The North Atlantic Flyway Revisited

Global Flyways – Credit FAO

 

# 9372

 

It is pretty clear from the way the HPAI H5N1 virus spread out of South East Asia to Europe and the Middle East in the middle of the last decade, that migratory birds can play a major role in its dissemination.  Many species are able to carry avian influenza viruses without ill effect, and when they encounter other birds, can `share’ their viral cargo along their migratory flyway.

 

Where flyways overlap, there is a greater chance of spreading a virus from one region to another. And as you can see by the map above, they overlap a lot.

 

During the peak of H5N1’s great expansion during the middle of the last decade, the number of countries affected by that emerging avian virus jumped from 16 to over 60 in less than 24 months (see OIE 63 Countries Report H5N1 Avian Influenza in Domestic Poultry/Wildlife 2003-2010).

 

And for awhile, there were concerns that the virus would eventually wing its way to North America – with the most likely route viewed as coming from Siberian birds crossing the Bering Straits into Alaska and Canada.  When that didn’t happen, and when the H5N1 threat in Europe retreated, many concluded we were `protected’ from such viral intrusions by both distance and oceans.

 

Last March, when our infectious disease attentions were pretty much evenly divided between MERS in the Middle East and the winding down of the second wave of H7N9 in China, I blogged on a study that appeared in PLoS One that looked at the potential for European Avian flu viruses to hop the Atlantic and end up in North America (see Thursday, March 20, 2014 PLoS One: North Atlantic Flyways Provide Opportunities For Spread Of Avian Influenza Viruses).

 

In view of the recent emergence of a new, highly pathogenic avian influenza virus (H5N8) now turning up in Europe – and the fact this study probably didn’t get the attention it deserved last spring -  it seems appropriate to revisit that study (funded by the USGS and NIAID) that confirms at least the potential of avian flu viruses to cross the Atlantic to reach North America.  

 

First the press release from the USGS, then a link to the study and some excerpts. I’ll have a bit more after.

North Atlantic May Be a New Route for Spread of Avian Flu to North America

Released: 3/19/2014 5:10:00 PM

The North Atlantic region is a newly discovered important pathway for avian influenza to move between Europe and North America, according to a U.S. Geological Survey report published today.

USGS scientists and Icelandic partners found avian flu viruses from North America and Europe in migratory birds in Iceland, demonstrating that the North Atlantic is as significant as the North Pacific in being a melting pot for birds and avian flu. A great number of wild birds from Europe and North America congregate and mix in Iceland's wetlands during migration, where infected birds could transmit avian flu viruses to healthy birds from either location.

By crossing the Atlantic Ocean this way, avian flu viruses from Europe could eventually be transported to the United States. This commingling could also lead to the evolution of new influenza viruses. These findings are critical for proper surveillance and monitoring of flu viruses, including the H5N1 avian influenza that can infect humans.

"None of the avian flu viruses found in our study are considered harmful to humans," said Robert Dusek, USGS scientist and lead author of the study. "However, the results suggest that Iceland is an important location for the study of avian flu and is worthy of special attention and monitoring."

The study also highlighted the new finding that gulls play an important role in moving avian flu viruses across the North Atlantic.

During the spring and autumn of 2010 and autumn of 2011, the USGS researchers and Icelandic partners collected avian influenza viruses from gulls and waterfowl in southwest and west Iceland (see map). By studying the virus’ genomes — an organism’s hereditary information — the researchers found that some viruses came from Eurasia and some originated in North America. They also found viruses with mixed American-Eurasian lineages.

"For the first time, avian influenza viruses from both Eurasia and North America were documented at the same location and time," said Jeffrey Hall, USGS co-author and principal investigator on this study. "Viruses are continually evolving, and this mixing of viral strains sets the stage for new types of avian flu to develop."

(Continue . . . )

Excerpts from PLoS One:

North Atlantic Migratory Bird Flyways Provide Routes for Intercontinental Movement of Avian Influenza Viruses

Robert J. Dusek mail, Gunnar T. Hallgrimsson, Hon S. Ip, Jón E. Jónsson, Srinand Sreevatsan, Sean W. Nashold, Joshua L. TeSlaa, Shinichiro Enomoto, Rebecca A. Halpin, Xudong Lin, Nadia Fedorova, Timothy B. Stockwell, Vivien G. Dugan,  [ ... ], Jeffrey S. Hall

Abstract

Avian influenza virus (AIV) in wild birds has been of increasing interest over the last decade due to the emergence of AIVs that cause significant disease and mortality in both poultry and humans. While research clearly demonstrates that AIVs can move across the Pacific or Atlantic Ocean, there has been no data to support the mechanism of how this occurs. In spring and autumn of 2010 and autumn of 2011 we obtained cloacal swab samples from 1078 waterfowl, gulls, and shorebirds of various species in southwest and west Iceland and tested them for AIV. From these, we isolated and fully sequenced the genomes of 29 AIVs from wild caught gulls (Charadriiformes) and waterfowl (Anseriformes) in Iceland. We detected viruses that were entirely (8 of 8 genomic segments) of American lineage, viruses that were entirely of Eurasian lineage, and viruses with mixed American-Eurasian lineage. Prior to this work only 2 AIVs had been reported from wild birds in Iceland and only the sequence from one segment was available in GenBank. This is the first report of finding AIVs of entirely American lineage and Eurasian lineage, as well as reassortant viruses, together in the same geographic location. Our study demonstrates the importance of the North Atlantic as a corridor for the movement of AIVs between Europe and North America.

<SNIP>

Our data demonstrate that the North Atlantic serves as a route for intercontinental movement of AIV and it will be important to track the further dissemination of these viruses, in whole, or in part, into the Icelandic avian community and, more significantly, into the avian communities of Europe or North America.

(Continue . . . )

For more on the geographic expansion of bird flu viruses, you may wish to revisit:

 

FAO On The Potential Threat Of HPAI Spread Via Migratory Birds

Bird Flu Spread: The Flyway Or The Highway?

FAO-EMPRES Report On The Emergence And Threat Of H5N6

PLoS One: North Atlantic Flyways Provide Opportunities For Spread Of Avian Influenza Viruses

Global Flyways – Credit FAO 

 

# 8389

 

It is pretty clear from the way the HPAI H5N1 virus spread out of South East Asia to Europe and the Middle East in the middle of the last decade, that migratory birds can play a major role in its dissemination.  These birds can often carry avian influenza viruses without ill effect, and when they encounter other birds, can `share’ their viral cargo along their migratory flyway.

 

Where flyways overlap, there is a greater chance of spreading a virus from one region to another. And as you can see by the map above, they overlap a lot.

 

Japan and Korea – both overwintering sites for migratory birds that summer in Asia and Siberia – have seen the seasonal arrival of H5N1 in years past (see What Goes Around, Comes Around), and this winter Korea has found itself battling a viral  foe: H5N8.  Again, thought to have been introduced by migratory birds from China (see Korea: Migratory Birds Likely Source Of H5N8 Outbreak).

