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Re-emerging Marburg virus disease in Africa: spillover ecology, geographic expansion, and surveillance vulnerabilities.

Marburg virus disease (MVD) is re-emerging across Africa as a high-consequence zoonosis shaped by expanding ecological suitability, repeated spillover, and uneven surveillance capacity. This review synthesizes current evidence on the ecological, epidemiological, and operational determinants of contemporary Marburg virus (MARV) emergence. We conceptualize MVD as an ecological-emergence system produced by interactions among reservoir-host biology, environmental change, human exposure, health-system readiness, and mobility, rather than as a series of isolated outbreaks. Recent detections in multiple African regions indicate wider enzootic circulation than previously recognized and support repeated, reservoir-associated introductions from distributed ecological foci. Spillover risk is heightened where mining, land-use change, agricultural encroachment, settlement growth, climate-sensitive habitat disruption, and population movement increase contact with Egyptian rousette bats (Rousettus aegyptiacus) and contaminated roost environments. Following primary spillover, diagnostic delays, fragmented surveillance, limited laboratory decentralization, healthcare-associated transmission, and mobility-linked exposure can enable outbreak amplification and delayed recognition. Serological findings further suggest possible "shadow epidemiology," with unrecognized or mild MARV infections occurring outside confirmed outbreak chains. Critical preparedness gaps persist in ecological risk mapping, longitudinal reservoir surveillance, decentralized molecular diagnostics, genomic sequencing, data integration, and cross-border early warning. Future preparedness should move beyond reactive containment toward integrated One Health approach combining predictive ecological surveillance, rapid community-level detection, real-time genomics, infection prevention, risk communication, and regional coordination to identify spillover early and prevent human transmission.

Animals

From spillover to systems: evidence gaps in One Health preparedness for emerging infectious diseases in Latin America and the Caribbean.

Latin America and the Caribbean are a global hotspot for emerging and re-emerging infectious diseases, yet regional One Health preparedness remains uneven and incompletely operationalized. This narrative Mini Review synthesizes evidence published mainly between 2015 and 2026 on One Health preparedness for emerging infectious diseases in the region, emphasizing how environmental disruption and climate change shape zoonotic and vector-borne spillover risk. Available regional surveys suggest broad professional familiarity with the One Health concept but limited operational implementation, with environmental health frequently identified as the least-integrated domain. We argue that spillover risk-and the failure to detect and contain spillover once it occurs-should be understood as a system-level outcome shaped by ecological disruption, socioeconomic vulnerability, surveillance capacity, and governance, rather than as an isolated biological event: deforestation, agricultural and extractive expansion-including illegal mining and logging-unplanned urbanization, and climate variability generate new human-animal-vector interfaces, while fragmented governance, uneven and poorly decentralized laboratory capacity, and limited reservoir and environmental surveillance leave these interfaces unmonitored. Environmental and climatic drivers are robustly linked to spillover, although the pathways are disease-specific rather than universal, and socioeconomic vulnerability concentrates the resulting burden in Indigenous, rural, and marginalized populations. We identify priority gaps in integrated surveillance, decentralized diagnostics, genomic capacity, reservoir ecology, governance, financing, and equity, and propose an agenda for anticipatory, climate-informed, and context-sensitive preparedness.

Latin America

An experimental analysis of "spillover" effects on the social interaction of behaviorally handicapped preschool children.

The effects of prompting and social reinforcement directed to target subjects on their social behavior and that of peers who never received prompting and reinforcement for positive social behavior, were examined. In a combined reversal and multiple-baseline design, three behaviorally handicapped preschool boys who exhibited divergent social behavior repertoires and varied histories with social reinforcement events were sequentially exposed to intervention conditions in order to investigate "spillover" of treatment effects. Prompting and reinforcement increased positive social behavior and decreased negative social behavior emitted by all target subjects. The results also demonstrated a "spillover" effect on two target subjects, who at various times were not under intervention, and on the peers as well. The findings suggest that: (a) the direct and indirect effects of intervention procedures may be enhanced by designing treatment based on the social repertoire and reinforcement histories of the subjects; and (b) the treatment "spillover" effect may be increased by applying procedures to two children at once, rather than at one at a time.

