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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
Treatment of TB uses antibiotics to kill the bacteria. Effective TB treatment is difficult, due to the unusual structure and chemical composition of the mycobacterial cell wall, which hinders the entry of drugs and makes many antibiotics ineffective. The two antibiotics most commonly used are isoniazid and rifampicin, and treatments can be prolonged, taking several months. Latent TB treatment usually employs a single antibiotic, while active TB disease is best treated with combinations of several antibiotics to reduce the risk of the bacteria developing antibiotic resistance. People with latent infections are also treated to prevent them from progressing to active TB disease later in life. Directly observed therapy, i.e., having a health care provider watch the person take their medications, is recommended by the WHO in an effort to reduce the number of people not appropriately taking antibiotics. The evidence to support this practice over people simply taking their medications independently is of poor quality. There is no strong evidence indicating that directly observed therapy improves the number of people who were cured or the number of people who complete their medicine. Moderate quality evidence suggests that there is also no difference if people are observed at home versus at a clinic, or by a family member versus a health care worker. Methods to remind people of the importance of treatment and appointments may result in a small but important improvement.
The BCG vaccine has limitations, and research to develop new TB vaccines is ongoing. A number of potential candidates are currently in phase I and II clinical trials. Two main approaches are being used to attempt to improve the efficacy of available vaccines. One approach involves adding a subunit vaccine to BCG, while the other strategy is attempting to create new and better live vaccines. MVA85A, an example of a subunit vaccine, currently in trials in South Africa, is based on a genetically modified vaccinia virus. Vaccines are hoped to play a significant role in treatment of both latent and active disease.
To encourage further discovery, researchers and policymakers are promoting new economic models of vaccine development, including prizes, tax incentives, and advance market commitments. A number of groups, including the Stop TB Partnership, the South African Tuberculosis Vaccine Initiative, and the Aeras Global TB Vaccine Foundation, are involved with research. Among these, the Aeras Global TB Vaccine Foundation received a gift of more than $280 million (US) from the Bill and Melinda Gates Foundation to develop and license an improved vaccine against tuberculosis for use in high burden countries.
A number of medications are being studied for multidrug-resistant tuberculosis, including bedaquiline and delamanid. Bedaquiline received U.S. Food and Drug Administration (FDA) approval in late 2012. The safety and effectiveness of these new agents are still uncertain, because they are based on the results of a relatively small studies. However, existing data suggest that patients taking bedaquiline in addition to standard TB therapy are five times more likely to die than those without the new drug, which has resulted in medical journal articles raising health policy questions about why the FDA approved the drug and whether financial ties to the company making bedaquiline influenced physicians' support for its use.
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.
The standard treatment recommended by the WHO is with isoniazid and rifampicin for six months, as well as ethambutol and pyrazinamide for the first two months. If there is evidence of meningitis, then treatment is extended to twelve months. The U.S. guidelines recommend nine months' treatment. "Common medication side effects a patient may have such as inflammation of the liver if a patient is taking pyrazinamide, rifampin, and isoniazid. A patient may also have drug resistance to medication, relapse, respiratory failure, and adult respiratory distress syndrome."
It usually strikes young adults with tuberculosis in other places of the body as well. It is common in Asia, but less common in sub-Saharan Africa.
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.
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.
Urogenital tuberculosis may cause strictures of the ureter, which, however, may heal when infection is treated.
The BCG vaccine prevents severe forms of TB in children, such as TB meningitis. It would be expected that BCG would have the same effect in preventing severe forms of TB in children, even if they were exposed to XDR-TB. The vaccine has shown to be less effective at preventing the most common strains of TB and in blocking TB in adults. The effect of BCG against XDR-TB would therefore likely be very limited. New vaccines are urgently needed, and WHO and members of the Stop TB Partnership are actively working on new vaccines.
