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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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Biochemical tests used in the identification of infectious agents include the detection of metabolic or enzymatic products characteristic of a particular infectious agent. Since bacteria ferment carbohydrates in patterns characteristic of their genus and species, the detection of fermentation products is commonly used in bacterial identification. Acids, alcohols and gases are usually detected in these tests when bacteria are grown in selective liquid or solid media.
The isolation of enzymes from infected tissue can also provide the basis of a biochemical diagnosis of an infectious disease. For example, humans can make neither RNA replicases nor reverse transcriptase, and the presence of these enzymes are characteristic of specific types of viral infections. The ability of the viral protein hemagglutinin to bind red blood cells together into a detectable matrix may also be characterized as a biochemical test for viral infection, although strictly speaking hemagglutinin is not an "enzyme" and has no metabolic function.
Serological methods are highly sensitive, specific and often extremely rapid tests used to identify microorganisms. These tests are based upon the ability of an antibody to bind specifically to an antigen. The antigen, usually a protein or carbohydrate made by an infectious agent, is bound by the antibody. This binding then sets off a chain of events that can be visibly obvious in various ways, dependent upon the test. For example, "Strep throat" is often diagnosed within minutes, and is based on the appearance of antigens made by the causative agent, "S. pyogenes", that is retrieved from a patients throat with a cotton swab. Serological tests, if available, are usually the preferred route of identification, however the tests are costly to develop and the reagents used in the test often require refrigeration. Some serological methods are extremely costly, although when commonly used, such as with the "strep test", they can be inexpensive.
Complex serological techniques have been developed into what are known as Immunoassays. Immunoassays can use the basic antibody – antigen binding as the basis to produce an electro-magnetic or particle radiation signal, which can be detected by some form of instrumentation. Signal of unknowns can be compared to that of standards allowing quantitation of the target antigen. To aid in the diagnosis of infectious diseases, immunoassays can detect or measure antigens from either infectious agents or proteins generated by an infected organism in response to a foreign agent. For example, immunoassay A may detect the presence of a surface protein from a virus particle. Immunoassay B on the other hand may detect or measure antibodies produced by an organism's immune system that are made to neutralize and allow the destruction of the virus.
Instrumentation can be used to read extremely small signals created by secondary reactions linked to the antibody – antigen binding. Instrumentation can control sampling, reagent use, reaction times, signal detection, calculation of results, and data management to yield a cost effective automated process for diagnosis of infectious disease.
Given the wide range of bacteria, viruses, and other pathogens that cause debilitating and life-threatening illness, the ability to quickly identify the cause of infection is important yet often challenging. For example, more than half of cases of encephalitis, a severe illness affecting the brain, remain undiagnosed, despite extensive testing using state-of-the-art clinical laboratory methods. Metagenomics is currently being researched for clinical use, and shows promise as a sensitive and rapid way to diagnose infection using a single all-encompassing test. This test is similar to current PCR tests; however, amplification of genetic material is unbiased rather than using primers for a specific infectious agent. This amplification step is followed by next-generation sequencing and alignment comparisons using large databases of thousands of organismic and viral genomes.
Metagenomic sequencing could prove especially useful for diagnosis when the patient is immunocompromised. An ever-wider array of infectious agents can cause serious harm to individuals with immunosuppression, so clinical screening must often be broader. Additionally, the expression of symptoms is often atypical, making clinical diagnosis based on presentation more difficult. Thirdly, diagnostic methods that rely on the detection of antibodies are more likely to fail. A broad, sensitive test for pathogens that detects the presence of infectious material rather than antibodies is therefore highly desirable.
Opportunistic infections caused by Feline Leukemia Virus and Feline immunodeficiency virus retroviral infections can be treated with Lymphocyte T-Cell Immune Modulator.
Individuals at higher risk are often prescribed prophylactic medication to prevent an infection from occurring. A patient's risk level for developing an opportunistic infection is approximated using the patient's CD4 T-cell count and sometimes other markers of susceptibility. Common prophylaxis treatments include the following:
The immune reconstitution inflammatory syndrome (IRIS) has been described in those with normal immune function with meningitis caused by "C. gattii" and "C. grubii". Several weeks or even months into appropriate treatment, there can be deterioration with worsening meningitis symptoms and progression or development of new neurological symptoms. IRIS is however much more common in those with poor immune function (≈25% vs. ≈8%).
