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Deep Learning Technology: Sebastian Arnold, Betty van Aken, Paul Grundmann, Felix A. Gers and Alexander Löser. Learning Contextualized Document Representations for Healthcare Answer Retrieval. The Web Conference 2020 (WWW'20)
Funded by The Federal Ministry for Economic Affairs and Energy; Grant: 01MD19013D, Smart-MD Project, Digital Technologies
A number of factors make people more susceptible to TB infections. The most important risk factor globally is HIV; 13% of all people with TB are infected by the virus. This is a particular problem in sub-Saharan Africa, where rates of HIV are high. Of people without HIV who are infected with tuberculosis, about 5–10% develop active disease during their lifetimes; in contrast, 30% of those coinfected with HIV develop the active disease.
Tuberculosis is closely linked to both overcrowding and malnutrition, making it one of the principal diseases of poverty. Those at high risk thus include: people who inject illicit drugs, inhabitants and employees of locales where vulnerable people gather (e.g. prisons and homeless shelters), medically underprivileged and resource-poor communities, high-risk ethnic minorities, children in close contact with high-risk category patients, and health-care providers serving these patients.
Chronic lung disease is another significant risk factor. Silicosis increases the risk about 30-fold. Those who smoke cigarettes have nearly twice the risk of TB compared to nonsmokers.
Other disease states can also increase the risk of developing tuberculosis. These include alcoholism and diabetes mellitus (three-fold increase).
Certain medications, such as corticosteroids and infliximab (an anti-αTNF monoclonal antibody), are becoming increasingly important risk factors, especially in the developed world.
Genetic susceptibility also exists, for which the overall importance remains undefined.
If left untreated, miliary tuberculosis is almost always fatal. Although most cases of miliary tuberculosis are treatable, the mortality rate among children with miliary tuberculosis remains 15 to 20% and for adults 25 to 30%. One of the main causes for these high mortality rates includes late detection of disease caused by non-specific symptoms. Non-specific symptoms include: coughing, weight loss, or organ dysfunction. These symptoms may be implicated in numerous disorders, thus delaying diagnosis. Misdiagnosis with tuberculosis meningitis is also a common occurrence when patients are tested for tuberculosis, since the two forms of tuberculosis have high rates of co-occurrence.
Progression from TB infection to overt TB disease occurs when the bacilli overcome the immune system defenses and begin to multiply. In primary TB disease (some 1–5% of cases), this occurs soon after the initial infection. However, in the majority of cases, a latent infection occurs with no obvious symptoms. These dormant bacilli produce active tuberculosis in 5–10% of these latent cases, often many years after infection.
The risk of reactivation increases with immunosuppression, such as that caused by infection with HIV. In people coinfected with "M. tuberculosis" and HIV, the risk of reactivation increases to 10% per year. Studies using DNA fingerprinting of "M. tuberculosis" strains have shown reinfection contributes more substantially to recurrent TB than previously thought, with estimates that it might account for more than 50% of reactivated cases in areas where TB is common. The chance of death from a case of tuberculosis is about 4% as of 2008, down from 8% in 1995.
Patients with miliary tuberculosis often experience non-specific signs, such as coughing and enlarged lymph nodes. Miliary tuberculosis can also present with enlarged liver (40% of cases), enlarged spleen (15%), inflammation of the pancreas (<5%), and multiple organ dysfunction with adrenal insufficiency (adrenal glands do not produce enough steroid hormones to regulate organ function). Miliary tuberculosis may also present with unilateral or bilateral pneumothorax rarely. Stool may also be diarrheal in nature and appearance.
Other symptoms include fever, hypercalcemia, chorodial tubercles and cutaneous lesions.
Firstly, many patients can experience a fever lasting several weeks with daily spikes in morning temperatures.
Secondly, hypercalcemia prevails in 16 to 51% of tuberculosis cases. It is thought that hypercalcemia occurs as a response to increased macrophage activity in the body. Such that, 1,25 dihydroxycholecalciferol (also referred to as calcitriol) improves the ability of macrophages to kill bacteria; however, higher levels of calcitriol lead to higher calcium levels, and thus hypercalcemia in some cases. Thus, hypercalcemia proves to be an important symptom of miliary tuberculosis.
