A role for zinc in the mitigation of zoonotic disease attributable to RNA viruses—a review with application to One Health perspective

One health the future of rural health?

In this issue of Environmental Health Perspectives, Feingold et al. (2010) propose a unique step forward for toxicology: incorporating infectious disease agents and theory into the toxicological paradigm. The fields of infectious disease and toxicology intersect on many different levels. First, they can act concurrently, as when global bands of various tropical diseases widen due to increased atmospheric temperatures. For example, in A Human Health Perspective on Climate Change, the Interagency Working Group on Climate Change and Health (2010) identified health effects from climate change, as well as the health benefits from mitigating climate change. These various health effects range from respiratory and cardiovascular disease, to developmental and neurological disorders, to food- and waterborne illness, and vectorborne and zoonotic disease. It is increasingly clear that climate change—a marquee issue in the field of environmental health—and infectious disease are linked. Second, the two fields can also act antagonistically: For example, the newly renewed appeals for global use of DDT (dichlorodiphenyltrichloroethane) to combat malaria will pit the well-known hazardous effects of DDT against the scourge of malaria. In many countries DDT has been banned for agricultural use; it is considered a Class II or “moderately hazardous” pesticide by the World Health Organization (International Programme on Chemical Safety 2005), and its use is strictly limited by the 2001 Stockholm Convention. However, use of DDT is still permitted for vector control. This balance of risks and benefits is a conundrum for scientists and policy makers, but it reveals the serious issues raised when infectious disease and environmental health interests clash. Third, these two disciplines can act synergistically, as in the interactions between hepatitis B and aflatoxin in hepatic cancer. Both hepatitis B and aflatoxin are independent factors in liver cancer. However, when combined, they act powerfully to raise the risk of hepatic cancer up to 60 times that of unexposed individuals (Groopman et al. 2005). This National Institute of Environmental Health Sciences (NIEHS)-funded research is a primary example of the interaction between environmental health and infectious disease and can serve as a model for future research efforts. Supression of the immune response by polychlorinated biphenyls (PCBs) was first shown in mice and nonhuman primates. Recently, in another example of concurrent interaction, NIEHS-funded studies led by Philippe Grandjean have shown that perinatal and developmental exposure to PCBs adversely impact immune responses to childhood vaccinations (Heilmann et al. 2006, 2010). We have an opportunity at the NIEHS to embrace this new paradigm. As we have shown with our investment in research into the aflatoxin–hepatitis B and PCB–vaccine interactions, the NIEHS has a track record that could promote a wider interest in this field of inquiry. Ideas like these are supported not only at the institute level but also throughout the National Institutes of Health (NIH). Recently, NIH director Francis Collins (2010b) wrote, “NIH can play a major role in ramping up the discovery of novel targets in both pathogen and host and work to facilitate advances in prevention . . . .” Collins (2010a) also wrote, “the best outcomes are generally when you don’t have walls between parts of the organization that prevent people from learning from each other.” A recent presentation at the NIEHS outlined a vision for the institute that included the infectious disease and environmental health intersection within the context of the rapid evolution in the field of environmental health, specifically in epigenetics. As we recognize that our old assumptions about toxicants and how they affect our bodies are being changed by modern science (e.g., exposure effects are not only dose dependent but are also affected by both time and context), the field of environmental health is moving fast and the NIEHS needs to be at the front with innovative, bold ideas so we can participate and lead with the best science possible. The idea of incorporating infectious disease into the toxicological paradigm is exactly the kind of pioneering concept that can take environmental health to the next level. The NIEHS Office of the Director will be working with division leaders to develop an initiative on infectious disease and environmental health—to incorporate infectious disease into the toxicological paradigm. We look forward to the possibilities to strengthen the field of environmental health science.

