Contact
Colubridae
Crotalidae
Elapidae
Viperidae
Boidae
Pythonidae
(Hyndman et al., Su et al., 2020; Pees et al., 2019)
Ferlaviruses, formally referred to as ophidian paramyxovirus, cause viral infections that affect various species of snakes, most commonly colubrids, crotalids, boids, viperids, elapids, and pythonids [5,14,18]. These viruses belong to the genus Ferlavirus within the family Paramyxoviridae. These are described as enveloped, negative-sense, single-stranded RNA viruses.
As a negative-sense RNA virus, ferlaviruses must first transcribe its genome into a form that the host cell can use before replication can occur. Viral replication is most commonly observed in respiratory tissue, leading to inflammation, cellular damage, and a disruption of airway function. These contribute to its classification as a respiratory disease and to its vulnerability to secondary infections [10,14,19]. It replicates optimally at 28-30 °C [9].
Ferlaviruseses have also been observed to exhibit hemagglutination (i.e., clumping of red blood cells) and neuraminidase (i.e., preventing newly formed viruses from sticking to the same cell, which allows infection to spread more easily) activity [5,9].
History
Although the exact origin of ferlaviruses remains unknown, the first recorded outbreak occurred in 1972 in a Switzerland serpentarium. This infection was initially called the fer-de-lance virus after the deaths of captive fer-de-lance vipers (Bothrops moojeni) [14,16,18]. The name was later changed to ophidian paramyxovirus, but this term is currently avoided since the creation of the genus Ferlavirus. Ophidian paramyxovirus is the general term, but confusion can arise as multiple diseases can fall under it [5].
The first reported case in the United States occurred in Florida in 1980, when suspected paramyxovirus infection cases were identified in rock rattlesnakes exhibiting characteristics similar to those of fer-de-lance virus [6]. In Louisiana, around the 1990s, a similar situation occurred in which the majority of snakes in an exhibit collection were found dead, linked to paramyxovirus infection [7]. Both cases were highlighted due to the lack of quarantine for captive snakes placed on exhibit [6,7]. Most recently, in 2012, an outbreak at the Phoenix Zoo in Arizona was associated with a genotype C Ferlavirus infection [11].
The reported cases of possible or confirmed ferlaviruses infection are predominantly seen in captive snakes; however, wild snakes are also known to be affected by this virus. For instance, in South Florida, a free-range eastern indigo snake presenting with no clinical signs was found to harbor genotype C Ferlavirus [3]. Additional cases of wild snakes infected with ferlaviruses have been reported; however, the method used to detect the causative agent is unreliable [1,2,4]. Because detecting this viral disease in wild snake populations is difficult, continued surveillance and testing are needed before the disease becomes more severe.
Clinical Signs and Progression
Clinical signs of ferlaviruses infection vary in severity and are often non-specific. Infection is, however, closely associated with respiratory tract signs, but it may also affect other organs, including the liver, small intestine, pancreas, brain, and kidneys. Microscopic changes in these organs could include the presence of intracytoplasmic inclusion bodies, necrosis, or giant cell formation.
Non-specific signs include regurgitation, anorexia, lethargy, and foul-smelling or mucus in stool [5,13,14]. Infected snakes have also shown no clinical signs before passing away [3].
Clinical signs associated with the respiratory tract include nasal discharge (i.e., including clear, brownish, or bloody), mouth discharge (i.e., including clear mucus, brownish, or bloody), stomatitis (“mouth rot”), dyspnea (i.e., shown as mouth gaping or mouth breathing), and pneumonia [5,17,18]. Additional signs at a deeper level or on microscopic examination of the tissue include inflammation, lung lesions, tissue thickening, lung congestion, and pulmonary edema [5,13,18]. Not as common, pale eosinophilic intracytoplasmic inclusion bodies can be found in lung epithelial cells. Airways were also found to be full of exudate and cellular debris [5].
Neurological signs included head tremors, apathy, and flaccid paralysis [17,5]. Microscopic signs observed on pathological examination included demyelination and degeneration of axon fibers, ballooning of axon sheaths, and perivascular cuffing in the brain [5].
Transmission and Epidemiology
Ferlaviruses are highly contagious [15]. The disease can spread through direct contact with infected snakes and exposure to respiratory secretions, including nasal, oral, or cloacal discharge [16]. Facilities where snakes are housed in proximity are especially vulnerable to rapid spreads and outbreaks. Animal trade and the transport of fresh raw meat can serve as additional routes for introducing ferlaviruses into a new snake population. Currently, no reports support the vertical transformation (i.e., transfer of infection from parent to offspring) of ferlaviruses. [15].
