Factors Affecting Outbreaks and Prevention and Control Strategies of Wildlife ‌Infectious Diseases

Severity and harmfulness of wildlife infectious diseases

Wildlife generally refers to animals that have not been artificially bred or domesticated for a medium or long time. Wildlife infectious diseases generally refer to mass infection, abnormal health, and death of wildlife caused by pathogens, which may come from wildlife, people, livestock and poultry, pets, etc. Pathogens carried or infected by wildlife can also cause mass infections, abnormal health and death of people, livestock and poultry or pets, and even major public health and security incidents. Because there is an evolutionary relationship between humans and animals, sharing common or similar pathogens is natural and common. Zoonotic diseases imply those that can be cross-infected and transmitted between humans and wild or domestic animals and are related to livestock and poultry. There are many kinds of wildlife infectious diseases in China, involving viral, bacterial, and parasitic types. Their infection and transmission paths are complex and diverse, which poses a major threat to human health, livestock and poultry breeding, and the protection of rare and endangered animals. It is estimated that about 61% of human diseases are zoonotic diseases; among viral zoonotic diseases related to animals, about 60% come from rodents, 30% from bats, 23% from primates, 21% from ruminants, and 21% from carnivores. Therefore, the control of wildlife infectious diseases is crucial to the security of human public health, livestock, poultry, and fish aquaculture, biodiversity protection, and eco-safety.

In history, wildlife infectious diseases have brought great disasters to humans. For example, plague is a very dangerous zoonotic disease caused byYersinia pestiscarried by rodents, which is classified as a Class A infectious disease in China and abroad. According to historical records, three plague pandemics occurred worldwide, which began in 541 AD, in 1347 AD, and in 1855, respectively. It has been estimated that the death toll of each plague pandemic reached tens of millions, even hundreds of millions. In 1910, the plague broke out in Northeast China and lasted for more than six months, causing more than 60,000 deaths. Based on the analysis of the DNA sequence of modernY. pestis, it was thought that plague originated in China or near China. However, the recent analysis of the ancient DNA sequence ofY. pestisshows that the origin of plague can be traced back to Europe in Bronze Age, and the bubonic plague originated in Europe about 3,800 years ago.

In recent years, affected by global climate change and increasing human activities, major infectious diseases related to wild or domestic animals have become increasingly serious. It is estimated that there have been more than 10 global pandemics in the past 20 years, e.g., severe acute respiratory syndrome (SARS), influenza A, coronavirus disease 2019 (COVID-19), dengue fever, Zika virus disease, Ebola virus disease, Lassa fever, hemorrhagic fever, Lyme disease, plague, avian influenza, and African swine fever Since 2005, influenza A H1N1 epidemic (2009), Ebola epidemic (2014, 2018–2019), Zika virus epidemic (2016), wild poliomyelitis epidemic (2014), and COVID-19 epidemic (2020) have been declared as “public health emergencies of international concern” (PHEIC) by the World Health Organization (WHO). Studies show that Lassa fever, hemorrhagic fever, Lyme disease, and plague are transmitted by rodents and vector insects, Dengue fever and Zika virus disease by mosquitoes, influenza A and African swine fever by domestic pigs and vector insects, avian influenza by wild birds, and poultry, malaria by mosquitoes, Ebola, Hendra, and Nipah viruses diseases possibly by bats and rodents. SARS virus and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have high homology to coronavirus carried by bats, but their natural hosts and interspecific transmission routes have yet to be ascertained. Highly pathogenic avian influenza virus H5N1 carried by wild migratory birds can pose a serious threat to human health and the livestock and poultry breeding industry.

At the end of 2019, the COVID-19 epidemic broke out and became a global pandemic. Until January 31, 2021, the COVID-19 epidemic had caused 103 million infections and more than 2.2 million deaths worldwide. Besides, it further aggravated the global economic crisis and recession. From 2019 to 2020, China suffered multiple impacts from major infectious diseases such as COVID-19, African swine fever, and plague, which have caused immeasurable losses in people’s health, animal husbandry production, and economic and social development. Therefore, increasing the research and prevention and control of wildlife infectious diseases is necessary and urgent to ensure national bio-safety and eco-safety.

