Measles Classification and external resources ICD-10 B05 ICD-9 055 DiseasesDB 7890 MedlinePlus 001569 eMedicine derm/259 emerg/389 ped/1388 MeSH D008457 Measles Virus classification Group: Group V ((-)ssRNA) Family: Paramyxovirus Genus: Morbillivirus Species: Measles virus

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 (also sometimes known as English 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^[1] 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).^[2]

An alternative name for measles in English-speaking countries is rubeola, which is sometimes confused with rubella (German measles); the diseases are unrelated.^[3][4]

Signs and symptoms[link]

A person infected with measles.

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

The classical symptoms of measles include four-day fevers and the three Cs—cough, coryza (head cold) and conjunctivitis (red eyes). 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 head 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 initial symptoms, and lasts for up to eight days.^[5]

Complications[link]

Complications with measles are relatively common, ranging from relatively mild and less serious diarrhea, to pneumonia, Otitis media and acute encephalitis (and rarely subacute sclerosing panencephalitis,or SSPE); 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%.^[6] In underdeveloped nations with high rates of malnutrition and poor healthcare, fatality rates have been as high as 28%.^[6] In immunocompromised patients (e.g. people with AIDS) the fatality rate is approximately 30%.^[7]

Cause[link]

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^{[8] [9]}

Diagnosis[link]

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[link]

Rates of measles vaccination worldwide

Measles cases reported in the United States before and after introduction of the vaccine

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.^[10] 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.^[11]

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.^[12] 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.^[13] Later investigation by Sunday Times journalist Brian Deer discovered the lead author of the article, Andrew Wakefield, had multiple undeclared conflicts of interest,^[14] 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.^[15] 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.^[16] 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.^[17] The research was declared fraudulent in 2011 by the BMJ.^[18] Scientific evidence provides no support for the hypothesis that MMR plays a role in causing autism.^[19]

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.^[20] A 2005 measles outbreak in Indiana was attributed to children whose parents refused vaccination.^[21]

Treatment[link]

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.^[22] Some research has shown aspirin may not be the only medication associated with Reye's, and even antiemetics have been implicated,^[23] with the point being the link between aspirin use in children and Reye's syndrome development is weak at best, if not actually nonexistent.^[22][24] Nevertheless, most health authorities still caution against the use of aspirin for any fevers in children under 16.^{[25][26][27][28]}

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.^[29][30][31]

Prognosis[link]

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.^[32]

Epidemiology[link]

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%. On average, ~450 children die every day from measles.^{[citation needed]}

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.^[11] 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.^[33]

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.^[34][35]

Evolution[link]

The measles virus evolved from the then-widespread rinderpest virus, most probably in the 11th and 12th centuries.^[36] The earliest likely origin is within the seventh century: for this earlier origin there is some linguistic evidence.^[37][38] The current epidemic strain evolved at the beginning of the 20th century—most probably between 1908 and 1943.^[39]

Genotypes[link]

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 regions: D strains are the most common in Europe, the Middle East, India and Japan; B strains in Africa; and H in China. Type C occur in North Africa and southern Europe. Several types appear to have become extinct - D1, E, F, G1 - not having been isolated in many years. The measles vaccine strains are representatives of genotype A.

Monitoring of the genotypes isolated with a country or region can help determine the status 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[link]

History[link]

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.^[40] 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.^[41] 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.^[42]

In roughly the last 150 years, measles has been estimated to have killed about 200 million people worldwide.^[43] During the 1850s, measles killed a fifth of Hawaii's people.^[44] In 1875, measles killed over 40,000 Fijians, approximately one-third of the population.^[45] In the 19th century, the disease decimated the Andamanese population.^[46] 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.^[47] To date, 21 strains of the measles virus have been identified.^[48] While at Merck, Maurice Hilleman developed the first successful vaccine.^[49] Licensed vaccines to prevent the disease became available in 1963.^[50]

Recent outbreaks[link]

Maurice Hilleman's measles vaccine is estimated to prevent 1 million deaths every year.^[51]

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.^[52] 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.^[53] By mid-October, there were at least 940 recorded cases, and four deaths.^[54]

On February 19, 2009, 505 measles cases were reported in twelve provinces in northern Vietnam, with Hanoi accounting for 160 cases.^[55] A high rate of complications, including meningitis and encephalitis, has worried health workers,^[56] and the U.S. CDC recommended all travelers be immune to measles.^[57]

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.

