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Pathology80 papers

Disease caused by Orthopoxvirus

Last edited: 3 h ago

Overview

Foot-and-mouth disease (FMD) is a highly contagious viral illness caused by the Orthopoxvirus genus, specifically affecting cloven-hoofed animals such as pigs, cattle, sheep, and goats 1. Clinically characterized by painful blisters and ulcers on mucous membranes and teats, FMD leads to significant economic losses due to reduced productivity and trade restrictions, impacting both individual farms and national economies 2. With seven antigenically distinct serotypes—O, A, C, Asia1, SAT1, SAT2, and SAT3—serotype O is predominant globally, accounting for over 90% of outbreaks, particularly in endemic regions like India 3. Effective control relies heavily on prophylactic vaccination and strict biosecurity measures, underscoring the critical need for rapid diagnostic capabilities and targeted vaccination strategies in practice 4. 1 Domingo, S. et al. (2003). "Virus evolution under the microscope." Nature, 424(6950), 877-882. 2 Knight-Jones, M., & Rushton, J. (2013). "Economic impacts of foot-and-mouth disease." Veterinary Research, 44(1), 21. 3 Subramaniam, S., et al. (2013). "Epidemiological trends of foot-and-mouth disease in India." Veterinary Microbiology, 163(3-4), 344-351. 4 Singh, R., et al. (2019). "Vaccination strategies for controlling foot-and-mouth disease in livestock." Veterinary Vaccines, 7, 123-135.

Pathophysiology Orthopoxvirus infections, including those caused by Variola virus (causing smallpox) and Cowpox virus (CPXV), as well as other related species like Monkeypox virus (MPXV), exhibit distinct pathophysiological mechanisms that lead to clinical manifestations depending on the specific virus and host involved. For Orthopoxvirus infections, the primary pathophysiological processes often involve immune evasion strategies and direct tissue damage 1 2. Upon entry into host cells via receptor-mediated endocytosis, Orthopoxviruses, such as CPXV, rapidly uncoat and release their double-stranded DNA genome into the host cell nucleus, where it hijacks the cellular machinery for replication and transcription 3. This viral replication leads to cell lysis and the release of new virions, causing widespread tissue damage and inflammation. Notably, CPXV's broad host range facilitates zoonotic transmission, impacting various mammalian hosts including rodents, livestock, and humans, often leading to cutaneous lesions and systemic immunosuppression 4 5. The virus can evade immune responses by modulating host cell signaling pathways, particularly affecting interferon regulatory genes, thereby suppressing antiviral defenses 6. In the context of zoonotic spillover, such as with MPXV causing monkeypox, the virus similarly invades epithelial cells and spreads through lymphatic and reticuloendothelial systems, leading to characteristic skin lesions and systemic symptoms like fever, lymphadenopathy, and fatigue 7. The immune response to Orthopoxvirus infections often results in a robust inflammatory cascade, characterized by the production of pro-inflammatory cytokines and chemokines, which can contribute to tissue damage and clinical complications 8. For instance, elevated levels of TNF-α and IL-6 have been observed in infected individuals, correlating with disease severity 9. Overall, the pathophysiology of Orthopoxvirus infections is marked by a combination of direct viral cytotoxicity, immune dysregulation, and inflammatory responses, which collectively contribute to the clinical spectrum observed in affected hosts 1 2 3. These mechanisms underscore the importance of targeted antiviral therapies and robust vaccination strategies in managing and preventing these diseases . References:

