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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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Viral entry is the earliest stage of infection in the viral life cycle, as the virus comes into contact with the host cell and introduces viral material into the cell. The major steps involved in viral entry are shown below. Despite the variation among viruses, there are several shared generalities concerning viral entry.
In virology, defective interfering particles (DIPs), also known as defective interfering viruses, are spontaneously generated virus mutants in which a critical portion of the particle's genome has been lost due to defective replication. DIPs are derived from and associated with their parent virus, and particles are classed as DIPs if they are rendered non-infectious due to at least one essential gene of the virus being lost or severely damaged as a result of the defection. A DIP can usually still penetrate host cells, but requires another fully functional virus particle (the 'helper' virus) to co-infect a cell with it, in order to provide the lost factors. The existence of DIPs has been known about for decades, and they can occur within nearly every class of both DNA and RNA viruses.
LCMV infection manifests itself in a wide range of clinical symptoms, and may even be asymptomatic for immunocompetent individuals. Onset typically occurs between one or two weeks after exposure to the virus and is followed by a biphasic febrile illness. During the initial or prodromal phase, which may last up to a week, common symptoms include fever, lack of appetite, headache, muscle aches, malaise, nausea, and/or vomiting. Less frequent symptoms include a sore throat and cough, as well as joint, chest, and parotid pain. The onset of the second phase occurs several days after recovery, and consists of symptoms of meningitis or encephalitis. Pathological findings during the first stage consist of leukopenia and thrombocytopenia. During the second phase, typical findings include elevated protein levels, increased leukocyte count, or a decrease in glucose levels of the cerebrospinal fluid).
Occasionally, a patient improves for a few days, then relapses with aseptic meningitis, or very rarely, meningoencephalitis.
Patients with meningitis may have a stiff neck, fever, headache, myalgia, nausea and malaise. In some occasions, meningitis occurs without a prodromal syndrome. Meningoencephalitis is characterized by more profound neurological signs such as confusion, drowsiness, sensory abnormalities and motor signs. Under reported complications include myelitis, Guillain–Barré-type syndrome, cranial nerve palsies, transient or permanent hydrocephalus, sensorineural hearing loss, orchitis, arthritis and parotitis. LCMV infections have also been associated with pancreatitis, pneumonitis, myocarditis and pericarditis. The entire illness usually lasts 1 to 3 weeks, nonetheless, temporary or permanent neurological damage is possible in all central nervous system infections, especially in cases of meningoencephalitis. Chronic infections have not been reported in humans and deaths rarely occur.
Human parainfluenza viruses (HPIVs) are the viruses that cause human parainfluenza. HPIVs are a group of four distinct single-stranded RNA viruses belonging to the Paramyxoviridae family. These viruses are closely associated with both human and veterinary disease. Virions are approximately 150–250 nm in size and contain negative sense RNA with a genome encompassing ~15,000 nucleotides.
The viruses can be detected via cell culture, immunofluorescent microscopy, and PCR. HPIVs remain the second main cause of hospitalisation in children under 5 years of age suffering from a respiratory illness (only respiratory syncytial virus causes more respiratory hospitalisations for this age group).
Pathogenesis occurs in the same manner in hamsters as in mice. Symptoms in hamsters are highly variable, and typically indicate that the pet has been infected and shedding the virus for several months. Early signs may include inactivity, loss of appetite, and a rough coat. As the disease progresses, the animal may experience weight loss, hunched posture, inflammation around the eyes, and eventually death. Alternatively, some infected hamsters may be asymptomatic.
Paravaccinia virus presents itself with blisters, nodules, or lesions about 4 mm in diameter, typically in the area that has made contact with livestock that is infected with bovine papular stomatitis. Lesions may begin forming as late as three weeks after contact has been made with an infected animal. In rare cases, lesions may be seen systemic. General signs of infection are also common, such as fever and fatigue.
Infected livestock may present with blisters or lesions on their udders or snout. Often, however, infected livestock show little to no symptoms.
Avian reoviruses belong to the genus "Orthoreovirus", and "Reoviridae" family. They are non-enveloped viruses that undergo replication in the cytoplasm of infected cells. It has icosahedral symmetry and contains a double-shelled arrangement of surface protein. Virus particles can range between 70–80 nm. Morphologically, the virus is a double stranded RNA virus that is composed of ten segments. The genome and proteins that are encoded by the genome can be separated into three different sizes ranging from small, medium, or large. Of the eleven proteins that are encoded for by the genome, two are nonstructural, while the remaining nine are structural.
Avian reoviruses can withstand a pH range of 3.0–9.0. Ambient temperatures are suitable for the survival of these viruses, which become inactive at 56 °C in less than an hour. Common areas where this virus can survive include galvanized metal, glass, rubber, feathers, and wood shavings. Avian reovirus can survive for up to ten days on these common areas in addition to up to ten weeks in water.