Magnetic resonance imaging shows increase in the size of brain lesions, and CSF abnormalities (white cell count, protein, glucose) increase. Radiographic appearance of cryptococcal IRIS brain lesions can mimic that of toxoplasmosis with ring enhancing lesions on head computed tomography (CT). CSF culture is sterile, and there is no increase in CSF cryptococcal antigen titre.
The increasing inflammation can cause brain injury or be fatal.
The mechanism behind IRIS in cryptococcal meningitis is primarily immunologic. With reversal of immunosuppression, there is paradoxical increased inflammation as the recovering immune system recognises the fungus. In severe IRIS cases, treatment with systemic corticosteroids has been utilized - although evidence-based data are lacking.
The CDC states that PCR testing from a single blood draw is not sufficiently sensitive for "B." "henselae" testing, and can result in high false negative rates due to a small sample volume and levels below the limit of molecular detection.
"Bartonella" spp. are fastidious, slow-growing bacteria that are difficult to grow using traditional solid agar plate culture methods due to complex nutritional requirements and potentially a low number of circulating bacteria. This conventional method of culturing "Bartonella" spp. from blood inoculates plated directly onto solid agar plates requires an extended incubation period of 21 days due to the slow growth rate.
Fungal pneumonia can be diagnosed in a number of ways. The simplest and cheapest method is to culture the fungus from a patient's respiratory fluids. However, such tests are not only insensitive but take time to develop which is a major drawback because studies have shown that slow diagnosis of fungal pneumonia is linked to high mortality. Microscopy is another method but is also slow and imprecise. Supplementing these classical methods is the detection of antigens. This technique is significantly faster but can be less sensitive and specific than the classical methods.
A molecular test based on quantitative PCR is also available from Myconostica. Relying on DNA detection, this is the most sensitive and specific test available for fungi but it is limited to detecting only pneumocystis jirovecii and aspergillus.
"Bartonella" growth rates improve when cultured in an enrichment inoculation step in a liquid insect-based medium such as "Bartonella" α-Proteobacteria Growth Medium (BAPGM) or Schneider’s Drosophila-based insect powder medium. Several studies have optimized the growing conditions of "Bartonella" spp. cultures in these liquid media, with no change in bacterial protein expressions or host interactions "in vitro". Insect-based liquid media supports the growth and co-culturing of at least seven "Bartonella" species, reduces bacterial culturing time and facilitates PCR detection and isolation of "Bartonella" spp. from animal and patient samples. Research shows that DNA may be detected following direct extraction from blood samples and become negative following enrichment culture, thus PCR is recommended after direct sample extraction and also following incubation in enrichment culture. Several studies have successfully optimized sensitivity and specificity by using PCR amplification (pre-enrichment PCR) and enrichment culturing of blood draw samples, followed by PCR (post-enrichment PCR) and DNA sequence identification.
Cryptococcosis is a very subacute infection with a prolonged subclinical phase lasting weeks to months in persons with HIV/AIDS before the onset of symptomatic meningitis. In Sub-Saharan Africa, the prevalence rates of detectable cryptococcal antigen in peripheral blood is often 4–12% in persons with CD4 counts lower than 100 cells/mcL.
Cryptococcal antigen screen and preemptive treatment with fluconazole is cost saving to the healthcare system by avoiding cryptococcal meningitis. The World Health Organization recommends cryptococcal antigen screening in HIV-infected persons entering care with CD4<100 cells/μL. This undetected subclinical cryptococcal (if not preemptively treated with anti-fungal therapy) will often go on to develop cryptococcal meningitis, despite receiving HIV therapy. Cryptococcosis accounts for 20-25% of the mortality after initiating HIV therapy in Africa. What is effective preemptive treatment is unknown, with the current recommendations on dose and duration based on expert opinion. Screening in the United States is controversial, with official guidelines not recommending screening, despite cost-effectiveness and a 3% U.S. cryptococcal antigen prevalence in CD4<100 cells/μL.
Vaccination helps prevent bronchopneumonia, mostly against influenza viruses, adenoviruses, measles, rubella, streptococcus pneumoniae, haemophilus influenzae, diphtheria, bacillus anthracis, chickenpox, and bordetella pertussis.
