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02 Inclusion Body Disease
Photo shows a large python showing signs of inclusion body disease, including opisthotonus where there is hyperextension of neck and back. Image reproduced with permission from Douglas R. Mader, originally published on Reptiles Magazine, 2014. Used with permission.  
Photo shows an 8-month-old albino Boa imperator exhibiting suspected stargazing behavior, a clinical sign that may indicate inclusion body disease. Image by u/aamutossu, posted on Reddit,  2024. Used with permission.

Known Species Affected:
Acranthophis madagascariensis
Boa constrictor
Bothriechis marchi
Corallus annulatus
Corallus hortulanus
Elaphe guttata
Eunectes murinus
Eunectes notaeus
Epicrates cenchris
Epicrates striatus
Lampropeltis getula
Morelia spilota variegata
Morelia spilota
Python bivittatus
Python molurus
Python reticulatus
Python regius
(Chang et al., 2010; Fleming et al., 2003; Hetzel et al., 2013; Raymond et al., 2001) Cause of the Disease

Inclusion body disease (IBD) is a viral disease caused by infection with reptarenaviruses. The genus Reptarenavirus, within the family Arenaviridae, is an enveloped single-stranded RNA virus that is typically spherical or displaying shape variability (i.e., plomorphism), with particles ranging from 40 to 200 nm in diameter [5]. These viruses primarily affect snakes in the families Boidae and Pythonidae [11]. Infected snakes may carry genetically diverse reptarenaviruses, which may influence disease severity [5].

IBD is characterized by the formation of inclusion bodies in multiple organs [5]. As with many viral infections, viruses can disrupt normal cellular function and damage tissues in their hosts. In IBD, viral nucleoproteins accumulate in infected cells, leading to the formation of inclusion bodies. The continued formation of inclusion bodies interferes with normal cellular processes over time, potentially leading to increasing cellular damage [3]. This progressive cellular disruption likely contributes to the progressive and chronic nature of the disease [6].

History

Inclusion body disease was first reported in the United States in the 1970s, based on samples collected from different captive snake species, including boa constrictors and Burmese pythons (Python bivittatus) [13]. During this time, the species Burmese pythons were the most susceptible to IBD, but in the 1990s, the number of cases that primarily affected boa constrictors increased [6]. For many years, the causative agent of IBD remained unidentified, and research focused mainly on the histopathological finding of cytoplasmic inclusion bodies. Further advances in molecular diagnostics during the 2010s led to the identification of arenaviruses as the primary cause of the disease, with the genus Reptarenavirus being formally described in 2015 [1].

The disease has been reported mainly in captive snakes from North America, Europe, Asia, Australia, Brazil, and Costa Rica; however, a study by Alfaro-Alarcón and colleagues (2022) in Costa Rica confirmed that IBD can occur in wild boa constrictors [2]. This study additionally found that wild boa constrictors have been affected since the 1980s. This has increased recognition and investigation of the disease.

Clinical Signs and Progression

Figure 1.  Captive annulated tree boa (C. annulatus) with inclusion body disease. (A,B) Brain steam with cytoplasmic inclusion bodies in neurons.  (C) Epithelial cells in pancreas with inclusion bodies.  Right image  of C is cells with diffuse cytoplasmic viral antigen expression. (D) Hepatocytes in liver with inclusion bodies. (E) Red blood cells with inclusion bodies as indicated by arrowheads. Hemogregarine infection shown through arrow.

Note. from Alfaro-Alarcón et al. (2022),  Boid inclusion body disease is also a disease of wild boa constrictors, licensed under CC BY 4.0.   http://creativecommons.org/licenses/by/4.0/
The severity of inclusion body disease differs between boas and pythons. However, both groups exhibit clinical signs, including neurological signs, regurgitation, lymphoproliferative disorder (an abnormal number of lymphocytes, a type of white blood cell), and secondary infections (e.g., pneumonia, hepatitis, or enteritis). In most studies, snakes are euthanized after progressive decline with infection by reptarenavirus identified, as the disease is usually fatal.

Infected boas may remain clinically healthy with no observable symptoms for some time following infection. A study by Stenglein and colleagues (2017) reported that clinical signs in a boa with IBD first appeared 2 years after infection.

Infected pythons appear to be more susceptible and typically develop these same clinical signs more rapidly and are more fatal. The same study by Stenglein and colleagues (2017) reported clinical signs in pythons within just 2 months of infection. Although inclusion bodies were not as common as in boas, inflammation was, however. Inflammation was found in the brain, spinal cord, and ganglia.

Symptoms may include head tremors, unequal pupil size, disorientation, opisthotonus (an abnormal posture caused by hyperextension of muscles, “stargazing”), anorexia, and lethargy. Inclusion bodies are widely present across multiple tissues (Figure 1). Additionally, paralysis affecting the majority of their body can occur [2,10,15,16].

