Human Disease Burden Research Articles

[Translated article] Retrospective Study of Risk Markers for Developing High-Grade Anal Intraepithelial Neoplasm in Men Who Have Sex With Men Living With HIV

BackgroundHigh-grade anal intraepithelial squamous lesion is significantly prevalent among men who have sex with men and are infected with the human immunodeficiency virus (HIV). This condition—the precursor to anal cancer—significantly increases the risk of developing it. Conversely, low-grade anal intraepithelial squamous typically follow a benign course and usually regress spontaneously. Materials and methodsTo describe a population of men who have sex with men living with HIV followed in a specialized anal cancer screening unit we conducted an observational, retrospective, and single-center study. ResultsNinety-four patients were analyzed, with a mean age of 39±9 years, and a 87% positivity rate for high-risk human papillomavirus (HR-HPV). At the initial visit, 47% presented with low-grade squamous intraepithelial lesions. The progression rate to high-grade squamous intraepithelial lesion was 37.2 per 100,000 patients/year. None of the patients developed anal cancer. Tobacco and alcohol consumption were associated with this progression. DiscussionIn this series, longer duration of HIV infection, tobacco and alcohol use and the presence of HR-HPV were significantly associated with the occurrence of high-grade intraepithelial lesions. A lower risk of progression was seen in patients with higher education. ConclusionIn men who have sex with men living with HIV, the association of factors such as smoking, alcohol, the presence of HR-HPV and an increased burden of human papillomavirus disease makes these patients more susceptible to develop high-grade anal squamous lesions.

Understanding the transmission of bacterial agents of sapronotic diseases using an ecosystem-based approach: A first spatially realistic metacommunity model.

Pathogens such as bacteria, fungi and viruses are important components of soil and aquatic communities, where they can benefit from decaying and living organic matter, and may opportunistically infect human and animal hosts. One-third of human infectious diseases is constituted by sapronotic disease agents that are natural inhabitants of soil or aquatic ecosystems. They are capable of existing and reproducing in the environment outside of the host for extended periods of time. However, as ecological research on sapronosis is infrequent and epidemiological models are even rarer, very little information is currently available. Their importance is overlooked in medical and veterinary research, as well as the relationships between free environmental forms and those that are pathogenic. Here, using dynamical models in realistic aquatic metacommunity systems, we analyze sapronosis transmission, using the human pathogen Mycobacterium ulcerans that is responsible for Buruli ulcer. We show that the persistence of bacilli in aquatic ecosystems is driven by a seasonal upstream supply, and that the attachment and development of cells to aquatic living forms is essential for such pathogen persistence and population dynamics. Our work constitutes the first set of metacommunity models of sapronotic disease transmission, and is highly flexible for adaptation to other types of sapronosis. The importance of sapronotic agents on animal and human disease burden needs better understanding and new models of sapronosis disease ecology to guide the management and prevention of this important group of pathogens.

Estudio retrospectivo que evalúa marcadores de riesgo de desarrollar lesión escamosa intraepitelial anal de alto grado en hombres que tiene sexo con hombres y viven con el virus de inmunodeficiencia humana

BackgroundHigh-grade anal intraepithelial squamous lesion is significantly prevalent among men who have sex with men and are infected with the human immunodeficiency virus (HIV). This condition—the precursor to anal cancer—significantly increases the risk of developing it. Conversely, low-grade anal intraepithelial squamous typically follow a benign course and usually regress spontaneously. Materials and methodsTo describe a population of men who have sex with men living with HIV followed in a specialized anal cancer screening unit we conducted an observational, retrospective, and single-center study. ResultsNinety-four patients were analyzed, with a mean age of 39±9 years, and a 87% positivity rate for high-risk human papillomavirus (HR-HPV). At the initial visit, 47% presented with low-grade squamous intraepithelial lesions. The progression rate to high-grade squamous intraepithelial lesion was 37.2 per 100,000 patients/year. None of the patients developed anal cancer. Tobacco and alcohol consumption were associated with this progression. DiscussionIn this series, longer duration of HIV infection, tobacco and alcohol use and the presence of HR-HPV were significantly associated with the occurrence of high-grade intraepithelial lesions. A lower risk of progression was seen in patients with higher education. ConclusionIn men who have sex with men living with HIV, the association of factors such as smoking, alcohol, the presence of HR-HPV and an increased burden of human papillomavirus disease makes these patients more susceptible to develop high-grade anal squamous lesions.

