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01 Fibropapillomatosis

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Known Species Affected:
Caretta caretta
Chelonia mydas
Dermochelys coriacea
Eretmochelys imbricata
Lepidochelys kempii
Lepidochelys olivacea
Natator depressus

(Manes et al., 2023b; Rittenburg et al., 2021) Cause of Disease

Fibropapillomatosis (FP) is a disease that causes tumors and affects all seven species of sea turtles. However, research has shown that green sea turtles (Chelonia mydas) and juvenile turtles are particularly vulnerable to FP. The location of both external and internal tumors varies among individuals, and their effects can significantly diminish quality of life and, in some cases, reduce survival rates.

FP is associated with a herpesvirus infection, with Chelonid herpesvirus 5 (ChHV5) as the primary causative agent [5,6,17]. ChHV5 is a linear double-stranded deoxyribonucleic acid (DNA) virus belonging to the subfamily Alphaherpesvirinae and the genus Scrutavirus [3]. Multiple variants of ChHV5 are present in different geographic regions and can co-infect an individual. For example, variants A, B, C, and D have been found in waters around Florida [5].

Tumor formation is not solely caused by ChHV5 infection, and not all turtles with the virus exhibit tumors. Additional viral agents have been detected in the tumor tissues of turtles with FP, including: Chelonia mydas papillomavirus 1 (CmPV1) and sea turtle tornovirus (STTV1). However, their precise role in disease pathogenesis remains unclear. Additionally, FP demonstrates molecular features consistent with neoplastic disease, including altered gene expression and dysregulation of oncogenic signaling pathways, supporting parallels with human cancers [3,17]. These findings further support the characterization of FP as a complex, multifactorial disease, with tumor initiation and progression by environmental, microbial, and host immune factors [10].

History

The first case of FP was documented in 1938 by Smith and Coates from green sea turtles in Key West, Florida. Before the causative agent, Chelonid herpesvirus 5 (ChHV5), was identified, it was known as the chelonid fibropapilloma-associated herpesvirus (C-FP-HV). Reports noted the presence of growths in the neck, axillae, groin, and eyelid regions. However, the microscopic examination of their lesions was very similar to that of a previous case involving a single green sea turtle from a New York Aquarium that presented with multiple warts. Two years before being transported to the New York Aquarium, this turtle was originally from Key West, Florida [16].

In the 1980s, cases of FP became more common and better known worldwide. The most affected regions in the United States were Florida and Hawaii [4, 15]. However, in 2010, Texas reported tumors and suspected growths relating to FP in green sea turtles. To address concerns that FP may have been underreported before 2010, the Sea Turtle Stranding and Salvage Network and researchers established ongoing surveillance of turtle populations in Texas. In 2015, cases of FP within green turtles increased at an alarming rate [9,15]. Over time, it became evident that all seven species of sea turtles can be affected [5].

Clinical Signs and Progression

FP is characterized by the development of tumors that may occur internally or externally throughout the body. External tumors can occur on the skin, mouth, eyes, flippers, and shell. Internal organs could also be affected, including the lungs, kidneys, esophagus, heart, spleen, and liver [8,14]. The clinical signs of FP can cause weakness and overall physiological compromise, as FP tumors can disrupt growth, reproduction, vision, breathing, digestion, predator avoidance, and mobility [7,12,14].

FP tumors present with a variety of morphological appearances. They may be pedunculated (i.e., attached by a thin stalk or stem) or sessile (i.e., directly attached) in shape and may have smooth or rugose surfaces (Figure 1) [7,10]. Additional classifications include white, pink, brown, dark grey, or black pigments. Additionally, studies on tumors in juvenile and adult green turtles suggest a correlation between tumor texture and stage, with growing tumors having a rugose texture and regressed tumors having a smooth texture (Figure 1) [7].

The number of FP tumors presented on a single turtle can vary, for example Page-Karjian et al., 2021 found 1-11 tumors per turtles on Kemp’s ridley turtles with FP and Rossi et al., 2016 reported 1-129 tumors in green sea turtles with FP in Brazil. Tumor diameters also vary significantly between individuals, ranging from 0.1cm to greater than 30cm in diameter [2]. Tumors have been observed to recur after appearing to resolve. However, the appeareance of tumors is not always present in ChHV5 infection. Microscopic examination of the tumors show irregular growth of the connective tissue beneath the skin along with a thickened outer skin layer. This causes the raised, rough, or smooth growths seen on sea turtles infected with FP  [5,10,11].

