Maggot Therapy in Medicine

maggot therapy mechanisms of action

Medicinal maggots have at least two confirmed beneficial effects on wounds that can be supported by laboratory investigations. They are debridement, or elimination of necrotic tissue, and removal of pathogenic bacteria. There is moreover, evidence from recent studies that they may also accelerate wound healing by promoting the formation of granulation tissue as suggested by the early literature,

Wound debridement activity

Necrophagous larvae feed on the dead tissue, cellular debris, and serous drainage (exudate) of corpses or necrotic wounds. Maggots, contrary to popular belief, do not have teeth and therefore cannot actively `chew away' dead tissue. They feed mainly by a process of extracorporeal digestion. Secreted collagenases and trypsin-like and chymotrypsin-like enzymes have been described1-8, which breakdown the necrotic tissue into a semi-liquid form that the creatures can ingest. Because of this mode of action they have previously be likened to `living chemical factories'9, or carpet `shampooers'10.

Casu et al..8 purified two chymotrypsin-like proteases from the secretory and excretory material of first instar larvae. At least one of these proteases was thought to degrade collagen, confirming the earlier observations of Ziffren4.

Maggots also have a pair of mandibles or hooks, which they use to assist in locomotion and provide attachment to the tissue. It has been observed that these hooks are also used during feeding to disrupt membranes and thus facilitate the penetration of their proteolytic enzymes10. The debridement process may be further aided by the maggots crawling about within the wound dislodging small amounts of necrotic material

Antimicrobial activity

As the natural habitats of blow fly larvae, (corpses, wounds and excrement), abound with bacteria, it has long been realized that the maggots must be able to tolerate, if not eradicate, resident pathogens3,11,12. In the 1930s, it was proposed that microbial killing resulted from bacterial ingestion and digestion by the maggots13-15. This was demonstrated by Robinson et al.15,16 who dissected maggots that had been feeding on necrotic tissue to examine the distribution of bacteria within their alimentary tract. In all the specimens examined abundant bacterial growth was found in the fore-stomach but no growth at all was detected in the intestine; an intermediate area called the hind-stomach showed slight growth in one third of cases. A progressive destruction of bacteria was therefore found to take place in the alimentary canal. It is perhaps significant that the majority of this activity is found in the hind-stomach, a region which Hobson3 demonstrated to contain marked proteolytic activity.

The fact that bacteria have lysed as they pass through the insects' gut has been elegantly confirmed by Mumcuoglu using the technique of confocal microscopy17.

It was also suggested that wound exudate, abundant in response to the activity of the maggots, facilitated the irrigation of bacteria out of wounds14 and that the alkalinity of maggot-treated wounds contributed to wound disinfection.

Baer18 first demonstrated that wound fluid was alkaline during maggot therapy, and Messer and McClellan19 believed that ammonia secreted by the maggots was the cause. Subsequently, ammonia and ammonium derivatives such as ammonium bicarbonate were suggested as the factors responsible for disinfection and wound-healing20,21. Stewart's studies led him to conclude that calcium and calcium carbonate produced by the maggots killed bacteria directly, stimulated phagocytosis, and possibly promoted the growth of granulation tissue22.

In 1935, Simmons reported that L. sericata excretions were antimicrobial23,24 and Pavillard and Wright25 in 1957 isolated and partially purified a substance from the secretions of Phormia terraenovae larvae, which killed Streptococcus pyogenes and Streptococcus pneumoniae (pneumococcus). They showed that Staphylococcus aureus was much less sensitive to this substance and Escherischia coli and Proteus vulgaris were both highly resistant. Injection of this isolate into mice protected the mice from the lethal effects of intraperitoneal injections of pneumococcus. Unfortunately, Pavillard and Wright never identified the chemical structure of this agent.

In 1968, Greenberg26 suggested that the ability of maggots to kill bacteria was due metabolic products of Proteus mirabilis, a commensal of the larval gut. These chemical which he called `mirabilicides', were highly lethal to gram positive and gram negative bacteria under acidic conditions. Erdmann and Khalil27,28 subsequently identified two antibacterial substances, phenylacetic acid and phenylacetaldehyde, produced by Proteus mirabilis isolated from the gut of screwworm larvae (Cochliomyia hominivorax).

The ability of larval secretions to kill or prevent the growth of a range of potentially pathogenic bacteria was investigated in a preliminary laboratory study conducted within the Biosurgical Research Unit29,30. Marked antimicrobial activity was detected against Streptococcus A and B and Staphylococcus aureus. Some activity was also detected against Pseudomonas sp. and a clinical isolate of a resistant strain of S. aureus (MRSA). No evidence of inhibition was recorded against Enterococcus or the Gram negative bacteria Escherischia coli and Proteus, although it is believed that in a wound, larvae may prevent proliferation of at least some of these other organisms by other means.

No attempts were made in this preliminary study to isolate or identify the agent or agents responsible for the observed antimicrobial activity and the possibility of a significant pH effect could not be ruled out. Elevated pH alone, however, could not be responsible for the inhibitory effects of larval secretions as S. aureus was able to grow in broth buffered to pH 9. It was considered that the results of this laboratory-based investigation represented a significant underestimate of the ability of maggots to overcome infection in vivo when secretions are produced continuously by the feeding larvae.

The test method took no account of the ability of the actively feeding larvae to ingest bacteria and destroy them in their gut as described by Robinson and Norwood16. This second, and possibly more important mechanism, may explain the reported ability of maggots to eliminate clinical infection from wounds caused by MRSA31,32 and pseudomonas - organisms that are less susceptible to their external secretions under laboratory conditions. In such situations, however, it is important to ensure that a sufficient number