Creepy-crawly care: maggots move into mainstream medicine.

Pamela Mitchell is no stranger to modern medical care. Now 52, the former waitress from Akron, Ohio, began getting regular insulin injections at the age of 10, after she was diagnosed with type 1 diabetes. Twenty years ago, she received a life-saving kidney donation from her brother. In 2001, Mitchell faced yet another harrowing health threat. An infected cut on her left foot had turned into a persistent, festering wound. Her doctors recommended that the foot be amputated.

That's when Mitchell began lobbying for a treatment that could have been concocted by the directors of Fear Factor. She pinned her hopes on a mass of writhing, munching maggots.

Hospital treatment of infected wounds with maggots--specifically, blowfly larvae--dates back more than 70 years. But use of these immature insects to remove dead and infected tissue, known as maggot-debridement therapy, long languished on the periphery of accepted practice. Improvements in surgical techniques and antibiotics displaced maggot therapy, as earlier advances had largely supplanted the medical use of leeches (see box, page 267).

Earlier this year, both organisms received approval from the Food and Drug Administration to be marketed as medical devices. Neither had been strictly prohibited, but FDA's imprimatur, as well as some recent research findings, has given long-awaited credibility to the inclusion of live organisms in the medical armamentarium.

In the United States, maggots have been tested for use against several types of wounds and skin ulcers. Among these are diabetic ulcers, such as the one on Mitchell's foot, which nearly 15 percent of diabetics experience at some time. Roughly one in five of those ulcers eventually leads to limb amputation. In the United States, some 60,000 limbs per year are lost to diabetic ulcers.

Another major problem that seems amenable to maggot therapy is bedsores, or pressure ulcers, which bedridden patients commonly develop. Sores increase both the length and cost of hospital stays. The most severe bedsores can lead to fatal complications.

In Europe and Israel, researchers have tested maggots in cases of burn injury, surgical wounds, traumatic injuries, and infections by flesh-eating bacteria. In all these conditions, removal of the dying tissue encourages healing.

While most U.S. medical institutions don't use maggot therapy, "more and more people recognize it as a viable option" says geriatric nurse practitioner Courtney Lyder of the University of Virginia in Charlottesville. He predicts that maggots will eventually rank second only to the scalpel in debridement, eclipsing tools he has analyzed in medical review articles, such as tissue-consuming enzymes. In some cases, maggot therapy may even be superior to surgery, Lyder says.

MAGGOTS MAKE THE CUT Three years ago, as Mitchell's foot festered, scalpels and topical medications held sway in wound care. Her physicians cut away infected tissue--including the tips of two toes--and administered antibiotics, but those treatments didn't halt the spread of infection. Next, the surgeons told her that they would need to remove the entire foot.

"If I'd listened to them, I'd be in a wheelchair right now," Mitchell says. Having recently heard about maggot therapy on a television show, Mitchell urged her caregivers, including Akron-based dermatologist Eliot Mostow, to give the insects a chance.

Mostow, a faculty member of Northeast Ohio Universities College of Medicine, had used maggots therapeutically once before. He initially told Mitchell that her infection was too severe for maggot treatment, but when she remained adamant, he acquiesced.

He placed an order with pathologist Ronald A. Sherman of the University of California, Irvine, who raises, studies, and sells blowfly (Phaenicia sericata) maggots for medical purposes. Eggs of that species can be disinfected before they hatch into maggots. Just as important, the immature flies eat only dead and dying, or necrotic, tissue, which they break down by excreting digestive enzymes that don't harm healthy skin and bone.

Using a bandage, Mostow trapped the sterilized larvae in Mitchell's wound and let them feed for 2 days. After a series of treatments with fresh maggots over a period of weeks, Mitchell's wound was healing.

The maggots "really cleaned those ulcers out," says Mostow, who has since used maggots on several other patients. "Maggots do a phenomenal job of cleaning out dead tissue [in portions of a wound] where your curette or scalpel blade can't go."

