amr Review Article Bugs as Drugs, Part Two: Worms, Leeches, Scorpions, Snails, Ticks, Centipedes, and Spiders E. Paul Cherniack, MD Abstract and Roman texts.1-3 !e popularity of the use of In this second of a two-part series analyzing the evidence for leeches in the 18th and 19th century in Europe the use of organisms as medicine, the use of a number of caused them to become scarce.1,4 di!erent “bugs” (worms, leeches, snails, ticks, centipedes, and Leeches are placed on the skin and guided to the spiders) is detailed. Several live organisms are used as desired site by applying a sucrose solution.5 !ey treatments: leeches for plastic surgery and osteoarthritis and can be prevented from migrating by cutting a hole the helminths Trichuris suis and Necator americanus for in the center of a piece of gauze, where the head of in"ammatory bowel disease. Leech saliva is the source of a the leech is inserted. Leeches are then allowed to number of anticoagulants, including the antithrombin agent feed for 10-20 minutes, after which they stop on hirudin and its synthetic analogues, which have been their own and detach from the site. Although a approved for human use. Predatory arthropods, such as leech only consumes about 5 mL of blood, once certain species of snails, spiders, scorpions, centipedes, and they are removed they can cause leakage of blood ticks provide a trove of potential analgesic peptides in their from the host for a number of hours.5 venom. A synthetic analogue of a snail venom peptide, ziconotide, has been approved for human use and is used as Wound Healing an alternative to opioids in severe pain cases. Arthropods, such Leeches have been used to aid wound healing as ticks, have venom that contains anticoagulants and after plastic surgery. In certain parts of the world, centipede venom has a protein that corrects abnormalities in leeches are commonly applied to treat venous lipid metabolism. congestion at surgical wound sites. A questionnaire (Altern Med Rev 2011:16(1):50-58) given to 62 plastic surgery units in Great Britain and Ireland found that 80 percent had used leeches Introduction 10 times per year on the average.2 !e majority of Part one of this series delineated the use of surgical units provided patient education prior to insects as a source of medical therapy. However, application, and in only 10 percent of cases did many other organisms are present on earth in vast patients refuse leeches. Safety precautions E. Paul Cherniack, MD – The Geriatrics Institute, University quantities and, like insects, have been used globally included written protocols about the use of leeches, of Miami Miller School of in traditional medicine for centuries (Figure 1). In wound disinfection prior to use, nurse monitoring Medicine, Division of Geri- some cases, whole live arthropods or extracts have (including remaining during the whole course of atrics and Gerontology, and the Geriatrics and Extended been utilized; in others, individual substances have treatment), and leech counting before and after use Care Service and Geriatric been refined. In addition, as with insects, other to make sure none remained in the wound. Research Education, and organisms might potentially be a source of new Leech therapy is appropriate in plastic surgical Clinical Center (GRECC) of the Miami Veterans A!airs medicines or be more readily available in some situations in which there is more arterial repair Medical Center parts of the world than conventional medicines. than venous repair, such as fingers, auricles, and Correspondence address: skin flaps.1 Leeches have also been used after Miami VA Medical Center, Room 1D200, 1201 NW 16th Leeches breast surgery to relieve the possible complication Street, Miami, FL 33125 Leeches have been used to treat human illness of venous congestion at the nipple.6 An additional Email: for centuries. !e tombs of Egyptian pharaohs use of leeches in plastic surgery is in the treatment [email protected] contained pictures of leeches, and descriptions of of ring avulsion injuries.7 leech medical treatments appear in ancient Greek Volume 16, Number 1 Alternative Medicine Review 50 Copyright © 2011 Alternative Medicine Review, LLC. All Rights Reserved. No Reprint Without Written Permission. Review Article amr Figure 1. Therapeutic Bene"ts of Various Organisms and Their Products Leeches Snails Scorpions Surgical Wounds Osteoarthritis Hematomas Whipworm/Hookworm Pain Anticoagulants Pain Inflammation Hirudin Lepirudin Ticks Inflammatory Bowel Disease Allergies Anticoagulants Earthworms Centipedes Spiders Anticoagulants Hyperlipidemia Pain While there are many descriptions of leech use, subjects did not receive leeches.12 All subjects were there are no published clinical trials of the efficacy able to have physical therapy