Behavior Therapy

Effect of the dopamine D2 receptor agonist quinpirole on renal sympathetic nerve activity and renal norepinephrine spillover in anesthetized rabbits.

Cardiovascular and sympathetic nervous system effects of the dopamine D2 receptor-selective agonist quinpirole were studied in anesthetized rabbits. Sodium nitroprusside was administered for comparison. The animals received a tracer infusion of [3H] norepinephrine i.v. Arterial and renal venous concentrations of endogenous norepinephrine and epinephrine and [3H]norepinephrine, the firing rate of the renal sympathetic nerves and renal blood flow were determined. Quinpirole (100 micrograms kg-1 + 5 micrograms kg-1 min-1 i.v.) lowered blood pressure and renal vascular resistance. The firing rate of the renal sympathetic nerves was increased, but there was no reflex tachycardia. Despite the increase in renal sympathetic firing, the renal spillover of norepinephrine into blood was decreased. The increase in total body norepinephrine spillover during quinpirole-induced hypotension was less than expected from baroreflex activation. Effects of quinpirole were antagonized by domperidone (1000 micrograms kg-1 + 200 micrograms kg-1 h-1). The distinguishing feature of this study is the simultaneous measurement of sympathetic firing and norepinephrine spillover in the same organ, the kidney, under conditions of intact sympathetic impulse traffic. Quinpirole activated presynaptic D2 receptors and thus reduced the released norepinephrine per action potential. Consequences of the presynaptic inhibition were reductions of blood pressure and renal vascular resistance and absence of reflex tachycardia.

Animals

Assessing the emergence time of SARS-CoV-2 zoonotic spillover.

Understanding the evolution of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) and its relationship to other coronaviruses in the wild is crucial for preventing future virus outbreaks. While the origin of the SARS-CoV-2 pandemic remains uncertain, mounting evidence suggests the direct involvement of the bat and pangolin coronaviruses in the evolution of the SARS-CoV-2 genome. To unravel the early days of a probable zoonotic spillover event, we analyzed genomic data from various coronavirus strains from both human and wild hosts. Bayesian phylogenetic analysis was performed using multiple datasets, using strict and relaxed clock evolutionary models to estimate the occurrence times of key speciation, gene transfer, and recombination events affecting the evolution of SARS-CoV-2 and its closest relatives. We found strong evidence supporting the presence of temporal structure in datasets containing SARS-CoV-2 variants, enabling us to estimate the time of SARS-CoV-2 zoonotic spillover between August and early October 2019. In contrast, datasets without SARS-CoV-2 variants provided mixed results in terms of temporal structure. However, they allowed us to establish that the presence of a statistically robust clade in the phylogenies of gene S and its receptor-binding (RBD) domain, including two bat (BANAL) and two Guangdong pangolin coronaviruses (CoVs), is due to the horizontal gene transfer of this gene from the bat CoV to the pangolin CoV that occurred in the middle of 2018. Importantly, this clade is closely located to SARS-CoV-2 in both phylogenies. This phylogenetic proximity had been explained by an RBD gene transfer from the Guangdong pangolin CoV to a very recent ancestor of SARS-CoV-2 in some earlier works in the field before the BANAL coronaviruses were discovered. Overall, our study provides valuable insights into the timeline and evolutionary dynamics of the SARS-CoV-2 pandemic.

Animals

MERS-CoV in the Middle East and Africa: from surveillance gaps in humans and dromedary camels to One Health frameworks for spillover, prevention, research and response preparedness.

