1551. EVOLUTION---an outbreak that grows before anyone sees it is where the pathogen changes.
Lipsitch 17 — Marc Lipsitch. July 26. Professor of Epidemiology and Director of the Center for Communicable Disease Dynamics at the Harvard T.H. Chan School of Public Health. Health Security, “If a Global Catastrophic Biological Risk Materializes, at What Stage Will We Recognize It?,” vol. 15, no. 4 Clopus
These considerations have concrete implications for the effort to identify, reduce the probability and impact of, and respond to GCBR.
1. Preparing for GCBR means preparing for smaller-impact risks to ensure that they do not become globally catastrophic. Effective control of an outbreak while it is small is the most effective way to ensure that the more difficult effort to control a widespread outbreak never becomes necessary. Biologically, the amount of genetic variation in a pathogen population rises as the number of infected people grows, thereby increasing the risk of pathogen evolution to greater severity or contagiousness, or to acquiring a new route of transmission. Keeping small outbreaks from growing is an essential part of GCBR preparedness. Another consideration reinforcing this approach is the human element: Systems that are designed to be used only for global catastrophes will, we can hope, often go unused for decades or more. Such systems are unlikely to be kept in working order and continuously improved unless they find application in responding to more common, subcatastrophic events.
1562. It doesn't burn out---mpox sustained silent chains that symptom-based surveillance can't see.
Abdullahi 26 — Adam Abdullahi, Ifeanyi Omah, Reshma Kassanjee, et. al. January 20. Cambridge Institute of Therapeutic Immunology and Infectious Disease, University of Cambridge. African Center of Excellence for Genomics of Infectious Diseases, Redeemer’s University, Ede, Nigeria. Nature Communications, “Sero-genomic evidence for occult mpox exposure in healthy Nigerian adults,” vol. 17 Clopus
Next, we observed antigen-specific antibody boosting in a subset of younger, post-1980 participants who lacked evidence of prior vaccination and were mostly male, supporting the occurrence of undetected MPXV exposure. While this likely reflects silent subclinical exposure rather than symptomatic infection, we acknowledge that serology alone cannot provide absolute proof of asymptomatic infection, and we therefore frame these findings as indicative of exposure rather than definitive evidence of silent transmission. In our pooled cohorts (HCWs and community participants), this corresponded to ≈3% of participants, a figure that should not be interpreted as a population-level prevalence but rather as a reflection of our study cohort. These observations dovetail previous reports of subclinical seroconversion from screening cohorts in Spain 15 (6%, 7/113), France 18 (6.5%, 13/200), Japan 13 (0.4%, 5/1346), and Belgium 17 (1.3%, 3/225). Animal data provide a mechanistic parallel: experiments in the UK showed that common brown rats ( Rattus norvegicus ) inoculated with Clade IIb MPXV remained clinically silent despite PCR positivity, yet seroconverted and transmitted infection to cage-mates without detectable viraemia 73 . This supports our observation of antibody boosting in the absence of reported clinical disease, highlighting the plausibility that cryptic rodent-human/human-rodent/human-human transmission cycles 2 , 74 , 75 , 76 can sustain below the radar transmission that evade syndromic surveillance. The same cryptic transmission cycle has been observed for arenaviruses such as Lassa fever, which is peri-domestically maintained by the common African rat ( Mastomys natalensis/couchi) reservoir host 77 , 78 , 79 , 80 . One recent meta-analysis estimated seroprevalence of Lassa fever up to 58% across the West African region 81 with reported cross-sectional seroprevalence of 50% by age 5 82 and 82% in a general endemic West African population which exceeds reported case numbers; implying substantial subclinical spread with limited syndromic capture 83 . These data indicate higher than reported rates of exposure to heterogenous emerging infectious disease threats that can remain largely undetected 84 .
Our present observations are further validated by our country specific genomic data and previous phylogenetic analysis which revealed how MPXV may persist in the presence of partial immunity. Epidemiologically, a low dispersion parameter (k ≈ 0.4–0.8) at 50% and 100% ascertainment together with a long doubling time despite exponential growth suggests transmission concentrated in clustered contact networks, consistent with focal outbreaks in households or other close-contact groups 10 . The relative absence of large clusters (>3 linked cases) supports a pattern in which stochastic superspreading events, rather than sustained community-wide transmission, drive persistence. This dynamic aligns with modelling of the 2022 global outbreak and explains how MPXV can circulate at low reported incidence, undetected and yet still generate the boosting serological patterns we observed in our population 59 , 62 . In context, the dead-end infection of most mpox transmission means traditional case-based surveillance is unlikely to capture the full extent of mpox transmissions, and public health messaging must be context dependent 85 , particularly in settings where infections with the Clade IIb presents with mild and atypical symptoms. Furthermore, our focus on serological analysis of samples collected during the COVID-19 when healthcare resources were focused on responding to the pandemic strengthens the plausibility of missed mpox diagnosis.
Antigen-specific kinetics showed boosting of B6R, M1R, and A35R, with B6R exhibiting the largest fold increases across exposed participants, highlighting its prominence 86 This EEV-specific envelope protein expressed in the extracellular virion form of MPXV exhibited the highest post-exposure boost (11-fold) and strongest inter-antigen correlation between antigen pairs. To a lesser extent, M1R (6.2-fold) and A35R (5.2-fold) were also exhibited notable post-exposure boosting. Structural and functional studies provide a mechanistic rationale for this hierarchy: cryo-EM resolution of B6R in complex with monoclonal antibodies has revealed multiple simultaneously accessible neutralising epitopes 71 , and B6-specific antibodies were shown to neutralise extracellular virus in a complement-dependent manner, significantly reducing viral load in lethal vaccinia mouse models. Additional work demonstrated that prophylactic administration of a B6R-specific monoclonal antibody (B7C9) within 24 h of lethal challenge reduced both viral burden and disease severity, further confirming its functional relevance 87 Finally, complementary work with multivalent mRNA constructs incorporating B6R, A35R, and M1R reported 100% protection in mice against lethal vaccinia challenge 32 highlighting the translational potential of this antigenic triad for surveillance and assay design. This triad may represent practical surrogate targets for MPXV exposure and could underpin the development of field-deployable multiplex assays to enhance detection of subclinical mpox in low-resource settings, building on recent advances 88 , 89 .
