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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 the subgroup of patients where an inoculating event was noted, the mean incubation period of acute melioidosis was 9 days (range 1–21 days). Patients with latent melioidosis may be symptom-free for decades; the longest period between presumed exposure and clinical presentation is 62 years. The potential for prolonged incubation was recognized in US servicemen involved in the Vietnam War, and was referred to as the "Vietnam time-bomb". A wide spectrum of severity exists; in chronic presentations, symptoms may last months, but fulminant infection, particularly associated with near-drowning, may present with severe symptoms over hours.
Symptoms usually appear 2 to 4 weeks after exposure. There are four general types of infection including localized, pulmonary, blood-borne, or disseminated throughout the body. The type and location of the infection usually determines which symptoms appear first as well as which symptoms are more prominent.
Patients with melioidosis usually present with fever. Pain or other symptoms may be suggestive of a clinical focus, which is found in around 75% of patients. Such symptoms include cough or pleuritic chest pain suggestive of pneumonia, bone or joint pain suggestive of osteomyelitis or septic arthritis, or cellulitis. Intra-abdominal infection (including liver and/or splenic abscesses, or prostatic abscesses) do not usually present with focal pain, and imaging of these organs using ultrasound or computed tomography should be performed routinely. In one series of 214 patients, 27.6% had abscesses in the liver or spleen (95% confidence interval, 22.0% to 33.9%). "B. pseudomallei" abscesses may have a characteristic "honeycomb" or "swiss cheese" architecture (hypoechoic, multiseptate, multiloculate) on CT.
Regional variations in disease presentation are seen: parotid abscesses characteristically occur in Thai children, but this presentation has been described only once in Australia. Conversely, prostatic abscesses are found in up to 20% of Australian males, but are rarely described elsewhere. An encephalomyelitis syndrome is recognised in northern Australia.
Patients with melioidosis usually have risk factors for disease, such as diabetes, thalassemia, hazardous alcohol use, or renal disease, and frequently give a history of occupational or recreational exposure to mud or pooled surface water. However, otherwise healthy patients, including children, may also get melioidosis.
In up to 25% of patients, no focus of infection is found and the diagnosis is usually made on blood cultures or throat swab. Melioidosis is said to be able to affect any organ in the body except the heart valves (endocarditis). Although meningitis has been described secondary to ruptured brain abscesses, primary meningitis has not been described. Less common manifestations include intravascular infection, lymph node abscesses (1.2–2.2%), pyopericardium and myocarditis, mediastinal infection, and thyroid and scrotal abscesses and ocular infection.
Glanders (from Middle English ' or Old French ', both meaning glands; , ; also known as "equinia", "farcy", and "malleus") is an infectious disease that occurs primarily in horses, mules, and donkeys. It can be contracted by other animals, such as dogs, cats, goats and humans. It is caused by infection with the bacterium "Burkholderia mallei", usually by ingestion of contaminated feed or water. Signs of glanders include the formation of nodular lesions in the lungs and ulceration of the mucous membranes in the upper respiratory tract. The acute form results in coughing, fever, and the release of an infectious nasal discharge, followed by septicaemia and death within days. In the chronic form, nasal and subcutaneous nodules develop, eventually ulcerating. Death can occur within months, while survivors act as carriers.
Glanders is endemic in Africa, Asia, the Middle East, and Central and South America. It has been eradicated from North America, Australia, and most of Europe through surveillance and destruction of affected animals, and import restrictions.
"B. mallei" is able to infect humans, so is classed as a zoonotic agent. Transmission occurs by direct contact with infected animals and entry is through skin abrasions, nasal and oral mucosal surfaces, or by inhalation.
The mallein test is a sensitive and specific clinical test for glanders. Mallein (ATCvet code: ), a protein fraction of the glanders organism ("B. mallei"), is injected intradermopalpebrally or given by eye drop. In infected animals, the eyelid swells markedly in 1 to 2 days.
Glanders has not been reported in the United States since 1945, except in 2000 when an American lab researcher suffered from accidental exposure. It is a notifiable disease in the UK, although it has not been reported there since 1928.
Chronic melioidosis is usually defined by a duration of symptoms greater than two months and occurs in about 10% of patients. The clinical presentation of chronic melioidosis is protean and includes such presentations as chronic skin infections, chronic lung nodule, and pneumonia. In particular, chronic melioidosis closely mimics tuberculosis, and has sometimes been called "Vietnamese tuberculosis".
