Thursday, December 14, 2017

The Lancet: Estimates Of Global Seasonal Flu Respiratory Mortality


Getting a decent handle on the annual incidence of - or mortality from - any illness or disease has always been daunting, and in truth, nearly all of the numbers you see quoted are rough estimates. As the chart above illustrates, only a fraction of cases - even in the most highly developed nations  - are ever tested and confirmed by public health officials.
Add to that ambiguity the fact that many diseases vary widely from year-to-year in severity, and many deaths may occur weeks or even months removed from an initial illness, and the best we can hope for is some kind of broad range.
For years, the mantra has been that seasonal influenza (excluding pandemic years) claims as many as 500,000 lives each year.  It's a very rough estimate.  But it is an easily remembered round number, and so it gets mentioned a lot.

Overnight a new study was published in The Lancet which attempts to refine that number - based on better surveillance numbers and new modeling - and finds that 500,000 mark is probably a substantial underestimate.

Their new estimate, however, is based strictly on respiratory-mortality, and that likely under-counts other influenza-associated causes of death (heart attack, stroke, etc.) that can occur in the weeks following infection (see Int. Med. J.: Triggering Of Acute M.I. By Respiratory Infection and Study: Flu Vaccine May Reduce Heart Attack Risk). 
It is, however, a start.
First, a press release on this study from the CDC, then a link to the Lancet Abstract.
Seasonal flu death estimate increases worldwide

Embargoed Until: Wednesday, December 13, 2017, 6:30 p.m. ET
Contact: Media Relations
(404) 639-3286

According to new estimates published today, between 291,000 and 646,000 people worldwide die from seasonal influenza-related respiratory illnesses each year, higher than a previous estimate of 250,000 to 500,000 and based on a robust, multinational survey.

The new estimate, from a collaborative study by CDC and global health partners, appears today in The Lancet. The estimate excludes deaths during pandemics.

“These findings remind us of the seriousness of flu and that flu prevention should really be a global priority,” says Joe Bresee, M.D., associate director for global health in CDC’s Influenza Division and a study co-author.

The new estimates use more recent data, taken from a larger and more diverse group of countries than previous estimates. Forty-seven countries contributed to this effort. Researchers calculated annual seasonal influenza-associated respiratory deaths for 33 of those countries (57 percent of the world’s population) that had death records and seasonal influenza surveillance information for a minimum of four years between 1999 and 2015. Statistical modeling with those results was used to generate an estimate of the number of flu-associated respiratory deaths for 185 countries across the world. Data from the other 14 countries were used to validate the estimates of seasonal influenza-associated respiratory death from the statistical models.

Poorest nations, older adults hit hardest by flu

Researchers calculated region-specific estimates and age-specific mortality estimates for people younger than 65 years, people 65-74 years, and people 75 years and older. The greatest flu mortality burden was seen in the world’s poorest regions and among older adults. People age 75 years and older and people living in sub-Saharan African countries experienced the highest rates of flu-associated respiratory deaths. Eastern Mediterranean and Southeast Asian countries had slightly lower but still high rates of flu-associated respiratory deaths.

Despite World Health Organization recommendations to use flu vaccination to help protect people in high-risk populations, few developing countries have seasonal flu vaccination programs or the capacity to produce and distribute seasonal or pandemic vaccines.

Global flu surveillance protects all nations, including U.S.

CDC works with global partners to improve worldwide capacity for influenza prevention and control. CDC has helped more than 60 countries build surveillance and laboratory capacity to rapidly detect and respond to influenza threats, including viruses with the potential to cause global pandemics.  These efforts, along with technical support, has helped some partners generate estimates of influenza-associated deaths, which contributed to this global effort.

Global surveillance also provides the foundation for selecting the viruses used to make seasonal flu vaccines each year. This helps improve the effectiveness of flu vaccines used in the United States. Global surveillance also is crucial to pandemic preparedness by identifying viruses overseas that might pose a human health risk to people in the United States.

“This work adds to a growing global understanding of the burden of influenza and populations at highest risk,” says CDC researcher Danielle Iuliano, lead author of The Lancet study. “It builds the evidence base for influenza vaccination programs in other countries.”

The study authors note that these new estimates are limited to flu-associated respiratory deaths and therefore may underestimate the true global impact of seasonal influenza. Influenza infection can create or exacerbate other health factors which are then listed as the cause of death on death certificates, for example cardiovascular disease, diabetes, or related complications. Additional research to estimate non-respiratory causes of flu-associated deaths are ongoing.
        (Continue . . . )

Estimates of global seasonal influenza-associated respiratory mortality: a modelling study

A Danielle Iuliano, PhD'Correspondence information about the author PhD A Danielle IulianoEmail the author PhD A Danielle Iuliano, Katherine M Roguski, MPH, Howard H Chang, PhD, David J Muscatello, PhD, Rakhee Palekar, MD, Stefano Tempia, PhD, Cheryl Cohen, PhD, Jon Michael Gran, PhD, Dena Schanzer, MSc, Prof Benjamin J Cowling, PhD, Peng Wu, PhD, Jan Kyncl, MD , Li Wei Ang, MSc, Minah Park, MPH, Monika Redlberger-Fritz, MD, Hongjie Yu, MD, Laura Espenhain, MPHS, Prof Anand Krishnan, PhD, Gideon Emukule, PhD, Liselotte van Asten, PhD, Susana Pereira da Silva, MSc, Suchunya Aungkulanon, MSc, Udo Buchholz, MD, Marc-Alain Widdowson, VetMB
, Joseph S Bresee, MD 
Published: 13 December 2017


Estimates of influenza-associated mortality are important for national and international decision making on public health priorities. Previous estimates of 250 000–500 000 annual influenza deaths are outdated. We updated the estimated number of global annual influenza-associated respiratory deaths using country-specific influenza-associated excess respiratory mortality estimates from 1999–2015.

EMR-contributing countries represented 57% of the global population. The estimated mean annual influenza-associated respiratory EMR ranged from 0·1 to 6·4 per 100 000 individuals for people younger than 65 years, 2·9 to 44·0 per 100 000 individuals for people aged between 65 and 74 years, and 17·9 to 223·5 per 100 000 for people older than 75 years. We estimated that 291 243–645 832 seasonal influenza-associated respiratory deaths (4·0–8·8 per 100 000 individuals) occur annually. The highest mortality rates were estimated in sub-Saharan Africa (2·8–16·5 per 100 000 individuals), southeast Asia (3·5–9·2 per 100 000 individuals), and among people aged 75 years or older (51·3–99·4 per 100 000 individuals). For 92 countries, we estimated that among children younger than 5 years, 9243–105 690 influenza-associated respiratory deaths occur annually.

These global influenza-associated respiratory mortality estimates are higher than previously reported, suggesting that previous estimates might have underestimated disease burden. The contribution of non-respiratory causes of death to global influenza-associated mortality should be investigated.
         (Continue . . . . )

The old adage (attributed to George E. P. Box (18 October 1919 – 28 March 2013), Professor Emeritus of Statistics at the University of Wisconsin) is that:
“All models are wrong, but some models are useful.”
While there will undoubtedly be debate over the accuracy of these newest estimates - as well as over what constitutes an `influenza-associated death' -  the simple reality is that seasonal influenza is a substantial and largely under-appreciated cause of morbidity and mortality around the world.

Finding ways to reduce its burden - either through better, more efficient vaccines or by encouraging better flu hygiene - could save a great many lives.

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