Fwd: Think FLIES are just a Nuisance? Beware! Read this -

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My wife got this post out of another group she belongs to.   laz

 Micro-Myiasis  disease

Introduction

This research describes an affliction of myiasis, but focuses on small, primitive fly species, that cause the infestation of small fly larvae, causing generalized, chronic myiasis.  It discusses the possibility that the unusual entities leached from sufferer's skin and their symptoms, can be explained via the anatomy, physiology and secretions from these small fly larvae.

Myiasis is defined as the infestation of live human and vertebrate animals by larvae of the order Diptera (true flies; i.e., those whose adults have two wings) that feed for varying time periods on the host's dead or living tissue, body substances, or ingested food (1). There are 36 types of fly known to cause myiasis in humans (20).

Many reports are concerning myiasis infecting travelers and, in general, myiasis is thought to be much less common in temperate regions than in tropical countries. However, human cases also originate from North America, UK, Netherlands, Portugal, Turkey and Greece amongst others. Myiasis is endemic in the United States, where it is thought to be caused by larvae of flies of the genus Cuterebra.

Billions of livestock and domestic animals are infected by fly larvae (known as 'Fly strike'), every year, all over the world. The increasing number of cases is thought to be caused by global warming and a resistance to pesticides (42).Myiasis disease is a systemic, medical condition that began to be recognised in 2002. Myiasis is barely recognised by main stream medical communities and it's cause has not been established to date. It has a variety of symptoms including itchy skin; with crawling, biting sensations, white granules from skin and hair follicles, chronic fatigue, sores/lesions and fibrous material coming from skin (2).  Sufferers often test positive for Lyme disease along with other bacterial and fungal infections. Very few sufferers have managed to find a cure.

Myiasis disease sufferers often observe activities related to small flies (Table 1). Some describe themselves as being 'saturated' with small larvae and many sufferers talk of seeing worms coming from their skin.  This study outlines published myiasis research and primarily relates it to attributes and cases of Myiasis disease.

 

Myiasis

Myiasis is caused by parasitic fly larvae that infect animals and humans. Obligatory parasites require living tissue for larval development. Facultative parasites usually develop on carrion or vegetable matter, but may occasionally develop on living tissue. Some facultative myiasis-causing flies have adapted so well to a parasitic existence that they essentially become obligatory parasites. In such cases, the distinction blurs between the two categories. In accidental parasitism, the eggs or larvae are accidentally ingested and are not killed in the intestine (6).

The scientific community have not yet established the biological, chemical and behavioural traits of myiasis causing flies (30). So out of the 158,000 recorded species of fly, why is it believed that only certain species manage to infest animals or humans?

Experts question whether it is simply the ability of the fly larvae to overcome the immune defence response of the living host (30). If this is the case, then it may indicate that humans and animals maybe susceptible to infections from a wider variety of fly families with various attributes, than currently thought.

Furthermore, in terms of evolution, experts believe that arthropods parasitising vertebrates is a switch, which is not thought to have happened with other groups, e.g. protozoa, nematodes and platyhelminths (30). If this evolutionary switch/switches took place with flies, then there is a possibility that this switching has actually taken place with a wider variety of flies than presently recorded.

Children, the elderly, the disabled and the immuno-compromised are particularly susceptible to myaisis infections, due to lack of physical movement (inability to scratch), decreased personal hygiene and therefore greater odourous attractants for flies.

Myiasis is responsible for severe economic losses for animal farming and affects domestic and wild animals including cattle, sheep, horses, cats, dogs, rabbits, rodents, amphibians and even elephants. It causes abortions, reduced milk production, weight and fertility loss and poor quality hides (30). There are also scientific reports that consider whether the extensive use of pesticides is driving flies to find new hosts, which has been proposed as another theory to explain the increase in animal myiasis recorded, as well as climate change.

A simulated climate change model predicted a potential increase in fly populations of 244% by 2080 (43).

 

Sites of infection

Myiasis can cause a broad range of infections depending on where the larvae inhabit the host (5). The main infection sites are orifices and body cavities. Myiasis is classified by area of infestation in the body, typically: cutaneous (dermal/sub-dermal), enteric (intestines), ophthalmic, nasopharyngeal, auricular, oral, mammary, urogenital and anal (6). In one review of 25 myiasis cases, the scalp was the most commonly affected region (40%) (11).

Often, the species causing the infestation prefer particular sites of the host. For example, in cutaneous myiasis the common sites for lesions are the scalp, face, forearms, and legs for the Myiasis causing D. hominis, and the trunk, buttocks and thighs for C. anthropophaga.

Over 50 species of fly larvae have been found in human intestine after surviving the stomach acid(43), and some end up parasitizing in the region of the rectum. Larvae of the fly families Muscidae, Sarcophagidae, Calliphoridae and Phoridae, as well as mosquitoes of the families Anisopodidae and Scenobinidae are known to cause urogenital myiasis.

Nasal-pharyngeal myiasis is known to be caused by 8 families of flies which are able to enter the eyes (e.g. Oestrus ovis into the nose and within the eye). Dermal and subdermal myiasis is the commonest form, since the eggs or larvae can enter wounds or may even enter healthy skin regions. Some larvae (e.g. Hypodermatidae) are able to wander around under the skin (creeping eruptions).

Generalised myiasis is the term used when their are multiple sites of infection.

Table two lists the main recorded myiasis causing species and the hosts/sites they prefer.

Below are the more well known myiasis causing adults and corresponding larvae:

Figure 1 -Myiasis causing adults, Figure 2- corresponding Myiasis causing larvae

KEY: 1) Cochliomyia hominivorax; 2) Chrysomya bezziana; 3) Lucilia sericata; 4) Calliphora vicina; 5) Phormia regina; 6) Protophormia terraenovae; 7) Auchmeromyia luteola; 8) Cordylobia anthropophaga; 9) Wohlfahrtia magnifica; 10) Sarcophaga cruentata; 11) Musca domestica; 12) Megaselia scalaris; 13) Dermatobia hominis; 14) Gasterophilus nasalis; 15) Hypoderma bovis; 16) Rhinoestrus purpureus; 17) Cephalopina titillator; 18) Oestrus ovis.

