Helminthic therapy, an experimental type of immunotherapy, is the treatment of autoimmune diseases and immune disorders by means of deliberate infestation with a helminth or with the ova of a helminth. Helminths are parasitic worms such as hookworms, whipworms, and threadworms that have evolved to live within a host organism on which they rely for nutrients. These worms are members of two phyla; nematodes, which are primarily used in human helminthic therapy, and flat worms.(Trematodes)

Helminthic therapy consists of the inoculation of the patient with specific parasitic intestinal nematodes (helminths). A number of such organisms are currently being investigated for their use as treatment including: "Trichuris suis" ova, commonly known as pig whipworm eggs; "Necator americanus", commonly known as hookworms; "Trichuris trichiura" ova, commonly referred to as human whipworm eggs; and "Hymenolepis diminuta", commonly known as rat tapeworm cysticerci.

While the latter four species may be considered to be mutualists - providing benefit to their host without causing longterm harm - there are other helminth species that have demonstrated therapeutic effects but which also have a potential to cause less desirable or even harmful effects and therefore do not share the ideal characteristics for a therapeutic helminth. These include "Ascaris lumbricoides", commonly known as human giant roundworm; "Strongyloides stercoralis", commonly known as human roundworm; "Enterobius vermicularis", commonly known as pinworm or threadworm; and "Hymenolepis nana", also known as dwarf tapeworm.

Current research targets Crohn's disease, ulcerative colitis, inflammatory bowel disease, multiple sclerosis, and asthma.

Helminthic infection has emerged as one possible explanation for the low incidence of autoimmune diseases and allergies in less developed countries, together with the significant and sustained increase in autoimmune diseases in industrialized countries.

Most conditions of STH have a light worm burden and usually have no discernible symptoms. Heavy infections however cause a range of health problems, including abdominal pain, diarrhoea, blood and protein loss, rectal prolapse, and physical and mental retardation.

Severe ascariasis is typically a pneumonia, as the larvae invades lungs, producing fever, cough and dyspnoea during early stage of infection.

Hookworm infections insinuate a skin reaction (dermatitis), increased white blood cells (eosinophils), a pulmonary reaction (pneumonitis), and skin rash (urticarial).

Iron deficiency anaemia due to blood loss is a common symptom.

Infection first presents with severe abdominal pain, nausea, vomiting, and weakness, which gradually lessens and progresses to fever, and then to CNS symptoms and severe headache and stiffness of the neck.

CNS symptoms begin with mild cognitive impairment and slowed reactions, and in a very severe form often progress to unconsciousness. Patients may present with neuropathic pain early in the infection. Eventually severe infection will lead to ascending weakness, quadriparesis, areflexia, respiratory failure, and muscle atrophy, and will lead to death if not treated. Occasionally patients present with cranial nerve palsies, usually in nerves 7 and 8, and rarely larvae will enter ocular structures. Even with treatment, damage to the CNS may be permanent and result in a variety of negative outcomes depending on the location of the infection, and the patient may suffer chronic pain as a result of infection.

Physiological reactions to "Toxocara" infection depend on the host’s immune response and the parasitic load. Most cases of "Toxocara" infection are asymptomatic, especially in adults. When symptoms do occur, they are the result of migration of second stage "Toxocara" larvae through the body.

Covert toxocariasis is the least serious of the three syndromes and is believed to be due to chronic exposure. Signs and symptoms of covert toxocariasis are coughing, fever, abdominal pain, headaches, and changes in behavior and ability to sleep. Upon medical examination, wheezing, hepatomegaly, and lymphadenitis are often noted.