But some patients find the procedure repulsive, Mostow says. When applied to the wound, day-old larvae are a millimeter or two long, but they grow to about a centimeter within a few days. The emerging larvae "are like Rice Krispy kernels, only oozing and falling all over each other," he says.

In Europe, where maggots are more widely used, some physicians place the larvae in permeable, plastic or nylon envelopes the size of tea bags. Enzymes and digested tissues can flow back and forth, while the growing maggots stay out of sight.

Mitchell still has her foot, and only a small sear to show for her ordeal. She now occasionally lectures doctors and nurses on maggot therapy and serves on the board of directors of the BioTherapeutics Education and Research Foundation. Sherman founded that organization last year to promote the study and use of maggots, leeches, and other living animals, including bees and pets, in medical care. This year, it began marketing "Medical Maggots."

IMMORTAL WOUNDS Sherman is just the latest champion of maggots in medicine. Military surgeons of the Renaissance and in Napoleon's armies noted that wounds that became infested with maggots healed quickly and resulted in relatively few deaths or complications from infections. During the U.S. Civil War, at least one Confederate doctor applied maggots to soldiers' wounds. But the practice didn't leave the battlefield until after World War I.

In France in 1917, William Baer of Johns Hopkins University treated two gravely wounded American soldiers who, for a week, had lain unattended and unable to move in the contested turf between enemy lines. Maggots swarmed over the men's injuries, but beneath the larvae, the surgeon found surprisingly healthy tissue.

Baer was sufficiently impressed that, after returning to Baltimore, he used maggots to treat 21 non-military patients over several years. After his results were published posthumously in 1931, maggots took hold in the medical community. By 1934, more than 1,000 surgeons in North America and Europe were using maggot-debridement therapy for a variety of wounds.

From the 1940s onward, however, improved surgical techniques for debriding wounds and the advent of antibiotics contributed to the decline of maggot therapy, says Sherman. By the final quarter of the 20th century, the practice was nearly forgotten.

Sherman, one of the few physicians who kept maggot therapy from disappearing in the United States, has spent more than 20 years researching the treatment of skin ulcers with blowfly larvae.

In 1990, Sherman began a study of the safety and effectiveness of using maggots in patients with persistent pressure ulcers. He followed 103 candidates for maggot therapy that were referred to him over the next 5 years.

Some patients did not receive maggot therapy because they, their family members or their primary physicians rejected the idea or because their wounds responded satisfactorily to conventional treatments. Others simultaneously received maggot therapy and conventional treatments, including surgery and topical gels.

Sherman collected data on 92 pressure ulcers--some as large as a business card--in 67 patients. Of these wounds, 49 were treated with conventional means alone and 43 were treated with maggots either alone or with conventional therapy.

During the first month of treatment, 79 percent of the wounds treated with maggots decreased in surface area, and the average area of dead or dying tissue fell by a third. In wounds that didn't receive the maggots' ministrations, only 44 percent shrank within the first month and there was no overall change in necrotic area. Within 5 months, 39 percent of the maggot-debrided wounds had healed completely, whereas only 21 percent of the others did so. Sherman reported these findings in 2002.

Sherman performed a separate evaluation of maggot therapy for treating patients with diabetic foot ulcers. He examined 20 such wounds in 18 patients, whom he treated between 1990 and 1995. These wounds received maggot therapy, conventional surgical and topical procedures, or both approaches.

His results, reported in the February 2003 Diabetes Care, resemble his pressure-ulcer data. During the first 2 weeks of maggot therapy, sometimes combined with conventional treatment, the average percentage of each wound covered by necrotic tissue fell markedly, and 36 percent of those wounds ultimately closed completely. Conventional therapy had no significant effect on the necrotic area during the first 2 weeks, and only 21 percent of the conventionally treated wounds ultimately healed fully.

Maggot therapy may carry yet another advantage. Among 10 deep wounds that were cleaned by maggots before surgical repair, there were no postoperative infections. But there were six infections among 19 similar wounds that were not exposed to maggots, Sherman and Kathleen Shimoda of Veterans Affairs Long Beach Healthcare System in California report in the Oct. 1 Clinical Infectious Diseases.

