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Maggot therapy (also known as maggot debridement therapy (MDT), larval therapy, larva therapy, larvae therapy, biodebridement or biosurgery) is a type of biotherapy involving the intentional introduction by a health care practitioner of live, disinfected maggots (fly larvae) raised in special facilities into the non-healing skin and soft tissue wound(s) of a human or other animal for the purposes of selectively cleaning out only the necrotic tissue within a wound (debridement), disinfection, and promotion of wound healing.

Contents 1 History of use 1.1 Early use 1.2 Modern use 1.3 Reintroduction 1.4 Regulation 1.5 Veterinary maggot therapy 2 Application of maggot wound dressings 3 Mechanisms of action 3.1 Debridement 3.2 Disinfection 3.3 Wound healing 4 Limitations of maggot therapy 5 Comparative studies 6 Biology of flies and maggots used in maggot therapy 7 Depictions in Literature, Film, and Television 8 References 9 External links 10 See also

[edit] History of use

[edit] Early use

Written records have documented that maggots have been used since antiquity as a wound treatment.^[1] There are reports of the successful use of maggots for wound healing by Maya Indians and Aboriginal tribes in Australia. There also have been reports of the use of maggot treatment in Renaissance times. During warfare, many military physicians observed that soldiers whose wounds had become colonized with maggots experienced significantly less morbidity and mortality than soldiers whose wounds had not become colonized. These physicians included Napoleon’s surgeon general, Baron Dominique Larrey, who reported during France's Egyptian campaign in Syria, 1829, that certain species of fly destroyed only dead tissue and had a positive effect on wound healing.^[2]

Dr. Joseph Jones, a ranking Confederate medical officer during the American Civil War, is quoted as follows, "I have frequently seen neglected wounds ... filled with maggots ... as far as my experience extends, these worms only destroy dead tissues, and do not injure specifically the well parts." The first therapeutic use of maggots is credited to a second Confederate medical officer Dr. J.F. Zacharias, who reported during the American Civil War that, "Maggots ... in a single day would clean a wound much better than any agents we had at our command ... I am sure I saved many lives by their use. " He recorded a high survival rate in patients he treated with maggots.^[3]

During World War I, Dr. William S. Baer, an orthopedic surgeon, recognized on the battlefield the efficacy of maggot colonization for healing wounds. He observed one soldier left for several days on the battlefield who had sustained compound fractures of the femur and large flesh wounds of the abdomen and scrotum. When the soldier arrived at the hospital, he had no signs of fever despite the serious nature of his injuries and his prolonged exposure to the elements without food or water. When his clothes were removed, it was seen that "thousands and thousands of maggots filled the entire wounded area." To Dr. Baer's surprise, when these maggots were removed "there was practically no bare bone to be seen and the internal structure of the wounded bone as well as the surrounding parts was entirely covered with most beautiful pink tissue that one could imagine." This case took place at a time when the death rate for compound fractures of the femur was about 75-80%.

[edit] Modern use

While at Johns Hopkins University in 1929, Dr. Baer introduced maggots into 21 patients with intractable chronic osteomyelitis. He observed rapid debridement, reductions in the number of pathogenic organisms, reduced odor levels, alkalinization of wound beds, and ideal rates of healing. All 21 patients' open lesions were completely healed and they were released from the hospital after 2 months of maggot therapy.

After the publication of Dr. Baer's results in 1931,^[4] maggot therapy for wound care became very common, particularly in the United States. The Lederle pharmaceutical company commercially produced "Surgical Maggots", larvae of the green bottle fly, which primarily feed on the necrotic tissue of the living host without attacking living tissue. Between 1930 and 1940, more than 100 medical papers were published on maggot therapy. Medical literature of this time contains many references to the successful use of maggots in chronic or infected wounds including osteomyelitis, abscesses, burns, sub-acute mastoiditis,^[5][6] and chronic empyema.^[7]

More than 300 American hospitals employed maggot therapy during the 1940s. Maggot therapy’s extensive use prior to World War II was curtailed when the discovery and growing use of penicillin caused it to be deemed outdated.

