References

Sherman RA, Hall MJ, Thomas S. Medicinal maggots: an ancient remedy for some contemporary afflictions. Annu Rev Entomol. 2000; 45:(1)55-81 https://doi.org/10.1146/annurev.ento.45.1.55

Manring MM, Calhoun JH. Biographical sketch: William S. Baer (1872–1931). Clin Orthop Relat Res. 2011; 469:(4)917-919 https://doi.org/10.1007/s11999-010-1415-4

Baer WS. The classic: the treatment of chronic osteomyelitis with the maggot (larva of the blow fly). 1931. Clin Orthop Relat Res. 2011; 469:(4)920-944 https://doi.org/10.1007/s11999-010-1416-3

Hunter S, Langemo D, Thompson P Maggot therapy for wound management. Adv Skin Wound Care. 2009; 22:(1)25-27 https://doi.org/10.1097/01.ASW.0000343730.76308.6a

Nair HK, Wasi Ahmad N, Teh CH Maggot debridement therapy in Malaysia. Int J Low Extrem Wounds. 2020; 20:(3)208-216 https://doi.org/10.1177/1534734620932397

Paul AG, Ahmad NW, Lee H Maggot debridement therapy with Lucilia cuprina: a comparison with conventional debridement in diabetic foot ulcers. Int Wound J. 2009; 6:(1)39-46 https://doi.org/10.1111/j.1742-481X.2008.00564.x

Nair HKR, Ahmad NW, Ismail AA Maggot debridement therapy in the treatment of diabetic foot ulcers. Wounds Asia. 2021; 4:(1)30-36

Wolff H, Hansson C. Larval therapy–an effective method of ulcer debridement. Clin Exp Dermatol. 2003; 28:(2)134-137 https://doi.org/10.1046/j.1365-2230.2003.01226.x

Beasley WD, Hirst G. Making a meal of MRSA—the role of biosurgery in hospital-acquired infection. J Hosp Infect. 2004; 56:(1)6-9 https://doi.org/10.1016/j.jhin.2003.09.002

Courtenay M, Church JC, Ryan TJ. Larva therapy in wound management. J R Soc Med. 2000; 93:(2)72-74 https://doi.org/10.1177/014107680009300206

Sherman RA. Maggot therapy for treating diabetic foot ulcers unresponsive to conventional therapy. Diabetes Care. 2006; 26:(2)446-451 https://doi.org/10.2337/diacare.26.2.446

Sherman RA. Maggot versus conservative debridement therapy for the treatment of pressure ulcers. Wound Repair Regen. 2002; 10:(4)208-214 https://doi.org/10.1046/j.1524-475X.2002.10403.x

Armstrong DG, Salas P, Short B Maggot therapy in “lower-extremity hospice” wound care: fewer amputations and more antibiotic-free days. J Am Podiatr Med Assoc. 2005; 95:(3)254-257 https://doi.org/10.7547/0950254

Wayman J, Nirojogi V, Walker A The cost effectiveness of larval therapy in venous ulcers. J Tissue Viability. 2000; 10:(3)91-94 https://doi.org/10.1016/S0965-206X(00)80036-4

Chambers L, Woodrow S, Brown AP Degradation of extracellular matrix components by defined proteinases from the greenbottle larva Lucilia sericata used for the clinical debridement of non-healing wounds. Br J Dermatol. 2003; 148:(1)14-23 https://doi.org/10.1046/j.1365-2133.2003.04935.x

Bexfield A, Nigam Y, Thomas S, Ratcliffe NA. Detection and partial characterisation of two antibacterial factors from the excretions/secretions of the medicinal maggot Lucilia sericata and their activity against methicillin-resistant Staphylococcus aureus (MRSA). Microbes Infect. 2004; 6:(14)1297-1304 https://doi.org/10.1016/j.micinf.2004.08.011

Robinson W. Ammonium bicarbonate secreted by surgical maggots stimulates healing in purulent wounds. Am J Surg. 1940; 47:(1)111-115 https://doi.org/10.1016/S0002-9610(40)90125-8

Mumcuoglu KY, Miller J, Mumcuoglu M Destruction of bacteria in the digestive tract of the maggot of Lucilia sericata (Diptera: Calliphoridae). J Med Entomol. 2001; 38:(2)161-166 https://doi.org/10.1603/0022-2585-38.2.161

