Measles (probably from Middle Dutch or Middle High German masel(e), meaning "blemish, blood blister") is a highly contagious, vaccine-preventable infectious disease caused by the measles virus. Other names include morbilli, rubeola, 9-day measles, red measles, and English measles. Symptoms usually develop 10–12 days after exposure to an infected person and last 7–10 days. Initial symptoms typically include fever, often greater than , cough, runny nose, and inflamed eyes. Small white spots known as Koplik spots may form inside the mouth two or three days after the start of symptoms, followed by a rash which usually starts on the face and then spreads to the rest of the body. Common complications include diarrhea (in 8% of cases), middle ear infection (7%), and pneumonia (6%). These occur in part due to measles-induced immunosuppression. Less commonly, seizures, blindness, or inflammation of the brain may occur.
Meases is caused by the measles virus, an RNA virus which is closely related to rinderpest (affecting cattle) and canine distemper. Measles is an airborne disease which spreads easily from one person to the next through the coughs and sneezes of infected people. People are infectious to others from four days before to four days after the start of the rash. Immunity is lifelong once it has been acquired, either through vaccination or after recovering from the disease. Diagnosis of measles by symptoms is difficult, as many of the symptoms can be caused by a number of diseases; laboratory tests are necessary for a conclusive diagnosis.
There is no specific antiviral treatment if measles develops. Instead the medications are aimed at preventing or treating secondary infections, maintaining good hydration, and pain relief.
The measles vaccine is safe and effective at preventing the disease. It is generally delivered in combination with other vaccines, with the first dose administered to infants between 9 and 18 months of age, and a second dose a few months later. Due to the ease of transmission more than 95% of the community must be vaccinated in order to achieve herd immunity.
Measles is currently estimated to infect about 10 million people and cause 95 thousand deaths a year, primarily in countries with low per capita income and poor health systems. It is a significant cause of death among children. Vaccination programs resulted in an 80% decrease in deaths from measles between 2000 and 2017, with about 85% of children worldwide having received their first dose as of 2017. There has been little progress since then, in part due to the COVID-19 pandemic, and in part due to the difficulty of delivering vaccination programs in poor and conflicted areas of the world.
Genomic analysis indicates that measles as a human disease evolved from rinderpest, between 900 and 2,400 years ago; historical accounts of a disease closely resembling measles exist from the 7th century. Prior to the introduction of vaccination programs, measles was endemic worldwide, causing an estimated 2 million deaths every year.
Signs and symptoms The initial symptoms of measles are non-specific, resembling a common cold - raised temperature, runny nose, sneezing, cough, and sore eyes (conjunctivitis). These symptoms begin 7–23 days (most commonly, 10–14 days) after exposure to an infected person. The fever may reach or exceed . After a couple more days, little white spots may appear inside the mouth (Koplik spots); they are short lived and may not be noticed. At this stage of infection a characteristic skin rash appears, initially on the face and behind the ears, spreading to the rest of the body.
Uncomplicated cases of measles typically improve within days of rash onset and resolve within 7–10 days. The virus is contagious from four days before to four days after the rash appears.
Because development of the rash and conjunctivitis requires a functional immune system, immunocompromised people may not be diagnosed as readily.
Complications Immediate complications of measles are common, affecting approximately 30% of cases. Common complications are middle ear infections, conjunctivitis, severe diarrhea (leading to dehydration), and breathing problems such as croup and pneumonia.
Complications can be severe, such as encephalitis, deafness, blindness and rare but usually fatal subacute sclerosing panencephalitis (SSPE). In the US, the CDC estimates 1 out of every 5 unvaccinated people who get measles will need to be hospitalized; and that between 1 and 3 out of every 1,000 children with the disease will die of its complications. Mortality is worse in places with poor nutrition and poor healthcare - in parts of Africa, the case fatality rate is estimated up to 6% for settled populations, rising as high as 30% in refugee settlements. Pneumonia and encephalitis are the leading causes of death following measles.
Pregnancy Measles during pregnancy can have serious consequences for both mother and child. Pregnant women infected with measles are significantly more likely to need hospitalisation and are at greater risk of pneumonia and death. There are also increased risks of miscarriage, premature delivery, and of babies having low birth weight,
Underlying mechanisms Some complications are caused directly by the virus, while others are caused by viral suppression of the immune system.
The virus damages the membranes lining the respiratory tract (nose, throat and lungs), sometimes causing viral pneumonia but also making it easy for bacteria to cause secondary pneumonia and bronchitis. It can also damage the lining of the Eustachian tube, allowing bacteria to penetrate to and infect the middle ear (otitis media). Viral infection of the intestine leads to diarrhea, sometimes severe causing dehydration. In rare cases, the virus directly invades the central nervous system, triggering severe inflammatory responses or autoimmune demyelination, which can lead to post-infectious encephalitis.