Growing concern that phthalic acid esters (PAE) may present a health hazard and possible deleterious effects on the ecological system has led to increased interest in the more subtle toxicity of those compounds. Although the acute toxicity of PAEs as a group is quite low, the intrinsic cellular toxicity increases with molecular weight. Whether the intrinsic toxicity is great enough to exert a significant effect in vivo at the typically low levels of solubility of PAEs is of primary importance to the assessment of their potential hazard. This paper reviews work reported on the teratogenicity of PAEs and new work on the mutagenicity, cellular toxicity, and absorption, excretion, and distribution of those compounds. The relationship of in vitro and in vivo response is discussed.

Uptake and Fate of Di-2-Ethylhexyl Phthalate in Aquatic Organisms and in a Model Ecosystem

ARTICLESEffects of metal ions and sulfhydryl inhibitors on glucose metabolism by adipose tissuePK Dixit, and A LazarowPK Dixit, and A LazarowPublished Online:01 Oct 1967https://doi.org/10.1152/ajplegacy.1967.213.4.849MoreSectionsPDF (3 MB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat Previous Back to Top Next Download PDF FiguresReferencesRelatedInformation Cited ByPeroxisomal Oxidases and Suggestions for the Mechanism of Action of Insulin and Other Hormones22 November 2006Arsenic Exposure and Type 2 Diabetes: A Systematic Review of the Experimental and Epidemiologic EvidenceEnvironmental Health Perspectives, Vol. 114, No. 5Boron, Manganese, Molybdenum, Nickel, Silicon and Vanadium14 December 2009Enzymatic and cellular level effects of chromium∗Toxicological & Environmental Chemistry, Vol. 19, No. 3-4Enzymatic and cellular level effects of cadmiumToxicological & Environmental Chemistry, Vol. 19, No. 3-4The inhibition of mammalian d-amino acid oxidase by metabolites and drugs. Inferences concerning physiological functionBioorganic Chemistry, Vol. 11, No. 3Multiple effects of sulphydryl reagents on sugar transport by rat soleus muscleBiochimica et Biophysica Acta (BBA) - Biomembranes, Vol. 689, No. 2Serum enzyme changes due to trace amounts of some transition metal ions on the induction of experimental diabetes1 June 1980 | Zeitschrift für Ernährungswissenschaft, Vol. 19, No. 2Serum mineral changes due to exogenous ATP and certain trace elements in experimental diabetes1 March 1979 | Zeitschrift für Ernährungswissenschaft, Vol. 18, No. 1Endogenous hydrogen peroxide and peroxidative metabolism in adipocytes in response to insulin and sulfhydryl reagentsBiochemical Pharmacology, Vol. 27, No. 22Reduced nicotinamide adenine dinucleotide phosphate oxidase in adipocyte plasma membrane and its activation by insulinArchives of Biochemistry and Biophysics, Vol. 184, No. 1The effect of ATP and certain trace elements on the induction of experimental diabetes1 September 1977 | Zeitschrift für Ernährungswissenschaft, Vol. 16, No. 3Trace Metals in EndocrinologyMedical Clinics of North America, Vol. 60, No. 4Effects of sulfhydryl inhibition on the regulation of basal lipolysis and glucose uptake in human adipose tissueBiochemical Pharmacology, Vol. 24, No. 9Sensitization of adipose tissue to insulin by rat serumNaunyn-Schmiedeberg's Archives of Pharmacology, Vol. 283, No. 1The non-involvement of cysteine or cystine in the membrane receptor site of insulinActa Diabetologica Latina, Vol. 9, No. 1Glucose Transport in Plasma Membrane Vesicles from Rat Adipose TissueJournal of Biological Chemistry, Vol. 247, No. 9Transport of Carbohydrates by Animal CellsRegulation of Pyrimidine Ribonucleoside Incorporation in Isolated Bone CellsJournal of Biological Chemistry, Vol. 246, No. 14Non-suppressible insulin-like activity of human serumBiochimica et Biophysica Acta (BBA) - General Subjects, Vol. 230, No. 1Sulfhydryl Groups in Membrane Structure and FunctionStudies of the Insulin-like Actions of Thiols upon Isolated Fat CellsJournal of Biological Chemistry, Vol. 245, No. 1Methodology of Zinc Determinations and The Role of Zinc in Biochemical ProcessesInsulin-Receptor Interaction in Isolated Fat CellsJournal of Biological Chemistry, Vol. 244, No. 19The effect of sulfhydryl blockade on insulin action and glucose transport in isolated adipose tissue cellsBiochimica et Biophysica Acta (BBA) - General Subjects, Vol. 177, No. 3The effect of zinc on the uptake of glucose by adipose tissueBiochimica et Biophysica Acta (BBA) - General Subjects, Vol. 177, No. 3Incorporation and utilization of radioglucose in the fish embryoOryzias latipes during teratogenesisTeratology, Vol. 1, No. 4 More from this issue > Volume 213Issue 4October 1967Pages 849-856 Copyright & PermissionsCopyright © 1967 by American Physiological Societyhttps://doi.org/10.1152/ajplegacy.1967.213.4.849PubMed6051180History Published online 1 October 1967 Published in print 1 October 1967 Metrics

