[Development characteristics, problems and countermeasures of major scientific and technological infrastructures in the field of life sciences].

The major science and technology infrastructure in the field of life science is an indispensable and important content in the large-science facility landscape. It encompasses cutting-edge, strategic, and fundamental aspects. This field differs from traditional facilities such as particle physics, astronomy and nuclear energy. Moreover, it represents a relatively underdeveloped area in China's facility landscape. Unique characteristics are observed in terms of capital investment, physical form, facility lifespan, digitization degree, organizational structure, project risk, and development effect when compared to traditional facilities. Despite its importance, challenges persist in project establishment, investment, management, and construction. Therefore, it is necessary to strengthen the condensing mechanism for addressing major scientific issues in the life science field, improve the strategic investment layout, facilitate the localization of technical equipment based on original scientific ideas, and strengthen the differentiated management capacity of life science facilities.

Treatment Efficacy of Cidofovir and Brincidofovir against Clade II Monkeypox Virus isolates.

While historically confined to endemic areas, Monkeypox virus (MPXV) infection has increasingly garnered international attention due to sporadic outbreaks in non-endemic countries in the last two decades and its potential for human-to-human transmission. In 2022, a multi-country outbreak of mpox disease was declared by the World Health Organization (WHO) and nearly 100,000 mpox cases have been reported since the beginning of this pandemic. The clade II variant of the virus appears to be responsible for the vast majority of these infections. While there are no antiviral drugs currently approved to treat mpox specifically, the use of tecovirimat (TPOXX®) and brincidofovir (Tembexa®) is recommended by the Centers for Disease Control and Prevention (CDC) for compassionate use in severe mpox cases, since both are FDA-approved for the treatment of the closely related smallpox disease. Given the emergence of multiple tecovirimat-resistant infections, we aimed to evaluate the treatment efficacy of brincidofovir and its active compound, cidofovir, against MPXV clade II strains. Following intranasal infection, we show that cidofovir and brincidofovir can strongly reduce the viral replication of MPXV clade IIa and IIb viruses in the respiratory tract of susceptible mice when administered systemically and orally, respectively. The high antiviral activity of both compounds against historical and currently circulating MPXV strains supports their therapeutic potential for clinical application.

Case Report: A report on the countermeasures after PICC line breakage in 3 postoperative breast cancer patients.

Peripherally inserted central catheter (PICC) is a widely used technique in oncology chemotherapy, characterized by safety, reliability, and long dwell time. However, a catheter can break due to various causes. When an acute rupture occurs, it always lead to sever complications which may threaten patients' safety and potentially result in medical disputes. In this study, we collected and analyzed 3 cases of PICC line breakage causing drug leakage in our hospital from 2018 to 2023. All these 3 cases were postoperative breast cancer patients accepting chemotherapy, with 2 cases involving external partial breakage and 1 case involving internal partial breakage. Due to timely and appropriate management, no acute rupture occurred. We propose some ideas such as selecting high-quality catheter materials and avoiding over extension or repeated bending are crucial in preventing PICC line breakage. In addition, we also recommend establishing a standardized and scientific management pattern of PICC to ensure the safety and effectiveness of its clinical application, including comprehensive assessment, "four-element" intervention, and continuous evaluation.

An update on nonhuman primate usage for drug and vaccine evaluation against filoviruses.

INTRODUCTION: Due to their faithful recapitulation of human disease, nonhuman primates (NHPs) are considered the gold standard for evaluating drugs against Ebolavirus and other filoviruses. The long-term goal is to reduce the reliance on NHPs with more ethical alternatives. In silico simulations and organoid models have the potential to revolutionize drug testing by providing accurate, human-based systems that mimic disease processes and drug responses without the ethical concerns associated with animal testing. However, as these emerging technologies are still in their developmental infancy, NHP models are presently needed for late-stage evaluation of filovirus vaccines and drugs, as they provide critical insights into the efficacy and safety of new medical countermeasures. AREAS COVERED: In this review, the authors introduce available NHP models and examine the existing literature on drug discovery for all medically significant filoviruses in corresponding models. EXPERT OPINION: A deliberate shift toward animal-free models is desired to align with the 3Rs of animal research. In the short term, the use of NHP models can be refined and reduced by enhancing replicability and publishing negative data. Replacement involves a gradual transition, beginning with the selection and optimization of better small animal models; advancing organoid systems, and using in silico models to accurately predict immunological outcomes.

BioTrojans: viscoelastic microvalve-based attacks in flow-based microfluidic biochips and their countermeasures.