Thirdly, chorodial tubercules, pale lesions on the optic nerve, typically indicate miliary tuberculosis in children. These lesions may occur in one eye or both; the number of lesions varies between patients. Chorodial tubercules may serve as important symptoms of miliary tuberculosis, since their presence can often confirm suspected diagnosis.
Lastly, between 10 and 30% of adults, and 20–40% of children with miliary tuberculosis have tuberculosis meningitis. This relationship results from myobacteria from miliary tuberculosis spreading to the brain and the subarachnoid space; as a result, leading to tuberculosis meningitis.
The risk factors for contracting miliary tuberculosis are being in direct contact with a person who has it, living in unsanitary conditions, and having an unhealthy diet. In the U.S., risk factors for contracting the disease include homelessness and HIV/AIDS.
A study conducted on 452 patients revealed that the genotype responsible for higher IL-10 expression makes HIV infected people more susceptible to tuberculosis infection. Another study on HIV-TB co-infected patients also concluded that higher level of IL-10 and IL-22 makes TB patient more susceptible to Immune reconstitution inflammatory syndrome (IRIS). It is also seen that HIV co-infection with tuberculosis also reduces concentration of immunopathogenic matrix metalloproteinase (MMPs) leading to reduced inflammatory immunopathology.
Urogenital tuberculosis may cause strictures of the ureter, which, however, may heal when infection is treated.
The infection may affect the kidneys, ureter and bladder and may cause significant damage to each.
Fungi and parasites may also cause the disease. Fungi and parasites are especially associated with immunocompromised patients. Other causes include: "Nocardia asteroides", "Mycobacterium", Fungi (e.g. "Aspergillus", "Candida", "Cryptococcus", "Mucorales", "Coccidioides", "Histoplasma capsulatum", "Blastomyces dermatitidis", "Bipolaris", "Exophiala dermatitidis", "Curvularia pallescens", "Ochroconis gallopava", "Ramichloridium mackenziei", "Pseudallescheria boydii"), Protozoa (e.g. "Toxoplasma gondii", "Entamoeba histolytica", "Trypanosoma cruzi", "Schistosoma", "Paragonimus"), and Helminths (e.g. "Taenia solium"). Organisms that are most frequently associated with brain abscess in patients with AIDS are poliovirus, "Toxoplasma gondii", and "Cryptococcus neoformans", though in infection with the latter organism, symptoms of meningitis generally predominate.
These organisms are associated with certain predisposing conditions:
- Sinus and dental infections—Aerobic and anaerobic streptococci, anaerobic gram-negative bacilli (e.g. "Prevotella", "Porphyromonas", "Bacteroides"), "Fusobacterium", "S. aureus", and Enterobacteriaceae
- Penetrating trauma—"S. aureus", aerobic streptococci, Enterobacteriaceae, and "Clostridium" spp.
- Pulmonary infections—Aerobic and anaerobic streptococci, anaerobic gram-negative bacilli (e.g. "Prevotella", "Porphyromonas", "Bacteroides"), "Fusobacterium", "Actinomyces", and "Nocardia"
- Congenital heart disease—Aerobic and microaerophilic streptococci, and "S. aureus"
- HIV infection—"T. gondii", "Mycobacterium", "Nocardia", "Cryptococcus", and "Listeria monocytogenes"
- Transplantation—"Aspergillus", "Candida", "Cryptococcus", "Mucorales", "Nocardia", and "T. gondii"
- Neutropenia—Aerobic gram-negative bacilli, "Aspergillus", "Candida", and "Mucorales"
When HIV-negative children take isoniazid after they have been exposed to tuberculosis, their risk to contract tuberculosis is reduced. A Cochrane review investigated whether giving isoniazid to HIV-positive children can help to prevent this vulnerable group from getting tuberculosis. They included three trials conducted in South Africa and Botswana and found that isoniazid given to all children diagnosed with HIV may reduce the risk of active tuberculosis and death in children who are not on antiretroviral treatment. For children taking antiretroviral medication, no clear benefit was detected.
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.
Tuberculous meningitis is also known as TB meningitis or tubercular meningitis. Tuberculous meningitis is "Mycobacterium tuberculosis" infection of the meninges—the system of membranes which envelop the central nervous system.
