NIH Study: Climate & Influenza Transmission

Credit PloS Pathogens

 

# 6990

 

 

Over the past couple of years we’ve examined several studies looking at the seasonality of influenza – both in temperate and tropical climes – the most recent being earlier this week in PLoS One: High Humidity Reduces Flu’s Infectivity.

 

In that study researchers tested the viability of influenza viruses at various relative humidity (RH) levels between 7% and 73%. Infectivity was assessed by the viral plaque assay.

 

They found that above 40% RH, infectivity dropped sharply.

 

Which fits nicely with the yearly increase of influenza across temperate zones during the winter, when RH is often 75% lower than during the summer months.

 

But it does little to explain the year-round transmission of influenza in tropical climes.

 

Last December, we took a run at another study (see Influenza Virus Survival At Opposite Ends Of The Humidity Spectrum) conducted by researchers from Virginia Tech – that looked at a much broader range of humidity levels (up to 100%).

 

They found both extremely low and extremely high humidity humidity appeared to aid and abet the viability of the flu virus – 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.

 

These studies suggest that there is a `sweet spot’ in RH (approx 40%-95%) where flu viruses have difficulty surviving. At levels above or below, the virus fares much better.

 

This would help explain why influenza is primarily a winter event in temperate zones, but can still transmit in the exceptionally humid tropics year-round.

 

In 2008 researchers Jeffrey Shaman and Melvin Kohn established a 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 2010, Jeffrey Shaman returned with Virginia E. Pitzer, Cécile Viboud, Bryan T. Grenfell and Marc Lipsitch – and penned a study 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.

 

Shaman and Viboud  et al. return today with a new NIH/Fogarty study appearing in PloS Pathogens that finds it is both cold-dry and humid-rainy conditions that can exacerbate influenza outbreaks.

 

A finding that fits rather nicely with the Virginia Tech research mentioned above.

 

 

Environmental Predictors of Seasonal Influenza Epidemics across Temperate and Tropical Climates

James D. Tamerius, Jeffrey Shaman, Wladmir J. Alonso, Kimberly Bloom-Feshbach, Christopher K. Uejio, Andrew Comrie, Cécile Viboud

Abstract (reparagraphed for readability)

Human influenza infections exhibit a strong seasonal cycle in temperate regions. Recent laboratory and epidemiological evidence suggests that low specific humidity conditions facilitate the airborne survival and transmission of the influenza virus in temperate regions, resulting in annual winter epidemics. However, this relationship is unlikely to account for the epidemiology of influenza in tropical and subtropical regions where epidemics often occur during the rainy season or transmit year-round without a well-defined season.

 

We assessed the role of specific humidity and other local climatic variables on influenza virus seasonality by modeling epidemiological and climatic information from 78 study sites sampled globally.

 

We substantiated that there are two types of environmental conditions associated with seasonal influenza epidemics: “cold-dry” and “humid-rainy”.

 

For sites where monthly average specific humidity or temperature decreases below thresholds of approximately 11–12 g/kg and 18–21°C during the year, influenza activity peaks during the cold-dry season (i.e., winter) when specific humidity and temperature are at minimal levels. For sites where specific humidity and temperature do not decrease below these thresholds, seasonal influenza activity is more likely to peak in months when average precipitation totals are maximal and greater than 150 mm per month.

 

These findings provide a simple climate-based model rooted in empirical data that accounts for the diversity of seasonal influenza patterns observed across temperate, subtropical and tropical climates.

 

For more, we have a press release from the NIH/Fogarty International Center.

 

NIH study sheds light on role of climate in influenza transmission

Two types of environmental conditions—cold-dry and humid-rainy—are associated with seasonal influenza epidemics, according to an epidemiological study led by researchers at the National Institutes of Health's Fogarty International Center. The paper, published in PLOS Pathogens, presents a simple climate-based model that maps influenza activity globally and accounts for the diverse range of seasonal patterns observed across temperate, subtropical and tropical regions.

 

The findings could be used to improve existing current influenza transmission models, and could help target surveillance efforts and optimize the timing of seasonal vaccine delivery, according to Fogarty researcher Cecile Viboud, Ph.D., who headed the study. "The model could have a broader application, encouraging researchers to analyze the association between climatic patterns and infectious disease across a wide range of diseases and latitudes," said Viboud.

 

Human influenza infections exhibit a strong seasonal cycle in temperate regions, and laboratory experiments suggest that low specific humidity facilitates the airborne survival and transmission of the virus in temperate regions. Specific humidity is the ratio of water vapor to dry air in a particular body of air while relative humidity—commonly used in weather forecasts—is the amount of water vapor in the air relative to its capacity to hold water vapor, and is primarily a function of temperature.

