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Understanding the global distribution of atypical porcine pestivirus (APPeV)

Published online by Cambridge University Press:  24 March 2025

Ugonna Henry Uzoka Open the ORCID record for Ugonna Henry Uzoka [Opens in a new window]  and
Abelardo Silva-Júnior Open the ORCID record for Abelardo Silva-Júnior [Opens in a new window]
Ugonna Henry Uzoka*
Affiliation:
Department of Veterinary Medicine, Michael Okpara University of Agriculture Umudike, Abia, Nigeria Department of Veterinary Medicine, Universidade Federal de Viçosa, Minas Gerais, Brazil
Abelardo Silva-Júnior
Affiliation:
Sector of Immunology and Virology, Institute of Biological Sciences and Health, Universidade Federal de Alagoas (UFAL), Maceió, Brazil
*
Corresponding author: Ugonna Henry Uzoka; Email: uzoka.ugonna@mouau.edu.ng
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Abstract

Atypical porcine pestivirus (APPeV) is a pestivirus affecting pigs, notably causing high mortality in piglets due to neurological issues that impair suckling. This study reviews global literature from 2015 to March 2024, assessing APPeV prevalence. Analysing 40 relevant articles, it finds APPeV widely distributed across Europe, South America, North America, and Asia, with minimal presence in Africa and Australia. The scarcity in these regions might be due to geographical isolation, environmental factors, limited surveillance, diagnostics, or under-reporting. China leads in APPeV prevalence reports, followed by the USA, Germany, Sweden, and other countries. The main diagnostic methods are quantitative reverse transcription polymerase chain reaction (RT-qPCR) and RT-PCR, using tissue and serum samples. APPeV detection in the serum of boars and wild boars suggests possible persistent infections, indicating their role in APPeV epidemiology. Given the global outbreaks, particularly of congenital tremor (CT), the study calls for expanded research, especially in under-studied regions like Africa and Australia, focusing on healthy pigs, CT-affected piglets, and boars to better understand APPeV transmission dynamics.

Keywords

congenital tremorendemicityepidemiologyswinevirus

Information

Type
Systematic Review
Information
Animal Health Research Reviews , Volume 24 , Issue 2 , December 2023 , pp. 89 - 97
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Creative Common License - CCCreative Common License - BY
This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (http://creativecommons.org/licenses/by/4.0), which permits unrestricted re-use, distribution and reproduction, provided the original article is properly cited.
Copyright
© The Author(s), 2025. Published by Cambridge University Press.

Introduction

Background and significance

The family Flaviviridae includes pestiviruses, which are responsible for several economically significant animal diseases, particularly affecting livestock production worldwide (Aitkenhead et al., Reference Aitkenhead, Riedel, Cowieson, Rümenapf, Stuart and El Omari2024; Song et al., Reference Song, Gao, Li, Dong, Fu, Shao, Zhang, Qiu and Luo2024). Over recent decades, researchers have identified numerous novel pestiviruses in both domestic and wild ruminant species, expanding our understanding of their diversity and impact (Firth et al., Reference Firth, Bhat, Firth, Williams, Frye, Simmonds, Conte, Ng, Garcia, Bhuva and Lee2014; Kirkland et al., Reference Kirkland, Frost, Finlaison, King, Ridpath and Gu2007; Wu et al., Reference Wu, Ren, Yang, Hu, Yang, He, Zhang, Dong, Sun, Du and Liu2012).

Among these emerging viral threats, atypical porcine pestivirus (APPeV) was first identified in 2015 through metagenomic sequencing of pig serum (Hause et al., Reference Hause, Collin, Peddireddi, Yuan, Chen, Hesse, Gauger, Clement, Fang and Anderson2015). APPeV is a positive-sense single-stranded RNA (+ssRNA) virus approximately 11.5 kb in size, belonging to the Pestivirus genus within the Flaviviridae family (Hause et al., Reference Hause, Collin, Peddireddi, Yuan, Chen, Hesse, Gauger, Clement, Fang and Anderson2015). The virus exhibits significant genetic diversity and variability among strains (Postel et al., Reference Postel, Meyer, Cagatay, Feliziani, De Mia, Fischer, Grundhoff, Milićević, Deng, Chang and Qiu2017), which has important implications for molecular epidemiology research in swine populations.