Flow-based microfluidic biochips (FMBs) are widely used in biomedical research and diagnostics. However, their security against potential material-level cyber-physical attacks remains inadequately explored, posing a significant future challenge. One of the main components, polydimethylsiloxane (PDMS) microvalves, is pivotal to FMBs' functionality. However, their fabrication, which involves thermal curing, makes them susceptible to chemical tampering-induced material degradation attacks. Here, we demonstrate one such material-based attack termed "BioTrojans," which are chemically tampered and optically stealthy microvalves that can be ruptured through low-frequency actuations. To chemically tamper with the microvalves, we altered the associated PDMS curing ratio. Attack demonstrations showed that BioTrojan valves with 30:1 and 50:1 curing ratios ruptured quickly under 2 Hz frequency actuations, while authentic microvalves with a 10:1 ratio remained intact even after being actuated at the same frequency for 2 days (345,600 cycles). Dynamic mechanical analyzer (DMA) results and associated finite element analysis revealed that a BioTrojan valve stores three orders of magnitude more mechanical energy than the authentic one, making it highly susceptible to low-frequency-induced ruptures. To counter BioTrojan attacks, we propose a security-by-design approach using smooth peripheral fillets to reduce stress concentration by over 50% and a spectral authentication method using fluorescent microvalves capable of effectively detecting BioTrojans.

Deciphering the relative importance of genetic elements in hypervirulent Klebsiella pneumoniae to guide countermeasure development.

BACKGROUND: Quantitating the contribution of phenotype-responsible elements in hypervirulent Klebsiella pneumoniae is needed. METHODS: Isogenic mutants of four hypervirulent clinical isolates that produced K1 (ST23), K2 (ST86), K20 (ST1544), or K54 (ST29) capsules (mean 2.2 log10 LD50 (range 1.5-2.9)) were created to measure the effects on LD50 in a murine model of the hypervirulence-associated plasmid (pVir), iucA, prmpA, prmpA2 (truncated), irp2, and clbBC. FINDINGS: Curing pVir had the greatest increase in survival (mean LD50 to 7.6 (range 7.0-9.0, p ≤ 0.0001), a dosage comparable to classical K. pneumoniae. Results also showed increased mean LD50s for ΔprmpA (5.9, p ≤ 0.0001), ΔiucA (3.6, p ≤ 0.0001), Δirp2 (3.4), ΔrmpAΔiucA (6.3, p ≤ 0.0001), and ΔpVirΔirp2 (8.7, p ≤ 0.0001). Notably ΔpVir had an additional mean LD50 increase of 1.3 compared to the pVir-encoded ΔprmpAΔiucA (p ≤ 0.01), suggesting presence of additional pVir-virulence genes. Truncated pRmpA2 did not contribute to virulence. Odd ratios in the absence of pVir/yersiniabactin, pVir, pRmpA/aerobactin, pRmpA, aerobactin, yersiniabactin, and colibactin demonstrated a 250-fold, 67-fold, 20-fold, 16.7-fold, 9.6-fold, and 1.7-fold decrease in lethality respectively. INTERPRETATION: These data can guide countermeasure development. FUNDING: This work was supported by NIH R21 AI123558-01 and 1R21AI141826-01A1 (Dr. Russo) and the Department of Veterans Affairs VA Merit Review (I01 BX004677-01) (Dr. Russo). This study was also partially funded by the U.S. Defense Health Program (DHP) Operations and Maintenance.

Repurposing FDA-approved drugs to treat chemical weapon toxicities: Interactive case studies for trainees.

The risk of a terrorist attack in the United States has created challenges on how to effectively treat toxicities that result from exposure to chemical weapons. To address this concern, the United States has organized a trans-agency initiative across academia, government, and industry to identify drugs to treat tissue injury resulting from exposure to chemical threat agents. We sought to develop and evaluate an interactive educational session that provides hands-on instruction on how to repurpose FDA-approved drugs as therapeutics to treat toxicity from exposure to chemical weapons. As part of the Rutgers Summer Undergraduate Research Fellowship program, 23 undergraduate students participated in a 2-h session that included: (1) an overview of chemical weapon toxicities, (2) a primer on pharmacology principles, and (3) an interactive session where groups of students were provided lists of FDA-approved drugs to evaluate potential mechanisms of action and suitability as countermeasures for four chemical weapon case scenarios. The interactive session culminated in a competition for the best grant "sales pitch." From this interactive training, students improved their understanding of (1) the ability of chemical weapons to cause long-term toxicities, (2) impact of route of administration and exposure scenario on drug efficacy, and (3) re-purposing FDA-approved drugs to treat disease from chemical weapon exposure. These findings demonstrated that an interactive training exercise can provide students with new insights into drug development for chemical threat agent toxicities.