Causes for the outbreak of wildlife infectious diseases

In recent years, there are many causes for the outbreak, prevalence, and aggravation of wildlife infectious diseases, with climate change and human activities being the major ones.

Climate change leads to the frequent occurrence of global and regional wildlife infectious ‌diseases

Generally speaking, the occurrence and prevalence of large-scale infectious diseases are often related to large-scale climate anomalies or extreme weather. El Niño–Southern Oscillation (ENSO)  is an important large-scale climate factor resulting in climate anomalies in China and even the whole world. ENSO can change the normal atmospheric circulation, affect the global precipitation and temperature distribution patterns, induce major meteorological disasters and biological disasters. As the climate gets warmer and warmer, ENSO event has occurred more frequently in the past 50 years, which may be one of the important reasons for the frequent occurrence of major infectious diseases in the world. In the 1990s, Zhang et al.put forward the theory of “biological disasters caused by ENSO,” and believed that ENSO provided favorable conditions for harmful biological populations and triggered the frequent occurrence of biological disasters by changing the global atmospheric circulation, temperature, and precipitation patterns. Zhangalso pointed out that ENSO events can be used as an important indicator for forecasting large-scale and long-term biological disasters. In recent years, many studies in China and abroad have confirmed that ENSO is closely related to biological disasters. For example, Chinese scholars have successively found that ENSO event is closely related to the outbreaks of rodents in Europe, rodents and plague in China, hemorrhagic fever, or other infectious diseases. In the US, ENSO caused precipitation changes and increased the population of white-footed mice, thus inducing the Hantavirus epidemic. In Australia, ENSO-driven precipitation was increased, resulting in rodent outbreaks and a sharp increase in the number of small carnivores and endangering the survival of indigenous rare species. In Chile, accompanied by increased precipitation, the ENSO event led to the outbreak of local rodent populations.

Climate change usually has a complex effect on the occurrence of infectious diseases, which is related to the characteristics of hosts, pathogens, habitats, and human immunity. For example, dengue fever usually occurs in warm and humid summer, while influenza tends to occur in dry and cold winter,and the influenza virus spreads faster in winter.The influence of climate on the spread of SARS-CoV-2 is not clear. Some studies have shown that the transmission of SARS-CoV-2 may be negatively correlated with the temperature, and there might exist the optimum temperature range for the maximum infectivity. High precipitation is beneficial to the occurrence of

plague in arid areas, while drought is beneficial to the occurrence of plague in humid areas. In the past hundred years, the global average temperature has been rising continuously, and climate warming has been intensified, which can lead to the expansion of wildlife infectious diseases from low-latitude and low-altitude areas to high-latitude and high-altitude areas. Studies show that climate warming has caused the spread of the dengue virus and its host from subtropical zone to northern China and even the Tibet Autonomous Region in recent years.Rattus flavipectus, originally distributed in the south, has spread to northern China, increasing the incidence risk of plague. However, climate cooling will also increase the incidence of infectious diseases. For example, millennial-scale climate cooling has increased the incidence of various natural disasters (including infectious diseases) in China’s history. This may be due to the fact that the poor harvest of agriculture, the prevalence of famine, social unrest, and the decline of human immunity induced by extremely cold weather will make people more susceptible to catching and spreading diseases. Therefore, climate change may affect infectious diseases via different paths, exhibiting the non-monotonic characteristics of different effects.

Increasing human activities trigger the frequent occurrence of global and regional wildlife infectious diseases

Since the industrial revolution, human activities have exerted a huge impact on the earth’s ecosystem. In 2016, the world population had reached 7.26 billion, and 40% of the world’s land had been reclaimed for agriculture and industry. With the rapid development of the economy and society, transportation extends in all directions; people and goods flow frequently; the breeding industry is growing; the economic globalization is increasingly enhanced. In 2019, according toNature, a leading British scientific journal, a group of scientists voted for a new geological epoch, namely Anthropocene, which has produced a profound impact on the outbreak, prevalence, and spread of modern infectious ‌diseases.

