
Dr. Graham graduated with a baccalaureate degree in Biomedical Sciences from Grand Valley State University in 2009. He then went on to attain his Doctorate of Podiatric Medicine in 2014 from Barry University.Dr. Graham is currently in his 3rd year of podiatric medicine and surgical residency with the added credential of reconstructive rearfoot/ankle surgical training (PMSR/RRA) at Jackson North Medical Center in Miami, Florida. He also serves as the president of the Podiatry Overseas Association, a non-profit medical mission organization.
Graham_Current Dialogues in Wound Management_2016_Volume 2_Issue 2
Fly larvae have been used as an intentional biotherapy to debride infected wounds for the last thousand years, as written records show.1This ancient biotherapy has gone through a period of resurgence over the past several years. In current day medical use, maggot debridement therapy (MDT) is referred to as “biosurgery.” The purpose of this article is to describe maggot therapy, review the literature documenting the validity of this therapy, and to review the use of MDT as a method of infection control.
Documented indications for MDT include:
•Diabetic foot ulcers (DFU)
•Venous and arterial leg ulcers
•Gangrene and osteomyelitis
•Necrotizing fasciitis
•Traumatic necrotic leg wounds
•Intractable sacral wounds
•Burns
DEBRIDEMENT AND WOUND HEALING
Debridement represents the hallmark of wound bed preparation. This procedure facilitates wound inspection, removes bacteria and devitalized tissue, and stimulates the production of essential growth factors.
Steed (1996) observed that debridement created bleeding which could activate platelets to release the contents from their growth factor-rich alpha-granules, thus stimulating an inflammatory response.9 Williams, et al. (2005) noted the attraction of neutrophils and macrophages increased subsequent to debridement. The actions of these cells included secretion of growth factors and phagocytosis of bacteria. Researchers observed that cytokines and growth factors functioned more effectively in an exudate and slough-free environment.
Debridement may be accomplished in several ways:
•Surgical
•Enzymatic
•Autolytic
•Mechanical
•Biologic (such as MDT). Fly larva, Lucilia sericata, are used as a form of biological debridement for cleaning non-healing wounds
THE ROLE OF MAGGOTS IN WOUND MANAGEMENT
Maggots cause liquefaction and removal of necrotic tissue. Larvae kill bacteria by ingestion, digestion, and antibacterial secretions. Maggots stimulate healthy granulation tissue. Changes created by this therapy in the wound environment may further encourage growth, resulting from secretion of calcium carbonate, allantoin, and urea. Disinfection is presumed to occur as a result of digestion, possibly combined with secretion of antimicrobial molecules.
Maggots may enhance tissue formation within wounds via promotion of fibroblastic motility, providing for a wider distribution of viable fibroblasts. This therapy may be useful in patients where other aggressive treatments have failed or when sharp debridement is contraindicated; these include individuals who are not surgical candidates, and those with wounds exhibiting pathergy such as pyoderma gangrenosum, among others.
Anecdotally, biosurgery is generally well-tolerated with few side effects. In rare cases, patients have a mild febrile reaction.13Patients usually welcome any therapy that may heal their wounds and are often receptive to biosurgery when appropriately educated and counseled. Conversely, some clinicians, nurses, and administrators often have a different point of view (“yuk factor”) and are squeamish about the process.
Steenvoorde, et al. (2005) observed that patients utilizing maggot therapy usually tolerated the procedure without incident or side effects.15 A retrospective study of 41 patients treated with MDT concluded that in 78% of patients pain could be adequately treated outpatient with analgesic therapy.16 If pain symptoms were unmanageable, other options included hospitalization or cessation of therapy.
BIOSURGERY IS COST-EFFECTIVE
In a small randomized control trial, MDT appeared more economical than hydrogel. All wounds treated with larval therapy were successfully debrided following one application at a medical cost of £78.64 (approximately US $115), while in the hydrogel group, one-third of wounds still required treatment after one month, costing an average of £136.23 (~US $200).17 The sample size of this study was low, only 12 patients; however, this issue was discussed by the research group in their limitations, citing the need for a larger study.
In the United States, select biotherapy laboratories reproduce and distribute disinfected medical maggots. The average cost per unit (100 maggots) is between US $18-22. Medical Maggots™ are FDA cleared, and therapy is reimbursed by public and private insurances.
NEXT GENERATION MAGGOT THERAPY
The role of Platelet Derived Growth Factors (PDGF) in wound healing has been well established in the literature. PDGFs stimulate fibroblast proliferation and chemotaxis, actin reorganization, and production and secretion of other growth factors, metalloproteases, and ECM constituents.
