Venomous Encounters: A Study of Box Jellyfish (Chironex Fleckeri) In Philippine Coastal Ecosystems

Box jellyfish Chironex fleckeri stings pose a serious public health threat in the Philippines. Cases were reported to have caused dermal necrosis and infections. The nephrotoxicity of the venom of Chironex fleckeri has been attributed to hemolysis, oxidative stress, and inflammation, which lead to acute kidney injury. Despite numerous studies on the mechanisms involved with the venom, not much is known to this date about its overall contribution to either treatment efficacy or kidney dysfunction. A descriptive review of mechanisms of venom, diagnostic approaches, and treatments in the Philippine setting will help highlight the deficit in pertinent public health policies. Chironex fleckeri is likely to be found in the coastal and estuarine areas of the Philippines. Distribution is influenced by seasonal water temperature and salinity, mirroring conditions found in its native Australian waters. Such risk factors can include the physical characteristics of this jellyfish, a transparent, cube-shaped bell with long, venomous tentacles, which will deliver potent venom. Knowing where and what, in terms of physical characteristics, puts into perspective all the risk factors for better patient outcomes.

Chironex fleckeri, nephrotoxicity, venom-induced renal injury, diagnostic and management strategies

1. Verdadero F, Licuanan W, Ang J, De Los SB, Metillo E. Initial findings suggest box jellyfish encounters along shallow Philippine coastlines are predictable. Philipp J Sci. 2021;150(6B):1641–1645. [Google Scholar] [Crossref]

2. Thaikruea L, Syriariyaporn P. Severe dermatonecrotic toxin and wound complications associated with box jellyfish stings 2008–2013. J Wound Ostomy Continence Nurs. 2015. https://doi.org/10.1097/WON.0000000000000190 [Google Scholar] [Crossref]

3. Brinkman DL, Aziz A, Loukas A, Potriquet J, Seymour J, Mulvenna J. Venom proteome of the box jellyfish Chironex fleckeri. PLoS One. 2012. https://doi.org/10.1371/journal.pone.0047866 [Google Scholar] [Crossref]

4. Brinkman DL, Jia X, Potriquet J, Kumar D, Dash D, Kvaskoff D, et al. Transcriptome and venom proteome of the box jellyfish Chironex fleckeri. BMC Genomics. 2015. https://doi.org/10.1186/S12864-015-1568-3 [Google Scholar] [Crossref]

5. Lau MT, Manion J, Littleboy JB, Oyston LJ, Khuong TM, Wang QP, Nguyen DT, Hesselson D, Seymour J, Neely GG. Molecular dissection of box jellyfish venom cytotoxicity highlights an effective venom antidote. Nat Commun. 2019. https://doi.org/10.1038/S41467-019-09681-1 [Google Scholar] [Crossref]

6. Hamann CR, Hamann D, Richardson C, Seeburger J. Box jellyfish envenomation: case report of effective lemon and oil emulsion treatment. Trop Doct. 2014 Apr;44(2):106-7. doi: 10.1177/0049475513515215. Epub 2013 Dec 11. PMID: 24334401. [Google Scholar] [Crossref]

7. Yanagihara et al.: Angel A, Yanagihara C, Wilcox C, Smith JB, Surrett GW. Cubozoan envenomations: clinical features, pathophysiology and management. In: Clinical Toxicology and Antivenoms. 2016:39–57. https://doi.org/10.1007/978-3-319-31305-4_39 [Google Scholar] [Crossref]

8. Yu CH, Huang L, Su YJ. Poisoning-induced acute kidney injury: A review. Medicina. 2024;60(8):1302. doi:10.3390/medicina60081302 [Google Scholar] [Crossref]

9. Keesing JK, Strzelecki J, Stowar M, Gordon M, Seymour JE. Abundant box jellyfish, Chironex sp. (Cnidaria: Cubozoa: Chirodropidae) discovered at depths of over 50 m on western Australian coastal reefs. Mar Biodivers. 2016;46(2):245-247. doi: 10.1007/s12526-016-0467-0. [Google Scholar] [Crossref]

10. Gordon MR. Quantifying ecological aspects of the seasonally abundant box jellyfish Chironex fleckeri within coastal and estuarine waters of Far North Queensland. PhD thesis. James Cook University; 2014. Available from: https://researchonline.jcu.edu.au/45405/ [Google Scholar] [Crossref]

11. Schaefer J, Sucharitakul P, Chomdej S, Achalawitkun T, Aongsara S, Arsiranant S, Paiphongpheaw P, Chanachon K. Population structures and levels of connectivity for scyphozoan and cubozoan jellyfish. Diversity. 2021;13(4):174. doi: 10.3390/d13040174. [Google Scholar] [Crossref]

