Focal infection theory is the historical concept that many chronic diseases, including systemic and common ones, are caused by focal infections. In present medical consensus, a focal infection is a localized infection, often asymptomatic, that causes disease elsewhere in the host, but focal infections are fairly infrequent and limited to fairly uncommon diseases. (Distant injury is focal infection's key principle, whereas in ordinary infectious disease, the infection itself is systemic, as in measles, or the initially infected site is readily identifiable and invasion progresses contiguously, as in gangrene.) Focal infection theory, rather, so explained virtually all diseases, including arthritis, atherosclerosis, cancer, and mental illnesses.

An ancient concept that took modern form around 1900, focal infection theory was widely accepted in medicine by the 1920s. In the theory, the "focus of infection" might lead to secondary infections at sites particularly susceptible to such microbial species or toxin. Commonly alleged foci were diverse—appendix, urinary bladder, gall bladder, kidney, liver, prostate, and nasal sinuses—but most commonly were oral. Besides dental decay and infected tonsils, both dental restorations and especially endodontically treated teeth were blamed as foci. The putative "oral sepsis" was countered by tonsillectomies and tooth extractions, including of endodontically treated teeth and even of apparently healthy teeth, newly popular approaches—sometimes leaving individuals toothless—to treat or prevent diverse diseases.

Drawing severe criticism in the 1930s, focal infection theory—whose popularity zealously exceeded consensus evidence—was discredited in the 1940s by research attacks that drew overwhelming consensus of this sweeping theory's falsity. Thereupon, dental restorations and endodontic therapy became again favored. Untreated endodontic "disease" retained mainstream recognition as fostering systemic disease. But only alternative medicine and later biological dentistry continued highlighting sites of dental treatment—still endodontic therapy, but, more recently, also dental implant, and even tooth extraction, too—as foci of infection causing chronic and systemic diseases. In mainstream dentistry and medicine, the primary recognition of focal infection is endocarditis, if oral bacteria enter blood and infect the heart, perhaps its valves.

Entering the 21st century, scientific evidence supporting general relevance of focal infections remained slim, yet evolved understandings of disease mechanisms had established a third possible mechanism—altogether, metastasis of infection, metastatic toxic injury, and, as recently revealed, metastatic immunologic injury—that might occur simultaneously and even interact. Meanwhile, focal infection theory has gained renewed attention, as dental infections apparently are widespread and significant contributors to systemic diseases, although mainstream attention is on ordinary periodontal disease, not on hypotheses of stealth infections via dental "treatment". Despite some doubts renewed in the 1990s by conventional dentistry's critics, dentistry scholars maintain that endodontic therapy can be performed without creating focal infections.

With the 1950s introduction of antibiotics, attempts to explain unexplained diseases via bacterial etiology seemed all the more unlikely. By the 1970s, however, it was established that antibiotics could trigger bacteria's switch to their L phase. Eluding detection by traditional methods of medical microbiology, bacterial L forms and the similar mycoplasma—and, later, viruses—became the entities expected in the theory of focal infection. Yet until the 1980s, such researchers were scarce, largely via scarce funding for such investigations.

Despite the limited funding, research established that L forms can adhere to red blood cells and thereby disseminate from foci within internal organs such as the spleen, or from oral tissues and the intestines, especially during dysbiosis. Perhaps some of Weston Price's identified "toxins" in endodontically treated teeth were L forms, thought nonexistent by bacteriologists of his time and widely overlooked into the 21st century. Apparently, dental infections, including by uncultured or cryptic microorganisms, contribute to systemic diseases.

Usual diagnosis is via radiograph, patient history, biopsy is rarely needed. Periodic follow ups should included additional radiographs that show minimal growth or regression.

Differentiation between this and SCC would be based on a history of recent trauma or dental treatment in the area.

Immunohistochemistry may aid the diagnosis. If the lesion is NS, there will be focal to absent immunoreactivity for p53, low immunoreactivity for MIB1 (Ki-67), and the presence of 4A4/p63- and calponin-positive myoepithelial cells.

A reaction to past trauma or infection but it's difficult to rule out in some cases.

