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Measles vaccination schedules

 

In areas without recurrent measles transmission WHO recommends the first dose of measles immunisation is MMR at 12-15 months of age. In areas where there is recurrent measles transmission, a two-dose schedule is used with a monovalent vaccine given at nine months, followed by MMR at 15 months. Timing is important as maternal transplacental antibodies decline and infants face an unprotected gap before immunisation. Early protection might be beneficial where measles is more common. A randomised trial in Turkey examined the efficacy of the two approaches.

Trial

The subjects were 1000 healthy infants aged nine months in five different centres in Ankara. Those with no known history of chronic disease, like immunodeficiency, asthma, or atopy were included. Infants were randomly allocated to receive monovalent measles vaccine (MV) at nine months followed by MMR at 15 months (MV/MMR group) or MMR at 12 months (MMR group).

Blood samples were collected for serology before vaccination, and six weeks after MMR vaccination. Midwives visited children at home several times up to one month after vaccination to collect adverse reaction records made by parents. Families were followed up by telephone every three months for five years using a standard questionnaire. Measles infection in children was actively sought, and diagnosed clinically and serologically.

Results

The MV/MMR group had 58 withdrawals, 50 because a different batch of vaccine was used, four through immigration (sic) and four because of withdrawal of consent. In the MMR group there were five withdrawals, one through immigration (sic) and four withdrawals of consent.

Before vaccination, MV/MMR infants had higher antibody titres than MMR infants, reflecting their younger age at vaccination. Six weeks after the MMR vaccination, measles antibody titres were higher in children in the MMR group (Figure 1).

Figure 1: Measles antibody titres in infants before vaccination and six weeks after the MMR vaccination


The proportion of children with adequate levels of antibodies after MMR vaccination was similar for mumps and rubella, but significantly lower (at 70%) in MV/MMR infants than in MMR infants (90%) (Figure 2).

Figure 2: Percentages of infants with adequate antibody titres suggesting protection against measles, mumps and rubella six weeks after the MMR vaccination


Episodes of fever, cough, rash, diarrhoea, and local redness and swelling were similar in incidence between the two groups, though runny nose was more common at 4% after MMR in the MMR group.

Twelve children acquired measles in the follow up period, all at 12-36 months of age, and all in the MV/MMR group. Cases were scattered between the five centres, with no known epidemiological link. None was serious and none required hospital admission.

Comment

This study was interesting for a number of reasons. It tested a WHO recommendation that has major implications in parts of the world where measles continues to be an important cause of morbidity and mortality, as in Turkey. The results question the timing and structure of vaccination

They are also important for countries like the UK where vaccine uptake can be below ideal in some areas. The study could be seen as casting doubt on the reliability of some vaccines other than MMR. A 70% protection rate in MV/MMR children is underwhelming, though this should not be extrapolated to possible results for monovalent measles vaccines given in different regimens in places where measles is not endemic (though that is not the WHO recommendation).

Finally it reminds us that what is true of the UK, Europe or North America is not always true of the rest of the world. Taking unvaccinated children on hols to Turkey or other parts where measles is endemic puts them at significant risk either as small children or later in life. The unvaccinated infant is also an unvaccinated teenager and student. Children grow up, and increasingly they travel. Folk who doubt the importance or severity of measles, especially in the developing world, could do worse than refresh their memories with a quick dip into the Oxford Textbook of Medicine. It is not a fun read.

References:

  1. M Ceyhan et al. Immunogenicity and efficacy of one dose measles-mumps-rubella (MMR) vaccine at twelve months of age as compared to monovalent measles vaccination at nine months followed by MMR vaccination at fifteen months of age. Vaccine 2001 19: 4473-4478.
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