Pathophysiology
Clinical signs of sealpox virus infection include firm nodular skin lesions in pinnipeds and hyperpigmented skin lesions ('tattoo', 'ring', 'pinhole') in cetaceans, highlighting the diverse histopathological presentations (PMID: 41339018).
VP7 protein, forming the core surface of BTV with distinct top and bottom domains, is pivotal for virus assembly and serogroup specificity, impacting diagnostic methods such as competitive-ELISA (Hu XB et al., 2025; PMID: 40307924).
Bluetongue Virus predominantly impacts sheep but can also affect goats and certain deer species, with notable clinical manifestations in cattle during epizootic outbreaks involving BTV-8 (PMID: 34578322). This underscores the importance of diagnostic tools like the ELISA for monitoring across affected species (PMID: 34578322).
Non-human primates, including those in Costa Rica, can replicate flaviviruses without developing overt disease but exhibit strong immune responses, offering clues into viral pathogenesis (Dolz et al., 2019; PMID: 31276532).
The successful replication of PEDV in intestinal epithelial cells of young piglets leads to mal-absorptive diarrhea characterized by decreased efficacy of brush border membrane-bound digestive enzymes and leaky junctions in the small intestine, resulting in severe dehydration and a high mortality rate of nearly 100% in piglets exposed within 3–4 days post-infection (PMID: 29914846).
Although pigs tested positive for PCV2 antibodies or sequences were clinically healthy at slaughter, the study suggests a link between PCV2 and porcine multisystemic wasting syndrome (PMWS), implying potential subclinical pathology (PMID: 12418777).
A study on bovine viral diarrhea virus (BVDV), a pestivirus, revealed that introducing a Y2441C substitution in NS4B resulted in noncytopathic variants despite normal NS3 production levels, indicating NS4B's potential role in viral cytopathogenicity (Qu et al., 2001; PMID: 11602707).
Chemical cross-linking experiments demonstrated that NS3, NS4B, and NS5A form a multiprotein complex in infected cells, underscoring their collaborative role in viral pathogenicity (Qu et al., 2001; PMID: 11602707).
Although focused on porcine circovirus types, the study's findings on viral prevalence and circulation patterns may indirectly contribute to understanding broader viral pathogenesis mechanisms affecting similar systems (Magar et al., 2000; PMID: 10935885).
Epidemiology
A study conducted in Saudi Arabia identified seven significant viruses affecting olive trees across different regions, underscoring the economic importance of these pathogens despite limited prior research on olive viruses in the country (PMID: 41902236).
The research focused on the Al Jowf region, highlighting its significance as a productive agricultural area with notable olive virus prevalence, contributing to regional disease surveillance (PMID: 41902236).
Studies indicate that marine mammals infected with sealpox virus may not exhibit clinical signs but can transmit the virus to humans through close contact, as exemplified by a researcher bitten by a captive grey seal who later tested positive for sealpox without prior clinical manifestations (PMID: 41339018).
The paper discusses how Advanced Molecular Detection (AMD), which employs next-generation sequencing (NGS) technologies, significantly aids in the rapid identification and tracking of infectious diseases, thereby enhancing outbreak detection and control efforts (Ricaldi JN et al., 2025; PMID: 40359007).
Climate change has contributed to the expansion of BTV infection ranges beyond traditional endemic areas, affecting regions beyond the previously known tropical and subtropical zones (40°N to 35°S), impacting both wild and domestic ruminants (Hu XB et al., 2025; PMID: 40307924).
Studies indicate that approximately 50–60% of ruminants recovering from FMD may remain persistently infected, with live virus or viral RNA detectable in oropharyngeal fluid for extended periods, potentially up to six months or more (PMID: 40186280).
The increasing global range of BTV infection is now evident, as traditional northern and southern most limits of BTV distribution have expanded with incursions into Europe, Australia, America, Asia, and other countries that had never previously reported BTV infections (PMID: 39772121).
Clinical Presentation
NDRV infection is characterized by severe necrotic and hemorrhagic lesions primarily in the liver and spleen, causing notable clinical symptoms and morbidity in infected waterfowl (Yun et al., 2022; PMID: 36445088).
The detection of Zika virus nonstructural protein 1 (ZVNS1) in serum samples correlates with the active phase of infection, providing a biomarker for ongoing or recent infection, which can be beneficial for clinical monitoring (PMID: 33317184).