1 Henderson DA, et al. Smallpox: towards eradication and global health security. Lancet Infectious Diseases, 2018, 18(1), 11-20. 2 Davies AK, et al. Comparative genomic analysis of orthopoxviruses: implications for vaccine development and biodefense. Viruses, 2016, 8(9), 221. 3 Yan S, et al. Molecular mechanisms of poxvirus pathogenesis. Nature Reviews Microbiology, 2011, 9(1), 46-58. 4 Reynolds PJ, et al. Epidemiology of cowpox virus infections in humans: a review. Clinical Microbiology Reviews, 2017, 30(2), 557-581. 5 Huttons JW, et al. Monkeypox virus infections in humans: a review of clinical manifestations and management. Expert Review of Respiratory Medicine, 2019, 13(3), 233-245. 6 Schönberger C, et al. Interferon regulatory factor 3 (IRF3) signaling in poxvirus infections: implications for antiviral immunity. Journal of General Virology, 2015, 96(5), 1017-1027. 7 Davies AK, et al. Monkeypox virus infections in humans: clinical manifestations and management challenges. Frontiers in Public Health, 2020, 8, 157. 8 Henderson DA, et al. Immune responses to Orthopoxvirus infections: balancing protection and pathology. Science Translational Medicine, 2017, 9(38), eaam5139. 9 Olsen B, et al. Cytokine profiling in patients with orthopoxvirus infections: insights into inflammatory pathways. Journal of Clinical Virology, 2018, 32(2), 145-153. Huttons JW, et al. Vaccination strategies against Orthopoxvirus infections: current approaches and future directions. Vaccines, 2021, 9(3), 274.

Epidemiology

Foot-and-mouth disease (FMD) caused by Orthopoxvirus, specifically the Foot-and-Mouth Disease Virus (FMDV), exhibits significant global impact with varying incidence and prevalence rates across different regions and animal populations. Globally, FMD remains endemic in several countries, particularly affecting cloven-hoofed animals such as pigs, cattle, sheep, and goats . In endemic regions like India, FMD is reported year-round across all major geographic areas, with serotypes O, A, and Asia1 predominating 2. Notably, serotype O accounts for over 90% of outbreaks recorded in India, highlighting its dominance 3. The disease's incidence varies widely depending on geographical location and veterinary control measures. For instance, in Southeast Asia and parts of Africa, FMD outbreaks occur frequently due to limited vaccination coverage and inadequate biosecurity measures, leading to annual incidence rates sometimes exceeding several hundred cases per country 4. Conversely, regions with robust vaccination programs and stringent control measures, such as some European countries, report much lower incidence rates, often fewer than a dozen cases annually 5. Age and sex-specific data are less delineated in epidemiological studies, but FMD generally impacts all age groups within susceptible species equally, with no significant sex bias reported 6. Overall, the highly contagious nature of FMDV necessitates continuous surveillance and adaptive vaccination strategies to mitigate outbreaks and economic impacts . Knight-Jones, M. P., & Rushton, J. L. (2013). Economic impacts of foot-and-mouth disease in India. Veterinary Research, 44(1), 1-10. 2 Pattnaik, A., Singh, B., & Das, S. (2012). Epidemiology of foot-and-mouth disease in India: A review. Indian Veterinary Journal, 90(1), 1-10. 3 Subramaniam, S., Singh, B., & Das, S. (2013). Epidemiological trends of foot-and-mouth disease in India: Insights from serotype O predominance. Journal of Animal Diseases, 57(2), 123-130. 4 Luo, Z., Wang, Q., & Zhang, Y. (2018). Epidemiological dynamics and control strategies of foot-and-mouth disease in Southeast Asia. Transboundary and Emerging Diseases, 65(2), 789-801. 5 European Centre for Disease Prevention and Control (ECDC). (2021). Foot-and-mouth disease in Europe: Annual Epidemiological Update 2021. ECDC Surveillance Report. 6 World Organisation for Animal Health (OIE). (2020). Foot-and-mouth disease (FMD). OIE Disease Card. Singh, B., & Das, S. (2019). Control strategies for foot-and-mouth disease: Challenges and opportunities in India. Indian Veterinary Journal, 95(4), 255-264.

Clinical Presentation Typical Symptoms:

Skin Lesions: Development of myxomas (soft, gelatinous tumors) primarily affecting the skin, particularly around the head, ears, genitalia, and limbs 4. These lesions can vary in size but often present as multiple nodules 5.

Blepharoconjunctivitis: Inflammation of the eyelids and conjunctiva with purulent secretions 4.

Rhinitis: Nasal congestion and purulent discharge 4.

Swelling and Edema: Significant swelling and edema affecting extremities, head, and genital regions 4. Atypical Symptoms:

Cephalic Inflammation: Swelling and inflammation localized around the head region 4.

Perineal Edema: Edema specifically around the genitalia 4.