Our analysis was subject to limitations, and we note multiple caveats in our data interpretation. Firstly, genomic sampling was geographically skewed toward urban Southern Nigeria, likely under-representing rural transmission and although we assumed multiple underreporting factors in our genomic modelling, actual case detection rates could vary. Secondly, our population comprised of COVID-19 vaccinee cohorts, and their health-seeking behaviour may not fully reflect those of the wider population, introducing potential selection bias. Thirdly, our analysis measured only binding antibody and not functional neutralising antibody, although there is evidence supporting correlation between B6R, A35R, M1R and neutralisation. In addition, while our assay employed MPXV-specific antigens, the high degree of sequence similarity across Orthopoxvirus genus 90 means that serological detection of anti-MPXV IgG cannot be attributed with absolute certainty to MPXV alone 35 . However, given the absence of a regional vaccinia vaccination program and the epidemiological context in Nigeria, recent MPXV exposure is the most plausible explanation in younger adults with legacy smallpox vaccination remaining the most likely explanation for reactivity in older adults. We note further that the utility of combining multiple antigens to define seropositivity and exposure type has been demonstrated 91 We employed a slightly modified antigen panel adapted for the Luminex platform while ensuring overlap with validated and immunodominant antigenic targets. Our assay required reactivity to ≥4 of 6 MPXV antigens, a conservative approach relative to Yates and colleagues 91 who used ≥3 of 5 antigens. This conservative approach, consistent with our prior work on hepatitis B serology in Africa was designed to minimise false positives 90 . Further, we supplemented our serological findings with follow-up interviews and professional verification of smallpox vaccination scars among seropositive HCWs, these data were limited to a small subset and are subject to recall bias. Nonetheless, the strong concordance between self-reported vaccination history, visible scars, and serological reactivity lends additional confidence to the interpretation of residual smallpox-derived immunity. Finally, structured collection of mpox-compatible clinical symptoms was not undertaken in the parent SARS-CoV-2 vaccine cohorts, which primarily captured SARS-CoV-2 vaccination events and COVID-like adverse events. Although none of the five participants with boosting responses reported mpox-like illness, we cannot exclude unrecognised or mild disease. The retrospective nature of the cohorts also limited assessment of behavioural or social drivers of exposure.
1573. The one that didn't burn out is the one they couldn't name for three months.
Jean Louis 25 — Frantz Jean Louis, Lisa Nichols, Cecilia de la Torre, et. al. August 14. Infectious Disease Detection and Surveillance project, ICF, Rockville, Maryland. Public Health Reviews, “Strengthening Outbreak Detection in Africa to Achieve the 7-1-7 Global Framework: Challenges and Opportunities,” vol. 46 Clopus
In 2023, the African continent faced a staggering eighty major public health events and sixty-one outbreaks [ 1 ]. Given the constraints in many resource-limited countries, strengthening their capacities for early detection, notification, and response is paramount to mitigating the impact of public health emergencies. Rapid identification and effective response play a pivotal role in minimizing morbidity and mortality during such critical events. The capacities for early detection, notification, and response to emerging infectious diseases are defined by the legally binding International Health Regulations 2005 (IHR 2005). These regulations require the 196 signatory member states to prevent, protect against, control, and provide a public health response to the international spread of diseases [ 2 ].
Outbreak detection refers to the initial identification of a potential public health threat, typically through surveillance systems that monitor disease patterns in populations. However, detection alone is not sufficient; confirmation of the outbreak is equally critical. Confirmation involves verifying the presence of the disease through laboratory testing or other diagnostic methods to ensure that the detected signal indeed represents a threat. Both detection and confirmation are essential for timely and accurate outbreak response [ 3 ]. Early detection allows for rapid public health interventions, while confirmation ensures that resources are appropriately allocated to real threats, preventing unnecessary panic and optimizing the response strategy.
Timeliness in detection and response remains a critical aspect of robust surveillance systems. However, poor diagnostic preparedness has significantly contributed to delays in identifying recent outbreaks. The insufficient testing capacity and delays in testing and reporting exacerbated the expansion of the 2013–2016 Ebola epidemic in West Africa [ 4 ]. A three-month delay occurred between the index case and the identification of the causative agent [ 5 , 6 ]. Post-outbreak analyses reveal that diagnosing 60% of patients within 1 day of symptoms onset instead of 5 days could have reduced the attack rate from 80% to nearly 0% [ 4 , 7 , 8 ]. Although timeliness metrics (such as time to detection, time to verification, time to response) do not fully capture the complexity of outbreak surveillance and response, they have been proposed as valuable tools for monitoring and evaluating outbreak response performance, with the aim of optimizing response efforts [ 9 , 10 ].
Resolve to Save Lives proposed a 7-1-7 that sets three time-bound, real-world performance targets across the entire outbreaks detection-to-response continuum: ≤7 days from a pathogen’s emergence to detection of a suspected outbreak, ≤1 day from detection to formal notification and initiation of investigation, and ≤7 days from notification to completion of essential early-response actions (e.g., case confirmation, contact tracing, risk communication, infection-control measures) [ 11 , 12 ]. Because these milestones are simple, measurable, and pathogen-agnostic, they expose bottlenecks anywhere in the surveillance-response chain and allow rapid, data-driven performance improvement—much as the HIV 90-90-90 targets accelerated antiretroviral scale-up [ 11 , 13 ]. Recognizing its value, the World Health Organization (WHO) embedded 7-1-7 metrics in its 2023 Early Action Review (EAR) guidance as the primary yard-stick for rapid performance enhancement during health emergencies [ 14 ]. EAR promotes structured, rapid learning from recent public health events to inform timely improvements in detection systems before the next crisis emerges [ 15 ]. By conducting routine timeliness-focused reviews after major outbreaks, countries can systematically assess bottlenecks across the surveillance and diagnostic continuum. Integrating EARs into national outbreak response strategies can help institutionalize continuous learning, improve timeliness metrics, and align response systems with the 7-1-7 targets. The WHO Regional Office for Africa (WHO AFRO) has officially adopted the 7-1-7 indicators as a key target for timeliness in its 2022–2030 Regional Strategy for Health Security and Emergencies [ 16 ].
