Larval Therapy for Chronic Cutaneous Ulcers

Historical Review and Future Perspectives

Edoardo Raposio, MD, PhD, FICS; Sara Bortolini, MSc, PhD; Lara Maistrello, MSc, PhD; and Donato A. Grasso, MSc, PhD

Disclosures

Wounds. 2017;29(12):367-373. 

In This Article

Future of Larval Therapy

In the present authors' opinion, increased knowledge of fly biology and larval debridement benefits for chronic skin ulcer treatment as well as the clinical study focus on only 2 species (LS and Lucilia cuprina) call for an investigation of new optimal treatment protocols to find suitable, alternative maggot candidates.

An investigation of new potential species for maggot therapy should be focused on the Diptera order of flies, specifically those families such as the Calliphoridae (blowflies) and Sarcophagidae (fleshflies) (Table); the evolutionary patterns of these 2 families have shifted from scavenging animal matter to parasitism, moving from purely saprophagous free-living larvae feeding on decaying animals to facultative parasitic free-living larvae feeding on necrotic tissues and live animal wounds.[41,42] Species with obligatory parasitic habits, with larvae only able to live on the tissues of living animals, and those causing malign myiasis (parasitic infestation of a live mammal by fly larvae that grows inside the host while feeding on its tissue; eg, all species in the Oestridae family, known as bot flies, or the screwworms Cochliomyia hominivorax and Chrysomya bezziana) must be excluded from this range. Nevertheless, it should be noted that since myiasis is defined as any infestation of live vertebrates (humans and/or animals) with dipterous (order of insects comprising the true flies, characterized by a single pair of membranous wings and a pair of club-shaped balancing organs) larvae which, at least for a certain period, feed in the host's dead or living tissue, liquid body substances, or ingested food,[43] maggot therapy is otherwise known as therapeutic myiasis,[5] an artificially induced, benign myiasis performed in a controlled environment by an experienced medical practitioner, where the risks are outweighed by the benefits of debridement, disinfection, and enhanced healing.

Sherman et al[41] listed a summary of biological properties that could make good candidates for maggot therapy, such as the absence of host specificity, the fast rate of larvae development in the host, the ability to feed on necrotic tissues without invading healthy ones, and the straightforward in vitro rearing. As sterilization is a crucial step in maggot therapy, egg laying also was included among positive properties, as eggs are usually much easier to sterilize than larvae; this is why the mainly oviparous Calliphoridae (producing eggs that hatch outside the body of the mother) were probably better candidates than the larviparous species (laying living larvae instead of eggs).

Besides these characteristics, the authors also suggest considering larvae that have higher chances to survive and thrive in infected wounds/ulcers, create a better environment for wound healing, and produce substances that are recognized as being potentially useful in clinical therapy, such as antimicrobial compounds. For these reasons, other members of saprophagous fly families could represent potential maggot therapy candidates, provided their biology is at least fairly well known and that they are easy to rear and obtain in sterilized conditions. Species of interest in forensic entomology are therefore among the best models to choose from due to the extensive studies performed to obtain the development curves useful for the postmortem interval estimates.

A glance at the typical life cycle of the scavenging-necrophagous fly species (Figure 2) helps clarify its biology. The first instar larvae crawl on the substrate (dead tissue, cellular debris, exudates of wounds or corpses), probing and finely macerating it by means of their hook-like mouthparts. The larvae feed upon the substrate, performing an extracorporeal digestion by secreting proteolytic enzymes and ingesting the liquefied matter; by doing this, they grow bigger and molt twice. Upon maturity, the maggots cease feeding and leave the substrate, searching for a drier and suitably protected area to pupate; adult flies emerge 1 to 3 weeks later. The whole lifespan varies according to the species and is strictly related to the environmental temperature. The development of fly larvae is promoted by temperate climate temperatures and high humidity; wounds may, therefore, represent the optimum for maggot growth rate. Well adapted to living in habitats which typically contain a vast array of pathogenic microorganisms, these larvae have developed several effective mechanisms for survival in these conditions: physical removal of microorganisms by ingesting them, the release of antimicrobial substances by means of secretion/excretion, and specific adaptations of the cuticle and inner lipid.[44–49]

Figure 2.

Life cycle of flies used in larval therapy.

On the basis of these considerations, several other fly species have been shown in vitro to have qualities indicative of putative debridement, antifungal, and antibacterial potentialities.[50–56] These qualities make them potentially good candidates in clinical practice for chronic skin ulcer management. Among them are members of the Calliphoridae, Sarcophagidae, and Stratiomyidae families.

As such, the authors propose that larvae from Calliphora vicina, Calliphora vomitoria (Figure 3), Phormia regina, Chrysomya albiceps, Sarcophaga carnaria, and Hermetia illucens be investigated as new, useful biological agents for ulcer management as new maggot therapy species (NMTS). The authors hypothesize that the NMTS-debrided organic compounds found in salivary secretions and hemolymph, gut, cuticular, and internal lipids and the antimicrobial action of the aforementioned larvae may have the same as or greater therapeutic potentials than those of LS or conventional, mechanical debridement. These compounds include fatty acid methyl ester and alcohol fractions; defensin-like peptide 4; azelaic acid; phenylacetic and phenylpropionic acids; sebacic acid; 3-hydroxy-2-methyl-butanoic acid; (E,E)-2,4-decadienal; and synthetic BhSGAMP-1 peptide.

Figure 3.

Larva of Calliphora vomitoria.

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