Seasonal variation and etiologic inferences of childhood pneumonia and diarrhea mortality in India
Abstract
Future control of pneumonia and diarrhea mortality in India requires understanding of their etiologies. We combined time series analysis of seasonality, climate-region, and clinical syndromes from 243,000 verbal autopsies in the nationally-representative Million Death Study. Pneumonia mortality at 1 month-14 years was greatest in January (Rate ratio (RR) 1.66, 99%CI 1.51-1.82; versus the April minimum). Higher RRs at 1-11 months suggested respiratory syncytial virus (RSV) etiology. India's humid subtropical region experienced a unique summer pneumonia mortality. Diarrhea mortality peaked in July (RR 1.66, 1.48-1.85) and January (RR 1.37, 1.23-1.48), while deaths with fever and bloody diarrhea (indicating enteroinvasive bacterial etiology) showed little seasonality. Combining mortality at ages 1-59-months in 2015 with prevalence surveys, we estimate 40,600 pneumonia deaths from Streptococcus pneumoniae, 20,700 from RSV, 12,600 from influenza, and 7,200 from Haemophilus influenzae type b and 24,700 diarrheal deaths from rotavirus. Careful mortality studies can elucidate etiologies and inform vaccine introduction.
Data availability
Data from the Million Death Study cannot be redistributed outside of the Centre for Global Health Research due to legal agreements with the Registrar General of India. Access to MDS data can be granted via data transfer agreements, upon request to the Office of the Registrar General, RK Puram, New Delhi, India (rgoffice.rgi@nic.in). The public census reports can be found at http://www.censusindia.gov.in/vital_statistics/SRS_Statistical_Report.html. Source data files have been provided for Figure 3, Figure 3 - figure supplement 1, Figure 3 - figure supplement 2, Figure 4, Figure 4 - figure supplement 1, Figure 6, Figure 6 - figure supplement 1, and Figure 8. Meta-analyses include only previously published data, and all data sources have been listed in supplemental reference lists within the article file.
Article and author information
Author details
Funding
Canadian Institutes of Health Research (FDN154277)
- Prabhat Jha
Bill and Melinda Gates Foundation
- Prabhat Jha
National Institutes of Health (R01TW05991-01)
- Prabhat Jha
The funders had no role in study design, data collection, analysis or interpretation, preparation of the manuscript or the decision to submit the work for publication.
Reviewing Editor
- Mark Jit, London School of Hygiene & Tropical Medicine, and Public Health England, United Kingdom
Version history
- Received: February 19, 2019
- Accepted: August 21, 2019
- Accepted Manuscript published: August 27, 2019 (version 1)
- Version of Record published: September 24, 2019 (version 2)
Copyright
© 2019, Farrar et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Further reading
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- Epidemiology and Global Health
- Microbiology and Infectious Disease
Background: Few national-level studies have evaluated the impact of 'hybrid' immunity (vaccination coupled with recovery from infection) from the Omicron variants of SARS-CoV-2.
Methods: From May 2020 to December 2022, we conducted serial assessments (each of ~4000-9000 adults) examining SARS-CoV-2 antibodies within a mostly representative Canadian cohort drawn from a national online polling platform. Adults, most of whom were vaccinated, reported viral test-confirmed infections and mailed self-collected dried blood spots to a central lab. Samples underwent highly sensitive and specific antibody assays to spike and nucleocapsid protein antigens, the latter triggered only by infection. We estimated cumulative SARS-CoV-2 incidence prior to the Omicron period and during the BA.1/1.1 and BA.2/5 waves. We assessed changes in antibody levels and in age-specific active immunity levels.
Results: Spike levels were higher in infected than in uninfected adults, regardless of vaccination doses. Among adults vaccinated at least thrice and infected more than six months earlier, spike levels fell notably and continuously for the nine months post-vaccination. By contrast, among adults infected within six months, spike levels declined gradually. Declines were similar by sex, age group, and ethnicity. Recent vaccination attenuated declines in spike levels from older infections. In a convenience sample, spike antibody and cellular responses were correlated. Near the end of 2022, about 35% of adults above age 60 had their last vaccine dose more than six months ago, and about 25% remained uninfected. The cumulative incidence of SARS-CoV-2 infection rose from 13% (95% CI 11-14%) before omicron to 78% (76-80%) by December 2022, equating to 25 million infected adults cumulatively. However, the COVID-19 weekly death rate during the BA.2/5 waves was less than half of that during the BA.1/1.1 wave, implying a protective role for hybrid immunity.
Conclusions: Strategies to maintain population-level hybrid immunity require up-to-date vaccination coverage, including among those recovering from infection. Population-based, self-collected dried blood spots are a practicable biological surveillance platform.
Funding: Funding was provided by the COVID-19 Immunity Task Force, Canadian Institutes of Health Research, Pfizer Global Medical Grants, and St. Michael's Hospital Foundation. PJ and ACG are funded by the Canada Research Chairs Program.
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- Computational and Systems Biology
- Epidemiology and Global Health
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