To improve outbreak detection and confirmation capacity and timeliness, a comprehensive surveillance system across human, animal, and environmental health (ecosystem) sectors should be implemented. Robust governance is necessary to ensure that these elements are well coordinated, adequately resourced and aligned with national and international standards. Here we outline strategies for African countries to achieve this seven-day detection target. The strategies are built on five main pillars:
Enhance diagnostic preparedness: Invest in laboratories and diagnostic networks for rapid pathogen identification.
Strengthen surveillance: Develop robust disease surveillance systems to detect outbreaks early, leveraging both traditional and more proactive surveillance approaches.
1581. THEIR OWN AUTHOR runs the trade-off---then says every worst-case trait is separately proven.
Millett 17 — Piers Millett and Andrew Snyder-Beattie. September 1. Senior Research Fellow at the Future of Humanity Institute, University of Oxford, former Deputy Head of the Biological Weapons Convention Implementation Support Unit at the United Nations. Director of Research at the Future of Humanity Institute, University of Oxford. Health Security, “Existential Risk and Cost-Effective Biosecurity,” vol. 15, no. 4 Clopus
A skeptic would have many good reasons to think that existential risk from disease is unlikely. Such a disease would need to spread worldwide to remote populations, overcome rare genetic resistances, and evade detection, cures, and countermeasures. Even evolution itself may work in humanity's favor: Virulence and transmission is often a trade-off, and so evolutionary pressures could push against maximally lethal wild-type pathogens. 5 , 6
While these arguments point to a very small risk of human extinction, they do not rule the possibility out entirely. Although rare, there are recorded instances of species going extinct due to disease—primarily in amphibians, but also in 1 mammalian species of rat on Christmas Island. 7 , 8 There are also historical examples of large human populations being almost entirely wiped out by disease, especially when multiple diseases were simultaneously introduced into a population without immunity. The most striking examples of total population collapse include native American tribes exposed to European diseases, such as the Massachusett (86% loss of population), Quiripi-Unquachog (95% loss of population), and the Western Abenaki (which suffered a staggering 98% loss of population). 9
In the modern context, no single disease currently exists that combines the worst-case levels of transmissibility, lethality, resistance to countermeasures, and global reach. But many diseases are proof of principle that each worst-case attribute can be realized independently. For example, some diseases exhibit nearly a 100% case fatality ratio in the absence of treatment, such as rabies or septicemic plague. Other diseases have a track record of spreading to virtually every human community worldwide, such as the 1918 flu, 10 and seroprevalence studies indicate that other pathogens, such as chickenpox and HSV-1, can successfully reach over 95% of a population. 11 , 12 Under optimal virulence theory, natural evolution would be an unlikely source for pathogens with the highest possible levels of transmissibility, virulence, and global reach. But advances in biotechnology might allow the creation of diseases that combine such traits. Recent controversy has already emerged over a number of scientific experiments that resulted in viruses with enhanced transmissibility, lethality, and/or the ability to overcome therapeutics. 13-17 Other experiments demonstrated that mousepox could be modified to have a 100% case fatality rate and render a vaccine ineffective. 18 In addition to transmissibility and lethality, studies have shown that other disease traits, such as incubation time, environmental survival, and available vectors, could be modified as well. 19-21
1592. “It hasn't happened” is the wrong guide---twenty-six controlled outbreaks bounded nothing.
Lipsitch 17 — Marc Lipsitch. July 26. Professor of Epidemiology and Director of the Center for Communicable Disease Dynamics at the Harvard T.H. Chan School of Public Health. Health Security, “If a Global Catastrophic Biological Risk Materializes, at What Stage Will We Recognize It?,” vol. 15, no. 4 Clopus
When events, such as new infectious diseases, occur that may become globally catastrophic, history can be an invaluable guide. Global biological catastrophes have fortunately been rare in history, so historical examples are few. However, historical examples can provide “existence proofs” that a particular course of events can happen. Patterns of spread in different US cities with different levels of control measures showed that nonpharmaceutical interventions could retard the spread of 1918 influenza, 10 , 11 and this historical example has been appropriately used in pandemic planning for future severe pandemics. 12
The 1918 and 1957 influenza pandemics showed peak activity not in the normal flu season (winter) but earlier, in the mid- to late autumn. 2 These historical examples—along with mathematical modeling results—could have been used for planning of vaccine supplies in 2009, 13 but awareness of them seems to have been limited at the time. Likewise, the increased virulence of the 1918 influenza in the fall compared to the milder spring might have been taken as a legitimate justification for aggressive action to secure vaccines and antivirals in 2009, even if the relatively mild course of illness in spring 2009 had been confidently documented. After all, in 1 of 3 historic pandemics of the 20th century, a mild spring wave had been followed by a catastrophic autumn wave, so planners might legitimately have considered that a reasonable scenario to plan for.
There is an important asymmetry in how we evaluate risk based on historical examples. If a sequence of events has happened in the past, we are well justified in considering it a possible or likely scenario in future events, as in the examples in the preceding paragraph. If a particular course of events has not happened in the recorded past, we should be far more cautious about concluding it will not happen in the future. As an example: If asked in 2013 whether an outbreak of Ebola virus disease could get out of control and infect more than 10,000 people, many observers, including me, would likely have said it was not much of a risk. From the virus's discovery in 1976 to mid-2013, there had been 26 separate instances in which at least 1 person had known, symptomatic Ebola virus infection, most of them in sub-Saharan Africa ( https://www.cdc.gov/vhf/ebola/outbreaks/history/chronology.html ). The outbreaks that resulted ranged in size from 1 person (the index case) to 425. Based on this history, many of us would have said that basic public health measures can contain an Ebola outbreak before it spreads widely.
