus, which would indicate a previous infection. The simultaneous development of symptoms in two people does not support person-to-person spread but suggests a common exposure. Compared to previous human cases, the HA has two amino acid differences not observed before. Neither of the two mutations is known to modify virus ability to infect and spread among people. No additional cases have been identified within a 10-day follow-up period. CDC, ECDC
Minnesota Reports 2 H3N2v Flu Infections in Fairgoers
Two human infections with influenza A(H3N2) variant viruses were reported by the Minnesota Department of Health. Both patients are <18 years of age, sought healthcare during the week ending September 7, 2024, were not hospitalized, and have recovered from their illnesses. Investigators found that the patients were not contacts of each other but had each attended the same agricultural fair where they were exposed to pigs. CIDRAP, CDC
Is Bird Flu Spreading Among People? Data Gaps Leave Researchers in the Dark
All eyes are on Missouri. Researchers are anxiously awaiting data from the midwestern state about a mysterious bird flu infection in a person who had no known contact with potential animal carriers of the disease. The data could reveal whether the ongoing US bird flu outbreak in dairy cattle has reached a dreaded turning point: the emergence of a virus capable of spreading from human to human. Nature
Ghana Confirms Human H9N2 Avian Flu Infection
On 26 August 2024, the International Health Regulations (IHR) National Focal Point (NFP) for Ghana notified the World Health Organization (WHO) regarding the country’s first reported human case of infection with a zoonotic (animal) influenza virus. Subsequent laboratory tests confirmed the presence of the avian influenza A(H9N2) virus. According to epidemiological investigations, the patient, under five years old, had no known history of exposure to poultry or any sick person with similar symptoms prior to the onset of symptoms. The Ghanaian government has implemented a series of measures aimed at monitoring, preventing, and controlling the situation. WHO, CIDRAP
Broadening the Aims of Avian Influenza Surveillance According to the One Health Approach
A key aspect of infectious disease surveillance is the cycle of detecting, responding to, and—last but not least—preventing outbreaks. In the case of HPAI in wildlife, there are few if any response options to mitigate the impact of the disease once it has spilled over from poultry. Therefore, it is all the more important to prevent the upstream events that favor the genesis and spread of HPAI viruses on poultry farms, as well as the spillover of HPAI from poultry to wild waterbirds in wetland areas. mBio
Tamiflu: Could an Old Drug Protect Against a New Pandemic?
Health authorities have said that stockpiled Tamiflu (oseltamivir) should work well against H5N1. Some experts question that bet. While oseltamivir may help in cases of severe flu, some experts are concerned that the U.S. is banking far too much on a so-so drug while failing to prioritize research on new treatments. Undark
‘We Are Not Testing Enough’: New US Bird Flu Cases Stoke Fears Over Poor Response
After three more herds in California’s Central valley tested positive for bird flu, questions have been raised about the whether true extent of the outbreak in the US is much wider than recognized, given inadequate or nonexistent biosecurity and a persistent lack of testing. The Guardian
CHEMICAL + RADIOLOGICAL THREATS
Health Effects of Chemical Exposure: Toxidromes
A brief overview of nine common toxidromes, as defined by the Department of Homeland Security and National Library of Medicine. Understanding toxidromes is valuable for identifying effective treatments and appropriate PPE based on clinical observations when specific chemical/source information is unavailable. FEMA
First Advanced Wound Dressing to Treat Acute Cutaneous Radiation Injury Cleared by FDA
Silverlon (from Bravida Medical) is a silver-plated antimicrobial dressing, previously approved for treatment of thermal burns, skin wounds from sulfur mustard exposure, a limited range of CRIs, and radiation dermatitis injuries. Silverlon indications are now expanded to treat more severe acute cutaneous radiation injuries (CRIs) such as injuries caused by fallout after a nuclear detonation. BARDA
Evaluation of Resveratrol Compounds as Therapeutics in Organophosphorus Poisoning
The ability of butyrylcholinesterase (BChE) to bind OP compounds lowering their concentration in the circulation and preventing the inhibition of AChE represents a basis for potential therapy for organophosphorus poisoning (OP). This study investigated heterostilbene derivatives as potential drugs for OP poisoning focusing on their ability to reactivate cholinesterases, mostly circulating BChE in blood. These compounds were designed as analogs of resveratrol, a polyphenol known for its antioxidant, anti-inflammatory, and neuroprotective properties. CRO RIS