No vaccine is licensed for use in the U.S. Infection with either of these bacteria results in nonspecific symptoms and can be either acute or chronic, impeding rapid diagnosis. The lack of a vaccine for either bacterium also makes them potential candidates for bioweaponization. Together with their high rate of infectivity by aerosols and resistance to many common antibiotics, both bacteria have been classified as category B priority pathogens by the US NIH and US CDC, which has spurred a dramatic increase in interest in these microorganisms. Attempts have been made to develop vaccines for these infections, which would not only benefit military personnel, a group most likely to be targeted in an intentional release, but also individuals who may come in contact with glanders-infected animals or live in areas where melioidosis is endemic.
An emerging infectious disease (EID) is an infectious disease whose incidence has increased in the past 20 years and could increase in the near future. Emerging infections account for at least 12% of all human pathogens. EIDs are caused by newly identified species or strains (e.g. Severe acute respiratory syndrome, HIV/AIDS) that may have evolved from a known infection (e.g. influenza) or spread to a new population (e.g. West Nile fever) or to an area undergoing ecologic transformation (e.g. Lyme disease), or be "reemerging" infections, like drug resistant tuberculosis. Nosocomial (hospital-acquired) infections, such as methicillin-resistant Staphylococcus aureus are emerging in hospitals, and extremely problematic in that they are resistant to many antibiotics. Of growing concern are adverse synergistic interactions between emerging diseases and other infectious and non-infectious conditions leading to the development of novel syndemics. Many emerging diseases are zoonotic - an animal reservoir incubates the organism, with only occasional transmission into human populations.
The U.S. Centers for Disease Control and Prevention (CDC) publishes a journal "Emerging Infectious Diseases" that identifies the following factors contributing to disease emergence:
- Microbial adaption; e.g. genetic drift and genetic shift in Influenza A
- Changing human susceptibility; e.g. mass immunocompromisation with HIV/AIDS
- Climate and weather; e.g. diseases with zoonotic vectors such as West Nile Disease (transmitted by mosquitoes) are moving further from the tropics as the climate warms
- Change in human demographics and trade; e.g. rapid travel enabled SARS to rapidly propagate around the globe
- Economic development; e.g. use of antibiotics to increase meat yield of farmed cows leads to antibiotic resistance
- Breakdown of public health; e.g. the current situation in Zimbabwe
- Poverty and social inequality; e.g. tuberculosis is primarily a problem in low-income areas
- War and famine
- Bioterrorism; e.g. 2001 Anthrax attacks
- Dam and irrigation system construction; e.g. malaria and other mosquito borne diseases
Classically, patients with chronic granulomatous disease will suffer from recurrent bouts of infection due to the decreased capacity of their immune system to fight off disease-causing organisms. The recurrent infections they acquire are specific and are, in decreasing order of frequency:
- pneumonia
- abscesses of the skin, tissues, and organs
- suppurative arthritis
- osteomyelitis
- bacteremia/fungemia
- superficial skin infections such as cellulitis or impetigo
Most people with CGD are diagnosed in childhood, usually before age 5. Early diagnosis is important since these people can be placed on antibiotics to ward off infections before they occur. Small groups of CGD patients may also be affected by McLeod syndrome because of the proximity of the two genes on the same X-chromosome.
Chronic granulomatous disease (CGD) (also known as Bridges–Good syndrome, chronic granulomatous disorder, and Quie syndrome) is a diverse group of hereditary diseases in which certain cells of the immune system have difficulty forming the reactive oxygen compounds (most importantly the superoxide radical due to defective phagocyte NADPH oxidase) used to kill certain ingested pathogens. This leads to the formation of granulomata in many organs. CGD affects about 1 in 200,000 people in the United States, with about 20 new cases diagnosed each year.
This condition was first discovered in 1950 in a series of 4 boys from Minnesota, and in 1957 it was named "a fatal granulomatosus of childhood" in a publication describing their disease. The underlying cellular mechanism that causes chronic granulomatous disease was discovered in 1967, and research since that time has further elucidated the molecular mechanisms underlying the disease. Bernard Babior made key contributions in linking the defect of superoxide production of white blood cells, to the cause of the disease. In 1986, the X-linked form of CGD was the first disease for which positional cloning was used to identify the underlying genetic mutation.