Transmission and Epidemiology

Figure 2.  Boa constrictor, part of the Boidae family, at Hartleys Crocodile Adventures in Australia. Photo by David Clode on Unsplash.
Figure 3. Huge Python reticulatus, part of the Pythonidae family. Photo by David Clode on Unsplash. 
 As mentioned previously, snakes of the families Boidae and Pythonidae are most commonly affected by inclusion body disease (Figure 2 and 3). However, infection has also been suspected in snakes from other families, including corn snakes (Elaphe guttata) and palm vipers (Bothriechis marchi) [8,12]. Additionally, multiple reptarenavirus species have been shown to collectively infect a single snake [9,16]. Given the complexity of diverse host susceptibility and coinfection, understanding the routes of transmission is crucial.

Research on the routes of IBD transmission is very limited. Some suggest that IBD transmission may involve direct or indirect contact with an infected snake or with other potential carriers of the disease, including skin, saliva, or stool. This also includes vector-mediated transmission via snake mites (Ophionyssus natricis), blood-sucking ectoparasites. Additionally, vertical transmission (i.e., parent to offspring) could represent another form of infection [1,4,6,10]. As the majority of the cases involved captive snakes, this raises concern about the role of trade and smuggling in disease spread. In 2018, of the 20,000 snakes transported globally, 6,600 were pythonids, and 3,100 were boids [2]. The ability of some snakes to remain asymptomatic could pose a greater challenge to identifying potential cases and managing the spread.

Diagnosis
The testing for inclusion body disease evolved, with the principal tests involving cytological and histopathological examination and laboratory analysis. Before the discovery of the disease's causative agent, the presence of inclusion bodies was the only way to detect infection. Testing for inclusion bodies includes the microscopic evaluation of peripheral blood smears, particularly erythrocytes and white blood cells [14,16]. Other sites include samples from the brain, liver, kidney, reproductive and respiratory tract, spleen, pancreas, and intestines. These samples can be obtained as biopsies before or after death and undergo a complete postmortem examination [1,7]. However, as mentioned before, inclusion bodies are not always present in snakes with IBD or reptarenaviruses [15].

Modern molecular diagnostics use RT-PCR (Reverse-Transcription-Polymerase Chain Reaction), which converts RNA into complementary DNA. This is then amplified and specific sequences identified using PCR on the same type of samples used for inclusion body detection [14,16].

Samples from oropharyngeal and cloacal regions of snakes are also collected for analysis for bacteria or parasites, as IBD can be vulnerable to secondary infections [7,14] While specialists perform these tests in a lab setting, the earliest possible detection of inclusion body disease comes from observational reports of behaviors that mostly represent neurological signs [15].

Treatment and Prevention

There are no known antiviral medications or cures for inclusion body disease. IBD is described as a progressive and usually fatal disease whose solution for the worst cases could tend to be euthanization [10].

If there is a suspected case of IBD, then the individual should be isolated and quarantined until proven otherwise. It is highly recommended to clean the spaces of these individuals with disinfectants such as bleach to prevent transmission [6]. Additionally, owners should also place newly acquired snakes in quarantine as a precaution for contamination. The early identification of this disease should be the top priority [6,14]. The identification and control of snake mites can also help manage IBD, as they are potential carriers of the disease [1]. Although there is no single answer to treating IBD, the public, can play a role in containing its spread and raising our voices for the research needed to advance treatment.

Further Research

Additional research is needed to fill significant knowledge gaps. This includes the correlation between the formation of inclusion bodies and the ability of reptarenaviruses to cause disease. As well as understanding the transmission methods. Compared with other well-studied animals, the reptilian immune system is very understudied [16]. This could continue to limit our ability to understand the pathogenesis and treatment of inclusion body disease.

Readings

1.Alfaro-Alarcón, A., Hetzel, U., Smura, T., Baggio, F., Morales, J. A., Kipar, A. & Hepojoki, J. (2022). Boid inclusion body disease is also a disease of wild boa constrictors. Microbiology Spectrum, 10, 5. https://doi.org/10.1128/spectrum.01705-22

2. Argenta, F. F., Hepojoki, J., Smura, T., Szirovicza, L., Hammerschmitt, M. E., Driemeier, D., Kipar, A. & Hetzel, U. (2020). Identification of reptarenaviruses, hartmaniviruses, and a novel chuvirus in captive native Brazilian boa constrictors with boid inclusion body disease. Journal of Virology, 94(11). https://doi.org/10.1128/JVI.00001-20

3. Baggio, F., Hetzel, U., Nufer, L., Kipar, A. & Hepojoki, J. (2021). A subpopulation of arenavirus nucleoprotein localizes to mitochondria. Scientific Reports, 11, 21048. https://doi.org/10.1038/s41598-021-99887-5