Cultivation and observation of the effects of avian reovirus is most often performed in chicken embryos. If infected into the yolk sac, the embryo will succumb to death accompanied by hemorrhaging of the embryos and cause the foci on the liver to appear yellowish-green. There are several primary chicken cell cultures/areas that are susceptible to avian reoviruses, which include the lungs, liver, kidney, and fibroblasts of the chick embryo. Of the following susceptible areas, liver cells from the chick embryo have been found to be the most sensitive for primary isolation from clinical material.
Typically, the CPE effect of avian reoviruses is the production of syncytia. CPE, or cytopathic effects are the visible changes in a host cell that takes place because of viral infection. Syncytia is a single cell or cytoplasmic mass containing several nuclei, formed by fusion of cells or by division of nuclei.
The first HPIV was discovered in the late 1950s. The taxonomic division is broadly based on antigenic and genetic characteristics, forming four major serotypes or clades, which today are considered distinct viruses. These include:
HPIVs belong to two genera: "Respirovirus" (HPIV-1 & HPIV-3) and "Rubulavirus" (HPIV-2 & HPIV-4).
The most detailed study on the frequency, onset, and duration of MVD clinical signs and symptoms was performed during the 1998–2000 mixed MARV/RAVV disease outbreak. A maculopapular rash, petechiae, purpura, ecchymoses, and hematomas (especially around needle injection sites) are typical hemorrhagic manifestations. However, contrary to popular belief, hemorrhage does not lead to hypovolemia and is not the cause of death (total blood loss is minimal except during labor). Instead, death occurs due to multiple organ dysfunction syndrome (MODS) due to fluid redistribution, hypotension, disseminated intravascular coagulation, and focal tissue necroses.
Clinical phases of Marburg Hemorrhagic Fever's presentation are described below. Note that phases overlap due to variability between cases.
1. Incubation: 2–21 days, averaging 5–9 days.
2. Generalization Phase: Day 1 up to Day 5 from onset of clinical symptoms. MHF presents with a high fever (~40˚C) and a sudden, severe headache, with accompanying chills, fatigue, nausea, vomiting, diarrhea, pharyngitis, maculopapular rash, abdominal pain, conjunctivitis, & malaise.
3. Early Organ Phase: Day 5 up to Day 13. Symptoms include prostration, dyspnea, edema, conjunctival injection, viral exanthema, and CNS symptoms, including encephalitis, confusion, delirium, apathy, and aggression. Hemorrhagic symptoms typically occur late and herald the end of the early organ phase, leading either to eventual recovery or worsening & death. Symptoms include bloody stools, ecchymoses, blood leakage from venipuncture sites, mucosal & visceral hemorrhaging, and possibly hematemesis.
4. Late Organ Phase: Day 13 up to Day 21+. Symptoms bifurcate into two constellations for survivors & fatal cases. Survivors will enter a convalescence phase, experiencing myalgia, fibromyalgia, hepatitis, asthenia, ocular symptoms, & psychosis. Fatal cases continue to deteriorate, experiencing continued fever, obtundation, coma, convulsions, diffuse coagulopathy, metabolic disturbances, shock and death, with death typically occurring between Days 8 and 16.
Oropouche fever is characterized as a acute febrile illness, meaning that it begins with a sudden onset of a fever followed by severe clinical symptoms. It typically takes 4 to 8 days from the incubation period to first start noticing signs of infection, beginning from the bite of the infected mosquito or midge.
Fevers are the most common symptom with temperatures as high as 104F. Clinical symptoms include chills, headache, myalgia, arthralgia, dizziness, photophobia, vomiting, joint pains, epigastric pain, and rashes.
There also have been some cases where rashes resembles rubella and patients presented systematic symptoms including nausea, vomiting, diarrhea, conjunctive congestion, epigastric pain, and retro-orbitial pain.
The initial febrile episode typically passes after a few days, but it is very common to have a reoccurrence of these symptoms with a lesser intensity. Studies have shown this typically happens in about 60% of cases.
Signs and symptoms may vary and some individuals may not experience any symptoms at all. The most common reported symptom of polioencephalitis is fatigue. Fatigue is associated with difficulty in attention, cognition, and maintaining wakefulness Some individuals experience psychiatric symptoms that include anxious mood, pain, insomnia, and depressed mood. Confusion and disorientation of time and space have also been reported. Motor symptoms vary more from patient to patient, but can include incoordination and tremors, nystagmus, loss of conjugate eye movements, rigidity and hemiparesis.
