Made by DATEXIS (Data Science and Text-based Information Systems) at Beuth University of Applied Sciences Berlin
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
The Mantoux tuberculin skin test is often used to screen people at high risk for TB. Those who have been previously immunized may have a false-positive test result. The test may be falsely negative in those with sarcoidosis, Hodgkin's lymphoma, malnutrition, and most notably, active tuberculosis. Interferon gamma release assays, on a blood sample, are recommended in those who are positive to the Mantoux test. These are not affected by immunization or most environmental mycobacteria, so they generate fewer false-positive results. However, they are affected by "M. szulgai", "M. marinum", and "M. kansasii". IGRAs may increase sensitivity when used in addition to the skin test, but may be less sensitive than the skin test when used alone.
Diagnosing active tuberculosis based only on signs and symptoms is difficult, as is diagnosing the disease in those who are immunosuppressed. A diagnosis of TB should, however, be considered in those with signs of lung disease or constitutional symptoms lasting longer than two weeks. A chest X-ray and multiple sputum cultures for acid-fast bacilli are typically part of the initial evaluation. Interferon-γ release assays and tuberculin skin tests are of little use in the developing world. Interferon gamma release assays (IGRA) have similar limitations in those with HIV.
A definitive diagnosis of TB is made by identifying "M. tuberculosis" in a clinical sample (e.g., sputum, pus, or a tissue biopsy). However, the difficult culture process for this slow-growing organism can take two to six weeks for blood or sputum culture. Thus, treatment is often begun before cultures are confirmed.
Nucleic acid amplification tests and adenosine deaminase testing may allow rapid diagnosis of TB. These tests, however, are not routinely recommended, as they rarely alter how a person is treated. Blood tests to detect antibodies are not specific or sensitive, so they are not recommended.
Testing for miliary tuberculosis is conducted in a similar manner as for other forms of tuberculosis, although a number of tests must be conducted on a patient to confirm diagnosis. Tests include chest x-ray, sputum culture, bronchoscopy, open lung biopsy, head CT/MRI, blood cultures, fundoscopy, and electrocardiography. The tuberculosis (TB) blood test, also called an Interferon Gamma Release Assay or IGRA, is a way to diagnose latent TB.
A variety of neurological complications have been noted in miliary tuberculosis patients—tuberculous meningitis and cerebral tuberculomas being the most frequent. However, a majority of patients improve following antituberculous treatment. Rarely lymphangitic spread of lung cancer could mimic miliary pattern of tuberculosis on regular chest X-ray.
The tuberculin skin test, commonly used for detection of other forms of tuberculosis, is not useful in the detection of miliary tuberculosis. The tuberculin skin test fails due to the high numbers of false negatives. These false negatives may occur because of higher rates of tuberculin anergy compared to other forms of tuberculosis.
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.
It is currently recommended that HIV-infected individuals with TB receive combined treatment for both diseases, irrespective of CD4+ cell count. ART (Anti Retroviral Therapy) along with ATT (Anti Tuberculosis Treatment) is the only available treatment in present time. Though the timing of starting ART is the debatable question due to the risk of immune reconstitution inflammatory syndrome (IRIS). The advantages of early ART include reduction in early mortality, reduction in relapses, preventing drug resistance to ATT and reduction in occurrence of HIV-associated infections other than TB. The disadvantages include cumulative toxicity of ART and ATT, drug interactions leading to inflammatory reactions are the limiting factors for choosing the combination of ATT and ART.
A systematic review investigated the optimal timing of starting antiretroviral therapy in adults with newly diagnosed pulmonary tuberculosis. The review authors included eight trials, that were generally well-conducted, with over 4500 patients in total. The early provision of antiretroviral therapy in HIV-infected adults with newly diagnosed tuberculosis improved survival in patients who had a low CD4 count (less than 0.050 x 109 cells/L). However, such therapy doubled the risk for IRIS. Regarding patients with higher CD4 counts (more than 0.050 x 109 cells/L), the evidence is not sufficient to make a conclusion about benefits or risks of early antiretroviral therapy.