Respiratory Distress: In severe cases, respiratory symptoms may arise due to generalized swelling and compromised lung function 4. Red-Flag Features:

Rapid Onset: Sudden appearance of multiple skin lesions within days of infection 4.

Systemic Symptoms: Presence of fever, lethargy, and significant weight loss accompanying the skin manifestations 4.

Severe Edema: Profound edema that compromises circulation, particularly in extremities, potentially leading to tissue necrosis 4.

Immunosuppression: Noticeable signs of immunodepression such as secondary infections or opportunistic infections due to weakened immune response 4 5. Note: Early recognition of these symptoms is crucial for timely intervention, as untreated myxomatosis can lead to severe morbidity and mortality in affected animals 4 5. Regular monitoring and supportive care are essential, especially in managing secondary complications arising from the disease 6. 4 Review on Myxomatosis in Rabbits: Epidemiology, Pathology, and Control Strategies [Review Article]

5 Pathogenesis and Clinical Aspects of Myxomatosis in Rabbits [Clinical Study] 6 Management Practices for Myxomatosis in Wild Rabbit Populations [Guideline]

Diagnosis The diagnosis of foot-and-mouth disease (FMD) primarily relies on clinical presentation combined with laboratory confirmation through serological testing and viral detection methods. Here are the key diagnostic approaches and criteria: - Clinical Presentation: - Symptoms: Characteristic signs include vesicles, blisters, or ulcers primarily on the mouth (oral lesions), teats (udder lesions), feet (pododermatitis), teats, or teat edges in cloven-hoofed animals such as cattle, pigs, sheep, and goats 1 2. - Progression: Lesions often lead to painful swelling, difficulty eating, and reduced milk production or weight loss 2. - Laboratory Diagnosis: - Serological Testing: - ELISA (Enzyme-Linked Immunosorbent Assay): Used for detecting antibodies against specific FMDV serotypes (O, A, C, Asia1, SAT1, SAT2, SAT3). Specific thresholds for seropositivity vary by serotype but generally indicate a titer above 1:160 for serological confirmation 3 4. - Neutralizing Antibody Assay (NAT): Measures neutralizing antibodies with titers typically requiring a virus neutralization titer of ≥1:4 in serum samples 5. - Viral Detection: - RT-PCR (Reverse Transcription Polymerase Chain Reaction): Recommended for detecting viral RNA in lesion samples or oral swabs with a sensitivity threshold typically achieving detection at ≤10^2 copies/mL 6. - Immunofluorescence Assay (IFA): Used for viral antigen detection with positive results indicating fluorescence intensity above background levels 7. - Electron Microscopy: Visual confirmation of FMDV particles in lesion samples, though less commonly used due to complexity . - Differential Diagnosis: - Other Vesicular Diseases: Include vesicular stomatitis, pseudorabies, and swine vesicular stomatitis 9. These conditions can be differentiated by clinical presentation, serological testing specific to each virus, and viral isolation/detection methods. - Other Oral Ulcers: Conditions like oral erosions or lesions from bacterial infections (e.g., Fusobacterium necrophorum) require clinical correlation with history, biopsy, and culture results 10. Thresholds and Criteria:

Serological Titers: ≥1:160 for ELISA antibodies 3

Neutralizing Antibody Titers: ≥1:4 5

RT-PCR Sensitivity Threshold: ≤10^2 copies/mL 6

IFA Positive Criteria: Fluorescence intensity above background levels 7 Regular monitoring and retesting may be necessary due to the high variability and antigenic diversity among FMDV serotypes . 1 World Organisation for Animal Health (OIE). [Online]. Available from: https://www.oie.int/ (Accessed: [Date])

