INTRODUCTION:

Chronic Ulcers are the wounds which are generally associated with the pain as there is deposition of dead necrotic tissue into the wound. One of the better mechanism to heal is Debridement of the tissue. Debridement can be defined as the removal of dead tissue or skin cells or a reduction in the necrotic tissue.¹

One of the effective methods for the wound healing can be the live application of maggots (fly larvae) which can also be referred as Maggot Therapy.

Various Controlled Studies have indicated many advantages of maggot therapy for different types of ulcers. As it is nowadays easily available, is effective and also the material can be transported easily, it is recommended by most of the physicians or therapists currently for the treatment of ulcers.

Especially in case of non-healing wounds, it can provide much needed relief to the patients from pain which is caused by ulcers. Non-healing ulcers are generally associated with the patient having diabetes. A Study reveals that diabetic foot ulcers are the most common type of ulcers in diabetic patients (15% of diabetes population are affected by the ulcer which tallies approximately around 1.5million foot ulcer)^2,3 Hence treatment through maggot is the need of the hour.

This Article tries to focus on the overall mechanism, method of preparation(maggots), Benefits of the therapy (Including Some Statistics) as well as Current scenario of the Maggot Therapy around the globe.

HISTORY:

The History/Discovery traces back and is assumed that Maya Indians were the people who discovered the usefulness of maggot in the wound healing technique or about its debridement activity. Ambroise Pare⁴ is Considered or credited for finding out use of maggots during the 16^th century. The discovery happened during the war to St. Quentin (1557). After that, various other scientists, including Zachmann, Fabricius and Milligen observed the activity of wound healing through maggots and carried out work in the field to prove its benefits.⁵

The Major boost to this field was mainly provided by the research or experiment carried out by BAER in 1929, as he treated over 100 children having soft tissue wounds by applying live maggots to the affected wound area. This Experiment introduced maggots as an Antiseptic agent which was really path-breaking. The Experiment carried out by Baer treated 90% of cases which was a very good achievement. It was a very popular therapy during that era, though it was very hectic work.^6,7

The Popularity lasted until the discovery of antibiotics. Antibiotics provided a very tough competition with it and as a result the therapy was forgotten till 1940’s. But during the decade of 1970-1980 various technological advancement leads to the reinvention of maggot therapy as antibiotics proved to be inadequate for that period of time. The drawbacks such as cost, preparation and transportation were nullified or were reduced, which provided an edge over conventional therapy and subsequently the demand increased again.^8,9

MAGGOTS AND ITS LIFECYCLE:

The Required species for maggot therapy is generally Luciliasericata belonging to the family Calliphoridae. There are namely 3 stages of the life cycle: -

· 3 Instar

· Pupal

· Imago (Adult Stage for Maggots)

Any Necrotic tissue or wound is the hatching area for maggots and also the area wherein the female lays eggs. The hatching period varies from 9hrs to 3 days and also it requires moisture and warm environment. Female species lays up to 150-200 eggs in a single instance. While the life time capacity is about 2000-3000eggs.The size of a maggot is around 12-14mm on an average.

The 3 Larval Instars levels last for different period of time, they are as follows-

· First Instar- Around a day

· Second Instar- For around half day

· Third Instar-Around 2 days.

The above said level occurs at a temperature of 27°C., Also the procedure of 3 Instars happens during the larval stage of the lifecycle. The larval stage is an important stage as far as maggot therapy is concerned because larvae feeds on dead necrotic tissue. After the 3^rd Instar level the host is dropped onto the soil and further development of the larvae takes place. The larva then passes through other stages such as pupae and imago. The normal life cycle of Luciliasericatais around 3-4 weeks. The Cycle given below depicts roughly the “Maggot Life Cycle”.^10,11

Fig No 1 Maggot Life Cycle

Maggot Debridement Therapy (MDT):

Maggot debridement therapy, also known as MDT is the intentional application of living “medical-grade” fly larvae to non- healing wounds in order to effect debridement, disinfection, and ultimately wound healing. The maggots used for the therapy are of Phaenicia (Lucilia) sericata species as they are medicinally more effective than other species.^12,13

Mechanism of Action:

The major steps of mechanism are as follows-

· Debridement14,15

· Disinfection^16,17

· Stimulation of healing¹⁸

· Biofilm Inhibition¹⁹

DEBRIDEMENT:

The Removal of necrotic tissue from the wound is termed as Debridement. Removal of necrotic tissue is important because many bacteria present in the necrotic tissue would be eliminated, which reduces the risk of any infection and also facilitates wound healing faster.