Transmission and Epidemiology

The most commonly affected individuals are green sea turtles. Green sea turtles primarily inhabit coastal habitats and have a global distribution across tropical and subtropical regions. FP infection is most frequently observed in juvenile turtles as they move into coastal foraging grounds and is predominantly found in warm tropical waters [14,10]. ChHV5 can spread through horizontal transmission by direct contact and via shedding of urine or other bodily secretions [12]. These secretions may be transmitted through seawater and ocean currents, potentially contributing to viral dispersal [2]. The role of vector organisms (i.e., leeches), in disease transmission is inconclusive [2,13]; however, only leeches of the genus Ozobranchus have exhibited viral loads high enough to warrant consideration. These leeches are attracted to the increased vascularization of FP tumors, meaning the tumors contain a high density of blood vessels. This likely explains their tendency to aggregate around these lesions [13].

Environmental degradation, including chemical contamination associated with urban, industrial, and agricultural runoff, has been proposed as a contributing factor to increased FP prevalence. This may be due to the disruptions these contaminants cause to physiological functions in turtles, further weakening them [2,5]. Common pollutants previously linked to cancer in marine organisms and known to have tumor-initiating effects include polychlorinated biphenyls (PCBs), PAHs, and organochlorine pesticides [7]. In addition to chemical contaminants, naturally occurring biotoxins associated with harmful algae blooms have been shown to contribute to immune dysfunction, potentially increasing turtle susceptibility to FP [2].

Diagnosis

FP is typically identifiable with the preliminary examination of obvious tumors; however, confirmation of ChHV5 infection is performed by polymerase chain reaction (PCR) analysis of biological samples, including blood and tissue [12]. Additional confirmation is preformed through histopathological examination (Figure 2) [11]. Diagnosis of internal tumors could include X-ray, computerized axial tomography (CAT), or magnetic resonance imaging (MRI), if present at facilities. A biopsy is usually performed after using this equipment if internal tumors are suspected [3]. Tumors that have been surgically removed are later examined microscopically. However, endoscopic procedures are not recommended for severely weakened turtles. Additionally, this method may miss lesions in the dorsal lung and in tissues outside the lungs [10].

Treatment and Prevention


While there is no official vaccine or specific medication for FP, supportive care is considered essential. Supportive care includes providing fluid therapy, pain management, and water [10]. Disinfecting equipment and the environment is also crucial in preventing the spread of the disease. Scientists continue to study the use of human anti-cancer drugs in the treatment of FP tumors in sea turtles. Three drugs have been used for treatment, including acyclovir, 5-fluorouracil, and bleomycin [17]. The surgical removal of tumors using sterile techniques, a CO2 laser, radio-wave surgery, or a scalpel is an effective method for treating tumors [1,11]. Although this approach may improve quality of life, it is not an effective method for eliminating ChHV5 infection. Therefore, facilities should implement a post-treatment holding period and conduct further testing, as ChHV5 may persist even in the absence of visible tumors [17]. However, most cases lead to the humane euthanasia of FP-infected sea turtles [1].

Given that environmental factors contribute to the development of FP, public involvement in reducing these stressors is crucial. Controlling water contamination and reducing marine pollution are important preventative measures (Figure 3). Furthermore, addressing climate change may decrease thermal stress in sea turtles, thereby reducing their susceptibility to FP [1,2,9]. Ultimately, early detection and continued surveillance are vital in limiting disease spread.

Further Research

FP has been present in sea turtles for many years, but some aspects of this disease remain poorly understood. The roles of environmental factors (e.g., chemical contaminants, biotoxins, and temperature), the viral pathogen, transmission (e.g., vector organisms), and treatment require further research [2,3,5,13]. Continued efforts to monitor and prevent FP will benefit disease management.

Readings

1. Duffy, D. J., Schnitzler, C., Karpinski, L., Thomas, R., Whilde, J., Eastman, C., Yang, C., Krstic, A., Rollinson, D., Zirkelbach, B., Yetsko, K., Burkhalter, B., & Martindale, M. Q. (2018). Sea turtle fibropapilloma tumors share genomic drivers and therapeutic vulnerabilities with human cancers. Communications Biology, 1, 63. https://doi.org/10.1038/s42003-018-0059-x

2. Dujon, A. M., Schofield, G., Venegas, R. M., Thomas, F., & Ujvari, B. (2021). Sea turtles in the cancer risk landscape: A global meta-analysis of fibropapillomatosis prevalence and associated risk factors. Pathogens, 10(10), 1295. https://doi.org/10.3390/pathogens10101295

3. Dupont, S. M., Bustamante, P., Duffy, D. J., Fort, J., Le Loc’h, G., Lelong, P., Chevallier, D., & Giraudeau, M. (2024). Future research avenues for the study of fibropapillomatosis in sea turtles. Frontiers in Ecology and Evolution, 12, 1372096. https://doi.org/10.3389/fevo.2024.1372096

4. Herbst, L., Ene, A., Su, M., Desalle, R., & Lenz, J. (2004). Tumor outbreaks in marine turtles are not due to recent herpesvirus mutations. Current Biology, 14(17), R697-R699. https://doi.org/10.1016/j.cub.2004.08.040

