Everyone knows beetles. May beetles, ladybirds, glow worms and jewel beetles all belong to the enormous insect order of Coleoptera (Gr. "koleos" = sheath; "pteron" = wing). Many beetles have their front wings converted into hard wing sheaths (elytra) that cover two-thirds of the thorax and the complete dorsal side of the abdomen. In some this is not the case, as in short-winged beetles (the short elytra only cover part of the back). Although beetles have the greatest wealth of species of all insects, there are only a few that are directly harmful to human health. A few beetles, chiefly belonging to the Scarabaeidae and Tenebrionidae, can be intermediate hosts for worms, such as the tapeworm Hymenolepis diminuta (the cause of non-specific abdominal discomfort), the nematode Gongylonema pulchrum (causes mouth abscesses, among others) and the thorn-headed worm Macracanthorhynchus hirudinaceus (causes intestinal abscesses, among others). Occasional cases of nasal canthariasis have been reported.

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Diamphidea nigroornata, D. simplex and D. locusta belong to the Chrysomelidae. The larvae of these beetles are used by !Kung bushmen of the Kalahari in Southern Africa as a source of arrow-tip poison, often mixed with sap from plants such as Adenium boehmianum or Strophantus sp. Sometimes larvae of Lebistina and Polyclada sp. mixed with scorpion venom is used for this purpose. The beetles contain a poisonous protein, which causes extensive haemolysis, but the exact mechanism has yet to be fully established.

Carpet dermatitis is caused by beetles of the family of Dermestidae e.g. Anthrenus verbasci. The hairy larvae cause a pruritic papulovesicular eruption after contact with the skin. The insects are in principle scavengers. Beetles from this family are often used for cleaning animal skeletons. The museum beetle that causes so much damage to museum collections also belongs to this family.

Blister beetles are insects that cause skin lesions by direct contact. They are found on various continents. They contain highly poisonous substances such as cantharidin or pederin. Cantharidin is found in the haemolymph of the beetle and is released when the insect is crushed. A number of insects secrete the caustic fluid via their leg joints when they are disturbed ("reflex bleeding"). In Lytta vesicatoria cantharidin is also found in the wing sheath.

Blister beeteles belong principally to the families of Meloidae (include the "oil beetles"), Staphylinidae (short-winged beetles or "rove beetles") and Oedemeridae ("false blister beetles"). Some belong to the Cantharidae ("soldier beetles" or "soft-bodied beetles"). There are more than 1500 species of blister beetles. It is a difficult task to describe all of them. The most well-known of the Meloidae is probably the so-called "Spanish fly". This insect is not a fly as the name would suggest, but a beetle, Lytta vesicatoria, with a very bright green or blue sheen on the elytra. These insects occur in Central and Southern Europe. Other blister-producing Lytta species are found in other geographical regions, e.g. Lytta polita, Lytta magister. The eggs are laid on the ground. The larvae are very mobile and climb onto flowers that are visited by bees. They attach themselves with their claws to these insects and are so transported to their nest. There they devour larvae and food stores. Lytta larvae thus develop as parasites in the nests of solitary bees. Adult Lytta vesicatoria are often found on ash trees, elder trees and privet.

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The American blister beetles belong to the Meloidae, including those of the genus Epicauta. We know of Epicauta temexa and E. occidentalis or three-striped blister beetles, Epicauta vittata or striped blister beetle, Epicauta pennsylvanica and E. conferta or black blister beetles and E. paradalis or spotted blister beetle. The animals have a remarkable life cycle. Epicauta blister beetles undergo hypermetamorphosis (=heteromorphosis), a complex life cycle with several stadia. Hypermetamorphosis is common in predaceous and parasitic insects in which a change in habit occurs during the course of larval development. Two to three weeks after copulation, the females lay six clusters each of 50-300 eggs, from which leg-bearing active larvae appear 10-20 days later. The first stage larvae of Meloidae (and Strepsiptera) are known as triungulins referring to the three typical claws on the legs (Lat. "tri" = three, ungulus = claw). In this stage, they feed on grasshopper eggs. The beetles occur therefore in regions where there are large numbers of grasshoppers (predominantly Melanoplus sp.). The next stages are legless and maggot-like. The larvae of many other blister beetles feed on bee eggs or in beehives. The insects hibernate as sixth instar larvae 2.5-4 cm below ground. The following spring the larvae moult again and then pupate, so that adult beetles appear at the earliest around the end of May or beginning of June. Adult beetles are 12-19 mm long with an almost cylindrical body. The width of their heads is larger than the diameter of the pronotum (scutum on the first thoracic segment). The elytra can be black or metallic or striped. In the USA the adults sometimes invade parts of blooming alfalfa (lucerne, Medicago sativa) fields where they feed on nectar and pollen. They often group in swarms, as a result of which only part of a field is infested. When the alfalfa is harvested, some batches can be toxic and others from the same field completely harmless. The damage due to the beetles eating is insignificant, but they are important because of the consequences of direct contact with their toxin. Animals feeding on infested lucerne can become gravely ill and even die.

