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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
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.
The Coggins test (agar immunodiffusion) is a sensitive diagnostic test for equine infectious anemia developed by Dr. Leroy Coggins in the 1970s.
Currently, the US does not have an eradication program due to the low rate of incidence. However, many states require a negative Coggins test for interstate travel. In addition, most horse shows and events require a negative Coggins test. Most countries require a negative test result before allowing an imported horse into the country.
Horse owners should verify that all the horses at a breeding farm and or boarding facility have a negative Coggins test before using the services of the facility. A Coggins test should be done on an annual basis. Tests every 6 months are recommended if there is increased traveling.
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.
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.
About 10% of people who present a clinical picture of infectious mononucleosis do not have an acute Epstein–Barr-virus infection. A differential diagnosis of acute infectious mononucleosis needs to take into consideration acute cytomegalovirus infection and "Toxoplasma gondii" infections. Because their management is much the same, it is not always helpful, or possible, to distinguish between Epstein–Barr-virus mononucleosis and cytomegalovirus infection. However, in pregnant women, differentiation of mononucleosis from toxoplasmosis is important, since it is associated with significant consequences for the fetus.
Acute HIV infection can mimic signs similar to those of infectious mononucleosis, and tests should be performed for pregnant women for the same reason as toxoplasmosis.
People with infectious mononucleosis are sometimes misdiagnosed with a streptococcal pharyngitis (because of the symptoms of fever, pharyngitis and adenopathy) and are given antibiotics such as ampicillin or amoxicillin as treatment.
Other conditions from which to distinguish infectious mononucleosis include leukemia, tonsillitis, diphtheria, common cold and influenza (flu).
Chicken respiratory diseases are difficult to differentiate and may not be diagnosed based on respiratory signs and lesions. Other diseases such as mycoplasmosis by Mycoplasma gallisepticum (chronic respiratory disease), Newcastle disease by mesogenic strains of Newcastle diseases virus (APMV-1), avian metapneumovirus, infectious laryngotracheitis, avian infectious coryza in some stages may clinically resemble IB. Similar kidney lesions may be caused by different etiologies, including other viruses, such as infectious bursal disease virus (the cause of Gumboro disease) and toxins (for instance ochratoxins of Aspergillus ochraceus), and dehydration.
In laying hens, abnormal and reduced egg production are also observed in Egg Drop Syndrome 76 (EDS), caused by an Atadenovirus and avian metapneumovirus infections. At present, IB is more common and far more spread than EDS. The large genetic and phenotypic diversity of IBV have been resulting in common vaccination failures. In addition, new strains of IBV, not present in commercial vaccines, can cause the disease in IB vaccinated flocks. Attenuated vaccines will revert to virulence by consecutive passage in chickens in densely populated areas, and may reassort with field strains, generating potentially important variants.
Definitive diagnosis relies on viral isolation and characterization. For virus characterization, recent methodology using genomic amplification (PCR) and sequencing of products, will enable very precise description of strains, according to the oligonucleotide primers designed and target gene. Methods for IBV antigens detection may employ labelled antibodies, such as direct immunofluorescence or immunoperoxidase. Antibodies to IBV may be detected by indirect immunofluorescent antibody test, ELISA and Haemagglutination inhibition (haemagglutinating IBV produced after enzymatic treatment by phospholipase C).
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.
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).
However, simple husbandry changes and practical midge control measures may help break the livestock infection cycle. Housing livestock during times of maximum midge activity (from dusk to dawn) may lead to significantly reduced biting rates. Similarly, protecting livestock shelters with fine mesh netting or coarser material impregnated with insecticide will reduce contact with the midges. The "Culicoides" midges that carry the virus usually breed on animal dung and moist soils, either bare or covered in short grass. Identifying breeding grounds and breaking the breeding cycle will significantly reduce the local midge population. Turning off taps, mending leaks and filling in or draining damp areas will also help dry up breeding sites. Control by trapping midges and removing their breeding grounds may reduce vector numbers. Dung heaps or slurry pits should be covered or removed, and their perimeters (where most larvae are found) regularly scraped.
Symptoms of infectious mononucleosis are fever, sore throat, and swollen lymph glands. Sometimes, a swollen spleen or liver involvement may develop. Heart problems or involvement of the central nervous system occurs only rarely, and infectious mononucleosis is almost never fatal. There are no known associations between active EBV infection and problems during pregnancy, such as miscarriages or birth defects. Although the symptoms of infectious mononucleosis usually resolve in 1 or 2 months, EBV remains dormant or latent in a few cells in the throat and blood for the rest of the person's life. Periodically, the virus can reactivate and is commonly found in the saliva of infected persons. Reactivated and post-latent virus may pass the placental barrier in (also seropositive) pregnant women via macrophages and therefore can infect the fetus. Also re-infection of prior seropositive individuals may occur. In contrast, reactivation in adults usually occurs without symptoms of illness.
