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Fly larvae have been associated with infected wounds for millennia. Formal medical interest in their use stems from the 19th century battlefields, where maggots were seen to improve the healing of soldiers’ infected wounds. The practice continued into the World Wars, but larvae fell out of fashion with the advent of antibiotics in the 1940s. One reason they have started to make a comeback is the rise of antibiotic resistance in bacteria such as MRSA.

Larvae secrete antibacterial and antifungal compounds and, combined with their ability to dislodge and dissolve dead tissue while stimulating the healing process, they offer a means of cleaning wounds that may not respond to antibiotic therapy (see panel overleaf). The process is also relatively low risk, and can avoid more lengthy and expensive surgical-type debridement procedures. Another factor in their favour is that larvae can wriggle their way into areas that might not be as accessible with a blade or that liquid treatments can’t penetrate.

With an interest in helping reduce NHS costs by treating patients outside of hospital as much as possible, larval therapy is now increasingly being seen in the community setting. In 2012 there were 1,246 prescription items for larval debridement therapy (LDT) in England, but the trend is upwards.

“With regards usage, the split is 80 per cent acute and 20 per cent community and we are experiencing strong growth in both sectors,” says Ewan Murray, marketing director for BioMonde, the Anglo-German wound care company specialising in the manufacture and distribution of LDT.

“The vast majority of wounds do reside in the community setting and access to these is very much on the increase,” he says. “The increasing use in the community setting follows greater awareness of the therapy, and also increasing confidence in using the therapy.”

Prescribing LDT

Larvae are classed as medicines, rather than devices, but are currently unlicensed in the UK so must be prescribed on a named-patient basis. For patients deemed suitable for home treatment, GPs usually write prescriptions at the request of district or tissue viability nurses or vascular clinics.

Primary care use is unevenly spread, with most prescriptions issued where a cluster of practices is interested or a hospital team is working to encourage uptake of LDT in the community (see panel).

Reactions to using or handling larvae can be very different, says Mr Murray: “People’s ideas are based on the ones used in fishing – but that is when the maggots are grown.” BioMonde supplies larvae less than 2mm in length, but which grow to 10mm in four days, when they are removed or replaced. And in contrast to maggots used for fishing, which are kept in a fridge, medicinal larvae should be stored at room temperature because the cold impairs their activity.

Larvae should not be kept in stock at the pharmacy, but ordered for immediate use. BioMonde has customer accounts in all but one of the 125 UK postcodes, with 24-hour delivery services to all except the Northern and Western Isles and the Channel Islands, which are a 48-hour Royal Mail delivery.

Larvae in bags

BioBag dressings containing ‘medicinally clean’ larvae are now the principal source of supply, with free-range larvae reserved for very extensive or complicated wounds. Dressing bag size depends on the size of the wound, with the optimum number being five to eight larvae per cm2.

“The BioBag does overcome many historical barriers to use,” notes Mr Murray. “There are certain challenges in using the free- range larvae. Escapees are possible and people expect it to be like a scene from Indiana Jones.” However, as the larvae need to pupate before going on to the final fly stage, and a moist wound environment prevents this, such scenes are unlikely.

For those squeamish about the thought of handling larvae, they are supplied in a vial or ‘kit box’, so even if free-range larvae are requested, there is no need for any direct contact on dispensing. Treatment normally continues for four days and is repeated if necessary. Nurses can easily check progress with a BioBag, so if the wound is assessed at day three another bag can be ordered if necessary.

For disposal, the Biobag should be double bagged (secured in the second bag, the larvae suffocate) and treated as Class A disposal for incineration.

Using LDT in Blackpool

In 2011, Blackpool Teaching Hospitals set up an outpatient larval debridement service, which has been extended to the community team, including pharmacies. The hospital’s vascular team refers patients to the tissue viability nurse advisor.

The team involved in the service has published a report and notes that, “although there is an initial cost outlay in using LDT, the fact that patients can be treated at home, have few complications and good outcomes, often with a single application, has meant that LDT is now no longer used as a last resort, but as a proactive choice to clean and close the wound quickly.”

It points out that prescribing decisions are not based on cost alone, but also take into consideration that larval debridement is a fast, low-risk therapy.

When to use

Larvae are seen as a relatively low-risk option suitable for wounds that may not be healing appropriately or quickly, such as diabetic foot, venous or pressure ulcers. Larvae must be able to move around, so if the wound is on a pressure area, it needs to be suspended, which might require a certain amount of immobilisation.

LDT can be used with negative pressure wound therapy (NPWT) – providing oxygen is available – and is also an ideal preparation for NPWT, but there are some contraindications. Linda Rafter, honorary professor in nursing at De Montfort University, has recently written about the use of larvae, and comments that, in addition to certain wound types, larvae should not be used for patients on immunosuppressive or anticoagulant therapy in the community. Care should also be taken to protect healthy skin around the wound, using a hydrocolloid dressing, with Sudocrem applied around the wound edges.

One concern about the use of larvae is the apparent cost. It may look expensive when comparing individual dressing prices, but in overall treatment terms larvae as a debriding agent could be more effective and less expensive, says Mr Murray. “It’s definitely a good option.”

Data analysis backs this up. A study from the Swansea Centre for Health Economics compared LDT with other current debridement methods such as mechanical ultrasound, autolytic treatments (hydrogels or honey) and surgical treatments. The study took into account factors such as rates of clinical intervention and anticipated costs, as well as quality-adjusted life years.

The researchers found that “initiating treatment with LDT is estimated to be a less costly and more effective debridement strategy than initiating treatment with any of the comparator debridement methods evaluated in the base case.” While there was considerable uncertainty in the modelling results, “LDT remained cost-effective under all scenarios tested in a range of sensitivity analyses ... adopting the use of LDT may result in both cost savings and greater benefits for a patient over one year.”

The multiple facets of larvae

What makes larvae so effective in treating wounds? It’s a combination of the maggot mandibles and movement dislodging dead tissue and enzymes digesting it, the antimicrobial properties in the secretions, and the stimulation of the wound healing process while influencing the inflammatory response.

Larvae digest necrotic tissue by secreting proteolytic enzymes, such as chymotripsin, which can break down fibrin clots, and help in the healing processes. Ammonia secretions optimise wound pH. Chymotripsin also stops bacteria from sticking to the wound, helping to prevent the build up of a bacterial biofilm.

Many insect larvae secrete antimicrobial peptides called defensins. These “have the ability to kill especially Gram-positive bacteria and some fungi, but Gram-negative bacteria are more resistant against them. Among them are the medicinally important compounds lucifensin and lucifensin II, which have recently been identified in the medicinal larvae of the blowflies Lucilia sericata and L cuprina, respectively,” say the authors of a review of the bactericidal role of larval secretions in wound therapy.

Their studies showed that the free range larvae of L sericata (the species used by BioMonde) quickly eliminated most of the Gram-positive strains of bacteria and some Gram-negative strains in patients with infected diabetic foot ulcers. “In addition to killing bacteria directly, lucifensin and other antimicrobial compounds from maggots have a number of immunomodulatory functions that may be involved in the clearance of infection and support of wound healing, including the ability to influence host innate and adaptive immune response.”