Quantification of healthspan in aging mice: introducing FAMY and GRAIL.

The population around the world is graying, and as many of these individuals will spend years suffering from the burdens of age associated diseases, understanding how to increase healthspan, defined as the period of life free from disease and disability, is an urgent priority of geroscience research. The lack of agreed-upon quantitative metrics for measuring healthspan in aging mice has slowed progress in identifying interventions that do not simply increase lifespan, but also healthspan. Here, we define FAMY (Frailty-Adjusted Mouse Years) and GRAIL (Gauging Robust Aging when Increasing Lifespan) as new summary statistics for quantifying healthspan in mice. FAMY integrates lifespan data with longitudinal measurements of a widely utilized clinical frailty index, while GRAIL incorporates these measures and also adds information from widely utilized healthspan assays and the hallmarks of aging. Both metrics are conceptually similar to quality-adjusted life years (QALY), a widely utilized measure of disease burden in humans, and can be readily calculated from data acquired during longitudinal and cross-sectional studies of mouse aging. We find that interventions generally thought to promote health, including calorie restriction, robustly improve healthspan as measured by FAMY and GRAIL. Finally, we show that the use of GRAIL provides new insights, and identify dietary restriction of protein or isoleucine as interventions that robustly promote healthspan but not longevity in female HET3 mice. We suggest that the routine integration of these measures into studies of aging in mice will allow the identification and development of interventions that promote healthy aging even in the absence of increased lifespan.

Rat lungworm, Cryptosporidium and other zoonotic pathogens of Rattus rattus and native wildlife on Sydney's Northern beaches

ABSTRACT Urbanisation is disrupting natural habitats and potentially causing spillover of zoonotic diseases from animals common in highly populated areas to natural environments and native wildlife. The black rat (Rattus rattus) is a common commensal species abundant in urban areas and nearby bushland in Australia and globally. It can be a major reservoir of pathogens and vectors for diseases that affect humans, pets, and wildlife. We examined pathogen prevalence in black rats and native wildlife in peri-urban northern Sydney. We trapped rats and native wildlife at eight 1-ha bushland sites and sampled for a range of internal pathogens from necropsied individuals (n=85 rats) and animal/trap swabs (n=54 native individuals). We detected a high prevalence of rat lungworm (Angiostrongylus spp.) in black rats (67%) as well as native wildlife including long-nosed bandicoots (Perameles nasuta; 43%; previously undetected) and bush rats (R. fuscipes; 33%). Incidence of detection tended to be more frequent where rat activity was greatest. Non-zoonotic Cryptosporidium spp. was also recorded in 17% of black rats and Salmonella spp. in 21% of bandicoots. Our findings suggest black rats may be facilitating spill-over of disease into native wildlife. The detected prevalence of Angiostrongylus spp. suggests an increasing occurrence in this natural system. These data provide valuable insight for disease management highlighting important reservoirs of disease which could be targeted to reduce disease burden in humans, pets, and wildlife.

A meta-analysis on global change drivers and the risk of infectious disease.

Anthropogenic change is contributing to the rise in emerging infectious diseases, which are significantly correlated with socioeconomic, environmental and ecological factors1. Studies have shown that infectious disease risk is modified by changes to biodiversity2-6, climate change7-11, chemical pollution12-14, landscape transformations15-20 and species introductions21. However, it remains unclear which global change drivers most increase disease and under what contexts. Here we amassed a dataset from the literature that contains 2,938 observations of infectious disease responses to global change drivers across 1,497 host-parasite combinations, including plant, animal and human hosts. We found that biodiversity loss, chemical pollution, climate change and introduced species are associated with increases in disease-related end points or harm, whereas urbanization is associated with decreases in disease end points. Natural biodiversity gradients, deforestation and forest fragmentation are comparatively unimportant or idiosyncratic as drivers of disease. Overall, these results are consistent across human and non-human diseases. Nevertheless, context-dependent effects of the global change drivers on disease were found to be common. The findings uncovered by this meta-analysis should help target disease management and surveillance efforts towards global change drivers that increase disease. Specifically, reducing greenhouse gas emissions, managing ecosystem health, and preventing biological invasions and biodiversity loss could help to reduce the burden of plant, animal and human diseases, especially when coupled with improvements to social and economic determinants of health.