Declining biodiversity and ecosystem disorders may increase the incidence of some diseases. Generally speaking, the diversity of pathogens and hosts is positively correlated. Therefore, the areas with higher host biodiversity (such as tropical and subtropical regions) or groups (such as rodents) will have richer types of pathogens and higher risks of related diseases, which can explain why emerging diseases mostly start in tropical or subtropical regions. However, with the intensification of human activities, land use, overfishing, and overhunting, biodiversity is lost, and the risk of animal infectious diseases increases. In 2014, Dirzo et al.put forward the

“defaunation hypothesis,” claiming that the global biodiversity decline led to the loss of large animal communities and the increase in rodent population density, thus increasing the incidence of plague. Some scholars also put forward the “dilute hypothesis,” claiming that increasing the host diversity can reduce the incidence of infectious diseases while decreasing the biodiversity can increase the incidence of infectious diseases. The literature review and big data analysis have shown that some studies support this hypothesis, while some do not. A recent study found that there is a scale-dependent and non-monotonic relationship between disease occurrence and biodiversity: dilution effect exists in small-scale space and amplification effect exists in large-scale space. Sun et al.found that there was a positive correlation between the occurrence frequency of plague and rodent diversity in China, which supported the amplification effect.

Closer contact between humans and animals and more developed transportation have also accelerated the outbreak and spread of wildlife infectious diseases. Illegal animal hunting and trade will increase the chance of contracting pathogens and the risk of catching wildlife infectious diseases. Developed transportation networks, the Internet of Things, and the internet have accelerated people flow and logistics and also the global spread and transmission of wildlife infectious diseases. For example, Cheng et al.found that H1N1 and H3N2 viruses with humans as the main host spread farther and faster than H5N1 and H7N9 viruses with wild birds and livestock and poultry as the main hosts. Xu et al.discovered that traffic such as roads and rivers promoted the spread of plague in China’s history. The continuous development and expansion of livestock and poultry breeding and pet breeding industries in the world has increased the probability of outbreaks of zoonotic diseases. Studies show that zoonotic diseases often increase with the prolongation of animal domestication time. At present, excessive pursuit of high-efficiency, low-cost, rapid, high-density, intensive feeding mode can easily reduce animal immunity, making animals more susceptible to diseases, followed by excessive dependence on antibiotics in the breeding industry. According to statistics, about 50% of zoonotic diseases come from 12 kinds of domestic animals. In 2009, the global outbreak of influenza A H1N1 virus came from hogs. In 2020, SARS-CoV-2 broke out in European and American mink farms one after another, which caused a major blow to the European and American mink breeding industry. African swine fever virus caused a devastating blow to the hog industry in many countries around the world. At present, many countries (including some places in China) have found that wild boar is infected with the virus. Some deaths of pandas in China were attributed to canine distemper infection. Therefore, in modern society, frequent

personnel exchanges, accelerated cargo flow, high density of farmed animals, close contact between humans and animals, and ecological system disorder are the key factors for the growing infectious diseases.

Summary

In conclusion, there are many factors and pathways affecting the outbreaks of wildlife infectious diseases (Fig. 1). To sum up, the external driving factors are mainly climate change and human activities, which can directly or indirectly affect infectious animals, vectors, and pathogens. The internal factors are mainly the interactions of infectious animals, vectors, and pathogens with humans and the transmission. Therefore, to strengthen the research and prevention of wildlife infectious diseases, we should figure out the impacts of climate change and human activities on disease outbreaks, as well as the transmission rules and mechanisms from infectious animals, vectors, pathogens to humans, so as to find out the ways to control wildlife infectious diseases.

Monitoring, prevention, and control of wildlife infectious diseases in China

The relationship between wildlife and human infectious diseases has long been recognized in China. For example, Shi Daonan, a poet in the Qing Dynasty, recorded the relationship between plague and dead rodents for the first time in his poem “the Death of Rodents.” After the founding of the People’s Republic of China, China successfully controlled the plague that had seriously endangered people’s health for hundreds of years by taking measures such as finding out the plague foci, monitoring the density of rodents, and killing rodents from the foci. In addition, many zoonoses (such as malaria and various parasitoses) have also been well controlled by vigorously promoting patriotic health campaigns and applying new disease control technologies.

