Breakthrough Wound Therapy: Magic? No, Maggots

Intentionally introducing disease-ridden larvae into an open wound for days at a time sounds like some sort of medieval torture. But maggot therapy, first performed in the early 20th century, has been re-emerging as a useful standard of care and an alternative to amputation. This FDA-approved procedure involves applying germ-free larvae of “medical-grade maggots” to open wounds at a dose of five to ten larvae per square centimeter of surface area and covering with a special dressing for two to three days. The maggots use digestive enzymes to dissolve dead and infected tissue, which can disinfect the wound by secreting antimicrobial molecules and actually stimulate healthy tissue growth. These specialized medicinal maggots cannot eat healthy tissue, so they want to crawl elsewhere once the wounds are clean [3].

This phenomenon was first observed by injured soldiers during World War I, noting that wounds healed faster when they had been infected with maggots. William Baer, an orthopedic surgeon, was one of the witnesses to this, and upon his return, became the first to intentionally apply maggots to a wound. Throughout the 1920s, he bred specific species of larvae to treat 98 children with osteomyelitis and soft tissue infections. Within the next five years, American, Canadian and European surgeons promoted the use of maggots, with many hospitals creating their own insectaries for a maggot supply. Yet, by the 1940s, surgical techniques improved and antibiotics became widely available, thus the types of wounds receiving maggot therapy became much less common [5].

emerging threat, along with the rise of antimicrobial resistance. With more current medical technology, previously fatal diseases have now become chronic. Diabetic foot ulcers affect 15% of the diabetic population and are the cause of at least 70,000 amputations annually [5]. In addition, the increasing prevalence of nonhealing wounds has already led to over $20 billion for annual management costs and two million workdays lost [5].

Multiple clinical studies at the end of the 20th century showed that maggot debridement therapy (MDT) can be more effective in cleaning chronic wounds than conventional treatments [3]. These include topical antimicrobial therapy, hydrogels, chemical debriding agents, saline-moistened dressings and surgical debridement [4]. The studies also demonstrated that while MDT was effective as a last resort over amputation, with a limb salvage rate of over 40%, it was even more successful when used at an earlier time in the course of treatment [3]. The high limb salvage rates may be attributed to increased oxygen perfusion, cellular proliferation, restructuring of the extracellular matrix and rapid spread of connective tissue [5].

Some of the problems that existed with MDT in the past were making the dressings, obtaining germ-free maggots and expenses. There have been improvements to adhesives and synthetic fabrics as well as easier methods of disinfecting and raising maggots, and the cost is now relatively inexpensive due to the escalation of many other surgical treatments [2]. Current technology includes “maggot containment dressings,” which are cage-like designs that completely surround the larvae while restricting access to the wound, minimizing patient discomfort since

the maggots can’t crawl over exposed nerves. There is a simpler technique of “maggot confinement dressings,” which give complete access to the wound but don’t provide the same benefits [5].

From the patient’s perspective, MDTassociated pain is reported in 5-30% of cases [5]. However all of these

treated with secretions had lower levels of complement proteins than the control groups, which include the aforementioned standard treatments. Specifically, the researchers observed the secretions had ripped some of the proteins apart, reducing the protein levels by 19% to 55% in postoperative wounds [2]. Interestingly, the maggot secretions were just as effective after sitting on the shelf for a month and more effective after being boiled. This team is working to isolate these complement-inhibiting compounds for clinical drug development; however, a solution

instances also reported wound pain before receiving treatment. Pain most likely occurred within the first 24 hours as maggots increased in size and can usually be adequately controlled with analgesics [5].

Looking towards the future, there are some studies on how to isolate the wound-healing molecules without having to apply the maggots. Researchers at the Leiden University Medical Center in the Netherlands have introduced isolated maggot secretions into blood samples and measured the production of complement proteins, which contribute to inflammatory responses. Having complement proteins in the blood usually help restore healthy tissue, but in cases of chronic wounds, they can actually cause cell death and enhance inflammation, leading to further injury and impairment of wound healing [2]. In the experiment, every blood sample is still several years away, at least [2]. In all, this effort to create drugs from maggot secretions is likely more difficult than just combining a few chemicals. There seems to be a synergistic effect from the secreted mixture and the movement of the maggots also contributes by giving the enzymes access to deeper tissue [5].

For now, the resurgence of MDT as a standard practice will suffice. With new technology and research investments, this old 20th century treatment is still relevant, especially with concerns about antimicrobial resistance. While it has developed substantially from just letting diseased maggots loose into a wound, the principal and efficacy remain in these modern times. •