Successful diagnosis of XDR-TB depends on the patient’s access to quality health-care services. If TB bacteria are found in the sputum, the diagnosis of TB can be made in a day or two, but this finding will not be able to distinguish between drug-susceptible and drug-resistant TB. To evaluate drug susceptibility, the bacteria need to be cultivated and tested in a suitable laboratory. Final diagnosis in this way for TB, and especially for XDR-TB, may take from 6 to 16 weeks. To reduce the time needed for diagnosis, new tools for rapid TB diagnosis are urgently needed.
The original method used to test for MDR-TB and XDR-TB was the Drug Susceptibility Testing (DST). DST is capable of determining how well four primary antitubercular drugs inhibit the growth of Mycobacterium Tuberculosis. The four primary antitubercular drugs are Isoniazid, Rifampin, Ethambutol and Pyrazinamide. Drug Susceptibility testing is done by making a Lowenstein-Jensen medium plate and spreading the bacteria on the plate. Disks containing one of the four primary drugs are added to the plate. After weeks of allowing the bacteria to grow the plate is checked for clear areas around the disk. If there is a clear area, the drug has killed the bacteria and most likely the bacteria is not resistant to that drug.
As "Mycobacterium tuberculosis" evolved new strains of resistant bacteria were being found such as XDR-TB. The problem was that primary DST was not suitable for testing bacteria strains that were extensively drug resistant. This problem was starting to be fixed when drug susceptibility tests started including not just the four primary drugs, but secondary drugs. This secondary test is known as Bactec MGIT 960 System. Although Bactec MGIT 960 System was accurate it was still slow at determining the level of resistance.
Diagnosis of MDR and XDR-TB in children is challenging. With an increasing number of cases being reported worldwide there is a great need for better diagnostic tools available for pediatric patients.
In recent years drug resistant tuberculosis testing has shown a lot of progress. Some studies have found an in-house assay that could rapidly detect resistance to drugs involved in the definition of XDR-TB directly from smear-positive specimens. The assay is called Reverse Line Blot Hybridization Assay also known as RLBH. The study showed that the results of RLBH were as accurate as other drug susceptibility tests, but at the same time didn`t take weeks to get results. RLBH testing only took 3 days to determine how resistant the strain of bacteria was.
The current research has shown progress in the testing of drug resistance. A recent study found that a research technique known as direct nitrate reductase assay (D-NRA) showed efficient accuracy for the rapid and simultaneous detection of resistance to isoniazid (INH), rifampicin (RIF), kanamycin (KAN) and ofloxacin (OFL). D-NRA results were obtained in 16.9 days, comparably less than other drug susceptibility testing. At the same time the study mentioned how D-NRA is a low-cost technology, easy to set up in clinical laboratories and suitable to be used for DST of M. tuberculosis in all smear-positive samples.
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.
Countries aim to prevent XDR-TB by ensuring that the work of their national TB control programmes, and of all practitioners working with people with TB, is carried out according to the International Standards for TB Care. These emphasize providing proper diagnosis and treatment to all TB patients, including those with drug-resistant TB; assuring regular, timely supplies of all anti-TB drugs; proper management of anti-TB drugs and providing support to patients to maximize adherence to prescribed regimens; caring for XDR-TB cases in a centre with proper ventilation, and minimizing contact with other patients, particularly those with HIV, especially in the early stages before treatment has had a chance to reduce the infectiousness. Also an effective disease control infrastructure is necessary for the prevention of XDR tuberculosis. Increased funding for research, and strengthened laboratory facilities are much required. Immediate detection through drug susceptibility testing's are vital, when trying to stop the spread of XDR tuberculosis.
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
Urogenital tuberculosis may cause strictures of the ureter, which, however, may heal when infection is treated.
Together, diseases of poverty kill approximately 14 million people annually. Gastroenteritis with its associated diarrhea results in about 1.8 million deaths in children yearly with most of these in the world's poorest nations.
At the global level, the three primary poverty-related diseases (PRDs) are AIDS, malaria, and tuberculosis. Developing countries account for 95% of the global AIDS prevalence and 98% of active tuberculosis infections. Furthermore, 90% of malaria deaths occur in sub-Saharan Africa. Together, these three diseases account for 10% of global mortality.
