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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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Standard titer measles vaccine is recommended at 9 months of age in low-income countries where measles infection is endemic and often fatal. Many observational studies have shown that measles-vaccinated children have substantially lower mortality than can be explained by the prevention of measles-related deaths. Many of these observational studies were natural experiments, such as studies comparing the mortality before and after the introduction of measles vaccine and other studies where logistical factors rather than maternal choice determined whether a child was vaccinated or not.
These findings were later supported in randomized trials from 2003 to 2009 in Guinea-Bissau. An intervention group of children given standard titer measles vaccine at 4.5 and 9 month of age had a 30% reduction in all-cause mortality compared to the children in the control group, which were only vaccinated against measles at 9 month of age.
In a recent WHO-commissioned review based on four randomized trials and 18 observational studies, it was concluded that "There was consistent evidence of a beneficial effect of measles vaccine, although all observational studies were assessed as being at risk of bias and the GRADE rating was of low confidence. There was an apparent difference between the effect in girls and boys, with girls benefitting more from measles vaccination", and furthermore "estimated effects are in the region of a halving of mortality risk" and "if these effects are real then they are not fully explained by deaths that were established as due to measles". Based on the evidence, the WHO's Strategic Advisory Group of Experts on Immunization concluded that "the non-specific effects on all-cause mortality warrant further research".
The live attenuated BCG vaccine developed against tuberculosis has been shown to have strong beneficial effects on the ability to combat non-tuberculosis infections.
Several studies have suggested that BCG vaccination may reduce atopy, particularly when given early in life. Furthermore, in multiple observational studies BCG vaccination has been shown to provide beneficial effects on overall mortality. These observations encouraged randomised controlled trials to examine BCG vaccination's beneficial non-specific effects on overall health. Since BCG vaccination is recommended to be given at birth in countries that have a high incidence of tuberculosis it would have been unethical to randomize children into 'BCG' vs. 'no BCG' groups. However, many low-income countries delay BCG vaccination for low-birth-weight (LBW) infants; this offered the opportunity to directly test the effect of BCG on overall mortality.
In the first two randomised controlled trials receipt of BCG+OPV at birth vs. OPV only ('delayed BCG') was associated with strong reductions in neonatal mortality; these effects were seen as early as 3 days after vaccination. BCG protected against sepsis as well as respiratory infections.
Among BCG vaccinated children, those who develop a BCG scar or a positive skin test (TST) are less likely to develop sepsis and exhibit an overall reduction in child mortality of around 50%.
In a recent WHO-commissioned review based on five clinical trials and nine observational studies, it was concluded that "the results indicated a beneficial effect of BCG on overall mortality in the first 6–12 months of life. Relevant follow-up in some of the trials was short, and all of the observational studies were regarded as being at risk of bias, so the confidence in the findings was rated as very low according to the GRADE criteria and "There was a suggestion that BCG vaccination may be more beneficial the earlier it is given". Furthermore, "estimated effects are in the region of a halving of mortality risk" and "any effect of BCG vaccine on all-cause mortality is not likely to be attributable to any great extent to fewer deaths from tuberculosis (i.e. to a specific effect of BCG vaccine against tuberculosis)". Based on the evidence, the WHO's Strategic Group of Experts on Immunization concluded that "the non-specific effects on all-cause mortality warrant further research".
Because the risk of meningococcal disease is increased among USA's military recruits, all military recruits routinely receive primary immunization against the disease.
In the 2010 recommendations of the international Vaccination Guidelines Group (VGG), they emphasized the importance of administering "non-adjuvanted" vaccines whenever possible.
The VGG also prefers serological testing over unnecessary re-vaccination or boosters of core vaccines after the initial 12-month booster that follows the puppy/kitten series of modified live virus [MLV] vaccines. This is because core vaccines show an excellent correlation between the presence of antibody and protective immunity and have a long DOI (Duration of Immunity). Antibody tests can be used to demonstrate the DOI after vaccination with core vaccines, though not for non-core vaccines.
Vaccines should be given in specific areas in order to: ease identification of which vaccine caused an adverse reaction, and ease removal of any vaccine-associated sarcoma.
In North America, vets adopted the practice of injecting specific limbs as far from the body as possible, with the rear "right for rabies", the rear "left for leukemia", and the right front shoulder (being careful to avoid the midline or interscapular space) for other vaccines (such as FVRCP).
