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Measles Vaccination

NIHR Signal Measles vaccine still effective if given to infants under nine months old

Published on 5 February 2020

doi: 10.3310/signal-000872

A first vaccination dose against measles is a safe and somewhat effective option if given to infants earlier than usual, and before the age of nine months. However, vaccine effectiveness does increase when administered at older ages, as currently.

Two doses of measles-containing vaccines are recommended as part of a childhood immunisation programme. In countries with ongoing measles transmission, the first dose (MCV1) is recommended at nine months. In the UK, the MCV1 is recommended at 12 months as part of the measles, mumps and rubella (MMR) vaccination.

This review pooled data from 56 studies and found that the vaccine is around 58% effective when administered before nine months compared with 83% after nine months.

With measles on the rise in Europe and the UK, it is helpful to know that in the event of a measles outbreak, it could be used safely in younger infants as an additional measure.

Share your views on the research.

Why was this study needed?

Measles is a highly contagious viral infection that can lead to life-threatening complications.

In the UK, there were 966 cases of measles in 2018, a substantial increase from the 259 cases the previous year. This has been mostly attributed to travel in Europe and large events such as music festivals.

The World Health Organization (WHO) recommends a 95% vaccination population coverage in order to achieve herd immunity. However, coverage has been reducing resulting in the return of measles outbreaks. In Europe, Asia and Africa, measles incidence has particularly increased in children younger than nine months, teenagers and adults. For people who have not been immunised, 9 out of 10 would catch measles if they came into contact with someone infected.

Due to this increase in incidence, the researchers wanted to assess whether the age for the first dose could be brought forward.

What did this study do?

This systematic review and meta-analysis identified 56 studies in which MCV1 was administered to infants under the age of nine months. The outcomes of interest included seroconversion (a sign that the immune system is reacting to the presence of the virus), antibody concentrations (levels of a protein produced by the body when it detects harmful substances), vaccine effectiveness against measles and safety.

The researchers included randomised controlled trials, quasi-randomised controlled trials, cohort and case-control studies, and outbreak investigations.

This review included studies that were observational in design. Although potential confounders can be adjusted for when interpreting the findings, it’s important to bear in mind that it isn’t possible to fully rule out the effects of other variables.

What did it find?

  • Pooled results from 20 studies showed that the proportion of infants who seroconverted increased from 50% (95% confidence interval [CI] 29% to 71%) in those vaccinated with MCV1 at four months to 85% (95% CI 69% to 97%) in those vaccinated at eight months of age.
  • Infants vaccinated with MCV1 between the ages of four to eight months had lower antibody levels compared with infants vaccinated after nine months (pooled mean antibody titre ratio 0.46, 95% CI 0.33 to 0.66). However, there was very wide variability between the studies which reduces the confidence in this result.
  • The pooled vaccine effectiveness of MCV1 in infants younger than nine months was 58% (95% CI 9% to 80%) according to eight studies. A similar proportion was effectively vaccinated when using within-study comparisons from five studies, at 51% (95% CI -44% to 83%) compared with the increased effectiveness above nine months of 83% (95% CI 76% to 88%).
  • There were no differences in the risk of adverse events between infants administered with MCV1 under or over the age of nine months.

What does current guidance say on this issue?

The UK immunisation schedule: the green book (updated in 2020) recommends administering the first dose of the MMR vaccine in infants on their first birthday or soon after. MMR2 is recommended at age three and four months, or soon after.

The WHO recommendations for routine immunisation in countries with low levels of transmission are that MCV1 be administered at 12 months of age. MCV2 is suggested to be administered based on programmatic considerations to achieve the highest coverage. The WHO also has a range of recommendations for when to give measles vaccines earlier in countries with higher rates of measles, including an extra dose (MCV0) before nine months during an outbreak.

What are the implications?

This review’s findings indicate that vaccine administration before nine months can still provide useful protection against measles and could, therefore, be an effective solution in areas where there is a high risk of contracting the disease.

In the UK, administering the first dose of MCV under nine months is considered to be an extra dose, and is currently considered if an infant is in contact with a child with measles or as an emergency solution to contain any measles outbreaks. If this occurred, the usual doses would be subsequently given from 12 months to ensure full immunity.

Citation and Funding

Nic Lochlainn LM, de Gier B, van der Maas N et al. Immunogenicity, effectiveness, and safety of measles vaccination in infants younger than 9 months: a systematic review and meta-analysis. Lancet Infect Dis. 2019;19(11):1235-45.

Funding was provided by the World Health Organization (WHO).