A mechanism called "immune amnesia" (see below) underlies longer term consequences of measles. The virus targets the memory cells of the immune system; these are components of the adaptive immune system, providing the body with resistance to pathogens which have previously been encountered. Without these cells, the patient's body has little or no immunity to diseases which it had previously been immune to; the effect lasts for up to three years after the measles infection.
Risk factors
Those under 5 and over 20 are at higher risk for complications. Conditions which weaken or modify the immune response also increase risk for complications; these include pregnancy, malnutrition, hematologic cancer, HIV/AIDS, and use of immunosuppressive medication.
Immune amnesia The measles virus can deplete previously acquired immune memory by killing cells that make antibodies, and thus weakens the immune system, opening the body up to potentially severe infections from other diseases. Suppression of the immune system by measles lasts up to three years and has been epidemiologically implicated in an increase in childhood mortality from other infectious diseases during this period. The measles vaccine contains an attenuated strain of the virus which does not deplete immune memory.
This suppression phenomenon, known as "immune amnesia", increases the risk of subsequent infections. Shortly after recovering from measles, there is a significant decrease in antibodies against other bacteria and viruses that patients may have acquired during their lifetimes prior to infection with the measles virus. Primate studies suggest that immune amnesia arises during infection when the virus destroys existing memory lymphocytes; after recovery, the body generates new memory lymphocytes which are specific to measles virus alone. This creates lasting immunity to measles re-infection, but destroys existing immunities to other diseases. Comparison of childhood mortality statistics from before and after the introduction of measles vaccination suggests that immune amnesia continues for 2–3 years following infection with the measles virus.
Cause
Measles is caused by the measles virus, a single-stranded, non-segmented, negative-sense, enveloped RNA virus of the genus Morbillivirus within the family Paramyxoviridae. It is related most closely to rinderpest, a cattle virus eradicated in 2001, and canine distemper, a mammalian disease that causes neurologic deterioration. There are 24 strains of measles virus divided into eight clades designated A-H.
Humans are the only natural hosts of the virus, and no other animal host is known to exist, although mountain gorillas are believed to be susceptible to the disease.
Risk factors for measles virus infection include immunodeficiency caused by HIV/AIDS, immunosuppression following receipt of an organ or a stem cell transplant, alkylating agents, or corticosteroid therapy, regardless of immunization status; and travel to areas where measles commonly occurs or contact with travelers from such an area. Very young children may be protected by antibodies acquired from their mother during pregnancy, but this immunity fades out a few weeks or months after birth.
Pathophysiology
Infection begins when the virus enters the new host's airways in droplets exhaled by another infected person, and targets cells of the immune system (macrophages and dendritic cells) in the lining of the airways. The viral hemagglutinin protein (H) binds to SLAM receptors (signaling lymphocyte activation molecule, also called CD150) on the surface of these cells, and the viral fusion protein (F) then fuses the membranes of the virion and the cell, enabling the genetic material of the virus to invade the cell.
The cycle of infection within a cell covers approximately 24 hours, during this time, the infected cell generates progressively greater quantities of viral proteins and RNA. The H and F proteins are expressed on the cell's membrane and cause it to fuse with and infect neighbouring cells. New virus particles (virions) bud off until eventually the cell breaks apart and releases a payload of virions into the surrounding tissues.
Over the two to three days following initial infection, infected cells spread through the body's lymphatic system (lymph nodes and spleen) where they pass the virus on to other groups of immune cells, including B cells, T cells, thymocytes, and hematopoietic stem cells. Together with the action of the virus' V and C proteins, this compromises the body's ability to mount an immune response to the infection. Measles has been described as a "Trojan horse" infection as the immune system normally protects the body from infection. In measles, it has been infiltrated and instead becomes a conduit through which the infection grows and spreads.
Infective virions spread through the blood circulation, continuing to target cells of the immune system via SLAM receptors, as well as epithelial cells in the skin and respiratory tract by targeting nectin-4, a protein which normally binds epithelial cells together. The early symptoms of measles appear approximately 10 to 14 days after infection, driven by damage to epithelial cells and the beginning of an immune response. A persistent cough, conjunctivitis, and Koplik spots are caused by damage to epithelial cells, with the cough releasing highly infective droplets. Fever develops as the body begins to generate an immune response.
The typical measles rash which develops a few days later is caused by T-lymphocytes which recognise infected cells in the skin and destroy them.
Transmission