Emerging zoonotic diseases in Southeast Asia in the period 2011–2022: a systematic literature review

Abstract As COVID-19 has shown, pandemics and outbreaks of emerging infections such as Zika, Nipah, monkeypox and antimicrobial-resistant pathogens, especially emerging zoonotic diseases, continue to occur and may even be increasing in Southeast Asia. In addition, these infections often result from environmental changes and human behaviour. Overall, public health surveillance to identify gaps in the literature and early warning signs are essential in this region. A systematic review investigated the prevalence of emerging zoonotic diseases over 11 years from 2011 to 2022 in Southeast Asia to understand the status of emerging zoonotic diseases, as well as to provide necessary actions for disease control and prevention in the region. During the 2011–2022 period, studies on pigs, poultry, ruminants, companion animals and wildlife in Southeast Asia were reviewed thoroughly to assess the quality of reporting items for inclusion in the systematic review. The review was performed on 26 studies of pigs, 6 studies of poultry, 21 studies of ruminants, 28 studies of companion animals and 25 studies of wildlife in Southeast Asia, which provide a snapshot of the prevalence of the emerging zoonotic disease across the country. The findings from the review showed that emerging zoonotic diseases were prevalent across the region and identified a few zoonotic diseases associated with poultry, mainly stemming from Cambodia and Vietnam, as high priority in Southeast Asia. Clinical relevance: Appropriate prevention and control measures should be taken to mitigate the emerging zoonotic diseases in Southeast Asia.


Introduction
Livestock production is critical to human nutrition and health in low-and middle-income countries (LMICs) (Milton 2003).These animals play important roles in society, providing income and food, but also clothing, building materials, fertilizer, and draught power.However, the presence of endemic and emerging diseases, as well as other factors, impact livestock negatively, jeopardizing their contributions.
Many new science-based policy reports continue to focus on the global public health emergency caused by the COVID-19 pandemic following the fast spread of the infectious virus of possible zoonotic origin (Wu et al. 2022).As of 19 August 2023, about 7 million people had died of COVID-19 worldwide.This pandemic has had a staggering effect on the global economy and countless other effects in both developing and developed countries.The cost of controlling and containing it has reached several trillion US dollars.
Around 60% of all human diseases are zoonotic and 75% of all emerging diseases are considered zoonoses (Woolhouse and Gowtage-Sequeria 2005).Historically, the emergence of new human diseases from animals has been associated with major societal change.For example, during the neolithic transition from hunter-gathering to agricultural societies, humans lived shorter lives, ate less and poorer-quality foods, were smaller in size and were sicker than their hunter-gatherer ancestors (Larsen 1995).With the advent of agriculture, the dramatic rise in population and the settlement of people near their waste led to increases in human disease; the domestication of animals led to livestock pathogens jumping species into people, where they became the probable cause of diseases (Morand et al. 2014).These new emerging disease outbreaks followed rapid intensification of agricultural practices and systems to meet increased demand for animal protein, and dramatic changes in the ways animals were kept or farmed, often without proper precautionary measures (Jones et al. 2013).This was a demand-driven process, associated with increasing wealth and allowing people to consume more animal-source foods.
Although the origin of COVID-19 is currently not known, it may be associated with wildlife harvest, trade practices and the intensification of wildlife farming (Whitfort 2021).The latter is actively occurring in several countries, in which wildlife breeding and farming ventures have been established during the recent past.Although wealthy consumers in these countries tend to prefer wild-caught animals, the meat from these farms is often consumed by the rapidly growing middle-class in several parts of the world.
The socioeconomic crises caused by the recent outbreaks of COVID-19 (2019) (Huang et al. 2020); (Gaffar Sarwar and Mesfer Al 2021), African swine fever (2018) (Liu et al. 2020(Liu et al. ), avian influenza (2004) ) in Asia (Webster et al. 2005) with the most recent human case of avian influenza A(H3N8) and A(H5N1) was reported in 2023 from China and Cambodia, respectively (Venkatesan 2023).These diseases have served to heighten awareness of the wide-ranging negative impacts of infectious diseases on human health, food safety, livestock trade, and livelihoods of poor farming communities.All these diseases may have a wildlife reservoir and may also involve domestic animals.In addition to these outbreaks, continued losses of livestock belonging mainly to smallholders in Southeast Asia due to other transboundary animal and emerging diseases have clearly revealed major weaknesses in the public health and veterinary services.This literature review aims to understand the current status of emerging zoonotic diseases in Southeast Asia, as well as to provide necessary actions for disease control and prevention in the region.

