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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Ribavirin is one medication which has shown good potential for the treatment of HPIV-3 given recent in-vitro tests (in-vivo tests show mixed results). Ribavirin is a broadscale anti-viral and is currently being administered to those who are severely immuno-compromised, despite the lack of conclusive evidence for its use. Protein inhibitors and novel forms of medication have also been proposed to relieve the symptoms of infection.
Furthermore, antibiotics may be used if a secondary bacterial infection develops. Corticosteroid treatment and nebulizers are also a first line choice against croup if breathing difficulties ensue.
Neither the combination of antivirals and interferons (ribavirin + interferon alfa-2a or interferon alfa-2b) nor corticosteroids improved outcomes.
When rhesus macaques were given interferon-α2b and ribavirin and exposed to MERS, they developed less pneumonia than control animals. Five critically ill people with MERS in Saudi Arabia with ARDS and on ventilators were given interferon-α2b and ribavirin but all ended up dying of the disease. The treatment was started late in their disease (a mean of 19 days after hospital admission) and they had already failed trials of steroids so it remains to be seen whether it may have benefit earlier in the course of disease. Another proposed therapy is inhibition of viral protease or kinase enzymes. Researchers are investigating a number of ways to combat the outbreak of Middle East respiratory syndrome coronavirus, including using interferon, chloroquine, chlorpromazine, loperamide, and lopinavir, as well as other agents such as mycophenolic acid and camostat.
As of April 2020, there is no specific treatment for COVID-19. Research is, however, ongoing. For symptoms, some medical professionals recommend paracetamol (acetaminophen) over ibuprofen for first-line use. The WHO does not oppose the use of non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen for symptoms, and the FDA says currently there is no evidence that NSAIDs worsen COVID-19 symptoms.
While theoretical concerns have been raised about ACE inhibitors and angiotensin receptor blockers, as of 19 March 2020, these are not sufficient to justify stopping these medications. Steroids, such as methylprednisolone, are not recommended unless the disease is complicated by acute respiratory distress syndrome.
Medications to prevent blood clotting have been suggested for treatment, and anticoagulant therapy with low molecular weight heparin appears to be associated with better outcomes in severe COVID‐19 showing signs of coagulopathy (elevated D-dimer).
Antibiotics are ineffective, as SARS is a viral disease. Treatment of SARS is largely supportive with antipyretics, supplemental oxygen and mechanical ventilation as needed.
People with SARS must be isolated, preferably in negative pressure rooms, with complete barrier nursing precautions taken for any necessary contact with these patients.
Some of the more serious damage caused by SARS may be due to the body's own immune system reacting in what is known as cytokine storm.
As of 2017, there is no cure or protective vaccine for SARS that has been shown to be both safe and effective in humans. The identification and development of novel vaccines and medicines to treat SARS is a priority for governments and public health agencies around the world. MassBiologics, a non-profit organization engaged in the discovery, development and manufacturing of biologic therapies, is cooperating with researchers at NIH and the CDC developed a monoclonal antibody therapy that demonstrated efficacy in animal models.
Research into potential treatments started in January 2020, and several antiviral drugs are in clinical trials. Remdesivir appears to be the most promising. Although new medications may take until 2021 to develop, several of the medications being tested are already approved for other uses or are already in advanced testing. Antiviral medication may be tried in people with severe disease. The WHO recommended volunteers take part in trials of the effectiveness and safety of potential treatments.
The FDA has granted temporary authorisation to convalescent plasma as an experimental treatment in cases where the person's life is seriously or immediately threatened. It has not undergone the clinical studies needed to show it is safe and effective for the disease.
Antibiotics are given to treat any bacterial infection present. Cough suppressants are used if the cough is not productive. NSAIDs are often given to reduce fever and upper respiratory inflammation. Prevention is by vaccinating for canine adenovirus, distemper, parainfluenza, and "Bordetella". In kennels, the best prevention is to keep all the cages disinfected. In some cases, such as "doggie daycares" or nontraditional playcare-type boarding environments, it is usually not a cleaning or disinfecting issue, but rather an airborne issue, as the dogs are in contact with each other's saliva and breath. Although most kennels require proof of vaccination, the vaccination is not a fail-safe preventative. Just like human influenza, even after receiving the vaccination, a dog can still contract mutated strains or less severe cases.
In cases of viral pneumonia where influenza A or B are thought to be causative agents, patients who are seen within 48 hours of symptom onset may benefit from treatment with oseltamivir or zanamivir. Respiratory syncytial virus (RSV) has no direct acting treatments, but ribavirin in indicated for severe cases. Herpes simplex virus and varicella-zoster virus infections are usually treated with aciclovir, whilst ganciclovir is used to treat cytomegalovirus. There is no known efficacious treatment for pneumonia caused by SARS coronavirus, MERS coronavirus, adenovirus, hantavirus, or parainfluenza. Care is largely supportive.