Prete PE. Growth effects of Phaenicia sericata larval extracts on fibroblasts: Mechanism for wound healing by maggot therapy. Life Sci. 1997; 60:(8)505-510 https://doi.org/10.1016/S0024-3205(96)00688-1

Smith AG, Powis RA, Pritchard DI, Britland ST. Greenbottle (Lucilia sericata) larval secretions delivered from a prototype hydrogel wound dressing accelerate the closure of model wounds. Biotechnol Prog. 2006; 22:(6)1690-1696 https://doi.org/10.1002/bp0601600

Marineau ML, Herrington MT, Swenor KM, Eron LJ. Maggot debridement therapy in the treatment of complex diabetic wounds. Hawaii Med J. 2011; 70:(6)121-124

Richardson M. The benefits of larval therapy in wound care. Nurs Stand. 2004; 19:(7) https://doi.org/10.7748/ns.19.7.70.s60

Drisdelle R. Maggot debridement therapy. Nursing. 2003; 33:(6) https://doi.org/10.1097/00152193-200306000-00011

Leg ulcers

Wound dressing

Wound healing

Maggot debridement therapy to treat hard-to-heal diabetic foot ulcers: a single-centre study

01 December 2021

Practice

Abstract

Objective:

Maggot debridement therapy (MDT) has seen a resurgence in recent years in the treatment of hard-to-heal wounds, as a result of rising antibiotic resistance. The sterilised larvae of Lucilia cuprina have been used in MDT in Malaysia since 2003, with encouraging results for the treatment of hard-to-heal diabetic wounds. We report a case series of 30 patients selected from our clinic by convenient sampling with diabetic lower limb ulcers treated with MDT. The average age of patients receiving MDT was >50 years. Of the 30 patients in the study, nine were female and 21 were male. All patients had underlying diabetes, two patients had leg ulcers and 28 patients had diabetic foot ulcers. Sterilised Lucilia cuprina larvae were applied via a standard method of 10 maggots per square centimetre and dressed with sterile gauze. The study endpoint was defined as ≤5% coverage with slough or necrotic tissue following three successive applications of MDT. In this study, maximum debridement of wounds was achieved in 96.6% (29 patients) of our patients, with ≤5% coverage with slough or necrotic tissue, in addition to a reduction in wound-related pain, as assessed by a visual analogue scale. No adverse events were reported. The findings of this study support the use of MDT as a safe, efficacious, and cost-effective method of managing diabetic wounds.

Maggot infestations have long been associated with improved wound healing by clinicians throughout history. Dominique Larrey, who worked as a battlefield surgeon in the Napoleonic Wars, noted that maggot-infested wounds tended to heal more rapidly, and observed that the maggots fed only on dead and devitalised tissue while leaving healthy tissue intact.¹ Despite these observations, the deliberate introduction of maggots into infected wounds did not occur until the early twentieth century, when William Baer, the Professor of Orthopaedic Surgery at the Johns Hopkins School of Medicine in Maryland, US, pioneered the use of sterile maggots in the treatment of infected wounds and osteomyelitis with significant success.²

Following an initial wave of tetanus and gas gangrene in some patients treated with maggot therapy, Baer subsequently developed a method of sterilisation to reduce the risk of secondary infections from microorganisms present on the surface of non-sterile maggots.³ Maggot debridement therapy (MDT) proceeded to see ensuing utilisation within the treatment of wounds, only fading in popularity after the Second World War due to the discovery and widespread use of antibiotics.⁴ However, the increase in the prevalence of antibiotic-resistant strains in wound infections has led to a resurgence in maggot therapy since the 1980s.⁴

Maggot therapy was first introduced to Malaysia in 2003 at Lumut Navy Hospital, Perak, with the successful treatment of hard-to-heal diabetic wounds using the larvae of the blowfly Lucilia cuprina.⁵ The Australian sheep blowfly Lucilia cuprina is endemic to Southeast Asia and is a close relative of the common green bottle fly Lucilia sericata, of which the larvae has been widely used in maggot debridement therapy (MDT) in the West. The sterilisation of Lucilia cuprina eggs and first-instar larvae were established by the Institute for Medical Research (IMR) under the Ministry of Health of Malaysia. A number of clinical trials in Malaysia have shown MDT to be efficacious in the treatment of hard-to-heal wounds of various aetiology, being noninferior to conventional debridement while reducing hospital ward stay time and amputation rates.⁶

Our previous study involving nine patients treated with MDT demonstrated successful debridement with <5% of the wounds being covered by slough or necrotic tissue for six of these patients; whereas the remaining three patients had a ≥40% reduction in slough over their wound.⁷

This current study seeks to validate our findings with a larger patient population and further evaluate the efficacy of MDT in the treatment of hard-to-heal wounds.