 

Data from animal studies indicate low temperature and humidity increase the duration of the virus's reproduction and expulsion in infected organisms and virus stability in the environment, increasing the probability of transmission through coughing, sneezing or breathing. In contrast, high temperature seems to block airborne transmission.

(Continue . . . )

 

While climatic conditions appear to play a big role in the infectivity of influenza, it is by no means the only factor.  Again, from the press release:

 

"Further work should focus on examining the role of population travel and other factors in influenza transmission," notes Mark Miller, M.D., director of Fogarty's Division of International Epidemiology and Population Studies. "

 

Understanding the climatic conditions under which influenza (and perhaps other) viruses transmit best may provide us with an improved ability to forecast regional outbreaks.

 

But perhaps as importantly, this knowledge may also show us how to adjust indoor environments to curb flu transmission. The upshot from the NIOSH report from earlier this week (see press release Higher indoor humidity inactivates flu virus particles) reads:

 

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

 

Something that environmental managers at hospitals, office buildings, schools, and other locations may want to take notice of before we enter the next influenza epidemic.

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.

Influenza Virus Survival At Opposite Ends Of The Humidity Spectrum

Photo Credit PHIL (Public Health Image Library)

 

 

# 6763

 

Although just about everybody knows that winter heralds the arrival of influenza season, one of the enduring mysteries about influenza is why it is predominantly a winter phenomenon – at least in temperate zones of the world.

Numerous theories abound, including;

 

• 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 these may be factors, they don’t satisfactorily explain our yearly winter flu season. Nor are they very helpful in explaining why the flu transmits pretty well in the tropics, where there is little temperature variability. 

 

In recent years, researchers have been looking at relative humidity (RH) and absolute humidity (AB)as factors in aiding influenza virus survival (IVS). 

 

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.  

 

During the summer, ambient air often contains 4 times as much water as it does on a cool dry winter's day. This, increasingly, is beginning to look as if it is a significant factor in the spread of influenza viruses.

 

As a side note, 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 be 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.

 

All of which is neat and tidy until you consider that flu transmits readily in the tropics, where the atmosphere is often nearly saturated with water vapor.

 

Enter researchers from Virginia Tech who have found that both extremely low and extremely high levels of humidity appear to aid and abet the viability of the flu virus – at least when it resides in mucus and respiratory fluids like those found in your nose, throat, or lungs.

 

This is an open access article, available from PloS One.

 

Relationship between Humidity and Influenza A Viability in Droplets and Implications for Influenza’s Seasonality

PLoS ONE 7(10): e46789. doi:10.1371/journal.pone.0046789

Wan Yang, Subbiah Elankumaran, Linsey C. Marr

Abstract (excerpts reparagraphed for readability)

Humidity has been associated with influenza’s seasonality, but the mechanisms underlying the relationship remain unclear. There is no consistent explanation for influenza’s transmission patterns that applies to both temperate and tropical regions.

 

This study aimed to determine the relationship between ambient humidity and viability of the influenza A virus (IAV) during transmission between hosts and to explain the mechanisms underlying it.

 

We measured the viability of IAV in droplets consisting of various model media, chosen to isolate effects of salts and proteins found in respiratory fluid, and in human mucus, at relative humidities (RH) ranging from 17% to 100%.

 

In all media and mucus, viability was highest when RH was either close to 100% or below ~50%. When RH decreased from 84% to 50%, the relationship between viability and RH depended on droplet composition: viability decreased in saline solutions, did not change significantly in solutions supplemented with proteins, and increased dramatically in mucus.

(Continue. . . . )

 

 

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.

 

As these experiments were conducted on relatively large droplets, how these findings would relate to viruses carried by smaller, aerosolized particles (that would desiccate much faster, even at higher humidities) remains untested.

 

Still, it’s fascinating research, and it adds incrementally to our understanding of how the influenza virus survives outside of a host.

 

You may recall I featured another study by these same researchers in early 2011 (see Why Size Matters) where they analyzed the amount of influenza virus suspended in the air in several environments, including a daycare center, a healthcare waiting room,  and aboard commercial aircraft.

 

They found airborne virus particles in half of the air samples tested, and in quantities they believe sufficient to enable transmission of the virus.

 

Many of these virus particles were very small, less than 2.5 micrometers, which can remain aloft on a room’s air currents for hours. Larger droplets would settle far sooner, and theoretically present less of a threat.

 

"As a whole," the three authors concluded in the Journal of the Royal Society Interface, "our results provide quantitative support for the possibility of airborne transmission of influenza in indoor environments."

 

All of which makes the influenza virus a formidable foe, and highlights the importance of maintaining good flu hygiene (hand washing, covering coughs & sneezes & staying home when sick), and the wisdom of getting that flu shot every year.