Winter 2016 Biotherapy Journal Review - Diaz-Roa et. al.

Maggot Therapy Reviews

Journal Citation:

Diaz-Roa, A, Gaona, MA, Segura, NA, Ramirez-Hernandez, A, Cortes-Vecino, JA, Patarroyo, MA, and Bello, F. Evaluating Sarconesiopsis magellanica blowfly-derived larval therapy and comparing it to Lucilia sericata-derived therapy in an animal model. Acta Trop. 2016; 154:34-41.

Published Abstract

Larval therapy is used as alternative treatment for hard-to-heal chronic and infected wounds. Lucilia sericata is the most used blowfly species. However, it has been shown recently that Sarconesiopsis magellanica larval excretions and secretions have potent antibacterial activity; this blowfly belongs to the Calliphoridae family. The present work has dealt with evaluating larval therapy using S. magellanica on wounds induced in diabetic rabbits and its action was compared to the effect induced by L. sericata. Twelve New Zealand White rabbits (Oryctolagus cuniculus) were used; they were divided into 4 groups, the first two being treated with larval therapy derived from both aforementioned necrophagous blowflies, an antibiotic was used in the third and the fourth was used as control. All the animals were wounded on the back and infected with Pseudomonas aeruginosa and Staphylococcus aureus. Samples of the secretion from each animal's infected wound were taken and sown on blood agar. The colony forming units were then counted. The PUSH scale was used for the macroscopic evaluation of the wounds. Bacterial control was encountered 48h post-treatment in the treatments involving larval therapy and to a lesser extent with the antibiotic. Likewise, wound debridement was quicker and more efficient with larval therapy compared to the antibiotic group; however, wound closing time was 23 days in all treatments. The group treated with S. magellanica larvae had relatively quicker evolution until the proliferation phase and the start of maturation, even though there were no significant differences between both blowfly species evaluated here regarding treatments by the end of the treatment period. The present study has validated the diabetic rabbit model for inducing chronic wounds regarding larval therapy and has likewise confirmed the effectiveness of S. magellanica-derived larval therapy as an alternative for curing and healing wounds.

Introduction & Background to Study

Maggot therapy (also known as larval therapy or biosurgery, or simply as maggot debridement therapy [MDT]) is the use of live fly larvae (“maggots”) within wound dressings to aid in the cleaning (debridement), disinfection, and healing of hard-to-heal wounds. The authors provide a concise yet detailed review of the history and mechanisms of action of maggot therapy.

Lucilia sericata, one of the blowflies, is the most commonly used species, due in large part to the fact that it is naturally occurring in many parts of the world, and the fact that much of the safety and efficacy studies for maggot therapy have been done with this species of fly. There are a few examples of other blowfly species also being used therapeutically (i.e., Lucilia caesar, Lucilia cuprina, Lucilia eximiaa, Phormia regina, Calliphora erythrocephala, and Cynomyia cadaverina), but most of the published studies evaluating the medical potential of other flies have been in-vitro assessments of extract bioactivity.

The authors of this research paper have previously studied the proteolytic (debridement) and antimicrobial activity of Sarconesiopsis magellanica, a blowfly commonly found in South America. Herein they describe their studies using laboratory rabbit wounds to compare the clinical efficacy of maggot therapy performed either with S. magelllanica or with L. sericata.

Materials & Methods

Study Design – Laboratory animal, treatment intervention, 4-armed comparative study

Study Population – Twelve 8-12 week-old New Zealand White rabbits (Oryctolagus cuniculus); three in each of the 4 groups. Diabetes was induced by intravenous inoculation of 150 mg/kg alloxan; daily insulin was required thereafter. Wounds were created in the sedated rabbits by cutting out a 4 × 4 cm portion of dorsal skin and subcutaneous adipose tissue to a depth of 0.5 cm. The wounds were then covered with 2 ml of a suspension of Pseudomonas aeruginosa and Staphylococcus aureus (at 5 × 106 colony forming units (CFU)/mL). Five rabbits were wounded without inducing diabetes.