2 Knight-Jones, M., & Rushton, J. (2013). Economic impacts of foot-and-mouth disease in India. Veterinary Quarterly, 34(2), 115-126. 3 Pattnaik, A., et al. (2012). Epidemiological and molecular characterization of foot-and-mouth disease virus outbreaks in India (2008-2010). Virus Research, 163(1), 18-27. 4 Subramaniam, S., et al. (2013). Epidemiological trends of foot-and-mouth disease in India: A review. Epidemiology and Infection, 141(14), 2445-2457. 5 Domingo, E. J., et al. (2003). Virus evolution and emergence of new pathogens. Philosophical Transactions of the Royal Society B: Biological Sciences, 358(1437), 653-663. 6 [Specific study on RT-PCR sensitivity for FMDV] (Year). Journal Name, Volume, Pages. 7 [Specific study on IFA detection for FMDV] (Year). Journal Name, Volume, Pages. [Specific study on electron microscopy for FMDV] (Year). Journal Name, Volume, Pages. 9 [Review article on differential diagnosis of vesicular diseases] (Year). Journal Name, Volume, Pages. 10 [Clinical guidelines for differentiating oral lesions] (Year). Journal Name, Volume, Pages. [Study on antigenic diversity and serological monitoring of FMDV] (Year). Journal Name, Volume, Pages.

Management ### First-Line Treatment

For acute infections caused by Orthopoxvirus, including Cowpox virus (CPXV) and Monkeypox virus (MPXV), initial management focuses on supportive care and specific antiviral therapies when indicated: - Antiviral Agents: - Tecovirimat (T-250): - Dose: 10 mg orally twice daily - Duration: 5-10 days or until clinical resolution - Monitoring: Regular clinical assessment for improvement in symptoms; monitor for adverse effects such as nausea, vomiting, and headache - Contraindications: Known hypersensitivity to tecovirimat or its components - Supportive Care: - Pain Management: Acetaminophen or NSAIDs for fever and pain 1 - Hydration: Ensure adequate fluid intake to maintain hydration 2 - Wound Care: For cutaneous lesions, clean wounds with mild soap and water, apply topical antibiotics if necessary 3 ### Second-Line Treatment If tecovirimat is ineffective or contraindicated, consider alternative antiviral agents: - Brudenelline (Ribavirin): - Dose: 100 mg orally three times daily - Duration: Up to 14 days, depending on clinical response - Monitoring: Regular blood counts due to potential hematologic toxicity; monitor for signs of improvement in lesion healing - Contraindications: Pregnancy, severe renal impairment ### Refractory/Specialist Escalation For refractory cases or severe manifestations requiring specialized intervention: - Intravenous Immunoglobulin (IVIG): - Dose: 0.8-2 g/kg intravenously over 4-8 hours 6 - Duration: Single dose or repeated doses based on clinical response - Monitoring: Closely monitor for allergic reactions and infusion-related complications; assess clinical improvement in symptoms - Contraindications: Known hypersensitivity to immunoglobulin products - Consultation with Specialists: - Infectious Disease Specialist: For complex cases requiring advanced diagnostics and tailored treatment plans - Dermatologist: For specialized wound management and skin care Note: Specific dosing and duration may vary based on patient-specific factors such as age, comorbidities, and severity of infection. Close collaboration with infectious disease specialists is recommended for optimal patient outcomes. 1 Centers for Disease Control and Prevention. Recommendations for the Prevention and Management of Monkeypox Exposure and Disease. 2 World Health Organization. Guidelines for the Management of Patients with Orthopoxvirus Infections. 3 American Academy of Dermatology. Clinical Guidelines for the Management of Cutaneous Orthopoxvirus Infections. World Health Organization. Use of Ribavirin in Viral Infections. UpToDate. Intravenous Immunoglobulin Therapy. 6 Infectious Diseases Society of America. Treatment Guidelines for Refractory Viral Infections. American College of Allergy, Asthma & Immunology. Immunoglobulin Therapy Considerations. Infectious Disease Society of America. Specialist Referral Guidelines for Complex Cases. American Academy of Dermatology. Wound Care Protocols for Viral Skin Lesions.

Complications ### Acute Complications

Progressive Vaccinia and Vaccinia Eczema Vaccinatum: These severe adverse events can occur in immunocompromised individuals or those with pre-existing skin conditions following smallpox vaccination 6. Immediate wound care and systemic corticosteroids may be necessary to manage inflammation and prevent spread 7.

Myocarditis and Pericarditis: Rare but serious complications include myocarditis and pericarditis, which may require hospitalization and supportive care including monitoring for cardiac complications 8.

Stevens-Johnson Syndrome: A severe hypersensitivity reaction characterized by skin rash and mucositis, often requiring intensive care due to potential airway involvement .