This set of locations was not widely adopted outside of North America, and the international Vaccination Guidelines Group (VGG) made new recommendations that vaccines be administered:
- in subcutaneous (and not intramuscular) sites
- in the skin of the lateral thorax or abdomen (for easier excision of any FISS that occur)
- avoid the interscapular or intercostal regions (as more extensive surgical resection would be needed for sarcomas)
- in a different site on each occasion (either with general locations per species per year or diagrams of where administered on specific visit)
Diagnosis can be made in several ways, encompassing a range of multi-faceted techniques:
- Isolation and detection of the virus in cell culture.
- Detection of viral antigens directly within bodily respiratory tract secretions using immunofluorescence, enzyme immunoassays or fluroimmunoassays.
- Polymerase chain reaction (PCR).
- Analysis of specific IgG antibodies showing a subsequent rise in titre following infection (using paired serum specimens).
Because of the similarity in terms of the antigenic profile between the viruses, hemagglutination assay (HA) or hemadsorption inhibition (HAdI) processes are often used. Both complement fixation, neutralisation and enzyme linked immunosorbent assays – ELISA, can also be used to aid in the process of distinguishing between viral serotypes.
Polymerase chain reaction (PCR) assays have been proven to be more sensitive than either LAT or culture tests, and highly specific. However, PCR assays have not yet become routine in clinical settings. Countercurrent immunoelectrophoresis has been shown to be an effective research diagnostic method, but has been largely supplanted by PCR.
Health care people should receive routine immunization against meningococcal disease for laboratory personnel who are routinely exposed to isolates of "N. meningitidis". Laboratory personnel and medical staff are at risk of exposure to "N. meningitides" or to patients with meningococcal disease. Hospital Infection Control Practices Advisory Committee (HICPAC) recommendations regarding immunization of health-care workers that routine vaccination of health-care personnel is recommended, Any individual 11–55 years of age who wishes to reduce their risk of meningococcal disease may receive meningitis A,C,Y and W-135 vaccines and those older than 55 years of age. Under certain circumstances if unvaccinated health-care personnel cannot get vaccinated and who have intensive contact with oropharyngeal secretions of infected patients and who do not use proper precautions should receive anti-infective prophylaxis against meningococcal infection (i.e., 2-day regimen of oral rifampicin or a single dose of IM ceftriaxone or a single dose of oral ciprofloxacin).
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.
The latex particle agglutination test (LAT) is a more sensitive method to detect "H. influenzae" than is culture. Because the method relies on antigen rather than viable bacteria, the results are not disrupted by prior antibiotic use. It also has the added benefit of being much quicker than culture methods. However, antibiotic sensitivity testing is not possible with LAT alone, so a parallel culture is necessary.
Rubella virus specific IgM antibodies are present in people recently infected by rubella virus, but these antibodies can persist for over a year, and a positive test result needs to be interpreted with caution. The presence of these antibodies along with, or a short time after, the characteristic rash confirms the diagnosis.
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.
Diagnosis of infection with rotavirus normally follows diagnosis of gastroenteritis as the cause of severe diarrhoea. Most children admitted to hospital with gastroenteritis are tested for
Specific diagnosis of infection with is made by finding the virus in the child's stool by enzyme immunoassay. There are several licensed test kits on the market which are sensitive, specific and detect all serotypes of . Other methods, such as electron microscopy and PCR (polymerase chain reaction), are used in research laboratories. Reverse transcription-polymerase chain reaction (RT-PCR) can detect and identify all species and serotypes of human rotavirus.
Although infection of avian reovirus is spread worldwide, it is rarely the sole cause of a disease. For chickens, the most common manifestation of the disease is joint/limb lameness. Confirming infection of avian reovirus can be detected through an ELISA test by using and observing the expression of σC and σB proteins. However, isolating and identifying reoviruses from tissue samples is very time consuming. Isolation is most successfully attained through inoculation of material into chick embryo cultures or fertile chicken eggs. Inoculation of embryonic eggs through the yolk sac has shown that the virus usually kills the embryos within 5 or 6 days post inoculation. Analyzing the samples, the embryos appeared hemorrhagic and necrotic lesions on the liver were present. (Jones, Onunkwo, 1978). There have also been approaches to identify avian reoviruses molecularly by observing infected tissues with dot-blot hybridization, PCR, and a combination of PCR and RFLP. This combination allows for the reovirus strain to be typed.
