Measles

Measles
Specialty	Infectious diseases

Measles, also known as morbilli, English measles, or rubeola (and not to be confused with rubella or roseola) is a highly contagious viral infection of the respiratory system, immune system, and skin caused by a paramyxovirus of the genus Morbillivirus. Symptoms usually develop 7–14 days (average 10–12) after exposure to an infected person and the initial symptoms usually include a high fever (often > 40 °C [104 °F]), Koplik's spots (spots in the mouth, these usually appear 1–2 days prior to the rash and last 3–5 days), malaise, loss of appetite, hacking cough (although this may be the last symptom to appear), runny nose and red eyes. After this comes a spot-like rash that covers much of the body. The course of measles, provided there are no complications, such as bacterial infections, usually lasts about 7–10 days.

Measles is an airborne disease that is spread through respiration (contact with fluids from an infected person's nose and mouth, either directly or through aerosol transmission via coughing or sneezing). The virus is highly contagious—90% of people without immunity sharing living space with an infected person will catch it. An asymptomatic incubation period occurs nine to twelve days from initial exposure. The period of infectivity has not been definitively established, some saying it lasts from two to four days prior, until two to five days following the onset of the rash (i.e., four to nine days infectivity in total), whereas others say it lasts from two to four days prior until the complete disappearance of the rash. The rash usually appears between two and three days after the onset of illness.

Signs and symptoms

Skin of a patient after 3 days of measles infection

Presentation of “Koplik's spots” on the third pre-eruptive day, indicative of the beginning onset of measles

The classic signs and symptoms of measles include four-day fevers (the 4 D's) and the three C's—cough, coryza (head cold), and conjunctivitis (red eyes)—along with fever and rashes. The fever may reach up to 40 °C (104 °F). Koplik's spots seen inside the mouth are pathognomonic (diagnostic) for measles, but are temporary and therefore rarely seen. Their recognition, before the affected person reaches maximum infectivity, can be used to reduce spread of epidemics.

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, often causing itching. 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.

Complications

Complications with measles are relatively common, ranging from mild complications such as diarrhea to serious complications such as pneumonia (either direct viral pneumonia or secondary bacterial pneumonia), otitis media, acute brain inflammation (and very rarely SSPE—subacute sclerosing panencephalitis), and corneal ulceration (leading to corneal scarring). Complications are usually more severe in adults who catch the virus. The death rate in the 1920s was around 30% for measles pneumonia.

Between 1987 and 2000, the case fatality rate across the United States was three measles-attributable deaths per 1000 cases, or 0.3%. In underdeveloped nations with high rates of malnutrition and poor healthcare, fatality rates have been as high as 28%. In immunocompromised persons (e.g., people with AIDS) the fatality rate is approximately 30%. Risk factors for severe measles and its complications include: malnutrition; underlying immunodeficiency; pregnancy; and vitamin A deficiency.

Cause

An electron micrograph of the measles virus.

Measles is caused by the measles virus, a single-stranded, negative-sense, enveloped RNA virus of the genus Morbillivirus within the family Paramyxoviridae. The virus was first isolated in 1954 by Nobel Laureate John F. Enders and Thomas Peebles, who were careful to point out that the isolations were made from patients who had Koplik's spots. Humans are the natural hosts of the virus; no other animal reservoirs are known to exist. This highly contagious virus is spread by coughing and sneezing via close personal contact or direct contact with secretions. Risk factors for measles virus infection include: immunodeficiency caused by HIV or AIDS, leukemia, alkylating agents, or corticosteroid therapy, regardless of immunization status; travel to areas where measles is endemic or contact with travelers to endemic areas; and the loss of passive, inherited antibodies before the age of routine immunization.

Diagnosis

Clinical diagnosis of measles requires a history of fever of at least three days, with at least one of the three C's (cough, coryza, conjunctivitis). Observation of Koplik's spots is also diagnostic of measles.

Alternatively, laboratory diagnosis of measles can be done with confirmation of positive measles IgM antibodies or isolation of measles virus RNA from respiratory specimens. For people unable to undergo phlebotomy, saliva can be collected for salivary measles-specific IgA testing. Positive contact with other patients known to have measles adds strong epidemiological evidence to the diagnosis. The contact with any infected person in any way, including semen through sex, saliva, or mucus, can cause infection.