 

While the HPAI viruses originating in Asia have yet to make it to North America via these migratory birds, the concern remains that it could happen.   Accordingly, the Pacific Flyways have been viewed with the most interest, as this would be the most direct route for H5N1, H7N9, or H5N8 to jump to the Americas.   

 

But European birds can carry HPAI viruses as well, and new reassortant viruses can emerge anywhere, not just in Asia (see EID Journal: Predicting Hotspots for Influenza Virus Reassortment). 

Reassortment of two Avian Viruses Producing a Hybrid (Reassortant) Virus 

 

So while less obvious a threat, the North Atlantic Flyways are considered a potential air-bridge for the introduction of new (or components for a reassorted) virus to North America.  Yesterday, the open access journal PLoS One published a study funded by the USGS and NIAID that confirms this potential.  

First the press release from the USGS, then a link to the study and some excerpts. I’ll have a bit more after.

 

North Atlantic May Be a New Route for Spread of Avian Flu to North America

Released: 3/19/2014 5:10:00 PM

The North Atlantic region is a newly discovered important pathway for avian influenza to move between Europe and North America, according to a U.S. Geological Survey report published today.

USGS scientists and Icelandic partners found avian flu viruses from North America and Europe in migratory birds in Iceland, demonstrating that the North Atlantic is as significant as the North Pacific in being a melting pot for birds and avian flu. A great number of wild birds from Europe and North America congregate and mix in Iceland's wetlands during migration, where infected birds could transmit avian flu viruses to healthy birds from either location.

By crossing the Atlantic Ocean this way, avian flu viruses from Europe could eventually be transported to the United States. This commingling could also lead to the evolution of new influenza viruses. These findings are critical for proper surveillance and monitoring of flu viruses, including the H5N1 avian influenza that can infect humans.

"None of the avian flu viruses found in our study are considered harmful to humans," said Robert Dusek, USGS scientist and lead author of the study. "However, the results suggest that Iceland is an important location for the study of avian flu and is worthy of special attention and monitoring."

The study also highlighted the new finding that gulls play an important role in moving avian flu viruses across the North Atlantic.

During the spring and autumn of 2010 and autumn of 2011, the USGS researchers and Icelandic partners collected avian influenza viruses from gulls and waterfowl in southwest and west Iceland (see map). By studying the virus’ genomes — an organism’s hereditary information — the researchers found that some viruses came from Eurasia and some originated in North America. They also found viruses with mixed American-Eurasian lineages.

"For the first time, avian influenza viruses from both Eurasia and North America were documented at the same location and time," said Jeffrey Hall, USGS co-author and principal investigator on this study. "Viruses are continually evolving, and this mixing of viral strains sets the stage for new types of avian flu to develop."

(Continue . . . )

 

Excerpts from PLoS One:

 

North Atlantic Migratory Bird Flyways Provide Routes for Intercontinental Movement of Avian Influenza Viruses

Robert J. Dusek mail, Gunnar T. Hallgrimsson, Hon S. Ip, Jón E. Jónsson, Srinand Sreevatsan, Sean W. Nashold, Joshua L. TeSlaa, Shinichiro Enomoto, Rebecca A. Halpin, Xudong Lin, Nadia Fedorova, Timothy B. Stockwell, Vivien G. Dugan,  [ ... ], Jeffrey S. Hall

Abstract

Avian influenza virus (AIV) in wild birds has been of increasing interest over the last decade due to the emergence of AIVs that cause significant disease and mortality in both poultry and humans. While research clearly demonstrates that AIVs can move across the Pacific or Atlantic Ocean, there has been no data to support the mechanism of how this occurs. In spring and autumn of 2010 and autumn of 2011 we obtained cloacal swab samples from 1078 waterfowl, gulls, and shorebirds of various species in southwest and west Iceland and tested them for AIV. From these, we isolated and fully sequenced the genomes of 29 AIVs from wild caught gulls (Charadriiformes) and waterfowl (Anseriformes) in Iceland. We detected viruses that were entirely (8 of 8 genomic segments) of American lineage, viruses that were entirely of Eurasian lineage, and viruses with mixed American-Eurasian lineage. Prior to this work only 2 AIVs had been reported from wild birds in Iceland and only the sequence from one segment was available in GenBank. This is the first report of finding AIVs of entirely American lineage and Eurasian lineage, as well as reassortant viruses, together in the same geographic location. Our study demonstrates the importance of the North Atlantic as a corridor for the movement of AIVs between Europe and North America.

Discussion

In this study we isolated 11 unique AIVs in gulls and waterfowl from Iceland that contained unexpectedly high viral genetic diversity. Most significantly, we obtained viruses that were completely (all 8 segments) of Eurasian lineage or American lineage as well as reassortant American and Eurasian lineage viruses. Previous to this study there have been no reports of complete American or Eurasian lineage viruses in the same geographic location [12], [25].

When Eurasian AIV segments have been detected in the Americas, or American AIV segments in Eurasia, it has generally been only 1 or 2 segments per virus [12], [18], [19], [25]. However, 2 recent studies in North America have found viruses with near complete (7 of 8 segments) Eurasian lineage genomes [16], [19]. Both of these studies were conducted in regions where predominately Eurasian flyways overlap into North America (the East Asian Flyway and the East Atlantic Flyway). Iceland is within the East Atlantic Flyway (Figure 2); this flyway extends into North America (Greenland and eastern Canada) and tens of thousands of migratory birds move from North America into Europe along this route on their way to and from breeding and non-breeding grounds [31], [32].

Our data demonstrate that the North Atlantic serves as a route for intercontinental movement of AIV and it will be important to track the further dissemination of these viruses, in whole, or in part, into the Icelandic avian community and, more significantly, into the avian communities of Europe or North America.

(Continue . . . )

 

While we’ve seen a lot of evidence to support the idea that migratory birds play an important role in the spread of avian viruses, not everyone agrees. 

 

Last month in Korea: H5N8 Spreads, Debate Over Source Intensifies, the Scientific Task Force on Avian Influenza and Wild Birds argued against migratory birds being the source of that virus in Korea.  Similarly, in years past we’ve seen other experts decry the blaming of migratory birds in the spread of H5N1 (see India: The Role Of Migratory Birds In Spreading Bird Flu & Another Migratory Bird Study).

 

Despite these somewhat partisan assertions, there have been plenty of other studies that strongly associate migratory birds with the spread of avian flu viruses. A few include:

 

Korea: Migratory Birds Behind Spread Of H5N1

EID Journal: H5N1 Branching Out

Japan: Hooded Crane Positive For H5N1

Not One Of The Usual Suspects

FAO: On The Trail Of Avian Influenza

 

Whether this North Atlantic flyway will provide a route for new HPAIs to show up in the Americas is unknown, but it does illustrate the folly in becoming too focused on one area of the world, when others are perfectly capable of serving up a viral surprise.

PLoS One: Biodiversity of Influenza A in Wild Birds

Photo Source - FAO

 

# 8361

 

Thanks to the work of virologists like Dr. Robert Webster, we’ve known for decades that wild birds (most notably waterfowl) are the natural hosts of influenza A viruses - and that if you trace their lineage back far enough - all human, swine, and equine influenza A viruses are likely of avian origin.