APPeV possesses unique genomic and structural features that distinguish it from other porcine pestiviruses, such as Bungowannah virus (Pestivirus F) and LINDA virus. Notably, the APPeV genome lacks both N-terminal domains of the E2 glycoprotein, a structural difference that may influence immune evasion mechanisms and host cell entry. This contrasts with Bungowannah virus, which maintains a more complete E2 structure, and LINDA virus, which shows additional deletions within non-structural proteins. The virus’s genomic organization, particularly the conserved regions in NS3 and NS5B genes, establishes its position as a distinct pestivirus lineage (Beer et al., Reference Beer, Wernike, Dräger, Höper, Pohlmann, Bergermann, Schröder, Klinkhammer, Blome and Hoffmann2017; Postel et al., Reference Postel, Hansmann, Baechlein, Fischer, Alawi, Grundhoff, Derking, Tenhündfeld, Pfankuche, Herder and Baumgärtner2016; Riedel et al., Reference Riedel, Aitkenhead, El Omari and Rümenapf2021).

Congenital tremor (CT), also known as ‘dancing piglet’, was first documented approximately a century ago (Kinsley, Reference Kinsley1922). The condition is classified into types A and B, with type A characterized by distinct histological lesions in the central nervous system (CNS), while type B lacks such lesions (Done, Reference Done1968). Various factors, including dietary deficiencies, genetic conditions, and viral infections, have been identified as potential causes of CT (Knox et al., Reference Knox, Askaa, Basse, Bitsch, Eskildsen, Mandrup, Ottosen, Overby, Pedersen and Rasmussen1978). While the condition was long suspected to be caused by an unnamed virus (Arruda et al., Reference Arruda, Arruda, Magstadt, Schwartz, Dohlman, Schleining, Patterson, Visek and Victoria2016), technological advances in sequencing finally led to the identification of APPeV.

Pestivirus infections generally cause varied clinical symptoms depending on virus species, strain, and host factors including age and immune status (Ohmann and Babiuk, Reference Ohmann and Babiuk1988). In APPeV infections, neuropathological features include: demyelination and/or hypomyelination of white matter, neuronal necrosis of the brain, neuronophagia with satellitosis, gliosis, ballooning degeneration of the uroepithelium and respiratory epithelium (Possatti et al., Reference Possatti, de Oliveira, Leme, Zotti, Agnol, Alfieri, Headley and Alfieri2018). The neuropathological manifestations of APPeV infection appear to result from a combinationof direct viral effects and inflammatory responses of pathology which explains the severity and progression of neurological symptoms in affected piglets. The combination of these two creates a cascade effect that can significantly impact neurological function, particularly when the infection occurs during critical developmental periods (Postel et al., Reference Postel, Hansmann, Baechlein, Fischer, Alawi, Grundhoff, Derking, Tenhündfeld, Pfankuche, Herder and Baumgärtner2016; Schwarz et al., Reference Schwarz, Riedel, Högler, Sinn, Voglmayr, Wöchtl, Dinhopl, Rebel-Bauder, Weissenböck, Ladinig and Rümenapf2017).

It’s important to note that APPeV can be differentiated from other neurological pathogens affecting swine, such as porcine astrovirus type 3 (PAstV3). While APPeV predominantly causes CT type A-II, PAstV3 is associated with polioencephalomyelitis, characterized by inflammation and degeneration in the brain and spinal cord’s grey matter (Rawal et al., Reference Rawal, Franco, Nubia, Laura, Karen, Grant, Daniel and Bailey2020).

