Measles vaccine improves child survival beyond protecting against measles

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MeaslesIn the largest study to date on children in a low/middle income country, researchers from the Navrongo Health Research Centre, Ghana, OPEN, Institute of Clinical Research, University of Southern Denmark, Odense, research and development division, Ghana Health Service, Accra, Bandim Health Project, Indepth Network, Gineau-Bissau, Bandim Health Project, Statens Serum Institut, Copenhagen and the University of Health and Allied Scienes, Ho, Ghana, found that the timing of a measles vaccine in an overall vaccination schedule can have a profound impact on child survival rates beyond protecting against measles infection.

The findings suggest that measles vaccination in the recommended sequence may have made an important contribution towards achieving the Millennium Development Goal 4 of reducing child mortality.

Measles – along with tuberculosis, diphtheria, tetanus, pertussis and poliomyelitis – is one of the six childhood ‘killer diseases’ targeted by World Health Organisation (WHO) mass immunisation programmes. In addition to protecting against these diseases, previous studies suggest that these routine vaccines may provide other benefits that help to reduce child mortality.

Some studies also suggest that the sequence of administering vaccines could be important. In particular, child mortality was shown to be lower when the measles vaccine came after the third diphtheria, tetanus and pertussis (DTP3) vaccination, as recommend by the WHO, compared to before DTP or given together with DTP.

The latest study extends this to look at whether all-cause mortality is lower when a child’s most recent immunisation is a measles vaccine. Using routine vaccination and survival data for more than 38,000 children over a 17-year period in northern Ghana, the researchers assessed mortality differences between children vaccinated against measles after the DTP3 vaccine and those who were not vaccinated against measles.

Survival was assessed at two-time points: within the first 12 months after the initial assessment of vaccination status; and until five years of age. The researchers found that compared to measles-unvaccinated children, survival rates for measles-vaccinated children increased by a staggering 28% in the first 12 months of follow-up and 18% by five years of age. This effect was still present when children who had died from measles were excluded from the analysis – indicating that the measles vaccine has beneficial effects beyond direct prevention of measles.

“Evaluations of immunisation programs are usually based on the assumption that vaccines only protect against specific diseases,” says the study’s lead author, Dr Paul Welaga from the Navrongo Health Research Centre in Ghana. “Our new study adds to growing evidence that, when administered in the recommended sequence, measles vaccination helps to reduce child mortality through non-specific effects as well.”

The proportion of children in Ghana who received the measles vaccine after DTP3 increased from 45% in 1996 to 95% in 2012. The authors suggest this improved measles vaccination coverage in the recommended sequence may have contributed towards the Millennium Development Goal 4 of reducing child mortality.

“When children in Ghana are not fully vaccinated, it is usually the measles vaccination which is missing,” says Welaga. “Policy makers should ensure that children get vaccinated for measles after DTP3 because of the potential survival benefits.”

The study also found a significantly stronger beneficial effect of measles vaccination for boys in comparison to girls. Measles unvaccinated boys had a 69% higher risk of dying during one year of follow-up and a 43% higher mortality rate when followed until 5 years of age. For girls, there was little difference. The study’s authors say the reasons for this are unclear and recommend future studies to examine the sex-differential effect of measles vaccination on all-cause mortality.

Welaga says that researchers should consider testing the effect of measles vaccines and other routine vaccines on all-cause mortality in randomised trials. “It may be that measles infection is eliminated in the near future and thus measles vaccination is de-emphasised – but if the non-specific beneficial effects of measles vaccination are indeed positive then we should consider continued vaccination even if measles is eradicated.”

Abstract
Background: Measles vaccine (MV) administered as the last vaccine after the third dose of diphtheria-tetanus-pertussis (DTP) may be associated with better child survival unrelated to prevention of measles infection. Other studies have shown that MV administered after DTP was more beneficial and was associated with lower mortality compared with DTP administered after MV or DTP administered simultaneously with MV. We compared the difference in mortality between measles vaccinated after DTP3 and measles-unvaccinated children in Navrongo, Ghana.
Methods: This was a follow-up study involving annual cohort of children aged 9–23 months from 1996 to 2012. We assessed survival in relation to the measles vaccination status within the first 12 months from interview date and until 5 years of age using Cox proportional hazards models.
Results: In all, 38,333 children were included in the study. The proportion of children vaccinated with MV-after-DTP3 increased from 45% in 1996 to 95% in 2012. The adjusted hazard ratio (HR) for measles unvaccinated compared with MV-after-DTP3 vaccinated children was 1.38 (1.15–1.66) in the first 12 months after assessment of vaccination status and 1.22 (1.05–1.41) with follow-up to 5 years of age. The national immunization days campaigns with oral polio vaccine or MV might have reduced the effect of being MV-after-DTP3 vaccinated vs MV-unvaccinated. For 12 months of follow-up, the HR before a campaign for MV-unvaccinated children was 1.63 (1.23–2.17) compared to those who received MV-after-DTP3. After the campaign, the HR reduced to 1.23 (0.97–1.54). Stratifying the analysis by sex, measles-unvaccinated boys had a HR of 1.69 (1.33–2.61) compared to measles-unvaccinated girls who had a HR 1.06 (0.79–1.40) during 1-year follow-up. In 1989, only 7% of children in the area had received MV-after-DTP3; the increase in MV-after-DTP3 coverage from 1989 to 2012 may have lowered mortality rate among children aged 9 months to 3 years by 24%.
Conclusion: Though an observational study, our findings suggest that measles vaccination, administered in the recommended sequence, is associated with improved child survival and may have contributed importantly to the mortality decline toward the achievement of Millennium Development Goal 4.

Authors
Paul Welaga, Abraham Hodgson, Cornelius Debpuur, Peter Aaby, Fred Binka, Daniel Azongo, Abraham Oduro

Frontiers material
Frontiers in Public Health abstract


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