However, since the 1980s, emerging major infectious diseases have been constantly detected all over the world, posing serious challenges and threats to public health safety, animal husbandry production, and eco-safety. Because the interspecific transmission or origin of many infectious diseases are related to wildlife, it is urgent to build a wildlife infectious disease prevention system, which can be combined with the health and agricultural epidemic prevention system for better disease prevention and control.

After the outbreak of SARS during 2002–2003, driven by the Institute of Zoology of Chinese Academy of Sciences, the State Forestry Administration (now “National Forestry and Grassland Administration”) and the Chinese Academy of Sciences jointly proposed to build a national monitoring system for terrestrial wildlife infectious diseases and their foci, which was approved by the State Council, and then special funds were allocated by the National Development and Reform Commission and the Ministry of Finance. On March 15, 2005, the State Forestry Administration presided over the first national teleconference on the monitoring of wildlife infectious diseases and their foci. On December 8, 2005, the State Forestry Administration set up the national monitoring station of wildlife infectious diseases, which was responsible for monitoring the wildlife infectious diseases and their foci in China. From that time, the monitoring of wildlife infectious diseases and their foci in China officially kicked off. On January 31, 2013, the State Forestry Administration issued the Administrative Measures on Monitoring, Prevention and Control of Terrestrial Wildlife Infectious Diseases and Their Foci, which clearly defined the terrestrial wildlife infectious diseases and their foci as below: Terrestrial wildlife foci refer to terrestrial wildlife that carries dangerous pathogens endangering the safety of wildlife populations or possibly spreading to people and domestic animals; terrestrial wildlife infectious diseases refer to infectious diseases that spread among terrestrial wildlife, pose a threat to the terrestrial wildlife population or may be transmitted to people and domestic animals. The monitoring scope, content, specifications, and requirements have also been clearly stipulated.

Fig. 1Key factors and pathways affecting outbreaks of wildlife infectious diseases

As revealed by the system of the National Forestry and Grassland Administration, China has established 742 national-level monitoring stations for terrestrial wildlife infectious diseases and their foci, more than 1,000 provincial-level monitoring stations, and a large number of city-level and county-level monitoring stations. The construction of a monitoring system of terrestrial wildlife infectious diseases and their foci is essential for the forecasting and control of wildlife infectious diseases, such as highly pathogenic avian influenza, African swine fever, and canine distemper. At the same time, China has also made significant progress in the diagnosis of some emerging pathogens related to wildlife infectious diseases, as well as the application of unmanned aerial vehicles, the internet, and artificial intelligence in animal monitoring. Some scientific research institutions and departments in China have initially established more than 10 infrared camera-based wildlife monitoring platforms or networks, accumulating a lot of monitoring data.

However, since the construction of the monitoring system of the terrestrial wildlife infectious disease in China starts late, the basic condition and personnel team are relatively weak. In 2018, Ren et al.collected and analyzed the data of 343 national-level monitoring stations from China’s 31 provinces (autonomous regions and municipalities directly under the central government) through the questionnaire. They found that these national-level monitoring stations generally had problems such as “professional talent shortage, incomplete basic equipment, and insufficient funds.” As a result, the countermeasures and suggestions including “enhancing team capacity building, increasing capital investment and increasing the use of science and technology” were proposed. Faced with increasingly serious challenges and threats of wildlife infectious diseases, we should strengthen and improve China’s comprehensive capabilities in research, monitoring, diagnosis, forecasting, and control of wildlife infectious diseases.

