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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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There is no vaccine for SARS to date. Isolation and quarantine remain the most effective means to prevent the spread of SARS. Other preventative measures include:
- Handwashing
- Disinfection of surfaces for fomites
- Wearing a surgical mask
- Avoiding contact with bodily fluids
- Washing the personal items of someone with SARS in hot, soapy water (eating utensils, dishes, bedding, etc.)
- Keeping children with symptoms home from school
Many public health interventions were taken to help control the spread of the disease; which is mainly spread through respiratory droplets in the air. These interventions included earlier detection of the disease, isolation of people who are infected, droplet and contact precautions, and the use of personal protective equipment (PPE); including masks and isolation gowns. A screening process was also put in place at airports to monitor air travel to and from affected countries. Although no cases have been identified since 2004, the CDC is still working to make federal and local rapid response guidelines and recommendations in the event of a reappearance of the virus.
Antibiotics are ineffective, as SARS is a viral disease. Treatment of SARS is largely supportive with antipyretics, supplemental oxygen and mechanical ventilation as needed.
People with SARS must be isolated, preferably in negative pressure rooms, with complete barrier nursing precautions taken for any necessary contact with these patients.
Some of the more serious damage caused by SARS may be due to the body's own immune system reacting in what is known as cytokine storm.
As of 2017, there is no cure or protective vaccine for SARS that has been shown to be both safe and effective in humans. The identification and development of novel vaccines and medicines to treat SARS is a priority for governments and public health agencies around the world. MassBiologics, a non-profit organization engaged in the discovery, development and manufacturing of biologic therapies, is cooperating with researchers at NIH and the CDC developed a monoclonal antibody therapy that demonstrated efficacy in animal models.
Human-to-human transmission of SARS-CoV-2 has been confirmed during the 2019–20 coronavirus pandemic. Transmission occurs primarily via respiratory droplets from coughs and sneezes within a range of about 1.8 metres (6 ft). Indirect contact via contaminated surfaces is another possible cause of infection. Preliminary research indicates that the virus may remain viable on plastic and steel for up to three days, but does not survive on cardboard for more than one day or on copper for more than four hours; the virus is inactivated by soap, which destabilises its lipid bilayer. Viral RNA has also been found in stool samples from infected individuals.
The degree to which the virus is infectious during the incubation period is uncertain, but research has indicated that the pharynx reaches peak viral load approximately four days after infection. On 1 February 2020, the World Health Organization (WHO) indicated that "transmission from asymptomatic cases is likely not a major driver of transmission". However, an epidemiological model of the beginning of the outbreak in China suggested that "pre-symptomatic shedding may be typical among documented infections" and that subclinical infections may have been the source of a majority of infections.
There is some evidence of human-to-animal transmission of SARS-CoV-2, including examples in felids. Some institutions have advised those infected with SARS-CoV-2 to restrict contact with animals.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus strain that causes coronavirus disease 2019 (COVID-19), a respiratory illness. It is colloquially known as the coronavirus, and was previously referred to by its provisional name 2019 novel coronavirus (2019-nCoV). SARS-CoV-2 is a positive-sense single-stranded RNA virus. It is contagious in humans, and the World Health Organization (WHO) has designated the ongoing pandemic of COVID-19 a Public Health Emergency of International Concern. Because the strain was first discovered in Wuhan, China, it is sometimes referred to as "Wuhan virus" or "Wuhan coronavirus". Since the WHO discourages the use of names based on locations such as MERS, and to avoid confusion with the disease SARS, it sometimes refers to SARS-CoV-2 as "the COVID-19 virus" in public health communications. The general public frequently calls both SARS-CoV-2 and the disease it causes "coronavirus", but scientists typically use more precise terminology.