What has Myiasis been known to cause?

Skin Lesions

Multiple furuncle-like lesions may occur with crusted, odoriferous, purulent, or serosanguinous discharge, caused by larva proteins and feces, which may also be bloody. There is sometimes a central punctum with movements of spiracles of larva or bubbles in serous larva discharge. The patient complains of pruritus and a crawling sensation within the lesion and some maybe painful (which is often nocturnal) (11). The protein (enzyme) discharges may literally melt/burn the skin, causing scaring and hypo or hyperpigmentation.

There maybe satellite lesions near a central lesion and multiple larvae may aggregate together in certain places under the skin during cutaneous myiasis. Often more than one larva is present in a lesion (11).

Protrusion of the breathing tube of the larva frequently can be observed with the aid of a hand lens (12); a small white threadlike structure protruding from the lesion (39). Lesions are occasionally accompanied by enlargement of the draining lymph node (12).

The subsequent feeding activity of the larvae at the skin surface rapidly promotes extensive tissue damage, resulting in the development of inflamed, abraded and ulcerated areas of skin with progressive alopecia (hair loss).

Figures 3-6 - Myiasis furuncles

Lumps & nodules

Cutaneous myiasis can resemble a soft-tissue tumor when its in it's early phase, or in unusual places on the host. Breast lesions can appear as a palpable lump and as a corresponding mass at mammography (9). Myiasis is known to be a cause of granulomatous disease (44). This is due to the chronic granulomatous inflammatory response, which can mimick neoplasm, of a long-standing mass.

Also, decomposed larvae under the skin can cause areas of calcification (9).

Larvae such as Hypodermis can appear as nodules under the skin. Lymphadenopathy is associated with myiasis, causing swelling lymph nodes due to the infection (36).

Systemic inflammation

Patients with myiasis have been recorded as having systemic inflammation (34), sometimes associated with oedema (40) and joint pain (arthralgia).

Bony erosion

The interaction of toxin or enzyme released by the larvae-bacteria can also cause the erosion of bones and teeth(4).

Sensory organ infections

Auditory myiasis can cause hearing disturbances, including tinnitus, roaring/buzzing sounds, ear ache, itching, discharge and perforation (45).

Infestation of the nasal passages and sinuses maybe accompanied by severe headache, fever, swelling, and purulent bloody discharge. One case in Turkey was caused by the humble fruit fly, Drosophila melanogaster (62).

Cases of oral myiasis are increased in patients with preexisting gingivitis and may cause gum disease, tooth ache, destruction of teeth and tongue abscesses (64).

Respiratory and throat infections

Myiasis infections in the lungs have been associated with pneumonia and dypsnea (61). Infections of the throat cause the sensation of the presence of foreign bodies, a burning sensation and itching in the throat, followed by coughing (63).

Causing allergic reactions - asthma & rhinoconjunctivitis

Flies, their larvae and debris can cause allergic reactions in the lungs and nose (IgE type allergy), which may lead to asthma and blocked sinuses. The allergens are fly proteins (29) present in the whole body of the animal (adult or larva). Debris and dust from the breeding areas may also contain the allergen. (26) (29)

Intestinal infections

Even the common housefly has been known to cause myiasis in the gut, as eggs survived the stomach acid, to develop in the digestive tract. This can cause a bloated abdomen, abdominal cramps, anorexia, weight loss, dehydration, malabsorption, diarrhea, constipation and dyschezia (straining), or swelling around the anus causing rectal obstruction and fever (37).

Urogenital infections

Phorid flies have been recorded as causing human myiasis of the bladder (76). Cases of vulva and penial myiasis have also been recorded.

Headaches & seizures

Cutaneous myiasis has been known to cause diffuse headaches in patients (36), which maybe accompanied by scalp nodules (46). Severe cases of myiasis can cause seizures (49).

Down regulation of host immune system

Flies have evolved coping strategies (biological, physiological and biochemical) to survive the hosts immune responses - whether those are nonspecific eg. natural killer cells and complement proteins, or specific eg antibodies and T cells (30).

This is seen in Oestrid flies, where they downregulate the host immunological function, keeping parasite/host in dynamic equilibrium (30).

Anemia & changes in blood plasma

Myiasis can cause mild anemia and other blood serum abnormalities (64).

Psychological disturbance

Patients suffering from myiasis may present with depression, malaise, lethargy, insomnia and disturbed sleep cycles (34).

Secondary infections

Myiasis can be complicated by a secondary bacterial or fungal infection. Such secondary infections may include Borrelia sp. the etiologic agent of Lyme Disease (13) and Staphylococcus aureus (14).

Table 3 records the main bacteria and fungi found inside myiasis causing fly larvae.

There is strong evidence that flies play an important role in bacterial infections, including those resistant to antibiotics. For example, filth flies can carry over 100 human pathogens. Flies carry parasites such as Cryptosporidium and viral pathogens including Poliovirus, sackievirus and Enteroviruses. They can transfer the eggs and cysts of various cestodes and nematodes, particularly hookworms and ascarids (43).

Mechanisms of Infection

Infection of fly larvae can happen in a number of ways, depending on the species and host:

1) Phoresis

In a mechanism known as phoresis, some species of flies glue their eggs during flight, to the abdomen of other blood sucking arthropods, such as flies, mosquitos and ticks. When the vectors contact a host, the cutaneous heat of the host makes the larvae emerge from the eggs and fall on exposed skin (9).

When over the host, the larva actively penetrates normal skin or the orifice made by the intermediate insect(9).