Prevention

Rates of measles vaccination worldwide

Further information: Measles vaccine, MMR vaccine, and MMR vaccine controversy

In developed countries, children are immunized against measles at 12 months, generally as part of a three-part MMR vaccine (measles, mumps, and rubella). The vaccination is generally not given earlier than this because sufficient antimeasles immunoglobulins (antibodies) are acquired via the placenta from the mother during pregnancy may persist to prevent the vaccine viruses from being effective. A second dose is usually given to children between the ages of four and five, to increase rates of immunity. Vaccination rates have been high enough to make measles relatively uncommon. Adverse reactions to vaccination are rare, with fever and pain at the injection site being the most common. Life-threatening adverse reactions occur in less than one per million vaccinations (<0.0001%).

In developing countries where measles is highly endemic, WHO doctors recommend two doses of vaccine be given at six and nine months of age. The vaccine should be given whether the child is HIV-infected or not. The vaccine is less effective in HIV-infected infants than in the general population, but early treatment with antiretroviral drugs can increase its effectiveness. Measles vaccination programs are often used to deliver other child health interventions, as well, such as bed nets to protect against malaria, antiparasite medicine and vitamin A supplements, and so contribute to the reduction of child deaths from other causes.

Treatment

There is no specific treatment for measles. Most patients with uncomplicated measles will recover with rest and supportive treatment. It is, however, important to seek medical advice if the patient becomes more unwell, as they may be developing complications.

Some patients will develop pneumonia as a sequel to the measles. Other complications include ear infections, bronchitis (either viral bronchitis or secondary bacterial bronchitis), and brain inflammation. Brain inflammation from measles has a mortality rate of 15%. While there is no specific treatment for brain inflammation from measles, antibiotics are required for bacterial pneumonia, sinusitis, and bronchitis that can follow measles.

All other treatment addresses symptoms, with ibuprofen or paracetamol to reduce fever and pain and, if required, a fast-acting bronchodilator for cough. As for aspirin, some research has suggested a correlation between children who take aspirin and the development of Reye syndrome. Some research has shown aspirin may not be the only medication associated with Reye, and even antiemetics have been implicated, with the point being the link between aspirin use in children and Reye's syndrome development is weak at best, if not actually nonexistent. Nevertheless, most health authorities still caution against the use of aspirin for any fevers in children under 16.

The use of vitamin A in treatment has been investigated. A systematic review of trials into its use found no significant reduction in overall mortality, but it did reduce mortality in children aged under two years. A specific drug treatment for measles ERDRP-0519 has shown promising results in animal studies, but has not yet been tested in humans.

Prognosis

The majority of patients survive measles, though in some cases, complications may occur, which may include bronchitis, and—in about 1 in 100,000 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 breakout of the measles exanthem and begins with very high fever, severe headache, convulsions and altered mentation. A patient may become comatose, and death or brain injury may occur.

Epidemiology

Disability-adjusted life year for measles per 100,000 inhabitants in 2002.

  no data

  ≤ 10

  10–25

  25–50

  50–75

  75–100

  100–250

  250–500

  500–750

  750–1000

  1000–1500

  1500–2000

  ≥ 2000

Measles is extremely infectious and its continued circulation in a community depends on the generation of susceptible hosts by birth of children. In communities which 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 c. 250,000.

In 2011, the WHO estimated that there were about 158,000 deaths caused by measles. This is down from 630,000 deaths in 1990. In developed countries, death occurs in 1 to 2 cases out of every 1,000 (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%. Increased immunization has led to an estimated 78% drop in measles deaths among UN member states. This reduction made up 25% of the decline in mortality in children under five during this period.

Reported cases of disease, WHO statistics

WHO-Region	1980	1990	2000	2005	2014
African Region	1,240,993	481,204	520,102	316,224	12,125
Region of the Americas	257,790	218,579	1,755	19	3,100
Eastern Mediterranean Region	341,624	59,058	38,592	15,069	2,214
European Region	851,849	234,827	37,421	37,332	2,430
South-East Asia Region	199,535	224,925	61,975	83,627	1,540
Western Pacific Region	1,319,640	155,490	176,493	128,016	34,310
Worldwide	4,211,431	1,374,083	836,338	580,287	55,719

Even in countries where vaccination has been introduced, rates may remain high. In Ireland, vaccination was introduced in 1985. There were 99,903 cases that year. Within two years, the number of cases had fallen to 201, but this fall was not sustained. 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 Centers for Disease Control and Prevention (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.