HYBRID MODEL AND FRAMEWORK FOR PREDICTING AIR POLLUTANTS IN SMART CITIES

The pollution index of any urban area is indicated by its air quality. It also shows a fine balance is maintained between the needs of the populace and the industrial ecosystem. To mitigate such pollution in real-time, smart cities have a significant role to play. It's common knowledge that air pollution in a city severely affects the health of its dependents. More alarmingly, human health damage and disease burden are caused by phenomena like acid rain, and global warming. More precisely, lung ailments, CPOD, heart problems and skin cancer are caused by polluted air in congested urban places. Amongst the worst air pollutants, CO, C6H6, SO2, NO2, O3, RSPM/PM10, and PM2.5 cause maximum havoc. The climatic variables like atmospheric wind velocity, direction, relative humidity, and temperature control air contaminants in the air. Lately, numerous techniques have been applied by researchers and environmentalists to determine the Air Quality Index over a place. However, not a single technique has found acceptance from all quarters as being effective in every situation or scenario. Here, the main aspect relates to achieving authentic prediction in AQI levels by applying Machine Learning algorithms so worst situations can be averted by timely action. To enhance the performance of Machine Learning methods study adopted imputation and feature selection methods. When feature selection is applied, the experimental outcomes indicate a more accurate prediction over other techniques, showing promise for the application of the model in smart cities by syncing data from different monitoring stations.

Metagenomic analysis of individual mosquito viromes reveals the geographical patterns and drivers of viral diversity.

Mosquito transmitted viruses are responsible for an increasing burden of human disease. Despite this, little is known about the diversity and ecology of viruses within individual mosquito hosts. Here, using a meta-transcriptomic approach, we determined the viromes of 2,438 individual mosquitoes (81 species), spanning ~4,000 km along latitudes and longitudes in China. From these data we identified 393 viral species associated with mosquitoes, including 7 (putative) species of arthropod-borne viruses (that is, arboviruses). We identified potential mosquito species and geographic hotspots of viral diversity and arbovirus occurrence, and demonstrated that the composition of individual mosquito viromes was strongly associated with host phylogeny. Our data revealed a large number of viruses shared among mosquito species or genera, enhancing our understanding of the host specificity of insect-associated viruses. We also detected multiple virus species that were widespread throughout the country, perhaps reflecting long-distance mosquito dispersal. Together, these results greatly expand the known mosquito virome, linked viral diversity at the scale of individual insects to that at a country-wide scale, and offered unique insights into the biogeography and diversity of viruses in insect vectors.

Prevalence of Salmonella spp. and Escherichia coli in the feces of free-roaming wildlife throughout South Korea.

Wildlife can carry pathogenic organisms, including viruses, bacteria, parasites, and fungi, which can spread to humans and cause mild to serious illnesses and even death. Spreading through animal feces, these pathogens significantly contributes to the global burden of human diseases. Therefore, the present study investigated the prevalence of zoonotic bacterial pathogens, such as Salmonella spp., Escherichia coli, and Shiga toxin-producing E. coli (STEC), in animal feces. Between September 2015 and August 2017, 699 wildlife fecal samples were collected from various agricultural production regions and mountainous areas in South Korea. Fecal samples were collected from wild mammals (85.26%, 596/699) and birds (14.73%, 103/699). Salmonella spp. and E. coli were present in 3% (21/699) and 45.63% (319/699) of the samples, respectively. Moreover, virulence genes stx1 and both stx1 and stx2 were detected in 13.30% (93/699) and 0.72% (5/699) of the samples, respectively. The 21 Salmonella spp. were detected in badgers (n = 5), leopard cats (n = 7), wild boars (n = 2), and magpies (n = 7); STEC was detected in roe deer, water deer, mice, and wild boars. Through phylogenetic and gene-network analyses, the Salmonella spp. isolates (n = 21 laboratory isolates, at least one isolate from each Salmonella-positive animal fecal sample, and n = 6 widely prevalent reference Salmonella serovars) were grouped into two major lineages: S. enterica subsp. enterica and S. enterica subsp. diarizonae. Similarly, 93 E. coli isolates belonged to stx1, including three major lineages (groups 1-3), and stx1 and stx2 detected groups. To the best of our knowledge, this is the first report of a wild leopard cat serving as a reservoir for Salmonella spp. in South Korea. The research findings can help manage the potential risk of wildlife contamination and improve precautionary measures to protect public health.

