History of Maggot Therapy

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References to the use of maggot therapy in ancient times
The primitive, carrion-breeding habit of blowflies has been known and recorded for centuries. A very early reference can be found in the Hortus Sanitatus, one of the earliest European medical texts, published at Mainz in 1491. Fewer historical references are available on the habits of parasitic species that cause myiasis although some references do exist. In the Bible, Job (Job 7:5) complained `My body is clothed with worms and scabs, my skin is broken and festering'.
In contrast, there are some indications that some primitive societies have recognized that the larvae of certain flies can have beneficial effects upon the healing of infected wounds. In the early part of this century, the Ngemba tribe of New South Wales, Australia, commonly used maggots to cleanse suppurating or gangrenous wounds and it is said that the aborigines traced this practice back to their remote ancestors. The Hill Peoples of Northern Burma were observed during World War II placing maggots on a wound then covering them with mud and wet grass: the Mayans of Central America ceremoniously exposed dressings of beef blood to the sun before applying them to certain superficial tumours; after a few days the dressings were expected to pulsate with maggots.
Maggots in military conflicts
The opportunistic infestation of wounds, particularly those sustained in battle, has similarly been observed throughout the centuries. Ambroise Paré (1509-1590), Chief Surgeon to Charles IX and Henri III, recorded that in the battle of St. Quentin (1557) maggots frequently infested suppurating wounds.
Napoleon's Surgeon in Chief, Baron Dominic Larrey, quoted by Goldstein4 reported that when maggots developed in battle injuries, they prevented the development of infection and accelerated healing. `These insects, so far from being injurious to their wounds, promoted rather their cicatrization by cutting short the process of nature and causing the separation of cellular eschars which they devoured. These larvae are indeed greedy only after putrefying substances and never touched the parts endowed with life'. There is no evidence, however, that Larrey deliberately introduced maggots into his patients' wounds.
During the American Civil War, a Confederate medical officer Joseph Jones, quoted by Chernin5 noted the beneficial effects of wound myiasis 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. I have heard surgeons affirm that a gangrenous wound which has been thoroughly cleansed by maggots heals more rapidly than if it had been left to itself.'
According to Baer and McLellan the Confederate surgeon J. Zacharias, may have been the first western physician to intentionally introduce maggots into wounds for the purpose of cleaning or debriding the wound. Baer quotes Zacharias as stating: `During my service in the hospital in Danville, Virginia, I first used maggots to remove the decayed tissue in hospital gangrene and with eminent satisfaction. 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, escaped septicaemia, and had rapid recoveries'
A fascinating review of the early history of maggots in wound care was published in 1932 by Goldstein.
Maggot therapy in the early 20th century
The founder of modern maggot therapy is William Baer (1872-1931), Clinical Professor of Orthopaedic Surgery at the Johns Hopkins School of Medicine in Maryland.
He described how, during the First World War, he had treated two wounded soldiers who had remained overlooked on the battlefield for seven days having sustained compound fractures of the femur and large flesh wounds of the abdomen and scrotum. On arrival at the hospital they showed no sign of fever or septicaemia despite the very serious nature of their injuries and their prolonged exposure to the elements without food or water. On removal of their clothing Baer found `thousands and thousands of maggots that filled the entire wounded area.' To Baer's surprise, when these 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 granulation tissue that one could imagine'. This at a time when the mortality rate for compound fractures of the femur was about 75-80%. Support for Baer's observations was provided by Crile & Martin who also reported that soldiers whose wounds were infested with maggots did far better than their wounded comrades who wounds were not similarly afflicted.
Following these wartime experiences, Baer treated four children with intractable bone infections (osteomyelitis) at the Children's Hospital in Baltimore in 1928. His initial use of unsterilized maggots was very successful and the wounds healed within six weeks. Encouraged by these results, Baer began to use the technique more widely, but unfortunately several of his patients developed tetanus and he concluded that it would be necessary to use sterile maggots for future work.
The importance of sterility
Having once accepted the importance of using larvae that were free from microorganisms, Baer devoted some considerable efforts to developing a suitable sterilization process6. He initially attempted to sterilize maggots themselves by first exposing them to full strength hydrogen peroxide for two hours, and then immersing them in mercuric chloride solution 1 in 1000. Although he was able to demonstrate that this process effectively sterilized the outer surface of the larvae, viable bacteria persisted within their gut. He then decided to sterilize the eggs, believing correctly that the contents were sterile. He tried many different solutions including mercuric chloride, phenol, alcohol, Mercurochrome, gentian violet, hexylresorcinol and silver nitrate. These efforts were more successful at achieving sterility, but most also proved lethal to the eggs. Eventually a technique was developed which involved the use a solution containing mercuric chloride 1 in 1000, 25% alcohol and 0.5% hydrochloric acid.
