Maggot therapy

A wound cleaned by maggots

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 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 cleaning out the necrotic tissue within a wound (debridement) and disinfection. It was long believed that the debridement is selective on necrotic tissue but this has been questioned by recent literature.^[1]

History

Early history

Written records have documented that maggots have been used since antiquity as a wound treatment.^[2] 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 general surgeon, Baron Dominique Larrey, who reported during France's Egyptian campaign in Syria, 1798–1801, that certain species of fly destroyed only dead tissue and had a positive effect on wound healing.^[3]

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.^[4]

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%.^{[citation needed]}

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 two months of maggot therapy.

After the publication of Dr. Baer's results in 1931,^[5] 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,^[6][7] and chronic empyema.^[8]

More than 300 American hospitals employed maggot therapy during the 1940s. The extensive use of maggot therapy prior to World War II was curtailed when the discovery and growing use of penicillin caused it to be deemed outdated. Due to the lack of conventional medicines, maggot therapy was used by Allied military medical staff in Japanese prisoner of war camps in the Far East throughout World War II.^[9]

Reintroduction

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.^[10]

The therapeutic maggot used by Sherman is a strain of the green bottle fly (Phaenicia sericata) and marketed under the brand name Medical Maggots.^[11]

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, most of them are included in a British study financed by NHS.^[12]

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.^[13]

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.^[14]

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]}

Regulation

In January 2004, the U.S. Food and Drug Administration (FDA) granted permission to produce and market maggots for use in humans or animals as a prescription-only medical device for the following indications:^[15][16] "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 (NHS) permitted its doctors to prescribe maggot therapy. In Europe, Canada and Japan maggots are classified as medicinal drugs, needing a full market licence. In US maggots for medicinal use are classified as a device.

Veterinary use

The use of maggots to clean dead tissue from animal wounds is part of folk medicine ^[17] 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 Dr. 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.^[18]

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.^[19]

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.

Mechanisms of action

The maggots have one principal action reported in the medical literature:

• debride wounds by dissolving only necrotic, infected tissue.^[12]

Disinfection of the wound by killing bacteria and healing could not be proved by the largest clinical study available.^[12]

Maggot therapy has been shown to accelerate debridement of necrotic wounds and reduce the bacterial load of the wound, reduced wound odor, and lessening the pain in some cases. In about 1/3 of all patients pain is increased. ^[12] The combination and interactions of these actions make maggots an extremely potent tool in wound debridement.

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.

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 sepsis.

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 consume necrotic tissue far more precisely than is possible in a normal surgical operation, and can debride a wound in a day or two. While in the past it was believed that maggots do not damage healthy tissue, this is in doubt now.^[1] They derive nutrients through a process known as "extracorporeal digestion" by secreting a broad spectrum of proteolytic enzymes^[20] 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. When they stay longer or too many are used, healthy tissue is removed as well.^[1]

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 some 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.^[21] 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. Other bacteria like Pseudomonas aeruginosa, E.coli or Proteus spec are not attacked by maggots and in case of Pseudomonas even the maggots are in danger.^[22] Therefore, using maggots alone might lead to a change of bacteria flora on the wound. Maggot therapy therefore represents a cost-effective method for managing MRSA infection.

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 (EGF) 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.^{[23][24][25][26][27]} The by far biggest clinical study shows, that healing cannot be expected by maggots.^[1][12]

Maggot secretions also contain a substance called allantoin (also found in many shaving gels) which has a soothing effect on the skin.^[28] 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.^[29]

Limitations

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.^[30] Patients and doctors may find maggots distasteful, although studies have shown that this does not cause patients to refuse the offer of maggot therapy.^[31] 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.^[32] Dressings are also designed to minimize the uncomfortable tickling sensation that the maggots often cause.^[33]

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.^[12] 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.^[12][34]

Biology of flies and maggots used in maggot therapy

Green Bottle Fly

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. The infestation by maggots of live animals is called “myiasis.” Some 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.^[35]

In popular culture

In a scene set in 1809, the wound of Lt. Sharpe (Sean Bean) is left clean by applied maggots in the 1993 TV programme Sharpe's Eagle. Rather than being merely discussed, the maggots are shown on the skin around the wound. In the 2000 film Gladiator, Russell Crowe's character has a shoulder wound cleaned with maggots.