Middle East respiratory syndrome coronavirus (MERS-CoV) remains a low-incidence but high-consequence zoonotic coronavirus threat. Since its identification in Saudi Arabia in 2012, more than 2600 laboratory-confirmed cases have been reported from 27 countries, most from the Arabian Peninsula; the reported case fatality ratio is high but probably overestimates infection fatality because mild and asymptomatic infections are under-detected. Dromedary camels across the Middle East, North Africa, East Africa, the Horn of Africa, and parts of the Sahel show extensive evidence of MERS-CoV infection or exposure, yet PCR-confirmed human disease has rarely been reported from Africa. This "Africa paradox" is one of the most important unresolved issues in MERS-CoV epidemiology. We propose a dromedary camel-centered One Health framework for the connected Middle East-Africa dromedary belt. The framework is organized around two linked barriers: an upstream barrier that detects and reduces zoonotic spillover at the camel-human interface, and a downstream healthcare barrier that prevents amplification after human infection occurs. Preparedness should include sentinel surveillance for severe acute respiratory infection and atypical pneumonia in camel-exposed populations, linked animal-human genomic surveillance, culturally respectful and occupationally practical risk reduction, rapid diagnostic pathways, healthcare infection prevention and control, mass-gathering and travel preparedness, and preapproved research platforms. A Middle East-Africa preparedness compact aligned with the International Health Regulations, One Health governance, and equitable pathogen access and benefit sharing could transform fragmented surveillance into a standing transregional system for early detection, prevention, and research-ready response.

Africa paradox

Direct and spillover hospitalisation patterns during climate hazards across regions of different health-system resilience levels in China: a nationwide retrospective analysis.

BACKGROUND: Health-system resilience serves as a key contributor in mitigating adverse health impacts during climate hazards. However, quantitative insights into resilience-associated health-care utilisation patterns and targeted adaptation policies remain scarce. We aimed to capture the spatiotemporal health impacts in disaster-exposed counties and their neighbouring counties in China during storms, floods, tropical cyclones, and blizzards or winter storms; understand the association between health-system resilience metrics and hazard-attributable hospitalisations; and develop evidence-based adaptation policies towards climate extremes. METHODS: In this retrospective, observational analysis of county-level aggregated hospitalisation data, we used a propensity score matching-difference-in-differences framework to assess the spatiotemporal changes of nine types of disease-specific hospitalisations in both disaster-exposed and neighbouring regions during storms, floods, tropical cyclones, and blizzards in China. We quantified the relative importance and health gains of health-system metrics during such hazards through random forest approach with interpretable partial dependence plots to derive evidence-based adaptation recommendations. FINDINGS: We included hospitalisation data from Jan 1, 2016 to Dec 31, 2023. In this period, 3241 county-hazard event combinations and 41 747 482 hospitalisations were recorded across 955 Chinese counties. The disaster-exposed regions experienced an initial decline in hospitalisation rates, followed by admission surges after disasters. For example, infectious disease admissions decreased by 11·92% (95% CI -10·53 to -13·31) during the flood-active period but increased by 7·68% (6·46-8·91) after 1-2 weeks of floods. Neighbouring zones were also affected through spillover effects, with infectious disease admissions increasing by 3·18% (1·76-4·61) after 1-2 weeks of the floods. Cardiovascular disease, injuries, infectious, respiratory, and mental disorders were more sensitive across all regions. Particularly for disaster-exposed counties, cardiovascular hospitalisations increased by 14·31% (7·34-21·29) during the tropical cyclone-active period. Notably, compared with low-resilience counties, high-resilience counties were associated with 19·48-30·03% smaller hazard-related relative changes in hospitalisation rates during the hazard-active period and 27·07-31·08% smaller hazard-related relative changes in hospitalisation rates in post-hazard periods. For instance, during the storm-active period, the increase in respiratory hospitalisations was 7·21% (0·67-13·75) in high-resilience counties versus 12·13% (5·20-19·05) in low-resilience counties. Health workforce (relative importance 14·58% during the hazard-active period and 13·80% during the post-hazard period) and service delivery (14·10% during the hazard-active period and 14·17% during the post-hazard period) were identified as key contributors of health-system resilience. Empirical synergistic effects were observed when combining interventions during the post-hazard period, with the combined effect of service delivery (individual contribution 8%) and workforce (individual contribution 4%) exceeding the sum of their individual contributions (16% reduction in cumulative excess admissions) by 33%. INTERPRETATION: Climate hazards are associated with substantial changes in hospitalisation rates in both disaster-exposed and neighbouring regions. Health-system resilience is essential in addressing disaster-health challenges. Targeted adaptation interventions should be context-appropriate and threshold-aware, thereby maximising the public health benefits relative to resilience-oriented investments in health systems. FUNDING: Gates Foundation and the National Natural Science Foundation of China.