DENV-2 and DENV-3 serotypes are notably linked to severe dengue disease presentations, including hemorrhagic fever and shock, whereas DENV-1 and DENV-4 tend to cause less severe symptoms [PMID: 32579555].
PCV3 infection has been linked to diverse clinical manifestations in pigs, such as chronic reproductive issues, PDNS-like symptoms, and systemic inflammation, suggesting its broad pathogenic potential (Zhang et al., 2019; PMID: 30841883).
Höper D, Wylezich C, Beer M. Loeffler 4.0: Diagnostic Metagenomics. Advances in virus research (2017); PMID: 29029726. The presence of coinfections identified through metagenomic sequencing can contribute to understanding the variability in clinical symptoms, suggesting a multifaceted approach to diagnosing diseases linked to the California serogroup virus.
Most dengue infections are asymptomatic or present as a non-specific feverish illness, with asymptomatic infections predominating, indicating that clinical recognition and reporting may be challenging. [PMID: 28699560]
Given that NS1 antigen capture tests can be performed at the onset of symptoms, earlier detection of Dengue virus infections may facilitate more timely clinical interventions (PMID: 26293345).
Among older Vietnamese Americans surveyed, depression was notably prevalent, with those affected being more likely to be older adults, indicating a significant mental health concern in this demographic (PMID: 18637981).
Although the study focuses on diagnostic improvement rather than clinical signs, the enhanced sensitivity of the recombinant nucleocapsid protein IFA (Racine et al., 2004) implies potential for identifying more cases of postweaning multisystemic wasting syndrome, which could correlate with broader clinical presentations (PMID: 15242949).
Diagnosis
Given the diverse range of olive viruses identified, molecular methods are crucial for diagnosing specific viral infections in olive trees, which can inform targeted diagnostic approaches (PMID: 41902236).
Diagnosing sealpox virus infections in marine mammals without clinical signs remains challenging due to the absence of validated serodiagnostic tests specific to sealpox virus, complicating routine serosurveillance efforts (PMID: 41339018).
Next-generation sequencing (NGS) technologies provide a faster and more economical approach to pathogen identification compared to older methods like Sanger sequencing, facilitating quicker diagnosis of infectious diseases including those caused by the California serogroup virus (Ricaldi JN et al., 2025; PMID: 40359007).
A study expressed and characterized six monoclonal antibodies (mAbs) against the VP7 protein of BTV-1, demonstrating specific recognition capabilities that could enhance diagnostic accuracy for BTV serotypes and differentiate them from related orbiviruses such as EHDV and AHSV (Hu XB et al., 2025; PMID: 40307924).
RT-PCR has been utilized to detect FMDV RNA in oropharyngeal fluid obtained through probang cups, facilitating the identification of persistently infected animals where FMDV may still be present despite clinical recovery (PMID: 40186280).
WOAH-approved methods for confirmation of clinical infection with BTV in animals include pan-RT-PCR and RT-qPCR, with PCR also useful for assessing freedom from infection prior to movement (PMID: 39772121).
Competition/blocking ELISA formats employing monoclonal antibodies specific for epitopes on conserved viral structural proteins have become the preferred alternative for BTV-specific antibody detection, targeting VP2 for serotype and VP7 for serogroup identification (PMID: 39772121).
Non-structural protein (NSP) ELISA assays play a vital role in distinguishing between vaccinated and naturally infected animals with Foot-and-mouth disease (FMD), facilitating accurate diagnosis as demonstrated in Seeyo et al., 2024 (PMID: 39397089).
Development and validation of RT-LAMP for detecting yellow fever virus (YFV) RNA in non-human primate (NHP) samples demonstrates its potential as a rapid, sensitive, and cost-effective diagnostic tool, overcoming limitations of RT-qPCR such as specialized equipment requirements (Cardoso SF et al., 2024). [PMID: 39342022]
Bulk tank milk (BTM) sampling has proven to be a highly sensitive and cost-effective method for early detection of BTV incursions, employing ELISA tests based on the VP7 protein of the virus for diagnosing bluetongue in unvaccinated high-risk areas (Romero-Trancón et al., 2024). This method has been validated for both BTM and individual milk samples, demonstrating high sensitivity and specificity (Romero-Trancón et al., 2024).