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.
The diagnosis of actinomycosis can be a difficult one to make. In addition to microbiological examinations, magnetic resonance imaging and immunoassays may be helpful.
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.
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.
Bats recovering from white-nose syndrome (WNS) may be the first natural occurrence of IRIS, in a report released by the USGS. WNS is typified by a cutaneous infection of the fungus "Pseudogymnoascus destructans" during hibernation, when the immune system is naturally suppressed to conserve energy through the winter. This study suggests that bats undergoing an intense inflammation at the site of infection after a return to euthermia is a form of IRIS.
A skin and skin structure infection (SSSI), also referred to as skin and soft tissue infection (SSTI) or acute bacterial skin and skin structure infection (ABSSSI), is an infection of skin and associated soft tissues (such as loose connective tissue and mucous membranes). The pathogen involved is usually a bacterial species. Such infections often requires treatment by antibiotics.
Until 2008, two types were recognized, complicated skin and skin structure infection (cSSSI) and uncomplicated skin and skin structure infection (uSSSI). "Uncomplicated" SSSIs included simple abscesses, impetiginous lesions, furuncles, and cellulitis. "Complicated" SSSIs included infections either involving deeper soft tissue or requiring significant surgical intervention, such as infected ulcers, burns, and major abscesses or a significant underlying disease state that complicates the response to treatment. Superficial infections or abscesses in an anatomical site, such as the rectal area, where the risk of anaerobic or gram-negative pathogen involvement is higher, should be considered complicated infections. The two categories had different regulatory approval requirements. The uncomplicated category (uSSSI) is normally only caused by "Staphylococcus aureus" and "Streptococcus pyogenes", whereas the complicated category (cSSSI) might also be caused by a number of other pathogens. In cSSSI, the pathogen is known in only about 40% of cases.
Because cSSSIs are usually serious infections, physicians do not have the time for a culture to identify the pathogen, so most cases are treated empirically, by choosing an antibiotic agent based on symptoms and seeing if it works. For less severe infections, microbiologic evaluation via tissue culture has been demonstrated to have high utility in guiding management decisions. To achieve efficacy, physicians use broad-spectrum antibiotics. This practice contributes in part to the growing incidence of antibiotic resistance, a trend exacerbated by the widespread use of antibiotics in medicine in general. The increased prevalence of antibiotic resistance is most evident in methicillin-resistant "Staphylococcus aureus" (MRSA). This species is commonly involved in cSSSIs, worsening their prognosis, and limiting the treatments available to physicians. Drug development in infectious disease seeks to produce new agents that can treat MRSA.
Since 2008, the U.S. Food and Drug Administration has changed the terminology to "acute bacterial skin and skin structure infections" (ABSSSI). The Infectious Diseases Society of America (IDSA) has retained the term "skin and soft tissue infection".
IRIS is particularly problematic in cryptococcal meningitis as IRIS is fairly common and can be fatal.
IRIS has been described in immunocompetent hosts who have meningitis caused by "Cryptococcus gattii" and "Cryptococcus neoformans" var. "grubii", environmental fungi which often affect immunocompetent hosts. Several weeks or even months into appropriate treatment, there is a sudden onset deterioration with worsening meningitis symptoms and progression or development of new neurological symptoms.
Magnetic resonance imaging shows increase in the size of brain lesions, and CSF abnormalities (white cell count, protein, glucose) increase. CSF culture is typically sterile, and there is no increase in CSF cryptococcal antigen titer.
The increasing inflammation can cause brain injury or be fatal.
The general mechanism behind IRIS is increased inflammation as the recovering immune system recognizes the antigens of the fungus as immunosuppression is reversed. Cryptococcal IRIS has three phases:
1. before HAART, with a paucity of cerebrospinal fluid (CSF) inflammation and defects in antigen clearance;
2. during initial HAART immune recovery, with pro-inflammatory signaling by antigen-presenting cells without an effector response; and
3. at IRIS, a cytokine storm with a predominant type-1 helper T-cell interferon-gamma response.