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Some blister beetles of the family of Meloidae belong to the genus Mylabris (Mylabris phalerata, M. cichorii, M. alterna). These beetles contain more cantharidin than Spanish flies. The insects are still used in traditional Chinese medicine. Cylindrothorax sp. also belong to this family. Other blister beetles include Pyrota insultata, Cyaneolytta sp., Neopyrochroa flabellata (Pyrochroidae), Psalydolytta sp. and Coryna apicicornis. The Oedemeridae (false blister beetles) form a family of 1500 species that are found predominantly in temperate regions. The larvae live in wood. There are several genera with cantharidin-containing species within this family, e.g. Eobia (Sessinia) collaris and Eobia (Sessinia) decolor in Samoa, the Solomon Islands and Tahiti, Eobia kanack in Papua New Guinea, Fiji, New Caledonia and surrounding islands, Oxacis and Alloxacis sp. in the Bahamas, Oxycopis vittata and O. mcdonaldi in Florida and the Caribbean and Thelyphassa lineata in New Zealand.

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Among the Staphylinidae, the genus Paederus is known to contain at least 25 species. Paederus fusca is well known in the rice fields of Southeast Asia. Paederus crebinpunctatis and P. sabaeus occur in East Africa. P. cruenticollis is important in Australia. The most striking characteristic of these beetles is the very short elytra (hence the old name for this group: Brachyptera). They are often strikingly metallic and yellow coloured. The hindmost tip of the abdomen is often dark. The adults can fly well. The penultimate hindbody segment contains an extremely fine comb on the posterior border, which helps in the unfolding of the wings. At rest, the wings are folded up so as to find a place beneath the short wing sheaths. It is not so simple for the insect to fold up its wings again. In many cases, it has to raise its hindbody and support the wings with it. In this position, the large species at first sight resemble earwigs, but short-winged beetles have no pincers at the end of the abdomen. The adult beetles and their larvae often live in damp environments. The adults are active during the day and are attracted by light at night, which can bring them into contact with humans. In addition to Paederus sp., other short-winged beetles of the genera Anothylus, Atheta and Oxytelus also cause blister formation.

A complete different mechanism occurs in bombardier beetles. These curious insects belong to the Carabidae family. There are three separate subfamilies: the Carabinae (e.g. Brachinus sp.), Paussinae (e.g. Goniotropis sp.) and Metriinae (e.g. Metrinus sp.). They spray a hot jet of defensive chemicals when disturbed. This mechanism involves paired special glands which synthetise (1) hydroquinone and methylhydroquinone, (2) hydrogen peroxide and (3) the hydrocarbon pentadecane. The secretions are stored in the reservoir portion of the double-chambered gland. The second portion of the gland is the reaction chamber which contains catalase and peroxidase enzymes. Mixing of the quinones and H₂O₂ with the enzymes leads to exothermic catalytic conversion, with a rapid build-up of pressure from liberated oxygen, and explosive discharge of oxidised quinones. This can even be heard as a "pop". Studies on a Kenyan bombardier beetle (Stenaptinus insignis) showed that the discharge is pulsed. The explosive chemical oxidation produces a build-up of pressure in the reaction chamber which closes the one-way valve from the reservoir, thereby forcing discharge of the content through the anus. This relieves the pressure, allowing the valve to open, permitting refilling of the reaction chamber from the reservoir (which remains under muscle pressure). By this mechanism, a high-intensity pulsed jet is produced by the chemical reaction, rather than requiring extreme muscle pressure. In this way, the animal not so much resembles a hot water pistol than a caustic spraying machine gun. The temperature of the spray is about 60-100°C. Sufficient heat is released to vaporize about 20% of the reactant solution. Brachinus beetles have a very accurate aim. The hot caustic jet can be pointed in all directions by rotating the mobile abdominal tip and pointing it towards the target. If the jet touches the skin a local burn will result.