The research determined the highest cycle threshold (Ct) value of the Xpert Xpress SARS-CoV-2/Flu/RSV test that correlates with the presence of infectious SARS-CoV-2, suggesting its utility in diagnosing active viral replication (PMID: 38466093).
Current research highlights the potential of combining nucleic acid detection methods with immunological assays via digital ELISA to overcome limitations and enhance detection accuracy for RNA viruses, which could be particularly beneficial for diagnosing diseases like those caused by the California serogroup virus (PMID: 38235132).
Differential Diagnosis
Monoclonal antibodies specific to VP7 protein exhibit varying cross-reactivity patterns, enabling differentiation between BTV serotypes and related orbiviruses such as AHSV and EHDV in serological diagnostics (Hu XB et al., 2025; PMID: 40307924).
Evidence suggests that co-infections of PCV3 with pathogens like PRRSV can increase pathogenicity in pigs, necessitating careful differential diagnosis to identify co-infections accurately (Zhang et al., 2019; PMID: 30841883).
The study by Tyson et al. (2019) showed that a combination of DENV1-4 and ZIKV NS1 IgG ELISAs could distinguish ZIKV infections with prior DENV exposure and secondary DENV infections with high sensitivity (91.7% to 94.1%) and specificity (87.0% to 95.0%), facilitating precise differential diagnosis. [PMID: 30429254]
The antigenic typing of the rabies virus isolate from the patient showed a unique pattern closely matching those from Mexican free-tailed bats (Tadarida brasiliensis), distinguishing it from variants associated with terrestrial carnivores and hematophagous bats, aiding in differential diagnosis (Velasco-Villa A et al., 2008; PMID: 19046517).
The study by Artsob et al. (PMID: 6149231) noted extensive cross-reactions between Jamestown Canyon and South River strains, which is crucial for accurate differential diagnosis among California serogroup viruses.
Jensen MH (1981). Detection of antibodies against hog cholera virus and bovine viral diarrhea virus in porcine serum. Acta veterinaria Scandinavica. PMID: 6266240. The study indicates that while CF alone may not distinctly differentiate between HCV and BVDV antibodies, combining CF and PLA assays enhances the ability to differentiate between these viral infections in pigs.
Management
The study emphasizes the importance of comprehending viral genetic variability and distribution to enhance management practices and reduce economic impacts on olive production in Saudi Arabia (PMID: 41902236).
Given the potential for asymptomatic transmission from marine mammals to humans, management strategies should focus on minimizing close contact to prevent the spread of sealpox virus (PMID: 41339018).
The combination of bioinformatics analysis with NGS data supports more effective public health responses to infectious disease outbreaks, which could optimize management strategies for diseases such as those caused by the California serogroup virus (Ricaldi JN et al., 2025; PMID: 40359007).
Population serosurveys detecting antibodies against FMDV NSPs via ELISA can differentiate between infected and vaccinated animals (DIVA), highlighting the need for careful management to avoid false positives from residual vaccine components (PMID: 40186280).
Systematic routine serological screening for BTV-specific antibodies remains an essential component of a comprehensive approach to early detection of novel BTV incursions, utilizing sentinel animals strategically placed near endemic regions (PMID: 39772121).
In Thailand, the management of Foot-and-mouth disease (FMD) heavily relies on routine vaccination programs, particularly for ruminants which are mandated to be vaccinated three times yearly for dairy cattle and twice yearly for beef cattle, buffaloes, and small ruminants, as per Seeyo et al., 2024 (PMID: 39397089). Pig vaccination is voluntary but subsidized.
The implementation of RT-LAMP for YFV diagnostics in NHP tissues supports rapid identification of outbreaks, enabling timely preventive actions that could mitigate the spread of the virus to humans and reduce overall morbidity and mortality (Cardoso SF et al., 2024). [PMID: 39342022]
Early detection of bluetongue through bulk tank milk (BTM) surveillance facilitates timely implementation of control measures like vaccination and restricting animal movements between affected and unaffected areas, essential for managing outbreaks effectively (Romero-Trancón et al., 2024).
Identifying the Ct value threshold that indicates the absence of infectious SARS-CoV-2 can help healthcare providers make informed decisions regarding patient isolation duration and return-to-duty timelines (PMID: 38466093).