SURVEILLANCE + DETECTION
Novel Detection of Nipah Virus Based on a CRISPR/Cas12a System
Study of two rapid, sensitive for NiV detection based on a recombinase-aided amplification (RAA) assay and a CRISPR/Cas12a system by utilizing dual-labeled fluorophore–quencher or fluorophore-biotin ssDNA probes. Analyst
Support for Wastewater Monitoring and Influence on Protective Behavioral Intentions
In a survey of public support, U.S. adult residents (74.6%) strongly or somewhat support wastewater monitoring, with nearly all (95.3%) stating they would take steps to protect themselves if wastewater monitoring data indicated disease transmission in their area. MMWR
INFECTIOUS DISEASES
Whooping Cough Cases Spike in the U.S., After People Missed Vaccinations During Pandemic
The CDC has recorded 14,569 cases this year so far, an increase from the 3,475 total cases recorded last year. “The first week or so of illness looks like any other respiratory disease,” she said, “when, in fact, it could be pertussis and you’re just infecting people around you.” What sets whooping cough apart from other respiratory illness are the prolonged and fitful coughs, which last at least three weeks and can persist for many months. The CDC recommends the DTaP vaccine for babies and children under 7 years old. Older children and adults are advised to get the vaccine as well as a booster every 10 years. NPR
Global Leprosy (Hansen Disease) Update: Elimination of Leprosy Disease is Possible – Time to Act!
During 2023, a total of 182,815 new cases were reported globally, corresponding to a new case detection rate of 22.7 per million population. The number of new cases detected globally was 5% higher than in 2022 (174,094). Globally, the number of new cases decreased by 14.6% during the decade 2014–2023. World Health Organization
New York Resident Dies of Eastern Equine Encephalitis Infection
The first person to be diagnosed with Eastern equine encephalitis in New York in nearly a decade has died, prompting Gov. Kathy Hochul to declare the rare, mosquito-borne viral illness an imminent public health threat on Monday. The death in New York appears to be the second linked to E.E.E. this year in the United States. The first involved a 41-year-old New Hampshire man who died in August. New York Times
ANTIMICROBIAL RESISTANCE CRISIS
Discovery and Development of Novel Therapeutics for Select Fungal Pathogens
NIH funding opportunity supports milestone-driven, early-stage translational research focused on drug discovery and development of novel therapeutics against select fungal pathogens including: Candida species, specifically Candida auris; Aspergillus fumigatus; Coccidioides; and Mucorales. Grants.gov
WHO at UNGA: Call for Urgent, High-Level Action to Address Global Scourge of Antimicrobial Resistance
The second High-Level Meeting on Antimicrobial Resistance (AMR) on 26 September 2024 will be the principal official, health-focused event during the 79th session of the United Nations General Assembly (UNGA79 in New York. “Antimicrobial resistance threatens a century of medical progress and could return us to the pre-antibiotic era, where infections that are treatable today could become a death sentence. This is a threat for all countries at all income levels, which is why a strong, accelerated and well-coordinated global response is needed urgently.” World Health Organization
Epidemiology and Drug Resistance Among Candida Pathogens in Africa
Per estimates, Africa has a greater share of the invasive candidiasis burden than the rest of the world. These estimates are rough, and the paucity of accurate epidemiological data due to insufficient diagnostics for C. auris has restricted the understanding of the epidemiology of the fungus in Africa. The Lancet Microbe
Antimicrobial Resistance: A Concise Update
AMR represents a crucial global health threat that is associated with high morbidity and mortality, prolonged hospital admission, and increased health-care costs. With roughly 5 million deaths associated with bacterial AMR in 2019, and this number projected to increase substantially by 2050 if left unaddressed, urgent action is imperative. The Lancet Microbe
COVID-19 PANDEMIC
COVID-19 Variant Update
As of September 17, 2024, the SARS-CoV-2 Omicron variants KP.2, KP.2.3, KP.3 and KP.3.1.1, as well as LB.1, have high prevalence in the United States. CDC Nowcast projections estimate KP.3.1.1 to account for approximately 53% of new COVID-19 illnesses in the US. As of September 17, the estimated percentage of illnesses caused by KP.2.3 is 12.2% (a slight decrease from the previous four-week period), and the estimated percentage of illnesses caused by LB.1 is 10.0% (also a slight decrease from the previous four-week period). A very high proportion (>95%) of individuals currently have identifiable antibodies against SARS-CoV-2, either from infection or immunization or a combination of both. COVID-19 Real-Time Learning Network