Developing improved crash prevention approaches through in-depth investigation of motorcycle crash causation patterns.

Despite advancements in road safety, Powered Two-Wheelers (PTWs) remain a vulnerable group with disproportionately high crash rates. This paper presents an in-depth analysis of PTW crashes in six European countries, with a case study of Loss of Control in Curves (LoCC), to address the gap between crash causation and prevention. By examining crash causation factors and their linkage to prevention strategies, the study illustrates various approaches for connecting causes and countermeasures. These approaches, which are applicable to different crash scenarios, include looking forward in the crash causation chains, looking backward, looking at only the last cause (critical events), or the first cause, or following a systemic approach. The research introduces a set of guidelines following the safe system approach, aiming to enhance the understanding of crash prevention among policymakers. The systemic approach to countermeasures, bridges the shortcomings of traditional crash causation studies that may exhibit bias or a narrow focus on "root causes". The proposed approach emphasizes the need for a comprehensive view of crash scenarios (i.e., considering the entire crash causation chain or multiple causation chains) and ensuring that preventive measures address the full spectrum of the system. It also takes in to account external factors such as cost, benefits, and politics, leading to improved road safety outcomes. The study findings are significant for researchers, since it is a step forward in in-depth crash causation studies, as well as road practitioners and policymakers, in providing a strategic framework for more effective and efficient road safety interventions.

Multi-level decisions for addressing trade-off in the cross-regional water-environment-agriculture interactive system under constraint of water ecological carrying capacity.

The complex-enhanced hierarchical relationship among multiple stakeholders in the water-environment-agriculture interactive system has been overlooked. This study develops a leader-follower-enhanced framework (named as FCMLP) that integrates variable-weight combination prediction model, multi-level programming, and fuzzy credibility constrained programming, which can effectively address the above problems under uncertainties. Five water ecological carrying capacity (WECC) statuses are treated as a critical constraint into the modeling framework to improve the accuracy of decision-making. An interactive fuzzy satisfaction algorithm is advanced for solving this multi-level problem, in which COD discharge minimization, economic benefits maximization, and grain yield maximization are taken as the upper-, middle-, and lower-level goals, respectively. The framework is applied to plan the cross-regional water-environment-agriculture interactive system in the Beijing-Tianjin-Hebei and Yangtze River Economic Belt. Solutions reveal that increased WECC status and credibility level would decrease 1.40%-1.74%, 0.71%-9.61%, and 1.63%-2.26% of water resources allocation, COD emissions, and economic benefits, respectively. Crop area and grain yield would dramatically decline by 4.13%-4.46% and 4.03%-4.67% when a credibility level increases from 0.8 to 1, respectively. The overall satisfactory degree would range from 0.58 to 0.70, which illustrates interactive decision-making process of multiple stakeholders. Significant differences can be observed in the optimized schemes of water resources allocation and environmental-economic-agricultural performances among various models. The amounts of allocated water resources, pollutant discharge, and economic output from the FCMLP model would be respectively 11.30%-13.45%, 14.90%-15.21%, and 73.12%-73.48% higher than those from the environment- and agriculture-oriented schemes, yet 13.81%, 32.05%, and 15.29% lower than those from the economy-oriented scheme. Some water adaptability countermeasures are given for ensuring the scientific operation of the South-to-North Water Transfer Project and alleviating conflicts between water source and receiving areas. Further exploration of the optimization scheme of water-environment-energy-agriculture system driven by climate change is still required for guaranteeing the dynamic balance of regional resources.

[The current situation of occupational health in the Internet industry and countermeasures].

As an important force in promoting the transformation and upgrading of the national economy, the occupational health of the Internet industry's employees has received widespread attention. This paper examines the current situation of occupational health risks and management in the Internet industry at home and abroad, and on this basis reveals the physical and mental health problems of Internet industry employees. Combining the existing regulations, policies and standard documents at home and abroad, countermeasures are proposed to improve the relevant laws and regulations and their guidelines, implement relevant job design requirements, build a healthy working environment, optimise the work management system and carry out workplace health promotion, in order to provide ideas to accelerate the improvement of occupational health issues in the Internet industry.