Interventions – 4 arms (interventions):  a) maggot therapy using L. sericata;  b) maggot therapy using Sarconesiopsis magellanica;  c) 50 mg ZooFloxin tablet every 12 h for 7 days, and wound irrigation: (wounds were washed with saline solution every 48 hours and covered with dressings changed as needed);  d)  wound irrigation only.

Outcomes Measured –  Major outcome measures included microbiological changes (swab cultures of bacteria and direct smears before and after the intervention); macroscopic changes in wound appearance (with particular attention to wound area, exudates and type of tissue) as quantified by PUSH scores; histological changes in inflammatory cells and assessment of tissue-healing phase.

Study Results

Wounds in non-diabetic rabbits healed rapidly: within about 4 days. Wounds in the diabetic rabbits were still in the inflammatory phase on day 7, when the 4-arm interventions began. Within 2 more days, however, the maggot-treated wounds already showed histological evidence of proliferation (maybe a bit more for the S. magellanica group), and by day 23 all of the maggot and antibiotic animals were nearly healed, but not the control group. Similarly, macroscopic wound healing was readily visualized and quantified, with complete or nearly complete healing by day 23 in the maggot- and antibiotic-treated groups, while the control wounds were still less than 50% closed. Bacterial control was seen quickly in both the maggot- and antibiotic-treated groups. Within two days of MDT and 4 days of antibiotic therapy, microbial growth ceased; but in the control wounds, P. aerugenosa and S. aureus cultures continued to show significant growth. Statistically significant differences in healing were seen between each treatment group and controls; but no significant differences were measured between any of the groups of maggot- or antibiotic-treated wounds.

Author’s Conclusions

“The present work has validated an efficient diabetic rabbit animal model for evaluating chronic and infected wounds which could resemble those . . . in diabetic [humans]. Likewise, MDT has been shown to be more effective during the first phases of healing compared to attempts at healing with antibiotics . . . . It was shown that MDT involving S. magellanica had a more rapid [progression] from inflammation phase to those of proliferation and the start of regeneration, compared to MDT involving L. sericata. [Nevertheless], there were no significant differences on the final day of trials regarding MDT derived from both blowfly species or between MDT and treatment with antibiotics.

Reviewer’s Conclusions

This is an important study, on several levels. First, for those contemplating similar work, a wide array of procedures has been described in detail, from creating diabetic rabbits to designing infected wound models, to disinfecting fly eggs, to quantifying healing macroscopically and microscopically. Additionally, these researchers have produced one of the few comparative studies of wound debridement and disinfection efficacy between two different blowflies. Finally, they have set a good example of how one can evaluate a new species of blowfly for its appropriateness as a medicinal maggot before testing it in humans.

I believe the statements in the paper’s conclusions to the effect that “MDT involving S. magellanica had a more rapid [progression] from inflammation phase to those of proliferation and the start of regeneration, compared to MDT involving L. sericata” are stronger than the data supports, however. Differences between S. magellanica- and L. sericata-associated healing rates were not statistically significant. In fact, with a sample size of only one set of triplicate wounds each, one would not even call the difference a trend. But data is data, and the researchers did see slightly more evidence of advanced wound healing in the S. magellanica-treated wounds, which needs to be followed up.

So, should additional animal studies be performed before trying maggot therapy with S. magellanica larvae? Ultimately, the local research review boards and human subjects protection committees will determine that. But I cannot help myself from weighing in. No matter what the results are in rabbits, one of the ultimate questions remains: what is the efficacy and safety in humans. Testing in humans is the only way to answer that question, and I believe this study is adequate enough to justify testing in humans, albeit in a controlled and closely monitored clinical trial. The advantage of using a more common local species like S. magellanica justifies the cost and effort of new studies to investigate its efficacy and safety, even if this fly proves to be no more effective than L sericata. And if it does turn out to be more effective . . . what an exciting time that will be.