A physician's overall impression is most effective in initially making the diagnosis. Single factors are much less useful.
Methods used in laboratory diagnosis include culturing of nasopharyngeal swabs on a nutrient medium (Bordet-Gengou medium), polymerase chain reaction (PCR), direct fluorescent antibody (DFA), and serological methods (e.g. complement fixation test). The bacteria can be recovered from the person only during the first three weeks of illness, rendering culturing and DFA useless after this period, although PCR may have some limited usefulness for an additional three weeks.
Serology may be used for adults and adolescents who have already been infected for several weeks to determine whether antibody against pertussis toxin or another virulence factor of "B. pertussis" is present at high levels in the blood of the person. By this stage, they have been contagious for some weeks and may have spread the infection to many people. Because of this, adults, who are not in great danger from pertussis, are increasingly being encouraged to be vaccinated.
A similar, milder disease is caused by "B. parapertussis".
The primary method of prevention for pertussis is vaccination. Evidence is insufficient to determine the effectiveness of antibiotics in those who have been exposed, but are without symptoms. Preventive antibiotics, however, are still frequently used in those who have been exposed and are at high risk of severe disease (such as infants).
Despite decades of research, no vaccines currently exist.
Recombinant technology has however been used to target the formation of vaccines for HPIV-1, -2 and -3 and has taken the form of several live-attenuated intranasal vaccines. Two vaccines in particular were found to be immunogenic and well tolerated against HPIV-3 in phase I trials. HPIV-1 and -2 vaccine candidates remain less advanced.
Vaccine techniques which have been used against HPIVs are not limited to intranasal forms, but also viruses attenuated by cold passage, host range attenuation, chimeric construct vaccines and also introducing mutations with the help of reverse genetics to achieve attenuation.
Maternal antibodies may offer some degree of protection against HPIVs during the early stages of life via the colostrum in breast milk.
If a person with ILI also has either a history of exposure or an occupational or environmental risk of exposure to "Bacillus anthracis" (anthrax), then a differential diagnosis requires distinguishing between ILI and anthrax. Other rare causes of ILI include leukemia and metal fume fever.
MVD is clinically indistinguishable from Ebola virus disease (EVD), and it can also easily be confused with many other diseases prevalent in Equatorial Africa, such as other viral hemorrhagic fevers, falciparum malaria, typhoid fever, shigellosis, rickettsial diseases such as typhus, cholera, gram-negative septicemia, borreliosis such as relapsing fever or EHEC enteritis. Other infectious diseases that ought to be included in the differential diagnosis include leptospirosis, scrub typhus, plague, Q fever, candidiasis, histoplasmosis, trypanosomiasis, visceral leishmaniasis, hemorrhagic smallpox, measles, and fulminant viral hepatitis. Non-infectious diseases that can be confused with MVD are acute promyelocytic leukemia, hemolytic uremic syndrome, snake envenomation, clotting factor deficiencies/platelet disorders, thrombotic thrombocytopenic purpura, hereditary hemorrhagic telangiectasia, Kawasaki disease, and even warfarin intoxication. The most important indicator that may lead to the suspicion of MVD at clinical examination is the medical history of the patient, in particular the travel and occupational history (which countries and caves were visited?) and the patient's exposure to wildlife (exposure to bats or bat excrements?). MVD can be confirmed by isolation of marburgviruses from or by detection of marburgvirus antigen or genomic or subgenomic RNAs in patient blood or serum samples during the acute phase of MVD. Marburgvirus isolation is usually performed by inoculation of grivet kidney epithelial Vero E6 or MA-104 cell cultures or by inoculation of human adrenal carcinoma SW-13 cells, all of which react to infection with characteristic cytopathic effects. Filovirions can easily be visualized and identified in cell culture by electron microscopy due to their unique filamentous shapes, but electron microscopy cannot differentiate the various filoviruses alone despite some overall length differences. Immunofluorescence assays are used to confirm marburgvirus presence in cell cultures. During an outbreak, virus isolation and electron microscopy are most often not feasible options. The most common diagnostic methods are therefore RT-PCR in conjunction with antigen-capture ELISA, which can be performed in field or mobile hospitals and laboratories. Indirect immunofluorescence assays (IFAs) are not used for diagnosis of MVD in the field anymore.