In 2007, a large outbreak in Japan caused a number of universities and other institutions to close in an attempt to contain the disease.^[58][59]

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.^[60][61] As of 2008, the disease is endemic in the United Kingdom, with 1,217 cases diagnosed in 2008,^[62] and epidemics have been reported in Austria, Italy and Switzerland.^[63]

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.^[64] 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.^[65] 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,^[66] 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.^[67]

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.^[68]

In August 2011, an outbreak in New Zealand has seen 94 confirmed cases in Auckland alone.^[69]

In November 2011, an outbreak was reported in Canberra, the capital city of Australia with at least 12 reported cases.^[70]

In February 2012, an outbreak was registered in St. Petersburg with 87 cases.^[71]

In February 2012, an outbreak was declared in Liverpool, UK with 48 cases.^[72]

The Americas[link]

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.^[73] 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,.^[74]

Between January 1 and April 25, 2008, a total of 64 confirmed measles cases were preliminarily reported in the United States to the CDC,^[75][76] 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.^[77]

By July 9, 2008, a total of 127 cases were reported in 15 states (including 22 in Arizona),^[78] making it the largest U.S. outbreak since 1997 (when 138 cases were reported).^[79] 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.^[80]

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.^[81]

Additional images[link]

• 

  Intraoral rash of measles

• 

  Measles in African child

• 

  This European child shows a classic day-four rash with measles.

• 

  Histopathology of measles giant cell pneumonia

• 

  African child infected with measles.

See also[link]

• Infectious disease
• List of epidemics
• MMR vaccine controversy
• Roseola (baby measles)
• List of cutaneous conditions

References[link]

External links[link]

Wikimedia Commons has media related to: Measles

• 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
• Galindo, Belkys M., et al."Vaccine-Related Adverse Events in Cuban Children", 1999–2008. MEDICC Review. 2012;14(1):38–43.

Andrew Jeremy Wakefield (born 1957) is a British former surgeon and medical researcher, known as an advocate for the discredited claim that there is a link between the measles, mumps and rubella (MMR) vaccine, autism and bowel disease, and for his fraudulent 1998 research paper in support of that claim.^[1]

Four years after the publication of the paper, other researchers' results had still failed to reproduce Wakefield's findings or confirm his hypothesis of a relation between childhood gastrointestinal disorders and autism.^[2] A 2004 investigation by Sunday Times reporter Brian Deer identified undisclosed financial conflicts of interest on Wakefield's part,^[3] and most of his coauthors then withdrew their support for the study's interpretations.^[4] The British General Medical Council (GMC) conducted an inquiry into allegations of misconduct against Wakefield and two former colleagues.^[5] The investigation centred on Deer's numerous findings, including one that autistic children were subjected to unnecessary invasive medical procedures,^[6] such as colonoscopy and lumbar puncture, and that Wakefield acted without the required ethical approval from an institutional review board.

On 28 January 2010, a five-member statutory tribunal of the GMC found three dozen charges proved, including four counts of dishonesty and 12 counts involving the abuse of developmentally challenged children.^[7] The panel ruled that Wakefield had "failed in his duties as a responsible consultant", acted both against the interests of his patients, and "dishonestly and irresponsibly" in his published research.^[8][9][10] The Lancet immediately and fully retracted his 1998 publication on the basis of the GMC’s findings, noting that elements of the manuscript had been falsified.^[11] Wakefield was struck off the Medical Register in May 2010, with a statement identifying dishonest falsification in the Lancet research,^[12] and is barred from practising medicine in the UK.^[13]

In January 2011, an editorial accompanying an article by Brian Deer in BMJ identified Wakefield's work as an "elaborate fraud".^[1][14][15] In a follow-up article,^[16] Deer said that Wakefield had planned to launch a venture on the back of an MMR vaccination scare that would profit from new medical tests and "litigation driven testing".^[17] Wakefield's study and public recommendations against the use of the combined MMR vaccine were linked to a steep decline in vaccination rates in the United Kingdom and a corresponding rise in measles cases, resulting in serious illness and fatalities.^[18][19][20] Wakefield has continued to defend his research and conclusions, saying there was no fraud, hoax or profit motive.^[21][22]

Personal life and career[link]