Method

Participants were recruited via convenient sampling from patients attending the Wound Care Clinic at Kuala Lumpur General Hospital for diabetic foot ulcers (DFUs). Inclusion and exclusion criteria are given below.

Inclusion criteria:

Hard-to-heal DFUs with failure to heal >12 weeks from onset, but of <12 months' duration
Presence of slough, necrosis, eschar or inflammation, with or without infection.

Exclusion criteria:

Peripheral vascular disease with an ankle–brachial pressure index (ABPI) <0.5
Presence of ischaemia of the affected limb
Wounds secondary to hard-to-heal venous insufficiency.

Patients with hard-to-heal venous ulcers were excluded from the study although many such wounds had a degree of overlap with diabetic aetiology. This was done as the compression dressings used to treat these wounds would also kill any maggots in the wound bed, hence invalidating the use of MDT for these patients.

Written consent was obtained before enrolment for both medical photography as well as commencement of MDT, and for the use in educational purposes and publications. Parameters assessed during the study period were: wound size; wound bed tissue; and pain score as measured with the visual analogue scale (VAS).

Maggots adhered to a cage dressing of sterile gauze were applied to the wound bed, with a standardised coverage of 10 first-instar maggots per 1cm² of wound surface area. Washout and reassessment of the wound was conducted 72 hours after application, with re-application of first-instar maggots as needed.

The treatment endpoint was either successful wound healing or failure of the MDT, defined as absence of improvement following three consecutive applications of maggots as described above. MDT was then stopped for these patients and other methods of debridement were carried out as appropriate.

All patients included in the study had pre-existing subcutaneous insulin therapy, with regular monitoring of capillary blood to ensure optimal diabetic control.

Results

A total of 30 patients took part in this study (patient characteristics and location of wound are shown in Table 1), of whom 29 (96.6%) experienced maximum debridement of the wound surface area (defined as ≤5% coverage of the wound surface area by slough or necrotic tissue at the end of MDT). Only one patient (Case 6) had 10% of slough tissue at the end of MDT. Additionally, reduction in wound-related pain was reported across the study period.

Table 1. Patient characteristics and wound location

Case number	Age, years	Sex	Wound location
1	81	Male	Foot
2	71	Male	Abdomen
3	65	Male	Leg
4	59	Male	Foot
5	51	Female	Foot
6	57	Male	Foot
7	65	Male	Leg
8	76	Male	Foot
9	53	Female	Foot
10	57	Male	Foot
11	59	Male	Foot
12	47	Male	Foot
13	44	Female	Leg
14	65	Male	Foot
15	29	Male	Foot
16	70	Male	Foot
17	86	Female	Foot
18	60	Female	Foot
19	67	Male	Foot
20	69	Female	Foot
21	57	Male	Foot
22	63	Male	Foot
23	42	Female	Foot
24	70	Female	Foot
25	61	Male	Leg
26	69	Male	Foot
27	66	Male	Foot
28	71	Male	Foot
29	57	Female	Foot
30	39	Male	Foot

Of the patients, 14 (46.6%) cases showed >50% improvement in wound size reduction (length × width), eight (26.6%) showed a 30–40% improvement, and six (20%) cases showed a 10–20% improvement in the reduction of the wound size. The remaining two patients showed a <10% reduction in slough.

A selection of case studies showing the pre- and post-debridement outcomes of patients in this study treated with MDT are shown in Figs 1–10. The percentage of wound area reduction in patients is shown in Fig 11. Table 2 details wound size pre- and post treatment, duration of therapy and percentage wound area reduction.

