Larval Terapi ve Kronik Yaralar

Öz

İyileşmeyen yaralar günümüzde halk sağlığı için önemli bir sorun teşkil etmeye devam etmektedir ve antibiyotiğe dirençli mikroorganizmaların sebep olduğu cilt ve yumuşak doku enfeksiyon prevalansındaki artış gibi faktörler nedeniyle bugün ilişkili oldukları vaka sayıları hâlâ artmaktadır. Yara iyileşmesi, genellikle sorunsuz ilerleyen dört örtüşen fizyolojik aşamadan oluşur: homeostaz, iltihaplanma, çoğalma ve yeniden şekillenme / olgunlaşma. Bununla birlikte, iyileşmeyen yaralarda, iyileşme genellikle doku döküntülerinin uzaklaştırılması, lokal enfeksiyon ve / veya proteazlar gibi yıkıcı ürünlerin yara yatağından uzaklaştırılması ile alakalı olan enflamatuar fazda durur. Larval terapi (LT) umut verici tedavi yöntemlerinden biridir ve esas olarak nekrotize edilmiş dokularla beslenen yeşil şişe sineği Lucilia sericata'nın dezenfekte edilmiş larvalarının (kurtçukların) kullanılmasını içerir. LT'nin esas olarak üzerinde en fazla çalışmanın yayımlandığı debridmanın yanında  dezenfeksiyon ve büyüme uyarımı ile yara iyileşmesine yardımcı olduğu düşünülmektedir. Kronik yaraların tedavisi pahalıdır ve LT uygun maliyetli bir alternatif tedavi stratejisi sunar. Öte yandan, bakteriyel kaynaklı ülserlerin tedavisine ek olarak, mikotik enfeksiyon ve leishmaniasis ile ilişkili semptomlar için de kullanılabilir. Günümüzde LT, iyileşmeyen cilt ve yumuşak doku yaralarına karşı FDA onaylı bir terapidir. Bu derlemede, iyileşmeyen yaraların tedavisinde LT tarafından kullanılan etki mekanizmaları hakkındaki güncel literatürü özetledik.

Anahtar Kelimeler

• Larval tedavi,debridman,dezenfeksiyon,büyüme uyarımı

Larval Theraphy and Chronic Wounds

Öz

Non-healing wounds are still a burden to public health, and their prevalence in the population is increasing with the time due to antibiotic-resistant, microbe-associated skin and soft tissue infections as well as to the ever aging population. Wound healing is composed of four overlapping physiological phases which usually progress smoothly: homeostasis, inflammation, proliferation, and remodelling / maturing. In cases of nonhealing wounds, however, healing is usually trapped in inflammatory phase which is associated with the removal of tissue debris, local infection, and/or destructive products such as proteases from the wound bed. Maggot debridement therapy (MDT) is one of the promissing treatment modalities and it involves the use of disinfected larvae  (maggots) of the green bottle fly Lucilia sericata, which feed primarily on necrotized tissue. MDT is thought to aid wound healing mainly by debridement, disinfection, and growth stimulation, among which debridement is the best studied. Management of chronic wounds is expensive, and MDT provides a cost-effective alternative treatment. In addition to to the treatment of bacterial caused ulcers, it can also be used for symptoms associated with mycotic infection, and leishmaniasis. Today, MDT is a FDA-approved therapy against non-healing skin and soft tissue wounds. In this review we summarised the current literature regarding the action mechanisms used by MDT during the treatment of non-healing wounds.

