Seasonal variation and etiologic inferences of childhood pneumonia and diarrhea mortality in India
- St Michael's Hospital, Canada
- King George's Medical University, India
- Postgraduate Institute of Medical Education and Research, India
- Indian Council of Medical Research, India
- Johns Hopkins Bloomberg School of Public Health, United States
- Hospital for Sick Children, Canada
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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Seasonal variation and etiologic inferences of childhood pneumonia and diarrhea mortality in India
eLife 8:e46202.
https://doi.org/10.7554/eLife.46202
Further reading
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- Epidemiology and Global Health
Background:
Circulating omega-3 and omega-6 polyunsaturated fatty acids (PUFAs) have been associated with various chronic diseases and mortality, but results are conflicting. Few studies examined the role of omega-6/omega-3 ratio in mortality.
Methods:
We investigated plasma omega-3 and omega-6 PUFAs and their ratio in relation to all-cause and cause-specific mortality in a large prospective cohort, the UK Biobank. Of 85,425 participants who had complete information on circulating PUFAs, 6461 died during follow-up, including 2794 from cancer and 1668 from cardiovascular disease (CVD). Associations were estimated by multivariable Cox proportional hazards regression with adjustment for relevant risk factors.
Results:
Risk for all three mortality outcomes increased as the ratio of omega-6/omega-3 PUFAs increased (all Ptrend <0.05). Comparing the highest to the lowest quintiles, individuals had 26% (95% CI, 15–38%) higher total mortality, 14% (95% CI, 0–31%) higher cancer mortality, and 31% (95% CI, 10–55%) higher CVD mortality. Moreover, omega-3 and omega-6 PUFAs in plasma were all inversely associated with all-cause, cancer, and CVD mortality, with omega-3 showing stronger effects.
Conclusions:
Using a population-based cohort in UK Biobank, our study revealed a strong association between the ratio of circulating omega-6/omega-3 PUFAs and the risk of all-cause, cancer, and CVD mortality.
Funding:
Research reported in this publication was supported by the National Institute of General Medical Sciences of the National Institute of Health under the award number R35GM143060 (KY). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
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- Epidemiology and Global Health
Non-pharmaceutical interventions implemented to block SARS-CoV-2 transmission in early 2020 led to global reductions in the incidence of invasive pneumococcal disease (IPD). By contrast, most European countries reported an increase in antibiotic resistance among invasive Streptococcus pneumoniae isolates from 2019 to 2020, while an increasing number of studies reported stable pneumococcal carriage prevalence over the same period. To disentangle the impacts of the COVID-19 pandemic on pneumococcal epidemiology in the community setting, we propose a mathematical model formalizing simultaneous transmission of SARS-CoV-2 and antibiotic-sensitive and -resistant strains of S. pneumoniae. To test hypotheses underlying these trends five mechanisms were built into the model and examined: (1) a population-wide reduction of antibiotic prescriptions in the community, (2) lockdown effect on pneumococcal transmission, (3) a reduced risk of developing an IPD due to the absence of common respiratory viruses, (4) community azithromycin use in COVID-19 infected individuals, (5) and a longer carriage duration of antibiotic-resistant pneumococcal strains. Among 31 possible pandemic scenarios involving mechanisms individually or in combination, model simulations surprisingly identified only two scenarios that reproduced the reported trends in the general population. They included factors (1), (3), and (4). These scenarios replicated a nearly 50% reduction in annual IPD, and an increase in antibiotic resistance from 20% to 22%, all while maintaining a relatively stable pneumococcal carriage. Exploring further, higher SARS-CoV-2 R0 values and synergistic within-host virus-bacteria interaction mechanisms could have additionally contributed to the observed antibiotic resistance increase. Our work demonstrates the utility of the mathematical modeling approach in unraveling the complex effects of the COVID-19 pandemic responses on AMR dynamics.