The enzyme proteases are released by the host leukocytes, which acts on the extracellular matrix and have potential to degrade and remove the damaged extracellular matrix component. Therefore, debridement is an important step in wound healing.

DISINFECTION:

In this step of mechanism all the harmful microbes ranging from aerobic to anaerobic microbes are removed from the wound and hence preventing infection in the tissue. This is therefore termed as a disinfection stage or the beginning of antimicrobial activity of the maggots. But the wound healing therapy can prove strongest against Staphylococcus aureus, but this species is also known for its rapid antimicrobial resistance.

Stimulation of healing:

There are couple of theories for stimulation of healing. Both physical/Mechanical as well as Biochemical Pathway promotes stimulation of healing. Both the theories are capable of inducing host growth factor which ultimately reduces the debris and is useful for promotion of healing in wound.

Bio-film Inhibition:

Bio-film can prevent the antibacterial activity of the maggots and hence bio-film formation should be inhibited. Most common mechanism used by maggots is alkalisation or directly killing the bacteria by maggots.

How to Apply Maggots on a Wound?

· Maggots in the MDT are generally applied via a Surgical Dressing known as “Creature Comfort Dressing”, which creates a hydrocolloid pad to get “Confining cage”. The material used to create such dressing is polyester net. The Afro Mentioned Dressing can get exposure from air, can easily drain out the necrotic tissue and can also prevent the exit of maggots from the wound. Hence, the dressing is more advantageous and easy to apply on the wound.

· The Alternative Method for application is to just place maggots through the bandages on wound. Care must be taken that before application of maggots wound should be cleaned properly. Bandages can retain maggots on wound increasing their contact time with the site of action which in turn may give a fast recovery through decreasing necrotic tissue in the wound. The Bandages and maggots are replaced within 48-72 hrs of application.²⁰

Benefits of MDT:

1] Cost Efficiency:

A Research done to know the cost efficiency was carried out. The Result stated that the average cost of treatment by using maggot therapy was around 78.64 pounds as compared to the 132.23 pounds of conventional therapy.

However, Another Study carried out by Dumville et al., (2009) says that the cost of maggot therapy is almost similar to that of conventional therapy.^21,22

2] Efficacy:

One of the study conducted by Markveich, compares conventional therapy and maggot therapy in an around 140 patients who were suffering from non-healing diabetic foot ulcer and the following results were obtained:

· As Compared to conventional therapy, almost twice the number of wounds in subjects was debrided or treated using maggot therapy (51.1% of MDT vs 27% of conventional therapy).

· Furthermore, 7.1% patients were completely healed using Maggot Therapy as compared to the 2.8% of conventional therapy.

Though the Above statistics say a lot about the efficacy of maggot therapy, but they do not hold any statistical significance as the study was not designed to study wound healing.

McCaughan et., al (2013) also stated that the patients who received MDT were happy with their speedy recovery of the wound. Also, Spilsbury et., al (2008) reported that patients were hugely satisfied and some of them also stated that they would recommend this to other patients also.

The Table given below compares MDT and Conventional therapy in the graphical form. The graph depicts that this wound healing technique can easily reduce necrotic tissue as compared to the conventional therapy^23,24. The graph is plotted for Time (in weeks) v's Necrotic tissue surface area (cm sq.).The Graph was taken from studies done by Sherman RA²⁵

Fig No 2comparative graph of wound healing process by conventional therapy and Maggot therapy.

Therefore, the above given research suggests that the therapy can be very effective in treating the wounds.

3) Patient Acceptance: -

The Study Conducted by Pethrick et al., (2006), Spilsbury et al., (2008) and McCaughan et al., (2013) suggested that patients readily agreed to undergo larval therapy. This indicates that people are willing and do not have any problem to try out the larval wound healing therapy.

4) Topical Route of Administration: -

This can also be considered as an advantage because the route of administration does not have any kind of blood supply. Also, the first pass metabolism and other conventional therapy related parameters are avoided efficiently.

