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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Antibody (Ig) ELISAs are used to detect historical BVDV infection; these tests have been validated in serum, milk and bulk milk samples. Ig ELISAs do not diagnose active infection but detect the presence of antibodies produced by the animal in response to viral infection. Vaccination also induces an antibody response, which can result in false positive results, therefore it is important to know the vaccination status of the herd or individual when interpreting results. A standard test to assess whether virus has been circulating recently is to perform an Ig ELISA on blood from 5–10 young stock that have not been vaccinated, aged between 9 and 18 months. A positive result indicates exposure to BVDV, but also that any positive animals are very unlikely to be PI animals themselves. A positive result in a pregnant female indicates that she has previously been either vaccinated or infected with BVDV and could possibly be carrying a PI fetus, so antigen testing of the newborn is vital to rule this out. A negative antibody result, at the discretion of the responsible veterinarian, may require further confirmation that the animal is not in fact a PI.
At a herd level, a positive Ig result suggests that BVD virus has been circulating or the herd is vaccinated. Negative results suggest that a PI is unlikely however this naïve herd is in danger of severe consequences should an infected animal be introduced. Antibodies from wild infection or vaccination persist for several years therefore Ig ELISA testing is more valuable when used as a surveillance tool in seronegative herds.
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).
Antigen ELISA and rtPCR are currently the most frequently performed tests to detect virus or viral antigen. Individual testing of ear tissue tag samples or serum samples is performed. It is vital that repeat testing is performed on positive samples to distinguish between acute, transiently infected cattle and PIs. A second positive result, acquired at least three weeks after the primary result, indicates a PI animal. rtPCR can also be used on bulk tank milk (BTM) samples to detect any PI cows contributing to the tank. It is reported that the maximum number of contributing cows from which a PI can be detected is 300.
Antibiotics are given to treat any bacterial infection present. Cough suppressants are used if the cough is not productive. NSAIDs are often given to reduce fever and upper respiratory inflammation. Prevention is by vaccinating for canine adenovirus, distemper, parainfluenza, and "Bordetella". In kennels, the best prevention is to keep all the cages disinfected. In some cases, such as "doggie daycares" or nontraditional playcare-type boarding environments, it is usually not a cleaning or disinfecting issue, but rather an airborne issue, as the dogs are in contact with each other's saliva and breath. Although most kennels require proof of vaccination, the vaccination is not a fail-safe preventative. Just like human influenza, even after receiving the vaccination, a dog can still contract mutated strains or less severe cases.
Several consequent reports from China on some recovered SARS patients showed severe long-time sequelae exist. The most typical diseases include, among other things, pulmonary fibrosis, osteoporosis, and femoral necrosis, which have led to the complete loss of working ability or even self-care ability of these cases. As a result of quarantine procedures, some of the post-SARS patients have been documented suffering from posttraumatic stress disorder (PTSD) and major depressive disorder.
Dogs will typically recover from kennel cough within a few weeks. However, secondary infections could lead to complications that could do more harm than the disease itself. Several opportunistic invaders have been recovered from the respiratory tracts of dogs with kennel cough, including Streptococcus, Pasteurella, Pseudomonas, and various coliforms. These bacteria have the potential to cause pneumonia or sepsis, which drastically increase the severity of the disease. These complications are evident in thoracic radiographic examinations. Findings will be mild in animals affected only by kennel cough, while those with complications may have evidence of segmental atelectasis and other severe side effects.
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:
- 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.
The best prevention against viral pneumonia is vaccination against influenza, adenovirus, chickenpox, herpes zoster, measles, and rubella.
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.
MERS cases have been reported to have low white blood cell count, and in particular low lymphocytes.
For PCR testing, the WHO recommends obtaining samples from the lower respiratory tract via bronchoalveolar lavage (BAL), sputum sample or tracheal aspirate as these have the highest viral loads. There have also been studies utilizing upper respiratory sampling via nasopharyngeal swab.
Several highly sensitive, confirmatory real-time RT-PCR assays exist for rapid identification of MERS-CoV from patient-derived samples. These assays attempt to amplify upE (targets elements upstream of the E gene), open reading frame 1B (targets the ORF1b gene) and open reading frame 1A (targets the ORF1a gene). The WHO recommends the upE target for screening assays as it is highly sensitive. In addition, hemi-nested sequencing amplicons targeting RdRp (present in all coronaviruses) and nucleocapsid (N) gene (specific to MERS-CoV) fragments can be generated for confirmation via sequencing. Reports of potential polymorphisms in the N gene between isolates highlight the necessity for sequence-based characterization.
The WHO recommended testing algorithm is to start with an upE RT-PCR and if positive confirm with ORF 1A assay or RdRp or N gene sequence assay for confirmation. If both an upE and secondary assay are positive it is considered a confirmed case.