Lower body negative pressure as a research tool and countermeasure for the physiological effects of spaceflight: A comprehensive review.

Lower Body Negative Pressure (LBNP) redistributes blood from the upper body to the lower body. LBNP may prove to be a countermeasure for the multifaceted physiological changes endured by astronauts during spaceflight related to cephalad fluid shift. Over more than five decades, beginning with the era of Skylab, advancements in LBNP technology have expanded our understanding of neurological, ophthalmological, cardiovascular, and musculoskeletal adaptations in space, with particular emphasis on mitigating issues such as bone loss. To date however, no comprehensive review has been conducted that chronicles the evolution of this technology or elucidates the broad-spectrum potential of LBNP in managing the diverse physiological challenges encountered in the microgravity environment. Our study takes a chronological perspective, systematically reviewing the historical development and application of LBNP technology in relation to the various pathophysiological impacts of spaceflight. The primary objective is to illustrate how this technology, as it has evolved, offers an increasingly sophisticated lens through which to interpret the systemic effects of space travel on human physiology. We contend that the insights gained from LBNP studies can significantly aid in formulating targeted and effective countermeasures to ensure the health and safety of astronauts. Ultimately, this paper aspires to promote a more cohesive understanding of the broad applicability of LBNP as a countermeasure against multiple bodily effects of space travel, thereby contributing to a safer and more scientifically informed approach to human space exploration.

How Global Collaboration Can Improve the Medical Countermeasure Life Cycle for Infectious Disease Outbreaks.

Infectious disease outbreaks have become increasingly common and require global partnership for adequate preparedness and response. During outbreaks, medical countermeasures (MCMs)-vaccines, therapeutics, and diagnostics-need to reach patients quickly. Recent outbreaks exemplify that products with regulatory approval can expand access and reach patients quicker than investigational products. Unfortunately, insufficient funding globally and differences in funders' prioritization puts gains and future efforts at risk. Of primary concern is (1) lack of a feasible regulatory path and clinical capability to achieve regulatory approval for new MCMs for many diseases; and (2) the need for partners with the mandate, funding, and capabilities to support long-term sustainment of manufacturing capability and stockpiling of licensed products. Without collaboration, the global community runs the risk of losing the capabilities built through years of investment and being underprepared to combat future threats. Synergies between funders are critical to create long-term sustainment of products to ensure access.

Terrorism as Coalitional Predation: Explaining Definitional Ambiguities and Precautionary Responses.

Terrorism continues to be an enigmatic and contested concept, lacking a universally accepted definition despite extensive scholarly debate. Lay intuitions, however, demonstrate a notable convergence in identifying acts as "terrorism" when specific situational features are present, such as indiscriminate violence and out-group perpetration. These features elicit predictable and robust precautionary responses, raising the question: Is there a unified and parsimonious explanation for these phenomena? It is hypothesized that a situational template exists in the human mind, the coalitional predation template (CPT), which evolved not to detect modern-day terrorism, per se, but to identify and respond to situations of predatory coalitional conflict. The paper examines the potential cues and mechanisms that constitute the psychological systems activated by such threats, suggesting that matching the input cues of the CPT triggers well-documented precautionary responses to terrorism. However, this cue-based system may not align neatly with contemporary threats, leading to disproportionate responses to some threats while underestimating others. The model also posits that interpretations of violence can vary due to incomplete cues and the social position of the evaluator, leading to public disagreements and inconsistencies in defining terrorism. Consequently, arriving at an unambiguous and widely accepted definition of terrorism may not be possible. The model presented may account for a range of phenomena, including the inclination towards attributing mental illness to particular violent incidents and the uncanny surface similarities between terrorism and war crimes. The findings have significant implications for both the theoretical understanding of terrorism and practical policy responses.

The disaster liaison for pediatric and perinatal medicine: A new system in Japan.

BACKGROUND: Worldwide, children, newborns, and pregnant or postpartum women are vulnerable to disasters and emergency situations, and providing support to this population is of great concern. Japan is located in a disaster-prone area, so disaster response and risk reduction strategies are important priorities. METHODS: We introduce a system called the Disaster Liaison for Pediatric and Perinatal Medicine (DLPPM). This was created with a specific focus on perinatal children and pregnant women in Japan. We report the details of its activities, discuss its challenges, and draw on lessons learned for the further development of perinatal support systems, particularly for children. RESULTS: The lessons learned from the activities of the DLPPM include the following: (1) establish a support system for emergency specialists beyond those with pediatric and perinatal specialties; (2) mitigate the risk of indirect damage caused by primary disasters; and (3) establish a networking function linked to existing pediatric and perinatal medicine facilities. CONCLUSIONS: By establishing similar systems, we believe that it will be feasible to address pediatric and perinatal care needs in disaster response contexts in other countries and regions around the world.