Bibliography

NHS website. Measles. London: Department of Health and Social Care; 2018.

Oxford Vaccine Group. Vaccine Knowledge Project: authoritative information for all. Oxford: University of Oxford; updated 2019.

PHE. UK immunisation schedule: the green book, chapter 11. London: Public Health England; 2019.

WHO. Recommendations for routine immunization. Geneva: World Health Organization; 2019.

Why was this study needed?

Measles is a highly contagious viral infection that can lead to life-threatening complications.

In the UK, there were 966 cases of measles in 2018, a substantial increase from the 259 cases the previous year. This has been mostly attributed to travel in Europe and large events such as music festivals.

The World Health Organization (WHO) recommends a 95% vaccination population coverage in order to achieve herd immunity. However, coverage has been reducing resulting in the return of measles outbreaks. In Europe, Asia and Africa, measles incidence has particularly increased in children younger than nine months, teenagers and adults. For people who have not been immunised, 9 out of 10 would catch measles if they came into contact with someone infected.

Due to this increase in incidence, the researchers wanted to assess whether the age for the first dose could be brought forward.

What did this study do?

This systematic review and meta-analysis identified 56 studies in which MCV1 was administered to infants under the age of nine months. The outcomes of interest included seroconversion (a sign that the immune system is reacting to the presence of the virus), antibody concentrations (levels of a protein produced by the body when it detects harmful substances), vaccine effectiveness against measles and safety.

The researchers included randomised controlled trials, quasi-randomised controlled trials, cohort and case-control studies, and outbreak investigations.

This review included studies that were observational in design. Although potential confounders can be adjusted for when interpreting the findings, it’s important to bear in mind that it isn’t possible to fully rule out the effects of other variables.

What did it find?

  • Pooled results from 20 studies showed that the proportion of infants who seroconverted increased from 50% (95% confidence interval [CI] 29% to 71%) in those vaccinated with MCV1 at four months to 85% (95% CI 69% to 97%) in those vaccinated at eight months of age.
  • Infants vaccinated with MCV1 between the ages of four to eight months had lower antibody levels compared with infants vaccinated after nine months (pooled mean antibody titre ratio 0.46, 95% CI 0.33 to 0.66). However, there was very wide variability between the studies which reduces the confidence in this result.
  • The pooled vaccine effectiveness of MCV1 in infants younger than nine months was 58% (95% CI 9% to 80%) according to eight studies. A similar proportion was effectively vaccinated when using within-study comparisons from five studies, at 51% (95% CI -44% to 83%) compared with the increased effectiveness above nine months of 83% (95% CI 76% to 88%).
  • There were no differences in the risk of adverse events between infants administered with MCV1 under or over the age of nine months.

What does current guidance say on this issue?

The UK immunisation schedule: the green book (updated in 2020) recommends administering the first dose of the MMR vaccine in infants on their first birthday or soon after. MMR2 is recommended at age three and four months, or soon after.

The WHO recommendations for routine immunisation in countries with low levels of transmission are that MCV1 be administered at 12 months of age. MCV2 is suggested to be administered based on programmatic considerations to achieve the highest coverage. The WHO also has a range of recommendations for when to give measles vaccines earlier in countries with higher rates of measles, including an extra dose (MCV0) before nine months during an outbreak.

What are the implications?

This review’s findings indicate that vaccine administration before nine months can still provide useful protection against measles and could, therefore, be an effective solution in areas where there is a high risk of contracting the disease.

In the UK, administering the first dose of MCV under nine months is considered to be an extra dose, and is currently considered if an infant is in contact with a child with measles or as an emergency solution to contain any measles outbreaks. If this occurred, the usual doses would be subsequently given from 12 months to ensure full immunity.

Citation and Funding

Nic Lochlainn LM, de Gier B, van der Maas N et al. Immunogenicity, effectiveness, and safety of measles vaccination in infants younger than 9 months: a systematic review and meta-analysis. Lancet Infect Dis. 2019;19(11):1235-45.

Funding was provided by the World Health Organization (WHO).

Bibliography

NHS website. Measles. London: Department of Health and Social Care; 2018.

Oxford Vaccine Group. Vaccine Knowledge Project: authoritative information for all. Oxford: University of Oxford; updated 2019.

PHE. UK immunisation schedule: the green book, chapter 11. London: Public Health England; 2019.

WHO. Recommendations for routine immunization. Geneva: World Health Organization; 2019.