Protocol and eligibility criteria
As summarized in Table 1, developing the protocol for the search and evaluation of the articles was included in the objective, data source, and inclusion and exclusion criteria.Only articles in English and online databases were considered for this review.In the first screening, the titles and abstracts were examined thoroughly to see if they were suitable for the present review.The second screening examined the quality of the full publication based on different inclusion and exclusion criteria (Table 1).All procedures were performed independently by all the authors (TTN, TNM, XSD and HSL).Each article was classified as 'Yes' or 'No' for inclusion.The first reason for the exclusion of articles that passed the first screening was the lack of information on how the selection of farms and individuals was carried out.Additionally, the second reason was poor random selection at the farm level and of individual animals such as targeted sampling of individuals showing symptoms of the disease.If there was a conflict between the four reviewers, the final decision was made after a discussion among them.

Searching strategy and syntaxes
In the context of the present review, the term 'emerging zoonotic diseases' is to refer to diseases that are either newly recognized, newly introduced or newly evolved, or have recently and rapidly changed in incidence or expansion in their geographical, host or vector range and transmitted under natural conditions from vertebrate animals to humans (Stevenson and Halpin 2021).Databases are organized collections of resources of articles.The authors searched for relevant articles in the PubMed, Web of Science and Science Direct databases.The key syntaxes were divided into three topics -(i) (livestock OR swine OR pig OR cattle OR buffalo OR sheep OR goat OR poultry OR duck OR chicken OR pets OR dogs OR cats OR rats); AND (ii) (Brunei OR Cambodia OR Indonesia OR Laos PDR OR Malaysia OR Myanmar OR Philippines OR Singapore OR Thailand OR Timor-Leste OR Vietnam OR Southeast Asia); AND (iii) (zoonoses OR zoonotic diseases).
The full lists of titles and abstracts were imported into Endnote (version X7), and duplicates were manually identified and removed.The last search was performed on 11 March 2022.To ensure that the search strategy captured all relevant articles, we checked that known key articles were included in the results.In the second screening, we also crosschecked the grey literature on the reference lists of the articles against our search results to make sure we did not miss any relevant articles.The time span under review was 2011-2022.The management programs used were Endnote and Excel 365.

Data collection
The data extraction template included the authors, publication year, pathogen name, animal species, diagnostic method, study area, sample size, number of positive samples, prevalence, and 95% confidence interval (CI).In cases where several methods were applied to one sample, the highest prevalence was Avian influenze are defined as a regional priority transboundary animal diseases.
released.If the 95% CI of the prevalence or the number of positive animals was absent in an article, this information was derived using the data presented in the article.The data from eligible publications were reviewed and extracted into a Microsoft Excel file.Lastly, the extracted dataset was independently cross-checked against each original article by the same four authors (TTN, TNM, XSD and HSL).

Synthesis of results
Descriptive statistics were summarized by species like pigs, poultry, ruminants, companion animal and wildlife with the following information: pathogen, country, year of sampling, sample size, % positive, diagnostic test, 95% CI, author, and year.

Article finding and screening
A total of 2,329 articles were retrieved from PubMed (n = 1043), Web of Science (n = 994) and Science Direct (n = 292).In the first screening, 674 duplicates were identified and removed, and 1,302 publications were excluded due to not conducting in southeast Asia (n = 339) or due to focusing on influenza (n = 145).Also eliminated were review articles (n = 91), book chapters (n = 4) and articles not related to the targeted diseases (n = 723).Thus, a total of 358 articles were included in the full-text assessment (Figure 1).The list of articles (including titles, authors, abstracts and years of publication) is attached in the Annex (Excel) file.Subsequently, a total of 358 full-text articles were assessed in the second screening, where 263 articles were excluded because of the full text being unavailable (n = 23), the animal selection procedure being unclear (n = 156), or the results not being presented clearly (n = 84).Thus, 95 publications were included in the final qualitative synthesis (Figure 1).