 

Influenza A subtypes are categorized by two proteins they carry on their surface; their HA (hemagglutinin) and NA (neuraminidase).  Each of these subtypes can have many `clades’ (branches on the family tree), and within each clade there can be many minor variants.

 

If you count the recently discovered `bat flu’ viruses, there are now 18 known HA proteins, and 11 known NAs  (see PLoS Pathogens: New World Bats Harbor Diverse Flu Strains) – but to date, among birds - only HA types 1-16 and NA types 1-9 have been detected – making a total of 144 different avian subtypes possible.

Not all of these possible subtypes have actually been detected in the wild, but then, influenza is a constantly moving target, and subtypes may appear, and then disappear, over time. 

Our understanding of the prevalence, and biodiversity, of avian influenza viruses in birds has grown in recent years, but the sudden emergence of H7N9 in China a year ago, and the surprise eruption of H5N8 in Korean poultry in January, show that there is still much more to learn.

 

This week, an international group of researchers (hailing from the United States, Canada, Sweden & Australia) published an open access paper in PloS One providing perhaps the most detailed review of the biodiversity of influenza A viruses in wild birds to date.  Among their findings:

 

• Among wild birds, 112 subtypes were identified
• 49 (44%) of the 112 subtypes were also found in domestic birds
• Five subtypes were found in domestic birds, but not in the wild
• Globally, 79% (89/112) of wild bird subtypes were found in Mallards
• The top five wild host species for subtype richness (n) were: Mallard - Anas platyrhynchos (89), Ruddy Turnstone - Arenaria interpres (45), Northern Pintail - Anas acuta (43), Northern Shoveler - Anas clypeata (35), and Blue-winged Teal - Anas discors (33).
• 61% of all subtypes were found in > 1 order of birds, and 66% were detected on > 1 continent

 

Below you’ll find a link, and some excerpts, but by all means you’ll want to read the paper in its entirety.

 

Research Article

Sampling Strategies and Biodiversity of Influenza A Subtypes in Wild Birds

Sarah H. Olson, Jane Parmley, Catherine Soos, Martin Gilbert, Neus Latorre-Margalef, Jeffrey S. Hall, Phillip M. Hansbro, Frederick Leighton, Vincent Munster, Damien Joly

Published: March 05, 2014   DOI: 10.1371/journal.pone.0090826

Abstract

Wild aquatic birds are recognized as the natural reservoir of avian influenza A viruses (AIV), but across high and low pathogenic AIV strains, scientists have yet to rigorously identify most competent hosts for the various subtypes. We examined 11,870 GenBank records to provide a baseline inventory and insight into patterns of global AIV subtype diversity and richness. Further, we conducted an extensive literature review and communicated directly with scientists to accumulate data from 50 non-overlapping studies and over 250,000 birds to assess the status of historic sampling effort. We then built virus subtype sample-based accumulation curves to better estimate sample size targets that capture a specific percentage of virus subtype richness at seven sampling locations. Our study identifies a sampling methodology that will detect an estimated 75% of circulating virus subtypes from a targeted bird population and outlines future surveillance and research priorities that are needed to explore the influence of host and virus biodiversity on emergence and transmission.

Figure 1 - Subtypes found in Anseriformes (green), Charadriiformes (purple), Procellariiformes (blue), more than one order (gray), and occurrence in domestic birds (***)

While this study is not without its limitations (including geographic sampling bias, and a tendency for GenBank submissions to focus more on HPAI viruses), this study provides a number of interesting findings.  From the author’s Observations and findings.

 

We found that some subtypes appear to be limited to certain bird orders or flyways, which suggest the presence of a limited degree of subtype specificity to host or geographic region, but may also reflect sampling biases within GenBank. Fifty-six percent (5/9) of H9 subtypes were only found in Charadriiformes, of which four, H9N4, H9N5, H9N6, and H9N7, were only detected in Delaware Bay shorebirds. Fifty percent (8/16) of N3 subtypes were only found in Anseriformes. Australia alone had 75% (3/4) of known H15 subtypes; the other H15 subtypes have not been observed to date. We also identified H8, H13, and H15 subtypes where four or more combinations with NA subtypes had not been observed. Noticeably, N7 lacked eight combinations with HA subtypes.

 

And finally, some excerpts from a press release from the Wildlife Conservation Society, which participated in this research.

 

Birds of all feathers and global flu diversity

PUBLIC RELEASE DATE:

6-Mar-2014

A group of international scientists have completed the first global inventory of flu strains in birds by reviewing more than 50 published studies and genetic data, providing new insight into the drivers of viral diversity and the emergence of disease that can ultimately impact human health and livelihoods.

The research, published in the journal PLOS ONE and performed as part of the USAID PREDICT project, identified over 116 avian flu strains in wild birds. This is roughly twice the number that were found in domestic birds, and more than ten times the number found in humans. Additionally, an analysis of studies that sampled more than 5,000 birds suggested some regions may have more viral diversity than others.

<SNIP>

"This snapshot of the world of flu virus diversity in birds is the outcome of many years of ecology and evolution, as viewed through the lens of surveillance methods utilized by scientists from around the world," said study lead and Wildlife Conservation Society (WCS) Associate Director of Wildlife Epidemiology, Dr. Sarah Olson.

 

Understanding the natural diversity of viruses is critically important to identifying health risks. But authorities face a challenge, both in focusing efforts in the right places, and adequately financing surveillance to describe global flu diversity. To address this, the authors introduced a new method, which borrows on approaches used by ecologists, to estimate the diversity of flu viruses in a particular location. With this approach, health authorities can design surveillance programs to detect a given percentage of flu virus diversity.

 

The scientists also looked at patterns of flu diversity in different bird hosts. Mallards carry the highest number of strains at 89 and ruddy turnstones were second with 45. The more a strain was shared across wild bird types, the more likely it was to be found in domestic birds, a risk factor for spillover events. They also noted that some strains could be specific to certain bird types. For example, gulls and shorebirds (Charadriiformes) carried ten strains that have not been identified in any other bird order.

 

According to Dr. Olson, "This inventory isn't about blaming wild birds, but it allows us to map what we know, and informs our understanding of what drives viral diversity and the emergence of rare viral strains that can infect people. Given that flu viruses can jump from domestic poultry to people, ongoing efforts at improving biosecurity at poultry farms and markets remain key to outbreak prevention."

PLoS One: Limited Effectiveness Of Flu Vaccines In The Elderly

 

# 7869

 

 

A topic we’ve covered often in the past has been the limited effectiveness of influenza vaccines among the elderly (>=65) (see Flu Shots And The Elderly, NFID: The Challenges Of Influenza In Older Adults, BMC Infectious Diseases: Waning Flu Vaccine Protection In the Elderly)  or those with compromised or suppressed immune systems.  Those populations most endangered by influenza are, unfortunately, the least likely to be protected by the flu vaccine.

