Measles

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Measles

Measles (also sometimes known as English measles), also known as morbilli, is an infection of the respiratory system caused by a virus, specifically a paramyxovirus of the genus Morbillivirus. Morbilliviruses, like other paramyxoviruses, are enveloped, single-stranded, negative-sense RNA viruses. Symptoms include fever, cough, runny nose, red eyes and a generalized, maculopapular, erythematous rash.

Measles is spread through respiration (contact with fluids from an infected person's nose and mouth, either directly or through aerosol transmission), and 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] and infectivity 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).

Signs and symptoms

This patient presented on the third pre-eruptive day with “Koplik spots” indicative of the beginning onset of measles.

The classical signs and symptoms of measles include four-day fevers and the three Cs — cough, coryza (head cold), conjunctivitis (red eyes), fever, anorexia, 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 not often seen, even in real cases of measles, because they are transient and may disappear within a day of arising.

The characteristic measles rash is classically described as a generalized, maculopapular, erythematous rash that begins several days after the fever starts. It starts on the back of ears and, after a few hours, spreads to the head and neck before spreading to cover most of the body, often causing itching. The rash is said to "stain", changing color from red to dark brown, before disappearing.[citation needed] The measles rash appears two to four days after the initial symptoms and lasts for up to eight days.]

Complications

Complications with measles are relatively common, ranging from the relatively mild and less serious ones like diarrhea to more serious ones such as pneumonia, otitis media, acute encephalitis (rarely SSPE -- subacute sclerosing panencephalitis), and corneal ulceration (leading to corneal scarring). Complications are usually more severe in adults who catch the virus.

Between the years 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 patients (e.g. people with AIDS) the fatality rate is approximately 30%.]

Cause

Measles is caused by the measles virus, a single-stranded, negative-sense enveloped RNA virus of the genus Morbillivirus within the family Paramyxoviridae. Humans are the natural hosts of the virus; no 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 the following:

    Children with immunodeficiency due to 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

Infants who lose passive antibody before the age of routine immunization

Risk factors for severe measles and its complications include the following:

    Malnutrition
    Underlying immunodeficiency
    Pregnancy
    Vitamin A deficiency]]

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. In patients where phlebotomy is not possible, 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

Measles cases reported in England and Wales before and after the introduction of the vaccine, coverage was not widespread enough for herd immunity to interrupt episodic outbreaks until after the MMR vaccine was introduced in 1988.

In developed countries, most children are immunized against measles by the age of 18 months, generally as part of a three-part MMR vaccine (measles, mumps, and rubella). The vaccination is generally not given earlier than this because children younger than 18 months usually retain antimeasles immunoglobulins (antibodies) transmitted from the mother during pregnancy. 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. Even a single case in a college dormitory or similar setting is often met with a local vaccination program, in case any of the people exposed are not already immune.

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, but the risk of adverse reactions is low. 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.]

Unvaccinated populations are at risk for the disease. Traditionally low vaccination rates in northern Nigeria dropped further in the early 2000s when radical preachers promoted a rumor that polio vaccines were a Western plot to sterilize Muslims and infect them with HIV. The number of cases of measles rose significantly, and hundreds of children died. This could also have had to do with the aforementioned other health-promoting measures often given with the vaccine.

Claims of a connection between the MMR vaccine and autism were raised in a 1998 paper in The Lancet, a respected British medical journal. Later investigation by Sunday Times journalist Brian Deer discovered the lead author of the article, Andrew Wakefield, had multiple undeclared conflicts of interest, and had broken other ethical codes. The Lancet paper was later retracted, and Wakefield was found guilty by the General Medical Council of serious professional misconduct in May 2010, and was struck off the Medical Register, meaning he could no longer practise as a doctor in the UK. The GMC's panel also considered two of Wakefield's colleagues: John Walker-Smith was also found guilty and struck off the Register; Simon Murch "was in error" but acted in good faith, and was cleared. Walker-Smith was later cleared and reinstated after winning an appeal; the appeal court's finding was based on the panel's conduct of the case, and gave no support to the MMR-autism hypothesis, which the official judgement described as lacking support from any respectable body of opinion. The research was declared fraudulent in 2011 by the BMJ. Scientific evidence provides no support for the hypothesis that MMR plays a role in causing autism.

The autism-related MMR study in Britain caused use of the vaccine to plunge, and measles cases came back: 2007 saw 971 cases in England and Wales, the biggest rise in occurrence in measles cases since records began in 1995. A 2005 measles outbreak in Indiana was attributed to children whose parents refused vaccination.

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, and encephalitis. Acute measles encephalitis has a mortality rate of 15%. While there is no specific treatment for measles encephalitis, antibiotics are required for bacterial pneumonia, sinusitis, and bronchitis that can follow measles.

All other treatment addresses symptoms, with ibuprofen, or acetaminophen (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's syndrome. Some research has shown aspirin may not be the only medication associated with Reye's, 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.