Zoonotic diseases associated with domestic pigs in Southeast Asia
The qualitative synthesis yielded 26 published articles reporting on 35 studies related to pigs (Table 2).The three areas of research covered under this topic were bacteria, viruses and parasites.Specifically, diseases associated with pigs were as follows: Japanese encephalitis, Hepatitis E, rotavirus A, kobuviruses, Campylobacter, Streptococcus suis, trichinellosis, erysipelas, Salmonella, cryptosporidiosis, cysticercosis/taeniasis, leptospirosis and toxoplasmosis.Out of these, nine studies (30% of the total) were conducted in Cambodia, including 7 studies on parasites, 1 study on bacteria (Campylobacter) and 1 study on viruses (Japanese encephalitis).The largest number of studies was conducted in Vietnam (14 studies, or 39%).Among them, there were 3 studies on parasites, 7 studies on bacteria and 4 studies on viruses.Subsequently, there were 4 studies on bacteria, 1 study on viruses and 1 study on parasites in Cambodia.There were 2 studies (5%) on viruses in Laos, and only 1 study each (3%) in Indonesia (parasite), Malaysia (viruses) and the Philippines (parasites).In summary, these data highlighted the importance of zoonotic diseases originating from pigs, with Cambodia and Vietnam having the highest numbers of studies in Southeast Asia.

Zoonotic diseases associated with poultry in Southeast Asia
As depicted in Table 3, six of the articles reporting on 10 studies that were included in the qualitative synthesis were related to poultry.Out of these, 4 studies (40%) were conducted in Cambodia, including 4 studies on bacteria (Campylobacter).Most of the studies were conducted in Vietnam (5 studies, or 50%), comprising 4 studies on bacteria and 1 study on parasites.Subsequently, there was 1 study (10%) on viruses in Thailand.Specifically, the study investigating Campylobacter found the highest prevalence in poultry in Cambodia.Taken together, Salmonella, Streptococcus suis, Echinostome and Opisthorchis viverrine were the most common pathogen.The data indicated that only a few zoonotic diseases associated with poultry, mainly stemming from Cambodia and Vietnam, were identified as high priority in Southeast Asia.

Zoonotic diseases associated with ruminants in Southeast Asia
As shown in Table 4, twenty-one of the articles that were included in the qualitative synthesis were related to ruminants as described in 35 studies.Out of these, 11 studies (31%) were conducted in Thailand and another 11 (31%) in Laos; 4 (11%) in Malaysia; 3 (9%) in Indonesia; and 2 (6%) each in Cambodia, the Philippines and Vietnam.Diseases associated with ruminants were as follows: Campylobacter, Q fever, brucellosis, enterohaemorrhagic E. coli, listeriosis, bovine tuberculosis, chlamydiosis, cryptosporidiosis, cysticercosis/taeniasis, salmonellosis, toxoplasmosis, fascioliasis, and giardiasis.

Zoonotic diseases associated with companion animals in Southeast Asia
As depicted in Table 5, twenty-eight of the articles that were included in the qualitative synthesis were

Zoonotic diseases associated with wildlife in Southeast Asia
This report further investigates the role of wildlife in zoonotic diseases in Southeast Asia.Specifically, 25 of the articles that were included in the qualitative synthesis were related to wildlife as described in 36 studies (Table 6).Out of these, 12 studies (33%) were conducted in Vietnam; 8 studies (22%) in Malaysia; 7 studies (19%) in Thailand; 4 studies (11%) in Laos; 2 studies (6%) in Indonesia; and 1 study (3%) each in Cambodia, Myanmar and the Philippines.