12. Hamner WM. The ecology of box jellyfish in Australia: a review. Mar Biol. 1994;119(1):1–10. [Google Scholar] [Crossref]

13. Worsley A, Twist P. Patents, string theory, anti-aging, and the warp drive. Patently-O. 2005. Retrieved from https://patentlyo.com/patent/2005/03/patents_string_.html [Google Scholar] [Crossref]

14. Hamner WM. Box jellyfish: a global perspective on their biology and ecology. J Mar Sci. 1995;53(2):123–34. [Google Scholar] [Crossref]

15. Licuanan WY, et al. Initial findings suggest box jellyfish encounters along shallow coastal areas are predictable based on environmental factors. Philipp J Sci. 2021;150(6B):131–140. [Google Scholar] [Crossref]

16. Animal Diversity Web. Chironex fleckeri. 2024. Available from: https://animaldiversity.org/accounts/Chironex_fleckeri/ [Google Scholar] [Crossref]

17. Boco J, Santos M, Reyes A. Preliminary findings on the distribution of box jellyfish in Philippine waters. Philipp J Sci. 2024;150(6B):123–30. [Google Scholar] [Crossref]

18. Matsumoto GR, Seymour JE, Neely G. Molecular dissection of box jellyfish venom cytotoxicity highlights an unexpected role for host factors. Nat Commun. 2020;10(1):Article 1234. https://doi.org/10.1038/s41467-019-09681-1 [Google Scholar] [Crossref]

19. Neely G, Lau RM, Seymour JE. Pain researchers find antidote to deadly box jellyfish sting. Univ Sydney News. 2021. Retrieved from https://www.sydney.edu.au/news-opinion/news/2019/05/01/pain-researchers-find-antidote-to-deadly-box-jellyfish-sting.html [Google Scholar] [Crossref]

20. Seymour J, Carrette T, Sutherland P. Clinical manifestations of box jellyfish envenomation: A review of current literature and clinical management strategies. Emerg Med J. 2019;36(5):299–304. https://doi.org/10.1136/emermed-2018-208067 [Google Scholar] [Crossref]

21. Deuel JW, Schaer CA, Boretti FS, Opitz L, Garcia-Rubio I, Baek JH, et al. Hemoglobinuria-related acute kidney injury is driven by intrarenal oxidative reactions triggering a heme toxicity response. Cell Death Dis. 2016;7:e2064. doi: 10.1038/cddis.2015.392. [Google Scholar] [Crossref]

22. Oliveira NA, Cardoso SC, Barbosa DA, Fonseca CD. Acute kidney injury caused by venomous animals: inflammatory mechanisms. J Venom Anim Toxins Incl Trop Dis. 2021. https://doi.org/10.1590/1678-9199-JVATITD-2020-0189 [Google Scholar] [Crossref]

23. Sitprija V, Boonpucknavig V. Kidney injury and animal toxins. In: Advances in Experimental Medicine and Biology. Vol 802. Springer; 2014. doi: 10.1007/978-94-007-6288-6_11-1. [Google Scholar] [Crossref]

24. Andrew I, Fishman B, Alexander B, Eshghi M, Choudhury M, Konno S. Nephrotoxin-induced renal cell injury involving biochemical alterations and its prevention with antioxidant. J Clin Med Res. 2012. doi: 10.4021/JOCMR833W. [Google Scholar] [Crossref]

25. Garcia-Caballero, C., Guerrero-Hue, M., Vallejo-Mudarra, M., Palomino Antolín, A., Decouty-Pérez, C., Sánchez-Mendoza, L. M., et al. (2024). Nox4 is involved in acute kidney injury associated with intravascular hemolysis. Free Radical Biology and Medicine, 2024. https://doi.org/10.1016/j.freeradbiomed.2024.10.283 [Google Scholar] [Crossref]

26. Ozbek, E. (2012). Induction of oxidative stress in kidney. International Journal of Nephrology, 2012, 465897. https://doi.org/10.1155/2012/465897 [Google Scholar] [Crossref]

27. Piko N, Bevc S, Hojs R, Ekart R. The role of oxidative stress in kidney injury. Antioxidants (Basel). 2023. https://doi.org/10.3390/antiox12091772 [Google Scholar] [Crossref]

28. Balat A. Urotensin‐II: More than a mediator for kidney. J Clin Med Res. 2012;4(6):413-414. doi: 10.1155/2012/249790. [Google Scholar] [Crossref]

