At the end of 2018, we remember and respect Influenza, 100 years after the great pandemic

The Mother of All Pandemics
In the 1918-1919 calendar year, the world experienced the worst influenza pandemic in modern times. Coming on the heels of WWI, the H1N1 pandemic occurred in three waves – in the spring of 1918, fall 1918 and spring 1919. Estimates suggest that the pandemic infected a third of the world’s population, with 50 million people dying worldwide, including 675,000 Americans. Mortality was high at extremes of ages, but what sets this particular pandemic apart was the significant mortality (over half of all deaths) in young, healthy 20-40yr olds. Why such devastating morbidity and mortality? Perhaps a combination of war-ravaged, crowded conditions, malnourishment, inadequate healthcare resources (many doctors/nurses were deployed at war), and poor hygiene. In the early 20th century, there were no influenza vaccines to prevent flu or lessen its symptoms; no antivirals to help reduce transmission; no antibiotics to treat post-influenza bacterial pneumonia. The Smithsonian National Museum estimated that the total death toll of the 1918 pandemic outnumbered military deaths in both World War I and II. You can watch a video created by the CDC about the 1918 pandemic here. This avian-origin H1N1 pandemic has been called “The Mother of All Pandemics”, setting the stage for all of the subsequent epidemic and pandemic strains of influenza we have experienced.

After 1918: Influenza still deadly, though not as devastating
In 1957-1958 an H2N2 avian influenza virus caused a pandemic resulting in 1.1 million deaths worldwide including 116,000 Americans. 10 years later, another avian-based virus H3N2 triggered a similar sized pandemic with 1 million deaths worldwide and 100,000 Americans. The H3N2 still circulates as a seasonal flu virus and is included in seasonal vaccines. The next major pandemic was triggered by a novel influenza A virus called H1N1pdm09 in 2009, originating in the United States. By this time, seasonal influenza vaccines had included H1N1 but this variant was completely different from the seasonal flu vaccine, resulting in an estimated over half million deaths worldwide and up to 18,000 Americans.

Today: There is still work to be done
Since 2009's pandemic, seasonal influenza is still prevalent, with an estimate of over 291,000-645,000 deaths from seasonal influenza worldwide. The highest mortality rates are in poorer, developing countries, with individuals at extremes of age being most vulnerable to death from seasonal influenza. We still do not have a universal influenza vaccine, though research is moving in that direction. The 2017-2018 influenza season brought a serious influenza epidemic, with 48.8 million illnesses, 959,000 hospitalizations and 79,400 deaths estimated in the United States alone. This week, the Infectious Diseases Society of America (IDSA) released updated guidelines for diagnosis, and management of seasonal influenza. In the guidelines, they recommend testing for influenza in upper respiratory specimens of high risk patients, when testing can reduce unnecessary additional testing/inappropriate antibiotics, or when testing can influence chemoprophylaxis for high-risk household contacts. Annual seasonal flu vaccination reduces the risk of influenza by 40-60% and is still recommended as the best way to mitigate the impact of seasonal influenza, but antiviral prophylaxis may be necessary in outbreaks or for certain at-risk populations. Other ways to prevent spread include hand hygiene, limiting contact with people who have influenza-like illness, and if you have such an illness yourself, STAY HOME. 

More than 166.6Million influenza vaccines have been distributed in the US as of December 20, 2018.The influenza vaccine may not always be a 100% match to all circulating strains, as we saw with last year's flu season.  This year’s vaccine contains an influenza A H1N1pdm09-like strain, an influenza A H3N2-like strain, and influenza B strains from the Victoria and Yamagata lineages. Updated this year, the Advisory Committee on Immunization Practices (ACIP) also recommends the live-attenuated influenza vaccine (FluMist); however, the American Academy of Pediatrics suggests this only be used if the alternative would be no flu shot at all. The CDC can explain the types of vaccines available and who should get them. 

Final thoughts about the flu 

Regardless of which vaccine is more appropriate, our ancestors would probably encourage us to just get ANY vaccine if it would help avoid recreating the influenza pandemic of 1918. There's still time - it's not too late so if you haven't gotten your flu shot, consider getting it today!

Seasonal Flu Vaccine and Pandemic Severity: ICAAC 2012

Talk and discussion from Dr. Danuta Skowronski, BC Center for Disease Control, Vancouver, BC, Canada. Did receipt of seasonal flu vaccine increase the risk of pandemic virus infection?


More videos will be posted during the conference on MicrobeWorld's YouTube Channel

Helen Branswell, Canadian Press, covered this topic in an excellent article yesterday.

La Nina and Influenza Pandemics

A new study published in PNAS by Jeffrey Shaman and Marc Lipsitch finds that the four recent influenza pandemics (1918, 1957, 1968, and 2009) were all preceded by La Niña (colder sea surface) conditions in the Pacific Ocean. The authors suggest that the climate changes can alter migratory bird activity and thus possibly impact their mixing with domestic animals. They therefore hypothesize that La Niña results in a higher likelihood of divergent influenza subtypes coming together with a subsequent higher probability of emergence of novel "pandemic" influenza strains.