The treatment of TB meningitis is isoniazid, rifampicin, pyrazinamide and ethambutol for two months, followed by isoniazid and rifampicin alone for a further ten months. Steroids help reduce the risk of death in those without HIV. Steroids can be used in the first six weeks of treatment, A few people may require immunomodulatory agents such as thalidomide. Hydrocephalus occurs as a complication in about a third of people with TB meningitis. The addition of aspirin may reduce or delay mortality, possibly by reducing complications such as infarcts.
The formation of gummata is rare in developed countries, but common in areas that lack adequate medical treatment.
Syphilitic gummas are found in most but not all cases of tertiary syphilis, and can occur either singly or in groups. Gummatous lesions are usually associated with long-term syphilitic infection; however, such lesions can also be a symptom of benign late syphilis.
"TB Bacteria Are Spread Only from a Person with Active TB Disease ... In people who develop active TB of the lungs, also called pulmonary TB, the TB skin test will often be positive. In addition, they will show all the signs and symptoms of TB disease, and can pass the bacteria to others. So, if a person with TB of the lungs sneezes, coughs, talks, sings, or does anything that forces the bacteria into the air, other people nearby may breathe in TB bacteria. Statistics show that approximately one-third of people exposed to pulmonary TB become infected with the bacteria, but only one in ten of these infected people develop active TB disease during their lifetimes."
However, exposure to tuberculosis is very unlikely to happen when one is exposed for a few minutes in a store or in a few minutes social contact. "It usually takes prolonged exposure to someone with active TB disease for someone to become infected.
After exposure, it usually takes 8 to 10 weeks before the TB test would show if someone had become infected." "Depending on ventilation and other factors, these tiny droplets [from the person who has active tuberculosis] can remain suspended in the air for several hours. Should another person inhale them, he or she may become infected with TB. The probability of transmission will be related to the infectiousness of the person with TB, the environment where the exposure occurred, the duration of the exposure, and the susceptibility of the host." In fact, "it isn't easy to catch TB. You need consistent exposure to the contagious person for a long time. For that reason, you're more likely to catch TB from a relative than a stranger."
If a person had latent tuberculosis, they do not have active/contagious tuberculosis. Once exposed, people very often have latent tuberculosis. To convert to active tuberculosis, the bacteria must become active.
People have medical privacy or "confidentiality" and do not have to reveal their active tuberculosis case to family, friends, or co-workers; therefore, the person who gets latent tuberculosis may never know who had the active case of tuberculosis that caused the latent tuberculosis diagnosis for them. Only by required testing (required in some jobs)
A diagnosis of latent tuberculosis (LTB), also called latent tuberculosis infection (LTBI) means a patient is infected with "Mycobacterium tuberculosis", but the patient does not have active tuberculosis. Active tuberculosis can be contagious while latent tuberculosis is not, and it is therefore not possible to get TB from someone with latent tuberculosis. The main risk is that approximately 10% of these patients (5% in the first two years after infection and 0.1% per year thereafter) will go on to develop active tuberculosis. This is particularly true, and there is added risk, in particular situations such as medication that suppresses the immune system or advancing age.
The identification and treatment of people with latent TB is an important part of controlling this disease. Various treatment regimens are in use to treat latent tuberculosis, which generally need to be taken for several months.
Since its first description in the 1960s, only seven people worldwide have been reported to have survived PAM as of 2015, with three in the United States and one in Mexico; one of the US survivors had brain damage that is probably permanent. Less than 1% of people with naegleriasis survive.
The disease is rare and highly lethal: there have only been 300 cases as of 2008. Drug treatment research at Aga Khan University in Pakistan has shown that "in-vitro" drug susceptibility tests with some FDA approved drugs used for non-infectious diseases have proved to kill "Naegleria" "fowleri" with an amoebicidal rate greater than 95%. The same source has also proposed a device for drug delivery via the transcranial route to the brain.
The number of cases of infection could increase due to climate change, and was posited as the reason for 3 cases in Minnesota in 2010, 2012, and 2015. In 2016, an infection was contracted in Maryland, four miles south of the Pennsylvania border;
As of 2013, numbers of reported cases were expected to increase, simply because of better informed diagnoses being made both in ongoing cases and in autopsy findings.