Wakefield was born in 1957;^[23][24] his father was a neurologist and his mother was a general practitioner.^[25] After leaving the independent King Edward's School, Bath,^[26] Wakefield studied medicine at St Mary's Hospital Medical School^[25] (now Imperial College School of Medicine), fully qualifying in 1981. He became a fellow of the Royal College of Surgeons in 1985.^[24] At the University of Toronto (U of T) from 1986 to 1989, he was part of a team that studied tissue rejection problems with small intestine transplantation, using animal models.^[27][28] He continued his studies of small intestine transplantation under a Wellcome Trust traveling fellowship at U of T in Canada.^[24]

Back in the UK, he worked on the liver transplant programme at the Royal Free Hospital in London.^[24] In 1995, while conducting research into Crohn's disease, he was approached by Rosemary Kessick, the parent of an autistic child, who was seeking help with her son's bowel problems and autism; Kessick ran a group called Allergy Induced Autism.^[29] In 1996, Wakefield turned his attention to researching the connection between the MMR vaccine and autism.^[24] At the time of his MMR research study, Wakefield was senior lecturer and honorary consultant in experimental gastroenterology at the Royal Free Hospital School of Medicine (from 2008 UCL Medical School). He resigned in 2001,^[30] by "mutual agreement and was made a fellow of the Royal College of Pathologists",^[31] and moved to the US in 2001^[32] or 2004,^[31] both dates according to 'The Times'. One report noted he was asked to leave Royal Free Hospital in 2004 after he did not fulfill a request to duplicate the findings in his controversial Lancet paper.^[33]

Wakefield subsequently helped establish and served as the executive director of Thoughtful House Center for Children, a center for the study of autism in Austin, Texas where, according to The Times he "continued to promote the theory of a link between the MMR vaccine and autism, despite admitting it was 'not proved'."^[31] He resigned from Thoughtful House in February 2010, after the British General Medical Council found that he had been "dishonest and irresponsible" in conducting his earlier autism research in England.^[27][34] The Times reported in May 2010 that he was a medical advisor for Visceral, a UK charity that "researches bowel disease and developmental disorders".^[31]

Wakefield is no longer licensed in the UK as a physician,^[13] and is not licensed in the US.^[35] As of January 2011, he lives in the US where he has a following including celebrities like Jenny McCarthy^[36] who wrote the foreword for Wakefield's autobiography, Callous Disregard, and believes her son's autism is due to vaccines.^[20] According to Deer, as of 2011, he lives near Austin with his wife, Carmel, and four children.^[27]

In 2011, Wakefield was at the top of the list of the worst doctors of 2011 in Medscape's list of "Physicians of the Year: Best and Worst".^[37] In January 2012, TIME Magazine named Wakefield in a list of "Great Science Frauds".^[38]

MMR controversy[link]

On 28 February 1998, a paper written by Wakefield and twelve other authors about twelve autistic children was published in The Lancet.^[39] In it, the authors claimed to have identified a new syndrome which they called autistic enterocolitis, raising the possibility of a link between a novel form of bowel disease, autism, and the MMR vaccine. In the study's "findings", the authors noted that the parents of eight of the twelve children linked what were described as "behavioural symptoms" with MMR, and in its "results" reported that the onset of these symptoms began within two weeks of MMR vaccination.^[39] In the published Lancet summary, known as the "interpretation", the authors wrote:

"We identified associated gastrointestinal disease and developmental regression in a group of previously normal children, which was generally associated in time with possible environmental triggers."^[39]

These possible triggers were reported to be MMR in eight cases, and measles infection in one. The paper was instantly controversial, leading to widespread publicity in the UK and the convening of a special panel of the UK's Medical Research Council the following month.^[40] One study done based in Japan found that there was no causal relationship between the MMR vaccine and autism in groups of children given the triple MMR vaccine and children who received individual measles, mumps and rubella vaccinations. The MMR was replaced with individual vaccinations in 1993.^[41]

Although the paper said that no causal connection had been proven, and before it was published, Wakefield made statements at a press conference and in a video news release issued by the hospital, calling for suspension of the triple MMR vaccine until more research could be done.^[42] The press conference was later criticized as 'science by press conference'.^[43] According to BBC News, it was this press conference, rather than the Lancet paper, that fueled the MMR vaccination scare.^[44] According to the BBC, "He told journalists it was a 'moral issue' and he could no longer support the continued use of the three-in-one jab for measles, mumps and rubella. 'Urgent further research is needed to determine whether MMR may give rise to this complication in a small number of people,' Dr Wakefield said at the time."^[44] He said, "If you give three viruses together, three live viruses, then you potentially increase the risk of an adverse event occurring, particularly when one of those viruses influences the immune system in the way that measles does."^[42] He suggested parents should opt for single jabs against measles, mumps and rubella, separated by gaps of one year.