In 2006–07 there were 12,132 cases in 32 European countries: 85% occurred in five countries: Germany, Italy, Romania, Switzerland and the UK. 80% occurred in children and there were 7 deaths.

Five out of six WHO regions have set goals to eliminate measles, and at the 63rd World Health Assembly in May 2010, delegates agreed a global target of a 95% reduction in measles mortality by 2015 from the level seen in 2000, as well as to move towards eventual eradication. However, no specific global target date for eradication has yet been agreed to as of May 2010.

On January 22, 2014, the World Health Organization and the Pan American Health Organization declared and certified Colombia free of the measles while becoming the first Latin American country to abolish the infection within its borders.

In Vietnam, in the Measles Epidemic in the beginning of 2014, unto April 19 had 8,500 measles cases, 114 fatalities.

Recent outbreaks

Main article: Measles outbreaks in the 21st century

In 2007, a large outbreak in Japan caused a number of universities and other institutions to close in an attempt to contain the disease.

Many children in ultra-Orthodox Jewish communities were affected due to low vaccination coverage. As of 2008, the disease is endemic in the United Kingdom, with 1,217 cases diagnosed in 2008, and epidemics have been reported in Austria, Italy and Switzerland.

On February 19, 2009, 505 measles cases were reported in twelve provinces in northern Vietnam, with Hanoi accounting for 160 cases. A high rate of complications, including meningitis and encephalitis, has worried health workers, and the U.S. CDC recommended all travelers be immunized against measles.

Beginning in April 2009 there was a large outbreak of measles in Bulgaria, with over 24,000 cases including 24 deaths. From Bulgaria, the strain was carried to Germany, Turkey, Greece, Macedonia, and other European countries.

Beginning in September 2009, Johannesburg, South Africa reported about 48 cases of measles. Soon after the outbreak, the government ordered all children to be vaccinated. Vaccination programs were then initiated in all schools, and parents of young children were advised to have them vaccinated. Many people were not willing to have the vaccination done, as it was believed to be unsafe and ineffective. The Health Department assured the public that their program was indeed safe. Speculation arose as to whether or not new needles were being used. By mid-October, there were at least 940 recorded cases, and four deaths.

In early 2010, there was a serious outbreak of measles in the Philippines with 742 cases, leaving four unvaccinated children dead in the capital city of Manila.

As of May 2011, over 17,000 cases of measles have so far been reported from France between January 2008 and April 2011, including 2 deaths in 2010 and 6 deaths in 2011. Over 7,500 of these cases fell in the first three months of 2011, and Spain, Turkey, Macedonia, and Belgium have been among the other European countries reporting further smaller outbreaks. The French outbreak has been specifically linked to a further outbreak in Quebec in 2011, where 327 cases have been reported between January and June 1, 2011, and the European outbreaks in general have also been implicated in further small outbreaks in the USA, where 40 separate importations from the European region had been reported between January 1 and May 20.

Some experts stated that the persistence of the disease in Europe could be a stumbling block to global eradication. It has proven difficult to vaccinate a sufficient number of children in Europe to eradicate the disease, because of opposition on philosophical or religious grounds, or fears of side-effects, or because some minority groups are hard to reach, or simply because parents forget to have their children vaccinated. Vaccination is not mandatory in some countries in Europe, in contrast to the United States and many Latin American countries, where children must be vaccinated before they enter school.

In March 2013, an epidemic was declared in Swansea, Wales, UK with 1,219 cases and 88 hospitalizations to date. A 25-year-old male had measles at the time of death and died from giant cell pneumonia caused by the disease. There have been growing concerns that the epidemic could spread to London and infect many more people due to poor MMR uptake, prompting the Department of Health to set up a mass vaccination campaign targeted at one million school children throughout England.

In late 2013, it was reported in the Philippines that 6,497 measles cases occurred which resulted in 23 deaths.

In 2014 many unvaccinated US citizens visiting the Philippines, and other countries, contracted measles, resulting in 288 cases being recorded in the United States in the first five months of 2014, a twenty-year high.