While few other researchers in the United States have reported data on maggot therapy, several teams in Europe and Israel have been studying the use of the larvae during the past decade. A few studies have reported that some patients with painful skin wounds experience an intensification of pain during maggot treatment. However, most of the studies suggest that maggots are at least as effective, and possibly less expensive, than conventional therapy for infected skin wounds.

A decade ago, Sherman estimates, at most 20 vials of maggots were used in North America each year, excluding those he used himself. Last year, he shipped about 1,000 vials to U.S. doctors. Maggots, Sherman says, "have found their way back into the hearts and minds of many clinicians, and into the wounds of many patients."

Legit Leeches

Wriggling, biting, vein-imitating worms are back in vogue but face competition

Leeches have developed a long resume of medical employment in 2,500 or more years that doctors have been using them. In fact, the most widely used species is named Hirudo medicinalis.

But the three-jawed invertebrates' popularity among doctors has declined from its mid-19th-century peak, when France alone used as many as 30 million per year, medical historians estimate. A decision last June by the Food and Drug Administration, which cleared the way for more companies to sell medical leeches in the United States, is one indication that the organisms are making a comeback in the clinic. Companies that had sold leeches before FDA began regulating them 30 years ago were permitted to keep supplying the animals for medicinal use.

A prevalent current use of leeches is for treatment of a circulatory complication that's common after reconstructive surgeries. Known as venous congestion, it occurs when slow-healing veins are unable to draw blood away from a surgical site at an adequate pace. Blood flow stagnates, robbing the healing tissue of critical oxygen.

Leeches restore circulation by, in effect, acting as surrogate veins until the real vessels heal enough to take over.

"They withdraw blood and simultaneously inject a blood thinner and anticoagulant into the wound," says surgeon Nadine Connor of the University of Wisconsin--Madison. That facilitates slight but steady bleeding from the wound, which relieves venous congestion.

However, because each leech feeds for only an hour or so, a typical patient can require more than 200 animals during the week that treatment can last. The leeches cost little, but applying and monitoring them take time and effort. If the animals aren't watched, they may feed on healthy tissue rather than at the location where they are needed, or they may drop off.

"Also, there's a potential for infection," Connor says. To digest blood, leeches' guts contain certain bacteria of the genus Aeromonas, and those microbes occasionally infect people. "With infection, the success rate of salvaging [grafted or reattached] tissue goes down from about 80 percent to less than 30 percent," Connor says. Occasionally, the infection itself leads to serious complications.

Connor and her colleagues now are developing a device that can improve on the leech's useful function. Their cup-size contraption continually bathes the wound with an anticoagulant and provides gentle suction that keeps blood seeping out of the wound.

For a head-to-head test against leeches, the researchers simulated a skin-graft operation on each of 11 pigs. Six of the skin flaps were treated with up to three devices simultaneously. The rest each got 15 five-leech teams that worked consecutive 1-hour shifts. Both 15-hour treatments extracted the same small volume of congested blood, but subsequent examination of the skin flaps suggested that mild venous congestion occurred in all five of those treated by leeches and only two of the device-treated flaps.

The researchers reported their findings in the November 2003 Otolaryngology--Head and Neck Surgery. Connor says the device needs improvements but could be ready for testing in people within 2 years.

Even if leeches do someday lose their wound-repairing jobs, they have other medical talents to peddle. For example, their saliva harbors a still-unidentified agent that dulls pain, which is why their bites often cause no sensation. That has inspired researchers in Essen, Germany, to investigate leeches for relieving pain in osteoarthritic knees.

Preliminary observations indicate that a single treatment using leeches alleviates pain better during the subsequent week than do daily applications of a standard anti-inflammatory gel. Patients receiving the leech treatment also experienced freer movement and less stiffness in the knee, Andreas Michalsen of the Essen-Mitte Clinics and his colleagues reported in the Nov. 4, 2003 Annals of Internal Medicine.

The use of leeches to manage localized pain dates back to ancient times. If further research supports the findings from Germany, it might become increasingly common in the future as well.