[edit] Reintroduction

This section needs additional citations for verification. Please help improve this article by adding reliable references (ideally, using inline citations). Unsourced material may be challenged and removed. (October 2008)

With the advent of antibiotic-resistant bacteria, Dr. Ronald Sherman, a physician previously at the University of California, Irvine, sought to re-introduce maggot therapy into the armamentarium of modern medical care. In 1989, he set up fly breeding facilities at the Veterans Affairs Medical Center in Long Beach, California, in order to use maggots for the treatment of wounds. That year, using a Paralyzed Veterans of America grant, he initiated a prospective controlled clinical trial of maggot therapy for spinal cord patients with pressure ulcers who had failed two or more courses of conventional wound care.^{[citation needed]}

The therapeutic maggot used by Sherman is a strain of the green bottle fly (Phaenicia sericata) and marketed under the brand name Medical Maggots.^[8]

Over fifty scientific papers have been published that describe the medical use of maggots. Six thousand maggot therapy patients have been included in case histories or other studies. About 400 patients have been documented within clinical studies.^{[citation needed]}

In the medical literature, limb salvage rates with maggot therapy are about 40% to 50%. Some report success rates of 70% to 80%, though definitions of "success" can vary.^[9]

In a 2007 preliminary trial, maggots were used successfully to treat patients whose wounds were infected with MRSA, a bacterium (Staphylococcus aureus) with resistance to most antibiotics, including methicillin. Some of these strains include "flesh eating bacteria" causing frequent deaths upon infection of deep tissue. Maggots clean up the already dead tissue thus preventing further infection spread.^[10]

In 1995, a handful of doctors in 4 countries were using maggot therapy. Today, any physician in the U.S. can prescribe maggot therapy. There are over 800 health care centers in the United States that have utilized maggot therapy. Over 4,000 therapists are using maggot therapy in 20 countries. Approximately 50,000 treatments were applied to wounds in the year 2006.^{[citation needed]}

[edit] Regulation

In January 2004, the U.S. Food and Drug Administration granted permission to produce and market maggots for use in humans or other animals as a prescription only medical device for the following indications:^[11] "For debriding non-healing necrotic skin and soft tissue wounds, including pressure ulcers, venous stasis ulcers, neuropathic foot ulcers, and non-healing traumatic or post surgical wounds." In February 2004, the British National Health Service permitted its doctors to prescribe maggot therapy.

[edit] Veterinary maggot therapy

The use of maggots to clean dead tissue from animal wounds is part of folk medicine in many parts of the world. It is particularly helpful with chronic osteomyelitis, chronic ulcers, and other pus-producing infections that are frequently caused by chafing due to work equipment. Maggot therapy for horses in the United States was re-introduced after a study published in 2003 by veterinarian Scott Morrison. This therapy is used in horses for conditions such as osteomyelitis secondary to laminitis, sub-solar abscesses leading to osteomyelitis, post-surgical treatment of street-nail procedure for puncture wounds infecting the navicular bursa, canker, non-healing ulcers on the frog, and post-surgical site cleaning for keratoma removal.^[12]

[edit] Application of maggot wound dressings

Maggots are contained in a cage-like dressing over the wound for two days. The maggots may be allowed to move freely within that cage, with the wound floor acting as the bottom of the cage; or the maggots may be contained within a sealed pouch, placed on top of the wound. The dressing must be kept air permeable because maggots require oxygen to live. When maggots are satiated, they become substantially larger and seek to leave the site of a wound. Multiple two-day courses of maggot therapy may be administered depending on the severity of the non-healing wound.^[13]

Maggots can never reproduce in the wound since they are still in the larval stage and too immature to do so. Reproduction can only occur when they become adult flies and mate.

[edit] Mechanisms of action

The maggots have three principal actions reported in the medical literature:

• debride wounds by dissolving only necrotic, infected tissue;
• disinfect the wound by killing bacteria; and
• stimulate wound healing.

Maggot therapy has been shown to accelerate debridement of necrotic wounds and reduce the bacterial load of the wound, leading to earlier healing, reduced wound odor, and less pain. The combination and interactions of these actions make maggots an extremely potent tool in wound care.

Maggot therapy is further compatible with other wound care therapies such as antibiotics, negative pressure wound therapy (NPWT), skin grafting and hyperbaric oxygen therapy. While maggot therapy can not be used simultaneously with NPWT, it can be used prior to NPWT to debride a wound so that it can be later closed with NPWT. Similarly, while maggot therapy can not be used simultaneously with skin grafting, it can be used prior to skin grafting to debride a wound so that it can be later closed with skin grafting.