Fig 1. Case 1: An 81-year-old Malay male patient with diabetes presented with a left foot ulcer showing failure to heal despite six weeks of regular dressings at the nearby health clinic (a). Wound size reduced by 76% following 10 weeks of maggot debridement therapy with no adverse effects (b)

Fig 2. Case 8: A 76-year-old Indian male patient with diabetes with a hard-to-heal lower limb wound. He underwent conventional wound debridement and ray amputation of multiple toes for gangrene of the foot (a). Wound size reduced by 34% following three weeks of maggot debridement therapy with no adverse effects (b)

Fig 3. Case 11: A 59-year-old Chinese male patient with long-standing diabetes, presented post-wound debridement and ray amputation of the right 2nd, 3rd and 4th toes for wet gangrene with a non-healing surgical wound (a). Wound size reduced by 81% following 10 weeks of maggot debridement therapy with no adverse effects (b)

Fig 4. Case 12: A 47-year-old Indian male patient with diabetes, presenting with a non-healing wound over the right foot post-debridement and ray amputation for a diabetic ulcer with gangrene (a). A 68.6% reduction in wound size was observed following eight weeks of maggot debridement therapy with no adverse effects (b)

Fig 5. Case 13: A 44-year-old Indian female patient with diabetes with a right leg wound progressing from initial blisters to a non-healing wound increasing in size (a). Wound size reduced by 38% following 10 weeks of maggot debridement therapy with no adverse effects (b)

Fig 6. Case 20: A 69-year-old Malay female patient with long-standing diabetes presented with a hard-to-heal ulcer over the right heel (a). Wound size reduced by 44% following five weeks of maggot debridement therapy with no adverse effects (b)

Fig 7. Case 21: A 57-year-old Malay male patient with diabetes presented with an infected foot ulcer, failing to improve following wound debridement and antibiotic therapy (a). Wound size reduced by 90% following nine weeks of maggot debridement therapy with no adverse effects (b)

Fig 8. Case 22: A 63-year-old Indian male patient with underlying diabetes and peripheral vascular disease, presenting with a non-healing diabetic ulcer post-debridement complicated with wound breakdown (a). Wound size reduced by 33% following seven weeks of maggot debridement therapywith no adverse effects (b)

Fig 9. Case 23: A 42-year-old Malay female patient with diabetes with a deteriorating ulcer over the sole of the right foot (a). Wound size reduced by 29% following six weeks of maggot debridement therapy (b)

Fig 10. Case 25: A 61-year-old Chinese male patient with diabetes not on regular follow-up, presented with a traumatic wound with failure to heal after two weeks of regular dressing (a). Wound size reduced by 36% following four weeks of maggot debridement therapy (b)

Table 2. Wound size pre- and post treatment, duration of therapy and percentage wound area reduction

Case number	Pre-treatment wound size, cm	Post-treatment wound size, cm	Wound therapy, start date	Wound therapy, end date	Duration of wound therapy, wound healing, days	Duration of therapy, wound healing, weeks	Wound area reduction, %
1	8.5x12	6x4	3 Jun 20	10 Aug 20	68	10	76
2	5.5x5.7	5x5.5	2 Jun 20	5 Jun 20	3	1	12
3	10x5.5	7x5	15 Jun 20	30 Jul 20	45	6	36
4	7.5x6	5x3	3 Jun 20	22 Jun 20	19	3	66
5	8x4.5	0x0	25 Jun 20	2 Oct 20	99	14	100
6	3x8	2x6	30 Jun 20	13 Aug 20	44	6	50
7	7x5	4x3	17 Jul 20	4 Sep 20	49	7	65
8	8.5x5	7x4	22 Jul 20	10 Aug 20	19	3	34
9	12x9	9x5	7 Jul 20	24 Sep 20	79	11	58
10	16x7.5	2x2	24 Jul 20	5 Nov 20	132	19	96
11	7x5.5	2x1.5	24 Jul 20	5 Nov 20	104	15	92
12	27x20	10x15	23 Jul 20	28 Oct 20	97	14	72
13	11x7	4x2	8 Jul 20	10 Dec 20	155	22	89
14	5x3x4	3x3x3.5	19 Aug 20	30 Sep 20	42	6	47
15	14x10	12x9	18 Sep 20	9 Oct 20	21	3	22
16	15x7	9x7	11 Sep 20	13 Oct 20	32	5	40
17	5x4	5x4	18 Sep 20	29 Sep 20	11	2	0
18	6x5	3x3	27 Oct 20	6 Nov 20	10	2	70
19	5x5	4x3.5	27 Jan 21	5 Mar 21	37	5	44
20	10x8	4x2	18 Jan 21	25 Mar 21	66	9	90
21	8x5	6x4.5	26 Jan 21	19 Mar 21	52	7	32
22	13x6.5	12x5	9 Feb 21	22 Mar 21	41	6	30
23	10.3x7	10x6.5	23 Feb 21	8 Mar 21	13	2	10
24	4x3.5	3x3	23 Feb 21	23 Mar 21	28	4	36
25	7x2.5	5x2.5	22 Feb 21	19 Mar 21	25	4	28
26	6.5x5	5.5x2.5	22 Feb 21	19 Mar 21	25	4	58
27	8x2.5	4x2	23 Feb 21	23 Mar 21	28	4	60
28	11x5.5	10x5	22 Feb 21	19 Mar 21	25	4	17
29	12x9	11.5x9	25 Feb 21	23 Mar 21	26	4	4
30	4.5x4	4x3.5	17 Feb 21	8 Mar 21	19	3	22

