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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)
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For botulism in babies, diagnosis should be made on signs and symptoms. Confirmation of the diagnosis is made by testing of a stool or enema specimen with the mouse bioassay.
Physicians may consider diagnosing botulism if the patient's history and physical examination suggest botulism. However, these clues are often not enough to allow a diagnosis. Other diseases such as Guillain–Barré syndrome, stroke, and myasthenia gravis can appear similar to botulism, and special tests may be needed to exclude these other conditions. These tests may include a brain scan, cerebrospinal fluid examination, nerve conduction test (electromyography, or EMG), and an edrophonium chloride (Tensilon) test for myasthenia gravis. A definite diagnosis can be made if botulinum toxin is identified in the food, stomach or intestinal contents, vomit or feces. The toxin is occasionally found in the blood in peracute cases. Botulinum toxin can be detected by a variety of techniques, including enzyme-linked immunosorbent assays (ELISAs), electrochemiluminescent (ECL) tests and mouse inoculation or feeding trials. The toxins can be typed with neutralization tests in mice. In toxicoinfectious botulism, the organism can be cultured from tissues. On egg yolk medium, toxin-producing colonies usually display surface iridescence that extends beyond the colony.
In adults, botulism can be treated by passive immunization with a horse-derived antitoxin, which blocks the action of the toxin circulating in the blood. A trivalent antitoxin containing antibodies raised against botulinum toxin types A, B, and E is used most commonly, however a heptavalent botulism antitoxin has also been developed and was approved by the U.S. FDA in 2013. In infants, horse-derived antitoxin is sometimes avoided for fear of infants developing serum sickness or lasting hypersensitivity to horse-derived proteins. To avoid this, a human-derived antitoxin has been developed and approved by the U.S. FDA in 2003 for the treatment of infant botulism. This human-derived antitoxin has been shown to be both safe and effective for the treatment of infant botulism. However, the danger of equine-derived antitoxin to infants has not been clearly established, and one study showed the equine-derived antitoxin to be both safe and effective for the treatment of infant botulism.
Trivalent (A,B,E) botulinum antitoxin is derived from equine sources utilizing whole antibodies (Fab and Fc portions). In the United States, this antitoxin is available from the local health department via the CDC. The second antitoxin, heptavalent (A,B,C,D,E,F,G) botulinum antitoxin, is derived from "despeciated" equine IgG antibodies which have had the Fc portion cleaved off leaving the F(ab')2 portions. This less immunogenic antitoxin is effective against all known strains of botulism where not contraindicated.
The presence of avian botulism is extremely hard to detect before an outbreak. Frequent surveillance of sites at risk is needed for early detection of the disease in order to take action and remove carcasses. Vaccines are also developed, but they are expected to have limited effectiveness in stemming outbreaks in wild waterbird populations. However may be effective in reducing mortality for endangered island waterfowl and small non-migratory wild populations. Field tests are needed.
The botulinum neurotoxin is lethal because it causes paralysis. Field identification involves locating birds showing flaccidity in the legs, wings and neck, as well as the presence of protuberant nictitating membrane. The presence of several dozen, or even hundreds, of fresh waterbird carcasses is the stereotypical sign an outbreak has occurred. In this case the specimens need to be taken to disease laboratory to determine the cause of mortality. Most commonly, detection of "C. botulinum" in carcasses during lab work is accomplished through analysis of polymerase chain reactions (PCR) and is often the most successful method.
Biochemical tests used in the identification of infectious agents include the detection of metabolic or enzymatic products characteristic of a particular infectious agent. Since bacteria ferment carbohydrates in patterns characteristic of their genus and species, the detection of fermentation products is commonly used in bacterial identification. Acids, alcohols and gases are usually detected in these tests when bacteria are grown in selective liquid or solid media.
The isolation of enzymes from infected tissue can also provide the basis of a biochemical diagnosis of an infectious disease. For example, humans can make neither RNA replicases nor reverse transcriptase, and the presence of these enzymes are characteristic of specific types of viral infections. The ability of the viral protein hemagglutinin to bind red blood cells together into a detectable matrix may also be characterized as a biochemical test for viral infection, although strictly speaking hemagglutinin is not an "enzyme" and has no metabolic function.
Serological methods are highly sensitive, specific and often extremely rapid tests used to identify microorganisms. These tests are based upon the ability of an antibody to bind specifically to an antigen. The antigen, usually a protein or carbohydrate made by an infectious agent, is bound by the antibody. This binding then sets off a chain of events that can be visibly obvious in various ways, dependent upon the test. For example, "Strep throat" is often diagnosed within minutes, and is based on the appearance of antigens made by the causative agent, "S. pyogenes", that is retrieved from a patients throat with a cotton swab. Serological tests, if available, are usually the preferred route of identification, however the tests are costly to develop and the reagents used in the test often require refrigeration. Some serological methods are extremely costly, although when commonly used, such as with the "strep test", they can be inexpensive.
