Time Travel: Maggot Therapy

MEDICINAL TIME TRAVELING: MAGGOT THERAPY
By Jona Kristo

*WARNING: Read and view pictures at your own discretion.

           

Since my grandmother was diagnosed with diabetes many years ago, the disease has always caught my attention. With such profoundly advanced scientific knowledge and modern innovations, it was difficult for my family to grasp the loss of her battle to diabetes.  Instantly, I knew that diabetes would be a disease that would have my interest for the rest of my life. A few weeks ago, one of my professors lectured on the importance of using flies as vectors for medical benefit. He briefly mentioned that “maggot therapy” has been a topic of immense interest and study for many years now, yet evidently one that has not gained a lot of public support. Immediately, I was intrigued and did further research on the topic. How can maggots lead to healthier tissue? What is the data to support this rather ambitious and unpopular theory?

If you ever try to research “maggot therapy” most of the results you will find are ways to reach a doctor or therapist that will perform such controversial procedure. After all, because this is not fully studied and supported by the society, it is not the most conventional method that most physicians will use, or one that the patients would even allow to have performed. Therefore, it is rather difficult to find the chemistry and biology behind a rare procedure that is poorly studied. After narrowing down my search on Google Scholar and allowing for a longer time frame, I came across the first article that instantly grabbed my attention. The article by Dr. Ronald A. Sherman, dated February 2003, was titled

“Maggot Therapy for Treating Diabetic Foot Ulcers Unresponsive to Conventional Therapy.”

 According to the article, using larvae of flies on ulcer wounds cannot only get rid of the dead tissue, but it also disinfects and heals the wound. While my grandmother did not have any foot ulcers, I had heard that they were common and would be a part of her symptoms had she lived long enough with the progressive disease. I was intrigued at the article, however I needed more information to understand exactly how something as ghastly as maggots could be a cure for diabetic ulcers.

Before I delve into the article and the impressive results of the study, I wanted to do some research on exactly how maggot therapy works. Although fly larvae were successfully used as therapeutic intervention in historical times, in 2004 maggot therapy was supported by the FDA and began to relaunch itself in the medical field. Essentially, maggot therapy is used as the last method of treatment on ulcer wounds, prior to limb amputation. This is good to know, especially considering how negative the public must view this practice. In my opinion, it appears that essentially our knowledge and medical advancements are regressing, not necessarily progressing. Yet, maggot therapy is showing us exactly how sometimes our old ways of thinking are often more advantageous than what modern science can offer.

The mechanism of action for the process can be divided into three main segments: debridement, disinfection, and wound healing. Fly larvae are disinfected and sterilized, more often in sterilized laboratory settings. They are most suitable at a rather immature stage when they are most active and aggressive. In fact, medicinal maggots are available for purchase with a prescription. The first step of the process is debridement, in which the immature larvae feed on necrotic tissue, permitting only living and healthy tissue in the wound. Studies specifically support maggot therapy for this particular step because surgically it is difficult for physicians to precisely differentiate healthy versus necrotic tissue, especially in the limited time the patient is under anesthesia. As a result, when surgically debriding a wound, a larger wound can result due to excess healthy tissue being removed. Maggots, however, are very specific in their feeding. They secrete proteolytic enzymes, such as leucine aminopeptidase, collagenase, and chymotrypsin-like proteases that liquefy the necrotic tissue and prepare it for larval consumption. These enzymes are tissue-specific and only debride necrotic tissue by altering the extracellular matrix, an important component of the healing process. Collagenase, for example, is a specific enzyme that initiates proteolysis and can break down collagen into smaller compounds that can be digested by the larvae. This process, known as extracorporeal digestion, takes as little as 3-4 days and can remove necrotic tissue substantially more efficient and faster than surgical procedures!

FIGURE 1. Maggots released onto diabetic ulcer wound.

After debriding, maggots also disinfect the living tissue. Because antibiotic resistant bacterial strains are profoundly more common, it is difficult to treat bacterial infections using antibiotics. Maggots, however, can work even when antibiotic resistant strains are present. While feeding, maggots secrete a set of antibacterial substances, such as allantoin, urea, and phenylacetic acid. One of the most substantial secretions is that of ammonia, which is secreted by maggots and can modify the wound pH, creating an unfavorable environment for MRSA (Methicillin-resistant Staphylococcus aureaus) growth. In this manner, maggot therapy has proven to be effective in decreasing MRSA infections, which are extremely detrimental infections in many chronic patients in hospital settings.