4. Baggio, F., Hetzel, U., Prähauser, B., Dervas, E., Michalopoulou, E., Thiele, T., Kipar, A., & Hepojoki, J. (2023). A multiplex RT-PCR method for the detection of reptarenavirus infection. Viruses, 15(12), 2313. https://doi.org/10.3390/v15122313

5. Berbic, I. K., Neck, S. D., Ressel, L., Michalopoulou, E., Kipar, A., Hepojoki, J., Hetzel, U., & Baggio, F. (2025). Temperature affects reptarenavirus growth in a permissive hostderived in vitro model. Journal of General Virology, 106(4). https://doi.org/0.1099/jgv.0.002100

6. Chang, L. W. & Jacobson, E. R. (2010). Inclusion body disease, a worldwide infectious disease of boid snakes: a review. Journal of Exotic Pet Medicine, 19(3), 216-225. https://doi.org/10.1053/j.jepm.2010.07.014

7. Dervas, E., Michalopoulou, E., Hepojoki, J., Thiele, T., Baggio, F., Hetzel, U. & Kipar, A. (2025). Haemolymphatic tissues of captive boa constrictor (Boa constrictor): Morphological features in healthy individuals and with boid inclusion body disease. Developmental & Comparative Immunology, 162, 105302. https://doi.org/10.1016/j.dci.2024.105302

8. Fleming, G. J., Heard, D. J., Jacobson, E. R. & Buergelt, C. (2003). Cytoplasmic inclusions in corn snakes, Elaphe guttata, resembling inclusion body disease of boid snakes. Journal of Herpetological Medicine and Surgery, 13(2), 18-22. https://doi.org/10.5818/1529-9651.13.2.18

9. Hepojoki, J., Salmenperä, P., Sironen, T., Hetzel, U., Korzyukov, Y., Kipar, A. & Vapalahti, O. (2015). Arenavirus coinfections are common in snakes with boid inclusion body disease. Journal of Virology, 89. https://doi.org/10.1128/jvi.01112-15

10. Hetzel, U., Sironen, T., Laurinmäki, P., Liljeroos, L., Patjas, A., Henttonen, H., Vaheri, A., Artelt, A., Kipar, A., Butcher, S. J., Vapalahti, O. & Hepojoki, J. (2013). Isolation, identification, and characterization of novel arenaviruses, the etiological agents of boid inclusion body disease. Journal of Virology, 87, 10918-10935. https://doi.org/10.1128/jvi.01123-13

11. Radoshitzky, S. R., Buchmeier, M. J., Charrel, R. N., Gonzalez, J. J., Günther, S., Hepojoki, J., Kuhn, J. H., Lukashevich, I. S., Romanowski, V., Salvato, M. S., Sironi, M., Stenglein, M. D. & Torre, J. C. (2023). ICTV virus taxonomy profile: Arenaviridae 2023. Journal of General Virology, 104, 001891. https://ictv.global/report/chapter/arenaviridae/arenaviridae

12. Raymond, J. T., Garner, M. M., Nordhausen, R. W. & Jacobson, E. R. (2001). A disease resembling inclusion body disease of boid snakes in captive palm vipers (Bothriechis marchi). Journal of Veterinary Diagnostic Investigation, 13(1), 82-86. https://doi.org/10.1177/104063870101300118

13. Schumacher, J., Jacobson, E. R., Homer, B. L., & Gaskin, J. M. (1994). Inclusion Body Disease in Boid Snakes. Journal of Zoo and Wildlife Medicine, 25(4), 511–524. http://www.jstor.org/stable/20095411

14. Simard, J., Marschang, R. E., Leineweber, C. & Hellebuyck, T. (2020). Prevalence of inclusion body disease and associated comorbidity in captive collections of boid and pythonid snakes in Belgium. PLoS ONE, 15(3). https://doi.org/10.1371/journal.pone.0229667

15. Stenglein, M. D., Guzman, D. S. M., Garcia, V. E., Layton, M. L., Hoon-Hanks, L. L., Boback, S. M., Keel, M. K., Drazenovich, T., Hawkins, M. G. & DeRisi, J. L. (2017). Differential disease susceptibilities in experimentally reptarenavirus-infected boa constrictors and ball pythons. Journal of Virology, 91(15). https://doi.org/10.1128/jvi.00451-17

16. Windbichler, K., Michalopoulou, E., Palamides, P., Pesch, T., Jelinek, C., Vapalahti, O., Kipar, A., Hetzel, U. & Hepojoki, J. (2019). Antibody response in snakes with boid inclusion body disease. PLoS ONE, 14(9). https://doi.org/10.1371/journal.pone.0221863