Linger, et al. (2016) are attempting to bioengineer a breed of fly larvae which secrete/excrete human growth factors. By performing transgene insertion, this research group is changing the genetic makeup of the larvae. This research shows inducible production of human PDGF-b RNA and PDGF-BB protein. After altering the organism’s code, researchers detected PDGF-BB protein within maggot hemolymph. In theory, the concept of the natural debriding characteristics of the maggot coupled with the potential of excreting human growth factors into a wound bed could be world changing. These researchers from North Carolina State University refer to the use of these modified larvae for debridement, “Enhanced MDT
CONCLUSION
MDT represents a viable alternative for many wound types, particularly in those patients who are not candidates for sharp debridement or those who may develop pathergy. MDT works by debriding wounds while dissolving necrotic tissue, disinfecting wounds by killing bacteria, and stimulating wound healing with minimal pain.
Additionally, MDT may be useful in eradicating many bacteria, including MRSA, safely and cost-efficiently. Research remains ongoing and large randomized studies are required to justify MDT as a mainstay in modern wound management.
References
1.Whitaker IS, Twine C, Whitaker MJ, et al. Larval therapy from antiquity to the present day: mechanisms of action, clinical applications and future potential. Postgrad Med 2007;J83:409–413.
2.Azad AK, et al. “Maggot debridement therapy for diabetic foot ulcer: Experience from Maggot treatment Centers.” Asian Journal of Pharmacy and Pharmacology 2.1 (2016): 23-25.
3.Dumville JC, Worthy G, Bland JM, et al., for the VenUS II team. Larval Therapy for leg ulcers (VenUS II): randomised controlled trial. BMJ. 2009; 338:b773.
4.Mumcuoglu KY, Lipo M, Ioffe-Uspensky I, et al. Maggot therapy for gangrene and osteomyelitis Harefuah. 1997; 132, 323 325.
5.Dunn C, Raghavan U, Pfleiderer AG. The use of maggots in head and neck necrotizing fasciitis. J Laryngol Otol. 116 (2002):70–72.
6.Wollina U, Karte K, Herold C, Looks A. 2000. Biosurgery in wound healing—The renaissance of maggot therapy. J Eur Acad Dermatol Venereol. 2000;14: 285–289.
7.Namias N, Varela JE, Varas RP, et al. Biodebridement: a case report of maggot therapy for limb salvage after fourth-degree burns. J Burn Care Rehab, 2000;21: 254–7.
8.Mumcuoglu KY, Ingber A, Gilead L, et al. Maggot therapy for the treatment of intractable wounds. Int. J. Dermatol. 1999.
9.Steed DL, et al. “Effect of extensive debridement and treatment on the healing of diabetic foot ulcers. Diabetic Ulcer Study Group.” J Am Coll Surg 183.1 (1996): 61-64.
10.Williams D, et al. “Effect of sharp debridement using curette on recalcitrant nonhealing venous leg ulcers: a concurrently controlled, prospective cohort study.” Wound repair and regeneration 13.2 (2005): 131-137.
11.Greenberg B. “Host-Contaminant Biology of Muscoid Flies. 3. Effect of Hibernation, Diapause, and Larval Baactericides on Normal Flora of Blow-Fly Prepupae.” J Insect Pathology 4.4 (1962): 415.
12.Horobin A J, et al. “Maggots and wound healing: an investigation of the effects of secretions from Lucilia sericata larvae upon interactions between human dermal fibroblasts and extracellular matrix components.” British J Dermatology 148.5 (2003): 923-933.
13.Thomas S, et al. “Using larvae in modern wound management.” J Wound Care 5.2 (1996): 60-69.
14.Steenvoorde P, et al. “Maggot therapy and the “Yuk” factor: An issue for the patient?” Wound Rep and Regen. 2005;13.3:350-352.
15.Steenvoorde P, Budding T, Oskam J. “Determining pain levels in patients treated with maggot debridement therapy.” J Wound Care 14.10 (2005): 485-488.
16.Sherman RA, et al. “Maggot debridement therapy in outpatients.” Archives of physical medicine and rehabilitation 82.9 (2001): 1226-1229.
17.Wayman J et al. “The cost effectiveness of larval therapy in venous ulcers.” Journal of Tissue Viability 10.3 (2000): 91-94.
18.Monarch Labs Online. ©2016. [accessed 04/08/2016]. http://www.monarchlabs.com/
19.Heldin C-H, Westermark B. “Mechanism of action and in vivo role of platelet-derived growth factor.” Physiological reviews 79.4 (1999): 1283-1316.
20.Heldin CH, Westermark B. “Mechanism of action and in vivo role of platelet-derived growth factor.” Physiological reviews 79.4 (1999): 1283-1316.
21.Linger RJ, et al. “Towards next generation maggot debridement therapy: transgenic Lucilia sericata larvae that produce and secrete a human growth factor.” BMC biotechnology 16.1 (2016): 1.