High parasitic loads or repeated infection can lead to visceral larva migrans (VLM). VLM is primarily diagnosed in young children, because they are more prone to exposure and ingestion of infective eggs. "Toxocara" infection commonly resolves itself within weeks, but chronic eosinophilia may result. In VLM, larvae migration incites inflammation of internal organs and sometimes the central nervous system. Symptoms depend on the organ(s) affected. Patients can present with pallor, fatigue, weight loss, anorexia, fever, headache, rash, cough, asthma, chest tightness, increased irritability, abdominal pain, nausea, and vomiting. Sometimes the subcutaneous migration tracks of the larvae can be seen. Patients are commonly diagnosed with pneumonia, bronchospasms, chronic pulmonary inflammation, hypereosinophilia, hepatomegaly, hypergammaglobulinaemia (IgM, IgG, and IgE classes), leucocytosis, and elevated anti-A and –B isohaemagglutinins. Severe cases have occurred in people who are hypersensitive to allergens; in rare cases, epilepsy, inflammation of the heart, pleural effusion, respiratory failure, and death have resulted from VLM.

Ocular larva migrans (OLM) is rare compared with VLM. A light "Toxocara" burden is thought to induce a low immune response, allowing a larva to enter the host’s eye. Although there have been cases of concurrent OLM and VLM, these are extremely exceptional. OLM often occurs in just one eye and from a single larva migrating into and encysting within the orbit. Loss of vision occurs over days or weeks. Other signs and symptoms are red eye, white pupil, fixed pupil, retinal fibrosis, retinal detachment, inflammation of the eye tissues, retinal granulomas, and strabismus. Ocular granulomas resulting from OLM are frequently misdiagnosed as retinoblastomas. "Toxocara" damage in the eye is permanent and can result in blindness.

A case study published in 2008 supported the hypothesis that eosinophilic cellulitis may also be caused by infection with "Toxocara". In this study, the adult patient presented with eosinophilic cellulitis, hepatosplenomegaly, anemia, and a positive ELISA for "T. cani"s.

Adult flukes are known to be quite harmless, as they do not attack on the host tissue. It is the immature flukes which are most damaging as they get attached to the intestinal wall, literally and actively sloughing off of the tissue. This necrosis is indicated by haemorrhage in faeces, which in turn is a sign of severe enteritis. Under such condition the animals become anorexic and lethargic. It is often accompanied by pronounced diarrhoea, dehydration, oedema, polydipsia, anaemia, listlessness and weight loss. In sheep profuse diarrhoea usually develops two to four weeks after initial infection. If infection is not properly attended death can ensue within 20 days, and in a farm mortality can be very high. In fact there are intermittent reports of mortality as high as 80% among sheep and cattle. Sometimes chronic form is also seen with severe emaciation, anaemia, rough coat, mucosal oedema, thickened duodenum and oedema in the sub maxillary space. The terminally sick animals lie prostrate on the ground, completely emaciated until they die. In buffalos, severe haemorrhage was found to be associated with liver cirrhosis and nodular hepatitis.

Symptoms becomes evident only when the intensity of infection is relatively high. Thus the degree of negative outcomes is directly related to worm burden; more worms means greater severity of disease.

Amphistomiasis or paramphistomiasis (alternatively spelled amphistomosis or paramphistomosis) is a parasitic disease of livestock animals, more commonly of cattle and sheep, and humans caused by immature helminthic flatworms belonging to the order Echinostomida. The term amphistomiasis is used for broader connotation implying the disease inflicted by members of Echinostomida including the family Paramphistomidae/Gastrodiscidae (to be precise, the species "Gastrodiscoides hominis"); whereas paramphistomiasis is restricted to that of the members of the family Paramphistomatidae only. "G. discoides" and "Watsonius watsoni" are responsible for the disease in humans, while most paramphistomes are responsible in livestock animals, and some wild mammals. In livestock industry the disease causes heavy economic backlashes due to poor production of milk, meat and wool.

The incubation period for "Toxocara canis" and "cati" eggs depends on temperature and humidity. "T. canis" females, specifically, are capable of producing up to 200,000 eggs a day that require 2-6 weeks minimum up to a couple months before full development into the infectious stage. Under ideal summer conditions, eggs can mature to the infective stage after two weeks outside of a host. Provided sufficient oxygen and moisture availability, "Toxocara" eggs can remain infectious for years, as their resistant outer shell enables the protection from most environmental threats.However, as identified in a case study presented within the journal of helminthology, the second stage of larvae development poses strict vulnerabilities to certain environmental elements. High temperatures and low moisture levels will quickly degrade the larvae during this stage of growth.