5. Jones, K., Ariel, E., Burgess, G., & Read, M. (2016). A review of fibropapillomatosis in green turtles (Chelonia mydas). The Veterinary Journal, 212, 48-57. https://doi.org/10.1016/j.tvjl.2015.10.041

6. Loganathan, A. L., Palaniappan, P., & Subbiah, V. K. (2021). First evidence of chelonid herpesvirus 5 (ChHV5) infection in green turtles (Chelonia mydas) from Sabah, Borneo. Pathogens, 10(11), 1404. https://doi.org/10.3390/pathogens10111404

7. Manes, C., Carthy, R. R., & Hull, V. (2023a). A coupled human and natural systems framework to characterize emerging infectious diseases—the case of fibropapillomatosis in marine turtles. Animals, 13(9),1441. https://doi.org/10.3390/ani13091441

8. Manes, C., Herren, R. M., Page, A., Dunlap, F. D., Skibicki, C. A., Rollinson Ramia, D. R., Farrell, J. A., Capua, I., Carthy, R. R., & Duffy, D. J. (2023b). Green turtle fibropapillomatosis: Tumor morphology and growth rate in a rehabilitation setting. Veterinary Sciences, 10(7), 421. https://doi.org/10.3390/vetsci10070421

9. Manes, C., Pinton, D., Canestrelli, A., & Capua, I. (2022). Occurrence of fibropapillomatosis in green turtles (Chelonia mydas) in relation to environmental changes in coastal ecosystems in Texas and Florida: A retrospective study. Animals, 12 (10), 1236. https://doi.org/10.3390/ani12101236

10. Page-Karjian, A. (2019). Fibropapillomatosis in marine turtles. In R. E. Miller, N. Lamberski, & P. P. Calle (Eds.), Fowler's zoo and wild animal medicine current therapy (Vol. 9, 398-403). W.B. Saunders. https://doi.org/10.1016/B978-0-323-55228-8.00057-6

11. Page-Karjian, A., Whitmore, L., Stacy, B. A., Perrault, J. R., Farrell, J. A., Shaver, D. J., Walker, J. S., Frandsen, H. R., Rantonen, E., Harms, C. A., Norton, T. M., Innis, C., Yetsko, K., & Duffy, D. J. (2021). Fibropapillomatosis and chelonid alphaherpesvirus 5 infection in Kemp's ridley sea turtles (Lepidochelys kempii). Animals, 11(11), 3076. https://doi.org/10.3390/ani11113076

12. Perrault, J. R., Levin, M., Mott, C. R., Bovery, C. M., Bresette, M. J., Chabot, R. M., Gregory, C. R., Guertin, J. R., Hirsch, S. E., Ritchie, B. W., Weege, S. T., Welsh, R. C., Witherington, B. E., & Page-Karjian, A. (2021). Insights on immune function in free-ranging green sea turtles (Chelonia mydas) with and without fibropapillomatosis. Animals, 11(3), 861. https://doi.org/10.3390/ani11030861

13. Rittenburg, L. T., Kelley, J. R., Mansfield, K. L., & Savage, A. E. (2021). Marine leech parasitism of sea turtles varies across host species, seasons, and the tumor disease fibropapillomatosis. Diseases of Aquatic Organisms, 143, 1-12. https://doi.org/10.3354/dao03549

14. Rossi, S., Sánchez-Sarmiento, A. M., Vanstreels, R. E. T., dos Santos, R. G., Prioste, F. E. S., Gattamorta, M. A., Grisi-Filho, J. H. H., & Matushima, E. R. (2016). Challenges in evaluating the severity of fibropapillomatosis: A proposal for objective index and score system for green sea turtles (Chelonia mydas) in Brazil. PLoS ONE, 11(12), e0167632. https://doi.org/10.1371/journal.pone.0167632

15. Shaver, D. J., Walker, J. S., & Backof, T. F. (2019). Fibropapillomatosis prevalence and distribution in green turtles Chelonia mydas in Texas (USA). Diseases of Aquatic Organisms, 136, 175-182. https://doi.org/10.3354/dao03403

16. Smith, G. M. & Coates, C. W. (1938). Fibro-epithelial growths of the skin in large marine turtles, Chelonia mydas (Linnaeus). Zoologica: New York Zoological Society, 23(4), 93-98. https://biostor.org/reference/194392

17. Whilde, J., Mashkour, N., Koda, S. A., Eastman, C. B., Thompson, D., Burkhalter, B., Frandsen, H. R., Page, A., Blackburn, N. B., Jones, K., Ariel, E., Dupont, S. M., Wood, L., & Duffy, D. J. (2024). International overview of sea turtle fibropapillomatosis: A survey of expert opinions and trends. Frontiers in Cell and Development Biology, 12, 1445438. https://doi.org/10.3389/fcell.2024.1445438