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Larval Therapy: A Review of Clinical Human and Veterinary Studies


Authors

Janet Hinshaw,
Veterinary Student,
Kansas State University,
USA

Contents


Published in World Wide Wounds: October 2000
Version: 1.0

Introduction

The practice of using first instar larvae (maggots) of flies to heal wounds has been around for centuries. In the pre-antibiotic era, physicians noted that larvae would debride wounds of necrotic tissue and greatly improve the prognosis for disease in their patients. Larvae work continually to remove the dead tissue and cleanse it of bacteria while leaving the viable cells alone. Larval therapy gained acceptance and was widely used until the discovery of antibiotics in the 1940's. With the emergence of antibiotic-resistant strains of microbes, larval therapy is again being investigated as a viable treatment of wounds. Veterinary medicine appears to be falling behind human medicine in utilizing maggots. Fly larvae can be used to heal ulcerative lesions, burns, certain types of benign and malignant tumors, abscesses, and osteomyelitis when conventional treatments fail or are inappropriate. They are easy to apply, relatively inexpensive, and do not destroy normal gastrointestinal flora or leave violative residues as do systemic antibiotics.

History

Reports of the deliberate introduction of maggots into infected and gangrenous wounds, followed by successful healing, date back to ancient times and span various cultures world-wide. The Mayan Indians wrapped wounds with a dressing made of sun-exposed beef blood that would pulsate, apparently with maggots, a few days after it was applied. [1] [2] An aboriginal tribe in Australia cleansed wounds with maggots by following the protocols handed down for generations.[1] [3] In Newfoundland, a severe infection in a fisherman's hand was treated by an elderly woman who used maggots the, 'old way my mother show (sic) me.'[1]

One of the first written reports of larval therapy is credited to Ambroise Paré. Paré, chief surgeon to France's Charles IX and Henri III, noted the beneficial effects of maggots in the wounds of soldiers in 1557. [3] In 1829, Baron D.J. Larrey, while serving as a military surgeon for Napoleon's armies, observed that maggots only attacked necrotic tissue and promoted healing of wounds.[2] During the Civil War, Confederate surgeons Joseph Jones and J.F. Zacharias began using maggots to treat wounds. Zacharias noted that, 'in a single day [maggots] would clean a wound much better than any agents we had at our command . . . I am sure I saved many lives by their use.' [4] [5]

The first scientific studies of maggots' medicinal uses were conducted by Dr. W.S. Baer.[2] [3] [4] [5] [6] Baer began an extensive study of the blowfly after having treated two soldiers during World War I. He commented that although the soldiers had lain unattended for seven days on a battlefield, their compound fractures and abdominal wounds, which were infested with thousands of maggots, contained healthy granulation tissue. During this pre-antibiotic era, mortality from such types of wounds was close to 75%. During the 1920's and 1930's, Baer reported the successful treatment of osteomyelitis and chronic leg ulcers in over 90 patients by using maggots. He found that the maggots would debride necrotic wounds and promoted the formation of healthy granulation tissue. By 1935 over 200 hospitals and more than 600 doctors had used maggots to treat over 5,700 patients in the United States and Canada. [7] [8] Larval therapy has also been used to successfully treat malignant breast ulcers, burns, abscesses, squamous cell carcinomas, and subacute mastoiditis. The discovery of penicillin and sulfa drugs in the 1940's led to the decline of maggot therapy. However, with the emergence of antibacterial-resistant strains of microbes, human medicine is again "discovering" the benefits of larval therapy.

Human Case Histories

Necrotic, suppurative, draining, gangrenous wounds are best suited for larval therapy. Traditionally, larvae are applied to a lesion as the last line of defense--usually after the patient has endured months of antibiotic treatment and surgical debridement without successful healing. Larval therapy is also useful when the patient has compromised health or cannot tolerate antibiotics. Whereas oral antibiotics and phagocytic cells require an adequate blood supply to reach the affected area, maggots only require the oxygen in an open wound in order to debride a necrotic wound and cleanse it of bacteria. Larvae are also effective in eliminating all types of bacteria, including methicillin-resistant Staphylococcus aureus (MRSA). Case studies provide examples of the amazing capabilities of maggots.