Complex serological techniques have been developed into what are known as Immunoassays. Immunoassays can use the basic antibody – antigen binding as the basis to produce an electro-magnetic or particle radiation signal, which can be detected by some form of instrumentation. Signal of unknowns can be compared to that of standards allowing quantitation of the target antigen. To aid in the diagnosis of infectious diseases, immunoassays can detect or measure antigens from either infectious agents or proteins generated by an infected organism in response to a foreign agent. For example, immunoassay A may detect the presence of a surface protein from a virus particle. Immunoassay B on the other hand may detect or measure antibodies produced by an organism's immune system that are made to neutralize and allow the destruction of the virus.
Instrumentation can be used to read extremely small signals created by secondary reactions linked to the antibody – antigen binding. Instrumentation can control sampling, reagent use, reaction times, signal detection, calculation of results, and data management to yield a cost effective automated process for diagnosis of infectious disease.
Technologies based upon the polymerase chain reaction (PCR) method will become nearly ubiquitous gold standards of diagnostics of the near future, for several reasons. First, the catalog of infectious agents has grown to the point that virtually all of the significant infectious agents of the human population have been identified. Second, an infectious agent must grow within the human body to cause disease; essentially it must amplify its own nucleic acids in order to cause a disease. This amplification of nucleic acid in infected tissue offers an opportunity to detect the infectious agent by using PCR. Third, the essential tools for directing PCR, primers, are derived from the genomes of infectious agents, and with time those genomes will be known, if they are not already.
Thus, the technological ability to detect any infectious agent rapidly and specifically are currently available. The only remaining blockades to the use of PCR as a standard tool of diagnosis are in its cost and application, neither of which is insurmountable. The diagnosis of a few diseases will not benefit from the development of PCR methods, such as some of the clostridial diseases (tetanus and botulism). These diseases are fundamentally biological poisonings by relatively small numbers of infectious bacteria that produce extremely potent neurotoxins. A significant proliferation of the infectious agent does not occur, this limits the ability of PCR to detect the presence of any bacteria.
As of tissue or discharge are generally unreliable, the diagnosis of mucormycosis tends to be established with a biopsy specimen of the involved tissue.
A list of the more common and well-known diseases associated with infectious pathogens is provided and is not intended to be a complete listing.
The prognosis of nocardiosis is highly variable. The state of the host's health, site, duration, and severity of the infection all play parts in determining the prognosis. As of now, skin and soft tissue infections have a 100% cure rate, and pleuropulmonary infections have a 90% cure rate with appropriate therapy. The cure rate falls to 63% with those infected with dissemented nocardiosis, with only half of those surviving infections that cause brain abscess. Additionally, 44% of people who are infected in the spinal cord/brain die, increasing to 85% if that person has an already weakened immune system. Unfortunately, there is not a preventative to nocardiosis. The only recommendation is to protect open wounds to limit access.
Diagnosis during the acute phase can be made by obtaining a peripheral blood smear with Giemsa stain, Columbia blood agar cultures, immunoblot, indirect immunofluorescence, and PCR. Diagnosis during the chronic phase can be made using a Warthin-Starry stain of wart biopsy, PCR, and immunoblot.
Infectious pathogen-associated diseases include many of the most common and costly chronic illnesses. The treatment of chronic diseases accounts for 75% of all US healthcare costs (amounting to $1.7 trillion in 2009).
Diagnosis of nocardiosis can be done by a doctor using various techniques. These techniques include, but are not limited to: a chest x-rays of the lung, a bronchoscopy, a brain/lung/skin biopsy, or a sputum culture.
However, diagnosis may be difficult. Nocardiae are gram positive weakly acid-fast branching rod-shaped bacteria and can be visualized by a modified Ziehl–Neelsen stain like Fite-Faraco method. In the clinical laboratory, routine cultures may be held for insufficient time to grow nocardiae, and referral to a reference laboratory may be needed for species identification. Infiltration and pleural effusion are usually seen via x-ray.
The immune reconstitution inflammatory syndrome (IRIS) has been described in those with normal immune function with meningitis caused by "C. gattii" and "C. grubii". Several weeks or even months into appropriate treatment, there can be deterioration with worsening meningitis symptoms and progression or development of new neurological symptoms. IRIS is however much more common in those with poor immune function (≈25% vs. ≈8%).