Journal Article

Reassortment of Highly Pathogenic Avian Influenza as a Driver for Zoonotic Spillover, Asia.

Highly pathogenic avian influenza H5Nx viruses remain a major zoonotic threat, yet global attention has focused largely on clade 2.3.4.4b, potentially overlooking major changes within long-endemic H5N1 lineages in Asia. Recent reports from South and Southeast Asia describe the emergence of reassortant clade 2.3.2.1 viruses alongside renewed human infections after apparent prolonged epidemiologic stability. Collectively, those events suggest a regional pattern rather than isolated anomalies. In this article, we argue that reassortment, rather than point mutation alone, might be an underrecognized driver of zoonotic risk in endemic H5N1 lineages and is reshaping those lineages. We examine why such events might be underrecognized in settings with entrenched poultry influenza, identify limitations of current surveillance systems, and call for integrated, real-time approaches linking genomic detection with phenotypic assessment across animal and human health sectors to enable timely risk assessment and coordinated public health action.

Asia

Increased cardiac production of dihydroxyphenylalanine (DOPA) during sympathetic stimulation in anaesthetized dogs.

Entry of dihydroxyphenylalanine (DOPA) into plasma from specific organs may reflect regional activity of tyrosine hydroxylase, the enzyme responsible for the immediate synthesis of DOPA and rate-limiting for subsequent formation of catecholamines. Therefore, cardiac spillovers of DOPA, noradrenaline and the intraneuronal metabolite of noradrenaline, dihydroxyphenylglycol (DHPG), were examined during two periods of graded electrical stimulation of the sympathetic nerves to the heart in anesthetized dogs. Responses were examined before and after neuronal uptake blockade with desipramine. Cardiac spillover of DOPA increased by 1.8- and 4.4-fold during sympathetic stimulation before desipramine and by 1.6- and 3.3-fold after desipramine. Fold increases in cardiac spillover of DOPA were much lower than but positively related with fold increases in noradrenaline spillover (5.9- and 13.8-fold increases before and 9.0- and 15.8-fold increases after desipramine). Increases in cardiac spillover of DHPG (1.5- and 2.3-fold increases) were blocked by desipramine so that fold changes in spillover of DOPA were greater than and poorly related to changes in spillover of DHPG. Fold increases in cardiac spillover of DOPA showed a close one-to-one positive relationship with fold increases in the sum of cardiac spillovers of noradrenaline and dihydroxyphenylglycol before and after desipramine. For a given fold increase in noradrenaline release, transmitter turnover is increased fractionally and noradrenaline synthesis need also only increase fractionally to maintain transmitter stores constant. The close relationship between fold increases in cardiac spillover of DOPA and combined spillovers of noradrenaline and DHPG is consistent with regulation of tyrosine hydroxylase activity to match changes in noradrenaline synthesis with changes in noradrenaline turnover. Changes in cardiac spillover of DOPA appear to reflect local changes in tyrosine hydroxylase activity.

Animals

Sympathoadrenal contribution to plasma dopa (3,4-dihydroxyphenylalanine) in rats.