After invading the skin, the larva creates a cavity similar to a long-neck bottle, with an opening to the skin that allows it to breathe and eliminate larval excretions. The larva possesses two spiracles that give origin to two tracheas, and these are located in the posterior portion of the larva, close to the skin. These spiracles of certain species can be seen as two black dots protruding through the skin orifice (9).

The site of skin entrance usually appears as a pruriginous elevated lesion similar to a mosquito bite, whether or not it is related to a mosquito bite. After 2 or 3 weeks, a furuncle is formed. In this phase, the typical presentation is as a firm and red subcutaneous nodule (furuncle-like). Typically each nodular lesion contains one larva. An intermittent serohemorrhagic or purulent drainage, representing larval excretions or secondary infection, may occasionally emerge (9).

For some species, the larva remains in the subcutaneous tissue below the skin orifice until it reaches maturity, for others they are able to travel (9).

Possibly due to larval movement, an intermittent pain that lasts for 1–2 minutes and a sensation of movement under the skin are reported by some patients (9).

2) Direct burrowing

The parasitic larva penetrates unbroken skin directly using a hair follicle as a canal through the skin pore (35). This can sometimes take place without the host being aware. A number of cases record infections from larvae in clothing. Some larvae can embed themselves deep under the skin, integrating with the adipose fatty tissue.

3) Wounds & body openings

Fly larvae have caused myiasis through entering cuts and through laying eggs on wounds. In fact, there are a number of cases of myiasis being acquired in hospital, post surgery (59) and during adventure sports (56) and other outdoor activities. Larvae can also penetrate the host via orifices.

4) Ingestion of eggs, larvae or adult flies

Fly eggs are incredibly small. Some records of myiasis show that they can survive the stomach acid and have caused gastro-myiasis, even by a common house fly. Contaminated food is the most likely mechanism of intestinal myiasis, where food has not been cooked adequately or flies have laid eggs on cooked foods, waiting to be eaten.

Fly anatomy

Model fly: Drosophila

The fruit fly (Drosophila) has been the 'model' fly for lab studies for decades and had its genome mapped in 2000. They discovered that 75% of known human disease genes have a recognizable match in the genetic code of Drosophila (31).

Fly life-cycles

The fly life cycle contains four main stages; egg, larvae, pupae, adult. Different species of fly have different life cycles and rates of reproduction. The life cycle of the fruit fly is below:

Figure 7-Drosophila life cycle

Eggs

Fly eggs are very small and are able to survive in the environment for some time. The eggs of Drosophila, are about 0.5 millimetres long, and laid up to 5 at a time. The speed with which the larva will hatch from the egg is dependent upon temperature, although most will hatch within 24 hours after egg deposition. Below 10°C (50°F) and above 42°C (108°F) few, if any, eggs will survive. Optimum temperature for egg survival is about 18°C (64°F). Some species of fly attach the egg with glue on to a hair or other similar structure. Some eggs are white and turn black after 24 hours.

Figure 8-Drosophila egg (embryo)

Larvae

Flies spend most of their lives as larvae and this is the phase which the larvae often become parasitic. Fly larvae shed their cuticles four times, having four stages (instars), before becoming pupa on to adulthood. Often, the 3rd instar is parasitic, able to infect other hosts. Typical larvae are cylindrical, whitish, segmented, legless, and headless, ranging in length from 1 to 30 mm (41). Larvae are often a third longer than the adults they become.

Below are some different kinds of fly larvae:

Figures 9-11- fruit fly larva, biting midge (no see um, punkie), phantom midge

Leaping larvae

The final instar larvae of many species of piophilid flies (as well as flies of several other families) have the ability to leap up to 15cm in the air. The myiasis causing cheese skipper fly (Piophila casei) can use phoresis to infect a host but also through contaminating cured meats, smoked fish, cheeses, and decaying animals. These flies are common all over the world.

Figure 12-13- Cheese skipper fly larvae, Cheese skipper adult

Larvae Cuticle/casing

Fly larvae cuticles are the exoskeleton, the 'shell' or 'casing', which protects the larvae, and is one reason why they are very persistent in the environment. The fly larvae shed these casings four times before pupating. Below are some 'casings' photographed after being expelled from the back of a physician with myiasis (27):

Figure 14 - Bot fly larvae casings

Fly larvae cuticles are mainly made up of chitin, calcium carbonate and phosphate. 40% of the fly larvae cuticles is chitin compared to prawns which contain only 16% (25). Chitin is the second most abundant biopolymer in nature and is a polysaccharide that does not melt (24). In flies, chitin is present in the midgut as well as the cuticle. Flies secrete the enzyme chitin synthase which is responsible for the chitin polymer formation (24). This layer is very tough and can help even fly eggs to remain intact in the environment for some time, before becoming dehydrated.

Cuticle Spines

Some larva develop minute spines on their cuticles which are directed backward. These spines help the larva to anchor itself to the surrounding tissue. The presence of these spines make removal of the larva from its host difficult.(4)

Figure 15- Bot fly extracted from skin, Cuticle spines

Breathing apparatus

Fly larvae have an intricate respiratory system with two main tracheal branches supplying the channels for gaseous exchange to take place. Larvae have four main openings for air exchange, two at the anterior end and two at the posterior, called 'spiracles'.

Trachea

Figure 16-17 - respiratory system of 3rd instar larvae, Close up of anterior trachea network

Spiracles

The spiracles are the breathing holes of fly larvae and can appear as black dots on the cuticle surface. They are very distinctive and are often the only way of identifying the species without rearing it on to adulthood. Sometimes the anterior spiracles can extent out of the larvae, like so:

Figure 18-19 - Anterior of larvae with extending spiracle, Examples of spiracles under SEM

Digestive organs & body fluid

Flies have an open circulatory system in which fluid fills all of the interior cavity of the body and surrounds all cells and bathes the organs directly with oxygen and nutrients. There is no distinction between blood and interstitial fluid; this combined fluid is called hemolymph or haemolymph.

