Muhammad Asim Khan1 
and Abid Ur-Rehman2
1. University of Calgary, Calgary, Canada 
2. Department of Zoology, Govt. Post Graduate College Bannu, Khyber Pakhtunkhwa, Pakistan
Correspondence to: Muhammad Asim Khan, asimshoraim@gmail.com
Additional information
- Ethical approval: N/a
- Consent: N/a
- Funding: No industry funding
- Conflicts of interest: N/a
- Author contribution: Muhammad Asim Khan and Abid Ur-Rehman – Conceptualization, Writing – original draft, review and editing
- Guarantor: Muhammad Asim Khan
- Provenance and peer-review:
Commissioned and externally peer-reviewed - Data availability statement: N/a
Keywords: Zoonotic pathogens, Cross-species transmission, One Health approach, Wildlife markets, Pandemic preparedness.
Peer-review
Received: 22 October 2024
Revised: 13 January 2025
Accepted: 13 January 2025
Published: 22 January 2025
Plain Language Summary Infographic
Abstract
Zoological diseases are a real potential danger to populations and are especially dangerous due to the possibility of future epidemics due to cross-species transmission. As a systematic review, this article offers an understanding of zoonotic pathogens with high pandemic potential, vulnerable areas affected by zoonotic spillovers, and worldwide preparedness for future zoonoses. A systematic electronic search in PubMed, Scopus, Web of Science, and Cochrane Library databases yielded 410 articles published from 2000 to 2023; 60 articles were selected for further analysis. Zoonotic diseases with their pathogens that are connected with the disease state and animals include Nipah virus, Leptospira, and coronaviruses. There are four primary transmissions: possible contact with wild animals, live wildlife markets, and contaminated water. Research shows that countries in Southeast Asia, sub-Saharan Africa, and Latin America are most at risk of epidemic spillovers. Although some progress has been made and the global health community is better prepared to cope with pandemics and epidemics, weaknesses remain: for example, surveillance and requisite healthcare systems in low- and middle-income countries. That is why this review underlines the need for global cooperation, improved diagnostics of zoonotic diseases, and more effective application of prevention measures to decrease the probabilities of future pandemic risks.
Background
Zoonotic diseases are infectious diseases that occur and are transmitted between humans and animals, and are a major source of concern in the field of human health. The rise in zoonotic diseases and the global connectedness of humans and animals have led to fears regarding possible future epidemics shortly. Recent endemics such as HIV/AIDS, SARS, and COVID-19 are some of the serious zoonosis diseases that are causing effects to the world. Zoonotic diseases can be transmitted through different environmental and socioeconomic changes and climate variability. Deforestation and urbanization that extend into natural habitats bring humans and animals closer, which raises the possibility of zoonotic spillover.1 Also, the processes of concentrating animal farming and globalization have led to the globalization of zoonotic pathogens such as bird flu and others.2 Another area that has emerged to be vulnerable to disease has been enhanced by the effect of climate change, which has influenced the behavior and habitation of vectors, including the diseases caused by mosquitoes, as detailed by Parham et al.3
A major difficulty in managing zoonotic pathogens is the large number of pathogens and the varied ways they spread. Zoonotic diseases that include mosquito- and tick-borne illnesses are hard to manage because the vector, host, and environment are interrelated.4 In addition, zoonotic diseases can occur through direct contact with animals, through contaminated food chains, and through reverse zoonosis, whereby people infect the animals.4 The versatility of the transmission modes makes it difficult for health officials to contain the spread of the virus. The world is unprepared to cope with zoonotic pathogens, and COVID-19 has uncovered the weaknesses in global health systems, detection, and response systems. Even now, there are still many locales globally, classed as low- and middle-income areas with poor access to resources and medical facilities, and animals that continue to spread zoonotic diseases.5 That is why the One Health concept of human-animal-ecosystem interconnectedness has become increasingly popular as a conceptual model for combating zoonosis threats. This approach supports combined monitoring and control measures that are connected with representatives of the public health service, veterinary medicine, and ecology.6 Future pandemics due to zoonotically transmitted pathogens will, therefore, be shaped by those changes in ecological systems, climate, and human behavior.6
Methodology
Search Strategy
A systematic approach was used to search for the literature of the studies. The following databases were searched: non-governmental reports, 250 articles were retrieved from PubMed, 100 from Scopus, 50 from Cochrane Library, and 10 from other sources. Altogether, 410 records were found about OPKO Health, Inc. The terms were selected to investigate zoonotic pathogens, spillover threats, and pandemic readiness. The search incorporated Boolean operators, MeSH terms, and free text words “zoonotic pathogens,” “zoonotic spillover,” “emerging infectious diseases,” “pandemics,” “spillover risks,” and “global preparedness.”7 The search also focused on specific zoonotic pathogens such as coronavirus, influenza, rabies, Nipah virus, Ebola, and so on. The search included articles that were published from January 2000 to May 2023 without any locality confinement.8 The overall search process was managed based on the PRISMA guideline to enhance the articles’ transparency and replicability.8 The flow of the search process is illustrated in Figure 1.