In 1995, a 31-year-old male was diagnosed with an infection to a scratch he had sustained the previous week and was prescribed oral antibiotics. [4] One week later he was diagnosed with septicemia and was prescribed intravenous (IV) antibiotics. The infection was controlled, however a cavity wound developed at the site. At that time the wound was dressed with a hydrogel to promote autolytic debridement. One month later, the wound contained a malodorous exudate and measured 5 cm. Larval therapy was instituted at that time. Three days later, the odor was no longer evident, granulation tissue was present, the wound was reduced to 1 cm, and a second application of larvae was applied. During the dressing change three days later, granulation tissue was present up to the level of the dermis. The larval treatment was discontinued and the wound was dressed with a hydrocellular foam sheet to complete the healing.

Also in 1995, in another startling case, an 86-year-old female was presented with a four-year history of a circumferential ulceration of her leg. Nurses had been dressing her leg three times a week and she was being treated at a hospital twice a week. The wound "had a sloughy nature" and contained Pseudomonas and MRSA infections. After only four days of larval treatment, most of the slough was gone, healthy granulation tissue was present at the wound base and there were no longer clinical signs of infection.

The healing properties of maggots were also demonstrated in 1976 on a 67-year-old male with diabetes mellitus. [9] He was admitted to the hospital for coalescent mastoiditis which was infected with Pseudomonas aerogenes, Proteus mirabilis and Enterococcus species. He received antibiotics for three days and a simple mastoidectomy was performed. He was discharged five days later and more antibiotics were prescribed. One month later, there was swelling of the pinna and a purulent discharge from the postauricular incision which contained P.aerogenes, Klebsiella pneumoniae, Pr.mirabilis and -Streptococcus. At that point, the patient was subjected to a radical mastoidectomy and debridement of the necrotic pinna cartilage. He was finally discharged from the hospital 23 days later and prescribed a course of cephalexin monohydrate antibiotics. One month later, the patient was re-admitted to the hospital being unable to swallow. At this time, there was a cauliflower deformity of the pinna and an open incision with exposed bone which contained a purulent discharge. He then began a six-week course of gentamicin sulfate (intramuscularly three times a day) and carbenicillin disodium (IV every four hours). At the same time, the patient began receiving four Pseudomonas vaccinations (one per week). After five weeks of this treatment, the hospital staff began to irrigate the wound with 2% acetic acid and pack it with a desoxyribonuclease-bovine fibrinolysin ointment and iodoform gauze three times each day. During the first eight weeks of this hospital stay, the wound cavity had also been manually debrided two times daily. On the ninth week, larval therapy began. One week later, the larvae were removed and a skin graft was placed over the healthy granulation tissue of the wound cavity. The patient was discharged from the hospital ten weeks after he was first admitted. A culture of the healthy cavity tissue was taken one week post-discharge and revealed no bacteria. After five months of unsuccessful antibiotic treatment and surgical debridement, the larvae had debrided the wound and destroyed the bacteria in approximately one week.

Application of Larval Dressings

Not all fly maggots are suitable for use in larval therapy. Among those which should not be used are members of the family Sarcophagidae (flesh flies) and the species Cochliomyia hominovorax (screw worm) since they will devour living tissue. [2] [3] [4] [5] [7] The most commonly used larvae belong to the family Calliphoridae, specifically Lucilia (Phaenicia) sericata (greenbottle blowfly) and Phormia regina (blackbottle blowfly) which will only feed on necrotic tissue. It was reported in 1933 that for successful larval therapy, the maggots should be free of bacteria before being placed into wounds. [2] An early sterilization technique was to wash fresh fly eggs in a dilute solution of sodium hypochlorite, rinse in sterile water, then agitate the eggs in 4% formaldehyde. The eggs were then rinsed and placed on sterile meat-agar media for development. A much easier technique can now be utilized by simply purchasing sterile larvae from laboratories for as little as $60.00 for 1000 larvae. [10] [11] [12]