Hemolymph is composed of water, inorganic salts (mostly Na+, Cl-, K+, Mg2+, and Ca2+), and organic compounds (mostly carbohydrates, proteins, and lipids). There are free-floating cells, the hemocytes (like blood cells), within the hemolymph. They play a role in the arthropod immune system. Below are some types of hemocytes:

Figure 20-21 - Internal digestive organs of 3rd instar larvae, Types of hemocytes from an insect

Malpighian tubules

Malpighian tubules are an important part of the digestive system of flies. The mid gut has an alkaline pH to optimize chemical activity. Entomologists that dissected and removed the tubules from Drosophilia, have remarked that they have 'waved around' in the salt water, after extraction (55).

Figure 5 shows how the tubules become visible when stained:

Figure 21- Malpighian tubules image B (labelled 'Mt')

Pupae

In some species of fly, the pupae (like cocoons) are expelled from the skin and fall on the ground to complete their life cycle. Others bury down into sub dermal tissue to stay safe from harm, whilst developing.

Figures 22-23- Gall midge pupa, Fungus gnat pupa

Adults

Figure 24- Drosophilia adults

Eyes

A compound eye has a meshlike appearance because it consists of hundreds or thousands of tiny lens-capped optical units called ommatidia. Each ommatidium has its own cornea, lens, and photoreceptor cells for distinguishing brightness and color. As each unit is orientated in a slightly different direction, the honeycombed eye creates a mosaic image which, although poor at picking out detail, is excellent at detecting movement. Flies have specialized zones of ommatidia. These zones are organized into a fovea area that gives acute vision.

Figure 25- Compound eye of adult fly

Antennae

Fly antennae can be plumose (feather-like), short or long and segmented. Some flies, (eg Drosophila) can have leg looking antennae due to genetic mutations.

Figure 26- Male midge plumose anntennae

Mandible

The mouth of a larva contains two small pharyngeal bones also described as two sickle-shaped hooks (9).

In many families, the proboscis (rostrum) is adapted for sponging and/or lapping. These flies survive on honeydew, nectar, or the exudates of various plants and animals (dead or alive). In other families, the proboscis is adapted for cutting or piercing the tissues of a host. Some of these flies are predators of other arthropods (e.g., robber flies), but most of them are external parasites (e.g., mosquitoes and deer flies) that feed on the blood of their vertebrate hosts, including humans and most wild and domestic animals (16).

Legs

Flies have claw/s (pretarsus) on the ends of their legs to help them stick to things. They often have spurs half way up and have legs which they use to taste with. The hairs have receptors that detect the composition of the surface upon which they are walking.

Figures 27-28- Leg of Drosophila, leg spur

Wings

Fly wings are often used to identify adult species, as they have particular patterns.

Figure 29- Drosophila wing

Fly Physiology

Excretions & Secretions

Table 4 outlines the main chemicals found in myiasis causing fly larvae.

Faeces

Fly larvae excrete faeces, known as 'frass', see photos below of two different kinds of fly frass:

Figures 30-31 Frass deposited on celery, Frass deposited as thread mass

Enzyme Secretions

Larvae produce a mixture of proteolytic enzymes, including collagenase, which breaks down the collagen in skin tissue to a semi-liquid form, which can then be absorbed and digested (15).

Optimum pH for proteolytic activity is 8.0; proteolytic activity increases with temperature (10–50 °C) then drastically decreased at 60 °C. Serine proteases in salivary glands are most likely involved in larval nutrition and host immuno-modulation.(19)

Some species of fly larvae are being used to speed up the healing of wounds by the proteases present within larval secretions, that promote growth. This induces fibroblast migration into the wound space, facilitating tissue regeneration (7) (15) .

Further studies of screwworm suggest that phenylacetic acid and phenylacetaldehyde produced by Proteus mirabilis, a commensal of the larval gut, may contribute to the antibacterial effect of larvae (15).

Ammonia & Uric acid

Just one principle of myiasis is that acidic conditions starve larvae. They survive and thrive in alkaline conditions with a pH between 8-9, and have secretions that chemically induce alkalinity. They do this by secreting ammonia, causing wounds to become more alkaline, which is believed to inhibit bacterial growth (15).

Production of ammonia (NH3) makes the urine more alkaline. If left untreated, the increased alkalinity can lead to the formation of crystals of struvite, calcium carbonate, and/or apatite. Once the stones develop, over time they may grow large enough to cause obstruction and renal failure.

Figure 32- apatite crystals

Secretions attracting other flies and arthropods

Flies are attracted to strong odours, including bodily fluids, which puts those with decreased personal hygiene or with open wounds at greater risk of infection. Both adult and fly larva are also attracted to carbon dioxide (53).

Once a mammal is infected with fly larvae, it is more likely that they will attract further flies, as myiasis fly larvae release a smell that attracts gravid flies (like Phorids) (6). Other insects will also become attracted, including ladybirds, spiders, mites, thrips and louse - as they hunt for the fly larvae and eggs on skin, hair and clothing.

Reaction to light

Fly larvae are photophobic, disliking UV light and therefore tend to hide themselves deep into the tissues and also to secure a suitable niche to develop into pupa.(4)

Team work

In cutaneous myiasis the fly larvae tend to aggregate under the skin in certain places (11).

Effects of electromagnetic radiation

In a case studying the biological effects of electromagnetic fields on Drosophilia, 1.6 W/kg absorption caused survival and stress reactions and 4.0 W/kg caused cell death (67).

Heavy Metal accumulation

Fly larvae are known to accumulate heavy metals on their shells. The metal ions of iron, copper, lead, zinc, nickel, magnesium and cadmium attach to the chitin and chitosan of the larvae (54). It is known that midge larvae are known to particularly collect cadmium.