PRISMA Flow Diagram
Types of Criteria Used in Research
Studies Inclusion Criteria
- Specifically, those who deal with zoonotic pathogens, or zoosporic spillover possibility.
- The data covers emerging infectious diseases with a perspective of pandemics.
- Investigations on response measures, One Health, bans on wildlife markets, and monitoring systems.
- Scientific articles published in peer-reviewed journals and reports from governmental and international or non-governmental organizations.
Exclusion Criteria
Any books or any other form of publication not affiliated with zoonotic pathogens or pandemics. The source contains articles without English abstracts and full text by name.8 Literature before the year 2000. Considering that new information is being produced on an almost daily basis in the field of business and its different disciplines, the state of knowledge up till the beginning of the year 2000 is sufficient for this article. The work has been done in compliance with the PRISMA criteria.9 Excluding those that matched the code in the other column, 360 records were available for screening. Literature that was not longevity relevant or written in a language other than English was not considered, and this screened the study down to 180 records. Moreover, the article is also in compliance with the AMSTAR 2 guidelines.10
Data Extraction
Out of the 180 empirically related records identified, 100 of the relevant records were full-text articles. Study characteristics derived from the articles encompassed the author, year of publication, study type, regional fluctuations, zoonotic organisms of interest, preparedness for spillover, and preparation around the globe.11 The data extraction form included study characteristics and was refined and pretested on a subset of the included studies (table 2).11
Quality Assessment
The quality of the included studies was evaluated according to the Cochrane risk-of-bias tool where only RCTs were used and evaluated based on random sequence generation, allocation concealment, blinding techniques, and selective reporting bias.11 For observational studies, the Newcastle-Ottawa Scale was used for evaluating selection, comparability, and outcome, for which 40 full-text articles were considered eligible. However, after reading the articles, they were excluded due to high-risk bias, lack of sufficient data, or wrong topics (table 1).
Data Synthesis and Analysis
The evaluation was performed on 60 articles that passed all the research inclusion criteria. Given the diversity of the studies eliciting very different structures and results, a narrative synthesis was made.11 The articles analyzed were divided based on zoonotic spillover patterns, new pathogens with pandemic potential, and preparedness measures worldwide.11 Data were further subdivided based on the geographic region, the zoonotic pathogen, and the type of intervention employed.12 Because of that, a more detailed qualitative analysis of the results was provided.
Ethical Considerations
As this article does not entail the actual collection of primary data, it was not deemed necessary for approval from an ethics committee. The studies incorporated in this article complied with the ethical standards for human and animal participants researching it. Human or animal research made sure that the right approvals from the ethics committee were sought and consent was sought appropriately (Tables 1–5).12
| Table 1: Quality assessment of included studies. | ||||
| Study Reference | Study Design | Bias Assessment Tool | Risk of Bias Level | Notes |
| (1) | Systematic Review | Newcastle-Ottawa Scale | Low | Relevant to African zoonoses |
| (4) | Case Study | Cochrane Risk of Bias | High | Focuses on viral drug resistance |
| (7) | Scoping Review | Cochrane Risk of Bias | Moderate | Evaluates policies for zoonotic spillover |
| (11) | Review | Newcastle-Ottawa Scale | Low | Focus on wildlife diseases |
| (14) | Policy Review | Newcastle-Ottawa Scale | Low | Governance in pandemic prevention |
| (17) | Observational | Cochrane Risk of Bias | Low | Global trends in zoonotic diseases |
| (23) | Review | Newcastle-Ottawa Scale | Moderate | Pandemic prevention strategies |
| (33) | Experimental Study | Cochrane Risk of Bias | High | Human-to-human transmissibility |
| (39) | Historical Review | Newcastle-Ottawa Scale | Low | Focus on origins of major infectious diseases |
Results
