Maggot therapy

# Overview
Maggot therapy (also known as Maggot Debridement Therapy (MDT), larval therapy, larva therapy, or larvae therapy) is a type of biotherapy involving the intentional introduction by a health care practitioner of live, disinfected maggots (fly larvae) into the non-healing skin and soft tissue wound(s) of a human or animal for the purpose of selectively cleaning out only the necrotic (dead) tissue within a wound in order to promote wound healing.

# History of use
Written records have documented that maggots have been used since antiquity as a safe and effective wound treatment.  There are reports of the successful use of maggots for wound healing by Mayan Indians and Aboriginal tribes in Australia. There also have been reports of the use of maggot treatment in the 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 Napoleons 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. 
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.
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%.
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, alkalization of wound beds and ideal rates of healing.  All 21 of his 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, maggot therapy for wound care became very common, particularly in the United States.  The pharmaceutical company, Lederle, commercially produced in large numbers "Surgical Maggots", larvae of the green bottle fly (Phaenicia sericata), a facultative, necrophagous organism that only consumes necrotic 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 and sub-acute mastoiditis.
More than 300 American hospitals employed maggot therapy.  Maggot therapys extensive use prior to World War II was curtailed when the discovery and growing use of penicillin caused it to be deemed outdated.

# Recent clinical experience
With the advent of antibiotic-resistant bacteria, Dr. Ronald Sherman, a physician presently at the University of California, Irvine, successfully re-introduced maggot therapy into the armamentarium of modern medical care as a safe and effective therapy.  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, he initiated the first prospective controlled clinical trial of maggot therapy in spinal cord patients with pressure ulcers using a Paralyzed Veterans of America grant.  The successes of this clinical trial in patients who had failed two or more courses of conventional wound care, were published and generated significant international attention to maggot therapy.  The therapeutic maggot used by Dr. Ronald Sherman is a strain of the green bottle fly (Phaenicia sericata) and marketed as "Medical Maggots".
In just the last four years, 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.  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.
In a 2007 preliminary trial maggots were used successfully to treat patients with MRSA, a bacterium which has developed resistance to all penicillins.
The current use of maggot therapy is estimated to involve over 3,000 doctors, clinics, and hospitals in over 20 countries. In 2003 approximately 30,000 treatments were administered to an estimated 6,000 to 10,000 patients.

# United States Food and Drug Administration regulation
In the United States, Medical Maggots are regulated by the Food and Drug Administration as a prescription only medical device.  With acceptance of premarket notification 510(k) 033391 in January of 2004, the Food and Drug Administration granted Dr. Ronald Sherman permission to produce and market maggots for use in humans or other animals as a prescription use medical device for the following indications:
"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."
Monarch Labs is the exclusive supplier of Medical Maggots (disinfected Phaenicia sericata  larvae) for maggot debridement therapy in the United States.
Currently, there are over 500 health care centers in the United States that have utilized maggot therapy.
Medical Maggots represent the first living organism ever allowed by the Food and Drug Administration for production and marketing as a prescription medical device.

# 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.  While maggot therapy can not be used simultaneously with negative pressure wound therapy (NPWT), it can be used prior to NPWT to debride a wound so that it can be later closed with NPWT.

## 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.
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. 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": they secrete a broad spectrum of proteolytic enzymes 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.

## 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 1930's to possess potent antimicrobial activity.  As early as 1957, a specific antibiotic factor was found in maggot secretions and published in the journal Nature. 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, 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.  Maggot therapy therefore represents a highly cost-effective method for managing MRSA infection without exacerbating the problems of antibiotic resistance.

## 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 area of study by several researchers including Dr. Ronald Sherman.  
Maggot secretions also contain a substance called as allantoin (also found in many shaving gels) which has a soothing effect on the skin. 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.

## Application of maggot wound dressings
The application of maggot dressings is simple: maggots are contained in a cage-like dressing over the wound for 2 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.  Complete removal of maggots from a wound is easily accomplished.  Multiple two day courses of maggot therapy may be administered depending on the severity of the non-healing wound.

# Limitations of maggot therapy
Maggots have a short shelf life which prevents long term storage before use. Patients and doctors may find maggots distasteful, although studies have shown that this does not cause patients to refuse the offer of maggot therapy.  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 larvae. Dressings are also designed to minimize the uncomfortable tickling sensation that the maggots often cause. The maggots are sometimes painful to patients with ischemic wounds, possibly because they  anchor to the tissue.

# Therapy for horses and other animals
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 by work equipment. Formal maggot therapy for horses in the United States began in 2003 (after a study running from 1997 to 2003) by Kentucky hoof-specialist veterinarian Scott Morrison of Rood and Riddle Equine Hospital in Lexington, Kentucky.  Dr. Morrison is a frequent consultant on cases of complications of laminitis and other hoof diseases. He recommends maggot therapy 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.