Immunization: Reducing measles mortality in India
Measles is a highly infectious disease that can lead to serious complications and even death. The measles virus has been around for over 5,000 years and exclusively infects humans (Rota et al., 2016). However, measles can be prevented by a vaccine that is both safe and effective, so it should be possible to eradicate the disease, just as we did with smallpox and are very close to achieving with polio.
The measles vaccine is made of a live but weakened ('live attenuated') form of the measles virus that can induce immunity but does not cause disease, and costs less than a dollar per dose. It was first introduced in the United States in the 1960s, and in September 2016, the World Health Organization (WHO) declared the Americas free of endemic measles. So far, it is the only WHO region to have achieved this status, which, however, was lost in 2018 due to the poor immunization coverage that allowed endemic transmission to be reestablished in Venezuela and to spread to other countries. Vaccine hesitancy behavior, often fueled by misinformation, has also played a part (Dabbagh et al., 2018).
According to WHO estimates, measles vaccinations have prevented around 21 million deaths globally, and nearly 7 million deaths in the WHO region of South East Asia between 2000 and 2017 (Dabbagh et al., 2018). Nevertheless, in 2017, almost one-third (nearly 36,000) of global measles deaths occurred in South East Asia, many of which were in India due to the relativley large number of unvaccinated children.
In 2010, faced with such a high mortality burden from a vaccine-preventable disease, the Indian government introduced a second dose of measles vaccine into its immunization program through a two-pronged approach: routine immunization in 17 states, and mass immunization campaigns targeting children aged between 9 months and 10 years in 14 other states with historically low immunization uptakes. The campaigns were implemented between 2010 and 2013, targeting over 134 million children – a massive undertaking by any standards and one of the largest mass immunization campaigns ever conducted (Centers for Disease Control and Prevention, 2011).
India did not have a sensitive nationwide measles surveillance system that could demonstrate the possible impact of the campaign by providing reliable information about the number of measles cases and deaths before and after the campaign. In some states, such as Gujarat in the west, the number of measles cases went down after the campaign from nearly 1,000 in 2010 to none in 2012. However, the immunization campaign also triggered an interest for a better surveillance system leading to increased case identification, which in turn led to an apparent increase in reported measles cases after the campaign in some states. Therefore, the immunization program was unable to obtain definitive data to measure the impact of the campaign (WHO, 2013; Centers for Disease Control and Prevention, 2011).
Now, in eLife, Prabhat Jha of the University of Toronto and colleagues – including Benjamin Wong as first author – report how they were able to assess the full impact of this enormous immunization campaign (Wong et al., 2019). Wong et al. used data from the Million Death Study, which systematically ascertains the cause of death in a nationally representative sample of deaths in India, including 27,000 child deaths from 1.3 million households between 2005 and 2013 (The Million Death Study Collaborators, 2010; Fadel et al., 2017; Gomes et al., 2017).
The team – which also includes researchers from King George's Medical University, the Ministry of Health and Family Welfare in India, the Post Graduate Institute of Medical Education and Research, and the National Institute of Medical Statistics – used a number of statistical techniques, including an approach called interrupted time series that allowed them to measure the impact of a time-limited intervention (the measles campaign in this case) on events that are continuous (the measles deaths). The basic premise of their study was not to develop a model that could provide estimates of measles mortality: rather, they directly sampled death events before and after the immunization intervention and showed a significant reduction in measles deaths.
In addition, they also compared changes in the occurrence of measles deaths before and after the campaign to changes in child deaths from other causes during the same period. The latter group did not show any reduction, which suggests that the decrease in measles deaths was indeed related to the vaccination campaigns and not to other healthcare improvements.
The analyses revealed that the mass immunization campaigns prevented between 41,000 and 56,000 measles deaths in children (which corresponds to a reduction of 39–57%). In campaign states, mortality rates fell more than in states without a campaign, whereas the number of child deaths from other causes did not fall. The results reported by Wong et al. should help public health officials in India and elsewhere to take informed decisions in their efforts to control or eliminate measles cases and deaths using mass immunization campaigns.
References
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Progress in implementing measles mortality reduction strategies–India, 2010–2011MMWR. Morbidity and Mortality Weekly Report 60:1315–1319.
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Progress toward regional measles elimination–worldwide, 2000-2017Morbidity and Mortality Weekly Report 67:1323–1329.https://doi.org/10.15585/mmwr.mm6747a6
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- Version of Record published: April 9, 2019 (version 1)
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© 2019, Bose
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Further reading
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Measles vaccination campaigns have saved the lives of about 50,000 Indian children in three years.
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- Biochemistry and Chemical Biology
- Epidemiology and Global Health
Background: High levels of circulating adiponectin are associated with increased insulin sensitivity, low prevalence of diabetes, and low body mass index (BMI); however, high levels of circulating adiponectin are also associated with increased mortality in the 60-70 age group. In this study, we aimed to clarify factors associated with circulating high-molecular-weight (cHMW) adiponectin levels and their association with mortality in the very old (85-89 years old) and centenarians.
Methods: The study included 812 (women: 84.4%) for centenarians and 1,498 (women: 51.7%) for the very old. The genomic DNA sequence data were obtained by whole genome sequencing or DNA microarray-imputation methods. LASSO and multivariate regression analyses were used to evaluate cHMW adiponectin characteristics and associated factors. All-cause mortality was analyzed in three quantile groups of cHMW adiponectin levels using Cox regression.
Results: The cHMW adiponectin levels were increased significantly beyond 100 years of age, were negatively associated with diabetes prevalence, and were associated with SNVs in CDH13 (p = 2.21 × 10-22) and ADIPOQ (p = 5.72 × 10-7). Multivariate regression analysis revealed that genetic variants, BMI, and high-density lipoprotein cholesterol (HDLC) were the main factors associated with cHMW adiponectin levels in the very old, whereas the BMI showed no association in centenarians. The hazard ratios for all-cause mortality in the intermediate and high cHMW adiponectin groups in very old men were significantly higher rather than those for all-cause mortality in the low level cHMW adiponectin group, even after adjustment with BMI. In contrast, the hazard ratios for all-cause mortality were significantly higher for high cHMW adiponectin groups in very old women, but were not significant after adjustment with BMI.
Conclusions: cHMW adiponectin levels increased with age until centenarians, and the contribution of known major factors associated with cHMW adiponectin levels, including BMI and HDLC, varies with age, suggesting that its physiological significance also varies with age in the oldest old.
Funding: This study was supported by grants from the Ministry of Health, Welfare, and Labour for the Scientific Research Projects for Longevity; a Grant-in-Aid for Scientific Research (No 21590775, 24590898, 15KT0009, 18H03055, 20K20409, 20K07792, 23H03337) from the Japan Society for the Promotion of Science; Keio University Global Research Institute (KGRI), Kanagawa Institute of Industrial Science and Technology (KISTEC), Japan Science and Technology Agency (JST) Research Complex Program 'Tonomachi Research Complex' Wellbeing Research Campus: Creating new values through technological and social innovation (JP15667051), the Program for an Integrated Database of Clinical and Genomic Information from the Japan Agency for Medical Research and Development (No. 16kk0205009h001, 17jm0210051h0001, 19dk0207045h0001); the medical-welfare-food-agriculture collaborative consortium project from the Japan Ministry of Agriculture, Forestry, and Fisheries; and the Biobank Japan Program from the Ministry of Education, Culture, Sports, and Technology.