In December 2001, Wakefield resigned from the Royal Free Hospital, saying, "I have been asked to go because my research results are unpopular."^[30] The medical school said that he had left "by mutual agreement." In February 2002, Wakefield stated, "What precipitated this crisis was the removal of the single vaccine, the removal of choice, and that is what has caused the furore – because the doctors, the gurus, are treating the public as though they are some kind of moronic mass who cannot make an informed decision for themselves."^[45]

Aftermath of initial controversy[link]

Wakefield continued conducting clinical research in the US after leaving the Royal Free Hospital in December 2001. He joined a controversial American researcher, Jeffrey Bradstreet, at the International Child Development Resource Center, to conduct further studies on the possible relationship between the MMR vaccine and autism.^[46]

In 2004, Wakefield started work at the Thoughtful House research center in Austin, Texas.^[47] Wakefield served as Executive Director of Thoughtful House until February 2010, when he resigned in the wake of findings against him by the British General Medical Council.^[34][48]

In February 2004, controversy resurfaced when Wakefield was accused of a conflict of interest. The Sunday Times reported that some of the parents of the 12 children in the Lancet study were recruited via a UK lawyer preparing a lawsuit against MMR manufacturers, and that the Royal Free Hospital had received £55,000 from the UK's Legal Aid Board (now the Legal Services Commission) to pay for the research.^[49] Previously, in October 2003, the board had cut off public funding for the litigation against MMR manufacturers.^[50] Following an investigation of The Sunday Times allegations by the UK General Medical Council, Wakefield was charged with serious professional misconduct, including dishonesty.^[51] In December 2006, the Sunday Times further reported that in addition to the money they gave the Royal Free Hospital, the lawyers responsible for the MMR lawsuit had paid Wakefield personally more than £400,000, which he had not previously disclosed.^[52]

Twenty-four hours before the 2004 Sunday Times report, The Lancet responded to the investigation in a public statement, describing Wakefield's research as "fatally flawed". The Lancet's editor said he believed the paper would have been rejected as biased if the peer reviewers had been aware of Wakefield's conflict of interest.^[53] Ten of Wakefield's twelve co-authors of the Lancet paper later published a retraction of an interpretation:^[54] The section of the paper retracted read as follows:

"Interpretation. We identified associated gastrointestinal disease and developmental regression in a group of previously normal children, which was generally associated in time with possible environmental triggers."

The retraction stated:^[54]

"We wish to make it clear that in this paper no causal link was established between (the) vaccine and autism, as the data were insufficient. However the possibility of such a link was raised, and consequent events have had major implications for public health. In view of this, we consider now is the appropriate time that we should together formally retract the interpretation placed upon these findings in the paper, according to precedent."^[55]

Wakefield v Channel 4 and others[link]

In November 2004, Channel 4 broadcast a one-hour Dispatches investigation by reporter Brian Deer; the Toronto Star said Deer had "produced documentary evidence that Wakefield applied for a patent on a single-jab measles vaccine before his campaign against the MMR vaccine, raising questions about his motives".^[27][56]

In addition to Wakefield's unpublished initial patent submission,^[56] Deer released a copy of the published patent application.^[57] At page 1, the first paragraph of this stated:

"The present invention relates to a new vaccine/immunisation for the prevention and/or prophylaxis against measles virus infection and to a pharmaceutical or therapeutic composition for the treatment of IBD (Inflammatory Bowel Disease); particularly Crohn's Disease and Ulcerative Colitis and regressive behavioural disease (RBD) (also referred to as "Pervasive Developmental Disorder)."

Before describing the research in Wakefield's 1998 Lancet paper, at the same page this patent explicitly states that the MMR vaccine causes autism:

"It has now also been shown that use of the MMR vaccine (which is taken to include live attentuated measles vaccine virus, measles virus, mumps vaccine virus and rubella vaccine virus, and wild strains of the aforementioned viruses) results in ileal lymphoid nodular hyperplasia, chronic colitis and pervasive developmental disorder including autism (RBD), in some infants."