Discussion
To the best of our knowledge, this systemic literature review was the first conducted on emerging zoonotic diseases between 2011 and 2022 in Southeast Asia.It is well known that animal brucellosis is endemic in Southeast Asia (Suresh et al. 2022).This disease is associated with economic losses and significant impacts on human health.Brucellosis in humans can present as an acute or chronic infection.Livestock keepers in Timor-Leste rely on small-scale farming systems (Smith et al. 2019).While there have not been any studies published on human brucellosis in this region, it is known that the activities of abattoir workers are associated with a high risk of infection.There is a high rate of abortion during late gestation in cattle and buffalo, and in rural areas, there is also a high rate of abortion in humans and low fertility among farmers.In line with cultural traditions, abortions are blamed on black magic or superstitious powers.Therefore, literature relating to brucellosis in Timor-Leste is limited.The number of cattle is expected to continue to increase worldwide, thus the role and impact of cattle on the future of public health will likely remain compelling in Southeast Asia.Bovine tuberculosis (TB) is an illness characterized by pneumonia, enlarged lymph nodes and signs of weakness.There are different strains, but Mycobacterium bovis is the most common, with most infections occurring in cattle.The organism can also affect other domestic animal species but cattle are the main reservoir for the pathogen and also the main source of infection for humans.In Laos, TB is endemic and is recognized as a major health risk (Lassausaie et al. 2014).However, the current prevalence in humans is unknown.Notably, the literature on tuberculosis in Laos is also very limited.Laotians consume raw meat regularly (Suwansrinon et al. 2007).For example, the national dish, 'larb' , is prepared by mixing different types of raw meat, blood and intestines.It may be made from raw chicken, beef, duck, fish or pork, is very popular in rural areas, and, as with other dishes, is often made from home-slaughtered animals.In addition, Laotians also often prefer raw meat in large community events.In some areas of Laos, people also consume blood and raw milk.In addition to risks associated with consumption, occupational risks are present for those in close contact with animals in Laos.An example is abattoir workers who are at high risk due to frequent exposure to blood from slaughtered animals in an environment with poor hygiene measures (Suwansrinon et al. 2007).
Among the zoonoses diseases in this review, viral diseases such as Japanese encephalitis can infect pets and be transmitted to humans.Cutaneous contamination with Leptospira spp. is also emerging/ re-emerging pathogens that can be transmitted by our pets, as well as flu-like illness pathogens such as brucellosis (Chomel 2014).Parasitic and fungal pathogens, such as rickettsia, echinococcosis, giardiasis or sporotrichosis, are also re-emerging or emerging pet-related zoonoses (Rahman et al. 2020).Therefore, this report highlighted the role of small companion animals in zoonotic disease risk in Southeast Asia.
Notably, there is no available information that the government of Brunei conducts surveillance of zoonotic disease.That could be a possible reason that there was no published data available on emerging zoonotic diseases in Brunei.On the contrary, there is publicly evidence that the government of Singapore has a One health framework for the surveillance and reporting of zoonotic disease.However, to date no reported case was recorded through the surveillance system (Lysaght et al. 2016).Furthermore, livestock farming is the principal source of livelihood for most countries in Southeast Asia except Singapore and Brunei (Hassan 2014).As a result, it may be explained that we could find any evidence regarding the zoonotic diseases in Singapore in the period 2011 − 2022.
It should be noted that rabies is incurable and has the highest fatality rate of any zoonosis (Lavan et al. 2017).Rabies was first reported in Indonesia in 1889 and it is currently endemic in 33 provinces.Indonesia's national strategic plan highlights the importance of control and eradication of the disease as a national priority.Indonesia is identified as having the fourth-highest number of human rabies cases after India, Bangladesh and Myanmar, with 150 − 300 cases reported yearly in Indonesia (World Health Organization 2016).In 2008, Bali experienced an outbreak of rabies leading to many human fatalities (Putra et al. 2013).In response to this outbreak, a mass culling of stray dogs was implemented, along with mass vaccination of owned dogs.Initial efforts did not control the outbreak and by 2010, rabies cases had spread across all nine regencies in Bali (Putra et al. 2013).It was recognized that an understanding of the relationship between dogs and people, along with cultural understanding, was required to make the control program effective.The program needed to include local community knowledge, particularly of behaviours towards dogs.It is clear that a complex relationship between dogs and humans, which contributes to the spread of rabies (Widyastuti et al. 2015).For example, in some regions and ethnic groups, people regard free-roaming or stray dogs as a blessing and keep them in the house as a religious obligation.Many people also believe that washing the wound after a dog bite is unimportant, and instead believe that allowing the dog to lick the wound will help in healing.In addition, (Widyastuti et al. 2015) reported that while most people were supportive of the control program, a subset of the population with specific religious beliefs were opposed to dog culling.An island-wide mass dog vaccination campaign commenced in October 2010 and continued over subsequent years, resulting in a decrease in the number of rabies cases in both dogs and humans (Putra et al. 2013).This could explain why few rabies cases are detected in Indonesia.