[edit] Debridement

The debridement of necrotic tissue is a prerequisite for successful wound care. If debridement does not take place, wound repair is significantly impaired. Necrotic tissue in the wound is not only an obstacle for localized treatment, but becomes an ideal breeding ground for bacteria and may lead to gangrene, necessitating limb amputation, and potentially fatal septicemia.

Surgeons cannot be very precise in debriding dead tissue while leaving living tissue. The human eye is simply not very discriminating in identifying healthy tissue from necrotic tissue, and surgeons only have a very limited time to operate while their patient is under anesthesia. Consequently, surgeons use their scalpels to remove far more viable tissue than is needed, producing a wound larger than necessary that has more bleeding and a greater chance of becoming infected. Patients also experience more wound-associated pain after removal of healthy tissue. Wound care therapists can find themselves needing to debride a wound day after day, deeper and deeper; this is impractical as surgeons simply do not have the time to perform frequent surgical debridements. The requirement for frequent surgical debridement complicates and lengthens wound healing, lengthening hospital stays and increasing costs.

In maggot therapy, a large number of small maggots selectively consume only necrotic tissue far more precisely than is possible in a normal surgical operation, and can debride a wound in a day or two. These maggots do not damage healthy tissue: they operate with precision at the boundary between healthy and necrotic tissue. They derive nutrients through a process known as "extracorporeal digestion" by secreting a broad spectrum of proteolytic enzymes^[14] that liquefy necrotic tissue, and absorb the semi-liquid result within a few days. In an optimum wound environment maggots molt twice, increasing in length from 1-2 mm to 8-10 mm, and in girth, within a period of 3-4 days by ingesting necrotic tissue, leaving a clean wound free of necrotic tissue when they are removed.

[edit] Disinfection

Any wound infection is always a serious medical complication. Infected living tissue cannot heal. If the wound is infected with an antibiotic-resistant bacterial strain, it becomes difficult or impossible to treat the underlying infection and for any healing to occur. Wound infection could further be limb- and life-threatening. When maggots successfully debride a necrotic wound, a source of wound infection is removed.

For wounds already infected, maggot therapy is effective even against antibiotic-resistant bacteria. Maggot secretions were first experimentally shown in the 1930s to possess potent antimicrobial activity. As early as 1957, a specific antibiotic factor was found in maggot secretions and published in the journal Nature.^[15] Secretions believed to have broad-spectrum antimicrobial activity include allantoin, urea, phenylacetic acid, phenylacetaldehyde, calcium carbonate, and proteolytic enzymes. Bacteria not killed by these secretions are subsequently ingested and lysed within the maggots.

In vitro studies have shown that maggots inhibit and destroy a wide range of pathogenic bacteria including methicillin-resistant Staphylococcus aureus (MRSA), group A and B streptococci, and Gram-positive aerobic and anaerobic strains. In a published review of five patients who were infected with MRSA, some having failed conventional therapy for up to 18 months, maggot therapy was able to eliminate the bacterium from all wounds in an average of 4 days.^{[citation needed]} Maggot therapy therefore represents a highly cost-effective method for managing MRSA infection without exacerbating the problems of antibiotic resistance.

[edit] Wound healing

Maggot therapy has been shown by multiple researchers to have wound healing properties. Maggot secretions appear to amplify the wound healing effects of host epidermal growth factor and IL-6. Recent studies have shown that maggot secretions are able to stimulate the growth of human fibroblasts and slow-growing chondrocytes. Chondrocyte proliferation, as well as the synthesis of cartilage-specific type II collagen, increases in the maggot secretion environment. Micromassage of the wound by maggot movement is further thought to stimulate the formation of granulation tissue and wound exudates by the host. The precise mechanism(s) of maggot stimulation of wound healing is an active area of study by several researchers including Dr. Ronald Sherman. ^{[16][17][18][19][20]}

Maggot secretions also contain a substance called allantoin (also found in many shaving gels) which has a soothing effect on the skin.^[21] Some patients with leg ulcers with a significant arterial component complain that their wounds become more painful on the second or third day of maggot therapy.^[22]

[edit] Limitations of maggot therapy

The wound must be of a type which can actually benefit from the application of maggot therapy. A moist, exudating wound with sufficient oxygen supply is a prerequisite. Not all wound-types are suitable: wounds which are dry, or open wounds of body cavities do not provide a good environment for maggots to feed. In some cases it may be possible to make a dry wound suitable for larval therapy by moistening it with saline soaks, applied for 48 hours.

