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Measles

Disease Details

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Description: Measles is a highly contagious viral infection characterized by fever, cough, runny nose, inflamed eyes, and a red, blotchy skin rash.
Type: Measles is caused by the measles virus, which is a type of single-stranded, negative-sense RNA virus. Measles is not genetically transmitted; it is an infectious disease spread through respiratory droplets from coughing and sneezing.
Signs And Symptoms: Symptoms typically begin 10–14 days after exposure. The classic symptoms include a four-day fever (the four Ds) and the three Cs—cough, coryza (head cold, fever, sneezing), and conjunctivitis (red eyes)—along with a maculopapular rash. Fever is common and typically lasts for about one week; the fever seen with measles is often as high as 40 °C (104 °F).Koplik's spots seen inside the mouth are diagnostic for measles, but are temporary and therefore rarely seen. Koplik spots are small white spots that are commonly seen on the inside of the cheeks opposite the molars. They appear as "grains of salt on a reddish background." Recognizing these spots before a person reaches their maximum infectiousness can help reduce the spread of the disease.The characteristic measles rash is classically described as a generalized red maculopapular rash that begins several days after the fever starts. It starts on the back of the ears and, after a few hours, spreads to the head and neck before spreading to cover most of the body. The measles rash appears two to four days after the initial symptoms and lasts for up to eight days. The rash is said to "stain", changing color from red to dark brown, before disappearing. Overall, measles usually resolves after about three weeks.People who have been vaccinated against measles but have incomplete protective immunity may experience a form of modified measles. Modified measles is characterized by a prolonged incubation period, milder, and less characteristic symptoms (sparse and discrete rash of short duration).
Prognosis: Most people survive measles, though in some cases, complications may occur. About 1 in 4 individuals will be hospitalized and 1–2 in 1,000 will die. Complications are more likely in children under age 5 and adults over age 20. Pneumonia is the most common fatal complication of measles infection and accounts for 56–86% of measles-related deaths.Possible consequences of measles virus infection include laryngotracheobronchitis, 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 measles rash breaks out 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.For people having had measles, it is rare to ever have a symptomatic reinfection.The measles virus can deplete previously acquired immune memory by killing cells that make antibodies, and thus weakens the immune system, which can cause deaths from other diseases. Suppression of the immune system by measles lasts about two years and has been epidemiologically implicated in up to 90% of childhood deaths in third world countries, and historically may have caused rather more deaths in the United States, the UK and Denmark than were directly caused by measles. Although the measles vaccine contains an attenuated strain, it does not deplete immune memory.
Onset: The onset of measles typically occurs 7-14 days after exposure to the virus. Initial symptoms include high fever, cough, runny nose, and red, watery eyes. These symptoms are usually followed by the appearance of a red rash that starts on the face and spreads to the rest of the body.
Prevalence: The prevalence of measles can vary widely by region and vaccination coverage. In areas with high vaccination rates, measles is relatively rare. However, in regions with lower vaccination coverage, outbreaks can occur more frequently. Global efforts led by the World Health Organization (WHO) and other public health organizations aim to reduce measles prevalence through vaccination programs. Despite these efforts, vaccine hesitancy and other barriers can lead to periodic outbreaks.
Epidemiology: Measles is extremely infectious and its continued circulation in a community depends on the generation of susceptible hosts by birth of children. In communities that 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.In 2011, the WHO estimated that 158,000 deaths were caused by measles. This is down from 630,000 deaths in 1990. As of 2018, measles remains a leading cause of vaccine-preventable deaths in the world. In developed countries the mortality rate is lower, for example in England and Wales from 2007 to 2017 death occurred between two and three cases out of 10,000. In children one to three cases out of every 1,000 die in the United States (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 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. There were 142,300 measles related deaths globally in 2018, of which most cases were reported from African and eastern Mediterranean regions. These estimates were slightly higher than that of 2017, when 124,000 deaths were reported due to measles infection globally.In 2000, the WHO established the Global Measles and Rubella Laboratory Network (GMRLN) to provide laboratory surveillance for measles, rubella, and congenital rubella syndrome. Data from 2016 to 2018 show that the most frequently detected measles virus genotypes are decreasing, suggesting that increasing global population immunity has decreased the number of chains of transmission.Cases reported in the first three months of 2019, were 300% higher than in the first three months of 2018, with outbreaks in every region of the world, even in countries with high overall vaccination coverage where it spread among clusters of unvaccinated people. The numbers of reported cases as of mid-November is over 413,000 globally, with an additional 250,000 cases in DRC (as reported through their national system), similar to the increasing trends of infection reported in the earlier months of 2019, compared to 2018. In 2019, the total number of cases worldwide climbed to 869,770. The number of cases reported for 2020 is lower compare to 2019. According to the WHO, the COVID-19 pandemic hindered vaccination campaigns in at least 68 countries, including in countries that were experiencing outbreaks, which caused increased risk of additional cases.In February 2024, the World Health Organization said more than half of the world was at risk of a measles outbreak due to Covid-19 pandemic-related disruptions in that month. All the world regions have reported such outbreaks with the exception of the Americas, though these could still be expected to become hotspots in the future. Death rates during the outbreaks tend to be higher among poorer countries but middle income nations are also heavily impacted, according to the WHO.
Intractability: Measles is not considered intractable. It is a highly contagious viral disease, but it can be effectively prevented with vaccination. The measles, mumps, and rubella (MMR) vaccine is highly effective in providing immunity against the disease. In most cases, once someone has been infected, they develop lifelong immunity. However, in unvaccinated populations, measles can spread rapidly and cause serious health complications.
Disease Severity: Measles is often considered a severe disease, especially in young children and immunocompromised individuals. It can lead to serious health complications, such as pneumonia, encephalitis (swelling of the brain), and even death in some cases. Despite being preventable through vaccination, measles remains a significant cause of morbidity and mortality in regions with low vaccination coverage.
Healthcare Professionals: Disease Ontology ID - DOID:8622
Pathophysiology: Once the measles virus gets onto the mucosa, it infects the epithelial cells in the trachea or bronchi. Measles virus uses a protein on its surface called hemagglutinin (H protein), to bind to a target receptor on the host cell, which could be CD46, which is expressed on all nucleated human cells, CD150, aka signaling lymphocyte activation molecule or SLAM, which is found on immune cells like B or T cells, and antigen-presenting cells, or nectin-4, a cellular adhesion molecule. Once bound, the fusion, or F protein helps the virus fuse with the membrane and ultimately get inside the cell.As the virus is a single-stranded negative-sense RNA virus, it includes the enzyme RNA-dependent RNA polymerase (RdRp) which is used to transcribe its genome into a positive-sense mRNA strand.After entering a cell, it is ready to be translated into viral proteins, wrapped in the cell's lipid envelope, and sent out of the cell as a newly made virus. Within days, the measles virus spreads through local tissue and is picked up by dendritic cells and alveolar macrophages, and carried from that local tissue in the lungs to the local lymph nodes. From there it continues to spread, eventually getting into the blood and spreading to more lung tissue, as well as other organs like the intestines and the brain. Functional impairment of the infected dendritic cells by the measles virus is thought to contribute to measles-induced immunosuppression.
Carrier Status: Measles does not have a carrier state. It is an acute viral infection, meaning individuals are either infected and symptomatic, or they are not infected at all. Those who contract measles are contagious from about four days before to four days after the characteristic rash appears. There is no asymptomatic or chronic carrier state for measles.
Mechanism: Measles is caused by the measles virus, a single-stranded, negative-sense RNA virus belonging to the Paramyxoviridae family.