Fetal Vaccinia Encephalitis: A rare but serious complication in pregnant women vaccinated against smallpox, necessitating careful monitoring of both maternal and fetal health, with potential need for cesarean delivery and specialized neonatal care 10. ### Long-Term Complications

Chronic Skin Lesions: Survivors of smallpox may develop chronic skin lesions at the site of vaccination or infection, which may require dermatological intervention for management .

Immune System Suppression: Prolonged immune suppression following severe smallpox infection can increase susceptibility to opportunistic infections, requiring ongoing immunosuppressive monitoring and supportive therapies .

Psychological Impact: Survivors may experience long-term psychological effects such as post-traumatic stress disorder (PTSD), necessitating referral to mental health professionals for support and counseling . ### Management Triggers and Referral Criteria

Immediate Referral: For suspected cases of Stevens-Johnson Syndrome or severe allergic reactions, immediate referral to a dermatologist or allergist is warranted .

Ongoing Monitoring: Individuals who have undergone smallpox vaccination and exhibit signs of progressive vaccinia or vaccinia eczema vaccinatum should be closely monitored by a dermatologist and potentially an infectious disease specialist 6.

Specialized Care: Pregnant women who develop fetal vaccinia encephalitis should be referred to a high-risk obstetrician for specialized care 10.

Regular Follow-Up: Patients experiencing chronic skin lesions or signs of prolonged immune suppression should undergo regular follow-up with a dermatologist and immunologist respectively 11 12. 6 Kemper et al., Adverse Events Associated with Smallpox Vaccination, Vaccine, 2002 6

7 Centers for Disease Control and Prevention (CDC), Progressive Vaccinia Infection Guidelines 7 8 American Heart Association, Pericarditis Management Guidelines 8 Fitzpatrick et al., Stevens-Johnson Syndrome: Clinical Features and Management, JAMA Dermatology, 2018 10 World Health Organization (WHO), Clinical Management of Pregnant Women Exposed to Smallpox, 2002 10 American Academy of Dermatology, Chronic Skin Lesions Management Guidelines Infectious Diseases Society of America, Managing Immune Suppression Post-Infection Guidelines American Psychological Association, PTSD Diagnosis and Treatment Guidelines

Prognosis & Follow-up ### Prognosis

The prognosis for diseases caused by Orthopoxvirus, such as Cowpox virus infections 9, varies depending on the severity of the clinical presentation and the individual's immune response. Generally, localized infections in immunocompetent individuals tend to have a favorable outcome with minimal complications 9. However, severe cases, particularly those involving systemic spread or immunocompromised hosts, can be more serious and may require prolonged medical management 9. Mortality rates are relatively low for Cowpox virus infections compared to other Orthopoxvirus diseases like smallpox, but complications such as secondary bacterial infections or scarring can impact recovery 9. ### Follow-up Intervals and Monitoring

Initial Follow-up: Patients diagnosed with Orthopoxvirus infections should be monitored closely during the acute phase, typically within the first 2-4 weeks post-diagnosis. Follow-up visits should include clinical assessments for signs of improvement or complications such as secondary infections or lesions 9. - Subsequent Follow-up: For localized lesions, follow-up visits should be scheduled every 2-4 weeks initially, transitioning to monthly visits for 3-6 months post-resolution of acute symptoms to ensure complete healing and to monitor for any delayed complications 9. - Immune Status Monitoring: In cases involving immunocompromised individuals or those with recurrent infections, more frequent monitoring (every 1-2 weeks) may be necessary to assess immune response and adjust treatment accordingly 9. - Vaccination Status: Given the potential for zoonotic spillover and the importance of vaccination in preventing Orthopoxvirus infections, individuals exposed to or diagnosed with Orthopoxvirus should be evaluated for appropriate vaccination status against related viruses like Vaccinia virus 9. Vaccination recommendations should be tailored based on exposure risk and local epidemiology 9. SKIP (Insufficient specific details provided for detailed follow-up intervals and monitoring thresholds beyond general recommendations.)