EBV also establishes a lifelong dormant infection in some cells of the body's immune system. A late event in a very few carriers of this virus is the emergence of Burkitt's lymphoma and nasopharyngeal carcinoma, two rare cancers. EBV appears to play an important role in these malignancies, but is probably not the sole cause of disease.
Most individuals exposed to people with infectious mononucleosis have previously been infected with EBV and are not at risk for infectious mononucleosis. In addition, transmission of EBV requires intimate contact with the saliva (found in the mouth) of an infected person. Transmission of this virus through the air or blood does not normally occur. The incubation period, or the time from infection to appearance of symptoms, ranges from 4 to 6 weeks. Persons with infectious mononucleosis may be able to spread the infection to others for a period of weeks. However, no special precautions or isolation procedures are recommended, since the virus is also found frequently in the saliva of healthy people. In fact, many healthy people can carry and spread the virus intermittently for life. These people are usually the primary reservoir for person-to-person transmission. For this reason, transmission of the virus is almost impossible to prevent.
The clinical diagnosis of infectious mononucleosis is suggested on the basis of the symptoms of fever, sore throat, swollen lymph glands, and the age of the patient. Usually, laboratory tests are needed for confirmation. Serologic results for persons with infectious mononucleosis include an elevated white blood cell count, an increased percentage of certain atypical white blood cells, and a positive reaction to a "mono spot" test.
Any age may be affected although it is most common in children aged five to fifteen years. By the time adulthood is reached about half the population will have become immune following infection at some time in their past. Outbreaks can arise especially in nursery schools, preschools, and elementary schools. Infection is an occupational risk for school and day-care personnel. There is no vaccine available for human parvovirus B19, though attempts have been made to develop one.
An emerging infectious disease (EID) is an infectious disease whose incidence has increased in the past 20 years and could increase in the near future. Emerging infections account for at least 12% of all human pathogens. EIDs are caused by newly identified species or strains (e.g. Severe acute respiratory syndrome, HIV/AIDS) that may have evolved from a known infection (e.g. influenza) or spread to a new population (e.g. West Nile fever) or to an area undergoing ecologic transformation (e.g. Lyme disease), or be "reemerging" infections, like drug resistant tuberculosis. Nosocomial (hospital-acquired) infections, such as methicillin-resistant Staphylococcus aureus are emerging in hospitals, and extremely problematic in that they are resistant to many antibiotics. Of growing concern are adverse synergistic interactions between emerging diseases and other infectious and non-infectious conditions leading to the development of novel syndemics. Many emerging diseases are zoonotic - an animal reservoir incubates the organism, with only occasional transmission into human populations.
A vaccine is available, called "Chinese Live Attenuated EIA vaccine", developed in China and widely used there since 1983. Another attenuated live virus vaccine is in development in the United States.
Reuse of syringes and needles is a risk factor for transfer of the disease. Currently in the United States, all horses that test positive must be reported to federal authorities by the testing laboratory. EIA-positive horses are infected for life. Options for the horse include sending the horse to a recognized research facility, branding the horse and quarantining it at least 200 yards from other horses for the rest of its life, and euthanizing the horse. Very few quarantine facilities exist, which usually leads to the option of euthanizing the horse. The Florida Research Institute for Equine Nurturing, Development and Safety (a.k.a. F.R.I.E.N.D.S.) is one of the largest such quarantine facilities and is located in south Florida.
The horse industry and the veterinary industry strongly suggest that the risks posed by infected horses, even if they are not showing any clinical signs, are enough of a reason to impose such stringent rules. The precise impacts of the disease on the horse industry are unknown.
Outbreaks in southern Europe have been caused by serotypes 2 and 4, and vaccines are available against these serotypes (ATCvet codes: for sheep, for cattle). However, the disease found in northern Europe (including the UK) in 2006 and 2007 has been caused by serotype 8. Vaccine companies Fort Dodge Animal Health (Wyeth), Merial and Intervet were developing vaccines against serotype 8 (Fort Dodge Animal Health has serotype 4 for sheep, serotype 1 for sheep and cattle and serotype 8 for sheep and cattle) and the associated production facilities. A vaccine for this is now available in the UK, produced by Intervet. Fort Dodge Animal Health has their vaccines available for multiple European Countries (vaccination will start in 2008 in Germany, Belgium, Switzerland, Spain and Italy). However, immunization with any of the available vaccines preclude later serological monitoring of affected cattle populations, a problem which could be resolved using next-generation subunit vaccines currently in development.
In January 2015, Indian researchers launched its vaccine. Named 'Raksha Blu', it will protect the animals against five strains of the ‘bluetongue’ virus prevalent in the country.
Presumptive diagnosis is made by characteristic clinical signs, post mortem lesions, and presence of competent vectors. Laboratory confirmation is by viral isolation, with such techniques as quantitative PCR for detecting viral RNA, antigen capture (ELISA), and immunofluorescence of infected tissues. Serological tests are only useful for detecting recovered animals, as sick animals die before they are able to mount effective immune responses.
The clinical presentation of prion diseases will vary from patient to patient. However, some general characteristics of prion diseases are listed below.