and take pain of leeches in surgery. Leech therapy can also cause medication as they desired. One month later, the infections, which occur in 2.4-20 percent of plastic subjects who received the leeches had a signifi- surgical repairs.8 Aeromonas hydrophila, a symbiote cantly lower pain score (1.3 on a 0-10 scale, found in the leech gut that aids in blood digestion, p<0.001), while those not receiving leeches did not is the most common organism found in these improve. infections.8-11 In a second study, 51 subjects with knee osteoar- thritis were provided either leech therapy or topical Post-phlebitis Syndrome diclofenac.13 Subjects assigned to leech application Leeches have also been used to alleviate post- were treated as in the pilot study; control subjects phlebitis syndrome, in which venous valves are applied diclofenac gel to their knees twice a day for obliterated by a deep vein thrombosis.1 In an 28 days. Subjects rated their symptoms using the uncontrolled case series, 40 patients had 7-12 Western Ontario and McMaster Universities leeches placed on their legs every 3-4 weeks. After Osteoarthritis Index (WOMAC) scale for pain, leech treatment, 70 percent of subjects claimed stiffness, and function. !ose individuals who they could walk further, 52 percent stated they had received leech therapy had a 12-point better score less pain, 40 percent had better leg skin color, and than those who applied diclofenac (p=0.0317). 12 percent had reduced leg swelling. !ere were no After one week, there was a significant difference infections or significant blood loss. between groups in pain score; but, by the end of Key words: arthropod, insect, leech, worm, snail, tick, three months, the differences in scores were no scorpion, centipede, spider, Osteoarthritis longer significant. helminth Leeches can treat osteoarthritis pain. In a small In an additional investigation, 113 individuals pilot trial, four leeches were applied for 60-90 with knee osteoarthritis were divided into three minutes to the joints of 10 subjects (mean age 69) groups: (1) subjects received a single application of with osteoarthritis of the knee, while six control leeches, (2) subjects received two leech treatments, 51 Alternative Medicine Review Volume 16, Number 1 Copyright © 2011 Alternative Medicine Review, LLC. All Rights Reserved. No Reprint Without Written Permission. amr Review Article and (3) subjects received a simulated leech therapy individuals tested had restoration of normal consisting of a needle prick and a wet gauze platelet levels. However, there was no lower risk of wrapped up to simulate the size and shape of a bleeding in these subjects than in historical leech.14 Both leech therapy groups had significantly controls.21 In a multi-center investigation of 155 better pain scores on the WOMAC scale than the individuals with deep vein thrombosis, lepirudin- control group. Adverse effects of leech therapy treated subjects had fewer new pulmonary emboli were not observed in any of the three osteoarthri- than heparin-treated subjects (3% for 1.25/mg/ tis studies. kg/12h lepirudin versus 27% for heparin).22 Lepirudin and another modified hirudin, desirudin, Therapeutic Substances from Leeches have been produced by yeast and used as antico- !e therapeutic capacity of the leech is based on agulants in subjects with renal insufficiency.23 secreted anticoagulants that are released while A topical cream manufactured from hirudin was feeding. Specific substances have been refined and used to shrink hematomas caused by musculoskel- utilized in situations where it is necessary to etal injuries.24 Sixty individuals (ages 18-65), who prevent thrombosis.15 Unlike conventional antico- had a bruise created by musculoskeletal injury, and agulants, these anticoagulants have the advantage pain, warmth, or discoloration rated greater than of being selective for specific clotting factors, 50 on a 0-100 visual analogue scale, were random- without affecting others. At least 14 different ized to the hirudin or a placebo cream for five days. anticoagulants have been obtained from leeches.1 Although both creams resulted in a significant Hirudin, which is a specific inhibitor for throm- reduction in hematoma symptoms, the hirudin bin, was initially isolated from the leech salivary cream resulted in a larger absolute reduction in gland.15 It has been applied in the treatment of visual analogue scale score. coronary ischemic syndromes, heparin-induced thrombocytopenia, and disseminated intravascular Worms coagulation (DIC). Probably the most widespread Earthworms provide another source of medici- use in clinical investigation has been its use to treat nally-useful products. Baked earthworms with coronary ischemia.16 In the Organization to Assess bread have been used to treat