Effects of radiation mitigating amino acid mixture on mice of different sexes.

To date, few FDA-approved medical countermeasures are available for addressing hematopoietic acute radiation syndrome (H-ARS). In this study, we present our latest research findings focusing on the evaluation of a novel radiation mitigator known as the mitigating amino acid mixture (MAAM). MAAM is composed of five amino acids as the recently reported amino acid-based oral rehydration solution for mitigating gastrointestinal (GI)-ARS. CD2F1 male and female mice were exposed to 60Co-γ total body irradiation (TBI) at 9.0 or 9.5 Gy. Following irradiation, mice were orally administered with MAAM or a saline vehicle control once daily for a duration of 14 days, commencing 24 h after TBI. Mouse survival and body weight change were monitored for 30 days after irradiation. Complete blood counts (CBCs), bone marrow (BM) stem and progenitor cell survival (clonogenicity), and a serum cytokine antibody array were analyzed using samples from day 30 surviving mice. Our data revealed that MAAM treatment significantly enhanced survival rates in irradiated male CD2F1 mice, and the survival rate increased from 25% in the vehicle control group to 60% in the MAAM-treated group (p < 0.05) after 9.0 Gy TBI. The number of BM colonies significantly increased from 41.8 ± 6.4 /104 cells (in the vehicle group) to 78.5 ± 17.0 /104 cells (in the MAAM group) following 9.0 Gy TBI. Furthermore, MAAM treatment led to a decrease in the levels of six cytokines/proteins [cluster of differentiation 40 (CD40), interleukin (IL)-17A, C-X-C motif chemokine 10 (CXCL10/CRG-2), cutaneous T cell-attracting chemokine (CTACK), macrophage inflammatory protein (MIP)-3ß, and IL-1ß] and an increase in the levels of five other cytokines/proteins [IL-3Rß, IL-5, leptin, IL-6, and stem cell factor (SCF)] in mouse serum compared to the vehicle group after 9.0 Gy TBI. However, similar alleviating effects of MAAM were not observed in the irradiated CD2F1 female mice. The serum cytokine profile in the irradiated female mice was different compared to the irradiated male mice. In summary, our data suggest that the beneficial effects of the mitigative amino acid combination treatment after radiation exposure may depend on sex.

Pandemic preparedness and response: a new mechanism for expanding access to essential countermeasures.

As the world comes together through the WHO design and consultation process on a new medical counter-measures platform, we propose an enhanced APT-A (Access to Pandemic Tools Accelerator) that builds on the previous architecture but includes two new pillars - one for economic assistance and another to combat structural inequalities for future pandemic preparedness and response. As part of the APT-A, and in light of the Independent Panel on Pandemic Preparation & Response's call for an enhanced end-to-end platform for access to essential health technologies, we propose a new mechanism that we call the Pandemic Open Technology Access Accelerator (POTAX) that can be implemented through the medical countermeasures platform and the pandemic accord currently under negotiation through the World Health Assembly and supported by the High-Level Meeting review on Pandemic Prevention, Preparedness, and Response at the United Nations. This mechanism will provide (1) conditional financing for new vaccines and other essential health technologies requiring companies to vest licenses in POTAX and pool intellectual property and other data necessary to allow equitable access to the resulting technologies. It will also (2) support collective procurement as well as measures to ensure equitable distribution and uptake of these technologies.

Evaluation methods of BDS-3 ground-segment defensive capability oriented to satellite navigation countermeasures.