The diagnosis is established by a computed tomography (CT) (with contrast) examination. At the initial phase of the inflammation (which is referred to as cerebritis), the immature lesion does not have a capsule and it may be difficult to distinguish it from other space-occupying lesions or infarcts of the brain. Within 4–5 days the inflammation and the concomitant dead brain tissue are surrounded with a capsule, which gives the lesion the famous ring-enhancing lesion appearance on CT examination with contrast (since intravenously applied contrast material can not pass through the capsule, it is collected around the lesion and looks as a ring surrounding the relatively dark lesion). Lumbar puncture procedure, which is performed in many infectious disorders of the central nervous system is contraindicated in this condition (as it is in all space-occupying lesions of the brain) because removing a certain portion of the cerebrospinal fluid may alter the concrete intracranial pressure balances and causes the brain tissue to move across structures within the skull (brain herniation).

Ring enhancement may also be observed in cerebral hemorrhages (bleeding) and some brain tumors. However, in the presence of the rapidly progressive course with fever, focal neurologic findings (hemiparesis, aphasia etc.) and signs of increased intracranial pressure, the most likely diagnosis should be the brain abscess.

A brain biopsy will reveal the presence of infection by pathogenic amoebas. In GAE, these present as general inflammation and sparse granules. On microscopic examination, infiltrates of amoebic cysts and/or trophozoites will be visible.

In most instances, the diagnosis of toxoplasmic retinochoroiditis is made clinically on the basis of the appearance of the characteristic lesion on eye examination.

Seropositivity (positive blood test result) for Toxoplasma is very common and therefore not useful in diagnosis; however, a negative result i.e. absence of antibodies is often used to rule out disease. Others believe that serology is useful to confirm active toxoplasmic retinochoroiditis, not only by showing positivity but by also showing a significant elevation of titers: The mean IgG values were 147.7 ± 25.9 IU/ml for patients with active disease versus 18.3 ± 20.8 IU/ml for normal individuals.

Antibodies against Toxoplasma:

- IgG : appear within the first 2 weeks after infection, typically remain detectable for life, albeit at low levels;and may cross the placenta.

- IgM : rise early during the acute phase of the infection, typically remain detectable for less than 1 year, and do not cross the placenta.

- IgA : Measurement of IgA antibody titers may also be useful in a diagnosis of congenital toxoplasmosis in a fetus or newborn because IgM production is often weak during this period and the presence of IgG antibodies may indicate passive transfer of maternal antibodies in utero. IgA antibodies however usually disappear by 7 months.

In atypical cases, ocular fluid testing to detect parasite DNA by polymerase chain reaction or to determine intraocular production of specific antibody may be helpful for establishing etiology.

Neuroimaging is warranted in AIDS patients presenting with these findings because intracranial toxoplasmic lesions have been reported in up to 29% of these patients who have toxoplasmic chorioretinitis.

GAE, in general, must be treated by killing the pathogenic amoebas which cause it.

In "Acanthamoeba" infections, the diagnosis can be made from microscopic examination of stained smears of biopsy specimens (brain tissue, skin, cornea) or of corneal scrapings, which may detect trophozoites and cysts. Cultivation of the causal organism, and its identification by direct immunofluorescent antibody, may also prove useful. Laboratory workers and physicians often mistake the organisms on wet mount for monocytes and a diagnosis of viral meningitis is mistakenly given if the organisms are not motile. Heating a copper penny with an alcohol lamp and placing it on the wet mount slide will activate sluggish trophozoites and more rapidly make the diagnosis. If the person performing the spinal tap rapidly looks at the heated wet mount slide the trophozoites can be seen to swarm while monocytes do not.

Healing is prolonged, and usually takes 6–10 weeks. The ulcer heals by secondary intention.

While the progression of dysfunction is variable, it is regarded as a serious complication and untreated can progress to a fatal outcome. Diagnosis is made by neurologists who carefully rule out alternative diagnoses. This routinely requires a careful neurological examination, brain scans (MRI or CT scan) and a lumbar puncture to evaluate the cerebrospinal fluid. No single test is available to confirm the diagnosis, but the constellation of history, laboratory findings and examination can reliably establish the diagnosis when performed by experienced clinicians. The amount of virus in the brain does not correlate well with the degree of dementia, suggesting that secondary mechanisms are also important in the manifestation of ADC.

