The Use of Maggot Therapy for the Treatment of Chronic Wounds - Literature review Example

LITERATURE REVIEW A chronic wound becomes a challenge to treat because it does not follow the natural pathway of healing comprising of the four stages of wound healing. A chronic wound usually gets halted at the inflammatory stage owing to the presence of necrotic material and wound infection. The conventional method of treatment of chronic wound is aimed at removing the necrotic material and debris from the wound to allow the normal stages of wound healing to take place. Sterile dressings are applied and wound regularly cleaned in order to prevent further infection. Although new techniques have been developed improving the conventional method of wound debridement including hyperbaric oxygen, negative pressure wound therapy, adjuvant growth factors and tissue-engineered products as discussed by 7 Attinger CE. (2006) and Collier M. (2006), maggot debridement therapy has appeared as an alternate to surgical debridement of wounds. Clinically, wound debridement is the conventional method in use for many years for gaining wound closure. Wound debridement comprises of removal of the dead and devitalized tissue from a wound to minimized the number of toxins, microbes and other harmful substances inhibiting wound healing. Since now, five main methods of wound debridement are in use by medical professionals. These include: 1. Surgical/sharp debridement, 2. Autolytic debridement, 3. Enzymatic debridement, 4. Mechanical debridement and 5. Biosurgical debridement. The choice of debridement technique is dependent upon the nature of wound, effectiveness of debridement technique, pain management, exudates levels, risk of infection and cost effectiveness of procedure. Surgical debridement Surgical debridement is amongst the fastest known methods of debridement till now, but it is very painful and was earlier restricted only to treatment of diabetic foot ulcers which already have lost sensations and do not have much need of anesthesia. Side effects include bleeding and possible damage to viable tissue as well which can be controlled by pressure application and hemostatic calcium alginate dressing. Autolytic debridement Autolytic debridement is the natural method of debridement experienced by all kinds of wounds to some extent. It is a process of breakdown of necrotic wound material with the help of endogenous proteolytic enzymes produced by neutrophils. These include acid hydrolase, myeloperoxidase, elastase, collegenase and lysosomal enzymes. It is not a fast method of debridement and needs assistance by occlusive dressings in order to maintain a moist wound bed. It is painless but produces significant quantities of exhudate which is managed by use of hydrogel covered with an absorptive dressing. Autolytic debridement takes much longer time for wound to heal and have shown failure in cases where antibiotic resistant pathogens evolve. Enzymatic debridement It makes use of especially prepared proteolytic enzymes meant for wound debridement. These exogenous enzymes concomitantly work with the endogenous enzymes. Some of these include bacterial collegenase, trypsin, streptokinase and fibrinolysin. The main difficulty in their application becomes their availability and high cost. Mechanical debridement It is a physical method of removal of necrotic material from wound using mechanical force. It is a relatively easy procedure and has faster rate of debridement than other methods. However, it carries a risk of damaging the viable tissue at wound margins. These methods include wet-to-dry dressings, pressurized irrigation, whirlpool therapy and vacuum-assisted closure. However, some of these techniques carry a risk of damaging viable tissue as well, but their overall acceptance is satisfactory. Biosurgical debridement (Myiasis) This is the method of wound debridement by maggots also known as MDT (Maggot Debridement Therapy) using maggots as a tool for debridement of necrotic wound material. It has shown significantly improved results and much of research is still being carried out to improve this technique. MECHANISM OF MAGGOT DEBRIDEMENT THERAPY Much of the research done till now make use of the larvae of green bottle fly Lucilia sericata, which belongs to Diptera order of insects which are parasitic invaders. The larvae hatch in about 12-24 hours, being 1-2 mm in size at birth, and gain a size of about 10 mm after maturing in 4-5 days. (Wollina U. 2000). In order to prevent maggot induced infection, these maggots are medically prepared and disinfected under sterile conditions. Newborn larvae are recommended for use within 8 hours of birth or they can be used by slowing down their metabolism down by preserving them at a temperature of about 8 to 10 degrees Centigrade (Richardson M. 2004). Further recommendations include: 1. Adequate oxygen supply, 2. Optimal body temperature, 3. Controlled levels of