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Far-UVC light: A new tool to control the spread of airborne-mediated microbial diseases

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Airborne-mediated microbial diseases such as influenza and tuberculosis represent major public health challenges. A direct approach to prevent airborne transmission is inactivation of airborne pathogens, and the airborne antimicrobial potential of UVC ultraviolet light has long been established; however, its widespread use in public settings is limited because conventional UVC light sources are both carcinogenic and cataractogenic. By contrast, we have previously shown that far-UVC light (207-222 nm) efficiently inactivates bacteria without harm to exposed mammalian skin. This is because, due to its strong absorbance in biological materials, far-UVC light cannot penetrate even the outer (non living) layers of human skin or eye; however, because bacteria and viruses are of micrometer or smaller dimensions, far-UVC can penetrate and inactivate them. We show for the first time that far-UVC efficiently inactivates airborne aerosolized viruses, with a very low dose of 2 mJ/cm2 of 222-nm light inactivating >95% of aerosolized H1N1 influenza virus. Continuous very low dose-rate far-UVC light in indoor public locations is a promising, safe and inexpensive tool to reduce the spread of airborne-mediated microbial diseases.
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Far-UVC light: A new tool to control
the spread of airborne-mediated
microbial diseases
David Welch, Manuela Buonanno, Veljko Grilj, Igor Shuryak, Connor Crickmore,
Alan W. Bigelow, Gerhard Randers-Pehrson, Gary W. Johnson & David J. Brenner
Airborne-mediated microbial diseases such as inuenza and tuberculosis represent major public
health challenges. A direct approach to prevent airborne transmission is inactivation of airborne
pathogens, and the airborne antimicrobial potential of UVC ultraviolet light has long been established;
however, its widespread use in public settings is limited because conventional UVC light sources are
both carcinogenic and cataractogenic. By contrast, we have previously shown that far-UVC light
(207–222 nm) eciently inactivates bacteria without harm to exposed mammalian skin. This is because,
due to its strong absorbance in biological materials, far-UVC light cannot penetrate even the outer
(non living) layers of human skin or eye; however, because bacteria and viruses are of micrometer or
smaller dimensions, far-UVC can penetrate and inactivate them. We show for the rst time that far-UVC
eciently inactivates airborne aerosolized viruses, with a very low dose of 2 mJ/cm2 of 222-nm light
inactivating >95% of aerosolized H1N1 inuenza virus. Continuous very low dose-rate far-UVC light
in indoor public locations is a promising, safe and inexpensive tool to reduce the spread of airborne-
mediated microbial diseases.
Airborne-mediated microbial diseases represent one of the major challenges to worldwide public health1.
Common examples are influenza2, appearing in seasonal3 and pandemic4 forms, and bacterially-based
airborne-mediated diseases such as tuberculosis5, increasingly emerging in multi-drug resistant form.
A direct approach to prevent the transmission of airborne-mediated disease is inactivation of the correspond-
ing airborne pathogens, and in fact the airborne antimicrobial ecacy of ultraviolet (UV) light has long been
established68. Germicidal UV light can also eciently inactivate both drug-sensitive and multi-drug-resistant
bacteria9, as well as diering strains of viruses10. However, the widespread use of germicidal ultraviolet light in
public settings has been very limited because conventional UVC light sources are a human health hazard, being
both carcinogenic and cataractogenic11,12.
By contrast, we have earlier shown that far-UVC light generated by ltered excimer lamps emitting in the 207
to 222 nm wavelength range, eciently inactivates drug-resistant bacteria, without apparent harm to exposed
mammalian skin1315. e biophysical reason is that, due to its strong absorbance in biological materials, far-UVC
light does not have sucient range to penetrate through even the outer layer (stratum corneum) on the surface of
human skin, nor the outer tear layer on the outer surface of the eye, neither of which contain living cells; however,
because bacteria and viruses are typically of micron or smaller dimensions, far-UVC light can still eciently
traverse and inactivate them1315.
e earlier studies on the germicidal ecacy of far UVC light13,1518 were performed exposing bacteria irradi-
ated on a surface or in suspension. In that a major pathway for the spread of inuenza A is aerosol transmission3,
we investigate for the rst time the ecacy of far-UVC 222-nm light for inactivating airborne viruses carried by
aerosols – with the goal of providing a potentially safe alternative to conventional 254-nm germicidal lamps to
inactivate airborne microbes.
Results
Virus inactivation. Figure1 shows representative uorescent 40× images of mammalian epithelial cells
incubated with airborne viruses that had been exposed in aerosolized form to far-UVC doses (0, 0.8, 1.3 or 2.0
mJ/cm2) generated by ltered 222-nm excimer lamps. Blue uorescence was used to identify the total number of
Center for Radiological Research, Columbia University Medical Center, New York, New York, 10032, USA.