According to Deer, a letter from Wakefield's lawyers to him dated 31 Jan 2005 said: "Dr Wakefield did not plan a rival vaccine."^[56]

In the Dispatches programme, Deer also revealed that Nicholas Chadwick, a researcher working under Wakefield's supervision in the Royal Free medical school, had failed to find measles virus in the children reported on in The Lancet.^[58]

In January 2005, Wakefield initiated libel proceedings against Channel 4, the independent production company Twenty Twenty and Brian Deer. At the same time, Wakefield issued libel proceedings against The Sunday Times, and against Deer personally over his website briandeer.com.^[59] Within weeks of issuing his claims, however, Wakefield sought to have the action frozen until after the conclusion of General Medical Council proceedings against him. Fighting back, Channel 4 and Deer obtained a High Court order compelling Wakefield to continue with his action, or discontinue it. After a hearing in court on 27 and 28 October 2005, Mr Justice David Eady ruled against a Stay of proceedings, stating:

"It thus appears that the Claimant wishes to use the existence of the libel proceedings for public relations purposes, and to deter other critics, while at the same time isolating himself from the “downside” of such litigation, in having to answer a substantial defence of justification."

He also said in his judgment:

"I am quite satisfied, therefore, that the Claimant wished to extract whatever advantage he could from the existence of the proceedings while not wishing to progress them or to give the Defendants an opportunity of meeting the claims."^[60]

The judgment identified Channel 4's "very lengthy extracts" regarding Wakefield, where Deer's allegations are that he had:^[60]

i) Spread fear that the MMR vaccine might lead to autism, even though he knew that his own laboratory had carried out tests whose results dramatically contradicted his claims in that the measles virus had not been found in a single one of the children concerned in his study and he knew or ought to have known that there was absolutely no basis at all for his belief that the MMR should be broken up into single vaccines.

(ii) In spreading such fear, acted dishonestly and for mercenary motives in that, although he improperly failed to disclose the fact, he planned a rival vaccine and products (such as a diagnostic kit based on his theory) that could have made his fortune.

(iii) Gravely abused the children under his care by unethically carrying out extensive invasive procedures (on occasions requiring three people to hold a child down), thereby driving nurses to leave and causing his medical colleagues serious concern and unhappiness.

(iv) Improperly and/or dishonestly failed to disclose to his colleagues and to the public at large that his research on autistic children had begun with a contract with solicitors which were trying to sue the manufacturers of the MMR vaccine.

(v) Improperly and/or dishonestly lent his reputation to the International Child Development Resource Centre which promoted to very vulnerable parents expensive products for whose efficacy (as he knew or should have known) there was no scientific evidence.

In addition the Justice Eady's ruling states that "...the views or conclusions of the GMC disciplinary body would not, so far as I can tell, be relevant or admissible...", that Channel 4's allegations "...go to undermine fundamentally the Claimant's professional integrity and honesty..." and that "It cannot seriously be suggested that priority should be given to GMC proceedings for the resolution of issues...".

Other proceedings continued for two years, but in December 2006, Deer reported figures obtained from the Legal Services Commission showing that it had paid £435,643 in undisclosed fees to Wakefield for him to build a case against the MMR vaccine,^[61] payments which The Sunday Times reported had begun two years before the Lancet paper.^[52]

Within days of Deer's report, Wakefield dropped all his libel actions^[62] and was required to pay all the defendants' legal costs.^[63][64]

Other concerns[link]

Other concerns regarding Wakefield were that an extension of his project caused life-threatening complications in one child, who received substantial compensation in an out-of-court settlement.^[65] Wakefield's data were also questioned;^[19] a former graduate student, who appeared in Deer's programme, later testified that Wakefield ignored laboratory data which conflicted with his hypothesis. An independent investigation of a collaborating laboratory questioned the accuracy of the data underpinning Wakefield's claims.^[66]

In June 2005, the BBC programme Horizon reported on an unnamed and unpublished study of blood samples from a group of 100 autistic children and 200 children without autism. They reported finding 99% of the samples contained no trace of the measles virus, and the samples that did contain the virus were just as likely to be from non-autistic children, i.e. only three samples contained the measles virus, one from an autistic child and two from a neuro-typical child. The study's authors found no evidence of any link between MMR and autism.^[67]