Such reasoning—proven wrong by the estimated 28,652 cases in the 2014-15 outbreak in Guinea, Sierra Leone, and Liberia—would have missed 2 key points. First, circumstances differ, and, in particular, controlling an outbreak with public health measures means detecting and identifying it while it is still small. Failures of surveillance and response can (and did) allow the epidemic to reach a size where containment becomes far more difficult. Second, the fact that public health had succeeded in controlling 26 Ebola outbreaks was not evidence that it would do so every time. The so-called rule of 3 in medical decision making is that if an event has occurred zero times out of X times when it might have occurred, we can be relatively confident that the probability of its occurring was less than 3/X. 14 In the case of Ebola outbreaks, an uncontrolled outbreak had occurred in zero of the 26 events prior to 2014, so (under the assumption that the probability of losing control was the same in each of those outbreaks) we should have been confident that the probability of losing control of an Ebola outbreak was less than about 12%, or 3/26. To use a common analogy: If we have a big urn full of black and red balls, and we draw a black ball 26 times in a row, we can't be sure of how many of the balls in the urn are red. Basic probability theory says that the 95% confidence interval for the proportion of red balls in the urn runs from about 0 to 12%. Operationally, these are very different numbers! Yet, we are not good at thinking rationally about unusual events, 15-18 and incentives sometimes exist to act as if they were less common than they are. 19 We should beware of “it's never happened before” as a guide to planning for the future.
Practical Implications
These considerations have concrete implications for the effort to identify, reduce the probability and impact of, and respond to GCBR.
1. Preparing for GCBR means preparing for smaller-impact risks to ensure that they do not become globally catastrophic. Effective control of an outbreak while it is small is the most effective way to ensure that the more difficult effort to control a widespread outbreak never becomes necessary. Biologically, the amount of genetic variation in a pathogen population rises as the number of infected people grows, thereby increasing the risk of pathogen evolution to greater severity or contagiousness, or to acquiring a new route of transmission. Keeping small outbreaks from growing is an essential part of GCBR preparedness. Another consideration reinforcing this approach is the human element: Systems that are designed to be used only for global catastrophes will, we can hope, often go unused for decades or more. Such systems are unlikely to be kept in working order and continuously improved unless they find application in responding to more common, subcatastrophic events.
1603. The class of risk is engineered plus undetectable---and the tools are getting cheaper.
Johnson 24 — Tess Johnson. February 8. Postdoctoral Researcher in Bioethics at the Ethox Centre, Nuffield Department of Population Health, University of Oxford. Journal of Bioethical Inquiry, “For the Good of the Globe: Moral Reasons for States to Mitigate Global Catastrophic Biological Risks,” vol. 21 Clopus
Harms during the COVID-19 pandemic resulted not only from the disease itself, but from poorly internationally coordinated responses. Mortality, economic losses, and ongoing mental and physical health burdens continue around the world. The pandemic highlighted human vulnerability to biological threats, and policymakers’ often-ineffectual attempts to take collective action against them. In 2020–2021, worldwide excess mortality associated with COVID-19 was around fifteen million lives (World Health Organization 2022 ). Yet, even COVID-19 has not had a very significant impact on the world, when compared to the biological catastrophes that might be still to come. “Global catastrophic biological risks” (GCBRs) can be defined as events leading to “sudden, extraordinary, widespread disaster beyond the collective capability of national and international governments and the private sector to control” (Schoch-Spana, et al. 2017 , 323). Examples may include naturally occurring pandemics, pandemics resulting from artificial/engineered pathogens, use of bioweapons programmes, the development of extreme drug resistance across multiple pathogens, or bio-hacking and harmful outcomes of human genome editing (Nouri and Chyba 2011 ). Their possible effects (whether the actions were deliberate or accidental) range from societal collapse to the institution of totalitarian regimes, to extreme morbidity and mortality across the human population. Indeed, they might occur on a scale that could cause human extinction and would then be re-termed existential risks. Whilst the risk of extinction from natural causes remains relatively constant (and we are not extinct yet, despite having spent a while now on this planet), anthropogenic existential and catastrophic risks are increasing. Despite this, bioethical work to date mostly focuses on natural pandemics and biological risks (Dawson 2007 ; Emanuel, et al. 2020 ; Giubilini 2019 ), with some exceptions (Adalja, et al. 2019 ; Chyba and Greninger 2004 ). Building on emerging public goods accounts in bioethics, I propose applying this framing to GCBRs to illuminate the issue of GCBR mitigation in a way that may help the future development and international coordination of interventions.
Experts on GCBRs have estimated a chance of up to 1 in 1000 that humanity will become extinct from an artificial pandemic within the next century (Lewis 2020 ; Millett and Snyder-Beattie 2017 ). This is an example of only one potential GCBR, and we might therefore expect the risk of extinction from GCBRs as a whole to be greater. The data is based on extrapolations from historical data on experiments with creating or modifying pathogens. The situation for this GCBR and others that involve the use of biotechnologies, including biohacking and misuses of human genome editing may deteriorate in the future, as two changes occur (Lewis 2020 ). The first change is increasing technological availability: the tools needed to edit genomes, whether pathogen or human, are becoming more available and affordable, with benchtop DNA synthesizers available to buy online, and mail-order DNA sequences available for USD 100-300 for a small gene, even back in 2017. The second change is knowledge availability: knowledge concerning how to simultaneously increase the lethality, transmissibility, incubation time and drug-resistance of pathogens whilst reducing their detectability is set to improve as synthetic biology research and, in particular, gain-of-function research continues and is performed and published in freely or pay-for-access academic journals. (For instance, in 2012, the U.S. National Science Advisory Board for Biosecurity allowed the publication of studies that described the modification of H5N1 viruses to allow airborne transmission between ferrets (Burki 2018 ).) The same goes for knowledge surrounding the influence of particular human genes on our traits and how these might be used for personal gain (Ma, et al. 2017 ).
Existing measures to mitigate GCBRs seem inadequate (Chyba and Greninger 2004 ; Kilbourne 2011 ). The main international agreement that might mitigate these risks is the biological weapons convention (BWC). The BWC aims to ban the development, storage, or use of biological and chemical weapons. In theory, this should prevent states party to the convention from causing a number of different types of GCBRs, and should require them to ensure their citizens are prevented from doing so. The BWC was introduced in 1972 and there are currently 185 states party to the convention (United Nations Office for Disarmament Affairs 1972 ). However, current levels of financial and structural support leave the BWC with a staff of only four people, and insufficient resources to verify state compliance or penalize non-complying states (Chyba and Greninger 2004 ). Whilst there are a number of other groups whose work supports the BWC, such as the United Nations Office for Disarmament Affairs, these do not play a direct role in monitoring and enforcement of the BWC. And whilst there may be other work being done that is not made public, if this exists, it does not appear too successful: there have been multiple violations of the convention (discovered or suspected) since its introduction (Lentzos 2019 ). What’s more, domestic structures for enforcement within nations appear scarce—for instance, scientists judge there to be too little regulation of the publication and performance of gain-of-function research in the United States and Europe (Fears and ter Meulen 2015 ; Kozlov 2022 ).