moisture and 4. Avoiding the occlusive dressings as oxygen is required for their survival (Wollina U. 2000). Chambers L. (2003) identified three kinds of proteolytic enzymes in maggot’s excretions/secretions (ES) to be responsible for degradation of laminin and fibronectin in extracellular matrix. This leads to an effective wound debridement. Bexfield A. (2006) successfully showed the inhibitory effects of maggots on Gram positive and Gram negative bacteria. Later studies also revealed an excretion of ammonia by maggots increasing the wound pH making it unfavorable for bacterial growth (Robinson W.1940). POSSIBLE ‘YUK’ FACTOR What makes the maggot debridement therapy difficult to imply is the psychological factor associated with the use of maggots on one’s own body. Many patients find it an unacceptable phenomenon to tolerate. However, Richardson M. indicated that an adequate psychological preparation and complete information to patient from the surgeons performing it make the therapy more acceptable by the patients. The so called ‘yuk’ factor for larval therapy was studied by Evans P. (2002) and he reported that the weird appearance of applying maggots to a necrotic wound can be reduced by use of a nylon bag designed to contain maggots for therapy. The study was conducted on venous leg ulcers. Although, the rate of debridement was slower in this case, yet they could be easily observed and were easy to remove from the wound. This ‘camouflaged’ use of maggots was much accepted by both the patient and the medical staff. REVIEW OF DIFFERENT STUDIES In a study conducted by Gilead L. (2012) studied the effectiveness of maggot therapy in treatment of chronic wounds in hospitalized and ambulatory patients. The study was published in The Journal of Wound Care. A total of 435 patients comprising of 180 female and 255 male patients got treatment with the maggot 8 debridement treatment (MDT) from years 1996-2009 involving 723 wounds in all. The study was conducted at Hadassah Hospital in Jerusalum, Israel. Of these patients, 261 were treated during their hospital stay, while 174 received treatment as ambulatory patients. 90.5% of these patients had their wounds located on leg, while 48% had diabetic foot ulcers. The MDT treatment was applied using the sterile maggots of the green bottle fly Lucilia sericata. 90.6% patients received direct treatment with maggots applied directly on the wound, while only 9.4% patients were given therapy with tea-bag like polyvinyl netting concealed maggots, which were left on the wound for 2-3 days. Gilead L.. (2012) described the results to show a complete debridement of wound in 357 patients and partial debridement in 73 patients out of a total of 435 patients. Only five patients showed no improvement from maggot debridement therapy. 38% of these patients reported an increased pain during treatment. Gilead L. (2012) concluded his study by describing this therapy as a very safe and effective method for management of chronic wounds in hospitalized and ambulatory patients. Another study conducted by Opletalova K. (2012) performed a randomized multicenter trial for determining the effectiveness of maggot therapy for wound debridement when compared with the conventional method of wound debridement. The study was published in the Archieves of Dermatology. Opletalova K. used the bagged larvae for this study. The study was performed at two hospital setups in Caen and Lyon, France. 119 patients were studied having sloughy, non-healing wounds about 40cm (2) or smaller in diameter, depth less than 2cm and an ankle bacterial index of about 0.8 or more. All these patients stayed in the hospital for duration of two weeks. The patients were followed up at day 30. The results were assembled based on the percentage of wound sloughing present at day 15. When observed at day 8, a remarkable difference was found between the two groups. The percentage of slough present in wounds was 54.5% in MDT group as compared to 66.5% in control group. However, at day 15, the mean percentage came out to be about 55.4% in MDT group and 53.8% in the control group. 9 Although this study did not show any benefit in treatment by MDT at day 15 when compared with conventional treatment, yet MDT had a faster rate of wound debridement than conventional treatment and occurred during the first week of debridement. Opletalova K. concluded by suggesting that it is better to use another type of dressing after 2 or 3 applications of MDT as it did not show any significant benefit except for the first week of application. Cazander G. gave a relatively different approach in maggot debridement therapy by his study which showed that the maggots have specific excretions which positively affect the human complement system, which is important for the activation of inflammatory responses to injury. The study was hypothesized by stating that the maggot excretions have an influence on human complement system