Diagnosis of infection with rotavirus normally follows diagnosis of gastroenteritis as the cause of severe diarrhoea. Most children admitted to hospital with gastroenteritis are tested for
Specific diagnosis of infection with is made by finding the virus in the child's stool by enzyme immunoassay. There are several licensed test kits on the market which are sensitive, specific and detect all serotypes of . Other methods, such as electron microscopy and PCR, are used in research laboratories. Reverse transcription-polymerase chain reaction (RT-PCR) can detect and identify all species and serotypes of human rotavirus.
Rubella infections are prevented by active immunisation programs using live attenuated virus vaccines. Two live attenuated virus vaccines, RA 27/3 and Cendehill strains, were effective in the prevention of adult disease. However their use in prepubertal females did not produce a significant fall in the overall incidence rate of CRS in the UK. Reductions were only achieved by immunisation of all children.
The vaccine is now usually given as part of the MMR vaccine. The WHO recommends the first dose be given at 12 to 18 months of age with a second dose at 36 months. Pregnant women are usually tested for immunity to rubella early on. Women found to be susceptible are not vaccinated until after the baby is born because the vaccine contains live virus.
The immunisation program has been quite successful. Cuba declared the disease eliminated in the 1990s, and in 2004 the Centers for Disease Control and Prevention announced that both the congenital and acquired forms of rubella had been eliminated from the United States.
Screening for rubella susceptibility by history of vaccination or by serology is recommended in the United States for all women of childbearing age at their first preconception counseling visit to reduce incidence of congenital rubella syndrome (CRS). It is recommended that all susceptible non-pregnant women of childbearing age should be offered rubella vaccination. Due to concerns about possible teratogenicity, use of MMR vaccine is not recommended during pregnancy. Instead, susceptible pregnant women should be vaccinated as soon as possible in the postpartum period.
The influenza vaccine is recommended by the World Health Organization and United States Centers for Disease Control and Prevention for high-risk groups, such as children, the elderly, health care workers, and people who have chronic illnesses such as asthma, diabetes, heart disease, or are immuno-compromised among others. In healthy adults it is modestly effective in decreasing the amount of influenza-like symptoms in a population. Evidence is supportive of a decreased rate of influenza in children over the age of two. In those with chronic obstructive pulmonary disease vaccination reduces exacerbations, it is not clear if it reduces asthma exacerbations. Evidence supports a lower rate of influenza-like illness in many groups who are immunocompromised such as those with: HIV/AIDS, cancer, and post organ transplant. In those at high risk immunization may reduce the risk of heart disease. Whether immunizing health care workers affects patient outcomes is controversial with some reviews finding insufficient evidence and others finding tentative evidence.
Due to the high mutation rate of the virus, a particular influenza vaccine usually confers protection for no more than a few years. Every year, the World Health Organization predicts which strains of the virus are most likely to be circulating in the next year (see Historical annual reformulations of the influenza vaccine), allowing pharmaceutical companies to develop vaccines that will provide the best immunity against these strains. The vaccine is reformulated each season for a few specific flu strains but does not include all the strains active in the world during that season. It takes about six months for the manufacturers to formulate and produce the millions of doses required to deal with the seasonal epidemics; occasionally, a new or overlooked strain becomes prominent during that time. It is also possible to get infected just before vaccination and get sick with the strain that the vaccine is supposed to prevent, as the vaccine takes about two weeks to become effective.
Vaccines can cause the immune system to react as if the body were actually being infected, and general infection symptoms (many cold and flu symptoms are just general infection symptoms) can appear, though these symptoms are usually not as severe or long-lasting as influenza. The most dangerous adverse effect is a severe allergic reaction to either the virus material itself or residues from the hen eggs used to grow the influenza; however, these reactions are extremely rare.
The cost-effectiveness of seasonal influenza vaccination has been widely evaluated for different groups and in different settings. It has generally been found to be a cost-effective intervention, especially in children and the elderly, however the results of economic evaluations of influenza vaccination have often been found to be dependent on key assumptions.
In 2012, the World Health Organization estimated that vaccination prevents 2.5 million deaths each year. If there is 100% immunization, and 100% efficacy of the vaccines, one out of seven deaths among young children could be prevented, mostly in developing countries, making this an important global health issue. Four diseases were responsible for 98% of vaccine-preventable deaths: measles, "Haemophilus influenzae" serotype b, pertussis, and neonatal tetanus.