The interconnection between human, animal, and ecosystem health is crucial, particularly in rural areas, where several socio-economic and environmental risk factors heighten vulnerability to zoonotic diseases. This study aims to assess the vulnerability as well as knowledge and practices concerning zoonosis from a One Health perspective. A cross-sectional study was carried out in rural areas of Madurai district, Tamil Nadu, from July to December 2024, selected by simple random sampling. The socio-demographic and ecological risk factors, knowledge, attitudes, and practices regarding zoonosis were assessed utilizing a validated semi-structured questionnaire among 408 participants. Microsoft Excel (Microsoft, Redmond, WA, USA) and R programming (version 4.4.3; R Foundation for Statistical Computing, Vienna, Austria) were used for analyzing the data. The study sample, comprising 238 (58.3%) males, had a mean age of 43.32 years, with 46 (11.3%) being illiterate. Around 134 (32.84%) belonged to the lower middle class, with 50 (12.3%) worked in agriculture, and 118 (28.9%) were unemployed. Around 96 (23.53%) of the population lived in kutcha houses, 151 (37.01%) reported dampness, and 253 (62.01%) reported overcrowding. Environmental issues include mosquito breeding in 279 (68.38%), open drains in 268 (65.69%), stray animals in 308 (75.49%), and rat infestations in 155 (37.99%) of communities. Around 321 (79%) of individuals demonstrated good knowledge, while only 96 (24%) exhibited a positive attitude and 107 (26%) engaged in good practices. We noted a negative attitude and poor practices among 120 (29%) and 170 (42%), respectively. Individuals aged 41 years and older (p=0.02) and pet owners (p=0.01) demonstrated a higher level of knowledge. This study emphasizes the importance of addressing vulnerabilities in socially and ecologically disadvantaged populations to prevent zoonotic diseases. It identifies a gap between knowledge and practical application, advocating for behavior change for better rural health outcomes.

Snakebite envenoming has a substantial health and socioeconomic effect in rural communities. However, there are insufficient epidemiological and animal data, which prevents accurate assessment on the effects of snakebite. We aimed to assess the health and socioeconomic effect of snakebite using a One Health perspective. In this cross-sectional survey-based study, we assessed the health and socioeconomic effects of snakebite data using a multicluster survey that was previously done as part of the SNAKE-BYTE project in the Terai region, Nepal. Health effect was measured in terms of disability-adjusted life years (DALYs). Livelihood losses encompassed out-of-pocket health-care expenditures, losses of productivity due to days off work, and the losses due to mortality and treatment costs in domestic animals. Mortality losses in domestic animals were also estimated as animal loss equivalents, and overall human and animal health effect expressed using modified DALYs for zoonotic disease (zDALYs). We estimate an annual snakebite burden of 200 799 DALYs (95% CI 103 137-357 805), mostly due to mortality in children and women. Snakebite is estimated to lead to US$2·8 million in yearly livelihood losses associated with human and animal cases. Overall, we estimate a yearly human and animal health burden of 202 595 zDALYs (104 300-360 284). These findings present robust evidence on the extent of snakebite's health and socioeconomic effect and emphasise the need for a One Health perspective. The results also stress how improved data collection at the community level is crucial for improved assessments of its effect. Swiss National Science Foundation.

