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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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In addition to vaccine-specific factors, vets and owners should also consider pet-specific factors that have been shown to increase the risk of adverse reactions in both dogs and cats. Examples of such factors include:
- age,
- number of vaccinations per office visit,
- size,
- general health of the animal,
- breed,
- neutered status, and
- past vaccination history.
Fortunately, severe systemic reaction to vaccine allergy is very rare in dogs. When it does occur, however, anaphylaxis is a life-threatening emergency. More often, dogs will develop urticaria, or hives within minutes of receiving a vaccine. When this occurs, a veterinarian will treat the reaction with antihistamines and corticosteroid drugs and this is usually effective. Future vaccine protocols must be modified according to the vaccine component suspected to have triggered the reaction.
Non-specific effects are frequently different in males and females. There are accumulating data illustrating that males and females may respond differently to vaccination, both in terms of the quality and quantity of the immune response. If true, then we must consider whether vaccination schedules should differ for males and females, or as has been suggested "should we treat the sexes differently in order to treat them equally?"
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".
Persons with component deficiencies in the final common complement pathway (C3,C5-C9) are more susceptible to "N. meningitidis" infection than complement-satisfactory persons, and it was estimated that the risk of infection is 7000 times higher in such individuals. In addition, complement component-deficient populations frequently experience frequent meningococcal disease since their immune response to natural infection may be less complete than that of complement non-deficient persons.
Inherited properdin deficiency also is related, with an increased risk of contracting meningococcal disease. Persons with functional or anatomic asplenia may not efficiently clear encapsulated "Neisseria meningitidis" from the bloodstream Persons with other conditions associated with immunosuppression also may be at increased risk of developing meningococcal disease.
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).
The majority of people survive measles, though in some cases, complications may occur. Possible consequences of measles virus infection include bronchitis, sensorineural hearing loss, and—in about 1 in 10,000 to 1 in 300,000 cases—panencephalitis, which is usually fatal. Acute measles encephalitis is another serious risk of measles virus infection. It typically occurs two days to one week after the breakout of the measles rash and begins with very high fever, severe headache, convulsions and altered mentation. A person with measles encephalitis may become comatose, and death or brain injury may occur.
HIV-infected individuals are likely to be at increased risk for meningococcal disease; HIV-infected individuals who wish to reduce their risk of meningococcal disease may receive primary immunization against meningococcal disease. Although efficacy of meningitis A,C,Y and W-135 vaccines have not been evaluated in HIV-infected individuals to date, HIV-infected individuals 11–55 years of age may receive primary immunization with the conjugated vaccine. Vaccination against meningitis does not decrease CD4+ T-cell counts or increase viral load in HIV-infected individuals, and there has been no evidence that the vaccines adversely affect survival.
Globally, botulism is fairly rare, with approximately 1,000 cases yearly.
Tetanus is caused by the tetanus bacterium "Clostridium tetani". Tetanus is an international health problem, as "C. tetani" spores are ubiquitous. Spores can be introduced into the body through a puncture wound (penetrating trauma). Due to "C. tetani" being an anaerobic bacterium, it and its endospores thrive in environments that lack oxygen, such as a puncture wound.
The disease occurs almost exclusively in persons inadequately immunized. It is more common in hot, damp climates with soil rich in organic matter. Manure-treated soils may contain spores, as they are widely distributed in the intestines and feces of many animals such as horses, sheep, cattle, dogs, cats, rats, guinea pigs, and chickens. In agricultural areas, a significant number of human adults may harbor the organism.
The spores can also be found on skin surfaces and in contaminated heroin. Heroin users, particularly those that inject the drug subcutaneously, appear to be at high risk of contracting tetanus. Rarely, tetanus can be contracted through surgical procedures, intramuscular injections, compound fractures, and dental infections. The bite of a dog can transmit tetanus.