The larvae, which are 1-3mm long, must be retained in the necrotic wound in order for them to debride the tissue. [4] In human medicine, a hole is cut out of a hydrocolloid dressing the same size and shape as the lesion and the dressing is applied to the wound. This provides a base for the outer dressing and protects the surrounding skin from the proteolytic enzymes of the larvae. Alternatively, a zinc paste can be used. Approximately 10 larvae per square centimeter of lesion are then placed into the lesion. The wound and larvae are then covered by a fine nylon net which is attached with adhesive tape. An absorbent pad is then placed on top of the netting in order to absorb the exudate and liquefied necrotic tissue. The pad can be changed as often as necessary as its removal will not disturb the larvae. The larvae should be removed from the wound after three days. This is easily accomplished by removing the netting and rinsing the lesion with sterile saline. If necessary, another application of larvae may be made at that time. An average application of larvae can consume 10 to 15 grams of necrotic tissue each day. [3] Larvae can be used in conjunction with conventional systemic antibiotic treatments. [13] They also show no adverse effects from X-rays and can be left in place when radiographs are taken.

Mechanisms of Action

Proposed mechanisms of action of larval wound healing include:

The exact mechanism is unknown at this date, however studies indicate that it may be a combination of the above proposals.

One study collected hemolymph (HL), alimentary secretions (AS), and the insect molting hormone 20-hydroxyecdysone (EC) from L.sericata and tested their effects on human fibroblasts. [17] It was found that each of these extracts did stimulate fibroblast cultures, but only by a rate of 12% of epidermal growth factor alone. However, each extract had significant effects on stimulating the fibroblasts when used in conjunction with epidermal growth factor. (HL P<0.01, AS P<0.0081, EC P<0.0016) The alimentary secretions also had a significant effect on the fibroblasts when combined with the cytokine Interleukin 6 (P<0.009).

Another study tested the ability of larval secretions to debride collagenous burn eschar and necrotic dermal tissue. [18] Calliphora erythrocephala larvae were placed in a jar and their secretions collected. Rats were anesthetized and two burn wounds were made on each of their backs. One burn was treated with vanishing cream as a control and the other burn was treated with vanishing cream combined with the larval secretions. The wounds were significantly more debrided by the vanishing cream containing the secretions than the vanishing cream alone (23% 4.6% and 1% 0.7% respectively, P<0.005). The study also found that the enzymes in the secretions were stable for 24 to 48 hours and that the enzymes would diffuse through the dressing. It was hypothesized that the debridement noted in the control wounds may have actually been caused by diffusion of the secretions from the treated burns over to the control burns.

Continuing this study, it was found that the larval secretions contained enzymes which have similar molecular weights, characteristics, inhibitions, and sensitivities as those of trypsin, leucine aminopeptidase, carboxypeptidase A, and carboxypeptidase B. There was also evidence of minute amounts of elastase activity. The presence of these types of enzymes confirmed the proteolytic nature of the larval secretions.

Veterinary Case Histories

While literature is replete with reports of successful larval therapy being conducted in human medicine--the same cannot be said of veterinary literature. By including the previous rat dermal burn study, a search identified only three published reports. While one report was a historical view of maggot therapy, [7] the other was a case report involving actinomycosis.

In 1953, a six-year-old Guernsey bull was presented with a two-year history of actinomycosis (lumpy jaw) which involved the mandible. [19] The bull had a bony mass which was six inches deep, 10 inches in length, and involved the entire right side of the head. The mass contained deep sinuses which were plugged with excrement. Surrounding the mass, there were large areas of skin which were denuded, swollen, and inflamed. The bull was emaciated, had difficulty breathing, and was unable to masticate or swallow food. Since this bull was the herd sire and had a poor prognosis due to the advanced actinomycosis, the owner consented to larval therapy. It is interesting to note that in treating this bull, Dicke determined that it was not necessary to use sterile maggots which are "essential for human therapy." The first instar larvae of L.sericata were developed on strips of liver in a jar and used for the treatment. The maggots were applied to the wound with a spatula in "lots of several thousand." When the maggots matured, they fell from the wound onto the ground. During the next eight months, more larvae were intentionally applied at two-week intervals and it was noted that during the summer months, spontaneous infestations also occurred with P.regina and L.sericata.