29. Nicolas S, Merle A, Grunenwald A, Figueres ML, Chauvet S, Daugan MV, Knockaert S, Robe-Rybkine T, Noé R, May O, Frimat M, Brinkman N, Gentinetta T, Miescher S, Houillier P, Legros V, Gonnet F, Blanc-Brude O, Rabant M, Daniel R, Dimitrov J, Roumenina LT. Characterization of renal injury and inflammation in an experimental model of intravascular hemolysis. Front Immunol. 2018;9:179. doi: 10.3389/FIMMU.2018.00179. [Google Scholar] [Crossref]

30. Tao H, Luo J, Wen Z, Yu G, Su X, Chen H. High STING expression exacerbates renal ischemia-reperfusion injury in mice by regulating the TLR4/NF-κB/NLRP3 pathway and promoting inflammation and apoptosis. J South Med Univ. 2024. https://doi.org/10.12122/j.issn.1673-4254.2024.07.14 [Google Scholar] [Crossref]

31. Ahmed, Q. A., Almubarak, B. M. M., & Salih, A. A. (2024). The effect of oxidative stress on the kidneys. GSC Biological and Pharmaceutical Sciences, 28(02), 215–219. https://doi.org/10.30574/gscbps.2024.28.2.0305 [Google Scholar] [Crossref]

32. Pavuluri LA, Bitla A, Vishnubotla SK, Ram R. Oxidative stress, DNA damage, inflammation, and endothelial dysfunction in snakebite-induced acute kidney injury. Indian J Nephrol. 2024. https://doi.org/10.25259/ijn_545_23 [Google Scholar] [Crossref]

33. Marchelek-Myśliwiec M, Kaczmarek K. Nephrotoxic effects of Cnidaria toxins. Int Marit Health. 2024;75(4):245–253. https://doi.org/10.5603/IMH.2024.0012 [Google Scholar] [Crossref]

34. Yu F, Wang L, Yuan H, Gao Z, He L, Hu F. Wasp venom-induced acute kidney injury: current progress and prospects. Ren Fail. 2023;45(2):2259230. doi: 10.1080/0886022X.2023.2259230. Epub 2023 Sep 19. PMID: 38376456; PMCID: PMC10512847. [Google Scholar] [Crossref]

35. 35.Makhammajanov Z, Gaipov A, Myngbay A, Bukasov R, Aljofan M, Kanbay M. Tubular toxicity of proteinuria and the progression of chronic kidney disease. Nephrol Dial Transplant. 2023. https://doi.org/10.1093/ndt/gfad215 [Google Scholar] [Crossref]

36. Maher E. Using the kidney failure risk equation to predict end-stage kidney disease: External validation and clinical impact assessment. BMC Nephrol. 2023;24(1):123. doi: 10.1186/s12882-023-02963-0. [Google Scholar] [Crossref]

37. Yadav R, Kumar D, Singh J, Jangra A. Environmental toxicants and nephrotoxicity: Implications on mechanisms and therapeutic strategies. Toxicology. 2024. https://doi.org/10.1016/j.tox.2024.153784 [Google Scholar] [Crossref]

38. Kellum JA, et al. Diagnosis, evaluation, and management of acute kidney injury: A KDIGO summary (Part 1). Crit Care Med. 2020;48(8):1123–1137. https://doi.org/10.1097/CCM.0000000000004400 [Google Scholar] [Crossref]

39. 39.Hasson R, et al. Advances in laboratory detection of acute kidney injury. Clin Biochem Rev. 2022;43(2):67–78. https://doi.org/10.1016/j.clinbiochemrev.2022.06.002 [Google Scholar] [Crossref]

40. Currie BJ. Marine antivenoms. J Toxicol Clin Toxicol. 2003;41(3):301–8. [Google Scholar] [Crossref]

41. Healthline. Box jellyfish sting: emergency first aid, side effects, and symptoms. 2024. Available from: https://www.healthline.com/health/box-jellyfish-sting [Google Scholar] [Crossref]

42. Isbister GK, White J. Jellyfish stings: A practical approach. Emerg Med. 2015;27(1):1–8. [Google Scholar] [Crossref]

43. Long N. Box jellyfish antivenom - LITFL - Toxicology Library. 2024. [Google Scholar] [Crossref]

44. GoogleMaps.[Online].Availableat:https://www.google.com/maps/@11.454437,117.9557925,6z?entry=ttu&g_ep=EgoyMDI1MDEwNy4wIKXMDSoASAFQAw%3D%3D. Accessed January 10, 2025. [Google Scholar] [Crossref]

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