XDR-TB is defined as TB that has developed resistance to at least rifampicin and isoniazid (resistance to these first line anti-TB drugs defines Multi-drug-resistant tuberculosis, or MDR-TB), as well as to any member of the quinolone family and at least one of the following second-line anti-TB injectable drugs: kanamycin, capreomycin, or amikacin. This definition of XDR-TB was agreed by the WHO Global Task Force on XDR-TB in October 2006. The earlier definition of XDR-TB as MDR-TB that is also resistant to three or more of the six classes of second-line drugs, is no longer used, but may be referred to in older publications.
Tuberculoma is commonly treated through the HRZE drug combination (Isoniazid, Rifampin, Pyrazinamide, Ethambutol) followed by maintenance therapy.
Since opportunistic infections can cause severe disease, much emphasis is placed on measures to prevent infection. Such a strategy usually includes restoration of the immune system as soon as possible, avoiding exposures to infectious agents, and using antimicrobial medications ("prophylactic medications") directed against specific infections.
Individuals at higher risk are often prescribed prophylactic medication to prevent an infection from occurring. A patient's risk level for developing an opportunistic infection is approximated using the patient's CD4 T-cell count and sometimes other markers of susceptibility. Common prophylaxis treatments include the following:
There are several ways that drug resistance to TB, and drug resistance in general, can be prevented:
1. Rapid diagnosis & treatment of TB: One of the greatest risk factors for drug resistant TB is problems in treatment and diagnosis, especially in developing countries. If TB is identified and treated soon, drug resistance can be avoided.
2. Completion of treatment: Previous treatment of TB is an indicator of MDR TB. If the patient does not complete his/her antibiotic treatment, or if the physician does not prescribe the proper antibiotic regimen, resistance can develop. Also, drugs that are of poor quality or less in quantity, especially in developing countries, contribute to MDR TB.
3. Patients with HIV/AIDS should be identified and diagnosed as soon as possible. They lack the immunity to fight the TB infection and are at great risk of developing drug resistance.
4. Identify contacts who could have contracted TB: i.e. family members, people in close contact, etc.
5. Research: Much research and funding is needed in the diagnosis, prevention and treatment of TB and MDR TB.
"Opponents of a universal tuberculosis treatment, reasoning from misguided notions of cost-effectiveness, fail to acknowledge that MDRTB is not a disease of poor people in distant places. The disease is infectious and airborne. Treating only one group of patients looks inexpensive in the short run, but will prove disastrous for all in the long run."- Paul Farmer
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.
"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)
Community-based treatment programs such as DOTS-Plus, a MDR-TB-specialized treatment using the popular Directly Observed Therapy – Short Course (DOTS) initiative, have shown considerable success in the of the world. In these locales, these programs have proven to be a good option for proper treatment of MDR-TB in poor, rural areas. A successful example has been in Lima, Peru, where the program has seen cure rates of over 80%.
However, TB clinicians have expressed concern in the DOTS program administered in the Republic of Georgia because it is anchored in a passive case finding. This means that the system depends on patients coming to health care providers, without conducting compulsory screenings. As medical anthropologists like Erin Koch have shown, this form of implementation does not suit all cultural structures. They urge that the DOTS protocol be constantly reformed in the context of local practices, forms of knowledge and everyday life.
Erin Koch has utilized Paul Farmer’s concept of “structural” violence as a perspective for understanding how “institutions, environment, poverty, and power reproduce, solidify, and naturalize the uneven distribution of disease and access to resources”. She has also studied the effectiveness of the DOTS protocol in the widespread disease of tuberculosis in the Georgian prison system. Unlike the DOTS passive case finding utilized for the general Georgian public, the multiple-level surveillance in the prison system has proven more successful in reducing the spread of tuberculosis while increasing rates of cure.
Koch critically notes that because the DOTS protocol aims to change the individual’s behavior without addressing the need to change the institutional, political, and economic contexts, certain limitations arise, such as MDR tuberculosis.