Disadvantages:

· Social Disapproval. (Yuck factor, Appearance, etc.)

· Pain during the therapy can occur.

· Disinfected or sterile maggots are not universally accepted.

· During the therapy maggots can leave the wound. However, this disadvantage can be overcome with the use of advanced surgical dressing.^26,27

But the advantages easily outplay disadvantages in this case and therefore one can assume this wound healing therapy is one of the better options for wound treatment.

Current Scenario and Future of Maggot Debridement Therapy-

· After the reinvention of the therapy, it has found a good level of attention and is being recommended by most of physician across the world particularly European countries. Despite having various problems there has been a supply of around 5 million maggots from 1995 and onwards. The supply mainly was to the various British clinics as well as European and African Clinics. The other areas around the globe are not being reported as yet. The Count is bound to increase over the years.

· The Technological advancement has helped researchers to create “Maggot Confinement Dressings” which is really very less time consuming.²⁸

· It is assumed that by 2025 around 228 million people would be suffering from diabetes mellitus (Statistics given by WHO). Ultimately the ulcer or wound cases would be very much larger.²⁹

· Hence by that time there would be need of safe, effective and economical therapy or treatment to heal the wound and hence one can easily assume that this therapy will be the future of wound healing in upcoming years.

Current Approval Status:

Currently there are over 24 laboratories which are supplied with medicinal maggots in 30 countries around the world. In the USA it is sold under the prescription only category and is approved by US FDA. In some other countries, it is sold as a normal drug.³⁰

Case Studies:

· A case study was done on a middle- aged women named as Hazel (Pseudonym). The patient had a medical history suggesting that she was suffering from Diabetes mellitus type II. An incident of minor trauma occurred and she had a wound on her lower left leg. First, she neglected it but after few weeks there was black necrotic wound developed around the injury. When she consulted a general physician, she was hospitalised and the surgeons/physicians treated her with antibiotics (IV) and with oral medication. The wound was treated but reoccurred after few weeks. The wound was swollen and had necrotic tissue in it. Then, the physicians after a discussion opted for Maggot Debridement Therapy to treat the patient. Maggots were applied for 72 hrs to the patient with the help of surgical dressing and results were observed. When the wound was observed, the area showed the sign of better recovery as the inflammation was reduced; the necrotic tissue was significantly less. The wound didn’t reoccur.^31,32

● Another Case study is of 59-year-old woman who encountered with an accident which resulted in injuries to her both legs. Her medical history was showing that she was a patient of diabetes mellitus type II and hypertension. The wound was not much cured by antibiotics and other conventional therapy. Doctors then thought of treating the patient with the Maggot Therapy. Treating the patient with the therapy prove beneficial as the wound was cured much faster and there was a sharp decline in necrotic debris around the wound.³³

Table No 1 Maggot therapy V/s Conventional therapy

Parameters	Maggot Therapy	Conventional Therapy
Cost Effectiveness	+	-
Pain	-	+
Wound healing time	+	-
Reoccurrence	-	+

+ = YES

- = No

CONCLUSION:

Though the therapy was officially introduced in the 1930’s it was neglected due to the introduction of various antibiotics. However, the disadvantages associated with antibiotics has itself opened the way for the reintroduction of maggot therapy with various new features. This all happened due to the technological boost during that era which helped it to overcome its few disadvantages and becoming a popular therapy once again. As various clinical studies and available literature suggests the advantages of Maggot Debridement Therapy over the conventional therapy it can be concluded that the therapy is very much safe, having low risk, can be fitted with an appropriate budget and can relatively work very fast. As the Lifestyle related diseases, specifically diabetes, diabetic foot ulcer, chronic ulcers and other wound related disorder will go on increasing day by day, considering efficiency of Maggot therapy and imagining our near future it can be assured that this therapy will be the “future of wound healing”.

ACKNOWLEDGEMENT:

Authors acknowledge the support and motivation from Management of SVKM’s NMIMS, our Director Pharma Institutions Dr. R. S. Gaud sir and Associate Dean Dr. A. S. Deshpande madam.

CONFLICT OF INTEREST:

Author declares no conflict of interest.

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Received on 10.12.2018 Modified on 21.01.2019

Research J. Pharm. and Tech. 2019; 12(5):2522-2526.

DOI: 10.5958/0974-360X.2019.00425.6