APPeV transmission occurs through both horizontal (oronasal) and vertical (transplacental) routes (Gatto et al., Reference Gatto, Harmon, Bradner, Silva, Linhares, Arruda, De Oliveira and Arruda2018b, Reference Gatto, Sonálio and De Oliveira2019). Early studies in Germany and the United States revealed significant viral genome presence (22.4% and 2.4%, respectively) in apparently healthy pigs (Beer et al., Reference Beer, Wernike, Dräger, Höper, Pohlmann, Bergermann, Schröder, Klinkhammer, Blome and Hoffmann2017; Hause et al., Reference Hause, Collin, Peddireddi, Yuan, Chen, Hesse, Gauger, Clement, Fang and Anderson2015; Postel et al., Reference Postel, Hansmann, Baechlein, Fischer, Alawi, Grundhoff, Derking, Tenhündfeld, Pfankuche, Herder and Baumgärtner2016). While the full economic impact remains under investigation, infected farms have reported approximately 10% reduction in reproductive efficiency (Schwarz et al., Reference Schwarz, Riedel, Högler, Sinn, Voglmayr, Wöchtl, Dinhopl, Rebel-Bauder, Weissenböck, Ladinig and Rümenapf2017). Additionally, pre-weaning mortality increases in APPeV-infected newborn pigs developing CT due to impaired suckling ability (Pan et al., Reference Pedersen, Kristensen, Strandbygaard, Bøtner and Rasmussen2019).

Since its initial identification in the United States in 2015, APPeV has been reported across multiple continents, including Asia, Europe, and North and South America (Mósena et al., Reference Mósena, Weber, Da Cruz, Cibulski, Da Silva, Puhl, Hammerschmitt, Takeuti, Driemeier, De Barcellos and Canal2018; Gatto et al., Reference Gatto, Sonálio and De Oliveira2019). The presence of APPeV in both wild boar populations and domestic adult pigs suggests potential reservoir hosts worthy of epidemiological investigation. Reverse transcription polymerase chain reaction (RT-PCR) remains the primary diagnostic tool for detecting APPeV in tissue and serum samples, though comprehensive prevalence data are still lacking in many countries.

Objectives of the systematic review

A phylogenic study of the genomes of APPeV strain samples from pigs and wild boars in a variety of countries and regions uncovered a high level of genetic diversity among the strains, with some strains subdividing into numerous clusters (Shen et al., Reference Shen, Liu, Zhang, Wang, Liu, Zhang, Liang and Song2018; Sozzi et al., Reference Sozzi, Salogni, Lelli, Barbieri, Moreno, Alborali and Lavazza2019). According to the findings of numerous scientific investigations, the various strains of the APPeV virus can be divided into three distinct classes based on the genomic sequences that they carry: types I, II, and III (Guo et al., Reference Guo, Wang, Qiao, Deng and Zhang2020; Yan et al., Reference Yan, Li, He, Wu, Tang, Chen, Mai, Wu, Li, Chen and Sun2019). Multiple studies have reported the use of RT-PCR and quantitative RT-PCR for virus detection (Arruda et al., Reference Arruda, Arruda, Magstadt, Schwartz, Dohlman, Schleining, Patterson, Visek and Victoria2016; Possatti et al., Reference Possatti, de Oliveira, Leme, Zotti, Agnol, Alfieri, Headley and Alfieri2018). Metagenomic sequencing was used to identify the APPeV for the first time in swine in the United States (Hause et al., Reference Hause, Collin, Peddireddi, Yuan, Chen, Hesse, Gauger, Clement, Fang and Anderson2015). Real-time RT-PCR protocols have been developed to detect and quantify the APPeV in clinical samples (Arruda et al., Reference Arruda, Arruda, Magstadt, Schwartz, Dohlman, Schleining, Patterson, Visek and Victoria2016; Postel et al., Reference Postel, Meyer, Cagatay, Feliziani, De Mia, Fischer, Grundhoff, Milićević, Deng, Chang and Qiu2017; Mósena et al., Reference Mósena, Weber, Da Cruz, Cibulski, Da Silva, Puhl, Hammerschmitt, Takeuti, Driemeier, De Barcellos and Canal2018). The virus has also been identified by qPCR from various organs and tissues (Arruda et al., Reference Arruda, Arruda, Magstadt, Schwartz, Dohlman, Schleining, Patterson, Visek and Victoria2016; De Groof et al., Reference De Groof, Deijs, Guelen, Van Grinsven, van Os-galdos, Vogels, Derks, Cruijsen, Geurts, Vrijenhoek and Suijskens2016; Schwarz et al., Reference Schwarz, Riedel, Högler, Sinn, Voglmayr, Wöchtl, Dinhopl, Rebel-Bauder, Weissenböck, Ladinig and Rümenapf2017; Yuan et al., Reference Yuan, Han, Li, Huang, Yang, Ding, Zhang, Zhu, Zhang, Liao and Zhao2017). Serological assays are a useful tool for diagnosing APPeV infection, such as an indirect immunofluorescence test, virus neutralization, and an indirect enzyme-linked immunosorbent assay (ELISA) (Cagatay et al., Reference Gatto, Harmon, Bradner, Silva, Linhares, Arruda, De Oliveira and Arruda2019; Michelitsch et al., Reference Michelitsch, Dalmann, Wernike, Reimann and Beer2019; Schwarz et al., Reference Schwarz, Riedel, Högler, Sinn, Voglmayr, Wöchtl, Dinhopl, Rebel-Bauder, Weissenböck, Ladinig and Rümenapf2017) to the NS3, E2, and Erns proteins. These tests can be used for epidemiological investigations, and monitoring sickness in herds, and are cost-effective.