In an accompanying BBC story by Richard Black, professor Shaman explains the findings and also cautions that the link should not yet be used to predict pandemics. However, he is hopeful that increased influenza strain surveillance subsequent to recent novel H1N1 and avian H5N1 activity will soon be able to confirm whether their proposed hypothesis is correct.

Reference
Shaman and Lipsitch PNAS 1/17/2012

@eliowa

Contagion - September 9th!!

I know Mike posted about this a month ago, but I saw an ad of the upcoming movie Contagion while watching Cubs/Cards and they've released the opening date. Mark your calendars. If you haven't seen 'Rise of the Planet of the Apes', it's pretty clear that the next "Apes" movie will have a similar global pandemic theme.

Contagion

For those of you who didn't get worked over enough by the H1N1 pandemic, there's a movie entitled Contagion that will be released in September. It's about an epidemic of deadly avian influenza and the cast includes some major Hollywood stars. You can see the trailer here. Looks scary--maybe it will increase influenza vaccine compliance!

Hat tip:  Rebekah Moehring

Critique of the WHO pandemic response is now out

We blogged early and often about the H1N1 pandemic, including posts about the controversy surrounding the WHO response and whether there was any industry influence at play. An independent expert panel has now released a draft report on the 2009 H1N1 response. Here are the media summaries from the NY Times, Science Magazine, and the Nature blog The Great Beyond.

Regarding the industry conflict-of-interest (COI) issue, the report takes WHO to task for poor handling of COI and lack of transparency, but concludes that there is "no evidence of attempted or actual influence by commercial interests on advice given to or decisions made by WHO." I’m not sure what such evidence would be required…direct cash payments to members of the WHO advisory committee? Anyway, given that the panel felt that WHO waited too long to call the pandemic, it is unlikely they’d conclude that this decision was driven by industry COI.

Read the report yourself—now that Iowa has thawed out and the sun has appeared, I have no time to detail all 15 of the recommendations the panel made.

Pandemic Flu: Hit hard, but should we hit early?

Image courtesy of CU Boulder Applied Math
Mathematical Biology Group

When a new pandemic flu strain emerges, as happened in Mexico in 2009, public health interventions such as social distancing are often implemented in the hope of reducing transmission. It is often assumed that the more measures that can be implemented early in the epidemic, the better. However, social distancing policies, while sounding simple, are very costly and typically of finite duration.  It is also unclear, what the policy 'objectives' of the intervention should be. Is the aim to reduce total morbidity/mortality or is it to reduce peak prevalence? How are these aims to be balanced against the societal impact of the interventions? Heady questions indeed.  Fortunately, a new paper in PLoS Computational Biology by Deirdre Hollingsworth and colleagues (including Roy Anderson) poses many of these questions and attempts to explore the intertwined policy objectives of various pandemic flu mitigation strategies.

Using a mathematical model (deterministic SIR model) and assuming a mean infectious period of 2.6 days, an Ro=1.8 and a population size of 58 million (the population of the island of Great Britain), the authors estimated the impact of social distancing interventions on influenza dynamics. They looked at a three possible durations of the intervention: (1) indefinite (2) 12 weeks - the current US policy maximum and (3) until a pandemic vaccine becomes available at 6 months. The also incorporated the use of a limited stockpile of antiviral drugs to limit disease severity and reduce transmission and also looked at the utilization of a partially protective pre-pandemic vaccine during the first 6 months of the pandemic.

What did they find? Well, it is pretty messy, like the truth typically is. One finding that sticks out is that in long-term interventions, there is very little disease incidence before week five, so there is little overall benefit from starting social distancing policies too early. The authors estimate that a few weeks delay in implementing a long-term intervention may result in a higher peak prevalence, but a considerably shorter duration of the epidemic.

What about short-term (12-week) interventions, such as those recommended by the current US pandemic plan? In this scenario, strategies that might contain an epidemic size below a certain level would not be the same ones that could limit peak prevalence. In these scenarios there would be a second peak after the intervention is lifted and they may even result in almost no change in overall epidemic size. For these "short" duration interventions there are no easy answers. For example, if the social distancing intervention is 33% effective in reducing transmission and is started at week 5, it might minimize peak prevalence. However, the same intervention with 22% effectiveness and similar timing would be expected to minimize the epidemic size.

The authors describe and discuss various other scenarios and provide a multitude of estimates for what the effects might be.  However, I think their key contribution is to force us to confront very important policy questions head on.  We need to have discussions about what our policy objectives should be in a pandemic.  Should we aim to limit the total number of cases or should we care about the peak size of the pandemic when our hospital and other public health services are stretched to the limit?  Maybe we should just want the epidemic to end as quickly as possible, so that society can get back to the new normal? We should probably have these discussions before the next pandemic, so we can design the optimal policy to achieve our goal(s). 

Hollingsworth et al. PLoS Computational Biology February 2011