Countermeasures and suggestions for strengthening monitoring, prevention, and control of wildlife infectious diseases

Countermeasures

Breaking through the traditional concept of “public health,” and extending the epidemic monitoring and control to the level of “ecological health.” In the past, China’s health and epidemic control system focused more on human health and diseases, while the agricultural epidemic control system focused more on the health and diseases of domestic animals. At present, the occurrence and control of epidemics involve people, wild and domestic animals, and are affected by multiple factors, multiple pathways, and complex interactions of climate and environment. Therefore, epidemic prevention and control measures should be expanded from human or animal health to the level of “ecological health.” The infectious diseases across people,

wild and domestic animals as well as their relationships with climate and environment should be comprehensively investigated.

Strengthening the biological monitoring of epidemic foci and exploring the impacts of environmental and climate changes on epidemic outbreaks to improve the ability to predict the occurrence of infectious diseases. The outbreaks of global and regional epidemics are often affected by large-scale climate and environmental changes. Mastering the laws of climate and environmental changes affecting the occurrence and prevalence of diseases is pivotal to the early warning of epidemics, timely adoption of preventive measures, and reduction of the harm exerted by epidemics.

Reducing the contact of people, livestock, and pets with wild animals and cutting off the interspecific transmission chains. The vast majority of emerging and re-emerging infectious diseases come from wild and domestic animals, and the pathogens can spread and evolve across people, wild and domestic animals. Therefore, cutting off the pathogen and vector transmission chains across people, wild and domestic animals is essential to significantly lower the risk of disease occurrence. It is advised to strengthen the closed management and quarantine of the breeding areas and reduce the contact and cross infection between the breeding areas and people, wild and domestic animals as much as possible. The breeding environment and conditions should be improved to enhance the immunity of domestic animals. It is necessary to immunize pets and monitor, control, or immunize wildlife (including domestic animals returning to the wild state) in the vicinity of residential areas. Illegal hunting, trading, and overeating of wildlife shall be strictly prohibited and cracked down on. Tourists shall be strictly prohibited from entering the core areas of nature reserves and contacting the wildlife to avoid interspecific transmission and spread of diseases.

Strengthening the management of infectious animals, vectors, and foci to reduce the risk of infectious diseases. For epidemic prevention and control, monitoring alone is not enough. It is also necessary to intervene in and control the risk of the epidemic source. For example, the US has released oral rabies vaccines in the wild to reduce the rate of rabies infection of wildlife, thereby lowering the chance of transmission to domestic animals. There are more than 10 types of natural plague foci in China, which are distributed in 278 counties in 19 provinces (autonomous regions and municipalities directly under the central government), covering an area of more than 1 million square kilometers and posing a constant threat to the health and safety of people in the foci. Therefore, it is necessary to strengthen the monitoring and control of rodent population density in agriculture, forestry, and animal husbandry in China to cut off the plague transmission chain. In addition, it is necessary to find out theinfectious animals, vectors, and foci of major zoonotic diseases, such as highly pathogenic avian influenza, rabies, African swine fever, foot-and-mouth disease, brucellosis, hydatid disease, hemorrhagic fever, tsutsugamushi disease, and dengue fever, and then carry out the monitoring and control.

Suggestions

In response to the growing threat exerted by wildlife epidemics in the face of global change, we should fully implement the upcoming Biosecurity Law of the People’s Republic of China, and further upgrade China’s existing monitoring system for terrestrial wildlife infectious diseases and their foci. Therefore, it is recommended to strengthen and support the following eight aspects of work during the 14th “Five-Year Plan” period, relying on relevant national and local departments and related scientific research institutions, universities, and enterprises.

Improving the layout of monitoring stations and the building of monitoring teams, and enhancing the level and capacity of grassroots monitoring and control. According to the distribution characteristics of infectious animals, vector animals, pathogens, and natural foci, the national-, provincial-, and county-level monitoring networks and stations should be adjusted, supplemented, and improved. Advanced materials, equipment, and conditions for field monitoring, sample collection, sample storage, pathogen diagnosis, epidemic intervention, and information collating should be equipped. The construction of grassroots teams and personnel training and guidance should be strengthened.