That isn’t to say the flu vaccine is worthless, or not worth bothering with. 

I get the flu shot every year, and I encouraged my Dad to get one until he died at the age of 87, even knowing its limitations.  When dealing with a potentially life threatening illness . . . some protection beats no protection, any day of the week.  

 

But, like seat belts, flu shots can only offer so much protection.  For healthy adults under the age of 65, flu shots are generally described as being moderately effective. In October of 2011, in CIDRAP: A Comprehensive Flu Vaccine Effectiveness Meta-Analysis, we saw a major review indicating the TIV (Trivalent Influenza Vaccine) - during 8 of 12 flu seasons (67%) – produced a combined efficacy of only 59% among healthy adults (aged 18–65 years).

 

They found the protective effects of the flu vaccine could vary considerably from one season to the next, as well as among different age groups.

 

Also in 2011,  NFID - the National Foundation for Infectious Diseases - convened a group of experts to address the issues of influenza and the elderly. From that panel a 5-page brief has emerged, called: Understanding the Challenges and Opportunities in Protecting Older Adults from Influenza.

 

 

 

Yesterday the open access journal PLoS One published a new retrospective study conducted in Ontario, Canada that attempts to quantify the level of protection those over the age of 65 received from seasonal influenza vaccination.  Not surprisingly, they found that the VE (vaccine effectiveness) to be considerably lower than what has been seen with younger adults.

 

Research Article

Effectiveness of Inactivated Influenza Vaccines in Preventing Influenza-Associated Deaths and Hospitalizations among Ontario Residents Aged ≥65 Years: Estimates with Generalized Linear Models Accounting for Healthy Vaccinee Effects

Benjamin J. Ridenhour mail,Michael A. Campitelli, Jeffrey C. Kwong, Laura C. Rosella, Ben G. Armstrong, Punam Mangtani, Andrew J. Calzavara, David K. Shay

Abstract

Background

Estimates of the effectiveness of influenza vaccines in older adults may be biased because of difficulties identifying and adjusting for confounders of the vaccine-outcome association. We estimated vaccine effectiveness for prevention of serious influenza complications among older persons by using methods to account for underlying differences in risk for these complications.

Methods

We conducted a retrospective cohort study among Ontario residents aged ≥65 years from September 1993 through September 2008. We linked weekly vaccination, hospitalization, and death records for 1.4 million community-dwelling persons aged ≥65 years. Vaccine effectiveness was estimated by comparing ratios of outcome rates during weeks of high versus low influenza activity (defined by viral surveillance data) among vaccinated and unvaccinated subjects by using log-linear regression models that accounted for temperature and time trends with natural spline functions. Effectiveness was estimated for three influenza-associated outcomes: all-cause deaths, deaths occurring within 30 days of pneumonia/influenza hospitalizations, and pneumonia/influenza hospitalizations.

Results

During weeks when 5% of respiratory specimens tested positive for influenza A, vaccine effectiveness among persons aged ≥65 years was 22% (95% confidence interval [CI], −6%–42%) for all influenza-associated deaths, 25% (95% CI, 13%–37%) for deaths occurring within 30 days after an influenza-associated pneumonia/influenza hospitalization, and 19% (95% CI, 4%–31%) for influenza-associated pneumonia/influenza hospitalizations. Because small proportions of deaths, deaths after pneumonia/influenza hospitalizations, and pneumonia/influenza hospitalizations were associated with influenza virus circulation, we estimated that vaccination prevented 1.6%, 4.8%, and 4.1% of these outcomes, respectively.

Conclusions

By using confounding-reducing techniques with 15 years of provincial-level data including vaccination and health outcomes, we estimated that influenza vaccination prevented ~4% of influenza-associated hospitalizations and deaths occurring after hospitalizations among older adults in Ontario.

(Continue . . .)

 

Those whose eyes don’t bleed when reading about complex statistical methods will want to peruse the entire study. In an act of self preservation, I admit I only skimmed those areas. The bottom line is that by using statistical analyses far above my pay grade, these authors have determined that the seasonal flu vaccine had about a 22% VE rating for those over the age of 65.

 

In an accompanying press release from the University of Notre Dame, we get the following summation.

 

Notre Dame researchers look at benefits of flu vaccines in the elderly

Sarah Craig

October 16, 2013

(EXCERPT)

In their central findings of the research, the authors said, “By combining health data with climate data and developing novel statistical analyses, we found that vaccination was 19 percent effective at preventing pneumonia- or influenza-related hospitalizations and 25 percent effective at preventing death occurring subsequent to a pneumonia- or influenza-related hospitalization.”

The results indicate that, over a long time period, the influenza vaccine has performed worse than expected in elderly individuals, thus proving the need for improvements in influenza vaccine development.

(Continue . . . )

 

If that last observation sounds familiar, it is likely because it echo’s the sentiments of last year’s major report (see CIDRAP: The Need For `Game Changing’ Flu Vaccines).

 

The Compelling Need for Game-Changing Influenza Vaccines

An Analysis of the Influenza Vaccine Enterprise and Recommendations for the Future

Michael T. Osterholm, PhD, MPH, Nicholas S. Kelley, PhD, Jill M. Manske, PhD, MPH, Katie S. Ballering, PhD, Tabitha R. Leighton, MPH, Kristine A. Moore, MD, MPH

 

For those not ready to commit to reading a 160-page report, there is a 12-page Executive summary available.

 

While today’s study provides a disappointing result, and highlights the need for developing better influenza vaccines, the bottom line is that the current vaccine was found to be  `25 percent effective at preventing death occurring subsequent to a pneumonia- or influenza-related hospitalization’. 

 

Given the toll that influenza takes on the elderly, that 25% survival advantage has to be viewed as being better than no advantage at all.

PLoS One: Epidemiological & Clinical Description Of 6 H7N9 Cases - Shanghai

 

# 7961

 

With the specter of the possible return of the H7N9 virus looming large this fall and winter, we’ve a study today that looks at 6 early cases hospitalized between February and March of this year at Fifth People’s Hospital of Shanghai, providing us with both epidemiological and clinical details. 

 

Today’s report, when coupled with others we’ve examined in recent months (see Study: Hematological & Biochemical Abnormalities In H7N9 Patients & EID Journal: Clinical Course & Treatment Of Four Early H7N9 Cases) paint a picture of an emerging virus that may be difficult to catch, but once acquired, can produce profound (often fatal) illness in humans.

 

A link to the open-access study and some extended excerpts follow, although I would recommend reading it in its entirety.  When you return, I’ll have a bit more.