Taxonomically, SARS-CoV-2 is a strain of Severe acute respiratory syndrome-related coronavirus (SARSr-CoV). It is believed to have zoonotic origins and has close genetic similarity to bat coronaviruses, suggesting it emerged from a bat-borne virus. An intermediate animal reservoir such as a pangolin is also thought to be involved in its introduction to humans. The virus shows little genetic diversity, indicating that the spillover event introducing SARS-CoV-2 to humans is likely to have occurred in late 2019.
Epidemiological studies estimate each infection results in 1.4 to 3.9 new ones when no members of the community are immune and no preventive measures taken. The virus is primarily spread between people through close contact and via respiratory droplets produced from coughs or sneezes. It mainly enters human cells by binding to the receptor angiotensin converting enzyme 2 (ACE2).
The best prevention against viral pneumonia is vaccination against influenza, adenovirus, chickenpox, herpes zoster, measles, and rubella.
Neither the combination of antivirals and interferons (ribavirin + interferon alfa-2a or interferon alfa-2b) nor corticosteroids improved outcomes.
When rhesus macaques were given interferon-α2b and ribavirin and exposed to MERS, they developed less pneumonia than control animals. Five critically ill people with MERS in Saudi Arabia with ARDS and on ventilators were given interferon-α2b and ribavirin but all ended up dying of the disease. The treatment was started late in their disease (a mean of 19 days after hospital admission) and they had already failed trials of steroids so it remains to be seen whether it may have benefit earlier in the course of disease. Another proposed therapy is inhibition of viral protease or kinase enzymes. Researchers are investigating a number of ways to combat the outbreak of Middle East respiratory syndrome coronavirus, including using interferon, chloroquine, chlorpromazine, loperamide, and lopinavir, as well as other agents such as mycophenolic acid and camostat.
In cases of viral pneumonia where influenza A or B are thought to be causative agents, patients who are seen within 48 hours of symptom onset may benefit from treatment with oseltamivir or zanamivir. Respiratory syncytial virus (RSV) has no direct acting treatments, but ribavirin in indicated for severe cases. Herpes simplex virus and varicella-zoster virus infections are usually treated with aciclovir, whilst ganciclovir is used to treat cytomegalovirus. There is no known efficacious treatment for pneumonia caused by SARS coronavirus, MERS coronavirus, adenovirus, hantavirus, or parainfluenza. Care is largely supportive.
While the mechanism of spread of MERS-CoV is currently not known, based on experience with prior coronaviruses, such as SARS, the WHO currently recommends that all individuals coming into contact with MERS suspects should (in addition to standard precautions):
- Wear a medical mask
- Wear eye protection (i.e. goggles or a face shield)
- Wear a clean, non sterile, long sleeved gown; and gloves (some procedures may require sterile gloves)
- Perform hand hygiene before and after contact with the person and his or her surroundings and immediately after removal of personal protective equipment (PPE)
For procedures which carry a risk of aerosolization, such as intubation, the WHO recommends that care providers also:
- Wear a particulate respirator and, when putting on a disposable particulate respirator, always check the seal
- Wear eye protection (i.e. goggles or a face shield)
- Wear a clean, non-sterile, long-sleeved gown and gloves (some of these procedures require sterile gloves)
- Wear an impermeable apron for some procedures with expected high fluid volumes that might penetrate the gown
- Perform procedures in an adequately ventilated room; i.e. minimum of 6 to 12 air changes per hour in facilities with a mechanically ventilated room and at least 60 liters/second/patient in facilities with natural ventilation
- Limit the number of persons present in the room to the absolute minimum required for the person’s care and support
- Perform hand hygiene before and after contact with the person and his or her surroundings and after PPE removal.
The duration of infectivity is also unknown so it is unclear how long people must be isolated, but current recommendations are for 24 hours after resolution of symptoms. In the SARS outbreak the virus was not cultured from people after the resolution of their symptoms.
It is believed that the existing SARS research may provide a useful template for developing vaccines and therapeutics against a MERS-CoV infection. Vaccine candidates are currently awaiting clinical trials.