The development of integrated nucleic acid testing and immunoassays through digital ELISA technology promises to revolutionize RNA virus detection, potentially leading to more efficient patient management strategies for diseases including those caused by the California serogroup virus (PMID: 38235132).
The creation of a blocking ELISA for detecting NDRV antibodies provides a valuable tool for epidemiological surveillance and management strategies to control NDRV outbreaks in waterfowl (Yun et al., 2022; PMID: 36445088).
Effective management of PCV2 infection necessitates the development of simple, quick, and accurate detection methods due to the virus's immunosuppressive effects and propensity to enable secondary pathogen invasions (Zhang et al., 2022; PMID: 35937078).
Engineering recombinant empty viral capsids with stabilizing mutations may improve ELISA test reliability in detecting serotype-specific antibodies against FMDV, thereby aiding in better management and surveillance of vaccinated livestock populations (PMID: 35891476).
The ultrasensitive nanobody-HRP fusion protein ELISA platform shows promise for rapid detection of PCV2 antibodies, which could facilitate quicker diagnostic turnaround times and support more efficient management strategies in pig farming (PMID: 33526021).
Given the increasing trend of online donor registration, the use of buccal swab samples for CMV serostatus determination offers a practical solution for expanding CMV screening efforts without compromising accuracy (PMID: 32052845).
Given the economic devastation caused by FMD, with estimated costs ranging from US$6.5 billion to over $21 billion annually in endemic countries, robust serological surveillance tools like the evaluated ELISA kits are critical for early detection and management strategies in FMD-free regions (PMID: 33025858).
Early and accurate serotype identification via advanced diagnostic techniques such as the NS1-based ELISA can enhance patient management and epidemiological tracking during dengue outbreaks [PMID: 32579555].
Complications
BTV infection led to significant increases in total leucocyte count (TLC) in both sheep and goats, suggesting systemic inflammatory complications (PMID: 30406333).
Small-scale farms experienced a notable increase in cattle mortality rates by 3.2 times during the bluetongue outbreak period, though voluntary culling rates decreased (PMID: 18849575).
The presence of Neospora caninum antibodies was associated with a notably higher risk of abortion, highlighting potential complications related to this pathogen (Waldner CL, Animal Reproduction Science, 2005; PMID: 15893892).
Vaccination responses for infectious bronchitis virus (IBV) and Newcastle disease virus (NDV) were delayed or blocked in broiler flocks due to maternal antibodies or an IBD outbreak, potentially complicating flock health management (Snyder et al., 1986; PMID: 3015100).
Prognosis & Follow-up
Although the paper focuses on diagnostic advancements rather than specific prognostic details for California serogroup virus diseases, enhanced diagnostic capabilities via AMD could indirectly improve patient monitoring and follow-up protocols (Ricaldi JN et al., 2025; PMID: 40359007).
The Indian Council of Agricultural Research-National Institute on FMD (ICAR-NIFMD) conducts serosurveys on young animals aged 6–18 months to detect FMDV NSP antibodies, aiding in determining silent carriers and facilitating disease-free status declarations (PMID: 40186280).
Although detailed prognosis information is limited in Seeyo et al., 2024 (PMID: 39397089), effective implementation of vaccination programs and diagnostic tools like NSP-ELISA supports better disease control and potentially improved outcomes for affected populations.
Although detailed prognosis specifics are limited in this paper, early detection via bulk tank milk (BTM) sampling aids in monitoring long-lasting immunity post-vaccination, which can indirectly influence prognosis management strategies (Romero-Trancón et al., 2024).
Determining the Ct value correlating with infectious SARS-CoV-2 presence can indirectly influence follow-up strategies by aiding in assessing when patients are likely no longer infectious (PMID: 38466093).
While ELISAs are widely used for serological assessments, the virus neutralization test (VNT) is considered the gold standard due to its ability to detect serotype-specific antibodies indicative of protective immunity (PMID: 35891476).
The study's inclusion of samples from vaccinated and infected animals highlights the importance of follow-up serological testing with reliable kits like PrioCHECK and ID Screen for monitoring the efficacy of vaccination programs and assessing the risk of outbreaks (PMID: 33025858).
Special Populations
Spider monkeys (Ateles geoffroyi) in Costa Rica have been shown to harbor flavivirus infections without exhibiting overt disease, indicating their utility as sentinels for viral activity (Dolz et al., 2019; PMID: 31276532).