The effective combination therapies with irinotecan for colorectal cancer.

Colorectal cancer is the third most common type of cancer worldwide and has become one of the major human disease burdens. In clinical practice, the treatment of colorectal cancer has been closely related to the use of irinotecan. Irinotecan combines with many other anticancer drugs and has a broader range of drug combinations. Combination therapy is one of the most important means of improving anti-tumor efficacy and overcoming drug resistance. Reasonable combination therapy can lead to better patient treatment options, and inappropriate combination therapy will increase patient risk. For the colorectal therapeutic field, the significance of combination therapy is to improve the efficacy, reduce the adverse effects, and improve the ease of treatment. Therefore, we explored the clinical advantages of its combination therapy based on mechanism or metabolism and reviewed the rationale basis and its limitations in conducting exploratory clinical trials on irinotecan combination therapy, including the results of clinical trials on the combination potentiation of cytotoxic drugs, targeted agents, and herbal medicine. We hope that these can evoke more efforts to conduct irinotecan in the laboratory for further studies and evaluations, as well as the possibility of more in-depth development in future clinical trials.

Pre-exposure prophylaxis of non-HIV viral infections and the role of long-acting antivirals.

Viruses cause a large burden of human infectious diseases. During the past 50 years, antivirals have been developed to treat many pathogenic viruses, including herpesviruses, retroviruses, hepatitis viruses, and influenza. Besides being used as treatment, antivirals have shown efficacy for preventing certain viral infections. Following the success in the HIV field, a renewed interest has emerged on the use of antivirals as prophylaxis for other viruses. The development of formulations with extended half-life has pushed further this consideration in persons at risk for a wide range of viral infections. In this way, long-acting antivirals might behave as "chemovaccines" when classical vaccines do not exist, cannot be recommended, immune responses are suboptimal, escape mutants emerge, and/or immunity wanes. Five main caveats would temper its use, namely, selection of drug resistance, drug interactions, short- and long-term side effects, potential teratogenicity in women of child-bearing age, and high cost. Herein, we discuss the prospects for long-acting antivirals as prophylaxis of human viral infections other than HIV.

Mathematical assessment of control strategies against the spread of MERS-CoV in humans and camels in Saudi Arabia.

A new mathematical model for the transmission dynamics and control of the Middle Eastern respiratory syndrome (MERS), a respiratory virus caused by MERS-CoV coronavirus (and primarily spread to humans by dromedary camels) that first emerged out of the Kingdom of Saudi Arabia (KSA) in 2012, was designed and used to study the transmission dynamics of the disease in a human-camel population within the KSA. Rigorous analysis of the model, which was fitted and cross-validated using the observed MERS-CoV data for the KSA, showed that its disease-free equilibrium was locally asymptotically stable whenever its reproduction number (denoted by $ {\mathbb R}_{0M} $) was less than unity. Using the fixed and estimated parameters of the model, the value of $ {\mathbb R}_{0M} $ for the KSA was estimated to be 0.84, suggesting that the prospects for MERS-CoV elimination are highly promising. The model was extended to allow for the assessment of public health intervention strategies, notably the potential use of vaccines for both humans and camels and the use of face masks by humans in public or when in close proximity with camels. Simulations of the extended model showed that the use of the face mask by humans who come in close proximity with camels, as a sole public health intervention strategy, significantly reduced human-to-camel and camel-to-human transmission of the disease, and this reduction depends on the efficacy and coverage of the mask type used in the community. For instance, if surgical masks are prioritized, the disease can be eliminated in both the human and camel population if at least 45% of individuals who have close contact with camels wear them consistently. The simulations further showed that while vaccinating humans as a sole intervention strategy only had marginal impact in reducing the disease burden in the human population, an intervention strategy based on vaccinating camels only resulted in a significant reduction in the disease burden in camels (and, consequently, in humans as well). Thus, this study suggests that attention should be focused on effectively combating the disease in the camel population, rather than in the human population. Furthermore, the extended model was used to simulate a hybrid strategy, which combined vaccination of both humans and camels as well as the use of face masks by humans. This simulation showed a marked reduction of the disease burden in both humans and camels, with an increasing effectiveness level of this intervention, in comparison to the baseline scenario or any of the aforementioned sole vaccination scenarios. In summary, this study showed that the prospect of the elimination of MERS-CoV-2 in the Kingdom of Saudi Arabia is promising using pharmaceutical (vaccination) and nonpharmaceutical (mask) intervention strategies, implemented in isolation or (preferably) in combination, that are focused on reducing the disease burden in the camel population.