Formulating a biological list of major epidemic foci, identifying the natural foci, and carrying out large-scale management. In recent years, influenced by global climate change and intensified human activities, the animal distribution area has changed rapidly, and a new round of national surveys should be carried out as soon as possible. With the international data taken into consideration, the biological list covering major infectious animals, vector animals, pathogens, and natural foci in China should be formulated to identify the foci and carry out large-scale management. At the same time, the epidemic species that are rare, endangered, and beneficial should be protected from contacting people and domestic animals.

Improving the monitoring technology, informatization, and forecasting capabilities of infectious animals, vectors, and diseases. Efforts can be made to develop and improve standardized monitoring methods, data acquisition, and processing modes. The high-precision and advanced technologies such as the Internet of Things, big data, artificial intelligence, cloud computing, and satellite positioning should be utilized to build an automatic and intelligent monitoring network covering all stations across the country, thus achieving the real-time monitoring and forecasting of infectious animals, vectors and diseases. It is expected to play a supporting role in epidemic analysis, pathogen tracing, prevention and control, and resource deployment.

Enhancing the capability of rapid diagnosis, mass screening, and risk detection of wildlife infectious diseases. Considering the various species, abundant samples, and large variation of wildlife pathogens, the existing monitoring methods, reagents, and equipment fail to meet the needs of actual monitoring. Therefore, the methods and systems suitable for the monitoring and diagnosis of wildlife pathogens should be established and improved. For potential pathogens, the methods and systems for rapid and mass screening should be developed based on metagenomics and environmental genomics.

Improving the level and capacity of researching wildlife infectious diseases. A group of national and regional research centers and reference laboratories should be established or supported to provide the technology and analysis needed for the monitoring and control of wildlife infectious diseases and their foci. The state key laboratory of conservation biology and wildlife infectious diseases, the national epidemic biology database and sample database, and the state key laboratory of pest control and research should be constructed. A number of major national and departmental research programs or projects concerning wildlife infectious diseases should be launched. China’s existing bio-safety laboratory platform layout should be fully used to promote the sharing of resources and platforms and improve the capacities for prevention, control, monitoring, and intervention.

Supporting the development of diagnostic reagents and instruments, prevention and control drugs and equipment, automatic intelligent monitoring equipment, and safety protection facilities. The industrialization of monitoring, prevention, and control technologies of wildlife infectious diseases is beneficial to the development of the biological industry and equipment industry in China. The product standards and industry systems for monitoring and control of wildlife infectious diseases should be established or perfected. A batch of enterprises should be encouraged and supported to develop technology and products and promote industrialization.

Strengthening the science popularization and education and raising the public awareness of preventing and controlling the wildlife infectious diseases. The monitoring, prevention, and control of wildlife infectious diseases is a complex system involving human, animal, climate, and environmental factors. Therefore, it is necessary to raise public awareness of the prevention and control of wildlife infectious diseases and attract the public to participate in the monitoring, forecasting, and control of major epidemics. The grassroots stations should be encouraged and supported to carry out science popularization and education on a regular basis, so as to reduce the chances of people being infected with infectious diseases and cut off the transmission chains.

Strengthening international cooperation and exchanges and establishing an international mechanism for joint prevention and control of wildlife infectious diseases. With the rapid exchange of goods and personnel among countries, it is necessary to strengthen international cooperation and establish a global monitoring mechanism for joint prevention and control of wildlife infectious diseases. Internationally, there are not many international organizations dealing with wildlife infectious diseases. Most of them focus on academic research and their coordination ability at the government level is relatively weak. It is recommended that China should actively promote the establishment of international wildlife disease monitoring and prevention organizations or alliances, and the standardization of monitoring networks, diagnostic standards, prevention and control methods, information sharing, and technical exchanges. Besides, the exchange and cooperation mechanisms with WHO, the World Organization for Animal Health (OIE), and other international organizations should be enhanced. Meanwhile, China should actively assist the joint prevention and control of wildlife infectious diseases among countries and regions along the Belt and Road and promote the implementation of global bio-safety and eco-safety goals and strategies.

Author

Zhang Zhibin, Professor of Institute of Zoology, Chinese Academy of Sciences (CAS)

This article is contributed by Bulletin of Chinese Academy of Sciences