The results of a serological investigation suggested that APPeVs may be prevalent throughout the pig population in the United States (Hause et al., Reference Hause, Collin, Peddireddi, Yuan, Chen, Hesse, Gauger, Clement, Fang and Anderson2015). The earliest year that the APPeV isolate can now be linked to 1986, indicating that the virus has been present in Switzerland (Kaufmann et al., Reference Kaufmann, Stalder, Sidler, Renzullo, Gurtner, Grahofer and Schweizer2019). The objective of our research is to conduct a comprehensive analysis of reported cases of the prevalence APPeV outbreaks worldwide due its increasing frequency and also to examine the diagnostic techniques utilized for detecting APPeV infection in pigs.

Methodology and search strategy

A systematic review was conducted adhering to PRISMA guidelines. Literature from 2015 and March 2024 was sourced from including ScienceDirect (https://www.sciencedirect.com/), PubMed (https://pubmed.ncbi.nlm.nih.gov/), Scopus (https://www.scopus.com/search/), and Web of Science (http://accesss.webofknowledge.com/), using the search terms: ‘atypical porcine pestivirus’ AND ‘pestivirus K’ AND ‘prevalence’ AND ‘swine’ OR ‘pig’.

Inclusion criteria include studies reporting APPeV prevalence, articles published in English, studies employing validated diagnostic methods, and research focused on swine populations.

Exclusion criteria include reviews or meta-analyses, studies published before 2015, and articles not in English. Figure 1 reveals the flowchart of this review.

Figure 1.

PRISMA diagram for the systematic review on understanding the global distribution of atypical porcine pestivirus.

The following aspects were taken into consideration in each study: the country where the samples were taken, the year of sample collection for each study, the category of animal sampled (piglet, boar/wild boar, sow/gilt), clinical symptoms, detection method, samples used, and the prevalence recorded.

To reduce the likelihood of personal errors and/or bias, two independent reviewers conducted the screening in parallel and double-checked disagreements. The map was generated using the R studio environment (R Core Team, 2021).

A total of 328 references were collated in a bibliographic management system software (Zotero reference manager). A review of the remaining 40 articles was conducted.

Variations/presentations, transmission, and spread of APPeV

APPeV was detected in placenta, umbilical cords, and aborted piglet samples from abortion cases using viral metagenomic sequencing (Sun et al., Reference Sun, Zhang and Shan2023). Newborn piglets infected with APPeV experience clinical illness of CT, which subsequently hinders their capacity to suckle milk, leading to an elevated pre-weaning mortality rate (Gatto et al., Reference Gatto, Sonálio and De Oliveira2019). Additionally, it is demonstrated that piglets with persistent tremors have significantly reduced survivability. According to two reports, a farm in Austria lost 2.5 piglets per sow, while a farm in the United States saw an earthquake outbreak that resulted in the deaths of almost 700 pigs (Gatto et al., Reference Gatto, Sonálio and De Oliveira2019). Although the exact financial losses in the APPeV affected pig herds are unknown, a 10% decline in pig reproductive performance was predicted (Smith et al., Reference Smith, Meyers, Bukh, Gould, Monath, Scott Muerhoff, Pletnev, Rico-Hesse, Stapleton, Simmonds and Becher2017). Litters impacted by CT type A-II clinical symptoms. Typically, outbreaks happen in piglets between 1 and 2 months of age. It is noteworthy that there was just one initial outbreak of CT type A-II in the litters from the same sow, and there were no further outbreaks. The largest RNA load is seen in CT type A-II-affected piglets under 1 week of age, according to a link between RNA load and age distribution (Waage and Mumford, Reference Waage and Mumford2008). This finding could help explain why the disease is more common in piglets than in sows. In addition, a recent study demonstrates that piglet mortality increased when porcine teschovirus and APPeV were co-infected (Williamson, Reference Williamson2017). This indicates the clinical significance of APPeV infection in pigs and calls for greater research on this virus and its co-infections with those crucial porcine pathogens.