Fine Particulate Matter Exposure and Health Impacts from Indoor Activities

Exposure to fine particulate matter (PM2.5) is an important contributor to global human disease burden, particularly indoors where people spend the majority of their time and exposure is highest. We propose a framework linking indoor PM2.5 emissions from human activities to exposure and health impacts, expressed in Disability-Adjusted Life Years (DALY). Derived dynamic indoor PM2.5 concentrations—capturing temporal variations through different window-opening scenarios and air renewal rates—are used to estimate uncertainty for a parametric model (up to a factor of 114). Intake fractions (fraction of emitted substance taken in (μgintake/μgemitted)), effect factors (μDALY/μgintake), related impact characterisation factors (health impact per unit mass emitted (μDALY/μgemitted)), and impact scores (health impact per hour activity (μDALY/hactivity)) are provided for 19 one-hour indoor activities and can be flexibly scaled to real activity durations. Indoor concentrations exceeded recommended World Health Organization (WHO) limits for all activities at low ventilation rates. Per person, 98 to 119 μDALY/hactivity (52 to 63 minuteslost/hactivity) was associated with traditional fuel cook stoves, with high air renewal rates (3 and 14 h-1). The burning of candles, at low air renewal rates of 0.2 to 0.6 h-1, results in 7 to 11 μDALY/hactivity (4 to 11 minuteslost/hactivity). Derived impact scores and characterisation factors serve as a starting point for integrating indoor PM2.5 emissions and exposure into life cycle impact and public health assessments.

Evolution and diversity of nucleotide and dinucleotide composition in poxviruses.

Poxviruses (family Poxviridae) have long dsDNA genomes and infect a wide range of hosts, including insects, birds, reptiles and mammals. These viruses have substantial incidence, prevalence and disease burden in humans and in other animals. Nucleotide and dinucleotide composition, mostly CpG and TpA, have been largely studied in viral genomes because of their evolutionary and functional implications. We analysed here the nucleotide and dinucleotide composition, as well as codon usage bias, of a set of representative poxvirus genomes, with a very diverse host spectrum. After correcting for overall nucleotide composition, entomopoxviruses displayed low overall GC content, no enrichment in TpA and large variation in CpG enrichment, while chordopoxviruses showed large variation in nucleotide composition, no obvious depletion in CpG and a weak trend for TpA depletion in GC-rich genomes. Overall, intergenome variation in dinucleotide composition in poxviruses is largely accounted for by variation in overall genomic GC levels. Nonetheless, using vaccinia virus as a model, we found that genes expressed at the earliest times in infection are more CpG-depleted than genes expressed at later stages. This observation has parallels in betahepesviruses (also large dsDNA viruses) and suggests an antiviral role for the innate immune system (e.g. via the zinc-finger antiviral protein ZAP) in the early phases of poxvirus infection. We also analysed codon usage bias in poxviruses and we observed that it is mostly determined by genomic GC content, and that stratification after host taxonomy does not contribute to explaining codon usage bias diversity. By analysis of within-species diversity, we show that genomic GC content is the result of mutational biases. Poxvirus genomes that encode a DNA ligase are significantly AT-richer than those that do not, suggesting that DNA repair systems shape mutation biases. Our data shed light on the evolution of poxviruses and inform strategies for their genetic manipulation for therapeutic purposes.

Leptospirosis in humans and selected animals in Sub-Saharan Africa, 2014–2022: a systematic review and meta-analysis