Owing to intentional interference and destructions during satellite navigation countermeasures, the security application of global navigation satellite systems (GNSS) faces immense challenges. To ensure the safe application of the GNSS in complex electromagnetic environment, the system-level defensive capability need be assessed, which can make for maintaining GNSS normal service during countering and further realizing the optimal decision. Therefore, this study used the ground control segment in the GNSS as the evaluation object, the bottom indices related to the criterion layers including service performance and station function as the key evaluation indices, and the technical requirement of each index under a secure situation as the standard, to propose the evaluation system including index system and evaluation methods for the ground-segment defensive capability. As BeiDou navigation satellite system III (BDS-3) is a global navigation satellite system independently built and operated by China, it was taken as a case for method verification. Then, BDS-3 two-way observation data between the satellite and the ground and between stations, which was collected from Beijing flight Control Center, from March 5 to 12 (2022) were selected during tests, and the results were compared with the existing standards contained in BDS open service performance standard to evaluate the system-level defensive capability. Evaluation Results of positioning accuracy and error correction ability for the BDS-3's ground stations determined through seven damage experiments with different interference strength show that: Corresponding horizontal and vertical positioning accuracy of stations under test did not exceed 1 m in the statistical period and their convergence time did not exceed the limit (30 min); thus, the ground segment of the BDS-3 has a good defensive capability. Compared to comprehensive evaluation results of the BDS-3, based on the theoretical threshold (the ground-segment threshold ≤48.40 % and the space-segment threshold ≤51.60 %), we know that its ground-segment defense (14.06 %) was worse than GPS ground-segment defense (14.43 %), whereas the ground-segment defense of the BDS/GPS integrated system (15.29 %) was best and its capability evaluation grade was strong. They indicate system's future improvements should focus more on enhancing the development scale and service efficiency of the BDS-3's ground stations in the Western Hemisphere, and reasonably promote system compatibility and interoperability while considering facility cost and operating efficiency.

Risk-based public health impact assessment for drinking water contamination emergencies.

Chemical spills in surface waters pose a significant threat to public health and the environment. This study investigates the public health impacts associated with organic chemical spill emergencies and explores timely countermeasures deployable by drinking water facilities. Using a dynamic model of a typical multi-sourced New England drinking water treatment facility and its distribution network, this study assesses the impacts of various countermeasure deployment scenarios, including source switching, enhanced coagulation via poly­aluminum chloride (PACl), addition of powdered activated carbon (PAC), and temporary system shutdown. This study reveals that the deployment of multiple countermeasures yields the most significant reduction in total public health impacts, regardless of the demand and supply availability. With the combination PAC deployed first with other countermeasures proving to be the most effective strategies, followed by the combination of facility shutdowns. By understanding the potential public health impacts and evaluating the effectiveness of countermeasures, authorities can develop proactive plans, secure additional funding, and enhance their capacity to mitigate the consequences of such events. These insights contribute to safeguarding public health and improving the resilience of drinking water systems in the face of the ever-growing threat of chemical spills.

Effects of dynamic visual feedback system on seasickness.

Motion sickness (MS) poses challenges for individuals affected, hindering their activities and travel. This study investigates the effect of a visual dynamic device, forming an artificial horizon plane, on symptoms and physiological changes induced by MS. This device consists of vertical light-emitting diodes whose illumination varies according to the boat's movements. Fifteen subjects with moderate-to-severe MS susceptibility were exposed to a seasickness simulator with and without the device. Symptoms were assessed immediately after exposure. Time spent in the simulator, heart rate, and temperature were also recorded. Symptom intensity at the end of the experience did not differ, but the time spent in the simulator was significantly longer with the device (+46%). Variations in heart rate were also observed. The device delays symptom onset and can be used as a tool against MS. Further research is needed to evaluate its effects, for example, during more prolonged exposure to MS-inducing stimuli.

Underreporting or Failed Notification? Global Botulism Reporting, 2000-2022.

Botulism is a rare, potentially fatal illness caused by botulinum toxins produced by Clostridium bacteria. There are no coordinated worldwide reporting mechanisms for botulism cases and therefore few reliable case frequency estimates. This study aimed to establish an international benchmark for case frequency to determine estimated global rates of underreporting of botulism cases. To this end, a comprehensive, multilingual search of major global and national databases, including gray data and government sources, was performed. Data from case series were pooled, standardized against United Nations midyear population estimates, and analyzed using Kolmogorov-Smirnov tests to identify normally distributed data series. National incidence rates of normally distributed series were compared with that of the United States, which was considered the gold standard due to its extensive data reported for 2004-2018. A total of 6,932 botulism cases from 59 nations were identified in the literature, with a global case fatality rate of 1.37%. The national mean incidence rate ranged from 0.00 to 8.04 cases per million people, with an international mean incidence rate of 0.62 cases per million people. At the continent level, incidence rates tended toward normal distributions, although few countries outside of North America and Europe exhibited normal distributions. Based on comparisons with the US standard, an estimated 88.71% of botulism cases worldwide were unreported in 2016. Better awareness of botulism among healthcare professionals, coordinated global reporting mechanisms, and research on additional contributing factors to underreporting would enable better understanding of global case frequency, thereby potentially reducing the global incidence of botulism and improving outcomes.