 

A Detailed Epidemiological and Clinical Description of 6 Human Cases of Avian-Origin Influenza A (H7N9) Virus Infection in Shanghai

Jindong Shi equal contributor, Juan Xie equal contributor, Zebao He equal contributor, Yunwen Hu, Yanchao He, Qihui Huang, Beizheng Leng, Wei He, Ying Sheng, Fangming Li, Yuanlin Song, Chunxue Bai, Yong Gu mail, Zhijun Jie mail

hi J, Xie J, He Z, Hu Y, He Y, et al. (2013) A Detailed Epidemiological and Clinical Description of 6 Human Cases of Avian-Origin Influenza A (H7N9) Virus Infection in Shanghai. PLoS ONE 8(10): e77651. doi:10.1371/journal.pone.0077651

Abstract

Background

The world’s first reported patient infected with avian influenza H7N9 was treated at the Fifth People’s Hospital of Shanghai. Shortly thereafter, several other cases emerged in the local area. Here, we describe the detailed epidemiological and clinical data of 6 cases of avian influenza H7N9.

Methods and Findings

We analyzed the epidemiologic and clinical data from clustered patients infected with H7N9 in the Minhang District of Shanghai during a 2-week period. Of the 6 patients, 2 were from a single family. In addition, 3 patients had a history of contact with poultry; however, all 6 patients lived in the proximity of 2 food markets where the H7N9 virus was detected in chickens and pigeons. The main symptoms were fever, cough, and hemoptysis. At onset, a decreased lymphocyte count and elevated creatine kinase, lactate dehydrogenase, procalcitonin, and C-reactive protein levels were observed. As the disease progressed, most patients developed dyspnea and hypoxemia. Imaging studies revealed lung consolidation and multiple ground-glass opacities in the early stage, rapidly extending bilaterally. All patients were treated with oseltamivir tablets beginning on days 3–8 after onset. The main complications were as follows: acute respiratory distress syndrome (ARDS; 83.3%), secondary bacterial infection (66.7%), pleural effusion (50%), left ventricular failure (33.3%), neuropsychiatric symptoms (33.3%), and rhabdomyolysis (16.7%). Of the 6 patients, 4 died of ARDS, with 2 patients recovering from the infection.

Conclusions

An outbreak of H7N9 infection occurred in the Minhang District of Shanghai that easily progressed to acute respiratory distress syndrome. Two cases showed family aggregation, which led us to identify the H7N9 virus and indicated that human transmission may be involved in the spread of this infection.

<SNIP>

Demographic characteristics

All 6 patents were male, Han nationality, aged from 27 to 87 years old, 4 were retired individuals, 1 in-service worker, and 1 pork peddler. Four patients had history of tobacco, 1 had history of drinking, and 5 had at least 1 of the following underlying diseases: chronic obstructive pulmonary diseases, hypertension, dextrocardia, diabetes, coronary heart disease, hepatitis B, and/or gastric ulcer. (Table 1)

History of exposure to birds and residence state

Among the 6 patients, 5 were residents of the Minhang District of Shanghai and had not left Shanghai prior to the onset of illness. One patient, who was a pork seller at a market in the Minhang District, was originally from the Jingsu province and had been a resident of Minhang District for 9 months at the time of disease onset. All 6 patients lived in the proximity of 2 food markets where poultry were traded and H7N9 virus carrier birds had been discovered. Trading of poultry was banned in the markets on April 4. Two patients had a history of exposure to live birds and 1 had a history of suspected exposure.

The time course of case identification, treatment, and diagnosis

Disease onset in the 6 cases occurred within a 2-week period from 19 February and 5 March 2013. The time range from onset to hospitalization was 3–7 days (mean, 4.6 days). Cases 3 and 4 were admitted to the intensive care unit (ICU) because of disease progression on the first and second day of hospitalization, respectively. The length of hospital stay was 3–15 days (mean, 8 days). H7N9 was confirmed by RT-PCR and virus isolation in 4 cases and by elevated (4× that of normal) levels of specific antibodies to H7N9 in the acute phase and recovery stage in 2 cases. Case 2 was the son of case 1, whose other son (age, 55 years) developed severe pneumonia on February 11 and died on February 28. However, the H7N9 virus was not detected in respiratory specimens from the deceased son by RT-PCR or viral isolation. (Table 2)

<SNIP>

Treatment, complications, and outcome

Oseltamivir (tablet, 75 mg bid) therapy was initiated 3–8 days after disease onset in all patients. One recovering patient was treated with a combination of oseltamivir (tablet, 75 mg bid) and amantadine (tablet, 0.2, bid). Broad-spectrum antibiotics against Gram-positive and Gram-negative bacteria and atypical pathogens, such as penicillium, carbon alkene, and fluoroquinolone, were administered to all patients. Except for the recovering patient, all patients were treated with intravenous glucocorticoid as an anti-inflammatory at a dose of 80–240 mg/d. Intravenous immunoglobulin was administered in 4 patients, and thymosin was administered in 2 patients.

In terms of complications, 4 patients developed ARDS between days 3 and 9 (mean, day 6) after disease onset. Three patients had secondary bacterial infections, 3 had pleural effusion, 2 had left heart functional failure, 2 had neuropsychiatric symptoms, and 1 had rhabdomyolysis. Among the 2 recovering patients, 1 patient had no complications, while the other developed secondary bacterial infections. (Table 5).

(Continue . . . )

 

The extraordinary CFR of these first 6 cases (66%) was thankfully halved in the weeks and months that followed, as hospitals and doctors began to better understand what they were dealing with.  The actual identification of the H7N9 virus came several weeks after these six cases were hospitalized and treated.

 

Unlike what we’ve seen with the H5N1 avian virus – which has a history of infecting younger, generally healthier people –hospitalized H7N9 cases have tended to be older, and often suffering from pre-existing medical conditions.  H7N9 infections – for reasons not yet understood – have also been skewed heavily towards males (71% of cases).

 

With only 137 cases reported, and literally thousands of their close contacts monitored for illness with no additional illnesses reported, this virus doesn’t appear to have acquired the ability to transmit efficiently between humans.  Unknown, of course, is whether some of these close contacts may have experienced asymptomatic or subclinical infections.

 

Some researchers have estimated that the true number of cases in China last spring really ran into the thousands (see Lancet: Clinical Severity Of Human H7N9 Infection).  Their estimate?  Between 1500 and 27,000 symptomatic infections.

 

So we really don’t know just how big of the tip of this iceberg these 137 cases really represents. 

 

Of additional concern, patient reports and laboratory testing have revealed this virus is unusually well-adapted to mammalian physiology (see mBio: H7N9 Naturally Adapted For Efficient Growth in Human Lung Tissue), and we’ve seen some early signs of spontaneous antiviral resistance in patients (see mBio: Antiviral Resistance In H7N9).

 

Returning again to the PLoS One study, the authors conclude by writing:

 

In conclusion, the first ever patient infected with H7N9 was treated at the Fifth People’s Hospital of Shanghai in February 2013. Within a 2-week period, several other cases of H7N9 infection emerged around 2 markets near the hospital. Fever, cough, sputum with blood, low lymphocyte counts, elevated CK and LDH levels, and pulmonary exudative lesions are significant characteristics of H7N9 infection, which easily progresses to ARDS. Among the cases, there was family clustering, which led to a high suspicion of contagious respiratory virus infection. In the early stage, human infection with H7N9 can be diagnosed by RT-PCR and viral isolation from respiratory specimens. Smoking, drinking, underlying diseases, dyspnea, low platelet counts, elevated CK levels, hypoxemia, and complications may be related to poor prognosis. However, diagnosis and treatment may be delayed because of the limited experience with this infection and small number of cases, which were among the first cases of H7N9 infection to be identified. Future studies are needed to elucidate the pathogenicity, transmissibility, and clinical features of H7N9 infection. In addition, techniques for early diagnosis to enable early administration of antiviral therapy and determination of the the factors affecting prognosis require further investigation.