**Mechanism:**
1. **Transmission**: The virus is highly contagious and primarily spreads through respiratory droplets when an infected person coughs or sneezes. It can also spread through direct contact with nasal or throat secretions.
2. **Initial Infection**: After inhalation, the virus infects the respiratory epithelial cells and possibly spreads to local lymphoid tissues.
3. **Primary Viremia**: The virus enters the bloodstream and spreads to other tissues.
4. **Secondary Viremia**: After initial replication, the virus re-enters the bloodstream, leading to widespread dissemination.
5. **Clinical Symptoms**: Symptoms including fever, cough, coryza, conjunctivitis, and the characteristic maculopapular rash usually appear about 7-14 days after exposure.

**Molecular Mechanisms:**
1. **Viral Entry**: The virus uses the hemagglutinin protein (H protein) to attach to host cell receptors like CD150/SLAM (found on immune cells) and nectin-4 (found on epithelial cells).
2. **Membrane Fusion**: Following attachment, the fusion protein (F protein) facilitates the fusion of the viral envelope with the host cell membrane, allowing the viral RNA to enter the host cell.
3. **Replication and Transcription**: The viral RNA genome is transcribed and replicated in the cytoplasm. The virus uses its RNA-dependent RNA polymerase to transcribe its genes into mRNA, which are then translated into viral proteins needed for replication.
4. **Immune Evasion**: The virus can suppress the host immune response by inhibiting interferon signaling pathways and modifying antigen presentation, aiding in its dissemination.
5. **Assembly and Release**: Newly synthesized viral RNA and proteins are assembled into new virions, which are then released from the host cell to infect more cells.