No medications or vaccine is approved to treat the disease. International research on vaccines and medicines in COVID-19 are underway by government organisations, academic groups and industry researchers. In March, the World Health Organization initiated the "SOLIDARITY Trial" to assess treatment effects of four existing antiviral compounds with the most promise of efficacy.
There is no available vaccine, but various agencies are actively developing vaccine candidates. Previous work on SARS-CoV is being utilised because SARS-CoV and SARS-CoV-2 both use the ACE2 receptor to enter human cells. There are three vaccination strategies being investigated. First, researchers aim to build a whole virus vaccine. The use of such a virus, be it inactive or dead, aims to elicit a prompt immune response of the human body to a new infection with COVID-19. A second strategy, subunit vaccines, aims to create a vaccine that sensitises the immune system to certain subunits of the virus. In the case of SARS-CoV-2, such research focuses on the S-spike protein that helps the virus intrude the ACE2 enzyme receptor. A third strategy is that of the nucleic acid vaccines (DNA or RNA vaccines, a novel technique for creating a vaccination). Experimental vaccines from any of these strategies would have to be tested for safety and efficacy.
On 16 March 2020, the first clinical trial of a vaccine started with four volunteers in Seattle. The vaccine contains a harmless genetic code copied from the virus that causes the disease.
Antibody dependent enhancement has been suggested as a potential challenge for vaccine development for SARS-COV-2, but this is controversial.
Unfortunately a vaccine for malignant catarrhal fever (MCF) has not yet been developed. Developing a vaccine has been difficult because the virus will not grow in cell culture and until recently it was not known why. Researchers at the Agricultural Research Service (ARS) found that the virus undergoes changes within the animal's body, a process known as "cell tropism switching". In cell tropism switching, the virus targets different cells at different points in its life cycle. This phenomenon explains why it has been impossible to grow the virus on any one particular cell culture.
Because the virus is transmitted from sheep to bison and cattle, researchers are first focusing on the viral life cycle in sheep. The viral life cycle is outlined in three stages: entry, maintenance, and shedding. Entry occurs through the sheep's nasal cavity and enters into the lungs where it replicates. The virus undergoes a tropic change and infects lymphocytes, also known as white blood cells, which play a role in the sheep's immune system. In the maintenance stage the virus remains on the sheep's lymphocytes and circulates the body. Finally, during the shedding stage, the virus undergoes another change and shifts its target cells from lymphocytes to nasal cavity cells, where it is then shed through nasal secretions. This discovery undoubtedly puts scientists on the right track for developing a vaccine – starting with the correct cell culture for each stage of the virus lifecycle – but ARS researchers are also looking into alternative methods to develop a vaccine. Researchers are experimenting with the MCF virus that infects topi (an African antelope) because it will grow in cell culture and does not infect cattle. Researchers hope that inserting genes from the sheep MCF virus into the topi MCF virus will ultimately be an effective MCF vaccine for cattle and bison. While there is much ground left to cover, scientists are getting closer and closer to developing a vaccine.
Bovine malignant catarrhal fever (BMCF) is a fatal lymphoproliferative disease caused by a group of ruminant gamma herpes viruses including Alcelaphine gammaherpesvirus 1 (AlHV-1) and Ovine gammaherpesvirus 2 (OvHV-2) These viruses cause unapparent infection in their reservoir hosts (sheep with OvHV-2 and wildebeest with AlHV-1), but are usually fatal in cattle and other ungulates such as deer, antelope, and buffalo.
BMCF is an important disease where reservoir and susceptible animals mix. There is a particular problem with Bali cattle in Indonesia, bison in the US and in pastoralist herds in Eastern and Southern Africa.
Disease outbreaks in cattle are usually sporadic although infection of up to 40% of a herd has been reported. The reasons for this are unknown. Some species appear to be particularly susceptible, for example Pére Davids deer, Bali cattle and bison, with many deer dying within 48 hours of the appearance of the first symptoms and bison within three days. In contrast, post infection cattle will usually survive a week or more.