Helminths are extremely successful parasites capable of establishing long-lasting infections within a host. During this time, helminths compete with the host organism's cells for nutrient resources and thus possess the potential to cause harm. However, the number of organisms hosted by individuals undergoing helminthic therapy is very small and any side effects are typically only encountered in the first three months of infection. In the long term, the vast majority of clinically infected individuals are asymptomatic, with no significant nutrient loss. In fact, nutrient uptake can be enhanced in some subjects who are hosting a small number of helminths. If the side effects from helminthic therapy were to become unmanageable, they can be alleviated by the use of anthelminthic medications.[1][7][8] The most common clinical symptoms which may be encountered while undergoing helminthic therapy can include:

- Fatigue

- Gastrointestinal discomfort

- Anemia

- Fever

- Abdominal pain

- Weight loss

- Anorexia

- Diarrhea

- General malaise

Symptoms of opisthorchiasis (caused by "Opisthorchis" spp.) are indistinguishable from clonorchiasis (caused by "Clonorchis sinensis"). About 80% of infected people have no symptoms, though they can have eosinophilia. Asymptomatic infection can occur when there are less than 1000 eggs in one gram in feces. Infection is considered heavy when there are 10,000-30,000 eggs in one gram of feces. Symptoms of heavier infections with "Opisthorchis viverrini" may include: diarrhoea, epigastric and upper right quadrant pain, lack of appetite (anorexia), fatigue, yellowing of the eyes and skin (jaundice) and mild fever.

These parasites are long-lived and cause heavy chronic infections that may lead to accumulation of fluid in the legs (edema) and in the peritoneal cavity (ascites), enlarged non-functional gall-bladder and also cholangitis, which can lead to periductal fibrosis, cholecystitis and cholelithiasis, obstructive jaundice, hepatomegaly and/or fibrosis of the periportal system.

Opisthorchiasis is a parasitic disease caused by species in the genus Opisthorchis (specifically, "Opisthorchis viverrini" and "Opisthorchis felineus"). Chronic infection may lead to cholangiocarcinoma, a malignant cancer of the bile ducts.

Medical care and loss of wages caused by "Opisthorchis viverrini" in Laos and in Thailand costs about $120 million annually. Infection by "Opisthorchis viverrini" and other liver flukes in Asia affect the poor and poorest people. Opisthorchiasis is on the World Health Organization's list of neglected tropical diseases.

The infection causes a red, intensely pruritic (itchy) eruption. The itching can become very painful and if scratched may allow a secondary bacterial infection to develop. Cutaneous larva migrans usually heals spontaneously over weeks to months and has been known to last as long as one year. However, the severity of the symptoms usually causes those infected to seek medical treatment before spontaneous resolution occurs. Following proper treatment, migration of the larvae within the skin is halted and relief of the associated itching can occur in less than 48 hours (reported for thiabendazole).

This is separate from the similar cutaneous larva currens which is caused by "Strongyloides". Larva currens is also a cause of migratory pruritic eruptions but is marked by 1) migratory speed on the order of inches per hour 2) perianal involvement due to autoinfection from stool and 3) a wide band of urticaria.

Hookworm eggs are shed in the infected dog (or other animal) feces to the ground and beach sand, where they then develop over a period of 1–2 weeks into the infectious larval form (filariform larvae). The filariform larvae can burrow through intact skin that comes into contact with soil or sand that is contaminated with feces. Although they are able to infect the deeper tissues of animals (through to the lungs and then the intestinal tract), humans are incidental hosts and the larvae are only able to penetrate the epidermis of the skin and thus create the typical wormlike burrows visible underneath the skin. These parasites apparently lack the collagenase enzymes required to penetrate through the basement membrane deeper into the dermal layers of the skin.

The clinical findings in this disease can be divided into acute and end-stage manifestations:

In the acute phase, patients often present with decreased visual acuity, vitritis, papillitis, and crops of gray-white or yellow-white outer retinal lesions. The clustering of the retinal lesions is important because this often helps to localize the causative nematode.