There are several diseases that are caused by avian reovirus, which includes, avian arthritis/tenosynovitis, runting-stunting syndrome, and blue wing disease in chickens. Blue wing disease affects young broiler chickens and has an average mortality rate of 10%. It causes intramuscular and subcutaneous hemorrhages and atrophy of the spleen, bursa of Fabricius, and thymus. When young chickens are experimentally infected with avian reovirus, it is spread rapidly throughout all tissues. This virus is spread most frequently in the skin and muscles, which is also the most obvious site for lesions. Avian arthritis causes significant lameness in joints, specifically the hock joints. In the most severe cases, viral arthritis has caused the tendon to rupture. Chickens that have contracted runting-stunting syndrome cause a number of individuals in a flock to appear noticeably small due to its delayed growth. Diseased chicks are typically pale, dirty, wet, and may have a distending abdomen. Some individuals may display “helicopter-like” feathers in their wings and other feather abnormalities. The virus has also been shown to cause osteoporosis.
Marburg virus is a hemorrhagic fever virus of the "Filoviridae" family of viruses and a member of the species "Marburg marburgvirus", genus "Marburgvirus". Marburg virus (MARV) causes Marburg virus disease in humans and nonhuman primates, a form of viral hemorrhagic fever. Considered to be extremely dangerous, the WHO rates it as a Risk Group 4 Pathogen (requiring biosafety level 4-equivalent containment). In the United States, the NIH/National Institute of Allergy and Infectious Diseases ranks it as a Category A Priority Pathogen and the Centers for Disease Control and Prevention lists it as a Category A Bioterrorism Agent. It is also listed as a biological agent for export control by the Australia Group.
The virus can be transmitted by exposure to one species of fruit bats or it can be transmitted between people via body fluids through unprotected copulation and broken skin. The disease can cause bleeding (haemorrhage), fever and other symptoms much like Ebola. Funeral rituals are a particular risk. Actual treatment of the virus after infection is not possible but early, professional treatment of symptoms like dehydration considerably increase survival chances.
In 2009, expanded clinical trials of an Ebola and Marburg vaccine began in Kampala, Uganda.
Paravaccinia virus is a viral infection of the Parapoxvirus genus of viruses. Human can contract the virus from contact with livestock infected with Bovine papular stomatitis and is common with ranchers, milkers, and veterinarians. Infection will present with fever, fatigue, and lesion on the skin.
Characteristics of a viral infection can include pain, swelling, redness, impaired function, fever, drowsiness, confusion and convulsions.
An oncovirus is a virus that can cause cancer. This term originated from studies of acutely transforming retroviruses in the 1950–60s, often called oncornaviruses to denote their RNA virus origin.
It now refers to any virus with a DNA or RNA genome causing cancer and is synonymous with "tumor virus" or "cancer virus". The vast majority of human and animal viruses do not cause cancer, probably because of longstanding co-evolution between the virus and its host. Oncoviruses have been important not only in epidemiology, but also in investigations of cell cycle control mechanisms such as the Retinoblastoma protein.
The World Health Organization's International Agency for Research on Cancer estimated that in 2002, infection caused 17.8% of human cancers, with 11.9% caused by one of seven viruses. These cancers might be easily prevented through vaccination (e.g., papillomavirus vaccines), diagnosed with simple blood tests, and treated with less-toxic antiviral compounds.
The incubation period of the chikungunya virus ranges from one to twelve days, and is most typically three to seven. The disease may be asymptomatic, but generally is not, as 72% to 97% of those infected will develop symptoms. Characteristic symptoms include sudden onset with high fever, joint pain, and rash. Other symptoms may occur, including headache, fatigue, digestive complaints, and conjunctivitis.
Information gained during recent epidemics suggests that chikungunya fever may result in a chronic phase as well as the phase of acute illness. Within the acute phase, two stages have been identified: a viral stage during the first five to seven days, during which viremia occurs, followed by a convalescent stage lasting approximately ten days, during which symptoms improve and the virus cannot be detected in the blood. Typically, the disease begins with a sudden high fever that lasts from a few days to a week, and sometimes up to ten days. The fever is usually above and sometimes reaching and may be biphasic—lasting several days, breaking, and then returning. Fever occurs with the onset of viremia, and the level of virus in the blood correlates with the intensity of symptoms in the acute phase. When IgM, an antibody that is a response to the initial exposure to an antigen, appears in the blood, viremia begins to diminish. However, headache, insomnia and an extreme degree of exhaustion remain, usually about five to seven days.
Following the fever, strong joint pain or stiffness occurs; it usually lasts weeks or months, but may last for years. The joint pain can be debilitating, often resulting in near immobility of the affected joints. Joint pain is reported in 87–98% of cases, and nearly always occurs in more than one joint, though joint swelling is uncommon. Typically the affected joints are located in both arms and legs, and are affected symmetrically. Joints are more likely to be affected if they have previously been damaged by disorders such as arthritis. Pain most commonly occurs in peripheral joints, such as the wrists, ankles, and joints of the hands and feet as well as some of the larger joints, typically the shoulders, elbows and knees. Pain may also occur in the muscles or ligaments.