activation and modulation of the host’s inflammatory response. The study was performed by obtaining sera from these patients pre and post operatively, undergoing orthopedic surgery. Maggots excretions were found to 10 reduce the complement activation in post operatively immune activated human sera to about 99.9% through all pathways. Maggots excretions do not actually commence or inhibit the activation of complement system; they just affect the C3 and C4 complement proteins in a cation-independent manner. Moreover, this was found to be a temperature tolerant process. This study favors the wound debridement technique using maggots therapy in a way that it shows a complement activation reduction effect on part of the excretory material produced by the maggots. Also those diseases resulting from an over activation of the complement system may be treated on basis of the fact that the maggot excretions have an inhibitory effect on complement system activation. It has always been a concern in maggot debridement therapy that most of the patients complain of pain or discomfort during their treatment. Mumcuoglu KY. (2012) studied the pain related to maggot debridement therapy. The study was conducted at Hadassah Hospital in Jerusalem, Israel. A secondary data analysis was performed on 435 patients. Either a direct approach was used with the help of a cage like dressing (DA) or an indirect approach using hermetic tea bag like pouches (TBA). The levels of pain on part of the patients were measured before and during the maggot debridement therapy treatment. 38% (165) patients reported an increased level of pain during the treatment. 41% (17) patients treated with TBA technique and 38% (148) of those treated with DA technique also reported increased levels of pain and had to be given analgesics during and before MDT treatment. 5 patients could not bear the pain at all and the treatment had to be discontinued. Those patients who were already in intense pain before commencement of MDT as well as those complaining of intense pain during DA technique, some pain control measures had to be taken which included: 1. Shorter periods of application of maggots, 2. Replacement of DA by TBA, 3. Using small maggots and 4. Using smaller number of maggots. 11 Still others needed systemic analgesics and even peripheral nerve blocks. The study was concluded by saying that the maggot debridement therapy carries the concerns of being painful treatment and in some cases even becoming unbearable. Moreover, the therapy lasts for about 3 to 5 days requiring an average of 2 to 3 maggot cycles, thus there should be sufficient measures already taken in order to render a pain free treatment to the patient. These may require the use of analgesics like opiods, systemic medications and sometimes peripheral nerve blocks as well. Another study was performed by Telford G. (2012) published in Medical and Veterinary Entomology studying the potential of glycosidases found in the maggots of Lucilia sericata regarding treatment of chronic wounds. The study was based on fact that these specific maggots release certain enzymes that bring about the degradation of extracellular matrix. The study was aimed at investigating the glycosylation profiles of the wound slough and the presence of glycosidase activities in the first secretions, defining their properties. The study was conducted by determination of the prominent carbohydrate moieties found in the wound slough. This was made possible by probing one-dimensional Western blots with the conjugated lectins of known specifities. Chromogenic and fluorogenic substrates were made use of for determining the involvement of specific glycosidase activities in first instar excretions. Two dimensional electrophoresis and Emerald 300 glycoprotein staining was used to determine the removal of carbohydrate moieties from the slough proteins. α-D-glucosyl, α-D-mannosyl and N-acetylglucosamine residues were found in slough proteins. The study thus clearly indicates that maggots glycosidases do perform the action of removing sugars from slough proteins. This thus helps in the wound debridement. Wu JC. (2012) performed a research study in a severely burnt patient and proved the effectiveness of maggot therapy in repairing seriously infective wounds. 