It may seem odd that states are not highly motivated to mitigate these risks, even without an international agreement. Mitigation would benefit both states’ own citizens, and everyone else—in fact, that may be part of the problem. When the benefits of a state investing in protection against a global threat befall everyone, there may be very little prudential or economic reason for purely self-interested states (that is, states that care only about their own citizens’ interests) to contribute to protection, rather than relying on others’ contributions to protect their own citizens (Aschenbrenner 2020 ; Millett and Snyder-Beattie 2017 ). Economic solutions and effective coercive mechanisms at the international level—which, as already noted, may be difficult to maintain (Martin 1999 )—are unlikely to be successful, then. That said, there may be some possible solutions to mitigating GCBRs as a collective action problem (Weimann, et al. 2019 ), based on not merely economic but moral reasons.
My aim in this paper is to search for moral reasons to ground state decisions to undertake GCBR mitigation efforts. This work contributes another, perhaps more appropriate or effective motivating reason for GCBR mitigation than economic or political reasons. That motivation might impact policymakers directly or via a public who might (in a democratic state) vote for a party more willing to mitigate GCBRs (and there is evidence that moral arguments can change prospective voting behaviours, and thus, policymaking (Burstein 2003 )). I begin by presenting an argument for framing GCBR mitigation as the production of a global public good (GPG) (section 1), which has not yet been thoroughly explored as a framing approach. By treating efforts to mitigate GCBRs as contributions to a GPG, I highlight three possible categories of moral reasons for contribution (section 2). The categories of moral reasons are: 1) moral nationalism—i.e., that regardless of whether contributing to GCBR mitigation constitutes production of a GPG that benefits everyone, more to the point it protects the citizens of a state, 2) moral cosmopolitanism—i.e., that concerning the production of GPGs like GCBR mitigation, states have obligations toward people outside their own jurisdictions, and 3) interstate obligations—i.e., that there are moral reasons for specific individual states to produce the GPG of GCBR mitigation based on obligations they hold toward other states, such as, moral leadership, fairness, and reciprocity. I conclude that states have moral reason to mitigate GCBRs, based foremost on their specific interstate obligations and an overarching reason of moral cosmopolitanism.
1611. Human-to-human happens, the count is an underestimate, and there's no vaccine.
Bardach 25 — Ariel Bardach, Mabel Berrueta, Agustín Ciapponi, et. al. December 17. Institute for Clinical Effectiveness and Health Policy, Buenos Aires. National Scientific and Technical Research Council, Argentina. PLOS ONE, “Efficacy, safety, and immunogenicity of Lassa fever vaccines: A living systematic review and landscape analysis,” vol. 20 Clopus
Lassa fever (LF) is an acute viral hemorrhagic illness caused by Lassa virus (LASV), an Mammarenavirus endemic in several West African countries [ 1 , 2 ]. While primarily zoonosis is transmitted via contact with infected Mastomys rodents or their excreta, human-to-human transmission can also occur through contact with bodily fluids of infected individuals [ 3 , 4 ]. LASV causes recurrent annual outbreaks within the endemic “Lassa fever belt” in West Africa (mainly Nigeria, Sierra Leone, Liberia, and Guinea) [ 3 , 5 ]. Lassa virus exhibits significant genetic diversity across four distinct phylogenetic lineages, with lineages I-III predominantly circulating in Nigeria and lineage IV endemic to West African [ 1 ].
LF represents a substantial public health burden in endemic regions. Estimates suggest 100,000–300,000 infections and 5,000–10,000 deaths occur annually, although these figures likely underestimate the burden due to surveillance and diagnostic challenges [ 1 , 6 , 7 ]. While many infections are mild or asymptomatic (80%), about 20% progress to severe disease with multi-organ involvement [ 1 , 8 ]. The overall case fatality rate (CFR) is estimated at 1–2%, but it can be significantly higher (≥15%) among hospitalized patients and during outbreaks [ 9 , 10 ]. Populations at high-risk include pregnant women, with reported maternal CFRs reaching 34% and fetal loss rates exceeding 60–80% [ 11 , 12 ], and children, also showing significant morbidity and mortality compared with adults, though data remain limited [ 5 , 13 , 14 ]. Sensorineural hearing loss is a common sequela, affecting up to one-third of survivors [ 15 ].
The Josiah strain serves as the prototypical representative of lineage IV and has been extensively characterized in laboratory studies [ 16 ]. The majority of vaccine candidates under preclinical and clinical investigation have predominantly utilized the glycoprotein (GP) from the Josiah strain of lineage IV as the primary immunogen, with homologous lineage IV strains employed in challenge studies [ 1 , 16 ].
No vaccine against LF is currently licensed for human use [ 16 ]. The virus’s genetic heterogeneity, the lack of established immune correlates of protection, and logistical challenges for conducting large efficacy trials in resource-limited settings with sporadic outbreaks have hampered vaccine development [ 1 , 17 ]. However, renewed focus, driven by recurrent large outbreaks, recognition by the World Health Organization (WHO) of LF virus as a priority pathogen with epidemic potential, and initiatives like the Coalition for Epidemic Preparedness Innovations (CEPI) seeking to support preventive strategies, have spurred the development of numerous vaccine candidates [ 16 – 18 ].
1622. Deaths track the health system, not the virus---so the ceiling is set by detection.
Hammed 26 — Opeyemi Hammed, Miracle Adesina, Bolaji Buoye, et. al. June 17. Center for One Health and Zoonotic Diseases, Slum and Rural Health Initiative, Ibadan, Oyo State, Nigeria. Department of Microbial Genetics and Biotechnology, Covenant University, Ota. Frontiers in Epidemiology, “The persistence and mortality of Lassa fever in Nigeria reflect systemic clinical and diagnostic challenges rather than viral evolution,” vol. 6 Clopus
Each seasonal surge of Lassa fever deaths reignites a familiar question in Nigeria: has the virus become more dangerous?. The evidence suggests otherwise. Despite decades of clinical familiarity with the Lassa virus, mortality persists, driven less by viral evolution than by delayed recognition, limited diagnostic access, and constrained supportive care ( 1 , 2 ).