The Immunization Surveillance, Assessment and Monitoring program of the WHO monitors and assesses the safety and effectiveness of programs and vaccines at reducing illness and deaths from diseases that could be prevented by vaccines.
Vaccine-preventable deaths are usually caused by a failure to obtain the vaccine in a timely manner. This may be due to financial constraints or to lack of access to the vaccine. A vaccine that is generally recommended may be medically inappropriate for a small number of people due to severe allergies or a damaged immune system. In addition, a vaccine against a given disease may not be recommended for general use in a given country, or may be recommended only to certain populations, such as young children or older adults. Every country makes its own vaccination recommendations, based on the diseases that are common in its area and its healthcare priorities. If a vaccine-preventable disease is uncommon in a country, then residents of that country are unlikely to receive a vaccine against it. For example, residents of Canada and the United States do not routinely receive vaccines against yellow fever, which leaves them vulnerable to infection if travelling to areas where risk of yellow fever is highest (endemic or transitional regions).
Rotavirus is highly contagious and cannot be treated with antibiotics or other drugs. Because improved sanitation does not decrease the prevalence of rotaviral disease, and the rate of hospitalisations remains high despite the use of oral rehydrating medicines, the primary public health intervention is vaccination. In 1998, a rotavirus vaccine was licensed for use in the United States. Clinical trials in the United States, Finland, and Venezuela had found it to be 80 to 100% effective at preventing severe diarrhoea caused by rotavirus A, and researchers had detected no statistically significant serious adverse effects. The manufacturer, however, withdrew it from the market in 1999, after it was discovered that the vaccine may have contributed to an increased risk for intussusception, a type of bowel obstruction, in one of every 12,000 vaccinated infants. The experience provoked intense debate about the relative risks and benefits of a rotavirus vaccine.
In 2006, two new vaccines against infection were shown to be safe and effective in children, and in 2009, the WHO recommended that rotavirus vaccine be included in all national immunisation programmes.
The incidence and severity of rotavirus infections has declined significantly in countries that have acted on this recommendation. A 2014 review of available clinical trial data from countries routinely using rotavirus vaccines in their national immunisation programs found that rotavirus vaccines have reduced rotavirus hospitalisations by 49–92 percent and all cause diarrhoea hospitalisations by 17–55 percent. In Mexico, which in 2006 was among the first countries in the world to introduce rotavirus vaccine, diarrhoeal disease death rates dropped during the 2009 rotavirus season by more than 65 percent among children age two and under. In Nicaragua, which in 2006 became the first developing country to introduce a rotavirus vaccine, severe rotavirus infections were reduced by 40 percent and emergency room visits by a half. In the United States, rotavirus vaccination since 2006 has led to drops in rotavirus-related hospitalisations by as much as 86 percent. The vaccines may also have prevented illness in non-vaccinated children by limiting the number of circulating infections. In developing countries in Africa and Asia, where the majority of rotavirus deaths occur, a large number of safety and efficacy trials as well as recent post-introduction impact and effectiveness studies of Rotarix and RotaTeq have found that vaccines dramatically reduced severe disease among infants. In September 2013, the vaccine was offered to all children in the UK, aged between two and three months, and it is expected to halve the cases of severe infection and reduce the number of children admitted to hospital because of the infection by 70 percent. In Europe, hospitalisation rates following infection by rotavirus have decreased by 65% to 84% following the introduction of the vaccine. Globally, vaccination has reduced hospital admissions and emergency department visits by a median of 67%.
Rotavirus vaccines are licensed in over 100 countries, and more than 80 countries have introduced routine rotavirus vaccination, almost half with the support of Gavi, the Vaccine Alliance. To make rotavirus vaccines available, accessible, and affordable in all countries—particularly low- and middle-income countries in Africa and Asia where the majority of rotavirus deaths occur, PATH (formerly Program for Appropriate Technology in Health), the WHO, the U.S. Centers for Disease Control and Prevention, and Gavi have partnered with research institutions and governments to generate and disseminate evidence, lower prices, and accelerate introduction.
The CDC recommends real-time PCR as the method of choice for diagnosing H1N1. The oral or nasal fluid collection and RNA virus preserving filter paper card is commercially available. This method allows a specific diagnosis of novel influenza (H1N1) as opposed to seasonal influenza. Near-patient point-of-care tests are in development.