Tetanus is often associated with rust, especially rusty nails. Although rust itself does not cause tetanus, objects that accumulate rust are often found outdoors or in places that harbour anaerobic bacteria. Additionally, the rough surface of rusty metal provides a habitat for "C. tetani", while a nail affords a means to puncture skin and deliver endospores deep within the body at the site of the wound. An endospore is a non-metabolizing survival structure that begins to metabolize and cause infection once in an adequate environment. Hence, stepping on a nail (rusty or not) may result in a tetanus infection, as the low-oxygen (anaerobic) environment may exist under the skin, and the puncturing object can deliver endospores to a suitable environment for growth.
In the United States there are typically between a couple of hundred and a couple of thousand cases a year.
Tetanus toxoid can be given in case of a suspected exposure to tetanus. In such cases, it can be given with or without tetanus immunoglobulin (also called "tetanus antibodies" or "tetanus antitoxin"). It can be given as intravenous therapy or by intramuscular injection.
The guidelines for such events in the United States for non-pregnant people 11 years and older are as follows:
The paralysis caused by botulism can persist for 2 to 8 weeks, during which supportive care and ventilation may be necessary to keep the person alive. Botulism is fatal in 5% to 10% of people who are affected. However, if left untreated, botulism is fatal in 40% to 50% of cases.
Infant botulism typically has no long-term side effects but can be complicated by treatment associated adverse events. The case fatality rate is less than 1% for hospitalized babies.
The duration of the visible blistering caused by varicella zoster virus varies in children usually from 4 to 7 days, and the appearance of new blisters begins to subside after the fifth day. Chickenpox infection is milder in young children, and symptomatic treatment, with sodium bicarbonate baths or antihistamine medication may ease itching. It is recommended to keep new infants from birth up to age 6 months away from an infected person for 10 to 21 days because their immune systems are not developed enough to handle the stress it can bring on. Paracetamol (acetaminophen) is widely used to reduce fever. Aspirin, or products containing aspirin, should not be given to children with chickenpox, as it can cause Reye's Syndrome.
In adults, the disease is more severe, though the incidence is much less common. Infection in adults is associated with greater morbidity and mortality due to pneumonia (either direct viral pneumonia or secondary bacterial pneumonia), bronchitis (either viral bronchitis or secondary bacterial bronchitis), hepatitis, and encephalitis. In particular, up to 10% of pregnant women with chickenpox develop pneumonia, the severity of which increases with onset later in gestation. In England and Wales, 75% of deaths due to chickenpox are in adults. Inflammation of the brain, or encephalitis, can occur in immunocompromised individuals, although the risk is higher with herpes zoster. Necrotizing fasciitis is also a rare complication.
Varicella can be lethal to adults with impaired immunity. The number of people in this high-risk group has increased, due to the HIV epidemic and the increased use of immunosuppressive therapies. Varicella is a particular problem in hospitals, when there are patients with immune systems weakened by drugs (e.g., high-dose steroids) or HIV.
Secondary bacterial infection of skin lesions, manifesting as impetigo, cellulitis, and erysipelas, is the most common complication in healthy children. Disseminated primary varicella infection usually seen in the immunocompromised may have high morbidity. Ninety percent of cases of varicella pneumonia occur in the adult population. Rarer complications of disseminated chickenpox include myocarditis, hepatitis, and glomerulonephritis.
Hemorrhagic complications are more common in the immunocompromised or immunosuppressed populations, although healthy children and adults have been affected. Five major clinical syndromes have been described: febrile purpura, malignant chickenpox with purpura, postinfectious purpura, purpura fulminans, and anaphylactoid purpura. These syndromes have variable courses, with febrile purpura being the most benign of the syndromes and having an uncomplicated outcome. In contrast, malignant chickenpox with purpura is a grave clinical condition that has a mortality rate of greater than 70%. The cause of these hemorrhagic chickenpox syndromes is not known.
Common complications include pneumonia, bronchitis, encephalopathy, earache, and seizures. Most healthy older children and adults fully recover, but those with comorbid conditions have a higher risk of morbidity and mortality.