PLoS One: Selective Vaccination Against An Emerging Influenza Pandemic

 

Photo Credit PHIL

 

# 7891

 

 

In the face of any pandemic threat, the primary focus of public health officials will be to reduce the attack rate (AR); the number of people who become infected. Unless we are lucky enough to have a large quantity of experimental vaccine already stockpiled, these early efforts will revolve around NPIs, or non pharmaceutical interventions (i.e. Hand washing, social distancing, school closures, etc.).

 

But eventually a vaccine will probably become available, albeit first in limited quantities,  and decisions will have to be made on how best to deploy it.   To whom do we give priority?  

 

The elderly, who are historically most at risk from influenza?

Children or pregnant women who often suffer disproportionately during a pandemic?

Doctors, Nurses, and emergency responders who are badly needed, and most often exposed?

Essential workers or students?

 

As an example, during the summer of 2008 the HHS released their model of a pandemic vaccine allocation plan based on `the most up-to-date scientific information available and directly considers the values of our society and the ethical issues involved in planning a phased approach to pandemic vaccination.’  NOTE: The link to this plan is no longer operative and so it may no longer be part of the HHS’s pandemic playbook .

Their stated goals at that time were:

• Protect persons critical to the pandemic response and who provide care for persons with pandemic illness
• Protect persons who provide essential community services
• Protect persons who are at high risk of infection because of their occupation and
• Protect children

 

Of course, much will probably depend upon the demographics of the pandemic.   If – as we saw in 2009 – it preferentially targets younger people (or any other  specific demographic group), then adjustments would likely be made.

 

While the tier system above was based on `practical’ considerations, if the goal is to reduce the attack rate, this sort of prioritization system might not be the best solution.  

 

Which brings us to a study, just published in PLoS One, conducted by researchers at Japan’s Institute of Statistical Mathematics, that attempts to model different vaccine prioritization schemes in order to determine which allocation system reduces the spread of a pandemic the most.

 

It should be noted that this model is based on the demographics, population movements, and geography of a simplified subset of suburban Tokyo, and the results are not necessarily applicable to other communities or settings.  

Also, the assumptions made on the amount and timing of a vaccine, its effectiveness, and attack rate of the virus are arbitrarily set (albeit with various permutations considered) – and are not necessarily what would be encountered in a genuine pandemic outbreak.

Still, this study does provide some intriguing insights into how a pandemic virus is likely spread in a highly populated area, and provides a strategy to limit its impact.

 

 

Research Article

Enhancement of Collective Immunity in Tokyo Metropolitan Area by Selective Vaccination against an Emerging Influenza Pandemic

Masaya M. Saito mail, Seiya Imoto, Rui Yamaguchi, Masaharu Tsubokura, Masahiro Kami, Haruka Nakada, Hiroki Sato, Satoru Miyano, Tomoyuki Higuchi

Abstract

Vaccination is a preventive measure against influenza that does not require placing restrictions on social activities. However, since the stockpile of vaccine that can be prepared before the arrival of an emerging pandemic strain is generally quite limited, one has to select priority target groups to which the first stockpile is distributed. In this paper, we study a simulation-based priority target selection method with the goal of enhancing the collective immunity of the whole population. To model the region in which the disease spreads, we consider an urban area composed of suburbs and central areas connected by a single commuter train line. Human activity is modelled following an agent-based approach. The degree to which collective immunity is enhanced is judged by the attack rate in unvaccinated people.

The simulation results show that if students and office workers are given exclusive priority in the first three months, the attack rate can be reduced from 30% in the baseline case down to 1–2%. In contrast, random vaccination only slightly reduces the attack rate. It should be noted that giving preference to active social groups does not mean sacrificing those at high risk, which corresponds to the elderly in our simulation model. Compared with the random administration of vaccine to all social groups, this design successfully reduces the attack rate across all age groups.

 

 

Students and office workers are often the most mobile and interactive members of a society, and therefore have greater opportunities to contract and spread a virus. Once infected, they can bring the virus home, spreading it to other vulnerable cohorts. So in many ways, I can see how this analysis makes sense.

 

For those interested in methods and materials, and a lot of statistical analysis, the entire research article is available online (open access).

 

The authors summarize their findings in the discussion section:

We have showed that the AR can be reduced to or less if students and employees are intensively vaccinated in the first 90 days. This is the result of an intervention program that relies solely on vaccinations, and the AR can be further reduced by individual protection efforts (e.g., wearing masks and avoiding crowded places). If the encountered virus is not highly pathogenic, this value is acceptable. In this case, the goal of intervention is to avoid an excess of patients going to medical practitioners. However, early extinction of transmission chains is required in highly pathogenic cases, and vaccination alone is not sufficient. To achieve early extinction by using only the collective immunity induced by vaccinations, administration of the vaccine would need to be carried out at least three times as fast as the typical speed.

 

The rub to this (and other) pandemic vaccination models is the probable lack of any vaccine during the opening months of a novel pandemic, and the limited supply of vaccine for months after that.

 

As George E. P. Box, Professor Emeritus of Statistics at the University of Wisconsin, famously declared.

 

“All models are wrong, but some models are useful.”

 

So hopefully, even if this model’s assumptions turn out to be wrong, this study is useful and will provide some scientific rationale for vaccine distribution decisions, once a vaccine does become available.

PLoS One: Seroprevalence Of H5N1 Among Bangladeshi Poultry Workers

Photo Credit – CDC PHIL

 

# 7782

 

 

One of the more contentious topics among H5N1 researchers has been the argument over the `real’ CFR (Case Fatality Ratio) of the H5N1 virus in humans.

 

The `official’ number – a fatality rate of nearly 60% – is derived from the total known human infections by the virus (637 as of Aug 31st, 2013), and the total number of fatalities within that group (378)

 

Critics point out that only the sickest of the sick would end up in a testing environment, and that many mild cases would recover and never be counted. The numbers, they maintain, are badly skewed.

 

While I think most researchers would agree that the 60% CFR number is likely misleading, it has been difficult to put a `good’ number on the mortality rate of H5N1. The best way to get an idea of the uncounted number of people infected by a virus in a population is to conduct regional seroprevalence studies. You essentially check antibody levels against a specific virus in a representative group of the population.

 

Unfortunately, you don’t end up with a clear cut Infected/Not Infected reading from these tests. You get an antibody titer level, and that requires a subjective decision as to what level constitutes proof of a `previous infection’.

 

Set the bar too high, and you rule out possible cases whose antibodies have declined over time (or who were exposed to an antigenically different H5N1 strain).