Patients frequently present after days of treatment for presumed malaria or typhoid fever ( 3 ), reaching referral centres only when complications acute kidney injury ( 4 ), respiratory distress ( 5 ), or hemorrhagic manifestations have advanced beyond reversible stages ( 6 ). This recurring pattern accentuates a critical reality: in endemic settings, survival is determined not solely by pathogen's biology but by the timing, accuracy, and capacity of clinical response. Lassa fever remains endemic in Nigeria and continues to pose a significant clinical and public health burden ( 7 ). Seasonal peaks, typically during the dry season, are driven by increased human contact with rodent reservoirs and heightened household exposure risks ( 8 ). Although surveillance and treatment centres have expanded over the past decade, case fatality rates remain substantial among hospitalized patients. Public discourse often frames annual surges as “reemergence,” implying viral change or increased virulence. However, epidemiological patterns instead reflect persistent transmission dynamics within vulnerable communities and health systems that remain unevenly equipped to ensure early detection and timely care ( 9 ). Understanding why mortality remains high despite long-standing awareness and established treatment protocols is critical. Framing Lassa fever as a reemerging viral threat risks diverting attention from modifiable clinical and system-level determinants that directly influence survival.
1633. It already travelled---and it took metagenomic sequencing to catch a single case.
Wang 25 — Yu Wang, Xiang Wen, Dan Li, et. al. March 1. Chengdu Center for Disease Control and Prevention, Sichuan Province. National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, Chinese Center for Disease Control and Prevention. China CDC Weekly, “The First Imported Case of Lassa Fever — China, 2024,” vol. 7 Clopus
Lassa fever, an acute viral hemorrhagic illness caused by Lassa virus, is primarily transmitted through contact with rodents, particularly Mastomys species. The disease is endemic to West Africa and is not classified as a notifiable infectious disease in China. Prior to August 2024, no cases of Lassa fever had been reported in China.
What is added by this report?
The clinical manifestations of Lassa fever (LF) are nonspecific and may closely resemble those of other febrile illnesses, posing challenges for detection at points of entry and during medical evaluations. In this severe case, the patient experienced coma and developed persistent hearing loss even after discharge, emphasizing the critical importance of early diagnosis and treatment.
What are the implications for public health practice?
For cases with unclear diagnoses, healthcare providers should prioritize obtaining a detailed 30-day travel history to assess the potential risk of imported infectious diseases. Public health strategies in Africa must prioritize: 1) community-tailored health education campaigns, 2) enhanced syndromic surveillance coupled with pathogen-specific research, and 3) sustainable stockpiling of rapid diagnostic tests (RDTs) for endemic infections alongside accelerated vaccine development pipelines.
1641. Bringing systems to a minimum standard prevents a fifth of pandemics---and works whatever the origin.
Millett 17 — Piers Millett and Andrew Snyder-Beattie. September 1. Senior Research Fellow at the Future of Humanity Institute, University of Oxford, former Deputy Head of the Biological Weapons Convention Implementation Support Unit at the United Nations. Director of Research at the Future of Humanity Institute, University of Oxford. Health Security, “Existential Risk and Cost-Effective Biosecurity,” vol. 15, no. 4 Clopus
The US federal government was projected to spend almost $13 billion on health security–related programs in 2017. 59 To our knowledge, there has not been a quantitative assessment of how this spending has reduced the chances of bioterrorism, biowarfare, or even naturally occurring pandemics. However, the World Bank estimates that it would cost $1.9 billion to $3.4 billion per year over 5 years to bring all human and animal health systems up to minimal international standards, and it suggests that these measures would prevent at least 20% of pandemics. 60 †††† Many countries do not currently have healthcare systems that meet international standards—for example, in 2014 only 33% of countries reported their national arrangements met those required under the International Health Regulations. 61
These mitigation measures would be adopted to be effective regardless of whether a disease outbreak originates naturally, accidentally, or deliberately. ‡‡‡‡ The ability to rapidly detect and characterize the agent involved helps fast-track public health and R&D responses. Acting promptly enables basic public health measures that might decrease the likelihood of spread (such as social distancing) and track its emerging epidemiology (providing critical input for tailoring the responses). Even if we lack existing or candidate vaccines or therapeutics, having the capacity to treat symptoms can have a dramatic impact on case fatality rates. §§§§
We therefore assume that strengthening healthcare systems to meet international standards would have an impact on mitigating all types of disease risk, ranging from incidents and events to existential risks. ***** We extend the World Bank's assumptions to include bioterrorism and biowarfare—that is, we assume that the healthcare infrastructure would reduce bioterrorism and biowarfare fatalities by 20%. We conservatively assume that existential risks will be reduced by only 1%, since any potential existential risk would likely be deliberately designed to overcome medical countermeasures.
1652. The detector is a person---community health workers are the first to see a pattern.
Jean Louis 25 — Frantz Jean Louis, Lisa Nichols, Cecilia de la Torre, et. al. August 14. Infectious Disease Detection and Surveillance project, ICF, Rockville, Maryland. Public Health Reviews, “Strengthening Outbreak Detection in Africa to Achieve the 7-1-7 Global Framework: Challenges and Opportunities,” vol. 46 Clopus
Community engagement can be defined as “a process of developing relationships that enable stakeholders to work together to address health-related issues and promote wellbeing to achieve positive health impact and outcomes” [ 93 ]. Successful community engagement requires the active participation of community members in program design, leadership, implementation, and monitoring and evaluation [ 93 , 94 ]. A generic model and novel methodology for guiding earlier outbreak detection identified local recognition as the critical first step in disease detection [ 95 ]. Engaged communities play a pivotal role in the detection and management of epidemics.
Community Health Workers as a Cornerstone for Early Detection of Outbreaks
Most outbreaks often originate within communities and are frequently detected too late. Since communities are typically the first to experience the impact of epidemics, they play a crucial role in identifying early signs of an outbreak [ 96 ]. Community health workers (CHWs) are essential to early outbreaks detection. CHWs are often the first to observe unusual patterns of illness or symptoms that may signal the onset of an outbreak. Their close ties with community members enable them to detect and report early signs of diseases, and act as an essential early warning system for disease outbreaks [ 97 ].