Infection in newborns is particularly severe. Pertussis is fatal in an estimated 1.6% of hospitalized US infants under one year of age. First-year infants are also more likely to develop complications, such as: pneumonia (20%), encephalopathy (0.3%), seizures (1%), failure to thrive, and death (1%)—perhaps due to the ability of the bacterium to suppress the immune system. Pertussis can cause severe paroxysm-induced cerebral hypoxia, and 50% of infants admitted to hospital suffer apneas. Reported fatalities from pertussis in infants increased substantially from 1990 to 2010.
A "vaccine-preventable disease" is an infectious disease for which an effective preventive vaccine exists. If a person acquires a vaccine-preventable disease and dies from it, the death is considered a vaccine-preventable death.
The most common and serious vaccine-preventable diseases tracked by the World Health Organization (WHO) are: diphtheria, "Haemophilus influenzae" serotype b infection, hepatitis B, measles, meningitis, mumps, pertussis, poliomyelitis, rubella, tetanus, tuberculosis, and yellow fever. The WHO reports licensed vaccines being available to prevent, or contribute to the prevention and control of, 25 vaccine-preventable infections.
Measles is extremely infectious and its continued circulation in a community depends on the generation of susceptible hosts by birth of children. In communities which generate insufficient new hosts the disease will die out. This concept was first recognized in measles by Bartlett in 1957, who referred to the minimum number supporting measles as the critical community size (CCS). Analysis of outbreaks in island communities suggested that the CCS for measles is around 250,000. To achieve herd immunity, more than 95% of the community must be vaccinated due to the ease with which measles is transmitted from person to person. The disease was eliminated from the Americas in 2016.
In 2011, the WHO estimated that 158,000 deaths were caused by measles. This is down from 630,000 deaths in 1990. As of 2013, measles remains the leading cause of vaccine-preventable deaths in the world. In developed countries, death occurs in one to two cases out of every 1,000 (0.1% – 0.2%). In populations with high levels of malnutrition and a lack of adequate healthcare, mortality can be as high as 10%. In cases with complications, the rate may rise to 20–30%. In 2012, the number of deaths due to measles was 78% lower than in 2000 due to increased rates of immunization among UN member states.
Even in countries where vaccination has been introduced, rates may remain high. Measles is a leading cause of vaccine-preventable childhood mortality. Worldwide, the fatality rate has been significantly reduced by a vaccination campaign led by partners in the Measles Initiative: the American Red Cross, the United States' Centers for Disease Control and Prevention (CDC), the United Nations Foundation, UNICEF and the WHO. Globally, measles fell 60% from an estimated 873,000 deaths in 1999 to 345,000 in 2005. Estimates for 2008 indicate deaths fell further to 164,000 globally, with 77% of the remaining measles deaths in 2008 occurring within the Southeast Asian region.
Five out of six WHO regions have set goals to eliminate measles, and at the 63rd World Health Assembly in May 2010, delegates agreed on a global target of a 95% reduction in measles mortality by 2015 from the level seen in 2000, as well as to move towards eventual eradication. However, no specific global target date for eradication has yet been agreed to as of May 2010.
Worldwide, whooping cough affects around 16 million people yearly. One estimate for 2013 stated it resulted in about 61,000 deaths – down from 138,000 deaths in 1990. Another estimated 195,000 child deaths yearly from the disease worldwide. This is despite generally high coverage with the DTP and DTaP vaccines. Pertussis is one of the leading causes of vaccine-preventable deaths worldwide. About 90% of all cases occur in developing countries.
Before vaccines, an average of 178,171 cases was reported in the U.S., with peaks reported every two to five years; more than 93% of reported cases occurred in children under 10 years of age. The actual incidence was likely much higher. After vaccinations were introduced in the 1940s, pertussis incidence fell dramatically to approximately 1,000 by 1976. Incidence rates have increased since 1980. In 2015, rates in the United States were 20,762 people.
Pertussis is the only vaccine-preventable disease that is associated with increasing deaths in the U.S. The number of deaths increased from four in 1996 to 17 in 2001, almost all of which were infants under one year. In Canada, the number of pertussis infections has varied between 2,000 and 10,000 reported cases each year over the last ten years, and it is the most common vaccine-preventable illness in Toronto.