Correspondence and requests for materials should be addressed to D.W. (email: dw2600@cumc.columbia.edu)
Received: 7 November 2017
Accepted: 29 January 2018
Published: xx xx xxxx
OPEN
There are amendments to this paper
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cells in a particular eld of view, while green uorescence indicated the integration of live inuenza A (H1N1)
viruses into the cells. Results from the zero-dose control studies (Fig.1, top le) conrmed that the aerosol
irradiation chamber eciently transmitted the aerosolized viruses through the system, aer which the live virus
eciently infected the test mammalian epithelial cells.
Figure2 shows the surviving fraction, as a function of the incident 222-nm far-UVC dose, of exposed H1N1
aerosolized viruses, as measured by the number of focus forming units in incubated epithelial cells relative to
unexposed controls. Linear regressions (see below) showed that the survival results were consistent with a classi-
cal exponential UV disinfection model with rate constant k = 1.8 cm2/mJ (95% condence intervals 1.5–2.1 cm2/
mJ). e overall model t was good, with a coecient of determination, R2 = 0.95, which suggests that most of the
Figure 1. Antiviral ecacy of dierent low doses of 222-nm far-UVC light. Typical uorescent images of
MDCK epithelial cells infected with inuenza A virus (H1N1). e viruses were exposed in aerosolized form
in the irradiation chamber to doses of 0, 0.8, 1.3 or 2.0 mJ/cm2 of 222-nm far-UVC light. Infected cells uoresce
green (blue = nuclear stain DAPI; green = Alexa Fluor-488 conjugated to anti-inuenza A antibody). Images
were acquired with a 40× objective.
Figure 2. Quantication of the antiviral ecacy of 222-nm far-UVC light. Fractional survival, FFUUV/
FFUcontrols, is plotted as a function of the 222-nm far-UVC dose. Means and standard deviations refer to
triplicate repeat studies and the line represents the best-t regression to Eqn1 (see text).
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variability in virus survival was explained by the exponential model. e rate constant of 1.8 cm2/mJ corresponds
to an inactivation cross-section (dose required to inactivate 95% of the exposed viruses) of D95 = 1.6 mJ/cm2 (95%
condence intervals 1.4–1.9 mJ/cm2).
Discussion
We have developed an approach to UV-based sterilization using single-wavelength far-UVC light generated by l-
tered excilamps, which selectively inactivate microorganisms, but does not produce biological damage to exposed
mammalian cells and tissues1315. e approach is based on biophysical principles in that far-UVC light can trav-
erse and therefore inactivate bacteria and viruses which are typically micrometer dimensions or smaller, whereas
due to its strong absorbance in biological materials, far-UVC light cannot penetrate even the outer dead-cell
layers of human skin, nor the outer tear layer on the surface of the eye.
Here we applied this approach to test the ecacy of the 222-nm far-UVC light to inactivate inuenza A virus
(H1N1) carried by aerosols in a benchtop aerosol UV irradiation chamber, which generated aerosol droplets of
sizes similar to those generated by human coughing and breathing. Aerosolized viruses owing through the irra-
diation chamber were exposed to UVC emitting lamps placed in front of the chamber window.
As shown in Fig.2, inactivation of inuenza A virus (H1N1) by 222-nm far-UVC light follows a typical
exponential disinfection model, with an inactivation cross-section of D95 = 1.6 mJ/cm2 (95% CI: 1.4–1.9). For
comparison, using a similar experimental arrangement, but using a conventional 254 nm germicidal UVC lamp,
McDevitt et al.19 found a D95 value of 1.1 mJ/cm2 (95% CI: 1.0–1.2) for H1N1 virus. us as we13,15 and others1618
reported in earlier studies for bacterial inactivation, 222-nm far-UVC light and 254-nm broad-spectrum germi-
cidal light are also comparable in their eciencies for aerosolized viral inactivation. Other recent work compar-
ing viral inactivation across the UVC spectrum has shown variations in eciency are expected, but in general
both regions of the spectrum are eective in inactivation, though the precise cause of inactivation may dier20,21.
However as discussed above, based on biophysical considerations and in contrast to the known human health
safety issues associated with conventional germicidal 254-nm broad-spectrum UVC light, far-UVC light does not
appear to be cytotoxic to exposed human cells and tissues in vitro or in vivo1315.