Diapause, seasonal and lunar influences

Fly larvae have the ability to 'diapause' within the human body - stopping their development until environmental conditions are more favourable. This often results in a slowing of reproduction in the winter months. Myiasis is observed more frequently during the hot humid summer months.

Biting and non-biting midges are biologically linked with the lunar cycle (79) (80). One study found that sandflies significantly increased their abundance among lunar phases (52)

 

Treatments for Myiasis

Diagnosis & lab tests

For patients with myiasis that do not have a recent, exotic travel history, myiasis is rarely diagnosed. Most general doctors would not expect to see a case a myiasis in their careers and would have very little experience in this area of parasitology.

A gram stain of myiasis exudate may show polymorphonuclear leukocytes and amber-colored fecal granules, but neither bacteria nor fungi are always found.(47) Cultures are likewise often negative (48), as are stool samples (50).

When cultures are positive, the bacteria's found include: Enterobacteriaceae, Schineria larvae (a gram-negative bacterium)(57), and methicillin-susceptible Staphylococcus aureus.

Normally, doctors would target eosinophil and IgG rises to indicate a parasitic infection. Unfortunately, fly larvae downregulating the host's immune system can help the parasites avoid detection, causing suppressed eosinophil and IgG counts in blood tests. They might be elevated to begin with, but are lowered over time by the fly larvae.

In one recent case of myiasis in France (57), the laboratory results were as follows:

Body temperature was 37.8°CC-reactive protein 71 mg/L (reference value, <5 mg/L) leukocyte count 18.2 × 109/L (81% granulocytes)platelet and erythrocyte counts within normal limitsglucose 200 mg/dLhemoglobin A1c level 13.8%Serum protein electrophoresis showed hypoalbuminemia (20 g/L) and hypergammaglobulinemia (16.9 g/L) but no monoclonal gammopathy

Misdiagnoses

Cutaneous myiasis has been misdiagnosed as regular mosquito bites, cellulitis, impetigo, pyoderma, various infectious diseases (eg, staphylococcal furunculosis, mastitis, dracunculiasis, adenopathy, herpes zoster, leishmaniosis, onchocerciasis and tungiasis), delusional parasitosis, and disease simulation. In many cases, the initial diagnosis was just a furuncle or cellulitis that was unresponsive to treatment with antibiotics (10).

Doppler ultrasound

Doppler ultrasound can aid in the diagnosis of furuncular myiasis and is especially helpful in ensuring that all larvae are extracted from a multiple-infected lesion (11)

Treatment comprises of a combination of systemic and topical measures, outlined below.

Systemic treatments

Anti-parasitics

Ivermectin is often mentioned as being the main drug prescribed to humans and animals with myiasis (72). Doramectin, Albendazole and Fenbendazole are also given to livestock.

Antibiotics

Systemic treatment includes broad-spectrum antibiotics after the removal of larvae to help prevent secondary infections. Those used include ampicillin and amoxycillin(4), erythromycin, metronidazole (39), cephalosporin(46), oxacillin and ofloxacin (57).

The natural antibiotic, garlic, is suggested to farmers to add to animal feed to help prevent fly strike.

Topical treatments

Often, 70% ethanol or chloroform is first applied to the areas of skin infected.

A wide range of chemicals have been used to either kill or draw the parasites out of the skin as follows:

Larvicidals

Turpentine larvicidal drug like Negasunt (by Bayer), mineral oil, ether, ethyl chloride, mercuric chloride, creosote, saline, systemic butazolidine or thiobendazole(4).

Occlusion

Larvae that cause human furuncular myiasis and wound myiasis require contact with outside air via caudad respiratory spiracles for respiration. Topical application of a substance that blocks respiratory exchange exploits this need and either kills the larva directly or induces it to migrate upward, where it can be removed manually(6).

Occlusion with a variety of substances include; petrolatum, nail polish, animal/bacon fat, beeswax, paraffin, hair gel, mineral oil, 'Chimo' (a paste-like form of smokeless tobacco) and toothpaste cap. These substances are placed over the pore of the skin, or in the case of wound myiasis, directly over the location of the body that is infested (6).

Occlusion is required for at least 24 hours to allow the larva to migrate to the skin surface, thus allowing careful extraction. For C. anthropophaga lesions, manual pressure to lateral aspects of the lesion may permit expression of larva (9).

Surgical excision

Surgical excision is also an option although usually not always necessary. In all cases of myiasis, avoid breaking the larva. One must remove the entire larva to avoid a hypersensitivity or foreign body reaction to the larval antigens (3).

Occlusion may result in asphyxiation of the larva without inducing it to emerge. The retained larva may elicit an inflammatory response, leading to foreign body granuloma formation that may progress to calcification.(90)

Venom extractor kit

In one patient with furuncular myiasis, the fly larvae was completely and rapidly extracted with an inexpensive, disposable, commercial venom extractor (14).

Ironing clothing & using a hair dryer

Ironing clothes is recommended for helping to prevent reoccurring myiasis. The use of a hairdryer has also been stated as being helpful as the heat produced will attract maggots towards it and can further facilitate their removal (60).

Immunology - Future Vaccines

There no 'cure' for all types of myiasis, other than to wait for the larvae to develop and leave on their own or to remove by enticing them. However, a case of cutaneous myiasis was cured with topical ivermectin (80).

Current research and development is identifying each antigen for the major myiasis causing flies and testing their effectiveness as a vaccine.

 Depending on the species sufferers are infected with, may help explain the differences in symptoms. For example, some sufferers have chronic abdominal pain, fever, or reoccurring urinary tract infections, or an affliction of their nasal cavity in particular. Some sufferers believe themselves to be contagious, others not so - this could be explained by the species. ie true parasitic larvae (obligatory) or facultative/accidental.