Protocols for biologically safe immunofluorescence assays (IFA) have also been developed; however, antibodies against betacoronaviruses are known to cross-react within the genus. This effectively limits their use to confirmatory applications. A more specific protein-microarray based assay has also been developed that did not show any cross-reactivity against population samples and serum known to be positive for other betacoronaviruses. Due to the limited validation done so far with serological assays, WHO guidance is that "cases where the testing laboratory has reported positive serological test results in the absence of PCR testing or sequencing, are considered probable cases of MERS-CoV infection, if they meet the other conditions of that case definition."
According to World Health Organization, the interim case definition is that a confirmed case is identified in a person with a positive lab test by "molecular diagnostics including either a positive PCR on at least two specific genomic targets or a single positive target with sequencing on a second."
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.
Based on the low variability exhibited among known SARS-CoV-2 genomic sequences, the strain is thought to have been detected by health authorities within weeks of its emergence among the human population in late 2019. The earliest case of infection currently known is thought to have been found on 17 November 2019. The virus subsequently spread to all provinces of China and to more than 150 other countries in Asia, Europe, North America, South America, Africa, and Oceania. Human-to-human transmission of the virus has been confirmed in all of these regions. On 30 January 2020, SARS-CoV-2 was designated a Public Health Emergency of International Concern by the WHO, and on 11 March 2020 the WHO declared it a pandemic.
The basic reproduction number (R0) of the virus has been estimated to be between 1.4 and 3.9. This means that each infection from the virus is expected to result in 1.4 to 3.9 new infections when no members of the community are immune and no preventive measures are taken. The reproduction number may be higher in densely populated conditions such as those found on cruise ships. Many forms of preventive efforts may be employed in specific circumstances in order to reduce the propagation of the virus.
There have been about 82,000 confirmed cases of infection in mainland China. While the proportion of infections that result in confirmed cases or progress to diagnosable disease remains unclear, one mathematical model estimated that on 25 January 2020 75,815 people were infected in Wuhan alone, at a time when the number of confirmed cases worldwide was only 2,015. Before 24 February 2020, over 95% of all deaths from COVID-19 worldwide had occurred in Hubei province, where Wuhan is located. As of 17 April 2020, the percentage had decreased to 2.1%.
As of 17 April 2020, there have been 2,234,109 total confirmed cases of SARS-CoV-2 infection in the ongoing pandemic. The total number of deaths attributed to the virus is 153,379. Many recoveries from confirmed infections go unreported, but at least 567,695 people have recovered from confirmed infections.
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.
Vaccination helps prevent bronchopneumonia, mostly against influenza viruses, adenoviruses, measles, rubella, streptococcus pneumoniae, haemophilus influenzae, diphtheria, bacillus anthracis, chickenpox, and bordetella pertussis.
Diagnosis of BMCF depends on a combination of history and symptoms, histopathology and detection in the blood or tissues of viral antibodies by ELISA or of viral DNA by PCR. The characteristic histologic lesions of MCF are lymphocytic arteritis with necrosis of the blood vessel wall and the presence of large T lymphocytes mixed with other cells. The similarity of MCF clinical signs to other enteric diseases, for example blue tongue, mucosal disease and foot and mouth make laboratory diagnosis of MCF important. The world organisation for animal health recognises histopathology as the definitive diagnostic test, but laboratories have adopted other approaches with recent developments in molecular virology. No vaccine has as yet been developed.
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.
The WHO has published several testing protocols for the disease. The standard method of testing is real-time reverse transcription polymerase chain reaction (rRT-PCR). The test is typically done on respiratory samples obtained by a nasopharyngeal swab; however, a nasal swab or sputum sample may also be used. Results are generally available within a few hours to two days. Blood tests can be used, but these require two blood samples taken two weeks apart and the results have little immediate value. Chinese scientists were able to isolate a strain of the coronavirus and publish the genetic sequence so laboratories across the world could independently develop polymerase chain reaction (PCR) tests to detect infection by the virus. As of 4 April 2020, antibody tests (which may detect active infections and whether a person had been infected in the past) were in development, but not yet widely used. The Chinese experience with testing has shown the accuracy is only 60 to 70%. The FDA in the United States approved the first point-of-care test on 21 March 2020 for use at the end of that month.
Diagnostic guidelines released by Zhongnan Hospital of Wuhan University suggested methods for detecting infections based upon clinical features and epidemiological risk. These involved identifying people who had at least two of the following symptoms in addition to a history of travel to Wuhan or contact with other infected people: fever, imaging features of pneumonia, normal or reduced white blood cell count or reduced lymphocyte count.
A study asked hospitalized COVID-19 patients to cough into a sterile container, thus producing a saliva sample, and detected virus in eleven of twelve patients using RT-PCR. This technique has the potential of being quicker than a swab and involving less risk to health care workers (collection at home or in the car).
Along with laboratory testing, chest CT scans may be helpful to diagnose COVID-19 in individuals with a high clinical suspicion of infection but is not recommended for routine screening. Bilateral multilobar ground-glass opacities with a peripheral, asymmetric and posterior distribution are common in early infection. Subpleural dominance, crazy paving (lobular septal thickening with variable alveolar filling), and consolidation may appear as the disease progresses.