If left untreated, patients ultimately develop late sequel, which may include optic atrophy, retinal arterial narrowing, diffuse retinal pigment epithelial changes, and an abnormal electroretinogram. The late findings of this condition are often misinterpreted as unilateral retinitis pigmentosa.

Many people with Crohn's disease have symptoms for years before the diagnosis. The usual onset is between 15 and 30 years of age, but can occur at any age. Because of the 'patchy' nature of the gastrointestinal disease and the depth of tissue involvement, initial symptoms can be more subtle than those of ulcerative colitis. People with Crohn's disease experience chronic recurring periods of flare-ups and remission.

Abdominal pain may be the initial symptom of Crohn's disease usually in the lower right area. It is often accompanied by diarrhea, especially in those who have had surgery. The diarrhea may or may not be bloody. The nature of the diarrhea in Crohn's disease depends on the part of the small intestine or colon involved. Ileitis typically results in large-volume, watery feces. Colitis may result in a smaller volume of feces of higher frequency. Fecal consistency may range from solid to watery. In severe cases, an individual may have more than 20 bowel movements per day and may need to awaken at night to defecate. Visible bleeding in the feces is less common in Crohn's disease than in ulcerative colitis, but may be seen in the setting of Crohn's colitis. Bloody bowel movements typically come and go, and may be bright or dark red in color. In the setting of severe Crohn's colitis, bleeding may be copious. Flatulence and bloating may also add to the intestinal discomfort.

Symptoms caused by intestinal stenosis are also common in Crohn's disease. Abdominal pain is often most severe in areas of the bowel with stenoses. Persistent vomiting and nausea may indicate stenosis from small bowel obstruction or disease involving the stomach, pylorus, or duodenum. Although the association is greater in the context of ulcerative colitis, Crohn's disease may also be associated with primary sclerosing cholangitis, a type of inflammation of the bile ducts.

Perianal discomfort may also be prominent in Crohn's disease. Itchiness or pain around the anus may be suggestive of inflammation, fistulization or abscess around the anal area or anal fissure. Perianal skin tags are also common in Crohn's disease and may appear with or without the presence of colorectal polyps. Fecal incontinence may accompany perianal Crohn's disease. At the opposite end of the gastrointestinal tract, the mouth may be affected by recurrent sores (aphthous ulcers). Rarely, the esophagus, and stomach may be involved in Crohn's disease. These can cause symptoms including difficulty swallowing (dysphagia), upper abdominal pain, and vomiting.

Crohn's disease, like many other chronic, inflammatory diseases, can cause a variety of systemic symptoms. Among children, growth failure is common. Many children are first diagnosed with Crohn's disease based on inability to maintain growth. As it may manifest at the time of the growth spurt in puberty, up to 30% of children with Crohn's disease may have retardation of growth. Fever may also be present, though fevers greater than 38.5 °C (101.3 °F) are uncommon unless there is a complication such as an abscess. Among older individuals, Crohn's disease may manifest as weight loss, usually related to decreased food intake, since individuals with intestinal symptoms from Crohn's disease often feel better when they do not eat and might lose their appetite. People with extensive small intestine disease may also have malabsorption of carbohydrates or lipids, which can further exacerbate weight loss.

Diffuse unilateral subacute neuroretinitis (DUSN) is a rare condition that occurs in otherwise healthy, often young patients and is due to the presence of a subretinal nematode.

In spite of Crohn's and UC being very different diseases, both may present with any of the following symptoms: abdominal pain, vomiting, diarrhea, rectal bleeding, severe internal cramps/muscle spasms in the region of the pelvis and weight loss. Anemia is the most prevalent extraintestinal complication of inflammatory bowel disease. Associated complaints or diseases include arthritis, pyoderma gangrenosum, primary sclerosing cholangitis, and non-thyroidal illness syndrome (NTIS). Associations with deep vein thrombosis (DVT) and bronchiolitis obliterans organizing pneumonia (BOOP) have also been reported. Diagnosis is generally by assessment of inflammatory markers in stool followed by colonoscopy with biopsy of pathological lesions.