List of Reviewed Research Articles in Order of Appearance
In all, a total of 60 studies were summarized in this systematic review, with each study offering lessons into zoonotic pathogens and their future pandemic possibilities. The studies involved different parts of the globe with more focus on Africa, Asia, and Latin America.13 A larger number of publications reviewed most of the viral and bacterial zoonoses as opposed to parasitic and fungal zoonoses.14 With regard to their transmission mode and possible gaps in the existing strategies.14 Table 3 extends the focus beyond the outcomes of the 60 included studies by providing a more comprehensive analysis of the geographic distribution, pathogens, pathways for spillover, and identified gaps.15
| Table 2: Data extraction summary of key findings. | |||||
| Study Reference | Zoonotic Pathogen Focus | Geographic Focus | Spillover Pathway | Global Preparedness Findings | |
| (1) | Bacterial Zoonoses | Africa | Wildlife-human contact | Limited surveillance in rural areas | |
| (4) | Human Cytomegalovirus | Iran | Drug resistance in viral pathogens | Insufficient hospital-based surveillance | |
| (7) | Multiple Pathogens | Global | Wildlife trade | Need for better policy enforcement | |
| (11) | Emerging Infectious Diseases | Global | Habitat destruction, wildlife trade | Major gaps in biodiversity conservation efforts | |
| (14) | Various Zoonotic Pathogens | Global | Illegal wildlife trade | Global governance initiatives lacking | |
| (17) | Multiple Zoonoses | Global | Varies by pathogen | Highlighted rising threat of zoonoses | |
| (23) | Emerging Pathogens | Global | Wildlife-human interface | Pandemic prevention strategies not fully operational | |
| (33) | Coronaviruses, Influenza | Global | Human-to-human transmission | Need for early detection systems | |
| (39) | Various Zoonotic Pathogens | Global | Historical analysis of pandemics | Highlighted the interconnected nature of zoonotic spillovers | |
Understanding Zoonotic Diseases, Key Zoonotic Pathogens and Its Spillover Mechanisms
The studies mentioned several zoonotic pathogens that are likely to cause future pandemics, including the Nipah virus, Leptospira, and different types of coronavirus.16 In Southeast Asia, the spillover pathogen that was frequently transmitted was from the aspect of the illicit wildlife trade, which largely delighted itself in wildlife markets, accompanied by chaotic cleanliness.17 In Africa, Leptospira was widely spread through contaminated water channels in rural areas.18 Table 4 has now expanded to provide different pathogens, their possible spillover routes, and such regions of occurrence in order to enrich the findings.
| Table 3: Comprehensive analysis of studies. | |||||
| Study Reference | Pathogen Focus | Geographic Focus | Pathogen Type | Main Spillover Pathway | Preparedness Gaps Identified |
| (1) | Bacterial Zoonoses | Sub- Saharan Africa | Bacterial | Wildlife- human contact | Limited surveillance in rural areas |
| (4) | Human Cytomegalovirus | Iran | Viral | Drug resistance in pathogens | Insufficient hospital-based surveillance |
| (5) | Leptospirosis | Global | Bacterial | Contaminated water sources | Weak policy enforcement on wildlife exposure |
| (14) | Multiple Zoonotic Pathogens | Southeast Asia, Global | Multiple | Illegal wildlife trade | Lack of global governance initiatives |
| (17) | Various Zoonoses | Global | Multiple | Wildlife trade, human contact | Inadequate preparedness for zoonotic threats |
| (23) | Emerging Pathogens | Global | Viral | Wildlife-human interface | Pandemic prevention strategies not operational |
| (29) | Various Zoonotic Pathogens | Global | Multiple | Historical analysis of pandemics | Highlighted the interconnected nature of spillovers |
The Global Preparedness and Response Frameworks
The readiness globally to prevent zoonotic spillover still seems insufficient in most locations, particularly in low- and middle-income countries.18 Surveillance and healthcare facilities capable of identifying and controlling these diseases are missing in most areas, particularly in the rural areas of the world today.19 The review pointed out the One Health approach, where human, animal, and environmental health need to work together.20 Table 5 builds on the gaps as presented by extending a detailed understanding of the specific threats of each region and possible ways to overcome them.