Anahtar Kelimeler

• Maggot therapy,debridement,disinfection,growth stimulation

Kaynakça

1. 1. Oksuz E, Malhan S, Sonmez B, Numanoglu Tekin R. Cost of illness among patients with diabetic foot ulcer in Turkey. World J Diabetes [Internet]. 2016;7(18):462. Available from: http://www.wjgnet.com/1948-9358/full/v7/i18/462.htm
2. 2. Sherman RA. Maggot therapy takes us back to the future of wound care: New and improved maggot therapy for the 21st century. Journal of Diabetes Science and Technology. 2009. p. 336–44.
3. 3. Naik G, Harding K. Maggot debridement therapy: the current perspectives. Chronic Wound Care Manag Res. 2017;4:121-128. 4. Mumcuoğlu K, Taylan Özkan A. Dünyada Maggot Terapi. In: Multidisipliner Yaklaşımlı Biyolojik temelli Doğal Tedaviler- Biyoterapi (Apiterapi, Hirudoterapi, Maggot tedavi ve İhtiyoterapi), Tanyüksel M, Mumcuoğlu K, Ed., Meta Basım Matbaacılık ABC Yayın ve Eğitim Hizmetleri, İzmir, 2015
4. 5. Mumcuoğlu KY, Taylan Özkan A. Süpüratif kronik yaraların maggot debridman tedavisi. Turkiye Parazitol Derg. 2009;33(4):307-15.
5. 6. Whitaker LS, Twine C, Whitaker MJ, Welck M, Brown CS, Shandall A. Larval therapy from antiquity to the present day: Mechanisms of action, clinical applications and future potential. Postgraduate Medical Journal. 2007. p. 409–13.
6. 7. Davydov L. Maggot therapy in wound management in modern era and a review of published literature. Journal of Pharmacy Practice. 2011. p. 89–93.
7. 8. Sherman RA. Mechanisms of maggot-induced wound healing: What do we know, and where do we go from here? Evidence-based Complementary and Alternative Medicine. 2014.
8. 9. Sherman RA, Wyle F, Vulpe M. Maggot therapy for treating pressure ulcers in spinal cord injury patients. J Spinal Cord Med. 1995;18(2):71–4.