No specific treatment is available, but antibiotics can be used to prevent secondary infections.
Vaccines are available (ATCvet codes: for the inactivated vaccine, for the live vaccine; plus various combinations).
Biosecurity protocols including adequate isolation, disinfection are important in controlling the spread of the disease.
Treatments that may help with symptoms include simple pain medication and medications for fevers such as ibuprofen and acetaminophen (paracetamol). It, however, is not clear if acetaminophen helps with symptoms. It is not known if over the counter cough medications are effective for treating an acute cough. Cough medicines are not recommended for use in children due to a lack of evidence supporting effectiveness and the potential for harm. In 2009, Canada restricted the use of over-the-counter cough and cold medication in children six years and under due to concerns regarding risks and unproven benefits. The misuse of dextromethorphan (an over-the-counter cough medicine) has led to its ban in a number of countries. Intranasal corticosteroids have not been found to be useful.
In adults short term use of nasal decongestants may have a small benefit. Antihistamines may improve symptoms in the first day or two; however, there is no longer-term benefit and they have adverse effects such as drowsiness. Other decongestants such as pseudoephedrine appear effective in adults. Ipratropium nasal spray may reduce the symptoms of a runny nose but has little effect on stuffiness. The safety and effectiveness of nasal decongestant use in children is unclear.
Due to lack of studies, it is not known whether increased fluid intake improves symptoms or shortens respiratory illness, and there is a similar lack of data for the use of heated humidified air. One study has found chest vapor rub to provide some relief of nocturnal cough, congestion, and sleep difficulty.
No medications or herbal remedies have been conclusively demonstrated to shorten the duration of infection. Treatment thus comprises symptomatic relief. Getting plenty of rest, drinking fluids to maintain hydration, and gargling with warm salt water are reasonable conservative measures. Much of the benefit from treatment is, however, attributed to the placebo effect.
To increase their effectiveness, vaccines should be administered as soon as possible after a dog enters a high-risk area, such as a shelter. 10 to 14 days are required for partial immunity to develop. Administration of B. bronchiseptica and canine-parainfluenza vaccines may then be continued routinely, especially during outbreaks of kennel cough. There are several methods of administration, including parenteral and intranasal. However, the intranasal method has been recommended when exposure is imminent, due to a more rapid and localized protection. Several intranasal vaccines have been developed that contain canine adenovirus in addition to B bronchiseptica and canine-parainfluenza virus antigens. Studies have thus far not been able to determine which formula of vaccination is the most efficient. Adverse effects of vaccinations are mild, but the most common effect observed up to 30 days after administration is nasal discharge. Vaccinations are not always effective. In one study it was found that 43.3% of all dogs in the study population with respiratory disease had in fact been vaccinated.
There is no vaccine for SARS to date. Isolation and quarantine remain the most effective means to prevent the spread of SARS. Other preventative measures include:
- Disinfection of surfaces for fomites
- Wearing a surgical mask
- Avoiding contact with bodily fluids
- Washing the personal items of someone with SARS in hot, soapy water (eating utensils, dishes, bedding, etc.)
- Keeping children with symptoms home from school
Many public health interventions were taken to help control the spread of the disease; which is mainly spread through respiratory droplets in the air. These interventions included earlier detection of the disease, isolation of people who are infected, droplet and contact precautions, and the use of personal protective equipment (PPE); including masks and isolation gowns. A screening process was also put in place at airports to monitor air travel to and from affected countries. Although no cases have been identified since 2004, the CDC is still working to make federal and local rapid response guidelines and recommendations in the event of a reappearance of the virus.
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.
While the mechanism of spread of MERS-CoV is currently not known, based on experience with prior coronaviruses, such as SARS, the WHO currently recommends that all individuals coming into contact with MERS suspects should (in addition to standard precautions):
- Wear a medical mask
- Wear eye protection (i.e. goggles or a face shield)
- Wear a clean, non sterile, long sleeved gown; and gloves (some procedures may require sterile gloves)
- Perform hand hygiene before and after contact with the person and his or her surroundings and immediately after removal of personal protective equipment (PPE)
For procedures which carry a risk of aerosolization, such as intubation, the WHO recommends that care providers also:
- Wear a particulate respirator and, when putting on a disposable particulate respirator, always check the seal
- Wear eye protection (i.e. goggles or a face shield)
- Wear a clean, non-sterile, long-sleeved gown and gloves (some of these procedures require sterile gloves)
- Wear an impermeable apron for some procedures with expected high fluid volumes that might penetrate the gown
- Perform procedures in an adequately ventilated room; i.e. minimum of 6 to 12 air changes per hour in facilities with a mechanically ventilated room and at least 60 liters/second/patient in facilities with natural ventilation
- Limit the number of persons present in the room to the absolute minimum required for the person’s care and support
- Perform hand hygiene before and after contact with the person and his or her surroundings and after PPE removal.