Because of the popularity of maggot therapy in the 1930s, numerous papers were published describing techniques for breeding flies and producing sterile maggots.
Although Livingston and Weil's group claimed some success with the sterilisation of hatched larvae, the latter with a solution of iodine, most centres adopted Baer approach and concentrated on developing methods for sterilising the eggs. A commonly used method began with pretreatment in Dakin's solution (dilute sodium hypochlorite, or bleach) followed by immersion in mercuric chloride or formaldehyde. Simmons reported satisfactory sterilisation using 5% formalin, 1% sodium hydroxide; yet, even his method did not kill all spore forming bacteria such as Cl. perfringens or Cl. tetanii.
First commercial production of maggots
In the absence of any equally effective alternative for the treatment of osteomyelitis or infected soft tissue injuries, the use of maggots spread quickly during the 1930's. In the USA, Lucilia sericata larvae were produced by Lederle Corporation and sold for $5 per 1000 (now equivalent to about $100).
In the mid-1930s, Robinson surveyed 947 North American surgeons known to have employed maggot therapy. Of the 605 responding surgeons who had treated 5750 patients, 91.2 % expressed a favorable opinion; only 4.4% expressed an unfavorable view. The most common complaints raised by surveyed practitioners were the cost of the maggots, the time and effort required to construct the maggot dressings, and the degree of discomfort suffered by patients. Robinson's paper also included a list of 54 papers on maggot therapy that had been published by that time.
Other than Baer's cases of tetanus and one case of erysipelas, thought to be associated with the use of non-sterile larvae no other serious adverse reactions were reported.
During the 1930s, attempts to isolate the `maggot active principle' led to the use of a topical application of maggot extract to promote wound debridement and disinfection. Livingston described the treatment of 567 patients using maggot therapy alone or in combination with `maggot active principle' derived from Lucilia sericata. He also used a polyvalent vaccine of pyogenic organisms suspended in the maggot principle as a vehicle administered intra-muscularly. Using this technique they claimed a success rate of 88%, 38% higher than control cases treated by other methods. Perhaps not surprisingly, this was associated with significant systemic reactions, and eventually abandoned.
The demise of maggot therapy
These years also marked the beginning of the Antibiotic era. By 1940, sulfonamides already were available, and Chain et al. had discovered the methods for mass-producing Flemming's penicillin. As a result, by the mid-1940s, maggot therapy had virtually ceased, except as a treatment of last resort due largely to the ready availability of the new wonder drug and general improvements in surgical and wound management techniques.
Early evidence for the effectiveness of maggot therapy
The early maggot therapy literature contains many references to the successful treatment of chronic or acutely infected soft tissue injuries, including those infected with Clostridium welchii (Cl. perfringens) the `gas bacillus'. Wounds treated with maggots included abscesses carbuncles leg ulcers pressure ulcers, mastoiditis and compound fractures.
Maggots were primarily used, however, in the treatment of osteomyelitis, and although unable to digest or liquefy dead bone (sequestra) they were said to facilitate its separation at the interface with normal bone, leaving behind clean healthy granulation tissue. Very many dramatic accounts of its use appear in the literature summarized by Pomerantz who stated that following maggot therapy `the end product approximates more closely to normal bone structure than any of the hitherto accepted methods of treatment'
It was also claimed repeatedly that in addition to removing devitalized tissue, the application of maggots had a positive effect upon the speed of wound healing. This was first noted by Larrey in 1829 who reported that when maggots developed in wounds sustained in battle, they prevented the development of infection and accelerated healing. This view was also shared by Baer and Fine who stated that `Maggots produce rapid and thorough debridement and stimulate granulation tissue production' He was so convinced of their ability in this area that he stated that `when debridement is complete, fewer maggots are used and their function at this time is to complete to keep the wound clean and promote healing'.