In the Roman Mysteries series maggots were used on an injury as an alternative to amputation. In the story the therapy was successful and the man was able to walk again.

In addition, the television show House, M.D. included treatment of a burn by maggot therapy in the twelfth episode of the second season, titled "Distractions," on February 14, 2006.

Claire Frazier, a medical practitioner and principal character in Diana Gabaldon's Outlander series of novels, often uses maggots for debridement of necrotic tissue in her patients' wounds.

The titular character of Johnny Got His Gun claims that maggot therapy could have prevented his quadruple amputations.

See also

• Parasite
• Parasitology
• Lucilia sericata

References

1. ^ ^{a b c d} http://www.bmj.com/content/338/bmj.b773.abstract/reply#bmj_el_250988
2. ^ Whitaker IS, Twine C, Whitaker MJ, Welck M, Brown CS, Shandall A (2007). "Larval therapy from antiquity to the present day: mechanisms of action, clinical applications and future potential". Postgraduate medical journal 83 (980): 409–13. doi:10.1136/pgmj.2006.055905. PMC 2600045. PMID 17551073. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2600045. 
3. ^ Sherman RA, Hall MJ, Thomas S (2000). "Medicinal maggots: an ancient remedy for some contemporary afflictions". Annu. Rev. Entomol. 45: 55–81. doi:10.1146/annurev.ento.45.1.55. PMID 10761570. 
4. ^ Donnelly, Jean. 1998. Wound Healing - from poultices to maggots. (A short synopsis of wound healing throughout the ages). The Ulster Medical Journal. 67 (Suppl 1): 47-51.PDF
5. ^ Baer, W. S. (1931): The treatment of chronic osteomyelitis with the maggot (larvae of the blowfly). Journal of Bone and Joint Surgery 13: 438-475.
6. ^ Hewitt, F. (1932): Osteomyelitis; Development of the use of maggots in treatment. American Journal of Nursing 32: 31-38.
7. ^ McKeever, D. C. (1933): Maggots in treatment of osteomyelitis: A simple inexpensive method. Journal of Bone and Joint Surgery 15: 85-93.
8. ^ Bethune, N. (1935): A case of chronic thoracic empyema treated with maggots. Can Med Assoc J 32: :301-302. (Cited at Norman Bethune and Edward Archibald: sung and unsung heroes)
9. ^ http://web.archive.org/web/20070928212353/www.zoobiotic.org/maggots-in-wartime/
10. ^ Sherman RA, Wyle F, Vulpe M (1995). "Maggot therapy for treating pressure ulcers in spinal cord injury patients". J Spinal Cord Med 18 (2): 71–4. PMID 7640976. 
11. ^ http://www.monarchlabs.com/
12. ^ ^{a b c d e f g} http://www.bmj.com/content/338/bmj.b773.abstract
13. ^ Steenvoorde P, van Doorn LP, Jacobi CE, Oskam J (2007). "Maggot debridement therapy in the palliative setting". The American journal of hospice & palliative care 24 (4): 308–10. doi:10.1177/1049909107302300. PMID 17895494. 
14. ^ Nic Fleming, Maggots used to counter MRSA superbug, Telegraph.co.uk, March 5, 2007. available online
15. ^ FDA CDRH 510(k) summary LINK
16. ^ The Pink Sheets Panel To Recommend Classifications For Five Preamendments Medical Devices Aug. 25-26 LINK
17. ^ http://www.amazon.com/Honey-Maggots-Other-Medical-Marvels/dp/0395924928