The Institute of Medicine (IOM) of the United States National Academy of Sciences,^[68] along with the CDC^[69] and the UK National Health Service,^[70] have found no link between vaccines and autism. Reviews in the medical literature have also found no link between the MMR vaccine and autism or with bowel disease, which Wakefield called "autistic enterocolitis."^[71][72][73]

General Medical Council hearings[link]

Between July 2007 and May 2010, a 217-day "fitness to practise" hearing of the UK General Medical Council examined charges of professional misconduct against Wakefield and two colleagues involved in the Lancet paper.^[74][75] The charges included that he:

• "Was being paid to conduct the study by solicitors representing parents who believed their children had been harmed by MMR".^[74]
• Ordered investigations "without the requisite paediatric qualifications" including colonoscopies, colon biopsies and lumbar punctures ("spinal taps") on his research subjects without the approval of his department's ethics board and contrary to the children's clinical interests,^[74] when these diagnostic tests were not indicated by the children's symptoms or medical history.
• "Act[ed] 'dishonestly and irresponsibly' in failing to disclose ... how patients were recruited for the study".^[74]
• "Conduct[ed] the study on a basis which was not approved by the hospital's ethics committee."^[74]
• Purchased blood samples – for £5 each – from children present at his son's birthday party, which Wakefield joked about in a later presentation.^[74]

Wakefield denied the charges;^[76] on 28 January 2010, the GMC ruled against Wakefield on all issues, stating that he had "failed in his duties as a responsible consultant",^[8] acted against the interests of his patients,^[8] and "dishonestly and irresponsibly" in his controversial research.^[9] On 24 May 2010 he was struck off the United Kingdom medical register. It was the harshest sanction that the GMC could impose, and effectively ended his career as a doctor. In announcing the ruling, the GMC said that Wakefield had "brought the medical profession into disrepute," and no sanction short of erasing his name from the register was appropriate for the "serious and wide-ranging findings" of misconduct.^[13][77] Co-author John Walker-Smith was also struck off the medical register, while junior author Simon Murch was cleared.^[13][78][79] On the same day, Wakefield's autobiography, Callous Disregard was published. It argued that he had been unfairly treated by the medical and scientific establishment.^[80] John Walker-Smith appealed the decision and won.^[81][82]

Fraud and conflict of interest allegations[link]

In February 2009, The Sunday Times reported that a further investigation by the newspaper had revealed that Wakefield "changed and misreported results in his research, creating the appearance of a possible link with autism",^[83] citing evidence obtained by the newspaper from medical records and interviews with witnesses, and supported by evidence presented to the GMC.

In April 2010, Deer expanded on laboratory aspects of his findings in a report in the BMJ, recounting how normal clinical histopathology results (obtained from the Royal Free hospital) had been subjected to wholesale changes, from normal to abnormal, in the medical school and published in The Lancet.^[84] On 2 January 2011, Deer provided two tables comparing the data on the twelve children, showing the original hospital data and the data with the wholesale changes as used in the 1998 Lancet article.^[85]

On 5 January 2011, BMJ published an article by Brian Deer entitled "How the case against the MMR vaccine was fixed".^[86] Deer, funded by The Sunday Times of London and Channel 4 television network, said that, based on examination of the medical records of the 12 children in the original study, his research had found:^[86]

"The Lancet paper was a case series of 12 child patients; it reported a proposed “new syndrome” of enterocolitis and regressive autism and associated this with MMR as an “apparent precipitating event.” But in fact:

"Three of nine children reported with regressive autism did not have autism diagnosed at all. Only one child clearly had regressive autism;

"Despite the paper claiming that all 12 children were “previously normal,” five had documented pre-existing developmental concerns;

"Some children were reported to have experienced first behavioural symptoms within days of MMR, but the records documented these as starting some months after vaccination;

"In nine cases, unremarkable colonic histopathology results—noting no or minimal fluctuations in inflammatory cell populations—were changed after a medical school “research review” to “non-specific colitis”;

"The parents of eight children were reported as blaming MMR, but 11 families made this allegation at the hospital. The exclusion of three allegations — all giving times to onset of problems in months — helped to create the appearance of a 14 day temporal link;

"Patients were recruited through anti-MMR campaigners, and the study was commissioned and funded for planned litigation."^[86]

In an accompanying editorial, BMJ editors said:

Clear evidence of falsification of data should now close the door on this damaging vaccine scare ... Who perpetrated this fraud? There is no doubt that it was Wakefield. Is it possible that he was wrong, but not dishonest: that he was so incompetent that he was unable to fairly describe the project, or to report even one of the 12 children's cases accurately? No. A great deal of thought and effort must have gone into drafting the paper to achieve the results he wanted: the discrepancies all led in one direction; misreporting was gross. Moreover, although the scale of the GMC's 217 day hearing precluded additional charges focused directly on the fraud, the panel found him guilty of dishonesty concerning the study's admissions criteria, its funding by the Legal Aid Board, and his statements about it afterwards.^[1]

In a BMJ follow-up article on 11 January 2011,^[16] Deer said that based upon documents he obtained under Freedom of information legislation,^[87] Wakefield—in partnership with the father of one of the boys in the study—had planned to launch a venture on the back of an MMR vaccination scare that would profit from new medical tests and "litigation driven testing".^[17][56] The Washington Post reported that Deer said that Wakefield predicted he "could make more than $43 million a year from diagnostic kits" for the new condition, autistic enterocolitis.^[87] According to Deer's report in BMJ, the ventures, Immunospecifics Biotechnologies Ltd and Carmel Healthcare Ltd—named after Wakefield’s wife—failed after Wakefield's superiors at University College London's medical school gave him a two-page letter that said:

"We remain concerned about a possible serious conflict of interest between your academic employment by UCL, and your involvement with Carmel ... This concern arose originally because the company's business plan appears to depend on premature, scientifically unjustified publication of results, which do not conform to the rigorous academic and scientific standards that are generally expected."^[16]

WebMD reported on Deer's BMJ report, saying that the $43 million predicted yearly profits would come from marketing kits for "diagnosing patients with autism" and that "the initial market for the diagnostic will be litigation-driven testing of patients with AE [autistic enterocolitis, an unproven condition concocted by Wakefield] from both the UK and the US".^[88] According to WebMD, the BMJ article also claimed that Carmel Healthcare Ltd would succeed in marketing products and developing a replacement vaccine if "public confidence in the MMR vaccine was damaged".^[88]

Journal retractions[link]

On 2 February 2010, The Lancet formally retracted Wakefield's 1998 paper.^[89][90] The retraction states that "the claims in the original paper that children were 'consecutively referred' and that investigations were 'approved' by the local ethics committee have been proven to be false".^[11]

The following day the editor of a specialist journal, Neurotoxicology, withdrew another Wakefield paper that was in press. The article, which concerned research on monkeys, had already been published online and sought to implicate vaccines in autism.^[91]

In May 2010, The American Journal of Gastroenterology retracted a paper of Wakefield's that used data from the 12 patients of the Lancet article.^[92]

On 5 January 2011, BMJ editors recommended that Wakefield's other publications should be scrutinized and retracted if need be.^[36]

Wakefield response[link]

As of January 2011, Wakefield has continued to maintain his innocence. He said:

"I want to make one thing crystal clear for the record – my research and the serious medical problems found in those children were not a hoax and there was no fraud whatsoever. Nor did I seek to profit from our findings. ... despite media reports to the contrary, the results of my research have been duplicated in five other countries ... I continue to fully support more independent research to determine if environmental triggers, including vaccines, are causing autism and other developmental problems. ... Since the Lancet paper, I have lost my job, my career and my country. To claim that my motivation was profit is patently untrue. I will not be deterred – this issue is far too important."^[21]

According to BMJ, he says "he never claimed that the children had regressive autism, nor that he said they were previously normal. He never misreported or changed any findings in the study, and never patented a measles vaccine. None of the children were [attorney] Barr's clients before referral to the hospital, and he never received huge payments from the lawyer. There were no conflicts of interest. He is the victim of a conspiracy. He never linked autism with MMR."^[86]

In an internet radio interview, Wakefield said the BMJ series "was utter nonsense" and denied "that he used the cases of the 12 children in his study to promote his business venture".^[17] Although Deer is funded by The Sunday Times and Channel 4, he has filed financial disclosure forms and denies receiving any funding from the pharmaceutical industry, who Wakefield says is paying him.^[17] According to CNN, Wakefield said the patent he held was for "an 'over-the-counter nutritional supplement' that boosts the immune system".^[17] WebMD reported that Wakefield said he was the victim of "a ruthless, pragmatic attempt to crush any attempt to investigate valid vaccine safety concerns".^[88]