Emerging methods and diagnostic techniques

The development of diagnostic tools for APPeV has significantly evolved over the years, driven by the need for rapid, accurate, and cost-effective detection methods. Early advancements focused on serological assays like ELISA, while modern approaches emphasize molecular techniques such as RT-PCR, qPCR, and digital PCR, which offer enhanced sensitivity and precision. Recent innovations also explore multiplexing capabilities, antigen-based detection, and virus isolation, enabling improved surveillance and management strategies. Table 1 summarizes the major milestones and key features of these emerging diagnostic techniques, providing a comprehensive view of their evolution and application in APPV research.

Table 1.

Emerging methods and diagnostic techniques for detecting APPeV

Clinical signs and symptoms

CT is present and manifests as tremor and sometimes ataxia from birth. The tremor can be aggravated by ataxia or occasionally splay leg, and it can vary from a mild shiver of the head to a violent quiver of the entire piglet. Piglets may bounce off the floor due to intense twitches (Stenberg et al., Reference Stenberg, Jacobson and Malmberg2020b). According to the following studies (De Groof et al., Reference De Groof, Deijs, Guelen, Van Grinsven, van Os-galdos, Vogels, Derks, Cruijsen, Geurts, Vrijenhoek and Suijskens2016; Arruda et al., Reference Arruda, Arruda, Magstadt, Schwartz, Dohlman, Schleining, Patterson, Visek and Victoria2016; Schwarz et al., Reference Schwarz, Riedel, Högler, Sinn, Voglmayr, Wöchtl, Dinhopl, Rebel-Bauder, Weissenböck, Ladinig and Rümenapf2017), there are no reports of fever or altered demeanour linked to CT type A-II. When the muscles are activated, such as when the piglet is moving or under stress, there is an increase in tremor, known as CT action tremor, and there are no neurological symptoms when the muscles are relaxed, such as when the piglet is not moving. As of right now, there is no recognized medical cure for CT, and a piglet’s chances of survival are based on both its ability to grip the teat and suckle and its ability to escape getting crushed by the sow (Stenberg et al., Reference Stenberg, Jacobson and Malmberg2020b). Within 3 months of birth, the majority of pigs heal on their own; nevertheless, some may develop chronic shakers (Postel et al., Reference Postel, Hansmann, Baechlein, Fischer, Alawi, Grundhoff, Derking, Tenhündfeld, Pfankuche, Herder and Baumgärtner2016). It’s interesting to note that in pigs that no longer exhibit shaking in an unstressed animal, external stimuli such a sudden noise or handling may cause the tremor. As a result, recovered pigs may occasionally begin to shake when stressed, such as in a slaughterhouse (Schwarz et al., Reference Schwarz, Riedel, Högler, Sinn, Voglmayr, Wöchtl, Dinhopl, Rebel-Bauder, Weissenböck, Ladinig and Rümenapf2017).