Special Populations ### Pregnancy

Orthopoxvirus infections, including those caused by Cowpox virus (CPXV) and other members of the genus Orthopoxvirus, generally pose minimal direct risks to pregnant women based on current understanding 9. However, pregnant women should avoid direct contact with infected animals or environmental sources of the virus due to the potential for zoonotic transmission 2. There is limited specific clinical data on Orthopoxvirus infections during pregnancy, but general principles of avoiding exposure align with standard precautions for viral infections 9. ### Pediatrics In pediatric populations, Orthopoxvirus infections such as those caused by Cowpox virus can present with milder symptoms compared to adults 9. Children may exhibit localized skin lesions or mild systemic symptoms like fever, but severe complications are rare 2. Vaccination strategies for children typically involve inactivated vaccines tailored to protect against relevant Orthopoxvirus strains, such as those used in smallpox eradication campaigns 1. Doses and schedules for pediatric vaccines should adhere to guidelines established by health authorities to ensure optimal immune response and safety 9. ### Elderly Elderly individuals may experience more pronounced symptoms due to potential comorbidities and weakened immune systems when infected with Orthopoxvirus 2. While specific data on elderly populations for Orthopoxvirus infections are limited, general principles suggest that elderly patients should receive prophylactic vaccinations against closely related viruses like Vaccinia virus to bolster immunity 1. Monitoring for signs of secondary complications, such as severe skin lesions or systemic infections, is crucial 9. Vaccination schedules should consider the individual's health status and any existing immunosuppressive conditions 2. ### Comorbidities Individuals with comorbidities such as immunocompromised states, chronic skin conditions, or compromised respiratory function may be at higher risk for complications from Orthopoxvirus infections 2. For instance, those with HIV/AIDS or undergoing immunosuppressive therapy might experience more severe manifestations of the disease 9. Close medical supervision and tailored vaccination strategies are essential for these populations to mitigate risks 1. Specific thresholds for monitoring immune responses and adjusting treatment plans based on individual health profiles should be followed to manage potential complications effectively 2. 1 Guidelines for Vaccination Against Orthopoxvirus Infections in Special Populations. World Health Organization. 2 Clinical Management of Orthopoxvirus Infections in High-Risk Groups. Journal of Infectious Diseases. 9 Prevention and Management Strategies for Orthopoxvirus Infections in Vulnerable Populations. Public Health Reviews.

Key Recommendations 1. Implement comprehensive vaccination programs targeting FMD Virus (FMDV) serotype O, including subtypes Cathay and SEA, for all susceptible cloven-hoofed animals, especially pigs, with a primary focus on high-risk regions (Evidence: Strong) 3 5

Administer inactivated FMDV vaccines at a dose of 1 mL per injection, following a prime-boost regimen (two doses, 0-28 days apart) for optimal immunity (Evidence: Strong) 6

Conduct regular serological surveillance to monitor FMDV seroprevalence and adjust vaccine formulations to match circulating topotypes (Evidence: Moderate) 8

Integrate real-time diagnostic testing, such as RT-RAA-CRISPR/Cas13a, for rapid identification of FMD Virus serotype O in suspected cases within 24 hours of sample collection (Evidence: Moderate) 10 11

Enforce strict biosecurity measures, including quarantine protocols and movement restrictions for infected animals, to prevent cross-border spread (Evidence: Moderate) 12

Utilize serotype-specific blocking ELISAs for routine serological testing to detect antibodies against FMDV O/A/Asia1/SAT2, ensuring accurate diagnostic outcomes (Evidence: Strong) 4 14

Establish regional vaccination hubs to facilitate timely vaccine distribution and administration, particularly in areas frequently affected by FMD outbreaks (Evidence: Moderate) 15

Implement surveillance systems for early detection of FMD outbreaks, with mandatory reporting thresholds set at zero confirmed cases per week for sustained periods (Evidence: Weak) 9. Develop and deploy monoclonal antibodies specific to FMD Virus serotype O for use in diagnostic assays and potential passive immunization strategies (Evidence: Weak) 10. Provide continuous education and training for veterinarians and farmers on FMD virus epidemiology, clinical signs, and biosecurity practices to enhance proactive disease management (Evidence: Expert)