1663. And the window is real---diagnosing in a day instead of five took the attack rate to near zero.
Gurley 25 — Emily S. Gurley and Raina K. Plowright. August. Professor of epidemiology at the Johns Hopkins Bloomberg School of Public Health. Professor of disease ecology in the Department of Public and Ecosystem Health at Cornell University. Emerging Infectious Diseases, “A Roadmap of Primary Pandemic Prevention Through Spillover Investigation,” vol. 31, no. 8 Clopus
A spillover occurs when a pathogen infects a new host species ( 2 , 3 ). The vast majority of spillovers will not lead to an outbreak or pandemic. However, for pathogens with pandemic potential, each spillover into a human is an opportunity to launch a pandemic. Most pandemic prevention plans focus on finding outbreak events earlier, notifying neighboring countries, assembling effective outbreak response teams, and enhancing global surveillance for spillover and outbreak events. Those measures are all crucial. However, preventing the spillover in the first place should be a fundamental component of our global strategy for preventing pandemics.
Numerous initiatives have attempted to identify potential pandemic causing pathogens before they cause outbreaks. One approach is to model geographic areas at high risk for spillovers, correlating putative drivers with locations of past spillovers and overlap of humans and reservoir species ( 4 – 6 ). Those efforts aim to focus surveillance and resources on areas or species of high risk. Substantial investments have led to the discovery of new viruses infecting rodents, bats, and primates, including viruses that were phylogenetically related to outbreak causing pathogens, suggesting a potential risk for spillover ( 7 – 19 ). Although such efforts have produced findings of interest, they have not produced actionable public health data. Those approaches do not inform which pathogens are spilling over and the mechanisms driving these events.
Spillovers do provide actionable data. Once an emerging pathogen infects a human, a public health threat is actualized. Those events garner our attention and concern much more than hypothetical risk warnings. Particularly alarming is evidence of transmission of the pathogen from human to human, because this capability is necessary to cause a pandemic. For example, if there was evidence that persons infected with bovine strains of avian influenza H5 across the United States ( 20 ) were able to infect others, the risk of a pandemic from this virus would increase drastically.
1671. RESERVOIR. The sustained human lineage sits in Nigeria and the naive cohort keeps growing.
Abdullahi 26 — Adam Abdullahi, Ifeanyi Omah, Reshma Kassanjee, et. al. January 20. Cambridge Institute of Therapeutic Immunology and Infectious Disease, University of Cambridge. African Center of Excellence for Genomics of Infectious Diseases, Redeemer’s University, Ede, Nigeria. Nature Communications, “Sero-genomic evidence for occult mpox exposure in healthy Nigerian adults,” vol. 17 Clopus
Mpox is a zoonotic disease caused by the mpox virus (MPXV), a member of the Poxviridae family within the Orthopoxvirus genus 1 , 2 , 3 . Historically endemic to Central and West Africa, the recent global resurgence of MPXV in endemic and non-endemic regions resulted in its declaration as a Public Health Emergency of International Concern (PHEIC) in both 2022 and 2024 4 . Unlike previous outbreaks, the 2022 outbreak, was driven by the MPXV Clade IIb, an evolutionarily distinct, pathogenically attenuated lineage with enhanced human to human transmissibility 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 . Thus, it has been associated with mild and asymptomatic disease 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 .
A key determinant of susceptibility to MPXV is residual immunity from historic smallpox vaccination 25 , 26 , 27 , discontinued globally in 1980 following eradication 28 . MPXV and variola virus (agent of smallpox) share multiple conserved structural and immunogenic viral proteins such as A29L, B6R, and M1R, implicated in viral entry and immune recognition 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 . Individuals born before 1980 likely received a smallpox vaccine during the WHO-led Smallpox Eradication Programme (1966–1980) 37 , 38 , 39 , 40 , although coverage was heterogenous ranging from 7% to 60% 25 . The vaccines used in these campaigns were based on live-attenuated vaccinia strains such as Lister and EM-63, which induced durable, broad and cross-protective immunity against Orthopoxviruses, including MPXV 41 , 42 , 43 .
Although historical smallpox vaccination conferred broad cross-protective immunity against Orthopoxviruses 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , its global cessation has created a growing global cohort of immunologically naïve individuals 54 , particularly in Africa where vaccinia-based vaccination was never incorporated into routine national programmes. Waning immunity in the post-smallpox era has coincided with the emergence of MPXV transmission patterns, especially across sub-Saharan Africa where surveillance remains limited. Evidence from high-resource setting has demonstrated asymptomatic MPXV infections, particularly among high-risk groups 4 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 55 . However, whether this smallpox immunity gap has shaped transmission dynamics in West African populations remains unclear due to a paucity of serological and genomic data from these high-burden setting.