If these results are conrmed in other scenarios, it follows that the use of overhead low-level far-UVC light
in public locations may represent a safe and ecient methodology for limiting the transmission and spread of
airborne-mediated microbial diseases such as inuenza and tuberculosis. In fact the potential use of ultraviolet
light for airborne disinfection is by no means new, and was rst demonstrated more than 80 years ago8,22. As
applied more recently, airborne ultraviolet germicidal irradiation (UVGI) utilizes conventional germicidal UVC
light in the upper part of the room, with louvers to prevent direct exposure of potentially occupied room areas23.
is results in blocking more than 95% of the UV radiation exiting the UVGI xture, with substantial decrease
in eectiveness24. By contrast, use of low-level far-UVC xtures, which are potentially safe for human exposure,
could provide the desired antimicrobial benets without the accompanying human health concerns of conven-
tional germicidal lamp UVGI.
A key advantage of the UVC based approach, which is in clear contrast to vaccination approaches, is that
UVC light is likely to be eective against all airborne microbes. For example, while there will almost certainly
be variations in UVC inactivation eciency as dierent inuenza strains appear, they are unlikely to be large7,10.
Likewise, as multi-drug-resistant variants of bacteria emerge, their UVC inactivation eciencies are also unlikely
to change greatly9.
In conclusion, we have shown for the rst time that very low doses of far-UVC light eciently inactivate
airborne viruses carried by aerosols. For example, a very low dose of 2 mJ/cm2 of 222-nm light inactivates >95%
of airborne H1N1 virus. Our results indicate that far-UVC light is a powerful and inexpensive approach for pre-
vention and reduction of airborne viral infections without the human health hazards inherent with conventional
germicidal UVC lamps. If these results are conrmed in other scenarios, it follows that the use of overhead very
low level far-UVC light in public locations may represent a safe and ecient methodology for limiting the trans-
mission and spread of airborne-mediated microbial diseases. Public locations such as hospitals, doctors’ oces,
schools, airports and airplanes might be considered here. is approach may help limit seasonal inuenza epi-
demics, transmission of tuberculosis, as well as major pandemics.
Methods
Far-UVC lamps. We used a bank of three excimer lamps containing a Kr-Cl gas mixture that predomi-
nantly emits at 222 nm25,26. e exit window of each lamp was covered with a custom bandpass lter designed to
remove all but the dominant emission wavelength as previously described15. Each bandpass lter (Omega Optical,
Brattleboro, VT) had a center wavelength of 222 nm and a full width at half maximum (FWHM) of 25 nm and
enables >20% transmission at 222 nm. A UV spectrometer (SPM-002-BT64, Photon Control, BC, Canada) with
a sensitivity range between 190 nm and 400 nm was utilized to verify the 222 nm emission spectrum. A deute-
rium lamp standard with a NIST-traceable spectral irradiance (Newport Model 63945, Irvine, CA) was used to
radiometrically calibrate the UV spectrometer. An SM-70 Ozone Monitor (Aeroqual, Avondale, Auckland, New
Zealand) measured the ozone generation from the lamps to be <0.005 ppm, which is not a signicant level to
provide an antimicrobial eect to aerosolized viruses27.
Far-UVC dosimetry. Optical power measurements were performed using an 818-UV/DB low-power UV
enhanced silicon photodetector with an 843-R optical power meter (Newport, Irvine, CA). Additional dosimetry
to determine the uniformity of the UV exposure was performed using far-UVC sensitive lm as described in our
previous work28,29. is lm has a high spatial resolution with the ability to resolve features to at least 25 µm, and
exhibits a nearly ideal cosine response30,31. Measurements were taken between experiments therefore allowing
placement of sensors inside the chamber.
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A range of far-UVC exposures, from 3.6 µJ/cm2 up to 281.6 mJ/cm2, were used to dene a response calibration
curve. Films were scanned as 48 bit RGB TIFF images at 150 dpi using an Epson Perfection V700 Photo atbed
scanner (Epson, Japan) and analyzed with radiochromic lm analysis soware32 to calculate the total exposure
based on measured changes in optical density.
Measurements using both a silicon detector and UV sensitive lms were combined to compute the total dose
received by a particle traversing the exposure window. e three vertically stacked lamps produced a nearly
uniform dose distribution along the vertical axis thus every particle passing horizontally through the irradiation
chamber received an identical dose. e lamp width (100 mm) was smaller than the width of the irradiation
chamber window (260 mm) so the lamp power was higher near the center of the irradiation chamber window
compared to the edge. e UV sensitive lm indicated a power of approximately 120 µW/cm2 in the center third
of the window and 70 µW/cm2 for the outer thirds. e silicon detector was used to quantify the reectivity of
the aluminum sheet at approximately 15% of the incident power. Combining this data allowed the calculation of
the average total dose of 2.0 mJ/cm2 to a particle traversing the window in 20 seconds. Additionally, the silicon
detector was used to conrm the attenuation of 222-nm light through a single sheet of plastic lm was 65%. e
addition of one or two sheets of plastic lm between the lamps and the irradiation chamber window yielded aver-
age doses of 1.3 mJ/cm2 and 0.8 mJ/cm2, respectively.