12 However, in this study, he made use of the larvae of musca domestica. He used 50000 aseptic maggots accompanied by aseptic dressings. The second therapy was performed three days later using 20000 maggots. The result came with clearance of most of the necrotic wound material, appearance of new granulation tissue and complete healing occurred later on after skin grafting thrice. The study was concluded by suggesting the maggot therapy to be a safe and fruitful method for treatment of infective wounds and having no serious side effects except for the pain experienced by patient during therapy. Another study performed by Schoutan HW. (2009) studied the effects of maggot debridement therapy in an old patient having a chronic untreated large basosquamous carcinoma affecting his right ear. Most of his auricle had perished along with the part of tumor. Just two days before the surgery was planned, the patient felt irritating loud noises in his affected ear. On examination, his external acoustic meatus was found infiltrated with dozens of maggots. It was found that the wound was not smelly anymore and also it was much cleaner than before. This yielded the surgical procedure uneventful. The study was concluded by giving a positive result in favor of the wound debridement therapy using maggots. Dissemond J. (2002) performed a study for biosurgical management of a chronic leg ulcer considering the treatment of methicillin resistant strains of Staphlococcus aureus (MRSA) as this is an emerging problem regarding treatment of wounds as these resistant strains do not respond to the commonly used antibiotics. Dissemond J. used the larvae of the green bottle fly Lucilia sericata on a chronic leg ulcer with methicillin resistant strain of Staphlococcus aureus on ambulatory basis. They suggested that the maggots of Lucilia sericata secrete certain proteolytic enzymes which lead to necrolysis. Moreover, they also exert their effect by secretions containing phenylacetate and phenylacetaldehyde which have antimicrobial properties. Dissemond J. described the maggot debridement therapy to be a better treatment option both in regards of its effectiveness in controlling wound necrosis as well as its expenses as it is an affordable treatment. Another useful study was performed by Peck GW. (2012) and was published in Journal of Medical Entomology. This study discussed the biocompatibility of 13 certain antimicrobials to maggot debridement therapy. This study made use of the larvae of calliphorid flies for patients having severe tissue destruction. A concomitant use of the antibiotics ceftazimde, tobramycin, amikacin, gentamicin, polymyxin B., doxycycline, paromomycin, amphotericin B., sodium stibogluconate and miltefosine at 1, 10 and 100 x the maximum clinical dose (mg/kg/d) with the maggots for treatment of raw liver assays was performed. Out of these antibiotics sodium stibgluconate was found to have a strongest effect on maggot’s survival. The study was concluded by suggesting a simultaneous use of the tested antimicrobials with the maggot debridement therapy for treatment of chronic wounds. Mumcuoglu KY. (2001) studied the effects of maggots excretion/secretion (ES) to be dependent on concentration with maximum effect attained at specific doses. Thus a need was felt for an effective method of delivery to keep a well maintained amount of ES around the wound. Moreover repeated dressings are required for maggot therapy to be effective in case of use of live maggots because of a relatively shorter life cycle of larvae. Also, they must be used within 8 hours of their birth. A study conducted by Smith (2006), published in Biotechnology progress made use of a prototype hydrogel wound dressing containing ES from Lucilia sericata larvae. A significant difference was observed between the ES hydrogel dressing and the wounds of butterfly-only control group. The results of the treatment applied for 12 hours revealed 40 vs 120 megapixels of the mean wound areas. This study indicated that a controlled delivery of ES following maggot debridement therapy may effectively stimulate tissue regeneration in chronic wounds. DISCUSSION. In this literature review, eleven studies have been reviewed. Three of these are in vitro studies, two randomized controlled trials, three case studies, one secondary data analysis one retrospective study and one evaluation study. For maggots debridement therapy, special medically prepared maggots of Lucilia sericata are applied. These are commercially available and are disinfected maggots prepared for use in management of non-healing wounds. Maggots work by: 1. Carrying out the wound debridement, 2. Disinfecting the wound and 3. Enhancing the process of healing. Maggot debridement therapy was allowed and supported by the US Food and Drugs Administration (FDA) in January 2004. Since then, medicinal maggots called as the Medical Maggots ™ made from the strain of Phaenicia sericata larvae are available in market. The British National Health Service (NHS) allowed the use of maggot therapy in February 2004. It has also gained popularity because of its low cost as compared to the conventional debridement techniques. 