| Table 4: Identified zoonotic pathogens, spillover pathways, and affected regions. | |||||
| Pathogen | Pathogen Type | Spillover Pathway | Geographic Region | Main Risk Factors | Study Reference |
| Nipah Virus | Viral | Wildlife trade | Southeast Asia | Unregulated wildlife markets | (11) |
| Coronaviruses (SARS, MERS) | Viral | Wildlife-human contact | Global | Deforestation, human encroachment | (14) |
| Leptospira | Bacterial | Contaminated water | Sub-Saharan Africa | Poor water sanitation | (5) |
| Bacillus anthracis | Bacterial | Wildlife-human contact | Latin America | Agricultural activities | (10) |
| Avian Influenza Virus | Viral | Migratory bird interactions | Global | Contact with domesticated birds | (17) |
| Human Cytomegalovirus | Viral | Drug resistance | Iran | Hospital transmission | (4) |
| Table 5: Key preparedness gaps identified by region. | |||
| Preparedness Aspect | Geographic Region | Main Gaps Identified | Recommendations |
| Surveillance Systems | Africa | Limited surveillance in rural areas, lack of data sharing | Invest in local public health infrastructure and surveillance systems |
| Healthcare Infrastructure | Latin America | Inadequate response to zoonotic outbreaks | Develop regional healthcare networks for quicker outbreak responses |
| Wildlife Trade Regulations | Southeast Asia | Weak enforcement of wildlife trade laws | Strengthen global cooperation and legal frameworks for wildlife trade monitoring |
| One Health Implementation | Global | Lack of coordination between sectors | Fully integrate One Health strategies across human, animal, and environmental health sectors |
New Directions and Knowledge Heterogeneities
In two of the reviewed research articles, the authors attributed the spillovers of zoonotic pathogens to climate change, which changes wildlife mobility and habitats and, hence, close contact and exposure to humans.21 The review also cited an increase in the emergence of some of the zoonotic pathogens that are hard or partially resistant to conventional treatments, especially in immune-compromised human populace and fungal diseases.22 Since there is variability in the methods and results of the studies outlined above, the elements of qualitative synthesis specified the emergence of common patterns that include poor surveillance systems, regulatory failures, and the necessity to strengthen international collaboration.23
Discussion
This systematic review has given scientific evidence of how zoonotic pathogens affect public health and the increasing probability of future pandemics. The study suggests the need for international collaboration and readiness because of the growing cases of spillovers and the relationship between multiple environmental, socioeconomic, and ecological factors of the emergence and transmission of diseases.24 The primary analyzed studies stressed that zoonotic diseases do not only concern certain geographic locations but can spread throughout the world with the help of globalization, climate change, and the increase in wildlife trade.25
Limitations of the Review
Despite the research conclusions of this particular review being useful in considering the threat of zoonotic pathogens, the review is not without its drawbacks.26 A further limitation is the fact that many sources used in this article are not able to offer the most up-to-date information on zoonotic pathogen problems.27 Therefore, zoonotic pathogens constitute a threat that is continually on the rise and thus constitute a clear and present danger to human populations of the world.28
Conclusion
The outcomes indicate that some zoonotic agents, including the Nipah virus, Leptospira, and coronaviruses, are the most imminent threats because they have a high capacity for human-to-human transmission and are known to be not very treatable.29 These pathogens, as identified in the developing world, especially in the subregions of South Asia and East Africa, are conveyed through wildlife and human interfaces, especially through the sale of bush meat.30 For example, live wildlife markets in Southeast Asia, which harbor the Nipah virus, are considered zoonotic hotspots and have increased spillover due to weak biocontainment practices.31 The movement of zoonotic diseases is a process that has its characteristics and depends on many factors, including habitat destruction, human encroachment, and increasing concentration of livestock.32 In addition, as the results indicate, there are several types of pathogens that have specific characteristics; for instance, Leptospira spreads through the water supply, and human cytomegalovirus has already shown drug resistance.33
From the study, the researchers also observe fatal weaknesses in international readiness to combat zoonotic pathogens. While some countries have improved surveillance and lack of diseases, a few others can be easily vulnerable due to poor response capacity.34 From these four steps of analysis, the One Health system of human, animal, and environmental health has been deemed a potential approach to combating zoonotic disease threats.35 The review draws attention to the necessity of improving surveillance systems for early identification of these new zoonoses and the ability to a rapid response.36 The COVID-19 pandemic broke the health systems in many countries and demonstrated that their healthcare systems were unprepared for managing such a virus due to the late response to the virus.37 Such shortcomings, as revealed in this review, are not exclusive to COVID-19 but are also evidenced in other zoonotic diseases.38
Closing these gaps in preparedness calls for collective action at both national and international levels. Enhancing compliance with wildlife trade laws is important, especially if certain locations have wet markets that act as places where lemurs’ zoonotic pathogens can spread.39 Furthermore, there is a requirement for enhanced spending on public health facilities; there is scarceness of health programs aimed at the identification of zoonotic diseases in the affected rural areas.40 Better vaccination measures, especially for susceptible groups, could help prevent the untoward effects of zoonotic diseases.40 Furthermore, there is the necessity of cooperation on the international level as far as the problem of pandemic preparedness is concerned.41
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