Cases of MDR tuberculosis have been reported in every country surveyed. MDR-TB most commonly develops in the course of TB treatment, and is most commonly due to doctors giving inappropriate treatment, or patients missing doses or failing to complete their treatment. Because MDR tuberculosis is an airborne pathogen, persons with active, pulmonary tuberculosis caused by a multidrug-resistant strain can transmit the disease if they are alive and coughing. TB strains are often less fit and less transmissible, and outbreaks occur more readily in people with weakened immune systems (e.g., patients with HIV). Outbreaks among non immunocompromised healthy people do occur, but are less common.
As of 2013, 3.7% of new tuberculosis cases have MDR-TB. Levels are much higher in those previously treated for tuberculosis - about 20%. WHO estimates that there were about 0.5 million new MDR-TB cases in the world in 2011. About 60% of these cases occurred in Brazil, China, India, the Russian Federation and South Africa alone. In Moldova, the crumbling health system has led to the rise of MDR-TB. In 2013, the Mexico–United States border was noted to be "a very hot region for drug resistant TB", though the number of cases remained small.
It has been known for many years that INH-resistant TB is less virulent in guinea pigs, and the epidemiological evidence is that MDR strains of TB do not dominate naturally. A study in Los Angeles, California found that only 6% of cases of MDR-TB were clustered. Likewise, the appearance of high rates of MDR-TB in New York City in the early 1990s was associated with the explosion of AIDS in that area. In New York City, a report issued by city health authorities states that fully 80 percent of all MDR-TB cases could be traced back to prisons and homeless shelters. When patients have MDR-TB, they require longer periods of treatment—about two years of multidrug regimen. Several of the less powerful second-line drugs, which are required to treat MDR-TB, are also more toxic, with side effects such as nausea, abdominal pain, and even psychosis. The Partners in Health team had treated patients in Peru who were sick with strains that were resistant to ten and even twelve drugs. Most such patients require adjuvant surgery for any hope of a cure.
In syphilis, the gumma is caused by reaction to spirochaete bacteria in the tissue.
It appears to be the human body's way to slow down the action of this bacteria, it is a unique immune response that develops in humans after the immune system fails to kill off syphilis.
There are several elements of the Russian prison system that enable the spread of MDR-TB and heighten its severity. Overcrowding in prisons is especially conducive to the spread of tuberculosis; an inmate in a prison hospital has (on average) 3 meters of personal space, and an inmate in a correctional colony has 2 meters. Specialized hospitals and treatment facilities within the prison system, known as TB colonies, are intended to isolate infected prisoners to prevent transmission; however, as Ruddy et al. demonstrate, there are not enough of these colonies to sufficiently protect staff and other inmates. Additionally, many cells lack adequate ventilation, which increases likelihood of transmission. Bobrik et al. have also noted food shortages within prisons, which deprive inmates of the nutrition necessary for healthy functioning.
Comorbidity of HIV within prison populations has also been shown to worsen health outcomes. Nachega & Chaisson articulate that while HIV-infected prisoners are not more susceptible MDR-TB infection, they are more likely to progress to serious clinical illness if infected. According to Stern, HIV infection is 75 times more prevalent in Russian prison populations than in the civilian population. Therefore, prison inmates are both more likely to become infected with MDR-TB initially and to experience severe symptoms because of previous exposure to HIV.
Shin et al. emphasize another factor in MDR-TB prevalence in Russian prisons: alcohol and substance use. Ruddy et al. showed that risk for MDR-TB is three times higher among recreational drug users than non-users. Shin et al.’s study demonstrated that alcohol usage was linked to poorer outcomes in MDR-TB treatment; they also noted that a majority of subjects within their study (many of whom regularly used alcohol) were nevertheless cured by their aggressive treatment regimen.