In the literature, the Nipah virus is identified as a recently emerged pathogen from the family Paramyxoviridae.The family has two zoonotic viruses, the Hendra virus and the Nipah virus, both classed as henipahviruses.The clinical signs of the Nipah virus in humans fever, encephalitis, and respiratory and pulmonary disorders, which can lead to death (Ochani et al. 2021).The natural reservoir of the Nipah virus is pteropid bats.A recent report has also demonstrated that the fruit bat species (Pteropus) is regarded as the nature reservoir of the Nipah virus, which is a virus of concern for future epidemics and also seems to be spilling over from its animal reservoir to humans (Joshi et al. 2023).The bats do not show clinical signs but may excrete the virus in urine, saliva and blood.Spillover effects can occur to other species such as pigs and horses, which may then act as intermediate hosts.Transmission may occur through ingestion of contaminated food, direct contact with infected body fluids (human or animal) or through droplet or aerosol exposure.Nipah virus was first identified in Malaysia in 1998 (Chua 2003) when it was associated with an outbreak among pig farmers and abattoir workers.In 2014, a major outbreak of a probable was associated with two villages in the Philippines (Ching et al. 2015).A strong association was identified with direct exposure to infected horses.This included exposure to contaminated body fluids during slaughter and/or consumption of undercooked horse meat.Humanto-human transmission was also reported.This case study identifies the potential for transmission of pathogens from infected horses (or other spill-over hosts) and people (Ching et al. 2015).
Pathogens associated with zoonotic diseases may be broadly described as bacterial, viral, parasitic or fungal.While viral zoonoses are more commonly considered in large-scale events (ebola, coronaviruses), bacterial and parasitic zoonotic pathogens are implicated commonly on a local scale.Overall, diseases associated with wildlife in this review are giardiasis, leptospirosis, Q fever, ebola virus, rabies virus, West Nile virus and hantavirus.The data from the studies suggested that zoonotic diseases are mostly associated with wildlife in Southeast Asia.
In addition, wildlife has been an important source of infectious diseases transmissible to humans.Some environmental changes drive virus spillover from wildlife, including: (i) Species in global decline because of exploitation and habitat loss share more viruses with people; (ii) Exploitation of wildlife through hunting and the live wild animal trade create the perfect epidemiologic setting for spillover; (iii) Declines in habitat for wild mammals, due to deforestation, development and conversion to cropland, increase disease distribution and animal-human interactions.
It should be noted that a low number of reports on pig diseases were recorded in Southeast Asia.It may come from a few local veterinary journals reporting results that may not be indexed in the databases searched.Besides, relatively few studies were found to evaluate the distribution of both domestic and wildlife diseases in Southeast Asia.Notably, the concept of One Health has become the international standard for zoonotic disease control, which emphasizes a multi-sectoral and transdisciplinary understanding and approach to prevent and mitigate the threat of communicable diseases (Ng et al. 2020).Therefore, further epidemiological investigation using One health approach is necessary to reduce the gaps in disease surveillance and reporting systems as well as to support the prevention and reduction of further outbreaks.

Conclusion
Taken together, this review provides the current status of emerging zoonotic diseases in Southeast Asia, as well as suggesting the necessary actions for disease control and prevention in the region.Prevention of zoonotic diseases requires general and specific knowledge of pathogens, disease characteristics and transmission.In addition, there is a need for familiarity with potential control measures and the capacity to coordinate activities across human and animal health environments.

Figure 1 .
Figure 1.Schematic flow chart of the literature selection for the review on zoonotic diseases in Southeast asia.

Figure 2 .
Figure 2. Geographical distribution of studies on zoonotic pathogens in Southeast asia.

Figure 3 .
Figure 3. Focus of studies on zoonotic pathogens in Southeast asia.

Table 1 .
establishing inclusion and exclusion criteria in this study.

Table 2 .
list of studies focusing on zoonotic diseases in domestic pigs in Southeast asia.

Table 3 .
list of studies focusing on zoonotic diseases in poultry in Southeast asia.

Table 4 .
list of studies focusing on zoonotic diseases in ruminants in Southeast asia.

Table 5 .
list of studies focusing on zoonotic diseases in companion animals in Southeast asia.

Table 6 .
list of studies focusing on zoonotic diseases in wildlife in Southeast asia.