 

Fly Species associated with Sufferers

The species of flies mentioned in Table 1 often speak of small flies rather than species of flies that typically cause myiasis (apart from Phorids which are small and known to cause myiasis). Below are some of the flies mentioned by sufferers.

Cecidomyiidae (Gall midge)

Some sufferers have reported having small, delicate, orange bodied midge troubling them.

Cecidomyiidae are gall midges which are typically crop pests (eg larvae of the Hessian fly infects wheat plants) and are related to root maggots.

Gall midge that are crop pests lay their eggs upon the host plant or within its tissues. The eggs hatch into small larvae which must contact the meristematic cells of the cambium or growing parts. They induce host plants to form galls that provide immature life stages of the insect access to host plant nutrients and protection from natural enemies. (65).

Galls are the result of cell multiplication (hyperplasia) and quite often also the cells are enlarged (hypertrophy) (66). One of the resulting chemicals within galls is tannic acid which is traditionally used as dyes and can be red, blue, black, green etc. The larvae spend the major part of their life cycle within the gall of the host plant and has a waxy chamber where they can nurture their nymphs.

Cecidomyiidae and fungus gnats are the only flies to be known for the strange phenomenon of paedogenesis in which the larval stage reproduces without maturing first. The larvae are essentially born pregnant and reproduce quickly. Even stranger in some species the daughter larvae produced within a mother larva consume the mother and in others the reproduction occurs in the egg or pupa.

Below are photos of the growth stages of the gall midge Cranberry tipworm, Dasineura oxycoccana

Figures 33-37- 1st instar larvae, 2nd instar larvae, 3rd instar larvae, cocoons x2, adult

If some sufferers are truly infected with gall midges then it may help to explain the longevity of  symptoms.

Most myiasis should fade over time and for some sufferers this seems to be the case. For others, containing symptoms is a daily battle, which gives the notion that the parasite is able to reproduce very quickly, under the skin. Gall midge larvae are small enough to be a culprit, and have the reproductive capabilities, but are not known to parasitise mammals.

Another possible link is that agrobacterium was tested and found in 5 out of 5  patient's tissue samples (tests were negative on control group) (68). Some strains of agrobacterium are known to infect immunocompromised patients,

but other strains are used in genetic engineering to protect plants from diseases, environmental stresses or pests.

For example, Agrobacterium tumefaciens is used as a vehicle to introduce foreign genes into plant cells for there to be subsequent regeneration of transgenic crops. The crops can be altered to be resilient to environmental stresses and crop pests.

This is called horizontal gene transfer. It has recently been noted that Agrobacterium tumefaciens is the only known species of microbe capable of infiltration of the DNA of not only plant species, but animal species as well.

In the usual process of reproduction, genes are transferred vertically from parent to offspring; and such a process can occur only within a species or between closely related species. Horizontal gene transfer is the transfer of genetic material between cells or genomes belonging to unrelated species, by processes other than usual reproduction.

How could plant pests cause myiasis in humans?

Is it possible that gall midge larvae have been genetically modified through consuming the transgenic plants that they have always preyed upon? Has this made them change their diet? To complicate things, scientists do not know about the horizontal gene transfer capabilities of fly larvae (30)

It is known that myiasis causing flies made an evolutionary switch in predation, at some point in the past. Why not other flies under environmental stress?

Could this be true of fungus gnats and other related flies too? Read on....

Fungus gnats

Sufferers often report seeing creeping webs on their walls or single strands hanging from ceilings. This points to spiders or fungus gnats - to be able to create silk threads and webs. Fungus gnat larvae secrete amber muscus on to threads they produce to catch prey and they also build chitin tubes to hunt down at night.

Like some gall midge, fungus gnats are able to carry out the rare reproductive state of paedogenesis. The larvae, not adults, produce live young but in doing so the larva is killed in the process (81).

The species Orfelia fultoni (also known as Platyura fultoni) produce luminescent (vivid blue) larval fungus gnats that originate in North America. This species has turned to a carnivorous diet (69). The luminescence has also been found in the Malpighian tubules (part of digestive tract) of these fungus gnats.

For example, a species of Arachnocampa fungus gnat luciferin–luciferase system involves a 36 kDa luciferase to create the glow (86).

The Research Foundation reports fibre's auto-fluoresce (85). Could the malpighian tubules of the fungus gnat be responsible for this strange phenonomen?

Research via University of Arizona Proteonomics Laboratory (R ) analysed multiple fibres from a sufferer and analysed them to discover their fluorescing absorption and fluorescing protein. Five peptide fragments were listed that fitted within a 30-40 kDa molecular mass (83). Interestingly, one of the suspects was thought to be Nocardioides sp. JS614 - a luciferase family protein (84).

Some larvae samples from sufferers seem to have bioluminescent properties. Only 12 species of fungus gnat is known to have this capability.

Figures 38-44- Adult fungus gnat, fungus gnat larvae with black head capsule, American glowing fungus gnat larvae, Bioluminescence of larvae, larvae showing Pythium within intestines, Rhizoctonia sp, Australian fungus gnat larvae

The major pathogen carried within fungus gnats is the water mold, Pythium aphanidermatum (70).  Sufferers report seeing very small spores coming from their skin and some have cultured fungal hyphae, which resembles Pythium sp. The plant pathogenic fungus, Rhizoctonia sp., is also carried within fungus gnats.

Interestingly, phorids, gall midge, parasitic wasps, collembola, trogophytic tipulids, moths, stone flies, caddis flies, sand flies, red ants, spiders, millipedes, isopods, and even small snails are also captured by the snares of the glowing fungus gnat and it's web (82).

Our investigation of an adult fungus gnat - Click on the link to view disection.