18. ^ Sherman RA, Morrison S, Ng D (2007). "Maggot debridement therapy for serious horse wounds - a survey of practitioners". Vet. J. 174 (1): 86–91. doi:10.1016/j.tvjl.2006.05.012. PMID 16831562. 
19. ^ Monarch Labs package insert for Medical MaggotsTM http://www.monarchlabs.com/maggotpi.pdf
20. ^ Reames, M. K.; Christensen, C. & Luce, E. A. (1988): The use of maggots in wound debridement. Annals of Plastic Surgery 21(4): 388-391. PMID 3232928 (HTML abstract)
21. ^ Pavillard, E. R., Wright, E. A. An antibiotic from maggots. Nature 1957; 180: 916-917.74
22. ^ http://mic.sgmjournals.org/cgi/content/abstract/156/2/400
23. ^ Sherman RA (2003). "Maggot therapy for treating diabetic foot ulcers unresponsive to conventional therapy". Diabetes Care 26 (2): 446–51. doi:10.2337/diacare.26.2.446. PMID 12547878. 
24. ^ Sherman, R. A.; Wyle, F. & Vulpe, M. (1995): Maggot Debridement Therapy for treating pressure ulcers in spinal cord injury patients. Journal of Spinal Cord Medicine 18(2): 71-74. PMID 7640976 (HTML abstract)
25. ^ Sherman, R.A. & Pechter, E.A. (1988): Maggot Therapy: A review of the therapeutic applications of fly larvae in human medicine, especially for treating osteomyelitis. Medical and Veterinary Entomology 2(3): 225-230. PMID 2980178 (HTML abstract)
26. ^ Sherman, R. A.; Tran, J. & Sullivan, R.: (1996) Maggot Therapy for treating Venous Stasis Ulcers. Arch. Dermatol. 132: 254-256.
27. ^ Sherman, R. S. (2003): Maggot Therapy for treating diabetic foot ulcers unresponsive to conventional therapy. Diabetes Care 26(2): 446-451. PDF fulltext
28. ^ in the Introduction chapter by Borror et al., in "An introduction to the study of insects" 6th Ed.
29. ^ Todd Neale (March 2009). "Maggot Therapy: No Advantage for Leg Ulcers". York, England: MedPage Today. http://www.medpagetoday.com/PublicHealthPolicy/PublicHealth/13356. Retrieved 2009-07-07. 
30. ^ "The Role of Maggots in Modern Wound Therapy". Archived from the original on September 29, 2007. http://web.archive.org/web/20070929071855/http://www.telfordpct.nhs.uk/healthcare_professionals/nursing_services/maggots.pdf. Retrieved 2007-05-06. ^{[dead link]}
31. ^ Parnés, A.; Lagan, K. M.. "Larval Therapy in Wound Management: A Review". http://www.medscape.com/viewarticle/554795_1. Retrieved 2007-05-06. 
32. ^ V. Scavée, Fr.-X. Polis, J.-Cl. Schoevaerdts. "Maggot Therapy : Many Hands Make Light Work". Archived from the original on September 29, 2007. http://web.archive.org/web/20070929092907/http://www.belsurg.org/imgupload/RBSS/scavie_schoevaerdts.pdf. Retrieved 2007-05-06. 
33. ^ Rosemary Morgan. "Larval Therapy". http://www.studentbmj.com/issues/02/08/education/271.php. Retrieved 2007-05-06. 
34. ^ "Maggot therapy hope 'premature'". BBC News. 2009-03-20. http://news.bbc.co.uk/1/hi/health/7953091.stm. Retrieved 2010-05-12. 
35. ^ Sherman, R. A., M. J. R. Hall, and S. Thomas. “Medicinal Maggots: an Ancient Remedy for Some Contemporary Afflictions.” Annu. Rev. Entomol. 45(2000):55-81.

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