Maggots have a short shelf life which prevents long term storage before use.^[23] Patients and doctors may find maggots distasteful, although studies have shown that this does not cause patients to refuse the offer of maggot therapy.^[24] Maggots can be enclosed in opaque polymer bags to hide them from sight. Dressings must be designed to prevent any maggots from escaping, while allowing air to get to the maggots.^[25] Dressings are also designed to minimize the uncomfortable tickling sensation that the maggots often cause.^[26]

[edit] Comparative studies

In 2008, a scientific study published in the British Medical Journal compared the merits of maggot therapy and standard hydrogels to treat 270 British patients with leg ulcers from around the UK. Patients were treated with either maggots or hydrogel and their progress followed for up to a year.

The study revealed no significant differences in the time taken for the ulcer to heal, or in the patient's quality of life. Maggots were shown to be no more effective than hydrogel treatment at reducing the amount of bacteria present or in clearing MRSA. Although maggots were significantly more efficient at debridement of the wound, treatment with maggots was associated with more pain by patients. A separate study which compared the relative cost-effectiveness of maggot therapy with hydrogels estimated there was little to choose between the two therapies.^[27]

[edit] Biology of flies and maggots used in maggot therapy

Maggots are fly larvae, or immature flies, just as caterpillars are butterfly or moth larvae. Not all species of flies are safe and effective as medicinal maggots. There are thousands of species of flies, each with its own habits and life cycle. Some fly larvae feed on plants or animals, or even blood. Others feed on rotting organic material.

Those flies whose larvae feed on dead animals will sometimes lay their eggs on the dead parts (necrotic or gangrenous tissue) of living animals. When maggots are infesting live animals, that condition is called “myiasis.” Some of those maggots will feed only on dead tissue, some only on live tissue, and some on live or dead tissue. The flies used most often for the purpose of maggot therapy are "blow flies" (Calliphoridae); and the species used most commonly is Phaenicia sericata, the green blow fly. Another important species, Protophormia terraenovae, is also notable for its feeding secretions, which combat infection by Streptococcus pyogenes and Streptococcus pneumoniae. ^[28]

[edit] Depictions in Literature, Film, and Television

• In Bernard Cornwell's Richard Sharpe series, maggot therapy is a favored remedy of Sharpe's loyal sergeant, Patrick Harper, who keeps a tin of maggots handy as both fishing bait and to medicine officers' wounds.
• The 2000 film Gladiator directed by Ridley Scott has a brief scene depicting maggot therapy. The Roman general Maximus (Russell Crowe) suffers a deep laceration to his shoulder, which is left open and allowed to infest for several days. During a journey with a slave caravan, a Numidian slave named Juba (Djimon Hounsou) places maggots in the wound to clean it.
• In the fifth volume of The Roman Mysteries by Caroline Lawrence, The Dolphins of Laurentum, a Jewish doctor uses maggots collected from scraps at the local butchers to clean infected sores on a shipwrecked sea captain's feet. This therapy is likewise depicted in the film adaptation.
• In an episode of House, M.D., "Distractions," the team of doctors uses maggots to clean the dead skin off of a boy who was in an ATV accident.

Modern maggot therapy differs mainly in its use of supportive measures, such as using sterile dressings and maggots, maintaining moisture, restricting the maggots from leaving the wound site, and keeping the maggots out of view of squeamish patients and practitioners.

[edit] References

[edit] External links

• National Geographic video segment on Maggot Medicine on youtube.com
• The NIH Record; Medieval Miracle Workers — Are Maggots Making a Medical Comeback? The National Institutes of Health experience with maggot therapy
• Wound Care Information Network write-up on everything you want to know about maggot therapy

[edit] See also

• Parasite
• Parasitology
• Flies
• Lucilia sericata