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Measles

The measles vaccination, which the MRC tested in clinical trials in the 1960s, is one of the most effective vaccines that exist: one jab is enough to protect for life. It is also thought to be the most cost-effective public health intervention in the world, which is why it is used as a component of the MMR vaccine to this day. The MRC continues to study the basic biology of the virus, its long term effects and the body’s response to the virus and the vaccine, with the aim of further reducing the number of cases, especially in the developing world.

Measles has been around for a very long time – the first reference to it dates back to the seventh century. Also known as rubeola (not to be confused with rubella – German measles), it is caused by a virus and spread by contact with fluids from an infected person’s nose and mouth. Measles is so infectious that the large number of people who would suffer in an outbreak in a non-vaccinated community would quickly overwhelm available hospital resources. According to the World Health Organization (WHO), measles is the leading cause of vaccine-preventable childhood mortality.

Trials of a vaccine

Initial trials of a vaccine for measles took place in the UK in 1961, comparing three live attenuated vaccines – which are prepared from the live virus cultured under conditions that cause it to lose its virulence but not its ability to confer immunity1. Three years later, the MRC set up four trials of an improved, safer, vaccine2.

The measles vaccine was introduced in the US in 1963 and the UK in 1968. As the proportion of children vaccinated increased, notifications of measles gradually fell in the UK from half a million cases and 100 deaths each year to fewer than 100,000 cases and 13 deaths a year by the mid-1980s.

Between 1985 and 1988, many measles cases occurred in children who had been vaccinated. The children who received only one dose were not always protected –this triggered a recommendation that a second dose was necessary. After this, outbreaks occurred only in populations that refused vaccination. For example, in an epidemic in the US in 1989-1990, 90 per cent of those who lost their lives had not been vaccinated.

In developing countries, the measles vaccine is often combined with other ways of delivering life-saving interventions, such as malaria mosquito nets and vitamin A supplements. According to a United Nations Children’s Fund (UNICEF) study, globally, between 1999 and 2005, measles deaths have fallen by 60 per cent. Annual measles deaths have fallen in Africa by 75 per cent during the same period, and the vaccine is safe, cost-effective and affordable3. However, there are still puzzles that have not been solved. Professor Hilton Whittle at the MRC unit in The Gambia found, for example, that boys and girls respond differently to the measles vaccine4.

Measles, mumps and rubella

In 1988, the MRC funded a trial of a three-part vaccine for measles, mumps and rubella (MMR). The results indicated the most suitable age for vaccination – early in the second year of life – necessary to eliminate the three diseases5. Now, in developed countries, most children are immunised with the MMR vaccine at the age of 18 months, and receive a ‘booster’ between the ages of four and five. When the MMR vaccine was introduced in 1988, vaccination uptake rose to above 90 per cent in the UK and, by 1992, there were fewer than 10,000 notifications and an average of one death from measles each year in the UK.

In 1998, a paper was published suggesting a link between the MMR vaccine, bowel disease and autism. It triggered immediate criticism and concern and, at the request of the Chief Medical Officer for England, the MRC convened an expert group to look at the evidence. This group, as well as subsequent studies, found no evidence to support the claim. A recent Cochrane review – by the Cochrane Collaboration, which carries out systematic reviews of healthcare interventions –also concluded that exposure to the MMR vaccine is extremely unlikely to be associated with autism.

However, vaccine uptake dropped following the widespread media coverage of the MMR vaccine controversy. This may in part have been a result of a loss of public trust in politicians and health professionals. MRC scientists at the Social and Public Health Sciences Unit in Glasgow have explored this. They advised that the controversy may provide useful lessons for the future about trust and credibility, such as improving communication, acknowledging that parents may be suspicious if healthcare professionals receive payments for target numbers of immunisations, and disclosing conflicts of interest6.

A new vaccine or better delivery?