Overall, the molecular mechanisms of measles virus involve intricate interactions between viral proteins and host cell receptors, leading to efficient viral replication and potent host immune responses.
Treatment: There is no specific antiviral treatment if measles develops. Instead the medications are generally aimed at treating superinfections, maintaining good hydration with adequate fluids, and pain relief. Some groups, like young children and the severely malnourished, are also given vitamin A, which acts as an immunomodulator that boosts the antibody responses to measles and decreases the risk of serious complications.
Compassionate Use Treatment: Measles is primarily managed through supportive care, as there's no specific antiviral treatment for the virus. However, in certain situations, the following approaches have been considered:

1. **Vitamin A supplementation:** This is not off-label but is a standard supportive treatment, particularly in children with severe measles or those who have vitamin A deficiency. It can reduce the severity of the disease and the risk of complications.

2. **Ribavirin:** This antiviral drug has shown some efficacy against measles in vitro and may be considered an experimental treatment for severe cases, especially in immunocompromised patients. Its use is off-label and not widely adopted due to limited evidence.

3. **Intravenous Immunoglobulin (IVIG):** This can be used in severely immunocompromised patients who are exposed to measles or have developed the infection. It is an off-label use and aims to provide passive immunity.

These treatments are not standard care and should be considered on a case-by-case basis, preferably under the guidance of a medical expert. Vaccination remains the most effective method for preventing measles.
Lifestyle Recommendations: For measles, lifestyle recommendations typically include:

1. **Isolation:** Stay away from others to prevent the spread of the virus, especially to those who are not vaccinated or have weakened immune systems.
2. **Rest:** Adequate rest is crucial to help your body recover.
3. **Hydration:** Drink plenty of fluids to stay hydrated.
4. **Nutritional Support:** Maintain a balanced diet to support your immune system.
5. **Hygiene:** Practice good hygiene, including regular hand washing and using tissues or elbow to cover coughs and sneezes, to reduce the spread of the virus.
6. **Avoid Irritants:** Stay away from smoke and other irritants, as they can exacerbate respiratory symptoms.
7. **Monitor Symptoms:** Keep an eye on symptoms and seek medical attention if they worsen or complications arise.
Medication: Treatment is supportive, with ibuprofen or paracetamol (acetaminophen) to reduce fever and pain and, if required, a fast-acting medication to dilate the airways for cough. As for aspirin, some research has suggested a correlation between children who take aspirin and the development of Reye syndrome.The use of vitamin A during treatment is recommended to decrease the risk of blindness; however, it does not prevent or cure the disease. A systematic review of trials into its use found no reduction in overall mortality, but two doses (200,000 IU) of vitamin A was shown to reduce mortality for measles in children younger than two years of age. It is unclear if zinc supplementation in children with measles affects outcomes as it has not been sufficiently studied. There are no adequate studies on whether Chinese medicinal herbs are effective.
Repurposable Drugs: There are no widely recognized repurposable drugs for treating measles directly. The disease is generally managed with supportive care, including hydration, fever management, and vitamin A supplementation. Preventative measures primarily involve vaccination with the MMR (measles, mumps, rubella) vaccine.
Metabolites: Measles is an infectious viral disease. While specific metabolites unique to measles virus infection have not been well-described, the body’s metabolic response to the infection typically involves alterations in:

1. **Glucose metabolism**: Enhanced glycolysis and reduced glucose availability can occur as the body fights the infection.
2. **Amino acid metabolism**: Changes in amino acid levels, particularly those involved in immune response and repair processes, such as glutamine, can be observed.
3. **Lipid metabolism**: Alterations in lipid profiles, including changes in cholesterol and fatty acid metabolism, may be seen during infection.

Metabolomic studies on measles are limited, but the infection is generally marked by a combination of immune response and metabolic adjustments as the body works to counteract the virus.
Nutraceuticals: Nutraceuticals have not been established as an effective treatment for measles. The primary prevention method for measles is vaccination with the MMR (measles, mumps, rubella) vaccine. If someone contracts measles, supportive care is usually provided, including maintaining hydration, rest, and addressing fever with medications like acetaminophen. There are no conclusive studies indicating that nutraceuticals can prevent or treat measles.
Peptides: Measles is caused by the measles virus, a highly contagious pathogen. It triggers an immune response involving peptides, which are short chains of amino acids. These viral peptides are presented by immune cells to T cells, which learn to recognize and attack the virus. Antigenic peptides from the measles virus are crucial for the development of effective vaccines.

Regarding "nan," if you are referring to nanoparticles in the context of measles, researchers have been exploring the use of nanoparticles for vaccine delivery and diagnostic purposes. Nanoparticles can enhance the immune response by improving the delivery and stability of measles antigens, potentially leading to more effective vaccines and treatments.