Symptom may include pain in a specific bone with overlying redness, fever, and weakness. Onset may be sudden or gradual.
Osteomyelitis (OM) is an infection of bone. Symptoms may include pain in a specific bone with overlying redness, fever, and weakness. The long bones of the arms and legs are most commonly involved in children while the feet, spine, and hips are most commonly involved in adults.
The cause is usually a bacterial infection and rarely a fungal infection. It may occur via spread from the blood or from surrounding tissue. Risks for developing osteomyelitis include diabetes, intravenous drug use, prior removal of the spleen, and trauma to the area. Diagnosis is typically suspected based on symptoms. This is then supported by blood tests, medical imaging, or bone biopsy.
Treatment often involves both antimicrobials and surgery. In those with poor blood flow, amputation may be required. With treatment outcomes are often generally good when the condition has only been present a short time. About 2.4 per 100,000 people are affected a year. The young and old are more commonly affected. Males are more commonly affected than females. The condition was described at least as early as the 300s BC by Hippocrates. Before the availability of antibiotics the risk of death was significant.
Lung disease results from clogging of the airways due to mucus build-up, decreased mucociliary clearance, and resulting inflammation. Inflammation and infection cause injury and structural changes to the lungs, leading to a variety of symptoms. In the early stages, incessant coughing, copious phlegm production, and decreased ability to exercise are common. Many of these symptoms occur when bacteria that normally inhabit the thick mucus grow out of control and cause pneumonia.
In later stages, changes in the architecture of the lung, such as pathology in the major airways (bronchiectasis), further exacerbate difficulties in breathing. Other signs include coughing up blood (hemoptysis), high blood pressure in the lung (pulmonary hypertension), heart failure, difficulties getting enough oxygen to the body (hypoxia), and respiratory failure requiring support with breathing masks, such as bilevel positive airway pressure machines or ventilators. "Staphylococcus aureus", "Haemophilus influenzae", and "Pseudomonas aeruginosa" are the three most common organisms causing lung infections in CF patients. In addition to typical bacterial infections, people with CF more commonly develop other types of lung disease. Among these is allergic bronchopulmonary aspergillosis, in which the body's response to the common fungus "Aspergillus fumigatus" causes worsening of breathing problems. Another is infection with "Mycobacterium avium" complex, a group of bacteria related to tuberculosis, which can cause lung damage and does not respond to common antibiotics.
Mucus in the paranasal sinuses is equally thick and may also cause blockage of the sinus passages, leading to infection. This may cause facial pain, fever, nasal drainage, and headaches. Individuals with CF may develop overgrowth of the nasal tissue (nasal polyps) due to inflammation from chronic sinus infections. Recurrent sinonasal polyps can occur in 10% to 25% of CF patients. These polyps can block the nasal passages and increase breathing difficulties.
Cardiorespiratory complications are the most common cause of death (about 80%) in patients at most CF centers in the United States.
The main signs and symptoms of cystic fibrosis are salty-tasting skin, poor growth, and poor weight gain despite normal food intake, accumulation of thick, sticky mucus, frequent chest infections, and coughing or shortness of breath. Males can be infertile due to congenital absence of the vas deferens. Symptoms often appear in infancy and childhood, such as bowel obstruction due to meconium ileus in newborn babies. As the children grow, they exercise to release mucus in the alveoli. Ciliated epithelial cells in the person have a mutated protein that leads to abnormally viscous mucus production. The poor growth in children typically presents as an inability to gain weight or height at the same rate as their peers, and is occasionally not diagnosed until investigation is initiated for poor growth. The causes of growth failure are multifactorial and include chronic lung infection, poor absorption of nutrients through the gastrointestinal tract, and increased metabolic demand due to chronic illness.
In rare cases, cystic fibrosis can manifest itself as a coagulation disorder. Vitamin K is normally absorbed from breast milk, formula, and later, solid foods. This absorption is impaired in some cystic fibrosis patients. Young children are especially sensitive to vitamin K malabsorptive disorders because only a very small amount of vitamin K crosses the placenta, leaving the child with very low reserves and limited ability to absorb vitamin K from dietary sources after birth. Because factors II, VII, IX, and X (clotting factors) are vitamin K–dependent, low levels of vitamin K can result in coagulation problems. Consequently, when a child presents with unexplained bruising, a coagulation evaluation may be warranted to determine whether an underlying disease is present.