Diagnosis of autoimmune disorders largely rests on accurate history and physical examination of the patient, and high index of suspicion against a backdrop of certain abnormalities in routine laboratory tests (example, elevated C-reactive protein). In several systemic disorders, serological assays which can detect specific autoantibodies can be employed. Localised disorders are best diagnosed by immunofluorescence of biopsy specimens. Autoantibodies are used to diagnose many autoimmune diseases. The levels of autoantibodies are measured to determine the progress of the disease.

Death occurs in about 10% of cases and people do well about 70% of the time. This is a large improvement from the 1960s due to improved ability to image the head, better neurosurgery and better antibiotics.

Yersiniosis is usually self-limiting and does not require treatment. For severe infections (sepsis, focal infection) especially if associated with immunosuppression, the recommended regimen includes doxycycline in combination with an aminoglycoside. Other antibiotics active against "Y. enterocolitica" include trimethoprim-sulfamethoxasole, fluoroquinolones, ceftriaxone, and chloramphenicol. "Y. enterocolitica" is usually resistant to penicillin G, ampicillin, and cephalotin due to beta-lactamase production.

Eye and skin infections caused by "Acanthamoeba spp." are generally treatable. Topical use of 0.1% propamidine isethionate (Brolene) plus neomycin-polymyxin B-gramicidin ophthalmic solution has been a successful approach; keratoplasty is often necessary in severe infections. Although most cases of brain (CNS) infection with "Acanthamoeba" have resulted in death, patients have recovered from the infection with proper treatment.

"Toxoplasma" infection can be prevented in large part by:

- cooking meat to a safe temperature (i.e., one sufficient to kill "Toxoplasma")

- peeling or thoroughly washing fruits and vegetables before eating

- cleaning cooking surfaces and utensils after they have contacted raw meat, poultry, seafood, or unwashed fruits or vegetables

- pregnant women avoiding changing cat litter or, if no one else is available to change the cat litter, using gloves, then washing hands thoroughly

- not feeding raw or undercooked meat to cats to prevent acquisition of "Toxoplasma"

Prolonged and intense rainfall periods are significantly associated with the reactivation of toxoplasmic retinochoroiditis. Changes promoted by this climatic condition concern both the parasite survival in the soil as well as a putative effect on the host immune response due to other comorbidities.

Yersinia pseudotuberculosis is a Gram-negative bacterium that causes Far East scarlet-like fever in humans, who occasionally get infected zoonotically, most often through the food-borne route. Animals are also infected by "Y. pseudotuberculosis". The bacterium is urease positive.

Dempster-Shafer Theory is used for detecting skin infection and displaying the result of the detection process.

"Y. enterocolitica" infections are sometimes followed by chronic inflammatory diseases such as arthritis, erythema nodosum, and reactive arthritis. This is most likely because of some immune-mediated mechanism.

"Y. enterocolitica" seems to be associated with autoimmune Graves-Basedow thyroiditis.

Whilst indirect evidence exists, direct causative evidence is limited,

and "Y. enterocolitica" is probably not a major cause of this disease, but may contribute to the development of thyroid autoimmunity arising for other reasons in genetically susceptible individuals.

"Y. enterocolitica" infection has also been suggested to not be the cause of autoimmune thyroid disease, but rather is only an associated condition, with both having a shared inherited susceptibility.

More recently, the role for "Y. enterocolitica" has been disputed.

Vitamin D/Sunlight

Omega-3 Fatty Acids

Probiotics/Microflora

Antioxidants

In animals, "Y. pseudotuberculosis" can cause tuberculosis-like symptoms, including localized tissue necrosis and granulomas in the spleen, liver, and lymph nodes.

In humans, symptoms of Far East scarlet-like fever are similar to those of infection with "Yersinia enterocolitica" (fever and right-sided abdominal pain), except that the diarrheal component is often absent, which sometimes makes the resulting condition difficult to diagnose. "Y. pseudotuberculosis" infections can mimic appendicitis, especially in children and younger adults, and, in rare cases, the disease may cause skin complaints (erythema nodosum), joint stiffness and pain (reactive arthritis), or spread of bacteria to the blood (bacteremia).