1. To determine the sources of dopa (3,4-dihydroxyphenylalanine) in plasma, we measured regional arteriovenous differences, tissue concentrations and urinary excretion of dopa during systemic intravenous infusions of I-[3H]dopa into anaesthetized intact rats and rats pretreated with the sympathetic neurotoxin, 6-hydroxydopamine. 2. In intact rats, large arteriovenous increments in plasma dopa concentrations were noted in the femoral (47%) and adrenal (141%) beds, with a small arterial-portal venous increment (11%), whereas in the kidney there was a substantial (47%) arteriovenous decrement in plasma dopa levels. Skeletal muscle appeared to be a major source of dopa in arterial plasma. 3. Treatment with 6-hydroxydopamine abolished the afferent-efferent increment of plasma dopa concentrations in the femoral bed. The arteriovenous decrement of plasma dopa concentrations in the kidney was preserved, and the arteriovenous increment in the adrenal bed was decreased by about half. Arterial plasma dopa levels fell by 41%. 4. Regional extraction percentages of I-[3H]dopa were used to estimate the clearances and rates of appearance (spillovers) of dopa in plasma. Dopa spillover was detected in the femoral, renal, splanchnic and adrenal beds, with skeletal muscle accounting for about 44% and the kidneys accounting for about 18% of dopa in arterial plasma. Whereas chemical sympathectomy decreased the femoral and renal spillover of dopa by 90% or more, arterial dopa levels and estimated dopa spillover into arterial plasma were decreased by only about 45%. 5. The kidneys accounted for 22% of dopa clearance from arterial plasma. From the renal extraction of I-[3H]dopa and the urinary excretion of [3H]dopamine, it was estimated that 77% of dopa removed in the kidneys was excreted as dopamine in intact animals and 69% was excreted as dopamine in sympathectomized animals. Conversely, about 80% of urinary endogenous dopamine was derived from plasma dopa, regardless of 6-hydroxydopamine treatment. 6. The results indicate that endogenous dopa in arterial plasma is derived substantially but not exclusively from sympathetic nerve endings that are destroyed by 6-hydroxydopamine, especially in skeletal muscle and the kidneys. Regional dopa spillover therefore probably reflects regional catecholamine biosynthesis. In rats, urinary dopamine is derived mainly from renal decarboxylation of circulating dopa.

Adrenal Glands

A quantitative study of the slow decline of chlorophyll a fluorescence in isolated chloroplasts.

A detailed study of the photo-induced decline in chlorophyll a fluorescence intensity (Kautsky phenomenon) in coupled isolated chloroplasts from a high level (P) to a low stationary level (S) is presented. 1. A linear relationship between P leads to S quenching and intrathylakoid H+ concentration was found. When the light-induced proton gradient was abolished by uncoupling, the fluorescence emission at room temperature was lowered proportionally to increased H+ concentration in the medium. 2. Fluorescence spectra at -196 degrees C of samples frozen at the P and S states showed no significant differences in the Photosystem I/Photosystem II ratio of fluorescence emission. Furthermore, freezing to -196 degrees C reversed the P leads to S quenching. This indicates that the P leads to S quenching is not related to an increase of spillover of excitation energy from Photosystem II to Photosystem I. 3. When Mg2+ was added to thylakoids suspended in a medium free of divalent cations, the inhibition of spillover required lower Mg2+ concentrations (half saturation at 0.6 mM). Increased proton concentration in the medium also inhibited spillover. 4. The results are interpreted in terms of two sites of Mg2+ and H+ effects on excitation deactivation in Photosystem II. One site is located on the outer face of the thylakoid membrane; action of both Mg2+ and H+ at this side diminishes spillover. The second site is located on the inner face of the membrane; as Mg2+ is displaced there by protons, a non-photochemical quenching of Photosystem II fluorescence is induced, which is manifested by the P leads to S decline.

Chlorophyll

Genomic epidemiology of clade Ia monkeypox viruses circulating in the Central African Republic in 2022-24: a retrospective cross-sectional study.