BackgroundLeptospirosis is an emerging neglected tropical zoonotic disease of public health importance causing substantial morbidities and mortalities among humans. The infection is maintained within the population through interactions between humans, animals, and the environment. Understanding the burden of disease in both humans and animals is necessary for effective prevention and control in Sub-Saharan Africa (SSA). Therefore, we aimed to determine the seroprevalence of leptospirosis in humans, selected domestic animals, and rodents in SSA.MethodsA comprehensive search was done in six databases: Scopus, PubMed, Google Scholar, CINAHL, Web of Science, and African Journals Online databases for articles published between 01 January 2014 and 30 August 2022. Thirty-seven articles distributed across 14 out of 46 countries in SSA were included. The random effects meta-analysis model was used to pool the extracted seroprevalence data.ResultsThe overall pooled seroprevalence of leptospirosis among humans was 12.7% (95% CI: 7.5,20.8), 15.1% (95% CI: 9.4,23.5), and 4.5% (95% CI: 0.4, 35.6) based on results obtained using ELISA, MAT, and PCR diagnostic methods respectively. The pooled seroprevalence estimates among cattle were 29.2%, 30.1%, and 9.7% based on ELISA, MAT, and PCR respectively. Further, the pooled seroprevalence in goats was 30.0% for studies that used MAT, and among rodents, the pooled seroprevalence estimates were 21.0% for MAT and 9.6% for PCR diagnostic criteria. The seroprevalence of leptospirosis varied extensively between studies, across SSA regions and study setting (rural or urban).ConclusionLeptospirosis is widespread in SSA in both humans and animals based on the current results of the pooled seroprevalence in the limited studies available. The burden is high in animals and humans and underestimated due to limited studies and challenges with limited diagnostic capacity in most healthcare settings in SSA. Hence, we recommend that leptospirosis should be listed as a disease of concern and be included on the list of routine diagnostics among patients presenting with febrile illness in healthcare settings. Further, we recommend the enhancement of surveillance of leptospirosis in all countries in SSA and the development of strategies with a One Health perspective to effectively prevent and control leptospirosis.

Spatiotemporal organization of cryptic North American Culex species along an urbanization gradient.

Landscape heterogeneity creates diverse habitat and resources for mosquito vectors of disease. A consequence may be varied distribution and abundance of vector species over space and time dependent on niche requirements.We tested the hypothesis that landscape heterogeneity driven by urbanization influences the distribution and relative abundance of Culex pipiens, Cx. restuans, and Cx. quinquefasciatus, three vectors of West Nile virus (WNv) in the eastern North American landscape. We collected 9,803 cryptic Culex from urban, suburban, and rural sites in metropolitan Washington, District of Columbia, during the months of June-October, 2019-2021. In 2021, we also collected mosquitoes in April and May to measure early-season abundance and distribution. Molecular techniques were used to identify a subset of collected Culex to species (n = 2,461). Ecological correlates of the spatiotemporal distribution of these cryptic Culex were examined using constrained and unconstrained ordination.Seasonality was not associated with Culex community composition in June-October over three years but introducing April and May data revealed seasonal shifts in community composition in the final year of our study. Culex pipiens were dominant across site types, while Cx. quinquefasciatus were associated with urban environments, and Cx. restuans were associated with rural and suburban sites. All three species rarely coexisted.Our work demonstrates that human-mediated land-use changes influence the distribution and relative abundance of Culex vectors of WNv, even on fine geospatial scales. Site classification, percent impervious surface, distance to city center, and longitude predicted Culex community composition. We documented active Culex months before vector surveillance typically commences in this region, with Culex restuans being most abundant during April and May. Active suppression of Cx. restuans in April and May could reduce early enzootic transmission, delay the seasonal spread of WNv, and thereby reduce overall WNv burden. By June, the highest risk of epizootic spillover of WNv to human hosts may be in suburban areas with high human population density and mixed Culex assemblages that can transmit WNv between birds and humans. Focusing management efforts there may further reduce human disease burden.

Prioritization of zoonoses for multisectoral, One Health collaboration in Somalia, 2023