BackgroundMonkeypox (mpox) is an emerging zoonotic disease that has persistently impacted public health in endemic regions of West and Central Africa for over half a century. The Democratic Republic of the Congo (DRC) remains one of the countries most affected. Understanding the risk factors for disease transmission from a One Health perspective is of great importance in the risk assessment, prevention, and control of zoonotic diseases. Therefore, this study aimed to investigate the risk factors for human mpox transmission at the human–animal–environment interface in the DRC.MethodsEpidemiological, environmental, socioeconomic, and sociocultural data from the DRC from 2000 to 2015 were obtained from publicly available dataset. Using these data, we applied negative binomial regression model, least absolute shrinkage and selection operator regression model, and principal component analysis (PCA) to identify key environmental, socioeconomic, and sociocultural factors contributing to mpox transmission. Moreover, a grey prediction model GM (1, n) was constructed to predict the epidemic trend of mpox post-2015 and validated using suspected mpox case data in the DRC from 2016 to 2021, sourced from the United States Centers for Disease Control and Prevention.ResultsBetween 2000 and 2021, a total of 43,628 suspected mpox cases were reported in the DRC, with a peak of 6216 cases in 2020. From 2016 to 2021, suspected cases accounted for over half (24,379/43,628, 55.9%) of the total reported during the 2000–2021 period. The proportion of primary forest [incidence rate ratio (IRR): 1.023, 95% confidence interval (CI): 1.018–1.027], index of economic well-being (IRR: 1.046, 95% CI: 1.039–1.052), and mean annual precipitation (IRR 1.040, 95% CI: 1.031–1.049) were positively associated with mpox incidence. PCA identified five principal components, explaining 69% of the variance in the environmental, socioeconomic, and sociocultural variables. The first component was characterized by socioeconomic factors. The GM (1, n) model, based on the proportion of primary forest, index of economic well-being, and mean annual precipitation, predicted the epidemic trend (revealed relative error: 2.69).ConclusionsBoth socioeconomic and environmental factors play important roles in mpox transmission. Our study further highlighted the importance of considering the interconnectedness among humans, animals, and the environment, and treating these factors as a whole to explain the transmission and emergence of mpox outbreaks in the DRC according to the One Health concept.

The purpose of this review was to investigatethe microbial and chemical safety of camel meat and the zoonotic diseases associated with camels in the Middle East over the past decade, emphasizing the crucial role of a One Health approach. By systematically analyzing recent studies (in the past decade, from 2014), we assessed pathogen prevalence, contamination with heavy metals and pesticide residues, and the impact of zoonotic diseases like Middle East respiratory syndrome coronavirus (MERS-CoV). The findings revealed significant variability in pathogen prevalence, with the frequent detection of traditional foodborne pathogens (e.g., Salmonella and E. coli O157), as well as antibiotic-resistant strains like methicillin-resistant and vancomycin-resistant Staphylococcus aureus and extended-spectrum β-lactamase (ESBL)-producing E. coli, underscoring the need for stringent antibiotic use policies and robust food safety measures. Additionally, the review highlighted substantial contamination of camel meat with heavy metals and pesticide residues, posing significant public health concerns that necessitate stringent regulatory measures and regular monitoring. The persistent occurrence of zoonotic diseases, particularly MERS-CoV, along with other threats like trypanosomiasis, brucellosis, and Clostridium perfringens, emphasizes the importance of strengthening ongoing surveillance. Enhancing investment in diagnostic infrastructures, training programs, and planning capabilities is crucial to address these issues at the camel-human interface in the Middle East. Adopting a One Health perspective is vital to ensuring the safety and quality of camel meat and managing zoonotic risks effectively to ultimately safeguard public health and promote sustainable livestock practices.