Numerous diseases, intoxications, and infectious pathogens can cause neurological symptoms that resemble CT. But since CT is an action tremor that is absent or lessened during sleep or rest, it can be distinguished from these illnesses. Since hypoglycaemia and hypothermia can cause shivering in newborn pigs soon after delivery, these conditions are the most plausible differential diagnosis, even if these conditions also frequently cause tremors during rest or sleep (Stenberg et al., Reference Stenberg, Jacobson and Malmberg2020b). Numerous neurological symptoms, including tremor and ataxia, can be present in other conditions like PCV-2 systemic disease, Aujeszky’s disease, porcine reproductive and respiratory syndrome, otitis media, PoAstV3, aflatoxicosis, classical and African swine fever, and salt poisoning, despite the fact that the neurological symptoms are typically accompanied by a serious multisystemic illness and are not congenital (Segalés and Domingo, Reference Segalés and Domingo2002; Schulz et al., Reference Schwarz, Riedel, Högler, Sinn, Voglmayr, Wöchtl, Dinhopl, Rebel-Bauder, Weissenböck, Ladinig and Rümenapf2017; Rawal et al., Reference Rawal, Franco, Nubia, Laura, Karen, Adam, Grant, Daniel and Bailey2019, Reference Rawal, Franco, Nubia, Laura, Karen, Grant, Daniel and Bailey2020; Rawal and Linhares, Reference Rawal and Linhares2022).

Epidemiology and global distribution

Analysis of publications from 2015 to 2024 highlights a marked increase in global reporting of APPeV, with a notable peak in studies published in 2019. Geographical trends reveal the presence of APPeV in Asia, North and South America, and Europe (Fig. 2), with China emerging as the leading contributor to prevalence studies, followed by the United States. In contrast, Africa and Australia remain the only continents yet to document APPeV cases. This absence may stem from geographical isolation, environmental factors such as climate, or inadequate surveillance and diagnostic capabilities in these regions. Tables 2–5 provide a detailed summary of different articles in different continents that reported APPeV prevalence.

Figure 2.

Map revealing different continents that have reported atypical porcine pestivirus (APPeV) prevalence.

Table 2.

Data from the selected studies for the review showing different articles that reported the prevalence of atypical porcine pestivirus (APPeV) from 2015 to March 2024 revealing the countries in Asia

This sign (-) indicates that the sampled animal was healthy or not informed; CT, congenital tremor; PCR, polymerase chain reaction; RT-PCR, reverse transcription PCR; mRT-PCR, multiplex real-time PCR; sqRT-PCR, duplex semi-quantitative PCR; RT-qPCR, quantitative reverse transcription PCR; ELISA, enzyme-linked immunosorbent assay.

Table 3.

Data from the selected studies for the review showing different articles that reported the prevalence of atypical porcine pestivirus (APPeV) from 2015 to March 2024 revealing the countries in North America

This sign (-) indicates that the sampled animal was healthy or not informed; CT, congenital tremor; PCR, polymerase chain reaction; RT-PCR, reverse transcription PCR; mRT-PCR, multiplex real-time PCR; sqRT-PCR, duplex semi-quantitative PCR; RT-qPCR, quantitative reverse transcription PCR; ELISA, enzyme-linked immunosorbent assay.

Table 4.

Data from the selected studies for the review showing different articles that reported the prevalence of atypical porcine pestivirus (APPeV) from 2015 to March 2024 revealing the countries in Europe

This sign (-) indicates that the sampled animal was healthy or not informed; CT, congenital tremor; PCR, polymerase chain reaction; RT-PCR, reverse transcription PCR; mRT-PCR, multiplex real-time PCR; sqRT-PCR, duplex semi-quantitative PCR; RT-qPCR, quantitative reverse transcription PCR; ELISA, enzyme-linked immunosorbent assay.

Table 5.

Data from the selected studies for the review showing different articles that reported the prevalence of atypical porcine pestivirus (APPeV) from 2015 to March 2024 revealing the country in South America

This sign (-) indicates that the sampled animal was healthy or not informed; CT, congenital tremor; PCR, polymerase chain reaction; RT-PCR, reverse transcription PCR; mRT-PCR, multiplex real-time PCR; sqRT-PCR, duplex semi-quantitative PCR; RT-qPCR, quantitative reverse transcription PCR; ELISA, enzyme-linked immunosorbent assay.