One day after the initial treatment, Dicke noted "a copious, purulent discharge occurred from the sinuses of the principal lesion." Within several days, the swelling and inflammation had subsided and the bull was able to chew and swallow. Within three months, the bull's condition improved and it began normal feeding and breeding activities. The surrounding area had healed to the extent that the bull no longer rubbed the irritation. Six months after the initial treatment, the bull was in good condition, there was no evidence of inflammation, the skin was covered with normal hair, and the bull was returned as the principal herd sire. Unfortunately, 18 months after the initial larval treatment, the bull's condition deteriorated and was slaughtered. Dicke surmised that the Actinomyces bovis had unknowing also been present in the lungs. This case describes the ability of larvae to clear a chronic wound even under less than ideal circumstances. Dicke did not use sterile maggots and may have unintentionally introduced more bacteria into the wound cavity. He also did not use any type of dressing to cover the wound which left the tissue exposed to soil and infestation by other arthropods.

Treatment with Antibiotics

Since the discovery of antibiotics, their indiscriminate use has created resistant strains of bacteria in both human and veterinary medicine. This may be partially due to excessive use of broad-spectrum antibiotics and prescribing antibiotics for viral infections. [20] In order to combat resistance, the Food and Drug Administration (FDA) is placing increasingly restrictive regulations on the use of antibiotics in food animals. There is a danger that resistance to antimicrobials used in veterinary medicine may be transmitted to human pathogens via contaminated meat and dairy products. [21] In an idealized world, veterinarians would only prescribe narrow-spectrum antibiotics which target only the specific pathogen cultured and leave no residue. One problem is that open wounds are frequently infected with multiple bacteria genera, partly due to contamination with fecal material and soil.

Veterinary Implications

Human medicine has shown that larvae can cleanse a wound of Gram positive, Gram negative, aerobic and anaerobic bacteria. Maggots quickly debride necrotic lesions and promote the formation of healthy granulation tissue. The use of maggots to assist in healing infected scrapes, cuts, wire wounds, and compound fractures can help reduce antibiotic use in veterinary medicine. Maggots are easily applied to lesions and do not leave antibiotic residues which would violate FDA regulations. Infected wounds on feeder and certified organic beef cattle can be treated with larvae instead of sending them to immediate slaughter. This would allow time for the animal to reach its maximum growth and economic value. Maggot therapy on dairy cattle would also eliminate the need to destroy milk contaminated with antibiotics. The use of antibiotics on horses can affect the delicate balance of normal gastrointestinal flora which may result in colitis. [22] Maggot therapy would eliminate this additional stress when treating equine wounds. Companion animals would also benefit from larval therapy. As previously stated, human case histories have shown that maggots can eliminate abscesses and certain types of malignant or benign tumors. Veterinarians could add larval therapy to the treatment options for owners who cannot afford expensive surgery or chemotherapy for their pets.

Conclusion

Maggot therapy has been used for centuries to successfully treat necrotic wounds but declined in use with the advent of antibiotics. Anecdotal and scientific studies have shown that larvae can cleanse a wound of many genera of bacteria, including antibiotic-resistant strains. Maggots can quickly and efficiently debride necrotic tissue from a wound and promote healing of abscesses, dermal ulcers, and mastoiditis when conventional treatment has failed. Only larvae which do not feed on living tissue should be used for therapy. These larvae should also be sterilized of any bacteria residing on their surfaces. Treatment consists of a base dressing and a simple nylon net being placed over the larvae in a wound so that they do not escape. A pad is then placed on top of the netting in order to absorb the exudate and liquefied tissue. The larvae should remain in the wound for approximately three days then removed by rinsing with warm saline. While the exact mechanism of action has yet to be fully demonstrated, studies indicate that larval secretions significantly amplify the effects epidermal growth factor and Interleukin 6. It has also been shown that these secretions contain enzymes with proteolytic activities.