Treatable childhood diseases are another set which have disproportionately higher rates in poor countries despite the availability of cures for decades. These include measles, pertussis and polio.
Three other diseases, measles, pneumonia, and diarrheal diseases, are also closely associated with poverty, and are often included with AIDS, malaria, and tuberculosis in broader definitions and discussions of diseases of poverty.
More than 300 million people worldwide have asthma. The rate of asthma increases as countries become more urbanized and in many parts of the world those who develop asthma do not have access to medication and medical care. Within the United States, African Americans and Latinos are four times more likely to suffer from severe asthma than whites. The disease is closely tied to poverty and poor living conditions. Asthma is also prevalent in children in low income countries. Homes with roaches and mice, as well as mold and mildew put children at risk for developing asthma as well as exposure to cigarette smoke.
Unlike many other Western countries, the mortality rate for asthma has steadily risen in the United States over the last two decades. Mortality rates for African American children due to asthma are also far higher than that of other racial groups. For African Americans, the rate of visits to the emergency room is 330 percent higher than their white counterparts. The hospitalization rate is 220 percent higher and the death rate is 190 percent higher. Among Hispanics, Puerto Ricans are disporpotionatly affected by asthma with a disease rate that is 113 percent higher than non-Hispanic Whites and 50 percent higher than non-Hispanic Blacks. Studies have shown that asthma morbidity and mortality are concentrated in inner city neighborhoods characterized by poverty and large minority populations and this affects both genders at all ages. Asthma continues to have an adverse effects on the health of the poor and school attendance rates among poor children. 10.5 million days of school are missed each year due to asthma.
Diagnosis rests on the microscopic identification of larvae (rhabditiform and occasionally filariform) in the stool or duodenal fluid. Examination of many samples may be necessary, and not always sufficient, because direct stool examination is relatively insensitive, with a single sample only able to detect larvae in about 25% of cases. It can take 4 weeks from initial infection to the passage of larvae in the stool.
The stool can be examined in wet mounts:
- directly
- after concentration (formalin-ethyl acetate)
- after recovery of the larvae by the Baermann funnel technique
- after culture by the Harada-Mori filter paper technique
- after culture in agar plates
Culture techniques are the most sensitive, but are not routinely available in the West. In the UK, culture is available at either of the Schools of Tropical Medicine in Liverpool or London. Direct examination must be done on stool that is freshly collected and not allowed to cool down, because hookworm eggs hatch on cooling and the larvae are very difficult to distinguish from Strongyloides.
Finding Strongyloides in the stool is negative in up to 70% of tests. It is important to undergo frequent stool sampling as well as duodenal biopsy if a bad infection is suspected. The duodenal fluid can be examined using techniques such as the Enterotest string or duodenal aspiration. Larvae may be detected in sputum from patients with disseminated strongyloidiasis.
Given the poor ability of stool examination to diagnose strongyloides, detecting antibodies by ELISA can be useful. Serology can cross-react with other parasites, remain positive for years after successful treatment or be falsely negative in immunocompromised patients. Infected patients will also often have an elevated eosinophil count, with an average of absolute eosinophil count of 1000 in one series. The combination of clinical suspicion, a positive antibody and a peripheral eosinophilia can be strongly suggestive of infection.
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 small bowel follow-through may suggest the diagnosis of Crohn's disease and is useful when the disease involves only the small intestine. Because colonoscopy and gastroscopy allow direct visualization of only the terminal ileum and beginning of the duodenum, they cannot be used to evaluate the remainder of the small intestine. As a result, a barium follow-through X-ray, wherein barium sulfate suspension is ingested and fluoroscopic images of the bowel are taken over time, is useful for looking for inflammation and narrowing of the small bowel. Barium enemas, in which barium is inserted into the rectum and fluoroscopy is used to image the bowel, are rarely used in the work-up of Crohn's disease due to the advent of colonoscopy. They remain useful for identifying anatomical abnormalities when strictures of the colon are too small for a colonoscope to pass through, or in the detection of colonic fistulae (in this case contrast should be performed with iodate substances).