Paul Farmer believes that DOTS should be the cornerstone of tuberculosis control around the world.
Controlling the spread of tuberculosis infection can prevent tuberculous spondylitis and arthritis. Patients who have a positive PPD test (but not active tuberculosis) may decrease their risk by properly taking medicines to prevent tuberculosis. To effectively treat tuberculosis, it is crucial that patients take their medications exactly as prescribed.
Totally drug-resistant tuberculosis (TDR-TB) is a generic term for tuberculosis strains that are resistant to a wider range of drugs than strains classified as extensively drug-resistant tuberculosis. TDR-TB has been identified in three countries; India, Iran, and Italy. The emergence of TDR-TB has been documented in four major publications. However, it is not yet recognised by the World Health Organization.
TDR-TB has resulted from further mutations within the bacterial genome to confer resistance, beyond those seen in XDR- and MDR-TB. Development of resistance is associated with poor management of cases. Drug resistance testing occurs in only 9% of TB cases worldwide. Without testing to determine drug resistance profiles, MDR- or XDR-TB patients may develop resistance to additional drugs. TDR-TB is relatively poorly documented, as many countries do not test patient samples against a broad enough range of drugs to diagnose such a comprehensive array of resistance. The United Nations' Special Programme for Research and Training in Tropical Diseases has set up a TDR Tuberculosis Specimen Bank to archive specimens of TDR-TB.
Therapy for cutaneous tuberculosis is the same as for systemic tuberculosis, and usually consists of a 4-drug regimen, i.e., isoniazid, rifampin, pyrazinamide, and ethambutol or streptomycin.
With the passage of time " Mycobacterium tuberculosis" (also called" Bacillus Koch") can transform into crystals of calcium. These can affect any organ such as the brain, intestine, ovaries, breast, lungs, esophagus, intestine, liver, pancreas, bones, and many others.
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 treatment of gram negative bacteremia is also highly dependent on the causative organism. Empiric antibiotic therapy should be guided by the most likely source of infection and the patient's past exposure to healthcare facilities. In particular, a recent history of exposure to a healthcare setting may necessitate the need for antibiotics with "pseudomonas aeruginosa" coverage or broader coverage for resistant organisms. Extended generation cephalosporins such as ceftriaxone or beta lactam/beta lactam inhibitor antibiotics such as piperacillin-tazobactam are frequently used for the treatment of gram negative bacteremia.
Tuberculosis is the leading cause of death around the world for an infectious disease. This disease is especially prevalent in sub-Saharan Africa, and the Latin American and Caribbean region. While the tuberculosis rate is decreasing in the rest of the world, it is increasing by rate of 6 percent per year in Sub-Saharan Africa. It is the leading cause of death for people with HIV in Africa. Tuberculosis (TB) is closely related to lifestyles of poverty, overcrowded conditions, alcoholism, stress, drug addiction and malnutrition. This disease spreads quickly among people who are undernourished. According to the Center for Disease Control and Prevention, in the United States, tuberculosis is more prevalent among foreign born persons, and ethnic minorities. The rates are especially high among Hispanics, Blacks and Asians.
HIV infection and TB are also closely tied. Being infected with HIV increases the rate of activation of latent TB infections, and having TB, increases the rate of HIV replication, therefore accelerating the progression of AIDS.
The Infectious Disease Society of America (IDSA) recommends treating uncomplicated methicillin resistant staph aureus (MRSA) bacteremia with a 14-day course of intravenous vancomycin. Uncomplicated bacteremia is defined as having positive blood cultures for MRSA, but having no evidence of endocarditis, no implanted prostheses, negative blood cultures after 2–4 days of treatment, and signs of clinical improvement after 72 hrs.
The antibiotic treatment of choice for streptococcal and enteroccal infections differs by species. However, it is important to look at the antibiotic resistance pattern for each species from the blood culture to better treat infections caused by resistant organisms.