Discussion

It is evident that each patient has a different healing rate. Of the patients in this study, six (20%) required >10 weeks to show improvement in the wound bed; the majority of patients (n=24, 80%) took ≤10 less weeks to achieve an optimum wound bed condition, with <5% slough or necrotic area present at the end of MDT.

Multiple factors may affect the healing rate, for example diabetes control, concurrent peripheral vascular disease, the patient's adherence to treatment, and attendance and nutritional status. These factors are challenging to control in an outpatient setting. From our observation, wound size prior to MDT, however, does not seem to influence the healing rate. As an example, the patient in Case 13 started with a wound of 11×7cm in size, and took 22 weeks of MDT to achieve maximum debridement. On the other hand, the patient in Case 23 started with similar wound size (10.3×7cm); however, in this case it took only two weeks to accomplish maximum debridement.

MDT has been shown to be efficacious in the management of hard-to-heal wounds of various aetiologies, including DFUs, pressure injury, surgical wounds and wounds infected with meticillin-resistant Staphylococcus aureus (MRSA).^8,9,10,11,12 In the context of lower limb wounds with underlying diabetes and peripheral vascular disease, MDT has been shown to reduce amputation rates as well as the need for antibiotic therapy.¹³ Additionally, MDT has been demonstrated to be cost-effective, with one study on venous ulcers estimating the total expenditure on debridement of a wound with MDT (including dressing material and nursing costs) to be less than one fifth of the cost of a wound treated with conventional hydrogel dressings; most likely due to a reduced debridement time and fewer hospital visits.¹⁴

A number of proposed mechanisms may account for the improved wound healing observed in patients treated with MDT. Proteolytic enzymes found in the excretory/secretory products of Lucilia sericata larvae have been proposed to aid wound debridement via breakdown of the extracellular matrix.¹⁵ These excretory/secretory products have been shown to inhibit the growth of many pathogens responsible for severe soft tissue infections, including MRSA, Pseudomonas aeruginosa and Escherichia coli.¹⁶ Ammonium bicarbonate present in maggot excretions may also create an unfavourable environment for bacterial propagation by raising the local pH.¹⁷ Bacterial ingestion and destruction by maggots may be another mechanism for disinfection, with one study showing a reduction in the population of Escherichia coli bacteria following ingestion by Lucilia sericata from 67% in the proximal alimentary canal to 18% in the posterior hindgut.¹⁸ The excretory/secretory products of larvae may also enhance tissue growth by promoting the proliferation of fibroblasts as well as through the secretion of cytokines.^19,20

Our current study has shown maggot debridement therapy to be a safe and tolerable treatment modality, with no adverse effects documented for any of our 30 patients. Although no major complications were associated with the MDT, common patient complaints include minor discomfort, escape of larvae and lack of psychological acceptance.²¹

Certain wounds are known to be unsuitable for MDT, including dry and desiccated wounds, open wounds in body cavities, wounds in close proximity to vascular structures, and wounds in patients with known allergies to eggs, soybeans or fly larvae.^22,23

Limitations

Although this was a case series, limitations to the study include the relatively small sample size, and there was no secondary arm using standard of care, and so no comparisons could be drawn.

Conclusion

In conclusion, we report improvements in wound healing and reductions in wound sizes for DFUs treated with MDT, with no adverse effects and a reduction in wound-related pain over the duration of the treatment. No patients underwent amputation or required inpatient hospital admission for wound-related complications during the period of the study. Further studies comparing MDT to conventional dressings available to Malaysian healthcare facilities would serve to elucidate any advantages of efficacy and cost-effectiveness, and drive wider adoption of MDT in the management of diabetic foot wounds in the Malaysian setting.