BACKGROUND: The spread of monkeypox virus (Orthopoxvirus monkeypox) clade Ib from the Democratic Republic of the Congo to neighbouring countries has raised global concerns, leading to WHO declaring mpox a public health emergency on Aug 14, 2024. We applied genomic epidemiology to investigate the causes of recurrent mpox outbreaks in the Central African Republic. We aimed to determine whether frequent zoonotic spillovers or increased human-to-human transmissions are driving mpox epidemiology. METHODS: We performed a retrospective cross-sectional study of monkeypox virus genomic sequences among PCR-confirmed mpox cases detected in the Central African Republic between Feb 17, 2022, and Sept 17, 2024. We used hybridisation capture coupled to high throughput sequencing to analyse 46 samples from mpox outbreaks that occurred in eight of the 20 prefectures (14 of 35 health districts). Near-complete genomes were used for phylogenomic analyses. FINDINGS: Between Jan 10, 2022, and Sept 15, 2024, 89 mpox cases were confirmed, including 53 cases in the first 9 months of 2024. We generated 41 near-complete genomes from this period, including 33 from 2024. All new and already published monkeypox virus genomes from the Central African Republic belonged to clade Ia. These genomes spanned the phylogenetic diversity of clade Ia viruses, and most likely represented several dozen independent transmission events to humans. The monkeypox virus phylogenetic diversity was geographically structured within the country. Plausibly linked cases often showed indistinguishable genomes. Conversely, we detected identical genomes in cases that epidemiological information would suggest were independent outbreaks. Finally, we found that three distinct viruses caused cases in the capital city of Bangui in July, 2024, with all three detected on the same day (July 24, 2024). We did not detect substantial enrichment of APOBEC3 editing, suggesting limited human-to-human transmission. INTERPRETATION: The data indicate that mpox epidemiology in the Central African Republic is primarily driven by short-lived outbreaks resulting from many independent zoonotic spillover events, particularly in rural areas. Although evidence remains limited, in Bangui additional factors such as movement of people and importation of bushmeat from other regions might be introducing the virus into urban settings. Similar spillover patterns have been observed in the Democratic Republic of the Congo. The poorly understood nature of monkeypox virus reservoirs in both countries is a regional concern, as frequent spillovers increase the risk of outbreaks leading to sustained human transmission. Beyond strengthening surveillance and developing countermeasures, it is important to better understand the reservoirs and focus on reducing transmission opportunities to prevent further outbreaks. FUNDING: Pasteur Institute of Bangui, Africa CDC, AFROSCREEN, WHO, the Helmholtz Institute for One Health, and the Deutsche Forschungsgemeinschaft.

Humans

Liver releases galanin during sympathetic nerve stimulation.

To determine whether the gut or liver releases galanin during sympathetic neural activation, we performed bilateral thoracic splanchnic nerve stimulation (BTSNS) in halothane-anesthetized dogs. Using experimentally determined galanin extraction rates of 60% for gut and no extraction by liver, calculations demonstrated a minor increase in gut spillover during BTSNS (delta = +4.8 +/- 1.8 pmol/min), whereas liver spillover of galanin-like immunoreactivity (GLIR) increased markedly (delta = +27.9 +/- 9.5 pmol/min). To confirm the finding of liver galanin release, GLIR was measured in femoral artery, portal vein, and hepatic vein during hepatic nerve stimulation (HNS). GLIR spillover from gut was not increased by HNS (delta = +1.9 +/- 6.3 pmol/min). In contrast, liver GLIR spillover was greatly increased during HNS (delta = +53.3 +/- 16.4 pmol/min). Extracts of canine liver contained 2.7 +/- 0.4 pmol GLIR/g tissue. We conclude that, despite the known significant galanin content of the gut, little galanin is released from this organ during sympathetic activation. In contrast, the liver, heretofore not described to contain galanin, contains and releases significant amounts of the peptide during sympathetic activation.

Animals

Community-tailored One Health educational intervention to enhance knowledge and practices for zoonotic disease prevention in rural Thailand: A protocol for a prospective cluster randomised controlled Trial in Chanthaburi, Thailand (Saan Suk trial).