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Many blister beetles contain a specific bicyclic monoterpenoid, cantharidin (C₁₀H₁₂O₄) (Gr. "kantharis" or beetle). A related substance, anemonin, is found in certain plants (Ranunculaceae). Cantharidin is not soluble in water, but is fat-soluble. Cantharidin binds chemically to phosphatases 1 and 2A. These enzymes play a role in cell proliferation, membrane channels and receptors, modulation of protein kinases and modulation of other phosphatases. The toxin is very stable. Dead beetles are still dangerous. Consequently control by means of insecticides does not remove the danger. The toxin protects the beetles from predators and is found in the haemolymph and gonads. A beetle contains 1-5% cantharidin by dry weight. Males contain more toxin than females. A male beetle transfers cantharidin to a female during copulation ("nuptial gift"). This is then passed on with the eggs so that these too are protected against predators.

Sometimes cantharidin is swallowed. The toxin is readily absorbed from the intestine and excreted in the urine. If cantharidin is swallowed to arouse sexual appetite, in an attempted suicide, by accident, with criminal intent or to induce abortion, several symptoms may occur depending on the dose. The initial discomfort begins within 30 minutes. Dysphagia as a result of mucositis with irritation of oral, oesophageal and gastric mucosa is followed by abdominal pain, nausea and vomiting, possibly with blood. Oedema, bleeding and necrosis of the mucosa occur at an early stage. There is intense congestion of the genito-urinary tract, with bleeding in the renal pyelum, ureters and bladder. Bleeding can also occur in the ovaries. Sometimes there is internal bleeding and bruising. Priapism occurs, which was the origin of the use of the substance as an aphrodisiac (Gr. Aphrodite = goddess of love). Diarrhoea occurs, accompanied by leukocytosis, haematuria, renal tubular necrosis, uraemia, shock and coma. Approximately 30-60 mg is sufficient to kill an adult person. Cantharidin can be tested for by HPLC ("high performance liquid chromatography") and gas chromatography (gastric contents, urine, serum).

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On skin contact with cantharidin-containing blister beetles, local tissue irritation occurs after a few hours. This results from the disruption of tonofilaments in the desmosomes with acantholysis and intra-epidermal blister formation. Redness, oedema and vesicles can appear on the skin. Sometimes there are "kissing lesions" on the elbow or in the hollow of the knee. In contrast, the effect of pederin is not immediately noticeable and only becomes apparent after 1 to 2 days. The erythema is much more severe and can persist for months. On contact with the conjunctiva and/or cornea, Paederus sp. cause "Nairobi eye". This is associated with extensive painful peri-orbital swelling and purulent conjunctivitis. Corneal erosions and blindness can follow.

Cantharidin is toxic to sheep, goats and cattle, but above all horses. When the toxins are swallowed (e.g. horses that eat alfalfa containing live or dead beetles), mouth ulcerations, colitis and diarrhoea, painful micturition and general indisposition occur. With severe intoxications, fever, hypocalcaemia, shock and death will follow. For a horse a dose of 1 mg/kg is fatal.

There is no specific antidote. Steroids are not effective in controlling the ulcers in the gastro-intestinal tract. Fluid, calcium supplements, analgesics and broad spectrum antibiotics should be given. Gastric lavage should be carried out and activated charcoal administered. Cantharidin is to a large extent bound to albumin and is not removed by haemodialysis via a charcoal column. Physiological fluid should be administered IV. A blood transfusion might be necessary. Maximum diuresis must be obtained with IV fluid, mannitol and diuretics. No fat should be given orally because it increases the absorption of the toxin. For external lesions, the skin should be rinsed copiously as rapidly as possible. After disinfection, silver sulphadiazine cream should be applied. Subsequent care is the same as for a burn. Skin lesions caused by cantharidin practically always heal without leaving scars. An eye that is affected should be rinsed copiously. Afterwards an antibiotic- and steroid-containing eye ointment should be applied (cfr. eye lesions caused by spitting cobras).

Cantharidin is regarded by some poorly informed people as an aphrodisiac. The use of this substance has fortunately become rare. It is also used by some desperate people to induce home-abortions. Cantharidin-analogues are being studied for potential antitumour activity. Skin warts can be treated by cryotherapy, electrosurgery, laser therapy or topical application of cantharidin (Cantharone®), whether or not in combination with salicylic acid and/or podophyllin.