Vaccination helps prevent bronchopneumonia, mostly against influenza viruses, adenoviruses, measles, rubella, streptococcus pneumoniae, haemophilus influenzae, diphtheria, bacillus anthracis, chickenpox, and bordetella pertussis.
Antibiotics do not help the many lower respiratory infections which are caused by parasites or viruses. While acute bronchitis often does not require antibiotic therapy, antibiotics can be given to patients with acute exacerbations of chronic bronchitis. The indications for treatment are increased dyspnoea, and an increase in the volume or purulence of the sputum. The treatment of bacterial pneumonia is selected by considering the age of the patient, the severity of the illness and the presence of underlying disease. Amoxicillin and doxycycline are suitable for many of the lower respiratory tract infections seen in general practice.
Methicillin-resistant Staphylococcus aureus (MRSA) evolved from Methicillin-susceptible Staphylococcus aureus (MSSA) otherwise known as common "S. aureus". Many people are natural carriers of "S. aureus", without being affected in any way. MSSA was treatable with the antibiotic methicillin until it acquired the gene for antibiotic resistance. Though genetic mapping of various strains of MRSA, scientists have found that MSSA acquired the mecA gene in the 1960s, which accounts for its pathogenicity, before this it had a predominantly commensal relationship with humans. It is theorized that when this "S. aureus" strain that had acquired the mecA gene was introduced into hospitals, it came into contact with other hospital bacteria that had already been exposed to high levels of antibiotics. When exposed to such high levels of antibiotics, the hospital bacteria suddenly found themselves in an environment that had a high level of selection for antibiotic resistance, and thus resistance to multiple antibiotics formed within these hospital populations. When "S. aureus" came into contact with these populations, the multiple genes that code for antibiotic resistance to different drugs were then acquired by MRSA, making it nearly impossible to control. It is thought that MSSA acquired the resistance gene through the horizontal gene transfer, a method in which genetic information can be passed within a generation, and spread rapidly through its own population as was illustrated in multiple studies. Horizontal gene transfer speeds the process of genetic transfer since there is no need to wait an entire generation time for gene to be passed on. Since most antibiotics do not work on MRSA, physicians have to turn to alternative methods based in Darwinian medicine. However prevention is the most preferred method of avoiding antibiotic resistance. By reducing unnecessary antibiotic use in human and animal populations, antibiotics resistance can be slowed.
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
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
There is some evidence that there may be a relationship between BoDV-1 infection and psychiatric disease.
In 1990, Janice E. Clements and colleagues reported in the journal "Science" that antibodies to a protein encoded by the BoDV-1 genome are found in the blood of patients with behavioral disorders. In the early 1990s, researchers in Germany, America, and Japan conducted an investigation of 5000 patients with psychiatric disorders and 1000 controls, in which a significantly higher percentage of patients than controls were positive for BoDV-1 antibodies. Subsequent studies have also presented evidence for an association between BoDV-1 and human psychiatric disorders. However, not all researchers consider the link between BoDV-1 and human psychiatric disease to be conclusively proven. A recent study found no BoDV-1 antibodies in 62 patients with the deficit form of schizophrenia.
Additional evidence for a role of BoDV-1 in psychiatric disorders comes from reports that the drug amantadine, which is used to treat influenza infections, has had some success in treating depression and clearing BoDV-1 infection. Counter-claims state that Borna virus infections are not cleared by amantadine. The issue is further complicated by the fact that amantadine is also used in the treatment of Parkinson's disease and may have direct effects on the nervous system.
The mode of transmission of BoDV-1/2 is unclear but probably occurs through intranasal exposure to contaminated saliva or nasal secretions. Following infection, individuals may develop Borna disease, or may remain subclinical, possibly acting as a carrier of the virus.