Ferlaviruses are found globally, including Europe, Costa Rica, Brazil, the United States, and Asia [5,15,16,18]. Multiple ferlavirus genogroups have also been identified, including genogroups A, B, and C, and strains vary in virulence and snake host range. Various reptilian species, such as lizards and chelonians, have been reported to contain ferlavirus (Figure 1 and 2) [12]. Cross-infection between different reptile species has been documented, increasing their vulnerability and spread of disease [13].
Diagnosis
As with other disease diagnoses, polymerase chain reaction (PCR) is the gold standard for identifying Ferlavirus. This laboratory test is commercially available and specifically requires reverse transcriptase PCR, which converts the viral RNA into complementary DNA before amplification [5,8]. Another commercially available laboratory test is the hemagglutination inhibition assay, which detects antibodies in blood samples, but accuracy and reliability can decrease over time [12]. The serology method is considered complex and not a sole reliable test for ferlavirus infection [3].
Histological changes can be observed using a light microscope and a transmission electron microscope. Although there are no specific histological signs related to ferlavirus infection, the respiratory and neurological systems are closely examined. Samples for examination were obtained from the lung, liver, kidney, pancreas, brain, and gonads. Cloacal and oral swabs were also collected and tested for ferlavirus and other pathogens (e.g., bacterial and fungal) [17].
Treatment and Prevention
Despite research efforts dating back to the late 1980s, there remains no vaccine or treatment for ferlavirus infection. Given the high risk of transmission among snakes housed in proximity, both clinically ill snakes and newly acquired snakes should be quarantined. Quarantine should last at least 90 days. Additional precautions include regularly disinfecting cages and equipment, especially those of an infected individual, with 0.15% sodium hypochlorite. Areas that came into close contact with an infected snake should be avoided for a minimum of two weeks before being used again. The most critical preventive strategy for limiting transmission and protecting snake populations is early pathogen detection, a process in which the public could play a key role by reporting suspected cases [18,7].
Further Research
Although progress has been made, important aspects of ferlavirus infection, including treatment strategies and transmission dynamics, remain unclear and require further investigation. Specifically, limited data exist on shedding kinetics, the virus’s ability to survive in the environment outside of the host, pathogenicity between the different genotypes, appropriate sampling times and sample types, and the role of ectoparasites and endoparasites in transmission [5,12]. Long-term monitoring and reporting efforts are vital for maintaining population stability and for managing infectious diseases in snakes.
Readings
1. Allender, M. C., Mitchell, M. A., Dreslik, M. J., Phillips, C. A. & Beasley, V. R. (2008). Measuring agreement and discord among hemagglutination inhibition assays against different ophidian paramyxovirus strains in the Eastern massasauga (Sistrurus catenatus catenatus). Journal of Zoo and Wildlife Medicine, 39(3), 358-361. https://doi.org/10.1638/2007-0111.1
2. Allender, M. C., Mitchell, M. A., Phillips, C. A., Gruszynski, K. & Beasley, V. R. (2006). Hematology, plasma biochemistry, and antibodies to select viruses in wild-caught Eastern massasauga rattlesnakes (Sistrurus catenatus catenatus). Journal of Wildlife Diseases, 42(1), 107-114. https://doi.org/10.7589/0090-3558-42.1.107
3. Bogan, J. E. Jr., O'Hanlon, B. M., Steen, D. A., Horan, T., Taylor, R., Mason, A. K., Breen, T., Andreotta, H., Cornelius, B., Childress, A. & Elmore, M. (2024). Health assessment of free-ranging eastern indigo snakes (Drymarchon couperi) from hydrologic restoration construction sites in South Florida, USA. Journal of Wildlife Diseases, 60(1), 39-51. https://doi.org/10.7589/JWD-D-22-00184
4. Calle, P. P., Rivas, J., Muñoz, M., Thoebjarnarson, J., Holmstrom, W. & Karesh, W. B. (2001). Infectious disease serologic survey in free-ranging Venezuelan anacondas (Eunectes murinus). Journal of Zoo and Wildlife Medicine, 32(3), 320-323. https://doi.org/10.1638/1042-7260(2001)032[0320:IDSSIF]2.0.CO;2