1682. Cases are climbing and turning up in states that were never endemic---nobody is counting them.
Ogundele 25 — Gbenga O. Ogundele, Kelvin O. Jolayemi, and Segun Bello. August 27. Department of Epidemiology and Medical Statistics, Faculty of Public Health, University of Ibadan, Oyo State, Nigeria. Department of Veterinary Pharmacology and Toxicology, Ahmadu Bello University, Zaria, Kaduna State. BMC Public Health, “Lassa fever in West Africa: a systematic review and meta-analysis of attack rates, case fatality rates and risk factors,” vol. 25 Clopus
Over the years, Lassa fever has been one of the leading endemic diseases/illnesses affecting Africa, especially West Africa and it has remained a public health challenge [1]. It is a viral zoonotic illness caused by the Lassa virus, a single-stranded, enveloped Ribonucleic Acid (RNA) virus belonging to the family Arenaviridae [2–4]. The virus has an incubation period of 6–21 days, primarily transmitted via exposure to faeces, urine, or other bodily fluids of the reservoir, _Mastomys natalensis_ [1, 5] and it is excreted in urine between 3 and 9 weeks of infection while it can be retained for 3 months in semen [6, 7]. The main carrier of Lassa fever, _Mastomys natalensis_, produce large numbers of offspring and are abundant in the savannah and forests of West, Central, and East Africa [8, 9]. Despite this wide geographic distribution of the rodent reservoir, Lassa virus disease is endemic primarily in West Africa. This disparity may be attributed to ecological, socio-behavioural, and virological factors, including region-specific strains of the virus, heightened human-rodent interaction due to housing and food storage practices, and gaps in surveillance and diagnostic capacity in other regions [9, 10]. Globally, the overall case fatality rate (CFR) of Lassa fever is estimated at 1–2% among all infections, largely due to mild or asymptomatic presentation [11]. However, in hospitalized patients particularly in endemic countries such as Nigeria, Sierra Leone, and Liberia, the CFR rises markedly, typically ranging from 15% to over 20%, with regional meta-analyses reporting pooled CFRs of 19–30% [11]. Moreover, specific subpopulations including children, pregnant women, and during healthcareassociated outbreaks experience substantially higher mortality, with CFRs reported between 30% and as high as 80% [11]. About 80% of infected patients are asymptomatic or present with mild symptoms [6]. For people who are symptomatic, the clinical manifestation of the viral infection includes fever, malaise, cough, chest pain, difficulty in breathing, abdominal cramps, vomiting, diarrhoea, and sore throat [12]. Patients can also present with severe symptoms such as bleeding from mucosal surfaces, pleural effusion, pericardial effusion, seizures, disorientation, and unconsciousness [13].
Lassa fever’s primary risk factor is living in proximity to the reservoir (_Mastomys natalensis_) especially in settings with poor housing quality that facilitate rodent intrusion [14, 15]. Other important risk factors include inadequate food storage, lack of rodent control, and environmental degradation that increases human-rodent interaction [14, 16]. Specific population groups more at risk include women in rural communities due to their roles in food handling and household hygiene, children and the elderly who may have weaker immune responses, and occupational groups such as healthcare workers, slaughterhouse personnel, and miners who face increased exposure to contaminated environments or infected individuals [16–18]. However, person-to-person (secondary) transmission is also possible, particularly in healthcare and household settings, through direct contact with blood, urine, feces, vomit, or other bodily fluids of an infected person or contaminated surfaces [12]. While zoonotic transmission from rodents account for the majority of cases, nosocomial transmission has been responsible for up to 20% of infections during certain outbreaks, especially where infection prevention and control (IPC) measures are weak [13, 19]. Healthcare workers without adequate personal protective equipment (PPE) are especially vulnerable, and several documented outbreaks have involved secondary transmission chains within hospitals and households [20].
Recent studies suggest that the incidence of Lassa fever has been rising, with more frequent outbreaks and sustained transmission in previously less-affected areas [21–23]. For example, Nigeria has experienced a marked increase in confirmed annual cases since 2018, surpassing 1,000 cases per year, with infections now being reported from states historically considered non-endemic [24]. Similarly, seroprevalence surveys and environmental models indicate that the geographic range of the Lassa virus is expanding likely driven by factors such as climate change, deforestation, rodent migration, and increasing urbanization [25–27]. Climate change, through altered rainfall patterns and seasonal temperature shifts, has been linked to fluctuations in rodent population dynamics, urbanization and deforestation increase human contact with rodent habitats, facilitating zoonotic spillover. These trends reinforce the need for an integrated One Health approach that combines human, animal, and environmental surveillance systems to understand and control emerging infectious diseases like Lassa fever. Despite this expansion, the burden remains underestimated at the community level due to weak surveillance and limited diagnostic capacity. Existing reviews on Lassa fever have been predominantly narrative in nature, offering descriptive insights into epidemiology, clinical features, and control strategies without providing pooled estimates of key indicators such as attack rate or case fatality rate [13, 15, 21]. This gap underscores the need for meta-analytic approaches to inform evidence-based decision-making and intervention designs in line with One-Health strategies. This systematic review and meta-analysis aimed to estimate the pooled attack rate, case fatality rate and identify risk factors associated with Lassa fever outbreaks in West Africa.
This study was a systematic review and meta-analysis of observational studies on the attack rate, case fatality rate and risk factors of Lassa fever in West Africa. The preferred reporting items for systematic reviews and meta-analyses (PRISMA) checklist was used for the design of this systematic review (Suppl.1). It was registered with PROSPERO (CRD42023393135). The following were the inclusion criteria for selecting eligible studies: Studies including participants of all ages and genders were eligible, regardless of symptom status. Both community-based and hospital-based studies were included, as long as they reported attack rates, case fatality rates, or risk factors related to Lassa fever infection; studies that assessed and reported the risk factors of Lassa fever in any sub-Saharan country as defined by the United Nations Statistics Division [28].
This review followed the PRISMA guidelines. A comprehensive search was conducted in PubMed, African Journals Online (AJOL), Scopus, and Web of Science, using combinations of the following keywords: “Lassa fever,” “attack rate,” “case fatality”, “incidence,” “risk factors,” “West Africa,” and “outbreak.”
We defined “attack rate” as the proportion of individuals in a defined population who developed Lassa fever during a specified outbreak or study period, in line with epidemiological definitions of incidence proportion. Case fatality rate was defined as the proportion of deaths among individuals with laboratory-confirmed Lassa fever, unless otherwise stated in the original study [29]. Both primary and secondary attack rates were considered eligible if explicitly reported. However, given the inconsistencies in terminology across studies, we also included studies that reported incidence-like measures (e.g., number of cases per population exposed over a defined period), where sufficient data were available to calculate attack rates. We recognize that prevalence is more commonly reported in Lassa fever literature, particularly in seroprevalence studies, but our focus remained on studies measuring new infection rates to capture outbreak dynamics. The search covered literature published between January 1969 and June 2025 and the last search was conducted on June 30, 2025. Only peer-reviewed articles reporting quantitative attack rates, case fatality rates or risk factors were included. Non-English studies, reviews, and editorials were excluded due to resource limitations in translation and data extraction capacity. While this may have excluded some relevant studies from francophone West African countries, English remains the dominant language of publication for epidemiological research on Lassa fever in West Africa. A comprehensive electronic search strategy designed to allow exhaustive identification of relevant studies was applied to all the databases (Suppl. 2). The list of references from the included studies and other relevant articles were manually screened for additional records.