9. 10. Stoddard SR, Sherman RA, Mason BE, Pelsang DJ, Sherman RM. Maggot debridement therapy. An alternative treatment for nonhealing ulcers. Journal of the American Podiatric Medical Association. 1995. p. 218–21.
10. 11. Wayman J, Nirojogi V, Walker A, Sowinski A, Walker MA. The cost effectiveness of larval therapy in venous ulcers. J Tissue Viability. 2000;10(3):91–4.
11. 12. Markevich Y, McLeod-Roberts J, Mousley M, Melloy E. Maggot therapy for diabetic neuropathic foot wounds: a randomized study. In: 36th Annual Meeting of the European Association for the Study of Diabetes. 2000.
12. 13. Dumville JC, Worthy G, Bland JM, Cullum N, Dowson C, Iglesias C, et al. Larval therapy for leg ulcers (VenUS II): Randomised controlled trial. BMJ. 2009;338(7702):1047–9.
13. 14. Wang S yu, Wang J ning, Lv D cheng, Diao Y peng, Zhang Z. Clinical research on the bio-debridement effect of maggot therapy for treatment of chronically infected lesions. Orthop Surg. 2010;2(3):201–6.
14. 15. Mudge E, Price P, Neal W, Harding KG. A randomized controlled trial of larval therapy for the debridement of leg ulcers: Results of a multicenter, randomized, controlled, open, observer blind, parallel group study. Wound Repair Regen. 2014;22(1):43–51.
15. 16. Gilead L, Mumcuoglu KY, Ingber A. The use of maggot debridement therapy in the treatment of chronic wounds in hospitalised and ambulatory patients. J Wound Care [Internet]. 2012;21(2):78–85. Available from: http://www.magonlinelibrary.com/doi/10.12968/jowc.2012.21.2.78
16. 17. Tantawi T., Gohar Y., Kotb M., Beshara F., El-Naggar M. Clinical and microbiological efficacy of MDT in the treatment of diabetic foot ulcers. J Wound Care [Internet]. 2007;16(9):379–83. Available from:http://www.magonlinelibrary.com/doi/10.12968/jowc.2007.16.9.27868
17. 18. Tanyuksel M, Araz E, Dundar K, Uzun G, Gumus T, Alten B, et al. Maggot debridement therapy in the treatment of chronic wounds in a military hospital setup in Turkey. Dermatology. 2005;210(2):115–8.
18. 19. Taylan Özkan A, Mumcuoğlu KY. Kronik venöz ülserli bir olgunun maggot debridman tedavisi ile sağaltımı Türk Hij Den Biyol Derg, 2007; 64(1), 31-34.
19. 20. Marineau ML, Herrington MT, Swenor KM, Eron LJ. Maggot debridement therapy in the treatment of complex diabetic wounds. Hawaii Med J [Internet]. 2011;70(6):121–4. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22162609%5Cnhttp://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC3233395
20. 21. Ratcliffe NA, Mello CB, Garcia ES, Butt TM, Azambuja P. Insect natural products and processes: New treatments for human disease. Insect Biochemistry and Molecular Biology. 2011. p. 747–69. 22. Harris LG, Bexfield A, Nigam Y, Rohde H, Ratcliffe NA, Mack D. Disruption of Staphylococcus epidermidis biofilms by medicinal maggot Lucilia sericata excretions/secretions. Int J Artif Organs. 2009;32(9):555–64.
21. 23. Cazander G, Van Veen KEB, Bouwman LH, Bernards AT, Jukema GN. The influence of maggot excretions on pao1 biofilm formation on different biomaterials. Clin Orthop Relat Res. 2009;467(2):536–45.
22. 24. Cazander G, Van De Veerdonk MC, Vandenbroucke-Grauls CMJE, Schreurs MWJ, Jukema GN. Maggot excretions inhibit biofilm formation on biomaterials. Clin Orthop Relat Res. 2010;468(10):2789–96.
23. 25. Andersen AS, Sandvang D, Schnorr KM, Kruse T, Neve S, Joergensen B, et al. A novel approach to the antimicrobial activity of maggot debridement therapy. J Antimicrob Chemother. 2010;65(8):1646–54. 26. Bowling FL, Salgami E V., Boulton AJM. Larval therapy: A novel treatment in eliminating methicillin-Resistant Staphylococcus aureus from diabetic foot ulcers. Diabetes Care. 2007;30(2):370–1.
24. 27. Armstrong DG, Salas P, Short B, Martin BR, Kimbriel HR, Nixon BP, et al. Maggot therapy in “lower-extremity hospice” wound care: fewer amputations and more antibiotic-free days. J Am Podiatr Med Assoc. 2005;95(3):254–7.
25. 28. Nigam Y, Morgan C. Does maggot therapy promote wound healing? the clinical and cellular evidence. Journal of the European Academy of Dermatology and Venereology. 2016. p. 776–82.
26. 29. Sherman RA. Maggot therapy for treating diabetic foot ulcers unresponsive to conventional therapy. Diabetes Care. 2003;26(2):446–51.
27. 30. Sherman RA, Mumcuoglu KY. Maggot therapy: apparently a good treatment despite poor study and inadequate analysis (letter to editor in response to Dumville et al, BMJ, 2009, 338:b773
28. 31. Pečivová J, Mačičková T, Takáč P, Kovácsová M, Cupaníková D, Kozánek M. Effect of the extract from salivary glands of Lucilia sericata on human neutrophils. Neuroendocrinol Lett. 2008;29(5):794–7.
29. 32. Van Der Plas MJA, Baldry M, Van Dissel JT, Jukema GN, Nibbering PH. Maggot secretions suppress pro-inflammatory responses of human monocytes through elevation of cyclic AMP. Diabetologia. 2009;52(9):1962–70.
30. 33. van der Plas MJA, van der Does AM, Baldry M, Dogterom-Ballering HCM, van Gulpen C, van Dissel JT, et al. Maggot excretions/secretions inhibit multiple neutrophil pro-inflammatory responses. Microbes Infect. 2007;9(4):507–14.
31. 34. Tombulturk FK, Kasap M, Tuncdemir M, Polat E, Sirekbasan S, Kanli A, et al. Effects of Lucilia sericata on wound healing in streptozotocin-induced diabetic rats and analysis of its secretome at the proteome level. Hum Exp Toxicol. 2018;37(5):508–20.
32. 35. Menon J. Maggot therapy: a literature review of methods and patient experience. Bristish J Nurs. 2012;21(5):38–43.
33. 36. Shih AF, Little AJ, Panse G, Liu J, Yiu G, Yaggi HK, et al. Maggot therapy for calciphylaxis wound debridement complicated by bleeding. JAAD Case Reports. 2018;4(4):396–8.