In January 2015, it was reported that nineteen people from three states who visited Disneyland or Disney California Adventure between Dec. 15 and Dec. 20 fell ill with measles. Sixteen of the cases were in California, two in Utah, and one in Colorado. Officials in California said that of the 16 cases in the state they have only verified that two were fully vaccinated against the disease. Some were partially vaccinated and at least two were too young to be vaccinated. Between the dates of January 1 and 28, 2015, most of the 84 people who were diagnosed with measles were either infected during their visit to Disneyland or by someone who visited the theme park.

Americas

Indigenous measles was declared to have been eliminated in North, Central, and South America; the last endemic case in the region was reported on November 12, 2002, with only northern Argentina and rural Canada, particularly in Ontario, Quebec, and Alberta, having minor endemic status. Outbreaks are still occurring, however, following importations of measles viruses from other world regions. In June 2006, an outbreak in Boston resulted after a resident became infected in India.

Between January 1 and April 25, 2008, a total of 64 confirmed measles cases were preliminarily reported in the United States to the CDC, the most reported by this date for any year since 2001. Of the 64 cases, 54 were associated with importation of measles from other countries into the United States, and 63 of the 64 patients were unvaccinated or had unknown or undocumented vaccination status. By July 9, 2008, a total of 127 cases were reported in 15 states (including 22 in Arizona), making it the largest U.S. outbreak since 1997 (when 138 cases were reported). Most of the cases were acquired outside of the United States and afflicted individuals who had not been vaccinated. By July 30, 2008, the number of cases had grown to 131. Of these, about half involved children whose parents rejected vaccination. The 131 cases occurred in seven different outbreaks. There were no deaths, and 15 hospitalizations. Eleven of the cases had received at least one dose of measles vaccine. Children who were unvaccinated or whose vaccination status was unknown accounted for 122 cases. Some of these were under the age when vaccination is recommended, but in 63 cases, the vaccinations had been refused for religious or philosophical reasons.

In March 2014, there was an outbreak that started in a religious community in British Columbia's Fraser Valley.

History

16th century Aztec drawing of someone with measles

The Antonine Plague, 165–180 AD, also known as the Plague of Galen, who described it, was probably smallpox or measles. The epidemic may have claimed the life of Roman emperor Lucius Verus. Total deaths have been estimated at five million. Estimates of the timing of evolution of measles seem to suggest this plague was something other than measles. The first scientific description of measles and its distinction from smallpox and chickenpox is credited to the Persian physician Rhazes (860–932), who published The Book of Smallpox and Measles. Given what is now known about the evolution of measles, this account is remarkably timely, as recent work that examined the mutation rate of the virus indicates the measles virus emerged from rinderpest (Cattle Plague) as a zoonotic disease between 1100 and 1200 AD, a period that may have been preceded by limited outbreaks involving a virus not yet fully acclimated to humans. This agrees with the observation that measles requires a susceptible population of >500,000 to sustain an epidemic, a situation that occurred in historic times following the growth of medieval European cities.

Maurice Hilleman's measles vaccine is estimated to prevent 1 million deaths every year.

Measles is an endemic disease, meaning it has been continually present in a community, and many people develop resistance. In populations not exposed to measles, exposure to the new disease can be devastating. In 1529, a measles outbreak in Cuba killed two-thirds of the natives who had previously survived smallpox. Two years later, measles was responsible for the deaths of half the population of Honduras, and had ravaged Mexico, Central America, and the Inca civilization.

Between roughly 1855 to 2005 measles has been estimated to have killed about 200 million people worldwide. Measles killed 20 percent of Hawaii's population in the 1850s. In 1875, measles killed over 40,000 Fijians, approximately one-third of the population. In the 19th century, the disease decimated the Andamanese population. In 1954, the virus causing the disease was isolated from an 13-year-old boy from the United States, David Edmonston, and adapted and propagated on chick embryo tissue culture. To date, 21 strains of the measles virus have been identified. While at Merck, Maurice Hilleman developed the first successful vaccine. Licensed vaccines to prevent the disease became available in 1963. An improved measles vaccine became available in 1968.

See also

• Critical community size
• Pulse vaccination strategy
• Vaccine-naive

External links

• WHO.int—'Initiative for Vaccine Research (IVR): Measles', World Health Organization (WHO)
• Measles FAQ from Centers for Disease Control and Prevention in the United States
• Case of an adult male with measles (facial photo)
• Clinical pictures of measles
• Virus Pathogen Database and Analysis Resource (ViPR): Paramyxoviridae