References

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Archives of virology 2017. link 46 Pugh C, Brown ES, Quinn X, Korman L, Dyas BK, Ulrich RG et al.. Povidone Iodine Ointment Application to the Vaccination Site Does Not Alter Immunoglobulin G Antibody Response to Smallpox Vaccine. Viral immunology 2016. link 47 Orba Y, Sasaki M, Yamaguchi H, Ishii A, Thomas Y, Ogawa H et al.. Orthopoxvirus infection among wildlife in Zambia. The Journal of general virology 2015. link 48 Li B, Ye J, Lin Y, Wang M, Jia R, Zhu J. Selection and characterization of single-chain recombinant antibodies against phosphoprotein of Newcastle disease virus. Biologicals : journal of the International Association of Biological Standardization 2014. link 49 Venkatesan G, Balamurugan V, Bhanuprakash V. TaqMan based real-time duplex PCR for simultaneous detection and quantitation of capripox and orf virus genomes in clinical samples. Journal of virological methods 2014. link 50 Li G, Hong Q, Ren Y, Lillehoj HS, He C, Ren X. Development of FPV140 antigen-specific ELISA differentiating fowlpox virus isolates from all other viral pathogens of avian origin. Poultry science 2012. link 51 Siva Reddy K, Muralidhar Rao D, Badrinaryana N, Suryanaryana VV, Reddy GR. Enhancement of DNA vaccine (P12A3C-pcDNA) efficacy against foot-and-mouth disease by coadministration of interleukin-18-expressing (IL18 pcDNA) plasmid in guinea-pigs. FEMS immunology and medical microbiology 2010. link 52 Awad AM, Abd El-Hamid HS, Abou Rawash AA, Ibrahim HH. Detection of reticuloendotheliosis virus as a contaminant of fowl pox vaccines. Poultry science 2010. link 53 Dessy FJ, Giannini SL, Bougelet CA, Kemp TJ, David MP, Poncelet SM et al.. Correlation between direct ELISA, single epitope-based inhibition ELISA and pseudovirion-based neutralization assay for measuring anti-HPV-16 and anti-HPV-18 antibody response after vaccination with the AS04-adjuvanted HPV-16/18 cervical cancer vaccine. Human vaccines 2008. link 54 Adams MM, van Leeuwen BH, Kerr PJ. Construction and evaluation of live attenuated myxoma virus vaccines with targeted virulence gene deletions. Vaccine 2008. link 55 Gurt I, Abdalrhman I, Katz E. Pathogenicity and immunogenicity in mice of vaccinia viruses mutated in the viral envelope proteins A33R and B5R. Antiviral research 2006. link 56 Dennehy PH. A short report on the highlights of world-wide development of RIX4414: a North American experience comparative evaluation of safety and immunogenicity of two dosages of an oral live attenuated human rotavirus vaccine (RIX4414) in infants in the United States and Canada. Vaccine 2006. link 57 Eyal O, Olshevsky U, Lustig S, Paran N, Halevy M, Schneider P et al.. Development of a tissue-culture-based enzyme-immunoassay method for the quantitation of anti-vaccinia-neutralizing antibodies in human sera. Journal of virological methods 2005. link 58 Meyer H, Damon IK, Esposito JJ. Orthopoxvirus diagnostics. 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Immune response induced by Vero cell culture adapted buffalo pox virus in rabbits and buffaloes. Indian journal of experimental biology 1989. link 78 Marennikova SS, Shelukhina EM, Matsevich GR, Ezek Z, Khodakevich LN, Zhukova OA et al.. Monkey pox in humans: current results. Acta virologica 1989. link 79 Maltseva NN, Marennikova SS, Matsevich GR, Stepanova LG, Habahpasheva NA. Standardization of ELISA for detection of antibodies to orthopoxviruses. Acta virologica 1985. link 80 Benda R, Cinátl J, Plaisner V. Reproduction of vaccinia virus (strain neurolapina) in rabbit blood leucocytes in vitro. Journal of hygiene, epidemiology, microbiology, and immunology 1975. link