In 2009 Australia reported an average of 10,000 cases a year, and the number of cases had increased. In the U.S. pertussis in adults has increased significantly since about 2004.
The most common preventative measure against mumps is a vaccination with a mumps vaccine, invented by American microbiologist Maurice Hilleman at Merck. The vaccine may be given separately or as part of the MMR immunization vaccine that also protects against measles and rubella. In the US, MMR is now being supplanted by MMRV, which adds protection against chickenpox (varicella, HHV3). The WHO (World Health Organization) recommends the use of mumps vaccines in all countries with well-functioning childhood vaccination programmes. In the United Kingdom it is routinely given to children at age 13 months with a booster at 3–5 years (preschool) This confers lifelong immunity. The American Academy of Pediatrics recommends the routine administration of MMR vaccine at ages 12–15 months and at 4–6 years. In some locations, the vaccine is given again between four and six years of age, or between 11 and 12 years of age if not previously given. The efficacy of the vaccine depends on the strain of the vaccine, but is usually around 80 percent. The Jeryl Lynn strain is most commonly used in developed countries but has been shown to have reduced efficacy in epidemic situations. The Leningrad-Zagreb strain commonly used in developing countries appears to have superior efficacy in epidemic situations.
Because of the outbreaks within college and university settings, many governments have established vaccination programs to prevent large-scale outbreaks. In Canada, provincial governments and the Public Health Agency of Canada have all participated in awareness campaigns to encourage students ranging from grade one to college and university to get vaccinated.
Some anti-vaccine activists protest against the administration of a vaccine against mumps, claiming that the attenuated vaccine strain is harmful, and/or that the wild disease is beneficial. There is no evidence whatsoever to support the claim that the wild disease is beneficial, or that the MMR vaccine is harmful. Claims have been made that the MMR vaccine is linked to autism and inflammatory bowel disease, including one study by Andrew Wakefield. The paper was discredited and retracted in 2010 and Wakefield was later stripped of his license after his work was found to be an "elaborate fraud". Also, subsequent studies indicate no link between vaccination with the MMR and autism. Since the dangers of the disease are well known, and the dangers of the vaccine are quite minimal, most doctors recommend vaccination.
The WHO, the American Academy of Pediatrics, the Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention, the American Academy of Family Physicians, the British Medical Association and the Royal Pharmaceutical Society of Great Britain currently recommend routine vaccination of children against mumps. The British Medical Association and Royal Pharmaceutical Society of Great Britain had previously recommended against general mumps vaccination, changing that recommendation in 1987.
Before the introduction of the mumps vaccine, the mumps virus was the leading cause of viral meningoencephalitis in the United States. However, encephalitis occurs rarely (less than two per 100,000). In one of the largest studies in the literature, the most common symptoms of mumps meningoencephalitis were found to be fever (97 percent), vomiting (94 percent) and headache (88.8 percent). The mumps vaccine was introduced into the United States in December 1967: since its introduction there has been a steady decrease in the incidence of mumps and mumps virus infection. There were 151,209 cases of mumps reported in 1968. From 2001 to 2008, the case average was only 265 per year, excluding an outbreak of less than 6000 cases in 2006 attributed largely to university contagion in young adults.
After a chickenpox infection, the virus remains dormant in the body's nerve tissues. The immune system keeps the virus at bay, but later in life, usually in an adult, it can be reactivated and cause a different form of the viral infection called shingles (also known as herpes zoster).
The United States Advisory Committee on Immunization Practices (ACIP) suggests that every adult over the age of 60 years get the "herpes zoster" vaccine.
Shingles affects one in five adults infected with chickenpox as children, especially those who are immune-suppressed, particularly from cancer, HIV, or other conditions. Stress can bring on shingles as well, although scientists are still researching the connection. Shingles are most commonly found in adults over the age of 60 who were diagnosed with chickenpox when they were under the age of 1.