Older Vietnamese Americans, particularly those who migrated later in life as political refugees, exhibit higher risks for psychiatric disorders like posttraumatic stress disorder and preventable cancers, possibly linked to historical trauma and lifestyle factors such as higher smoking rates and lower rates of cancer screenings (PMID: 18637981).
The seropositive cattle predominantly originated from the Okanagan Valley, suggesting that this region might have unique risk factors contributing to higher viral exposure in cattle (PMID: 1653104).
Sows demonstrated an adjusted odds ratio of 9.78 compared to suckling pigs, highlighting their significant role in maintaining PCV3 exposure within swine populations (PMID: 41780290).
Given the specific geographic context of the study in high Andean regions, understanding localized seroprevalence patterns could inform targeted public health interventions for cattle in similar environments. [PMID:40628303]
Among different pig categories, sows demonstrated the highest seroprevalence of PCV4 antibodies at 67.8%, indicating a possible higher risk or exposure in sows compared to other groups (PMID: 34105246).
The study suggests that camels could act as sentinel animals due to their significantly higher seroprevalence for WNV (92%) and RVF (45%) compared to cattle, providing valuable epidemiological data (PMID: 33666802).
Despite residing in high-altitude areas with restricted animal movement, sheep in central Portugal exhibited detectable SBV antibodies, highlighting the virus's adaptability across diverse environments. [PMID: 29761919]
Key Recommendations
Given its high performance metrics, incorporating this ELISA into diagnostic protocols could significantly improve the accuracy of PRRSV strain identification and epidemiological tracking [PMID: 12414748]. (Evidence: Strong)
Given the high specificity and sensitivity of the ELISA method developed by Nishikawa et al. (2001) using recombinant NcSRS2 with PMID: 11682519, it is recommended to incorporate this technique into diagnostic workflows for Neospora caninum to enhance clinical management and patient outcomes. (Evidence: Strong)
Given the successful application of ELISA typing across various California serogroup viruses in Canada (PMID: 6149231), it is recommended to incorporate this method into routine diagnostic protocols for better strain differentiation and epidemiological surveillance. (Evidence: Strong)
Given its superior sensitivity and specificity, the implementation of the recombinant capsid protein-based single serum dilution ELISA is advised for enhancing diagnostic capabilities in porcine PCV2 infections (PMID: 38214798). (Evidence: Strong)
Given its enhanced specificity for DENV IgG detection compared to traditional methods, incorporating the ΔNS1-based ELISA test into diagnostic protocols in dengue-endemic areas with concurrent ZIKV transmission could significantly reduce diagnostic errors (PMID: 34555500). (Evidence: Strong)
The study concludes that sustained high vaccination coverage should be maintained to ensure continued protection against measles, rubella, diphtheria, tetanus, and varicella, reinforcing the importance of ongoing immunization efforts [PMID:31843668]. (Evidence: Strong)
A key recommendation from Gates et al. (2019) is to test all new breeding animals for BVD virus before introducing them into herds, ensuring they are confirmed negative before movement, even if originating herds tested negative via antibody screening. [PMID: 31104579] (Evidence: Strong)
Given the comparable diagnostic performance of I-ELISA and S-ELISA with overlapping credibility intervals, clinicians are advised to utilize either method based on availability and herd-specific needs for accurate PCV2 antibody detection in pigs (PMID: 28882762). (Evidence: Moderate)
The retrospective analysis underscores the utility of serological surveillance with competitive NP ELISA for identifying and monitoring the prevalence of LPAI viruses across different poultry species, aiding in proactive management strategies (PMID: 26629630). (Evidence: Moderate)
References
1 Contreras-Vilchez VE, Mendoza-Palomino E, Jiménez-Aparco C, Huamán-Lizana D, Acuña-Leiva A, Quispe-Ccasa HA. Cows of reproductive age in the high Andean region of Peru have seroprevalence of antibodies against bovine herpesvirus 1 and Neospora caninum. American journal of veterinary research 2025. link 2 Ng Y, Chua LAV, Cui L, Ang LW, Tee NWS, Lin RTP et al.. Seroprevalence of vaccine-preventable diseases among children and adolescents in Singapore: Results from the National Paediatric Seroprevalence Survey 2018. International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases 2020. link
2 papers cited of 322 indexed.