14 Although maggot debridement therapy seems a bit ‘weird’ on part of the patient, yet many patients agree for this sort of treatment if they are psychologically prepared for it and a complete knowledge of the benefits of MDT is given to them. MDT gains superiority over the conventional debridement techniques as requires only 2 to 3 days of multiple dressings applied as compared to 3 to 4 weeks of conventional debridement methods without having as much benefit as that seen with maggot therapy The maggot dressings are removed from the wound within 48-72 hours. This is the time till when the maggots secrete their proteolytic enzymes. After that, their natural instinct is to leave the wound themselves, which occurs when the dressing is opened. Further washing or irrigation of the wounds removes the remaining larvae, if any. The medically prepared maggots do not invade or feed on the healthy tissue. They are known as the ‘sterile maggots’ and they need about three weeks to mature and start reproducing. The larvae are immature and they are unable to reproduce as long as they are within the wound. Maggot debridement therapy however does contain a side effect of pain felt by the patient, which varies for different patients. This side effect is overcome by use of analgesics and sometimes even by the use of nerve blocks. However, it is always possible to discontinue the treatment whenever possible by removing the maggots from the wound and the pain disappears immediately. The pain may be the result of an increased pressure as the maggots enlarge in size, usually after 24 hours as a result of the nourishment they get from the wound. Or otherwise, it may be a result of the crawling of maggots on any exposed nerves if present in the wound. Most of the studies reviewed above made use of the larvae of common green bottle fly Lucilia sericata, except for the study performed by Wu JC. They made use of the larvae of musca domestica. However, the results of all these study indicate the fruitful effects of using this simple natural phenomenon of wound debridement using maggots. Both these types of maggots had the same result in improving the condition of the wounds where they were applied. 15 The study results of Opletalova K. did not show any significant improvement in the wounds of patients treated with maggot debridement therapy. However, he did accept the faster rate of wound debridement than the conventional method of treatment but only during the first week of treatment. He made use of only the bagged larvae. Here, we can’t comment on the possible outcomes if both free and bagged larvae were used in this study for comparison with conventional treatment. Opletalova K. does not suggest any further use or benefit of maggot debridement therapy after one week of application of maggot dressing. So he suggests using another type of dressing after initial 2 to 3 dressings of maggot therapy applied. The study performed by Cazander G. is an effort to determine the underlying mechanism involved in maggot debridement therapy. This study positively shows the effects of specific secretions produced by maggots to have an effect on the patient’s complement system, thereby leading to an activation of the inflammatory responses. Pre and post operative evaluation of human sra was done and there was found a reduction in the complement activation in post operative sera to about 99.9 %. Cazender G. explained this phenomenon by the fact that maggots actually do not play a role in commencement or inhibition of the complement activation, instead they only affect the C3 and C4 complement proteins in a cation independent manner. Although this study is an account to explain the possible mechanisms involved wound debridement caused by the maggot debridement therapy, yet it is another proof of successful management of chronic debilitating wounds using maggot therapy. Mumcuoglu KY’s study results are also a positive indicator of the beneficial effects of maggot debridement therapy in treatment of non-healing chronic wounds, yet it throws light on another aspect of this method of management; the pain experienced on part of the patient. As explained earlier, maggot debridement therapy is much under discussion for past few decades and is now an approved technique for management of chronic 16 wounds, however, pain is still an issue in this technique and needs to be actively managed, as many a times, the treatment needs to be discontinued due to this side effect. Mumcuoglu KY. used the cage like dressings and hermetic tea bag like pouches for the study purpose using a direct and indirect approach for wound management, respectively. This study also revealed improved wound condition in patients, however certain measures had to be taken for reducing pain levels. Mumcuoglu KY. thus suggested the use of shorter periods of maggot application, replacing the cage like dressings with tea bag like pouched maggots, using smaller maggots and also small number of maggots to overcome the problem of pain experienced by the patient. Systemic analgesics and peripheral nerve blocks are still another option. Telford proved in his study that maggots glycosidases utilize sugars from the slough protein, thereby helping in wound debridement. Wu JC. (2012) studied the effects of maggot debridement therapy making use of the larvae of musca domestica. The wounds showed remarkable improvement although after second therapy. Aseptic dressings were applied during the process. The wound was cured after three successful skin grafts. The study performed by Dissemond J. (2002) was a direct evidence of beneficial effects of maggot debridement therapy on resistant strains of Staphlococcus aureus. He also concluded his study by declaring it to be very cost effective as compared to the conventional methods of wound debridement. 