Immunogenicity, effectiveness, and safety of measles vaccination in infants younger than 9 months: a systematic review and meta-analysis

Published on 25 September 2019

Nic Lochlainn, L. M.,de Gier, B.,van der Maas, N.,Strebel, P. M.,Goodman, T.,van Binnendijk, R. S.,de Melker, H. E.,Hahne, S. J. M.

Lancet Infect Dis , 2019

BACKGROUND: Measles is an important cause of death in children, despite the availability of safe and cost-saving measles-containing vaccines (MCVs). The first MCV dose (MCV1) is recommended at 9 months of age in countries with ongoing measles transmission, and at 12 months in countries with low risk of measles. To assess whether bringing forward the age of MCV1 is beneficial, we did a systematic review and meta-analysis of the benefits and risks of MCV1 in infants younger than 9 months. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, EMBASE, Scopus, Proquest, Global Health, the WHO library database, and the WHO Institutional Repository for Information Sharing database, and consulted experts. We included randomised and quasi-randomised controlled trials, outbreak investigations, and cohort and case-control studies without restriction on publication dates, in which MCV1 was administered to infants younger than 9 months. We did the literature search on June 2, 2015, and updated it on Jan 14, 2019. We assessed: proportion of infants seroconverted, geometric mean antibody titre, avidity, cellular immunity, duration of immunity, vaccine efficacy, vaccine effectiveness, and safety. We used random-effects models to derive pooled estimates of the endpoints, where appropriate. We assessed methodological quality using the Grading of Recommendations, Assessment, Development, and Evaluation guidelines. FINDINGS: Our search identified 1156 studies, of which 1071 were screened for eligibility. 351 were eligible for full-text screening, and data from 56 studies that met all inclusion criteria were used for analysis. The proportion of infants who seroconverted increased from 50% (95% CI 29-71) for those vaccinated with MCV1 at 4 months of age to 85% (69-97) for those were vaccinated at 8 months. The pooled geometric mean titre ratio for infants aged 4-8 months vaccinated with MCV1 compared with infants vaccinated with MCV1 at age 9 months or older was 0.46 (95% CI 0.33-0.66; I(2)=99.9%, p<0.0001). Only one study reported on avidity and suggested that there was lower avidity and a shorter duration of immunity following MCV1 administration at 6 months of age than at 9 months of age (p=0.0016) or 12 months of age (p<0.001). No effect of age at MCV1 administration on cellular immunity was found. One study reported that vaccine efficacy against laboratory-confirmed measles virus infection was 94% (95% CI 74-98) in infants vaccinated with MCV1 at 4.5 months of age. The pooled vaccine effectiveness of MCV1 in infants younger than 9 months against measles was 58% (95% CI 9-80; I(2)=84.9%, p<0.0001). The pooled vaccine effectiveness estimate from within-study comparisons of infants younger than 9 months vaccinated with MCV1 were 51% (95% CI -44 to 83; I(2)=92.3%, p<0.0001), and for those aged 9 months and older at vaccination it was 83% (76-88; I(2)=93.8%, p<0.0001). No differences in the risk of adverse events after MCV1 administration were found between infants younger than 9 months and those aged 9 months of older. Overall, the quality of evidence ranged from moderate to very low. INTERPRETATION: MCV1 administered to infants younger than 9 months induces a good immune response, whereby the proportion of infants seroconverted increases with increased age at vaccination. A large proportion of infants receiving MCV1 before 9 months of age are protected and the vaccine is safe, although higher antibody titres and vaccine effectiveness are found when MCV1 is administered at older ages. Recommending MCV1 administration to infants younger than 9 months for those at high risk of measles is an important step towards reducing measles-related mortality and morbidity. FUNDING: WHO.

Expert commentary

Choosing the best age for immunising children is a matter of a ‘trade-off’ between providing protection against disease as soon as possible versus delaying vaccine administration to improve the immune response.

In an ideal world, this wouldn’t be an issue, as high measles vaccine uptake within a community eliminates virus circulation, providing protection to younger children via herd immunity.

This important review and re-analysis of the existing evidence provide reassurance that if young children are at high risk of exposure (for example, during a measles outbreak) then measles vaccination can be started from six months of age without any long-term impact on vaccine effectiveness.

Dr Matthew Snape, Associate Professor in Paediatrics and Vaccinology, Oxford Vaccine Group, Department of Paediatrics, University of Oxford; NIHR Oxford Biomedical Research Centre

The commentator conducts clinical trials on behalf of the University of Oxford that are sponsored and/or funded by vaccine manufacturers including GSK, Novavax, Pfizer, Janssen, MCM and Medimmune. He receives no personal payment for this work.