Weil et al. the first to coin the term `Larval Therapy' also asserted that; `Coincident with the removal of necrotic and devitalized soft structures, is the development of highly vascular granulation tissue which excretes abundant serum and which may be looked upon as a very beneficial factor in wound defense in this form of therapy. ... The apposition of wound margins following larval therapy brings about a rapid development of granulation tissue, which can often be noted within a few hours'.
Maggots appear to have another interesting and potentially very valuable ability. They are able to destroy unhealthy or abnormal tissue leaving healthy tissue in its place. Weil et al. observed, `when the larvae come into contact with exuberant and edematous granulations, they attack it vigorously, and remove it as any other abnormal structure, after which the change to healthy granulation tissue soon occurs. We have observed that the larvae will attack almost any type of abnormal viable structure, including malignant tissue as well as devitalized soft or bony tissues'.
This they illustrated by reference to two cases of inoperable Breast Cancer and two sarcomas of the thigh. `On admission, each breast ulcer measured the approximate size of half a dollar with the malignant tissue presenting itself upon a level with the surrounding skin. There was extensive invasion of almost the entire breast substance. Following four implantation of larvae in one case there was observed an excavation of the underlying malignant tissues for a depth of 3.5-4 cm but with only slight variation in the size of the original skin opening. As the larvae cleared away the malignant tissue, clean healthy granulation tissue appeared, the odour disappeared and the wound attempted to close'. The remaining cases showed a similar response and the authors concluded that malignant tissue has a very weak defense against the activity of larvae.
Subsequently, Bunkis et al. and Reames et al. described the benefits of debridement and odour control resulting from accidental myiasis of head and neck tumors, and Seaquist and colleagues. also reported benefits from naturally occurring Phormia regina myiasis in a malignant lesion. This infestation, however, was accompanied by pain.
Methods of application
Over the years, numerous techniques and dressing systems have been described for ensuring that maggots are contained within the area of the wound but many were difficult to construct and almost certainly very uncomfortable to wear. They typically consisted of layers of crinoline or gauze. but Child et al., used a piece of 80 mesh brass net set in a foam frame secured to the skin. Others including Weil. and Mckeever. adopted a similar approach using copper mesh or milk strainer wire held in place with adhesive tape or, sometimes, Unna's Paste - a mixture of zinc oxide, gelatin, glycerin, and water31.
Self retaining metal, or glass, devices were developed to hold wounds open during therapy and these allow drainage of the wound and providing access to the maggots. Ochsenhirt and Komara, described a complex technique for intraoral treatment, involving dentures with tubes through which the larvae were introduced.
As part of the application process, Livingston. recommended exposing the maggots, once applied, to a bright light in order to drive them deep into the wound, but this was considered unnecessary by Robinson, who also emphasized the need to control the number of larvae applied, proposing that as few as 6 might be sufficient for a finger tip injury although 500-600 may be required for more extensive wounds
Large quantities of larval enzymes can cause significant excoriation if they are allowed to run onto unprotected skin around the margin of a wound. In severe cases this resembles a superficial burn, but like such an injury, this will rapidly resolve over a few days. Robinson, who had also encountered this problem, suggested that the surrounding skin should be covered to protect it from larval secretions and to eliminate the tickling sensation caused by the maggots' movements. He considered that the collodion proposed by Weil et al.3 and adhesive plaster advocated by Child were not suitable as they tended to separate from the skin once wet. He suggested that a liquid adhesive system described by Buchman and Blair or the Unna's paste described by Jewett would both be far more satisfactory for this purpose. Early problems with maggot therapy
Although no serious side effects were noted following the use of maggots, a transient pyrexia was of 2-4°F was noted on a number of occasions by Fine21 Weil, 3 McLellan7 and Buchman13 who suggested that this was due to `the opening of chronically infected lymphatics' This invariably subsided upon removal of the maggots.
A more inconvenient problem, then as now, was the unexplained failure of some applications of maggots to survive on the wound. McKeever suggested that this could be due to the maggots drowning due to poor drainage but an alternative explanation is that the pH of the wound is not suitable for the young larvae. Hobson showed that secretions of Lucilia larvae contain proteolytic enzymes which function optimally at pH 8.5. As conditions become progressively more acidic the enzyme activity is reduced. It is possible, therefore, that in a wound with a relatively low pH, the enzymes will be unable to breakdown the necrotic tissue and the maggots will therefore starve to death. Some support for this theory was provided by Wilson et al. who showed that larvae do not survive well in an acid environment.
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