APPeV exhibits extensive tissue tropism, primarily detected in the CNS and lymphoid organs. Additional detections in peripheral nerves, heart, lungs, liver, kidney, bladder, pancreas, intestinal tract, salivary glands, and skeletal muscle demonstrate its widespread tissue distribution. The virus has also been identified in diverse biological samples, including umbilical blood, serum, cerebrospinal fluid, saliva, nasal and rectal swabs, and semen, suggesting multiple potential transmission routes. These findings underscore the need for a deeper understanding of its pathogenesis and transmission dynamics.

Higher prevalence rates are consistently observed in piglets, particularly those with CT symptoms. However, the detection of APPeV in asymptomatic adult pigs suggests a potential carrier state, which could complicate efforts to control its spread. The identification of APPeV in wild boar populations in Germany, Italy, South Korea, and Sweden raises epidemiological concerns about wildlife reservoirs and their role in disease maintenance and transmission.

Diagnostic methods for APPeV have predominantly utilized RT-qPCR and RT-PCR, focusing on conserved genomic regions such as NS3 and NS5B and structural protein genes E2 and Erns. These approaches provide consistent and reliable detection across diverse geographical locations and sample types. While tissue and serum samples are commonly used, cerebrospinal fluid has also proven instrumental in confirming APPeV-induced CT in newborn piglets, a condition challenging to diagnose clinically. Laboratory-based differential diagnosis is essential to differentiate CT caused by APPeV from other viral or non-infectious causes.

Concurrent infections and co-infections with other viral pathogens remain prevalent in APPeV cases, further complicating diagnosis and management. The lack of comprehensive knowledge about APPeV prevention and control strategies calls for more focused research on this emerging pathogen.

Conclusion

Understanding the global distribution of APPeV and refining diagnostic methods are critical to formulating effective control and management strategies for this emerging disease. APPeV prevalence is well-documented across Asia, Europe, and the Americas, with Europe providing the most extensive data. RT-qPCR and RT-PCR remain the primary diagnostic tools, with tissue and serum samples being the most commonly tested matrices. China, given its substantial swine population, has significantly contributed to the body of research on APPeV prevalence. However, comprehensive studies from underrepresented regions, particularly Africa and Australia, are essential to bridge surveillance gaps and achieve a global understanding of the disease’s impact. The detection of APPeV in asymptomatic herds and its association with CTs highlight its potential to compromise piglet health and productivity subtly. The prevalence of co-infections and secondary infections further underscores the need for improved diagnostic capabilities and control measures. Future research should prioritize studying asymptomatic carriers, the transmission dynamics of APPeV, and the role of wildlife reservoirs. Additionally, the potential for APPeV transmission via semen necessitates investigations into reproductive impacts and vertical transmission pathways. Given its significant economic implications for the swine industry, APPeV demands coordinated international research efforts. Collaboration among global researchers will be essential to develop effective surveillance programs, standardized diagnostic protocols, and sustainable control strategies. As our understanding of APPeV advances, these initiatives will play a vital role in mitigating the economic and health impacts of this emerging pathogen on global pork production.

Acknowledgements

The authors acknowledge the financial support from the TET Fund (Tertiary Education Trust Fund, Nigeria) and CAPES-001 (Coordination for the Improvement of Higher Education Personnel). A. Silva-Júnior is a researcher supported by fellowship from CNPq.

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Figure 0

Figure 1. PRISMA diagram for the systematic review on understanding the global distribution of atypical porcine pestivirus.

Figure 1

Table 1. Emerging methods and diagnostic techniques for detecting APPeV

Figure 2

Figure 2. Map revealing different continents that have reported atypical porcine pestivirus (APPeV) prevalence.

Figure 3

Table 2. Data from the selected studies for the review showing different articles that reported the prevalence of atypical porcine pestivirus (APPeV) from 2015 to March 2024 revealing the countries in Asia

Figure 4

Table 3. Data from the selected studies for the review showing different articles that reported the prevalence of atypical porcine pestivirus (APPeV) from 2015 to March 2024 revealing the countries in North America

Figure 5

Table 4. Data from the selected studies for the review showing different articles that reported the prevalence of atypical porcine pestivirus (APPeV) from 2015 to March 2024 revealing the countries in Europe

Figure 6

Table 5. Data from the selected studies for the review showing different articles that reported the prevalence of atypical porcine pestivirus (APPeV) from 2015 to March 2024 revealing the country in South America