Magnetic resonance imaging shows increase in the size of brain lesions, and CSF abnormalities (white cell count, protein, glucose) increase. Radiographic appearance of cryptococcal IRIS brain lesions can mimic that of toxoplasmosis with ring enhancing lesions on head computed tomography (CT). CSF culture is sterile, and there is no increase in CSF cryptococcal antigen titre.
The increasing inflammation can cause brain injury or be fatal.
The mechanism behind IRIS in cryptococcal meningitis is primarily immunologic. With reversal of immunosuppression, there is paradoxical increased inflammation as the recovering immune system recognises the fungus. In severe IRIS cases, treatment with systemic corticosteroids has been utilized - although evidence-based data are lacking.
In most cases, the prognosis of mucormycosis is poor and has varied mortality rates depending on its form and severity. In the rhinocerebral form, the mortality rate is between 30% and 70%, whereas disseminated mucormycosis presents with the highest mortality rate in an otherwise healthy patient, with a mortality rate of up to 90%. Patients with AIDS have a mortality rate of almost 100%. Possible complications of mucormycosis include the partial loss of neurological function, blindness and clotting of brain or lung vessels.
Dependent on the infectious syndrome, symptoms include fever, fatigue, dry cough, headache, blurred vision, and confusion. Symptom onset is often subacute, progressively worsened over several weeks. The two most common presentations are meningitis (an infection in and around the brain) and pulmonary (lung) infection.
Detection of cryptococcal antigen (capsular material) by culture of CSF, sputum and urine provides definitive diagnosis. Blood cultures may be positive in heavy infections. India ink of the CSF is a traditional microscopic method of diagnosis, although the sensitivity is poor in early infection, and may miss 15-20% of patients with culture-positive cryptococcal meningitis. Unusual morphological forms are rarely seen. Cryptococcal antigen from cerebrospinal fluid is the best test for diagnosis of cryptococcal meningitis in terms of sensitivity. Apart from conventional methods of detection like direct microscopy and culture, rapid diagnostic methods to detect cryptococcal antigen by latex agglutination test, lateral flow immunochromatographic assay (LFA), or enzyme immunoassay (EIA). A new cryptococcal antigen LFA was FDA approved in July 2011. Polymerase chain reaction (PCR) has been used on tissue specimens.
Cryptococcosis can rarely occur in the non-immunosuppressed people, particularly with "Cryptococcus gattii".
Outbreaks of zoonoses have been traced to human interaction with and exposure to animals at fairs, petting zoos, and other settings. In 2005, the Centers for Disease Control and Prevention (CDC) issued an updated list of recommendations for preventing zoonosis transmission in public settings. The recommendations, developed in conjunction with the National Association of State Public Health Veterinarians, include educational responsibilities of venue operators, limiting public and animal contact, and animal care and management.
The most significant zoonotic pathogens causing foodborne diseases are , "Campylobacter", "Caliciviridae", and "Salmonella".
In 2006, a conference held in Berlin was focusing on the issue of zoonotic pathogen effects on food safety, urging governments to intervene, and the public to be vigilant towards the risks of catching food-borne diseases from farm-to-dining table.
Many food outbreaks can be linked to zoonotic pathogens. Many different types of food can be contaminated that have an animal origin. Some common foods linked to zoonotic contaminations include eggs, seafood, meat, dairy, and even some vegetables. Food outbreaks should be handled in preparedness plans to prevent widespread outbreaks and to efficiently and effectively contain outbreaks.
There is no specific treatment for infectious mononucleosis, other than treating the symptoms. In severe cases, steroids such as corticosteroids may be used to control the swelling of the throat and tonsils. Currently, there are no antiviral drugs or vaccines available.
It is important to note that symptoms related to infectious mononucleosis caused by EBV infection seldom last for more than 4 months. When such an illness lasts more than 6 months, it is frequently called chronic EBV infection. However, valid laboratory evidence for continued active EBV infection is seldom found in these patients. The illness should be investigated further to determine if it meets the criteria for chronic fatigue syndrome, or CFS. This process includes ruling out other causes of chronic illness or fatigue.
The heterophile antibody test works by agglutination of red blood cells from guinea pig, sheep and horse. This test is specific but not particularly sensitive (with a false-negative rate of as high as 25% in the first week, 5–10% in the second, and 5% in the third). About 90% of patients have heterophile antibodies by week 3, disappearing in under a year. The antibodies involved in the test do not interact with the Epstein–Barr virus or any of its antigens.
The monospot test is not recommended for general use by the CDC due to its poor accuracy.