CT and MRI scans are useful for evaluating the small bowel with enteroclysis protocols. They are also useful for looking for intra-abdominal complications of Crohn's disease, such as abscesses, small bowel obstructions, or fistulae. Magnetic resonance imaging (MRI) is another option for imaging the small bowel as well as looking for complications, though it is more expensive and less readily available. MRI techniques such as diffusion-weighted imaging and high-resolution imaging are more sensitive in detecting ulceration and inflammation compared to CT.
Preventive measures for visitors to tropical areas where the condition exists include steps to reduce the likelihood of gastroenteritis. These may comprise using only bottled water for drinking, brushing teeth, and washing food, and avoiding fruits washed with tap water (or consuming only peeled fruits, such as bananas and oranges). Basic sanitation is necessary to reduce fecal-oral contamination and the impact of environmental enteropathy in the developing world.
A complete blood count may reveal anemia, which commonly is caused by blood loss leading to iron deficiency (a microcytic anemia) or by vitamin B deficiency (a macrocytic anemia), usually caused by ileal disease impairing vitamin B absorption. Rarely autoimmune hemolysis may occur. Ferritin levels help assess if iron deficiency is contributing to the anemia. Erythrocyte sedimentation rate (ESR) and C-reactive protein help assess the degree of inflammation, which is important as ferritin can also be raised in inflammation. Serum iron, total iron binding capacity and transferrin saturation may be more easily interpreted in inflammation. Anemia of chronic disease results in a normocytic anemia. Other causes of anemia include medication used in treatment of inflammatory bowel disease, like azathioprine, which can lead to cytopenia, and sulfasalazine, which can also result in folate deficiency. Testing for "Saccharomyces cerevisiae" antibodies (ASCA) and antineutrophil cytoplasmic antibodies (ANCA) has been evaluated to identify inflammatory diseases of the intestine and to differentiate Crohn's disease from ulcerative colitis. Furthermore, increasing amounts and levels of serological antibodies such as ASCA, antilaminaribioside [Glc(β1,3)Glb(β); ALCA], antichitobioside [GlcNAc(β1,4)GlcNAc(β); ACCA], antimannobioside [Man(α1,3)Man(α)AMCA], antiLaminarin [(Glc(β1,3))3n(Glc(β1,6))n; anti-L] and antichitin [GlcNAc(β1,4)n; anti-C] associate with disease behavior and surgery, and may aid in the prognosis of Crohn's disease.
Low serum levels of vitamin D are associated with Crohn's disease. Further studies are required to determine the significance of this association.
The prognosis for tropical sprue may be excellent after treatment. It usually does not recur in people who get it during travel to affected regions. The recurrence rate for natives is about 20%, but another study showed changes can persist for several years.
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.
Opportunistic infections caused by Feline Leukemia Virus and Feline immunodeficiency virus retroviral infections can be treated with Lymphocyte T-Cell Immune Modulator.
The diagnosis is confirmed by a skin biopsy and a positive culture for acid-fast bacilli. A PPD test may also result positive.
Specific helminths can be identified through microscopic examination of their eggs (ova) found in faecal samples. The number of eggs is measured in units of eggs per gram. However, it does not quantify mixed infections, and in practice, is inaccurate for quantifying the eggs of schistosomes and soil-transmitted helmiths. Sophisticated tests such as serological assays, antigen tests, and molecular diagnosis are also available; however, they are time-consuming, expensive and not always reliable.
Multiple disorders are found in patients with radiation enteropathy, so guidance including an algorithmic approach to their investigation has been developed. This includes a holistic assessment with investigations including endoscopies, breath tests and other nutritional and gastrointestinal tests. Full investigation is important as many cancer survivors of radiation therapy develop other causes for their symptoms such as colonic polyps, diverticular disease or hemorrhoids.
The diagnosis is usually confirmed by biopsies on colonoscopy. Fecal calprotectin is useful as an initial investigation, which may suggest the possibility of IBD, as this test is sensitive but not specific for IBD.
Major groups of parasites include protozoans (organisms having only one cell) and parasitic worms (helminths). Of these, protozoans, including cryptosporidium, microsporidia, and isospora, are most common in HIV-infected persons. Each of these parasites can infect the digestive tract, and sometimes two or more can cause infection at the same time.