After the wound has been removed of necrotic tissue, studies have shown that maggot therapy stimulates the production of fibroblast growth factors, which are key players in the proliferation of many types of cells and tissues. FGFs stimulate blood vessel growth in healing wounds and give rise to granulation tissue, which will fill in the empty wound space. In addition, cytokines promote proliferation and differentiation of leukocytes and directs them to the wound. Specialized dressings with added collagen have proven to be successful by speeding up the would healing process in the skin. Once again, we see collagen playing an important role on wound management and skin repair. These different factors allow for faster healing of granular tissue and dermal fibroblasts. 

FIGURE 2. Before and after Maggot Debridement Therapy

Now that I had a very thorough background of the process and could understand the importance of maggot therapy in relation to conventional surgical methods, I wanted to delve further into the original article I found and the results the authors found extremely significant. The article’s abstract made a very bold and admirable impression. The author studied 260 patients with nonhealing wounds and compared the results of conventional versus maggot therapy treatments. Their results are encouraging and impressive (Figure 3)!

FIGURE 3. Surface area of necrotic tissue over time of patients using maggot therapy (black) or standard therapy (white)

The results themselves speak wonders. It is evident that the maggots worked in comparison to the standard therapy. In just three short weeks, patients using maggot therapy found an impressive amount of necrotic tissue disappear. This definitely explains that, as far as debridement goes, maggot therapy is sufficiently able to treat diabetic foot ulcers. However, I wanted to know if the therapy’s success ended at the debridement; after all, it makes sense that eating away dead tissue would be the extent of maggots’ capabilities.

FIGURE 4. Percent of granulation tissue over time of patients using maggot therapy (black) or standard therapy (white).

Once again, I was proved wrong. These results are profound. The authors also noted that in the 8-week period of the study, 14% of the patients treated with maggot therapy had complete wound closure in comparison to the 0% of patients treated with conventional therapy. Although I'm sure that there are different circumstances to each patient that could have played a role in these results, this is pretty significant. I know that if my grandmother was faced with diabetic ulcers during her battle, I would recommend this kind of treatment to her- it appears to be not only extremely effective, but also inexpensive and painless!

            After reading about the extensive success from maggot therapy, I wondered what further applications maggot therapy can be used for and how more patients can benefit, specifically patients with cancer. Although extremely far-fetched, it would be intriguing if maggots can eat away dead cancerous cells, thereby hindering cancer metastasis. However, my own curiosity leads me to wonder whether maggots can be “tricked” into eating dead cells, not simply dead tissue. My thought process here is simple- if maggots are such aggressive feeders at this point in their life cycle, then exposing them to dead cells would not stop them from feeding on such cells. I wanted to look further into it and see if such idea had been attempted. As expected, maggots have been found successful in cancer treatment, but solely for cancerous wounds. Two cases of inoperable breast cancer and sarcomas used maggot therapy to eat away malignant tissue on open wounds. This is evidently my own personal wishful thinking, but it would be interesting to see further studies on such interest.

            After the extensive research I did regarding maggot therapy, it is fascinating to see how much chemistry and biology lies behind the process. After all, the initial thought behind the process is rather shallow- how can something this strange have such substantial science behind it? I think essentially maggot therapy could have profound implications in the future. If we can find a way to manipulate the biology of the larva and the specific stages of their life cycles, then the possibilities of treatment could be endless. In order to raise awareness of these possibilities, perhaps targeting developing countries is the first step in gaining public support and continuing to study maggot therapy.

JMOL of Collagen:
REFERENCES:

The original article: http://care.diabetesjournals.org/content/26/2/446.full

Modern maggot therapy uses: http://jpp.sagepub.com/content/24/1/89.full

Maggot Therapy and MRSA: http://www.sciencedaily.com/releases/2007/05/070503094447.htm

Bacterial Resistance: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1475942/

Cancer and Maggot Therapy: http://www.wellness.com/reference/health-and-wellness/maggot-therapy/practice-theory-and-evidence

Overall Review: “Maggot Therapy: A handbook of Maggot-assisted Wound Healing (Google EBook)”- Fleischmann, W. and M. Grassberger 2004