Rabies is a viral disease that exists in Haiti and throughout the world. It often causes fatal inflammation of the brain in humans and other mammals, such as dogs and mongooses in Haiti. The term "rabies" is derived from a Latin word that means "to rage"; rabid animals sometimes appear to be angry. Early symptoms can include fever and tingling at the site of exposure, followed by one or more of the following symptoms: violent movements, uncontrolled excitement, fear of water, an inability to move parts of the body, confusion, and loss of consciousness. Once symptoms appear, death is nearly always the outcome. The time period between contracting the disease and showing symptoms is usually one to three months; however, this time period can vary from less than a week to more than a year. The time between contraction and the onset of symptoms is dependent on the distance the virus must travel to reach the central nervous system.
Haiti is one of five remaining countries in the Americas where canine rabies is still a problem. It has the highest rate of human rabies deaths in the western hemisphere with an estimated two deaths each week. Only about seven deaths are reported to health authorities each year due to poor surveillance, limitations in diagnostic capacity, and lack of awareness and education about the disease among Haitians.
Globally, 59,000 people die from rabies each year. This is the equivalent of one person dying every nine minutes, with half of the people who die from rabies being under the age of 15. The Pan American Health Organization (PAHO) and the Pan American Center of foot-and-mouth disease (PANAFTOSA) led a mission to eliminate dog-mediated rabies in the American region by 2015. These organizations are cognizant of the regional control of rabies. The PAHO and PANAFTOSA visited Haiti in early December, 2013, and the objectives of the mission were to assess the status of Haiti’s rabies program as delivered by the Haitian Ministry of Agriculture, Natural Resources and Rural Development (MARNDR) and the Ministry of Health (MSPP). The mission was to seek opportunities for collaboration between Haiti, Brazil, and the Centers for Disease Control and Prevention (CDC) in Haiti.
Even in 2017, rabies in Haiti is still identified as a national problem, even with PEP proposed.
As research better explains the biochemistry of drug use, fewer ADRs are Type B and more are Type A. Common mechanisms are:
- Abnormal pharmacokinetics due to
- genetic factors
- comorbid disease states
- Synergistic effects between either
- a drug and a disease
- two drugs
Infection with Japanese encephalitis confers lifelong immunity. There are currently three vaccines available: SA14-14-2, IC51 (marketed in Australia and New Zealand as JESPECT and elsewhere as IXIARO) and ChimeriVax-JE (marketed as IMOJEV). All current vaccines are based on the genotype III virus.
A formalin-inactivated mouse-brain derived vaccine was first produced in Japan in the 1930s and was validated for use in Taiwan in the 1960s and in Thailand in the 1980s. The widespread use of vaccine and urbanization has led to control of the disease in Japan, Korea, Taiwan, and Singapore. The high cost of this vaccine, which is grown in live mice, means that poorer countries have not been able to afford to give it as part of a routine immunization program.
The most common adverse effects are redness and pain at the injection site. Uncommonly, an urticarial reaction can develop about four days after injection. Vaccines produced from mouse brain have a risk of autoimmune neurological complications of around 1 per million vaccinations. However where the vaccine is not produced in mouse brains but in vitro using cell culture there is little adverse effects compared to placebo, the main side effects are headache and myalgia.
The neutralizing antibody persists in the circulation for at least two to three years, and perhaps longer. The total duration of protection is unknown, but because there is no firm evidence for protection beyond three years, boosters are recommended every three years for people who remain at risk. Furthermore, there is also no data available regarding the interchangeability of other JE vaccines and IXIARO.
In September 2012 the Indian firm Biological E. Limited has launched an inactivated cell culture derived vaccine based on SA 14-14-2 strain which was developed in a technology transfer agreement with Intercell and is a thiomersal-free vaccine.
Due to the importance of disease caused by "S. pneumoniae" several vaccines have been developed to protect against invasive infection. The World Health Organization recommend routine childhood pneumococcal vaccination; it is incorporated into the childhood immunization schedule in a number of countries including the United Kingdom, United States, and South Africa.