Make it too low, and you may count people who were exposed to a non-H5 virus or who received such a low viral load as to not develop illness or immunity.

 

Over the years we’ve seen a number of seroprevalence studies on the H5N1 virus, and the results (and methods) have varied considerably.

 

In February of 2012 (see Science: Peter Palese On The CFR of H5N1), the journal Science published a meta-analysis by Taia T. Wang,  Michael K. Parides &  Peter Palese, that argued that we are likely missing a great many H5N1 infections (perhaps millions), and that the virus is far less lethal than has been assumed in the past.

 

This was published during a time of great debate over the safety and wisdom of conducting H5N1 gain of function (GOF) or Dual Use of Concern (DURC) research (see The Furor Over H5N1 Research Continues).  GOF H5N1 research seeks to create in the laboratory H5N1 strains with increased virulence, transmission, or host range in hopes to better understand how pandemic viruses evolve.

 

These findings were used to argue that the H5N1 virus, and by extension Gain of Function research, were not nearly as dangerous as many feared.

 

That argument was quickly countered by CIDRAP director Michael T. Osterholm and Nick Kelley in an mBio  article, where they found little serological evidence to suggest that we are missing `millions’ of uncounted H5N1 infections (see mBio: Mammalian-Transmissible H5N1 Influenza: Facts and Perspective).

 

A few months later the journal Science published a response to the Palese study – authored by a truly impressive group of virologists and researchers – that also found little evidence to support the notion that `millions’ of mild infections have gone undetected.

 

Comment on “Seroevidence for H5N1 Influenza Infections in Humans: Meta-Analysis”

Maria D. Van Kerkhove, Steven Riley, Marc Lipsitch, Yi Guan, Arnold S. Monto, Robert G. Webster, Maria Zambon, Angus Nicoll, J. S. Malik Peiris, Neil M. Ferguson

Abstract

A better understanding of the severity of H5N1 in humans is needed. Wang et al. (Brevia, 23 March 2012, p. 1463; published online 23 February 2012) over interpret the results of seroprevalence studies and take too little account of underlying uncertainties. Although the true risk of death from H5N1 infection will likely be lower than the 60% of reported laboratory-confirmed cases, there is little evidence of millions of missed infections.

 

 

Their entire rationale may be read here, and it strongly counters the assessment presented by Wang et al. in the original paper.

 

Meanwhile, the controversy over GOF research continues, which we looked at most recently in H7N9: Reigniting The `Gain Of Function’ Research Debate.

 

Today (h/t  @Laurie_Garrett for the link) we’ve a new H5N1 seroprevalence study, this time conducted on poultry workers in Bangladesh who were exposed to infected chickens during laboratory confirmed bird flu outbreaks in 2009.  Given their frequent and close contact to infected birds, they would be expected to have the highest risk of H5N1 infection.

Their findings are summed up in the last line of the abstract: Despite exposure to sick poultry, no farm or market poultry workers were seropositive for HPAI H5N1 virus antibodies (95% confidence interval 0–1%).

 

The entire study, which appears this month in the journal PloS One, may be accessed at the link below:

 

Seroprevalence of Antibodies against Highly Pathogenic Avian Influenza A (H5N1) Virus among Poultry Workers in Bangladesh, 2009

Sharifa Nasreen mail, Salah Uddin Khan, Eduardo Azziz-Baumgartner, Kathy Hancock, Vic Veguilla, David Wang, Mahmudur Rahman, A. S. M. Alamgir, Katharine Sturm-Ramirez, Emily S. Gurley, Stephen P. Luby, Jacqueline M. Katz, Timothy M. Uyeki

Abstract

We conducted a cross-sectional study in 2009 to determine the seroprevalence and risk factors for highly pathogenic avian influenza A (H5N1) [HPAI H5N1] virus antibodies among poultry workers at farms and live bird markets with confirmed/suspected poultry outbreaks during 2009 in Bangladesh. We tested sera by microneutralization assay using A/Bangladesh/207095/2008 (H5N1; clade 2.2.2) virus with confirmation by horse red blood cell hemagglutination inhibition and H5-specific Western blot assays. We enrolled 212 workers from 87 farms and 210 workers from three live bird markets. One hundred and two farm workers (48%) culled poultry. One hundred and ninety-three farm workers (91%) and 178 market workers (85%) reported direct contact with poultry that died during a laboratory confirmed HPAI H5N1 poultry farm outbreak or market poultry die-offs from suspected HPAI H5N1. Despite exposure to sick poultry, no farm or market poultry workers were seropositive for HPAI H5N1 virus antibodies (95% confidence interval 0–1%).

 

 

While none of the poultry workers tested seropositive for the H5N1 virus (using thresholds established by WHO for serological testing), a small number did show mildly elevated titers – well below the threshold for positivity. 

 

The authors explain:

 

It is difficult to interpret these low levels of HPAI H5N1 virus neutralizing antibodies in a cross-sectional study. First, low titers may indicate cross reactive antibodies from a previous influenza A virus infection with a different subtype rather than the presence of HPAI H5N1 virus-specific neutralizing antibodies [11,13]. Single or multiple-clade H5N1 influenza vaccines can generate cross-clade neutralizing antibodies in humans and mice [22,23]. Nevertheless, only HPAI H5N1 clade 2.2.2 viruses were identified among domestic poultry in Bangladesh during 2007–2009 [1]. Second, these low titers could potentially reflect a limited neutralizing antibody response in some individuals with HPAI H5N1 virus infection. One study in Vietnam of persons with serologic evidence of clinically mild or asymptomatic HPAI H5N1 virus infection reported relatively lower neutralizing antibody titers compared with severely ill cases [24]. Third, low titers may reflect past HPAI H5N1 virus infection with declining neutralizing antibody titers over time to when serum was sampled, to levels below our defined cut-off titer defining a seropositive result [24,25].

 

 

Admittedly, there have been other studies conducted in recent years that have come up with higher (although still low) levels of seropositivity for the H5N1 virus.

 

• Last year, in H5N1 Seroprevalence Among Jiangsu Province Poultry Workers, we saw a study that found across three locations tested (Gaochun, Jianhu and Gaoyou counties) the percentage of workers testing positive ranged from zero (Gaochun) to 5.38% (95%CI, 2.19%–10.78%) in Gaoyou.
• In 2011, a study (see Subclinical H5 & H9 Infections In Humans) tested 605 residents in and around Beijing China for antibodies to H5 and H9 avian flu viruses.  Of these, just  5 (less than 1%) had antibodies to H9 avian influenza, and only 1 was positive for antibodies to H5.
• In May of 2009 (see Cambodian Study Finds Rare Asymptomatic H5N1 Infections) we saw a study published in the Journal of Infectious Diseases on more than 600 members of a Cambodian village where 2 human H5N1 cases were detected in 2006. Antibody titers showed that only 1% (7 of 674) of the villagers tested had contracted, and fought off, the H5N1 virus.   A figure much lower than many had expected.
• In 2004 (see The Thailand Serological Study)  322 poultry farmers (in provinces where H5N1 had been detected)  were tested.  Researchers  found that "no poultry workers had microneutralization titers >80, whereas 7 (2%) had lower titers that did not meet the WHO definition for seropositivity".