A determination of whether or not the person has dehydration is an important part of the assessment, with dehydration typically divided into mild (3–5%), moderate (6–9%), and severe (≥10%) cases. In children, the most accurate signs of moderate or severe dehydration are a prolonged capillary refill, poor skin turgor, and abnormal breathing. Other useful findings (when used in combination) include sunken eyes, decreased activity, a lack of tears, and a dry mouth. A normal urinary output and oral fluid intake is reassuring. Laboratory testing is of little clinical benefit in determining the degree of dehydration. Thus the use of urine testing or ultrasounds is generally not needed.
The 2007 guideline “Official American Thoracic Society (ATS) and Infectious Diseases Society of America (IDSA) statement: diagnosis, treatment, and prevention of non-tuberculosis mycobacterial diseases”, notes that M. fortuitum isolates are usually susceptible to multiple oral antimicrobial agents, including the macrolides and quinolones, doxycycline and minocycline, and sulfonamides. Isolates of this mycobacterium are susceptible to the beta-lactam antibiotics, belonging to the carbopenam subgroup, such as Imipenem. Imipenem is a broad spectrum antibiotic produced by the bacteria Streptomyces cattleya. Ondansetron HCL (Zofran) is an antiemetic often given to offset the nausea and vomiting that are a common side effect of Imipenem. Severe infections require IV treatment combined with oral antibiotics for a prolonged period, up to several months. The guideline recommends “for serious skin, bone, and soft tissue M fortuitum disease, a minimum of 4 months of therapy with at least two agents with in vitro activity against the clinical isolate is necessary to provide a high likelihood of cure. Surgery is generally indicated with extensive disease, abscess formation, or where drug therapy is difficult.”
Because Carrion's disease is often comorbid with "Salmonella" infections, chloramphenicol has historically been the treatment of choice.
Fluoroquinolones (such as ciprofloxacin) or chloramphenicol in adults and chloramphenicol plus beta-lactams in children are the antibiotic regimens of choice during the acute phase of Carrion's disease. Chloramphenicol-resistant "B. bacilliformis" has been observed.
During the eruptive phase, in which chloramphenicol is not useful, azithromycin, erythromycin, and ciprofloxacin have been used successfully for treatment. Rifampin or macrolides are also used to treat both adults and children.
Because of the high rates of comorbid infections and conditions, multiple treatments are often required. These have included the use of corticosteroids for respiratory distress, red blood cell transfusions for anemia, pericardiectomies for pericardial tamponades, and other standard treatments.
Gram-positive, nonmotile and acid-fast rods (1-3 µm x 0.2-0.4 µm). Sometimes long rods with occasional beaded or swollen cells having non-acid-fast ovoid bodies at one end.
Colony characteristics
- Smooth hemispheric colonies, usually off-white or cream colored. May be butyrous, waxy, multilobate and even rosette clustered (dilute inocula).
- On Malachite green containing media, such as Löwenstein-Jensen media, colonies can absorb the green dye.
Physiology
- Rapid growth on Löwenstein-Jensen media within 2–4 days.
- No growth at 45 °C, but grows on MacConkey agar.
Differential characteristics
- Differentiation from "M. fortuitum subsp. acetamidolyticum" by its ability to use L-glutamate and its inability to use acetamide as simultaneous nitrogen and carbon source. Both subspecies share an identical 5'-16S rDNA sequence. However, the ITS sequences are different.
Serologic tests detect antibodies directed against the Epstein–Barr virus. Immunoglobulin G (IgG), when positive, mainly reflects a past infection, whereas immunoglobulin M (IgM) mainly reflects a current infection. EBV-targeting antibodies can also be classified according to which part of the virus they bind to:
- Viral capsid antigen (VCA):
- Early antigen (EA)
- EBV nuclear antigen (EBNA)
When negative, these tests are more accurate than the heterophile antibody test in ruling out infectious mononucleosis. When positive, they feature similar specificity to the heterophile antibody test. Therefore, these tests are useful for diagnosing infectious mononucleosis in people with highly suggestive symptoms and a negative heterophile antibody test.
Gastroenteritis is typically diagnosed clinically, based on a person's signs and symptoms. Determining the exact cause is usually not needed as it does not alter management of the condition.
However, stool cultures should be performed in those with blood in the stool, those who might have been exposed to food poisoning, and those who have recently traveled to the developing world. It may also be appropriate in children young than 5, old people, and those with poor immune function. Diagnostic testing may also be done for surveillance. As hypoglycemia occurs in approximately 10% of infants and young children, measuring serum glucose in this population is recommended. Electrolytes and kidney function should also be checked when there is a concern about severe dehydration.