The role of zinc in retroviral gag protein function has been addressed through the application of high-resolution nuclear magnetic resonance spectroscopy to samples of the nucleocapsid protein (NCP, p7) isolated directly from infectious HIV-1 particles. Unlike reports for the NCP from avian myeloblastosis virus (AMV) particles [Jentoft et al. (1988) Proc. Natl. Acad. Sci. U.S.A. 85, 7094], we find that the HIV-1 NCP binds 2 equiv of zinc tightly and stoichiometrically. Two-dimensional NMR spectroscopic studies reveal that zinc binding induces formation of folded domains that are conformationally similar to (if not identical with) structures observed previously for relevant retroviral-type (RT) zinc finger peptides [formerly called zinc fingerlike peptides; Summers et al. (1990) Biochemistry 29, 329]. This finding is consistent with the hypothesis that the inability of mutant proteins (with substituted Cys and His residues) to package viral RNA results from deficient zinc-binding capability, which may have significant consequences in the development of vaccines for the prevention of AIDS.

Hepatitis C virus (HCV) infection is a significant global public health problem. In clinical studies, zinc has been closely related to the pathogenesis of chronic hepatitis C. However, the role of zinc in both viral replication and the expression of viral proteins remains unclear. We aimed to clarify the effect of zinc on the replication of HCV in vitro. We incubated subgenomic HCV replicon cells (sO) and genome-length HCV RNA-replicating cells (O) treated with several chemicals including trace elements. Total RNAs were collected and subjected to real-time reverse-transcriptase polymerase chain reaction in order to examine the level of HCV RNA replication, and Western blotting was performed to confirm the expression of viral proteins. Iron salts and interferon-alpha suppressed HCV RNA replication and protein expression in both sO and O cells. Zinc salts effectively reduced the viral replication in the genome-length HCV RNA replication system but not in the subgenomic HCV replicon system. We demonstrated that zinc may play an important role as a negative regulator of HCV replication in genome-length HCV RNA-replicating cells. Zinc supplementation thus appears to offer a novel approach to the development of future strategies for the treatment of intractable chronic hepatitis C.

Toxoplasmosis is one of the most common zoonotic parasitic diseases infecting nearly all warm-blooded animals, including poultry (geese, turkeys, chickens, and ducks). It is caused by Toxoplasma gondii (T. gondii), which is an obligate intracellular protozoan belonging to the Apicomplexa group. In Thailand, duck meat production for domestic consumption and international trade is mainly bred and produced in the central and western parts of the country. Free-grazing ducks in integrated duck-rice production have significant benefits in rice cultivation, accounting for the popularity of this farming system in Thailand. However, ducks are considered particularly susceptible to consuming T. gondii oocysts from water contaminated with cat feces due to the fact of their feeding habits of free-grazing and dabbling. Hence, the prevalence of this zoonotic parasite in a large-scale integrated farming context is particularly challenging with respect to the contamination of the food chain of humans and farm animals. In the present study, we examined the overall prevalence of T. gondii infection in slaughtered free-grazing ducks originating from Central and Western Thailand, setting the stage for an in-depth One Health approach to assess and manage the risks of integrated farming practices. A representative sample size of 161 ducks was calculated using a two-stage sampling method. Specifically, serum samples were collected from 217 slaughtered free-grazing ducks originating in six provinces in Central and Western Thailand. Serum antibodies against T. gondii were detected using an indirect fluorescent antibody test (IFAT). The positive control serum samples were prepared from ducks experimentally immunized with T. gondii. Sixty-eight (31.3%) of the two hundred and seventeen ducks were seropositive with T. gondii. Two groups of fattening ducks and spent layers showed similar seropositivity rates at 29% and 32.3%, with the majority of positive samples being found in the low titer. In addition, a wide distribution of positive serum samples was observed in all six provinces in the present study. To the best of our knowledge, this is the first report on a serological prevalence snapshot in commercially produced duck populations that have high interaction with farmed environments in Thailand, revealing a high infection pressure in areas of integrated duck-rice farming. Importantly, contaminated duck meat for commercial use, as well as offal and carcasses from slaughterhouses, completes the transmission of T. gondii from the environment into the food chain of humans and domestic animals. Hence, from a One Health perspective, it is important to clarify whether this transmission chain extends further to the wild, i.e., predator-prey cycles that are independent of duck farming or are self-contained.

