In my previous post on maggot therapy, we discussed the differences between confinement and containment maggot therapy dressings. This post will examine the studies that address differences in efficacy and efficiency between these two methods of maggot therapy. The majority of contained maggot studies use a specific brand of containment bag (Biobag™ or VitaPad™ by Biomonde) because those products – if not the very act of applying maggots to the wound within a bag – were patented 14 years ago by Wim Fleischmann.¹ While numerous individual therapists have applied maggots to wounds by first placing them into bags of their own making, or into commercially available net bags, no company can legally sell contained maggot dressings in any country where the patent was filed. Therefore, the majority of formal studies have used the Biomonde products.

A Review of the Literature on Maggot Therapy

The largest prospective study to date that includes both contained (bagged) and confined (also called "free-range") maggots is the 3-armed study of maggot therapy vs. hydrogel for venous stasis ulcers.² Focusing on debridement (which is the FDA cleared indication for all maggot therapy products), the hydrogel-treated (control) patients were debrided in an average of 72 days, the bagged maggot therapy patients in an average of 28 days, and the free range maggot therapy patients in an average of 14 days; this difference was statistically significant (log rank test P<0.001). In a case-controlled study of free-range vs. bagged maggots, Steenvoorde et al (2005)³ also demonstrated that free-range maggots were more efficient and effective than bagged maggots.

Compared to confined "free-range" maggot dressings, patients receiving bagged maggot dressings required approximately twice the number of maggots per treatment, and twice the number of treatments to debride the wounds (p= 0.028 and p<0.001, respectively). In their contained dressing group, 6 of 15 patients (40%) eventually needed major amputation, compared with only 6 of 54 patients (11%) in their free range group (P<.01). The free range maggot-treated wounds had more "beneficial outcomes" (defined as wounds that were completely closed or at least clean, infection-free and no larger than at the start of treatment) than wounds treated with the contained maggot dressings (n = 43 [79.6%] vs. n = 7 [46.7%]; P = .028). It should be noted that their contained maggot dressings included both polyester net bags (Biobags™; Biomonde) and polyvinyl alcohol (PVA) foam pads (most were Vitapad™ by Biomonde, but some were self-sealed PVA bags).

There are two published laboratory studies of free-range vs. bagged maggots. Steven Thomas and his group at Zoobiotic (now Biomonde) demonstrated that maggots contained in bags, when applied to necrotic tissue, were less likely to survive, and those that did survive grew at half the rate and attained half the size of free-range maggots.⁴ The researchers point out that the volume of digestive juices produced by maggots is directly related to their size and physiologic age, and therefore the smaller, slower-growing bagged maggots are not able to produce as much proteolytic enzymes as their free-range maggot siblings. Indeed, their findings are consistent with controlled clinical studies that demonstrate that 2-4 times as many bagged larvae are needed to achieve debridement, and it takes 2-4 times as long.²

The group also made note of their discovery that some of the larger infected tissue and debris, which broke apart due to the maggots' digestive enzymes, was not able to get through the net bags and therefore was not being ingested by the maggots. This is important because much of the maggot-related microbial killing takes place in the maggot's gut. Still, no difference has yet been identified between the antimicrobial activity of contained vs. confined maggot therapy. In their laboratory study of bagged maggots placed over a strip of pork, Blake and colleagues (2007) demonstrated no differences between the debridement capacity of the free range vs. bagged maggots, as long as they were left for four days.⁵ However, Steenvoorde and Oskam (2008) criticized the experiment as not being representative of clinical cases because the experimental was tested in complete contact with the artificial wound by being sewn directly to the smaller, perfectly flat piece of porcine tissue.⁶

How Maggots Debride Wounds

Based on the results of these studies, it should not be surprising that contained maggots yielded different results than free-range maggots. According to a recent review of maggot-induced wound healing⁷, the efficacy of maggot therapy – whether we are talking about debridement, antimicrobial activity, or growth promotion – is a function of both enzymatic and physical properties of the maggots. Medicinal maggots are covered with microscopic spines which scratch and scrape the necrotic tissue and debris, essentially making the maggots function like micro-files or surgical "raspers". Since contained maggots do not have free access to the wound bed, they cannot provide this physical debridement action to the necrotic tissue nor the biofilm, and they have limited access to all of the tissues, sinus tracts, and undermined areas of the wound.

Bagged larvae are unable to migrate to the wound areas with the most necrotic tissue or greatest nutritional value, and since they cannot ingest the liquefied necrotic tissue unless it physically enters their containment bag, it is understandable that contained larvae develop more slowly and therefore produce their digestive enzymes at a slower rate than free-range maggots due to these limitations in access. In the next installment of this blog, we will explore when and why a therapist might choose contained maggots over free-range maggot therapy despite the higher cost and decreased efficacy of contained maggots.

References:

1. Grassberger M, Fleischmann W. The biobag - a new device for the application of medicinal maggots. Dermatology. 2002;204:306.

2. Dumville JC, Worthy G, Bland JM, Cullum N, Dowson C, Iglesias C, Mitchell JL, Nelson EA, Soares MO, Torgerson DJ; VenUS II team. Larval therapy for leg ulcers (VenUS II): randomised controlled trial. BMJ. 2009;338:b773.

3. Steenvoorde P, Jacobi CE, Oskam J. Maggot debridement therapy: free-range or contained? An in-vivo study. Adv Skin Wound Care. 2005;18:430-5.

4. Thomas S, Wynn K, Fowler T, Jones M. The effect of containment on the properties of sterile maggots. Br J Nurs. 2002; 11(12 Suppl):S21-2, S24, S26 passim.

5. Blake FA, Abromeit N, Bubenheim M, Li L, Schmelzle R. The biosurgical wound debridement: experimental investigation of efficiency and practicability. Wound Repair Regen. 2007;15:756-61.

6. Steenvoorde P, Oskam J. Comments on the paper, "The biosurgical wound debridement: experimental investigation of efficiency and practicability," by Blake FA et al. Wound Repair Regen. 2008 May-Jun;16(3):466.

7. Sherman RA. Mechanisms of maggot-induced wound healing: what do we know, and where do we go from here? Evid Based Complement Alternat Med. 2014;2014:592419.

Disclosure: Financial - The author is Co-founder and Laboratory Director of Monarch Labs.

About The Author

Ron Sherman MD, MSC, DTM&H has led a long career at the forefront of biotherapy, pioneering the development of medicinal maggots for over 25 years. He is now retired from his faculty position at the University of California, but continues to volunteer as Director and Board Chair of the BTER Foundation, and as Laboratory Director of Monarch Labs.