 

The debate over the true CFR of H5N1 continues, and no one really knows the answer.  It is most likely substantially lower than 60%, but how much lower is the question.  The great pandemic of 1918 carried a CFR of 2% or so for the United States and Europe, yet managed to kill tens of millions around the globe. 

 

Proving that even if the true mortality rate of this avian flu is 1/20th of the `official’ CFR (ie. 3%) , an H5N1 pandemic could prove disastrous.

PLoS One: High Humidity Reduces Flu’s Infectivity

Photo Credit PHIL (Public Health Image Library)

 

# 6983

 

Regular readers of this blog are aware that there has been a fair amount of research in recent years as to why influenza epidemics (in temperate zones) typically occur during the winter months.

 

Theories include:

• During the winter people tend to gather indoors, with less outside ventilation.
• Diminished sunlight exposure may reduced Vitamin D levels (see Study: Vitamin D And Flu-Like Illnesses)
• With schools in session, millions of children co-mingle and more efficiently share viruses

 

While all potential factors, they don’t satisfactorily explain our yearly winter flu season. Nor do they explain why the flu transmits reasonably well in the tropics, where there is little temperature variability.

 

Scientists know that during the summer, ambient air often contains 4 times as much water as it does on a cool dry winter's day.  That has led some researchers to wonder about the role that relative humidity (RH) and absolute humidity (AB) play in influenza transmission.

 

In 2007, we looked at a study (see Cold And Dry Statistics) that appeared in  PLoS Pathogens  entitled  Influenza Virus Transmission Is Dependent on Relative Humidity and Temperature  by Anice C. Lowen, Samira Mubareka, John Steel,  and Peter Palese. 

 

Using a guinea pig as a model host, they showed that airborne spread of the  influenza virus was at least partially dependent upon both ambient relative humidity and temperature.

 

The link was significant, but not overwhelming.

 

The following year researchers Jeffrey Shaman and Melvin Kohn and found an even stronger correlation between the AH (Absolute Humidity) and the survival, and transmission of the influenza virus (see It's Not So Much The Heat, It's The Humidity).

 

Absolute humidity modulates influenza survival, transmission, and seasonality

Jeffrey Shaman, and Melvin Kohn

 

In early 2010, Jeffrey Shaman returned – joined by Virginia E. Pitzer, Cécile Viboud, Bryan T. Grenfell and Marc Lipsitch – to pen a study published in PLoS Biology called:

 

Absolute Humidity and the Seasonal Onset of Influenza in the Continental United States

(Excerpt)

Here we extend these findings to the human population level, showing that the onset of increased wintertime influenza-related mortality in the United States is associated with anomalously low absolute humidity levels during the prior weeks. We then use an epidemiological model, in which observed absolute humidity conditions temper influenza transmission rates, to successfully simulate the seasonal cycle of observed influenza-related mortality.  

 

And just last December we looked at a study (see Influenza Virus Survival At Opposite Ends Of The Humidity Spectrum) that found both extremely low and extremely high humidity were conducive to flu transmission – at least when it resides in mucus and respiratory fluids like those found in your nose, throat, or lungs.

 

Essentially, these researchers inoculated droplets of simulated respiratory fluids (containing salts & proteins) with influenza viruses, and tested their survivability at different humidity levels.

• At low humidity (< 50%) the droplets evaporated quickly, and the virus survived well in a dry environment.
• At high humidity (near 100%), the droplets were stable, and the virus survived as well.

 

But at humidity levels in-between, the droplets slowly dried out, increasing the concentration of salts and proteins to which the viruses were exposed, decreasing their survival rate.

 

 

The latest study, which appeared last week in PLoS One, suggests that maintaining a higher indoor humidity level during flu season may curb influenza transmission:

 

High Humidity Leads to Loss of Infectious Influenza Virus from Simulated Coughs

John D. Noti, Francoise M. Blachere, Cynthia M. McMillen, William G. Lindsley, Michael L. Kashon, Denzil R. Slaughter, Donald H. Beezhold

Abstract

Background

The role of relative humidity in the aerosol transmission of influenza was examined in a simulated examination room containing coughing and breathing manikins.

Methods

Nebulized influenza was coughed into the examination room and Bioaerosol samplers collected size-fractionated aerosols (<1 µM, 1–4 µM, and >4 µM aerodynamic diameters) adjacent to the breathing manikin’s mouth and also at other locations within the room. At constant temperature, the RH was varied from 7–73% and infectivity was assessed by the viral plaque assay.

Results

Total virus collected for 60 minutes retained 70.6–77.3% infectivity at relative humidity ≤23% but only 14.6–22.2% at relative humidity ≥43%. Analysis of the individual aerosol fractions showed a similar loss in infectivity among the fractions. Time interval analysis showed that most of the loss in infectivity within each aerosol fraction occurred 0–15 minutes after coughing. Thereafter, losses in infectivity continued up to 5 hours after coughing, however, the rate of decline at 45% relative humidity was not statistically different than that at 20% regardless of the aerosol fraction analyzed.

Conclusion

At low relative humidity, influenza retains maximal infectivity and inactivation of the virus at higher relative humidity occurs rapidly after coughing. Although virus carried on aerosol particles <4 µM have the potential for remaining suspended in air currents longer and traveling further distances than those on larger particles, their rapid inactivation at high humidity tempers this concern. Maintaining indoor relative humidity >40% will significantly reduce the infectivity of aerosolized virus.

 

This study was supported by National Institute for Occupational Safety and Health NIOSH and the Centers for Disease Control and Prevention CDC. 

 

A press short press release summarized the findings:

 

Higher indoor humidity inactivates flu virus particles

Infectious capacity of influenza virus particles reduced at relative humidity of 40 percent or higher

Higher humidity levels indoors can significantly reduce the infectivity of influenza virus particles released by coughing, according to research published February 27 in the open access journal PLOS ONE by John Noti and colleagues from the National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention.

The researchers tested the effect of relative humidity on the capacity of flu virus released in a simulated 'cough' to re-infect cells. They found that an hour after being released in a room at a relative humidity of 23% or less, 70-77% of viral particles retained their infectious capacity, but when humidity was increased to about 43%, only 14% of the virus particles were capable of infecting cells. Most of this inactivation occurred within the first fifteen minutes of the viral particles being released in the high-humidity condition.

The study concludes that maintaining indoor relative humidity at levels greater than 40% can significantly reduce the infectious capacity of aerosolized flu virus.

 

 

A supporting point that I’ve made before is that the Chinese have long boiled vinegar in their homes to `ward off’ respiratory ailments, such as influenza.

 

The noxious odor was supposed to `purify' the air inside the home, and newspapers still recommend this practice during their influenza season.

 

It may well turn out that the `active ingredient' is really the water vapor being released, raising the absolute humidity in their homes to an unfavorable level for influenza virus survival and transmission.