Because FIP is an immune-mediated disease, treatment falls into two categories: direct action against the virus itself and modulation of the immune response.
Diagnosis of effusive FIP has become more straightforward in recent years: detection of viral RNA in a sample of the effusion, by reverse-transcriptase polymerase chain reaction (RT-PCR) is diagnostic of effusive FIP. However, that does require that a sample be sent to an external veterinary laboratory. Within the veterinary hospital there are a number of tests which can rule out a diagnosis of effusive FIP within minutes:
1. Measure the total protein in the effusion: if it is less than 35g/l, FIP is extremely unlikely.
2. Measure the albumin to globulin ratio in the effusion: if it is over 0.8, FIP is ruled out, if it is less than 0.4, FIP is a possible—but not certain—diagnosis
3. Examine the cells in the effusion: if they are predominantly lymphocytes then FIP is excluded as a diagnosis.
Few data are available about microscopic lesions and the pathophysiology of COVID-19. The main pathological findings at autopsy are:
- Macroscopy: pleurisy, pericarditis, lung consolidation and pulmonary oedema
- Four types of severity of viral pneumonia can be observed:
- minor pneumonia: minor serous exudation, minor fibrin exudation
- mild pneumonia: pulmonary oedema, pneumocyte hyperplasia, large atypical pneumocytes, interstitial inflammation with lymphocytic infiltration and multinucleated giant cell formation
- severe pneumonia: diffuse alveolar damage (DAD) with diffuse alveolar exudates. DAD is the cause of acute respiratory distress syndrome (ARDS) and severe hypoxemia.
- healing pneumonia: organisation of exudates in alveolar cavities and pulmonary interstitial fibrosis
- plasmocytosis in BAL
- Blood: disseminated intravascular coagulation (DIC); leukoerythroblastic reaction
- Liver: microvesicular steatosis
Lesions of paravaccinia virus will clear up with little to no scaring after 4 to 8 weeks. An antibiotic may be prescribed by a physician to help prevent bacterial infection of the lesion area. In rare cases, surgical removal of the lesions can be done to help increase rate of healing, and help minimize risk of bacterial or fungal infection. Upon healing, no long term side effects have been reported.
The important factors for successful prevention of GBS-EOD using IAP and the universal screening approach are:
- Reach most pregnant women for antenatal screens
- Proper sample collection
- Using an appropriate procedure for detecting GBS
- Administering a correct IAP to GBS carriers
Most cases of GBS-EOD occur in term infants born to mothers who screened negative for GBS colonization and in preterm infants born to mothers who were not screened, though some false-negative results observed in the GBS screening tests can be due to the test limitations and to the acquisition of GBS between the time of screening and delivery. These data show that improvements in specimen collection and processing methods for detecting GBS are still necessary in some settings. False-negative screening test, along with failure to receive IAP in women delivering preterm with unknown GBS colonization status, and the administration of inappropriate IAP agents to penicillin-allergic women account for most missed opportunities for prevention of cases of GBS-EOD.
GBS-EOD infections presented in infants whose mothers had been screened as GBS culture-negative are particularly worrying, and may be caused by incorrect sample collection, delay in processing the samples, incorrect laboratory techniques, recent antibiotic use, or GBS colonization after the screening was carried out.
Diagnosis of paravaccinia virus will often come from Polymerase chain reaction screening ordered by their physician. However, due to how common paravaccinia virus is in rural areas, individuals typically do not seek professional help in diagnosis. Instead individuals may refer to people with local knowledge of the cattle in their area such as ranchers, or veterinarians who have some familiarity with the infections in the region.
No current culture-based test is both accurate enough and fast enough to be recommended for detecting GBS once labour starts. Plating of swab samples requires time for the bacteria to grow, meaning that this is unsuitable as an intrapartum point-of-care test.
Alternative methods to detect GBS in clinical samples (as vaginorectal swabs) rapidly have been developed, such are the methods based on nucleic acid amplification tests, such as polymerase chain reaction (PCR) tests, and DNA hybridization probes. These tests can also be used to detect GBS directly from broth media, after the enrichment step, avoiding the subculture of the incubated enrichment broth to an appropriate agar plate.
Testing women for GBS colonization using vaginal or rectal swabs at 35–37 weeks of gestation and culturing them in enriched media is not as rapid as a PCR test that would check whether the pregnant woman is carrying GBS at delivery. And PCR tests, allow starting IAP on admission to the labour ward in those women in whom it is not known if they are GBS carriers or not. PCR testing for GBS carriage could, in the future, be sufficiently accurate to guide IAP. However, the PCR technology to detect GBS must be improved and simplified to make the method cost-effective and fully useful as point-of-care testing]] to be carried out in the labour ward (bedside testing). These tests still cannot replace antenatal culture for the accurate detection of GBS carriers.