Wakefield claims that Deer is a "hit man who was brought in to take [him] down" and that other scientists have simply taken Deer at his word. While on Anderson Cooper 360°, claiming he had not read the BMJ articles yet, he denied their validity and denied that Deer had interviewed the families of the children in the study. He also urged viewers to read his book, Callous Disregard, which he claimed would explain why he was being targeted, to which Anderson Cooper replied: "But, sir, if you're lying, then your book is also a lie. If your study is a lie, your book is a lie."^[93]

Wakefield would later imply that there is a conspiracy by public health officials and pharmaceutical companies to discredit him, including suggesting they pay bloggers to post rumors about him on websites or that they artificially inflated reports of deaths from measles.^[33]

Deer counter response[link]

Deer responded to Wakefield's charge by challenging Wakefield to sue him for libel:

If it is true that Andrew Wakefield is not guilty as charged, he has the remedy of bringing a libel action against myself, the Sunday Times of London, against the medical journal here, and he would be the richest man in America.^[94]

He also noted that Wakefield has previously sued him and lost.^[60][94] In January 2012 Wakefield filed a defamation lawsuit in Texas state court against Deer, Fiona Godlee and the BMJ for false accusations of fraud, seeking a jury trial in Travis County. The lawsuit said Wakefield is a resident of Austin.^[95][96] The suit cited the "Texas Long-Arm Statute" as justification for the venue. The journal said that it stood by the writings and would "defend the claim vigorously."^[97][98]

On 5 April 2011, Deer was named the UK's specialist journalist of the year in the British Press Awards, organised by the Society of Editors. The judges said that his investigation of Wakefield was a "tremendous righting of a wrong".^[99]

Epidemics and effects[link]

Physicians, medical journals, and editors^{[100][101][102][103][104]} have made statements tying Wakefield's fraudulent actions to various epidemics and deaths.^[105] Michael J. Smith, a professor of pediatrics at the University of Louisville, an "infectious diseases expert who has studied the autism controversy's effect on immunization rates", said, "Clearly, the results of this [Wakefield] study have had repercussions."^[106][107]

The Associated Press said:

"Immunization rates in Britain dropped from 92 percent to 73 percent, and were as low as 50 percent in some parts of London. The effect was not nearly as dramatic in the United States, but researchers have estimated that as many as 125,000 US children born in the late 1990s did not get the MMR vaccine because of the Wakefield splash."^[106]

ABC News Channel WWAY3 said:

"Since Dr. Andrew Wakefield's study was released in 1998, many parents have been convinced the measles, mumps and rubella vaccine could lead to autism. But that study may have done more harm than good. According to the Centers for Disease Control and Prevention, in the United States, more cases of measles were reported in 2008 than any year since 1997. More than 90 percent of those infected had not been vaccinated, or their vaccination status was not known."^[105]

Paul Hébert, editor-in-chief of the Canadian Medical Association Journal (CMAJ) said:

"There has been a huge impact from the Wakefield fiasco ... This spawned a whole anti-vaccine movement. Great Britain has seen measles outbreaks. It probably resulted in a lot of deaths."^[27]

A profile in a New York Times Magazine article noted:

"Andrew Wakefield has become one of the most reviled doctors of his generation, blamed directly and indirectly, depending on the accuser, for irresponsibly starting a panic with tragic repercussions: vaccination rates so low that childhood diseases once all but eradicated here — whooping cough and measles, among them — have re-emerged, endangering young lives."^[33]

Journalist Brian Deer called for criminal charges to be brought against Wakefield.^[94]

Despite the allegations of misconduct and fraud, Wakefield continues to rely on the monetary and emotional support of fans who continue to support him. J. B. Handley of the autism and anti-vaccine advocacy group Generation Rescue noted, "To our community, Andrew Wakefield is Nelson Mandela and Jesus Christ rolled up into one."^[33]

On April 1, 2011, the James Randi Educational Foundation awarded Wakefield the Pigasus Award for "refusal to face reality".^[108]

A 2011 journal article described the vaccine-autism connection as "the most damaging medical hoax of the last 100 years".^[109]

Selected publications[link]

Books

Journals

See also[link]

• List of vaccine topics

References[link]