Far East scarlet-like fever usually becomes apparent five to 10 days after exposure and typically lasts one to three weeks without treatment. In complex cases or those involving immunocompromised patients, antibiotics may be necessary for resolution; ampicillin, aminoglycosides, tetracycline, chloramphenicol, or a cephalosporin may all be effective.

The recently described syndrome "Izumi-fever" has been linked to infection with "Y. pseudotuberculosis".

The symptoms of fever and abdominal pain mimicking appendicitis (actually from mesenteric lymphadenitis) associated with "Y. pseudotuberculosis" infection are not typical of the diarrhea and vomiting from classical food poisoning incidents. Although "Y. pseudotuberculosis" is usually only able to colonize hosts by peripheral routes and cause serious disease in immunocompromised individuals, if this bacterium gains access to the blood stream, it has an LD comparable to "Y. pestis" at only 10 CFU.

Animal pathogens exist as facultative parasites. They are an exceptionally rare cause of meningoencephalitis.

clinical diagnosis include recurrent or recent herpes infection fever, headache, mental symptom, convulsion, disturbance of consciousness, focal signs.

CSF ,EEG, CT, MRI are responsive to specific antivirus agent.

Definite diagnosis – besides the above, the followings are needed

CSF: HSV－antigen,HSV－Antibody, brain biopsy or pathology: Cowdry in intranuclear

CSF: the DNA of the HSV(PCR)

cerebral tissue or specimen of the CSF:HSV

except other viral encephalitis

It is the lack of specific symptoms and its potential to appear anywhere that makes FMD a challenge to detect early on. The most accurate diagnosis comes from combining clinical presentation and angiographic imaging. According to the Michigan Outcomes Research and Reporting Program (MCORRP, 2013) the length of time from a patient’s first signs or symptoms to diagnosis is commonly 5 years.

FMD is currently diagnosed through the use of both invasive and non-invasive tests. Non-invasive testing includes duplex ultrasonography, magnetic resonance angiography (MRA), and computed tomographic angiography (CTA). Invasive testing through angiography is the gold standard. However, due to the higher risk of complications this is typically not done early on. Occasionally, FMD is diagnosed asymptomatically after an unrelated x-ray presents the classic ‘string of beads’ appearance of the arteries, or when a practitioner investigates an unexpected bruit found during an exam. When a diagnosis of FMD is considered for a patient thorough medical history, family history as well as vascular examination should be completed.

A definitive diagnosis of FMD can only be made with imaging studies. Catheter-based angiography (with contrast) has proven to be the most accurate imaging technique: this test involves a catheter is inserted into a large artery and advanced until it reaches the vessel of question. The catheter allows practitioners to view and measure the pressure of the artery aiding in the categorization and severity of the FMD diseased artery. According to Olin, “catheter-based angiography is the only imaging modality that can accurately identify the changes of FMD, aneurysm formation, and dissection in the branch vessels.” Practitioners believe it is important to utilize IVUS imaging because stenosis can sometimes only be detected through the methods of pressure gradient or IVUS imaging. In addition, computed tomography angiography and magnetic resonance angiography are commonly used to evaluate arteries in the brain. Doppler ultrasound may be used in both the diagnosis and follow-up of FMD.

The diagnosis of viral meningitis is made by clinical history, physical exam, and several diagnostic tests. Most importantly, cerebrospinal fluid (CSF) is collected via lumbar puncture (also known as spinal tap). This fluid, which normally surrounds the brain and spinal cord, is then analyzed for signs of infection. CSF findings that suggest a viral cause of meningitis include an elevated white blood cell count (usually 10-100 cells/µL) with a lymphocytic predominance in combination with a normal glucose level. Increasingly, cerebrospinal fluid PCR tests have become especially useful for diagnosing viral meningitis, with an estimated sensitivity of 95-100%. Additionally, samples from the stool, urine, blood and throat can also help to identify viral meningitis.

In certain cases, a CT scan of the head should be done before a lumbar puncture such as in those with poor immune function or those with increased intracranial pressure.