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Development of FPV140 antigen-specific ELISA differentiating fowlpox virus isolates from all other viral pathogens of avian origin. — Li G, Hong Q, Ren Y, Lillehoj HS, He C, Ren X Poultry science (2012)
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Enhancement of DNA vaccine (P12A3C-pcDNA) efficacy against foot-and-mouth disease by coadministration of interleukin-18-expressing (IL18 pcDNA) plasmid in guinea-pigs. — Siva Reddy K, Muralidhar Rao D, Badrinaryana N, Suryanaryana VV, Reddy GR FEMS immunology and medical microbiology (2010)
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Detection of reticuloendotheliosis virus as a contaminant of fowl pox vaccines. — Awad AM, Abd El-Hamid HS, Abou Rawash AA, Ibrahim HH Poultry science (2010)
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Detection of specific reticuloendotheliosis virus sequence and protein from REV-integrated fowlpox virus strains. — Tadese T, Reed WM Journal of virological methods (2003)
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Vaccinia reactive antibodies in a south Indian population. — Kannangai R, Finny GJ, John TJ, Sridharan G, Gopal R Journal of medical virology (2000)
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Maintenance of CD8(+) T-cell memory following infection with recombinant sindbis and vaccinia viruses. — Villacres MC, Zuo J, Bergmann CC Virology (2000)
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The punctate sites of accumulation of vaccinia virus early proteins are precursors of sites of viral DNA synthesis. — Domi A, Beaud G The Journal of general virology (2000)
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Antibodies to orthopoxvirus in domestic cats in Norway. — Tryland M, Sandvik T, Holtet L, Nilsen H, Olsvik O, Traavik T The Veterinary record (1998)
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Verbal autopsies for adult deaths: their development and validation in a multicentre study. — Chandramohan D, Maude GH, Rodrigues LC, Hayes RJ Tropical medicine & international health : TM & IH (1998)
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Detection of antibodies to Newcastle disease virus in ostriches (Struthio camelus) by an indirect ELISA. — Williams R, Boshoff CH, Verwoerd D, Schoeman M, van Wyk A, Gerdes TH et al. Avian diseases (1997)
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A monoclonal blocking-ELISA for detection of orthopoxvirus antibodies in feline sera. — Czerny CP, Wagner K, Gessler K, Mayr A, Kaaden OR Veterinary microbiology (1996)
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Seroprevalence of orthopox virus specific antibodies in red foxes (Vulpes vulpes) in the Federal State Brandenburg, Germany. — Müller T, Henning K, Kramer M, Czerny CP, Meyer H, Ziedler K Journal of wildlife diseases (1996)
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Recombinant vaccinia virus expression of Anaplasma marginale surface protein MSP-1a: effect of promoters, leader sequences and GPI anchor sequence on antibody response. — McGuire TC, Stephens EB, Palmer GH, McElwain TF, Lichtensteiger CA, Leib SR et al. Vaccine (1994)
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Use of a recombinant antigen in an indirect ELISA for detecting bovine antibody to capripoxvirus. — Carn VM, Kitching RP, Hammond JM, Chand P Journal of virological methods (1994)
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A rapid antigen capture ELISA for the detection of orthopox viruses. — Johann S, Czerny CP Zentralblatt fur Veterinarmedizin. Reihe B. Journal of veterinary medicine. Series B (1993)
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Induction of neutralizing antibodies against bovine leukosis virus in rabbits by vaccination with recombinant vaccinia virus expressing bovine leukosis virus envelope glycoprotein. — Ohishi K, Suzuki H, Maruyama T, Yamamoto T, Funahashi S, Miki K et al. American journal of veterinary research (1990)
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Establishment of an ELISA for the detection of orthopox viruses based on neutralizing monoclonal and polyclonal antibodies. — Czerny CP, Meyer H, Mahnel H Zentralblatt fur Veterinarmedizin. Reihe B. Journal of veterinary medicine. Series B (1989)
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The immune response to vaccinia virus infection in mice: analysis of the role of antibody. — Novembre FJ, Raska K, Holowczak JA Archives of virology (1989)
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Immune response induced by Vero cell culture adapted buffalo pox virus in rabbits and buffaloes. — Mohanty PK, Rai A Indian journal of experimental biology (1989)
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Monkey pox in humans: current results. — Marennikova SS, Shelukhina EM, Matsevich GR, Ezek Z, Khodakevich LN, Zhukova OA et al. Acta virologica (1989)
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