Veterinary literature contains few reports of maggot therapy. One report does show the successful treatment of a bull with advanced actinomycosis. The lack of reported cases may be partially due to the success of antibiotics. The indiscriminate use of antibiotics in both human and veterinary medicine has led to FDA restrictions in order to slow the emergence of resistant bacterial strains. Maggot therapy can be used in beef and dairy cattle without fear of violating FDA residual regulations. This therapy can also be used on equine wounds without upsetting the delicate balance of normal gastrointestinal flora. Companion animals can also benefit from larval therapy when owners cannot afford the expense of surgery or chemotherapy of certain types of malignant tumors. Over the centuries, the benefits of larval therapy have been researched and documented. In light of FDA regulations and microbial resistance, veterinarians should follow their colleagues in human medicine and take notice of this re-emerging treatment option.

References

1 - Church, JC. The Traditional Use of Maggots in Wound Healing, and the Development of Larva Therapy (Biosurgery) in Modern Medicine. J Altern Complement Med, Winter 1996;2(4):525-7.

2 - Weil GC, Simon RJ, Sweadner WR. A Biological, Bacteriological and Clinical Study of Larval or Maggot Therapy in the Treatment of Acute and Chronic Pyogenic Infections. American Journal of Surgery, Jan 1933;19(1):36-48.

3 - Pechter EA, Sherman RA. Maggot Therapy: The Surgical Metamorphosis. Plastic Recon. Surgery, Oct 1983;72(4):567-70.

4 - Thomas S, Jones M, Shutler S, Jones S. Using Larvae in Modern Wound Management.Journal of Wound Care, Feb 1996;5(2):60-9.

5 - Thomas S, Jones M, Shutler S, Andrews A. All You Need to Know About Maggots. Nursing Times, Nov 1996;92(46):63-76.

6 - Krajacic A. Consider Using Maggots. Todays Surgical Nurse, May-Jun 1998;20(3):28-32.

7 - Mulder JB. The Medical Marvels of Maggots. JAVMA, Dec 1989;195(11):1497-9.

8 - Waters J. The Benefits of Larval Therapy in Wound Care. Nursing Times, Jan 1998;94(2):62-3.

9 - Horn KL, Cobb AH, Gates GA. Maggot Therapy for Subacute Mastioditis. Arch Otolaryngol, Jun 1976;102:377-9.

10 - http://www.ucihs.uci.edu/path/sherman/order.htm

11 - http://www.biomaggot.com

12 - http://www.smtl.co.uk/WMPRC/Biosurgery/Ordering/

13 - Thomas S, Andrews A, Jones M. The Use of Larval Therapy in Wound Management. Journal of Wound Care, Nov 1998;7(10):521-4.

14 - Mumcuoglu KY, Ingber A, Gilead L, Stessman J, Friedmann R, Schulman H, Bichucher H, Ioffe-Uspensky I, Miller J, Galun R, Raz I. Maggot Therapy for the Treatment of Diabetic Foot Ulcers. Diabetes Care, Nov 1998;21(11):2030-1.

15 - Bunkis J, Gherini S, Walton R. Maggot Therapy Revisited. West J Med, Apr 1985;142(4):554-6

16 - Young T. Maggot Therapy in Wound Management. Community Nurse, Sep 1997;3(8):43-5.

17 - Prete PE. Growth Effects of Phaenicia sericata Larval Extracts on Fibroblasts: Mechanism for Wound Healing by Maggot Therapy. Life Sci, Feb 1997;60(8):505-10.

18 - Vistnes LM, Lee R, Ksander GA. Proteolytic Activity of Blowfly Larvae Secretions in Experimental Burns. Surgery, Nov 1981;90(5):835-41.

19 - Dicke RJ. Maggot Therapy of Actinomycosis. Journal Econ Entomol, Aug 1953;46(4): 706-7.

20 - Wise R, Hart T, Cars O, Streulens M, Helmuth R, Huovinen P, Sprenger M. Antimicrobial Resistance is a Major Threat to Public Health. BMJ, Sep 5, 1998;317(7159):609-10.

21 - McKellar QA. Antimicrobial Resistance: a Veterinary Perspective. BMJ, Sep 5 1998;317(7159):610-1.

22 - Reed SM, Bayly WM. Toxicologic Diseases: Antibiotic-Associated Diarrhea-Pathogenesis. Equine Internal Medicine, Philadelphia: Saunders Company, 1998, 672-3.


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