Phorids ('Scuttle flies')

Phoridae is a family of small, hump-backed flies resembling fruit flies. Phorid flies can often be identified by their escape habit of running rapidly across a surface rather than taking to the wing. Phorids are known to cause human myiasis (usually wound and urogenital, but also eyes, nose, torsoe & neck) and can parasitize vertebrates and invertebrates.

Some amazing facts about Phorids have been collated by Dr Disney at Cambridge University. For instance, the species Megaselia scalaris is a warm-climate fly that has been unwittingly carried around the world by man - to the point that it is now commonly found in pet shops and laboratory cultures of insects. They are also scavengers in the nests of honey bees (71).

Typically they are able to breed in fungi, decaying plant matter or drain pipes. Amazingly, they have also been known to breed in blue paint, boot polish, spaghetti from Italy, vermicelli from Singapore and had been reported to feed on curdled milk and bananas. Disney also reports that they have an extraordinary capacity for penetrating seemingly closed containers, such as crawling through the neck of a tied plastic bag (71).

Such phorids have evolved into smaller and smaller species capable of exploiting more and more resources according to Disney(77). In fact, he is in no doubt that M.scalaris can complete its life cycle within the human intestines, giving rise to emerging adults (71).

Photos of adult phorids (Scuttle fly) have been posted on forums and their larvae have been reported to be seen in sufferer's urine (identifable due to the nature of phorids to surface in liquids to gulp air).

Figures 45-46- Adult phorid, Phorid larvae

Lesions & expelled larvae

Lesions sometimes start as small pimples, skin bumps, white headed spots or black heads.

Careful examination can sometimes show a central puctum or darkened 'pore'. Often, if they are disturbed or squeezed, they hurt, as if the contents is attached to the tissue and nerves below. A yellow liquid is discharged, along with white or red debris and inflammation follows. If the lesion is squeezed further, the contents seems stubborn, refusing to be expelled. The lesion is now much larger, may now be rimmed and can often be accompanied by satellite lesions.

Typical lesions start to heal quickly, but superficially. It may be that the healing secretions from the larvae aid skin healing, with further larvae still intact underneath. Sufferers report having to soften and remove the cover or callus daily, to then clean the legion of white 'rice shapes'.

They are in agreement that their lesions do not heal properly until all the 'rice shapes' are removed. We believe these shapes to be aggregated fly larvae.

Could the liquid be a larva secretion (e.g. collegenase), causing surrounding skin to dissolve? -in turn increasing the circumference of the lesion and a 'melted' rim. Could the white or red debris be the posterior, breathing extension or 'tail' of the larvae? Is the dead larvae still hard to remove due to backward pointing spines on its cuticle? Could the inflammation be caused by the contents of the larvae leaching (proteins, bacteria, fungi etc.) causing an allergic reaction and/or super infection?

Sufferers report skin thinning, which may be attributed to larvae feeding from the collagen under the surface of the skin.

Table 6 - Sufferers skin lesions

Shedding white particles, 'skin'

The small larvae are often leached from intact skin and may appear as rolls of skin. Sufferers report shedding white matter daily. An infection of gall midge or fungus gnat larvae could explain this continual process, due to paedogenesis, where the larvae are amazingly able to produce live young.

Table 7 - Comparison of fly larvae and samples from the skin/orifices of sufferers.

The white flakes and debris that sufferers expel may be the chitinous casings of fly larvae and larva eggs. Sufferers sometimes report white particles in their homes and air and are conscious of others sneezing and coughing in their presence. This maybe due to the allergic reactions that the proteins from larvae casings are known to cause.

Table 8 - Eggs from the skin/orifices of sufferers

Shedding black specs, amber granules, 'feathers', hooks & hexagon shaped minerals

Sufferers report having black specs leaching out of their skin and being present in their environments. The specs vary in appearance. Under the microscope they are sometimes black filament bundles. Is is possible that some of the black specs that sufferers experience coming out of their skin, are fly larvae frass? Some may also be black fly eggs or capsules.

Sufferers have micrographs of 'feathers' that they have pulled from skin samples, that very much look like plumous fly antennae. They also report removing samples with 'hooks', which could be related to fly anatomy. Also, myiasis cases have recorded amber granules from lesions.

Some of the samples that sufferers extract from their skin, seem very 'unnatural', e.g. shiny hexagons. Could these be mineral crystals caused by a build up of ammonia turning to apatite?

Shedding Filaments

Sufferers often see a range of different filaments coming from intact skin, lesions, clothes or in their environments. The main filaments found:

Flat, ribboned, transparent filaments -'carpet lint' appearanceRed filaments, often unitary in appearance and lengthNavy blue, black or white filamentsBright blue plastic looking filamentsFilament bundles (appearing as 'specs' to the naked eye)

Typical filaments:Table 9

Could the ribboned filaments be the trachea of fly larvae?

Could the white filaments be the white thread breathing tubes of sub-dermal larvae?

Could some be the magpighan tubules...especially the ones that wave and auto-fluoresce?

One analysis of these filaments reported that they were made of cellulose or chitin. Also that the filaments tested did not melt. This could point to these filaments being part of the chitinous digestive tract of flies.

Our investigation of an adult fungus gnat showed that this sample is implicated in these filaments.

Other analysis of fibres showed them to be hollow tubes - filaments, that had within them the growth-promoting rhizobacteria Pseudomonas putida and Corynebacterium efficiens. Both of these bacteria and A. tumefaciens are soil dwelling, often found forming dense, complex biofilms on the roots of plants (73), (75) . If these particular filaments were part of fly larvae disgestive tract (e.g foregut or midgut of fungus gnats or gall midges), these bacteria may be found.

Sufferers also report seeing the filaments rise up in the air, particularly seen under halogen lighting. If the filaments were from fly anatomy, their molecular mass would likely to be lighter then air.

It is possible that some of these thread masses are types of fly frass?