Non-compliance with treatment plans is often cited as a contributor to MDR-TB transmission and mortality. Indeed, of the 80 newly-released TB-infected inmates in Fry et al.’s study, 73.8% did not report visiting a community dispensary for further treatment. Ruddy et al. cite release from facilities as one of the main causes of interruption in prisoner’s TB treatment, in addition to non-compliance within the prison and upon reintegration into civilian life. Fry et al.’s study also listed side effects of TB treatment medications (especially in HIV positive individuals), financial worries, housing insecurities, family problems, and fear of arrest as factors that prevented some prisoners from properly adhering to TB treatment. They also note that some researchers have argued that the short-term gains TB-positive prisoners receive, such as better food or work exclusion, may dis-incentivize becoming cured. In their World Health Organization article, Gelmanova et al. posit that non-adherence to TB treatment indirectly contributes to bacterial resistance. Although ineffective or inconsistent treatment does not “create” resistant strains, mutations within the high bacterial load in non-adherent prisoners can cause resistance.
Nachega & Chaisson argue that inadequate TB control programs are the strongest driver of MDR-TB incidence. They note that prevalence of MDR-TB is 2.5 times higher in areas of poorly controlled TB. Russian-based therapy (i.e., not DOTS) has been criticized by Kimerling et al. as “inadequate” in properly controlling TB incidence and transmission. Bobrik et al. note that treatment for MDR-TB is equally inconsistent; the second-line drugs used to treat the prisoners lack specific treatment guidelines, infrastructure, training, or follow-up protocols for prisoners reentering civilian life.
Cysts derived from CNS tissues are very common in America. They are a subtype of cerebrovascular diseases, which are the third leading cause of death in America. Generally, CNS cysts are present in all geographic regions, races, ages, and sexes. However, certain types of CNS cysts are more prevalent in certain types of individuals than others. Some examples of incidence rates in specific types of cysts include:
- Arachnoid cysts are more prevalent in males than females
- Colloid cysts are more prevalent in adults
- Dermoid cysts are more prevalent in children under 10 years of age
- Epidermoid cysts are more prevalent in middle-aged adults
Of the phenomena occurring in neurosarcoid, only facial nerve involvement is known to have a good prognosis and good response to treatment. Long-term treatment is usually necessary for all other phenomena. The mortality rate is estimated at 10%
Tuberculous pericarditis is a form of pericarditis.
Pericarditis caused by tuberculosis is difficult to diagnose, because definitive diagnosis requires culturing "Mycobacterium tuberculosis" from aspirated pericardial fluid or pericardial , which requires high technical skill and is often not diagnostic (the yield from culture is low even with optimum specimens). The Tygerberg scoring system helps the clinician to decide whether pericarditis is due to tuberculosis or whether it is due to another cause: night sweats (1 point), weight loss (1 point), fever (2 point), serum globulin > 40g/l (3 points), blood total leucocyte count <10 x 10/l (3 points); a total score of 6 or more is highly suggestive of tuberculous pericarditis. Pericardial fluid with an interferon-γ level greater than 50/ml is highly specific for tuberculous pericarditis.
There are no randomized trials which evaluate the length of anti-tuberculosis treatment required for tuberculous pericarditis. There is a small but not conclusive benefit for treatment with a schedule of steroids with anti-tuberculosis drugs. Open surgical drainage of fluid though effective in preventing cardiac tamponade was associated with more deaths.
There are five main causes of infections of the central nervous system (CNS): bacterial, viral, fungal, protozoal, and prionic.
Tuberculosis verrucosa cutis (also known as "lupus verrucosus", "prosector's wart", and "warty tuberculosis") is a rash of small, red papular nodules in the skin that may appear 2–4 weeks after inoculation by "Mycobacterium tuberculosis" in a previously infected and immunocompetent individual.
It is so called because it was a common occupational disease of prosectors, the preparers of dissections and autopsies. Reinfection by tuberculosis via the skin, therefore, can result from accidental exposure to human tuberculous tissue in physicians, pathologists and laboratory workers; or to tissues of other infected animals, in veterinarians, butchers, etc. Other names given to this form of skin tuberculosis are anatomist's wart and verruca necrogenica (literally, generated by corpses).
TVC is one of the many forms of cutaneous tuberculosis, such as the tuberculous chancre (which results from the inoculation in people without immunity), and the reactivation cutaneous tuberculosis (the most common form, which appears in previously infected patients). Other forms of cutaneous tuberculosis are: lupus vulgaris, scrofuloderma, lichen scrofulosorum, erythema induratum and the papulonecrotic tuberculid.
It was described by René Laennec in 1826.