BackgroundZoonotic diseases continue to be a public health burden globally. Uganda is especially vulnerable due to its location, biodiversity, and population. Given these concerns, the Ugandan government in collaboration with the Global Health Security Agenda conducted a One Health Zoonotic Disease Prioritization Workshop to identify zoonotic diseases of greatest national concern to the Ugandan government.Materials and methodsThe One Health Zoonotic Disease Prioritization tool, a semi-quantitative tool developed by the U.S. Centers for Disease Control and Prevention, was used for the prioritization of zoonoses. Workshop participants included voting members and observers representing multiple government and non-governmental sectors. During the workshop, criteria for prioritization were selected, and questions and weights relevant to each criterion were determined. We used a decision tree to provide a ranked list of zoonoses. Participants then established next steps for multisectoral engagement for the prioritized zoonoses. A sensitivity analysis demonstrated how criteria weights impacted disease prioritization.ResultsForty-eight zoonoses were considered during the workshop. Criteria selected to prioritize zoonotic diseases were (1) severity of disease in humans in Uganda, (2) availability of effective control strategies, (3) potential to cause an epidemic or pandemic in humans or animals, (4) social and economic impacts, and (5) bioterrorism potential. Seven zoonotic diseases were identified as priorities for Uganda: anthrax, zoonotic influenza viruses, viral hemorrhagic fevers, brucellosis, African trypanosomiasis, plague, and rabies. Sensitivity analysis did not indicate significant changes in zoonotic disease prioritization based on criteria weights.DiscussionOne Health approaches and multisectoral collaborations are crucial to the surveillance, prevention, and control strategies for zoonotic diseases. Uganda used such an approach to identify zoonoses of national concern. Identifying these priority diseases enables Uganda’s National One Health Platform and Zoonotic Disease Coordination Office to address these zoonoses in the future with a targeted allocation of resources.

BackgroundPrioritizing zoonotic diseases is one of the emerging tasks for developing multi-sectoral collaboration within One Health. Globally, many efforts have been made to prioritize zoonotic diseases at national levels, especially in low resource settings. Prioritization of zoonoses has been conducted in different countries at different levels (i.e. national, regional and local) for different purposes. India has also initiated prioritization of zoonotic diseases at the national level. However, in a country like India with wide climatic variations, different animal-human and vector densities, it is important to look at these zoonotic conditions in local settings too. The present study aims to determine which zoonoses should be prioritized for collaboration between stakeholders in the Indian city of Ahmedabad.MethodsThe present study followed a participatory research method, entailing a stakeholder workshop for prioritizing zoonotic diseases in Ahmedabad. It was carried out through a facilitated consultative process involving 19 experts in zoonoses from the human and animal health systems during a one-day workshop in September 2018. To prioritize the zoonotic diseases, the One Health Zoonotic Disease Prioritization (OHZDP) tool of the U.S. Centers for Disease Control and Prevention was adopted. The Analytical Hierarchical Process (AHP) and decision-tree analysis were used to rank the diseases.ResultsOut of 38 listed zoonotic diseases, 14 were selected for prioritization. These were scored and weighed against five criteria: severity of disease in humans, potential for epidemic and/or pandemic, availability of prevention and/or control strategies, burden of animal disease existing inter-sectoral collaboration.The top five diseases that have been prioritized for Ahmedabad are Rabies, Brucellosis, Avian Influenza (H5N1), Influenza A (H1N1) and Crimean-Congo Hemorrhagic Fever. Sensitivity analysis did not indicate significant changes in zoonotic disease prioritization based on criteria weights.ConclusionPrioritization of zoonotic diseases at the local level is essential for development of effective One Health strategies. This type of participatory disease prioritization workshop is highly recommended and can be replicated in other Indian cities, as well as in other low and middle-income countries.

The novel zoonotic Coronavirus disease 2019 (COVID-19) pandemic: Health perspective on the outbreak