Rash occurs in 40–50% of cases, generally as a maculopapular rash occurring two to five days after onset of symptoms. Digestive symptoms, including abdominal pain, nausea, vomiting or diarrhea, may also occur. In more than half of cases, normal activity is limited by significant fatigue and pain. Infrequently, inflammation of the eyes may occur in the form of iridocyclitis, or uveitis, and retinal lesions may occur.
Temporary damage to the liver may occur.
Rarely, neurological disorders have been reported in association with chikungunya virus, including Guillain–Barré syndrome, palsies, meningoencephalitis, flaccid paralysis and neuropathy. In contrast to dengue fever, Chikungunya fever very rarely causes hemorrhagic complications. Symptoms of bleeding should lead to consideration of alternative diagnoses or co-infection with dengue fever or coexisting congestive hepatopathy.
West Nile virus (WNV) is a single-stranded RNA virus that causes West Nile fever. It is a member of the family Flaviviridae, specifically from the genus Flavivirus which also contain the Zika virus, dengue virus, and the yellow fever virus. The West Nile virus is primarily transmitted through mosquitoes, mostly by the Culex species. However, ticks have been found to carry the virus. The primary hosts of WNV are birds, so that the virus remains within a "bird-mosquito-bird" transmission cycle.
The most common diseases caused by chronic viral infections are subacute-sclerosing panencephalitis, progressive multifocal leukoencephalopathy, retrovirus disease and spongiform encephalopathies.
Viremia (UK: viraemia) is a medical condition where viruses enter the bloodstream and hence have access to the rest of the body. It is similar to "bacteremia", a condition where bacteria enter the bloodstream. The name comes from combining the word virus with the Greek word for blood ("haima"). It usually lasts for 4 to 5 days in the primary condition.
Marburg virus disease (MVD) is the official name listed in the World Health Organization's International Statistical Classification of Diseases and Related Health Problems 10 (ICD-10) for the human disease caused by any of the two marburgviruses Marburg virus (MARV) and Ravn virus (RAVV). In the scientific literature, Marburg hemorrhagic fever (MHF) is often used as an unofficial alternative name for the same disease. Both disease names are derived from the German city Marburg, where MARV was first discovered.
The mortality rate of chikungunya is slightly less than 1 in 1000. Those over the age of 65, neonates, and those with underlying chronic medical problems are most likely to have severe complications. Neonates are vulnerable as it is possible to vertically transmit chikungunya from mother to infant during delivery, which results in high rates of morbidity, as infants lack fully developed immune systems. The likelihood of prolonged symptoms or chronic joint pain is increased with increased age and prior rheumatological disease.
DIPs are a naturally occurring phenomenon that can also be synthesized for experimental use. They are spontaneously produced by error-prone viral replication, something particularly prevalent in RNA viruses over DNA viruses due to the enzyme used (replicase, or RNA-dependent RNA polymerase.) DI genomes typically retain the termini sequences needed for recognition by viral polymerases, and sequences for packaging of their genome into new particles, but little else. The size of the genomic deletion event can vary greatly, with one such example in a DIP derived from rabies virus exhibiting a 6.1 kb deletion. In another example, the size of several DI-DNA plant virus genomes varied from one tenth of the size of the original genome to one half.
Oropouche fever is a tropical viral infection transmitted by biting midges and mosquitoes from the blood of sloths to humans. This disease is named after the region where it was first discovered and isolated at the Trinidad Regional Virus Laboratory in 1955 by the Oropouche River in Trinidad and Tobago. Oropouche fever is caused by a specific arbovirus, the Oropouche virus (OROV), of the Bunyaviridae family.
Large epidemics are common and very swift, one of the earliest largest having occurred at the city of Belém, in the Brazilian Amazon state of Pará, with 11,000 recorded cases. In the Brazilian Amazon, oropouche is the second most frequent viral disease, after dengue fever. Several epidemics have generated more than 263,000 cases, of which 130,000 alone occurred in the period from 1978 to 1980. Presently, in Brazil alone it is estimated that more than half a million cases have occurred. Nevertheless, clinics in Brazil may not have adequate testing reliability as they rely on symptoms rather than PCR viral sequencing, which is expensive and time consuming, in many cases there may be conviction with other similar mosquito borne viruses.
If someone is suspected of having polioencephalitis a sample of throat secretions, stool or cerebrospinal fluid is checked for the virus. Blood tests can be done to detect antibodies against viral antigens and foreign proteins. Virus isolation is the most sensitive method and it is most likely to be isolated from stool samples. Once isolated, RT-PCR is used to differentiate naturally occurring strains from vaccine-like strains.