Sufferers report expelling coloured filaments that match the colour of clothing they have been wearing a few days previously. Also expelling their own hair strands. It is possible that the eggs of flies that are attached to the threads of clothing and hair, hatch by body heat, burrow into the skin, with the thread still attached?  Some sufferers also report seeing multiple fibres being expelled from the abdomen of adult flies.

'Paper cuts' & 'Bites'

Sufferers complain of small paper cuts on their skin. These maybe caused by female adult flies cutting skin to feed on blood. It is known that female biting flies cannot lay their eggs until they have had a blood meal and have adapted mouth parts to cut with. Flies that cause myiasis are not known to have mouth parts to bite with.

Many sufferers report being bitten, often looking like insect bites, even on eye balls. Is it possible that the 'bite' is actually a hatched larvae burrowing into a skin pore?

Infected hair follicles

Sufferers often have major scalp infections, with some sufferers getting a S. aureus diagnosis. However, the problems persist and are infrequently resolved with antibiotics. Myiasis often affects the parts of the body that are exposed (head, neck, limbs). Likewise, sufferers often begin with pruritus at the back of the head and lesions most often occur on exposed skin.

Breast abnormalities

Sufferers report having white spots or lumps on breasts, nipples and areola, which is an area targeted by some myiasis causing flies.

Heavy metal accumulation

Sufferers have tested to having high levels of heavy metals. Fly larvae shells collect heavy metal ions which could have an accumulative effect within humans.

Ammonia

Sufferers have reported smelling ammonia on their skin and in their urine, which could be attributed to fly larvae secretions. Ammonia is a neurotoxin, causing depression, headaches and brain malfunctions. Sufferers have had elevated ammonia levels found in blood samples and as a result have experienced problems with kidney function.

Lyme Disease

Many sufferers have tested positive for Borrelia sp (2). This could be caused via two myiasis related mechanisms. Firstly, by a direct infection of fly larvae harbouring Borrelia bacteria or secondly, via phoresis- a tick bite, from a tick carrying fly eggs on it's abdomen, that migrate through the site of the tick bite.

Chronic Lyme Disease affects about 10% of people infected with the Borrelia bacteria. Scientists do not know why this 10% cannot shift the bacteria and even today the medical community do not readily recognise chronic Lyme Disease. Many of the sufferers with chronic Lyme describe the feeling that bugs are crawling under their skin.

Is it possible that the 10% have forms of myiasis, where the larvae are carrying the bacteria, prolonging the infection, even after antibiotics?

Seasons and lunar influences

Some sufferers experience greater pruritus (itching activity) in spring and summer when the moon is waxing and at full moon. This correlates with the activity and life cycle of many species of fly.

Remedy relief for sufferers

Normal myiasis is cured by mechanical extraction of the maggot/s. Well how do you extract multiple, tiny maggots that can reproduce without maturing? - with great difficulty!! Is this why very few sufferers have been cured?

All the remedies myiasis sufferers get relief from are effective against different species of maggots, as listed in Table 5. Plant enzymes sprays, fenbendazole, ivermectin, peppermint, teatree oil, sulphur, citric acid, neem oil, citronella, Diatomaceous earth, chilli pepper, Licorice, bees wax, UV light, turmeric, vinegar, saline...... coincidence?

After studying cases of myiasis, the authors of this report would recommend that by applying an alkaline substance to the skin, followed by an acid may disrupt the calcium carbonate and phosphate of the larvae shells. We are currently testing the best methods of inducing this disruption, with initial success to consistently leach larvae out of intact skin. This needs to be fully tested. It may bring some relief and could be a useful diagnostic tool at the very least.

Environmental considerations

Myiasis sufferers are very aware that their clothes, fabrics and homes are affected.

Plant enzyme sprays make fly larvae shed their casing prematurely and is a key product that myiasis sufferers use to help cleanse their homes and clothes.

Natural Pyrethrum is made of chrysanthemum petals and is a low toxicity insecticide - usually used for killing fleas, but also plant pest flies such as fungus gnats.  Myiasis sufferers have also found this useful around their homes.

Concluding remarks

In 1925, the ABC Children's health book taught kids the importance of killing flies (58). Due to immense advances in sanitation over the last century, flies are often discarded as 'just pests'.

Is this an oversight of the amazing capabilities flies possess to cause disease?

If some myiasis causing flies are particular about the site of infection, then this leads to further questions about the preferred sites of the small flies presently parasitizing humans and animals, unrecorded. Could they turn out to be the causes of some of the chronic diseases, with unknown aeitologies, in the world today?

It may not be a co-incidence that 75% of known human disease genes have a recognizable match in the genetic code of fruit flies (31).

It is quite possible that small flies have been causing disease in humans for years - completely undetected on the medical radar. Chronic wasting diseases, 'autoimmune' diseases, interstitial cystitis, hypothyroidism, idiopathic hypereosinophilic syndrome, aquagenic pruritus, Hogkin's disease, chronic rhinosinusitis, retroareolar breast cysts to name but a few.

Published research suggests that myiasis increases the risk of having a chronic wasting disease (21). This is due to prion rods being found in flies, and being implicated in at least five human diseases, including sporadic CJD which is responsible for 85% of all cases (cause currently unknown) (22).

It is curious that myiasis has been known since very ancient times and is recorded in the Bible in the book of Job (73).

Also, that one translation of the name of the devil, 'Beezlebub', is 'Lord of the flies'. In light of this, it is even more curious that there are 911 disease proteins in humans and 75% are a match to the fly Drosophila (75% of 911 = 666!) (32).

Furthermore, because an estimated 75% of all living species of insects remain unknown to science, the morphology of the majority of species is entirely undocumented (28). We believe that a range of flies are causing myiasis in humans and animals, undetected, around the globe.

We urge scientific investigation on fungus gnats, phorids, midges and primative small flies in particular.

 

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--  Laz