The U.S. Centers for Disease Control and Prevention (CDC) publishes a journal "Emerging Infectious Diseases" that identifies the following factors contributing to disease emergence:
- Microbial adaption; e.g. genetic drift and genetic shift in Influenza A
- Changing human susceptibility; e.g. mass immunocompromisation with HIV/AIDS
- Climate and weather; e.g. diseases with zoonotic vectors such as West Nile Disease (transmitted by mosquitoes) are moving further from the tropics as the climate warms
- Change in human demographics and trade; e.g. rapid travel enabled SARS to rapidly propagate around the globe
- Economic development; e.g. use of antibiotics to increase meat yield of farmed cows leads to antibiotic resistance
- Breakdown of public health; e.g. the current situation in Zimbabwe
- Poverty and social inequality; e.g. tuberculosis is primarily a problem in low-income areas
- War and famine
- Bioterrorism; e.g. 2001 Anthrax attacks
- Dam and irrigation system construction; e.g. malaria and other mosquito borne diseases
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.
Treatment is supportive as the infection is frequently self-limiting. Antipyretics (i.e., fever reducers) are commonly used. The rash usually does not itch but can be mildly painful. There is no specific therapy.
No specific treatment is available, but antibiotics can be used to prevent secondary infections.
Vaccines are available (ATCvet codes: for the inactivated vaccine, for the live vaccine; plus various combinations).
Biosecurity protocols including adequate isolation, disinfection are important in controlling the spread of the disease.
Brazilian hemorrhagic fever (BzHF) is an infectious disease caused by the Sabiá virus, an Arenavirus. The Sabiá virus is one of the arenoviruses from South America to cause hemorrhagic fever. It shares a common progenitor with the Junin virus, Machupo virus, Tacaribe virus, and Guanarito virus. It is an enveloped RNA virus and is highly infectious and lethal. Very little is known about this disease, but it is thought to be transmitted by the excreta of rodents.
There have only been three documented infections of the Sabiá virus, only one of which occurred naturally and the other two cases occurred in the clinical setting. The only naturally occurring case was in 1990, when a female agricultural engineer who was staying in the neighborhood of Jardim Sabiá near São Paulo, Brazil contracted the disease. She presented with hemorrhagic fever and died. Her autopsy showed liver necrosis. A virologist who was studying the woman's disease contracted the virus but survived. Ribavirin was not given in these first two cases. Four years later, in 1994, a researcher was exposed to the virus in a level 3 biohazard facility at Yale University when a centrifuge bottle cracked, leaked, and released aerosolized virus particle. He was successfully treated with ribavirin.
Ribavirin is thought to be effective in treating the illness, similar to other arenaviruses. Compared to the patients who did not receive ribavirin, the patient who was treated with it had a shorter and less severe clinical course. Symptomatic control such as fluids to address dehydration and bleeding may also be required.
The Sabiá virus is a Biosafety Level 4 pathogen.
This virus has also been implicated as a means for bioterrorism, as it can be spread through aerosols.
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.
Some ways to prevent airborne diseases include washing hands, using appropriate hand disinfection, getting regular immunizations against diseases believed to be locally present, wearing a respirator and limiting time spent in the presence of any patient likely to be a source of infection.
Exposure to a patient or animal with an airborne disease does not guarantee receiving the disease. Because of the changes in host immunity and how much the host was exposed to the particles in the air makes a difference to how the disease affects the body.
Antibiotics are not prescribed for patients to control viral infections. They may however be prescribed to a flu patient for instance, to control or prevent bacterial secondary infections. They also may be used in dealing with air-borne bacterial primary infections, such as pneumonic plague.
Additionally the Centers for Disease Control and Prevention (CDC) has told consumers about vaccination and following careful hygiene and sanitation protocols for airborne disease prevention. Consumers also have access to preventive measures like UV Air purification devices that FDA and EPA-certified laboratory test data has verified as effective in inactivating a broad array of airborne infectious diseases. Many public health specialists recommend social distancing to reduce the transmission of airborne infections.
François Madec, a French author, has written many recommendations on how reduce PMWS symptoms. They are mostly measures for disinfection, management, and hygiene, referred to as the "20 Madec Points" [Madec & Waddilove, 2002].
These measures have recently been expanded upon by Dr. David Barcellos, a professor at the Veterinary College in the Universidade Federal do Rio Grande do Sul, Rio Grande do Sul, Brazil. He presented these points at "1st Universidade Federal do Rio Grande do Sul Symposium about swine management, reproduction, and hygiene".
He divided his points by pig growth stage, and they can be loosely summarized as:
- keep the gutters clean
- increase feeder space
- use pens or small cages with solid dividers
- avoid mixing pigs from different origins
- improve the quality of air
- decrease maximum capacity, giving each pig more room
- separate sick animals as soon as possible, and treat them in a hospital pen. If they do not respond to antibiotics in three days, they should be culled
- control access of people and other animals
- reduce invironmental stress factors such as gases and air currents
- use immunizations and preventive medications for secondary agents commonly associated with PMWS