Prognosis

While the vast majority of patients survive measles, complications occur fairly frequently, and may include bronchitis, and panencephalitis which is potentially fatal. Also, even if the patient is not concerned about death or sequela from the measles, the person may spread the disease to an immunocompromised patient, for whom the risk of death is much higher, due to complications such as giant cell pneumonia. 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. 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

In 2000 the WHO estimated that there were ~45 million cases of measles worldwide with 800,000 deaths from it. Mortality in developed countries is ~1/1000. In sub-Saharan Africa, mortality is 10%. In cases with complications, the rate may rise to 20–30%. In 2010, approximately 380 deaths occurred every day from measles.

Even in countries where vaccination has been introduced, rates may remain high. In Ireland, vaccination was introduced in 1985. The number of cases was 99,903 in that year. Within two years, the number of cases had fallen to 201, but this fall was not sustained: case numbers in 1989, 1993 and 2000 were 1,248, 4,328 and 1,603, respectively. This country's example illustrates the need for vaccination rates greater than 95% to prevent the spread of measles.

According to the WHO, 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.
Evolution

The measles virus evolved from the formerly widespread rinderpest virus, which infects cattle. Sequence analysis has suggested that the two viruses most probably diverged in the 11th and 12th centuries, though the periods as early as the 5th century fall within the 95% confidence interval of these calculations. Other analysis has suggested that the divergence may be even older because of the technique's tendency to underestimate ages when strong purifying selection is in action. There is some linguistic evidence for an earlier origin within the seventh century. The current epidemic strain evolved at the beginning of the 20th century—most probably between 1908 and 1943.
Genotypes

The WHO currently recognises 8 clades of measles (A - H). Subtypes are designed with numerals - A1, D2 etc. Currently a total of 23 subtypes are recognised. The sequencing of the 450 nucleotides that code for the C‐terminal 150 amino acids of N are the minimum amount of sequence data required for genotyping a measles virus isolate. The genotyping scheme was introduced in 1998 and extended in 2002 and 2003.

The major genotypes differ between countries and restatus of measles circulation within that country or region. Indigenous transmission of measles virus was interrupted in the United States and Australia by 2000 and the Americas by 2002.
History and culture
History
16th century Aztec drawing of a measles victim

The Antonine Plague, 165–180 AD, also known as the Plague of Galen, who described it, was probably smallpox or measles. The disease killed as many as one-third of the population in some areas, and decimated the Roman army. 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.

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 a 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.

In roughly the last 150 years, measles has been estimated to have killed about 200 million people worldwide. During the 1850s, measles killed a fifth of Hawaii's people. 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 11-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.
Recent outbreaks
Main article: Measles outbreaks in the 2000s
Maurice Hilleman's measles vaccine is estimated to prevent 1 million deaths every year.

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

Approximately 1000 cases of the disease were reported in Israel between August 2007 and May 2008 (in sharp contrast to just some dozen cases the year before).[citation needed] 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 immune to measles.

On 1 April 2009, the disease broke out in two schools in North Wales. Ysgol John Bright and Ysgol Ffordd Dyffryn, two schools in Wales, have had the outbreak and are making sure every pupil has had the measles vaccine.

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.

Since the beginning of September, 2009, Johannesburg, a city in Gauteng, 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 is 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 March 2010, the Philippines declared an epidemic due to the continuously rising cases of measles.[citation needed]

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 stubborn 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 Europe, in contrast to the United States and many Latin American countries, where children must be vaccinated before they enter school.

As of July 2011, 1,145 children have died of 115 600 cases in the DRC, which is also battling deadly outbreaks of cholera and polio.

In August 2011, an outbreak in New Zealand has seen 94 confirmed cases in Auckland alone.

In November 2011, an outbreak was reported in Canberra, the capital city of Australia with at least 12 reported cases.

In February 2012, an outbreak was registered in St. Petersburg with 87 cases.

In February 2012, an outbreak was declared in Liverpool, UK with 48 cases.
The Americas

Indigenous measles were 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 the provinces of 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 the 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.

On May 24, 2011 the Centers for Disease Control and Prevention reported that the United States has had 118 measles cases so far this year. The 118 cases were reported by 23 states and New York City between Jan 1 and May 20. Of the 118 cases, 105 (89%) were associated with cases abroad and 105 (89%) of the 118 patients had not been vaccinated.

On September 29, 2011 Ecuador's Ministry of Health reported an outbreak with 42 cases of measles recorded inside a few adjacent communities of the central Andean province of Tungurahua. No fatalities had been reported as of that date. According to the Ecuadorean government, the viral strain responsible seemed to be linked to African outbreaks; the government also announced that it was launching a massive vaccination campaign to prevent further spreading of the disease.

On February 8, 2012 it was reported that hundreds of thousands of people at the Super Bowl Village in Indianapolis could have been exposed to the measles when the Indiana State Department of Health confirmed that a person infected with the disease went to the Super Bowl Village in downtown Indianapolis on Feb. 3.