In addition to the extent of involvement, people may also be characterized by the severity of their disease.

- "Mild disease" correlates with fewer than four stools daily, with or without blood, no systemic signs of toxicity, and a normal erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP). Mild abdominal pain or cramping may occur. Patients may believe they are constipated when in fact they are experiencing tenesmus, which is a constant feeling of the need to empty the bowel accompanied by involuntary straining efforts, pain, and cramping with little or no fecal output. Rectal pain is uncommon.

- "Moderate disease" correlates with more than four stools daily, but with minimal signs of toxicity. Patients may display anemia (not requiring transfusions), moderate abdominal pain, and low grade fever, .

- "Severe disease", correlates with more than six bloody stools a day or observable massive and significant bloody bowel movement, and evidence of toxicity as demonstrated by fever, tachycardia, anemia or an elevated ESR or CRP.

- "Fulminant disease" correlates with more than ten bowel movements daily, continuous bleeding, toxicity, abdominal tenderness and distension, blood transfusion requirement and colonic dilation (expansion). Patients in this category may have inflammation extending beyond just the mucosal layer, causing impaired colonic motility and leading to toxic megacolon. If the serous membrane is involved, a colonic perforation may ensue. Unless treated, the fulminant disease will soon lead to death.

As ulcerative colitis is believed to have a systemic (i.e., autoimmune) origin, patients may present with comorbidities leading to symptoms and complications outside the colon. The frequency of such extraintestinal manifestations has been reported as anywhere between 6 and 47 percent, and include the following:

- Aphthous ulcer of the mouth

- Ophthalmic

- Iritis or uveitis, which is inflammation of the eye's iris

- Episcleritis

- Musculoskeletal:

- Seronegative arthritis, which can be a large-joint oligoarthritis (affecting one or two joints), or may affect many small joints of the hands and feet

- Ankylosing spondylitis, arthritis of the spine

- Sacroiliitis, arthritis of the lower spine

- Cutaneous (related to the skin):

- Erythema nodosum, which is a panniculitis, or inflammation of subcutaneous tissue involving the lower extremities

- Pyoderma gangrenosum, which is a painful ulcerating lesion involving the skin

- Deep venous thrombosis and pulmonary embolism

- Autoimmune hemolytic anemia

- Clubbing, a deformity of the ends of the fingers.

- Primary sclerosing cholangitis, a distinct disease that causes inflammation of the bile ducts

Inflammatory bowel disease (IBD) is a group of inflammatory conditions of the colon and small intestine. Crohn's disease and ulcerative colitis are the principal types of inflammatory bowel disease. It is important to note that not only does Crohn's disease affect the small intestine and large intestine, it can also affect the mouth, esophagus, stomach and the anus whereas ulcerative colitis primarily affects the colon and the rectum.

In the acute stage of the disease, a catarrhal conjunctivitis is present, with signs of ocular pain, usually blepharospasm, increased lacrimation, and photophobia. Miosis is also usually present. After a few days, this will progress to a keratitis and iridocyclitis. Other ocular problems may also occur, including conjunctival and corneal oedema, and aqueous flare.

After an acute flare-up, no clinical signs of disease may be seen for a prolonged period, which can vary from a few hours to a few years. With frequent acute incidents, though, additional clinical signs may be seen, including anterior and posterior synechiae, poor pupillary responses, cataracts, and a cloudy appearance to the vitreous humour.

Patients with esophageal candidiasis present with odynophagia, or painful swallowing. Longstanding esophageal candidiasis can result in weight loss. There is often concomittant thrush.

Some patients present with esophageal candidiasis as a first presentation of systemic candidiasis.

Equine recurrent uveitis (ERU), also known as moon blindness, recurrent iridocyclitis or periodic ophthalmia, is an acute, nongranulomatous inflammation of the uveal tract of the eye, occurring commonly in horses of all breeds, worldwide. The causative factor is not known, but several pathogeneses have been suggested. It is the most common cause of blindness in horses. In some breeds, a genetic factor may be involved.