The MMR vaccine is administered to babies after the age of 12 months because, before then, maternal antibodies present in the child’s body prevent it from working. In Africa, however, as children become older, they lose contact with health services. The overall coverage for the measles vaccine is only 53 per cent in Africa – three million African children will not be vaccinated against measles in a year, even though they probably have access to immunisation services7. The Gates Foundation in the US is investing in the development of a new vaccine that is more stable in warm climates and can be administered to very young infants while they are still easily accessible by health services.

An alternative to a new vaccine is to use the same one but to improve its delivery so that more children in the developing world receive it. There has been a search to identify other routes of measles immunisation, which are rapid, reliable, cost-effective, needle-free and suitable for use in mass campaigns. A measles aerosol vaccine has been developed in Mexico, and clinical trials of the device have indicated that it is safe and has the desired effect8. Cost savings are yet to be demonstrated.

The molecular basis of measles

The MRC has played a large role in understanding the basic virology of measles – how the virus has changed over time and the comparison of different strains around the world. Different strains may vary in their virulence and also how effective a vaccine against them is, now and in the future. An important player in this research field is Professor Bert Rima at Queen’s University in Belfast. In 1991 he began identifying where in the world different types of the measles virus originate9.

A key effect of an infection with the measles virus is immunosuppression: a substantial suppression of the body’s immune functions that allows secondary infections, such as pneumonia and diarrhoea, to occur10. These other infections are serious in themselves, causing fever and leading to hospitalisation, and are the major causes of measles-associated death in the developing world. However, this mechanism of immunosuppression used by the measles virus could be advantageous and exploited in medical situations. Scientists are considering developing novel immunosuppressant drugs based on the properties of the virus, for example, for use after transplantation of organs to avoid rejection by the body’s immune system.

More mysterious is the measles virus’s association with a brain condition called subacute sclerosing panencephalitis (SSPE), a rare, progressive and fatal neurological disease caused by high levels of infection by the measles virus in the brain. It typically occurs 10-15 years after initial measles infection and affects only one in every 10,000 measles patients11. It is caused by the prolonged infection of the virus which is never cleared from a patient’s body after the initial attack. Scientists still do not know how the virus makes its way into the brain. Professor Rima, researchers at the MRC unit in The Gambia, and others are studying the long-term effects of the measles virus.

References

1. Aldous et al. (1961). Vaccination against measles. III. Clinical trial in British children. BMJ, 2, 1250.

2. Benson et al. (1964). Vaccination of infants with living attenuated measles vaccine (Edmonston strain) with and without gamma-globulin. BMJ, 2, 851.

3. Wolfson et al. (2007). Has the 2005 mortality reduction goal been achieved? A natural history modelling study. The Lancet, 369, 191.

4. Atabani et al. (2000). Sex-associated differences in the antibody-dependent cellular cytotoxicity antibody response to measles vaccines.
Clin Diagn Lab Immunol
, 7, 111.

5. Morgan-Capner et al. (1988). Surveillance of antibody to measles, mumps and rubella by age. BMJ, 297, 770.

6. Hilton et al. (2007). Parents’ champions vs. vested interests: who do parents believe about MMR? A qualitative study. BMC Public Health, 7, 42.

7. Edmunds et al. (2001). Measles vaccination in Africa: by how much could routine coverage be improved? Vaccine, 20, 16.

8. Valdespino-Gomez et al. (2006). Measles aerosol vaccination. Curr Top Microbiol Immunol. 304, 165.

9. Taylor et al. (1991). Identification of several different lineages of measles virus. J Gen Virol., 72, 83.

10. Schneider-Schaulies & Meulen (2002), Measles virus and immunomodulation: molecular bases and perspectives. Exp. Rev. Mol. Med., May.

11. Takasu et al. (2003). A continuing high incidence of subacute sclerosing panencephalitis (SSPE) in the Eastern Highlands of Papua New Guinea. Epidemiol. Infect., 131, 887.

MRC, July 2007

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