Three clinical predictors of cryptococcal-related paradoxical IRIS risk include:
1. lack of initial CSF pleocytosis (i.e. low CSF white blood cell count);
2. elevated C-reactive protein;
3. failure to sterilize the CSF before immune recovery.
IRIS may be the cause of paradoxically worse outcomes for cryptococcal meningitis in immunocompetent compared with immunocompromised hosts, in whom "Cryptococcus neoformans" is the usual pathogen. Treatment with systemic corticosteroids during IRIS may be beneficial in preventing death or progressive neurological deterioration. Steroids given to persons with anti-fungal treatment failure / cryptococcal relapse (in whom CSF cultures are not sterile) can be a fatal iatrogenic error.
Routine vaccination against meningococcus is recommended by the Centers for Disease Control and Prevention for all 11- to 18-year-olds and people who have poor splenic function (who, for example, have had their spleen removed or who have sickle-cell disease which damages the spleen), or who have certain immune disorders, such as a complement deficiency.
Some ways to prevent airborne diseases include washing hands, using appropriate hand disinfection, getting regular immunizations against diseases believed to be locally present, wearing a respirator and limiting time spent in the presence of any patient likely to be a source of infection.
Exposure to a patient or animal with an airborne disease does not guarantee receiving the disease. Because of the changes in host immunity and how much the host was exposed to the particles in the air makes a difference to how the disease affects the body.
Antibiotics are not prescribed for patients to control viral infections. They may however be prescribed to a flu patient for instance, to control or prevent bacterial secondary infections. They also may be used in dealing with air-borne bacterial primary infections, such as pneumonic plague.
Additionally the Centers for Disease Control and Prevention (CDC) has told consumers about vaccination and following careful hygiene and sanitation protocols for airborne disease prevention. Consumers also have access to preventive measures like UV Air purification devices that FDA and EPA-certified laboratory test data has verified as effective in inactivating a broad array of airborne infectious diseases. Many public health specialists recommend social distancing to reduce the transmission of airborne infections.
Though antibiotics are required to treat severe bacterial infections, misuse has contributed to a rise in bacterial resistance. The overuse of fluoroquinolone and other antibiotics fuels antibiotic resistance in bacteria, which can inhibit the treatment of antibiotic-resistant infections. Their excessive use in children with otitis media has given rise to a breed of bacteria resistant to antibiotics entirely.
Widespread use of fluoroquinolones as a first-line antibiotic has led to decreased antibiotic sensitivity, with negative implications for serious bacterial infections such as those associated with cystic fibrosis, where quinolones are among the few viable antibiotics.
In the absence of vaccination (often because calves are bought unvaccinated), antibiotics can help to stop the bacterial factors of the disease. The Virginia Cooperative Extension recommends Micotil, Nuflor, and Baytril 100 as newer antibiotics that do not need daily dosing, but also notes that Naxcel, Excenel, and Adspec are effective as well.
Because of the number of possible viral/bacterial precursors to BRD, there are a number of treatment options circling around the three main aggravators of the disease: Viruses, Bacteria, and Stress.
Common situations in which antibiotics are overused include the following:
- Apparent viral respiratory illness in children should not be treated with antibiotics. If there is a diagnosis of bacterial infection, then antibiotics may be used.
- When children with ear tubes get ear infections, they should have antibiotic eardrops put into their ears to go to the infection rather than having oral antibiotics which are more likely to have unwanted side effects.
- Swimmer's ear should be treated with antibiotic eardrops, not oral antibiotics.
- Sinusitis should not be treated with antibiotics because it is usually caused by a virus, and even when it is caused by a bacteria, antibiotics are not indicated except in atypical circumstances as it usually resolves without treatment.
- Viral conjunctivitis should not be treated with antibiotics. Antibiotics should only be used with confirmation that a patient has bacterial conjunctivitis.
- Older persons often have bacteria in their urine which is detected in routine urine tests, but unless the person has the symptoms of a urinary tract infection, antibiotics should not be used in response.
- Eczema should not be treated with oral antibiotics. Dry skin can be treated with lotions or other symptom treatments.
- The use of topical antibiotics to treat surgical wounds does not reduce infection rates in comparison with non-antibiotic ointment or no ointment at all.
Fungal pneumonia can be treated with antifungal drugs and sometimes by surgical debridement.
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.