5. Hyndman, T. H., Shilton, C. M. & Marschang, R. E. (2013). Paramyxoviruses in reptiles: A review. Veterinary Microbiology, 165(3-4), 200-213. https://doi.org/10.1016/j.vetmic.2013.04.002
6. Jacobson, E., Gaskin, J. M., Simpson, C. F. & Terrell, T. G. (1980). Paramyxo-like virus infection in a rock rattlesnake. Journal of the American Veterinary Medical Association, 177(9), 796-799. https://doi.org/10.2460/javma.1980.177.09.796
7. Jacobson, E. R., Gaskin, J. M., Wells, S., Bowler, K. & Schumacher, J. (1992). Epizootic of ophidian paramyxovirus in a zoological collection: pathological, microbiological, and serological finding. Journal of Zoo and Wildlife Medicine, 23(3), 318-327. https://www.jstor.org/stable/pdf/20095233.pdf
8. Kolesnik, E., Hyndman, T. H., Müller, E., Pees, M. & Marschang, R. E. (2019). Comparison of three different PCR protocols for the detection of ferlaviruses. BMC Veterinary Research, 15, 281. https://doi.org/10.1186/s12917-019-2028-0
9. Kurath, G., Batts, W. N., Ahne, W. & Winton, J. R. (2004). Complete genome sequence of fer-de-lance virus reveals a novel gene in reptilian paramyxoviruses. Journal of Virology, 78(4),2045-2056. https://doi.org/10.1128/jvi.78.4.2045-2056.2004
10. Papp, T., Gál, J., Abbas, M. D., Marschang, R. E. & Farkas, S. L. (2013). A novel type of paramyxovirus found in Hungary in a masked water snake (Homalopsis buccata) with pneumonia supports the suggested new taxonomy within the Ferlavirus genus. Veterinary Microbiology, 162 (1), 195-200. https://doi.org/10.1016/j.vetmic.2012.08.010
11. Pastor, A. R., West, G., Swenson, J., Garner, M. M., Childress, A. L. & Wellehan, J. F. X. Jr. Cross-species transmission of a genogroup c Ferlavirus in a zoological collection in the United States. Journal of Zoo and Wildlife Medicine, 56(1), 184-192. https://doi.org/10.1638/2023-0123
12. Pees, M., Möller, A., Schmidt, V., Schroedl, W. & Marschang, R. E. (2023). The role of host species in experimental ferlavirus infection: Comparison of a single strain in ball pythons (Python regius) and corn snakes (Pantherophis guttatus). Animals, 13, 2714. https://doi.org/10.3390/ani13172714
13. Pees, M., Neul, A., Müller, K., Schmidt, V., Truyen, U., Leinecker, N. & Marschang, R. E. (2016). Virus distribution and detection in corn snakes (Pantherophis guttatus) after experimental infection with three different ferlavirus strains. Veterinary Microbiology, 182, 213-222. https://doi.org/10.1016/j.vetmic.2015.11.024
14. Pees, M., Schmidt, V., Papp, T., Gellért, A., Abbas, M., Starck, J. M., Neul, A. & Marschang, R. E. (2019). Three genetically distinct ferlaviruses have varying effects on infected corn snakes (Pantherophis guttatus). PLoS ONE, 14(6). https://doi.org/10.1371/journal.pone.0217164
15. Piewbang, C., Wardhani, S.W., Poonsin, P., Yostawonkul, J., Chai-in, P., Lacharoje, S., Saengdet, T., Vasaruchapong, T., Boonrungsiman, S., Kongmakee, P., Banlunara, W., Rungsipipat, A., Kasantikul, T. & Techangamsuwan, S. (2021). Epizootic reptilian ferlavirus infection in individual and multiple snake colonies with additional evidence of the virus in the male genital tract. Scientific Reports, 11,12731. https://doi.org/10.1038/s41598-021-92156-5
16. Solis, C., Arguedas, R., Baldi, M., Piche, M. & Jimenez, C. (2017). Seroprevalence and molecular characterization of Ferlavirus in captive vipers of Costa Rica. Journal of Zoo and Wildlife Medicine, 48(2), 420-430. https://doi.org/10.1638/2014-0200R4.1
17. Starck, J. M., Neul, A., Schmidt, V., Kolb, T., Franz-Guess, S., Balcecean, D. & Pees, M. (2017). Morphology and morphometry of the lung in corn snakes (Pantherophis guttatus) infected with three different strains of ferlavirus. Journal of Comparative Pathology, 156(4), 419-435. https://doi/org/10.1016/j.jcpa.2017.02.001
18. Su, J. Y., Li, J., Que, T. C., Chen, H. L. & Zeng, Y. (2020). Detection and molecular epidemiology of ferlaviruses in farmed snakes with respiratory disease in Guangxi Province, China. Journal of Veterinary Diagnostic Investigation, 32(3)429-434. https://doi.org/10.1177/1040638720911023
19. Warncke, S. R. & Knudsen, C. R. (2021). Detection methods targeting the positive- and negative-sense RNA transcripts from plus-stranded RNA viruses. APMIS, 130(5), 284-292. https://doi.org/10.1111/apm.13202