Lower Mortality Risk Associated with Remdesivir + Dexamethasone Versus Dexamethasone Alone for Hospitalized COVID-19 Patients
Remdesivir + dexamethasone was associated with a significant reduction in 14- and 28-day mortality compared to dexamethasone alone in patients hospitalized for COVID-19 across all levels of baseline respiratory support, including IMV/ECMO. However, the use of remdesivir + dexamethasone still has low clinical practice uptake. Clinical Infectious Diseases
High-Grade Masks Evidence Weak, Covid Inquiry Told
Prof Susan Hopkins, chief medical adviser at the UK Health Security Agency (UKHSA), said respirator masks – known as FFP3s – may have performed no better than thin surgical masks in real-life situations. For most of the pandemic, national guidance across the whole UK said that healthcare workers should wear basic surgical masks rather than FFP3s, except in intensive care or a small number of medical situations. The decision was heavily criticized by some staff with the doctors’ union, the BMA, calling it a “matter of life and death”. BBC
Florida’s New COVID Booster Guidance is Straight-Up Misinformation
In what has become a pattern of spreading vaccine misinformation, the Florida health department is telling older Floridians and others at highest risk from COVID-19 to avoid most booster shots, saying they are potentially dangerous. The bulletin makes a number of false or unproven claims about the efficacy and safety of mRNA-based COVID vaccines by Pfizer and Moderna, including that they could threaten “the integrity of the human genome.” The state’s Surgeon General urged people under 65 to avoid COVID shots last year and has rejected public health protocols for fighting measles outbreaks. CBS News
SPECIAL INTEREST
A Shark Tank for Accelerating Innovation for Climate and Pandemic Preparedness
At the end of a year-long competition, three teams from a pool of 183 took the stage last week to pitch their visionary ideas to promote innovation for addressing climate change, pandemics, and public health. The German Federal Agency for Disruptive Innovation (SPRIND) took home the MSA Innovation Challenge Grand Prize of $290,000 for their proposal to develop and stockpile broad-spectrum antivirals. Center for Global Development
Apply Now for the ECDC Fellowship Programme Cohort 2025
Interested in a career in field epidemiology or public health microbiology? Embark on a two-year hands-on training that enables fellows to support prevention, preparedness, and surveillance activities, outbreak investigation, and control of communicable disease threats across the European Union. ECDC
College and Community Benefit from Strong Relationship with CDC’s Epidemic Intelligence Service Program
“The Epidemic Intelligence Service provides outstanding real-world training. I’m proud of our MEZCOPH PhD grads who have gone on to become EIS Officers. At the same time, I’m grateful to partner with state and local health leaders to supervise EIS Officers who have been placed with Pima County Health Department. These officers have worked on exciting projects with our MEZCOPH students while they improve health outcomes in our region. It’s a relationship that benefits students, benefits the community, and prepares the next generation of health professionals.” – Associate Professor and EIS alum Kate Ellingson, PhD. University of Arizona
ALSO READING
Epidemic and pandemic preparedness and response in a multi-hazard context. Environmental Research and Public Health
How the lessons of COVID-19 ensured a rapid response to the mpox outbreak. World Economic Forum
‘Our project, your problem?’ A case study of the WHO’s mRNA technology transfer programme in South Africa. PLOS Global Public Health
Insights into the Role of VPS39 and its Interaction with CP204L and A137R in African swine fever virus (ASFV) infection. Viruses
A cross-border biorisk toolkit for healthcare professionals. International Journal of Environmental Research and Public Health
Metagenomic next generation sequencing of plasma RNA for diagnosis of unexplained, acute febrile illness in Uganda. PLOS Neglected Tropical Diseases
Technical consultation on the WHO Antimicrobial Resistance Diagnostic Initiative. World Health Organization
Global Burden of Bacterial Antimicrobial Resistance 1990–2021: A systematic analysis with forecasts to 2050. The Lancet
Punicalagin inhibits African Swine Fever Virus replication by targeting early viral stages and modulating inflammatory pathways. Veterinary Sciences
Multiplex microscopy assay for assessment of therapeutic and serum antibodies against emerging pathogens. Viruses
Almost 30,000 suspected mpox cases in Africa this year, WHO says. Reuters