Porcine circoviral disease (PCVD) and Porcine circovirus associated disease (PCVAD), is a disease seen in domestic pigs. This disease causes illness in piglets, with clinical signs including progressive loss of body condition, visibly enlarged lymph nodes, difficulty in breathing, and sometimes diarrhea, pale skin, and jaundice. PCVD is very damaging to the pig-producing industry and has been reported worldwide. PCVD is caused by porcine circovirus type 2 (PCV-2).
The North American industry endorses "PCVAD" and European use "PCVD" to describe this disease.
Haemorrhagic septicaemia is one of the most economically important pasteurelloses. Haemorrhagic septicaemia in cattle and buffaloes was previously known to be associated with one of two serotypes of "P. multocida": Asian B:2 and African E:2 according to the Carter-Heddleston system, or 6:B and 6:E using the Namioka-Carter system.
The disease occurs mainly in cattle and buffaloes, but has also been reported in goats ("Capra aegagrus hircus"), African buffalo ("Syncerus nanus"), camels, horses and donkeys ("Equus africanus asinus"), in pigs infected by serogroup B, and in wild elephants ("Elephas maximus"). Serotypes B:1 and B:3,4 have caused a septicaemic disease in antelope ("Antilocapra americana") and elk ("Cervus canadensis"), respectively. Serotype B:4 was associated with the disease in bison ("Bison bison").
Serotypes E:2 and B:2 were associated with HS outbreaks in Africa and Asia respectively. Serotype E:2 was reported in Senegal, Mali, Guinea, Ivory Coast, Nigeria, Cameroon, the Central African Republic and Zambia. However, it is now inaccurate to associate outbreaks in Africa with serotype E:2 as many outbreaks of HS in Africa have now been associated with serogroup B. In the same manner, serogroup E has been associated with outbreaks in Asia. For instance, one record of "Asian serotype" (B:2) was reported in Cameroon. Some reports showed that serotype B:2 may be present in some East African countries. Both serogroups B and E have been reported in Egypt and Sudan.
Natural routes of infection are inhalation and/or ingestion. Experimental transmission has succeeded using intranasal aerosol spray or oral drenching. When subcutaneous inoculation is used experimentally, it results in rapid onset of the disease, a shorter clinical course and less marked pathological lesions compared to the longer course of disease and more profound lesions of oral drenching and the intranasal infection by aerosols.
When HS was introduced for the first time into a geographic area, morbidity and mortality rates were high, approaching 100% unless animals were treated in the very early stages of disease.
On post-mortem examination (necropsy), the most obvious gross lesion is subcutaneous oedema in the submandibular and pectoral (brisket) regions. Petechial haemorrhages are found subcutaneously and in the thoracic cavity. In addition, congestion and various degrees of consolidation of the lung may occur. Animals that die within 24–36 hours, have only few petechial haemorrhages on the heart and generalised congestion of the lung, while in animals that die after 72 hours, petechial and ecchymotic haemorrhages were more evident and lung consolidation are more extensive.
CAP may be prevented by treating underlying illnesses increasing its risk, by smoking cessation and vaccination of children and adults. Vaccination against "haemophilus influenzae" and "streptococcus pneumoniae" in the first year of life has reduced their role in childhood CAP. A vaccine against "streptococcus pneumoniae", available for adults, is recommended for healthy individuals over 65 and all adults with COPD, heart failure, diabetes mellitus, cirrhosis, alcoholism, cerebrospinal fluid leaks or who have had a splenectomy. Re-vaccination may be required after five or ten years.
Patients who are vaccinated against "streptococcus pneumoniae", health professionals, nursing-home residents and pregnant women should be vaccinated annually against influenza. During an outbreak, drugs such as amantadine, rimantadine, zanamivir and oseltamivir have been demonstrated to prevent influenza.
Mycoplasma is found more often in younger than in older people.
Older people are more often infected by Legionella.
When influenza outbreaks occur, medications such as amantadine or rimantadine may help prevent the condition; however are associated with side effects. Zanamivir or oseltamivir decrease the chance that those exposed will develop symptoms; however, it is recommended that potential side effects are taken into account.