17 While considering the concomitant use of antibiotics with maggots, Peck GW. (2012) performed a useful study taking in consideration, several antibiotics including ceftazimide, tobramycin, amikacin, gentamicin, polymyxin B., doxycycline, paromomycin, amphotericin B., sodium stibogluconate and miltefosine. The results revealed that maggot therapy can easily be applied along with the use of antibiotics for treatment of chronic wounds. Of these antibiotics, stibgluconate had the strongest effects on maggot’s survival as compared to other antibiotics. The study results of Gilead L. can be effectively used to explain the use of maggot therapy in treatment of chronic wounds. He made use of both the sterile live maggots as well as the maggots contained in tea bag like pouches. This study as well as the others considered show that the maggot therapy was not much affected by their direct or indirect; both ways, it was effective. It can’t be concluded from this literature review if maggots show a better result when used directly or when used as bagged larvae in tea bag like pouches as the only study mentioned above which did not prove any beneficial outcome by maggot therapy, conducted by Opletalova K., gave the results for conventional debridement methods more successful as compared to the maggot therapy, made use of the bagged larvae only. Also, maggot debridement therapy has gained much favor in emerging medical research because of its power to heal those non healing chronic wounds which are infected by methicillin resistant strains of Staphlococcus aureus, rendering even the latest antibiotics to fail. In such cases, nature overpowers the science, and maggots have played a good role in defeating such resistant strains of bacteria. 18 Moreover, maggots work very fast as compared to conventional treatment methods especially during the first week of application, they work quite rapidly. The cost effectiveness of this method also makes it more favorable to other methods of debridement. Our study was limited to the research done during past fifteen years for determining possible mechanisms involved in maggot debridement therapy and determining its success in providing beneficial results. The studies discussed explain different mechanisms to be involved in MDT including inhibition of complement system, antibacterial properties and action of glycosidases on carbohydrates. It has proved to be a successful treatment method for debridement of chronic wounds providing an alternate to other methods, although Gottrup F. has outlined certain contraindications for MDT. These include: 1. Open wounds in abdominal cavity as it can damage the internal organs, 2. Septic arthritis 3. Very dry wounds as moist environment is required for maggots survival and 4. Pyoderma gangrenosum in patients undergoing immunosuppressive treatment, 5. Open wounds in body cavities and 6. Wounds lying close to major vessels. But these studies do not give a clue about difference in effectiveness of using bagged or free larvae, or the effects of MDT on different wound types. CONCLUSION Maggot debridement therapy can be used as an effective way for debridement of chronically infected non-healing wounds. It successfully makes its effects by the action of the secretions ES produces by maggots. These contain certain proteolytic enzymes which degrade the necrotic debris and digest the carbohydrates rendering a cleaner wound. Another possible effect is by inhibition of certain complement proteins. Pain is the only major side effect studied yet which can be controlled with the help of analgesics or nerve blocks. MDT has a benefit of acting fast and carrying out debridement leaving healthy tissue behind as medically prepared maggots do not invade the healthy tissue. They are also effective against resistant strains of bacteria where wound fails to respond to conventional antibiotics used. The difficulties in its implications include psychological concerns on part of the patients as they don’t want to see maggots applied to their wounds. Proper psychotherapy and complete information provided to patient helps to overcome this problem. Also, this is still a relatively newer version of an old method, and still experienced staff and full facilities are not available worldwide. With advancement in this technique, we can hope to have better results especially after the discovery of the new hydrogel wound dressing which gave even better results regarding MDT. Read More