The duration of infectivity is also unknown so it is unclear how long people must be isolated, but current recommendations are for 24 hours after resolution of symptoms. In the SARS outbreak the virus was not cultured from people after the resolution of their symptoms.
It is believed that the existing SARS research may provide a useful template for developing vaccines and therapeutics against a MERS-CoV infection. Vaccine candidates are currently awaiting clinical trials.
The most commonly available antiviral drugs for treating FIP are either feline recombinant interferon omega (Virbagen Omega, Virbac) or human interferon. Since the action of interferon is species-specific, feline interferon is more efficacious than human interferon.
An experimental antiviral drug called GC 376 was used in a field trial of 20 cats: 7 cats went into remission, 13 cats responded initially but relapsed and were euthanazed. This drug is not yet commercially available: watch the University of California Davis website for progress updates.
The go-to immunosuppressive drug in FIP is prednisolone.
An experimental polyprenyl immunostimulant (PI) is manufactured by Sass and Sass and tested by Dr. Al Legendre, who described survival over 1 year in three cats diagnosed with FIP and treated with the medicine. In a subsequent field study of 60 cats with non-effusive FIP treated with PI, 52 cats (87%) died before 200 days, but eight cats survived over 200 days from the start of PI treatment for and four of those survived beyond 300 days. There are anecdotal reports on the internet of cats surviving even longer.
Treatment of bronchiolitis is usually focused on the symptoms instead of the infection itself since the infection will run its course and complications are typically from the symptoms themselves. Without active treatment half of cases will go away in 13 days and 90% in three weeks.
Measures for which the evidence is unclear include nebulized epinephrine, nasal suctioning, and nebulized hypertonic saline. Treatments which the evidence does not support include salbutamol, steroids, antibiotics, antivirals, chest physiotherapy, and cool mist.
Currently other medications do not yet have evidence to support their use. Ribavirin is an antiviral drug which does not appear to be effective for bronchiolitis. Antibiotics are often given in case of a bacterial infection complicating bronchiolitis, but have no effect on the underlying viral infection. Corticosteroids have no proven benefit in bronchiolitis treatment and are not advised. DNAse has not been found to be effective.
The non-specific effects of vaccines can be boosted or diminished when other immunomodulating health interventions such as other vaccines, or vitamins, are provided.
The best prevention against viral pneumonia is vaccination against influenza, adenovirus, chickenpox, herpes zoster, measles, and rubella.
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".
Neuraminidase inhibitors may be used to treat viral pneumonia caused by influenza viruses (influenza A and influenza B). No specific antiviral medications are recommended for other types of community acquired viral pneumonias including SARS coronavirus, adenovirus, hantavirus, and parainfluenza virus. Influenza A may be treated with rimantadine or amantadine, while influenza A or B may be treated with oseltamivir, zanamivir or peramivir. These are of most benefit if they are started within 48 hours of the onset of symptoms. Many strains of H5N1 influenza A, also known as avian influenza or "bird flu", have shown resistance to rimantadine and amantadine. The use of antibiotics in viral pneumonia is recommended by some experts, as it is impossible to rule out a complicating bacterial infection. The British Thoracic Society recommends that antibiotics be withheld in those with mild disease. The use of corticosteroids is controversial.
Antibiotics improve outcomes in those with bacterial pneumonia. Antibiotic choice depends initially on the characteristics of the person affected, such as age, underlying health, and the location the infection was acquired. In the UK, treatment before culture results with amoxicillin is recommended as the first line for community-acquired pneumonia, with doxycycline or clarithromycin as alternatives. In North America, where the "atypical" forms of community-acquired pneumonia are more common, macrolides (such as azithromycin or erythromycin), and doxycycline have displaced amoxicillin as first-line outpatient treatment in adults. In children with mild or moderate symptoms, amoxicillin remains the first line. The use of fluoroquinolones in uncomplicated cases is discouraged due to concerns about side-effects and generating resistance in light of there being no greater clinical benefit.
For those who require hospitalization and caught their pneumonia in the community the use of a β-lactam such as cephazolin plus macrolide such as azithromycin or a fluoroquinolones is recommended. The addition of corticosteroids also appears to improve outcomes.
The duration of treatment has traditionally been seven to ten days, but increasing evidence suggests that shorter courses (three to five days) are similarly effective. Recommendations for hospital-acquired pneumonia include third- and fourth-generation cephalosporins, carbapenems, fluoroquinolones, aminoglycosides, and vancomycin. These antibiotics are often given intravenously and used in combination. In those treated in hospital, more than 90% improve with the initial antibiotics.
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.