BACKGROUND: Zoonotic infectious disease risk arises at human-animal-environment interfaces where pathogen spillover can occur. Rural communities living in biodiverse settings may experience frequent contact with wildlife and shared environments through livelihoods, food practices, and economic activities. Reducing spillover risk and strengthening pandemic prevention requires both structural and individual-level change. Community-based interventions that promote awareness, risk perception, self-efficacy, pro-environmental behaviour, and safe coexistence with wildlife may support prevention by shifting behavioural determinants of zoonotic disease risk. The Saan Suk intervention was co-developed with rural communities in Thailand using a Human-Centred Design approach and is grounded in the Health Belief Model and One Health principles. The intervention is intended to be feasible, acceptable, and deliverable through Thailand's established Village Health Volunteer (VHV) system. METHODS: This protocol describes a parallel-arm, cluster-randomised controlled superiority trial that will be conducted during July - October 2026, in Chanthaburi Province, Thailand. 24 villages will be equally randomised to the Saan Suk intervention or the current practice (control). In intervention villages, trained VHVs will deliver, once a week over four weeks, a multimodal One Health educational intervention designed to improve knowledge of zoonotic spillover, promote protective behaviours, reduce risky wildlife-related contacts, and support respectful coexistence with wildlife. Trained outcome assessment teams will conduct structured interviews with 42 adult participants per village, yielding a total sample size of 1,008 participants. The sample size was calculated for the primary outcome, accounting for clustering, with 90% power to detect a medium effect size (6 points on the 0-100 knowledge scale) at a significance level of 0.05, accounting for a design effect with an ICC of 0.028. The primary outcome is knowledge of zoonotic spillover, transmission pathways, risk factors, protective and risky behaviours, and safe coexistence with wildlife. Secondary outcomes include attitudes, self-efficacy, preventive and risky behaviours, and reported contacts with major local reservoir hosts. A structured questionnaire was developed, expert-reviewed, and piloted for the outcome assessment. Outcomes will be analysed using mixed-effects regression models with random effects for village and adjustment for relevant pre-specified confounders. Primary analyses will follow the intention-to-treat principle. DISCUSSION: This trial will evaluate whether a co-designed, VHV-delivered One Health educational programme can improve knowledge of zoonotic disease prevention and behavioural determinants in rural communities living in close contact with wildlife and shared ecosystems. If effective and feasible, Saan Suk could inform integration into routine VHV training and community-based zoonotic disease and pandemic prevention strategies. TRIAL REGISTRATION: The Saan Suk trial is registered with the German Clinical Trials Register (DRKS). Registration ID: DRKS00038582; date of registration: 11 May 2026.

Zoonoses

Respiratory pandemic risk in the Anthropocene: A One Health framework and GISRS+ agenda.

Recent epidemics and pandemics caused by respiratory viruses, alongside the animal panzootic spread of highly pathogenic avian influenza A(H5Nx), have become a structural feature of the Anthropocene, yet responses remain largely reactive. This review integrates findings from WHO's Global Influenza Surveillance and Response System (GISRS) and related surveillance data (2000-2024), epidemiological studies of influenza A virus, SARS-CoV, MERS-CoV, SARS-CoV-2, and H5Nx, and One Health literature. We examine major groups of respiratory viruses and identify mismatches between risk and surveillance by focusing on spillover potential from animal hosts, human-to-human transmission and its controllability, and Anthropocene characteristics that increase epidemic risk. The analysis indicated that SARS-related coronaviruses and influenza A viruses, particularly H5Nx, are among the leading candidates based on currently available evidence because they have large reservoirs in animal hosts and spillover to humans is highly probable. The previous presymptomatic spread of SARS-CoV-2 and recent mammalian adaptation in H5N1 clade 2.3.4.4b highlight limitations of the traditional symptom-based and pathogen-specific surveillance system. Spillover events tend to occur in tropical and subtropical regions in low- and middle-income countries, but most genomic surveillance is in high-income countries. We propose interventions that address the upstream, midstream, downstream processes of epidemics. Upstream interventions are primary prevention measures related to land use, livestock, wildlife, and urban environments; midstream interventions are GISRS+-based pathogen-agnostic genomic and metagenomic early warning systems triggered by One Health; and downstream interventions include vaccines, antivirals, non-pharmaceutical interventions, and engineering with equity-centred global governance and sustainable financing.

Anthropocene