BackgroundThe human population of Somalia is vulnerable to zoonoses due to a high reliance on animal husbandry. This disease risk is exacerbated by relatively low income (poverty) and weak state capacity for health service delivery in the country as well as climate extremes and geopolitical instability in the region. To address this threat to public health efficiently and effectively, it is essential that all sectors have a common understanding of the priority zoonotic diseases of greatest concern to the country. MethodsRepresentatives from human, animal (domestic and wildlife), agriculture, and environmental health sectors undertook a multisectoral prioritization exercise using the One Health Zoonotic Disease Prioritization (OHZDP) tool developed by the United States CDC. The process involved: reviewing available literature and creating a longlist of zoonotic diseases for potential inclusion; developing and weighting criteria for establishing the importance of each zoonoses; formulating categorical questions (indicators) for each criteria; scoring each disease according to the criteria; and finally ranking the diseases based on the final score. Participants then brainstormed and suggested strategic action plans to prevent, and control prioritized zoonotic diseases. ResultsThirty-three zoonoses were initially considered for prioritization. Final criteria for ranking included: 1) socioeconomic impact (including sensitivity) in Somalia; 2) burden of disease in humans in Somalia); 3) availability of intervention in Somalia; 4) environmental factors/determinants; and 5) burden of disease in animals in Somalia. Following scoring of each zoonotic disease against these criteria, and further discussion of the OHZDP tool outputs, seven priority zoonoses were identified for Somalia: Rift Valley fever, Middle East respiratory syndrome, anthrax, trypanosomiasis, brucellosis, zoonotic enteric parasites (including Giardia and Cryptosporidium), and zoonotic influenza viruses. ConclusionsThe final list of seven priority zoonotic diseases will serve as a foundation for strengthening One Health approaches for disease prevention and control in Somalia. It will be used to: shape improved multisectoral linkages for integrated surveillance systems and laboratory networks for improved human, animal, and environmental health; establish multisectoral public health emergency preparedness and response plans using One Health approaches; and enhance workforce capacity to prevent, control and respond to priority zoonotic diseases.

Yersinia deploys type III-secreted effectors to evade caspase-4 inflammasome activation in human cells.

Yersinia are responsible for significant disease burden in humans, ranging from recurrent disease outbreaks (yersiniosis) to pandemics (Yersinia pestis plague). Together with rising antibiotic resistance rates, there is a critical need to better understand Yersinia pathogenesis and host immune mechanisms, as this information will aid in developing improved immunomodulatory therapeutics. Inflammasome responses in human cells are less studied relative to murine models of infection, though recent studies have uncovered key differences in inflammasome responses between mice and humans. Here, we dissect human intestinal epithelial cell and macrophage inflammasome responses to Yersinia pseudotuberculosis. Our findings provide insight into species- and cell type-specific differences in inflammasome responses to Yersinia.

Beyond Plants: The Ultra-Processing of Global Diets Is Harming the Health of People, Places, and Planet.

Global food systems are a central issue for personal and planetary health in the Anthropocene. One aspect of major concern is the dramatic global spread of ultra-processed convenience foods in the last 75 years, which is linked with the rising human burden of disease and growing sustainability and environmental health challenges. However, there are also calls to radically transform global food systems, from animal to plant-derived protein sources, which may have unintended consequences. Commercial entities have moved toward this "great plant transition" with vigor. Whether motivated by profit or genuine environmental concern, this effort has facilitated the emergence of novel ultra-processed "plant-based" commercial products devoid of nutrients and fiber, and sometimes inclusive of high sugar, industrial fats, and synthetic additives. These and other ingredients combined into "plant-based" foods are often assumed to be healthy and lower in calorie content. However, the available evidence indicates that many of these products can potentially compromise health at all scales-of people, places, and planet. In this viewpoint, we summarize and reflect on the evidence and discussions presented at the Nova Network planetary health meeting on the "Future of Food", which had a particular focus on the encroachment of ultra-processed foods into the global food supply, including the plant-sourced animal protein alternatives (and the collective of ingredients therein) that are finding their way into global fast-food chains. We contend that while there has been much uncritical media attention given to the environmental impact of protein and macronutrient sources-meat vs. novel soy/pea protein burgers, etc.-the impact of the heavy industrial processing on both human and environmental health is significant but often overlooked, including effects on cognition and mental health. This calls for a more nuanced discourse that considers these complexities and refocuses priorities and value systems towards mutualistic solutions, with co-benefits for individuals, local communities, and global ecology.

Mapping diversity in African trypanosomes using high resolution spatial proteomics

African trypanosomes are dixenous eukaryotic parasites that impose a significant human and veterinary disease burden on sub-Saharan Africa. Diversity between species and life-cycle stages is concomitant with distinct host and tissue tropisms within this group. Here, the spatial proteomes of two African trypanosome species, Trypanosoma brucei and Trypanosoma congolense, are mapped across two life-stages. The four resulting datasets provide evidence of expression of approximately 5500 proteins per cell-type. Over 2500 proteins per cell-type are classified to specific subcellular compartments, providing four comprehensive spatial proteomes. Comparative analysis reveals key routes of parasitic adaptation to different biological niches and provides insight into the molecular basis for diversity within and between these pathogen species.