Benchtop aerosol irradiation chamber. A one-pass, dynamic aerosol / virus irradiation chamber was
constructed in a similar conguration to that used by Ko et al.33, Lai et al.34, and McDevitt et al.19,35. A schematic
overview of the system is shown in Fig.3 and is pictured in Fig.4. Aerosolized viruses were generated by adding
a virus solution into a high-output extended aerosol respiratory therapy (HEART) nebulizer (Westmed, Tucson,
AZ) and operated using a dual-head pump (ermo Fisher 420–2901–00FK, Waltham, MA) with an input
ow rate of 11 L/min. e aerosolized virus owed into the irradiation chamber where it was mixed with inde-
pendently controlled inputs of humidied and dried air. Humidied air was produced by bubbling air through
water, while dry air was provided by passing air through a desiccant air dryer (X06–02–00, Wilkerson Corp,
Richland, MI). Adjusting the ratio of humid and dry air enabled control of the relative humidity (RH) within the
irradiation chamber which, along with the nebulizer settings, determined the aerosol particle size distribution.
An optimal RH value of 55% resulted in a distribution of aerosol particle sizes similar to the natural distribution
from human coughing and breathing, which has been shown to be distributed around approximately 1 µm, with
a signicant tail of particles less than 1 µm3638.
Aer combining the humidity control inputs with the aerosolized virus, input ow was directed through
a series of baes that promoted droplet drying and mixing to produce an even particle distribution and sta-
ble humidity34. The RH and temperature inside the irradiation chamber were monitored using an Omega
RH32 meter (Omega Engineering Inc., Stamford, CT) immediately following the baes. A Hal Technologies
HAL-HPC300 particle sizer (Fontana, CA) was adjoined to the irradiation chamber to allow for sampling of
particle sizes throughout operation.
During UV exposure, the 222-nm lamps were placed 11 cm from the irradiation chamber window. e lamps
were directed at the 26 cm × 25.6 cm chamber window which was constructed of 254-µm thick UV transparent
plastic lm (Topas 8007x10, Topas Advanced Polymers, Florence, KY), and which had a transmission of ~65% at
222 nm. e wall of the irradiation chamber opposite the transparent window was constructed with polished alu-
minum in order to reect a portion of the UVC light back through the exposure region, therefore increasing the
overall exposure dose by having photons pass in both directions. e depth of the irradiation chamber between
the window and the aluminum panel was 6.3 cm, creating a total exposure volume of 4.2 L.
Figure 3. Schematic diagram of the custom UV irradiation chamber. e chamber is depicted in a top down
view. Components of the setup include: water bubbler for humidied air input (A), a desiccator for dry air input
(B), a nebulizer (C), baes (D), an RH and temperature meter (E), a particle sizer (F), far-UVC lamps (G), band
pass lters (H), a far-UVC transmitting plastic window (I), a reective aluminum surface (J), and a BioSampler
(K). Pumps are used to pressurize the nebulizer for aerosol generation and to control ow through the system.
Flow control valves allow adjustments through the system. HEPA lters are included on all air inputs and
outputs. A set of three way valves controls ow to or around the BioSampler. e vertically stacked lamps are
directed at the window in the side of the chamber to expose the aerosols passing horizontally. e additional
lms to uniformly decrease the dose were placed between the lters and the window. e path of the aerosolized
virus within the system during sampling is indicated with the red dotted line.
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Flow of the aerosols continues out of the irradiation chamber to a set of three way valves that could be cong-
ured to either pass through a bypass channel (used when no sampling was required), or a BioSampler (SKC Inc,
Eighty Four, PA) used to collect the virus. e BioSampler uses sonic ow impingement upon a liquid surface to
collect aerosols when operated at an air ow of 12.5 L/min. Finally, ow continued out of the system through a
nal HEPA lter and to a vacuum pump (WP6111560, EMD Millipore, Billerica, MA). e vacuum pump at the
end of the system powered ow through the irradiation chamber. e ow rate through the system was governed
by the BioSampler. Given the ow rate and the total exposure volume of the irradiation chamber, 4.2 L, a single
aerosol droplet passed through the exposure volume in approximately 20 seconds.
e entire irradiation chamber was set up inside a certied class II type A2 biosafety cabinet (Labconco,
Kansas City, MO). All air inputs and outputs were equipped with HEPA lters (GE Healthcare Bio-Sciences,
Pittsburgh, PA) to prevent unwanted contamination from entering the chamber as well as to block any of the virus
from releasing into the environment.
Irradiation chamber performance. e custom irradiation chamber simulated the transmission of aero-
solized viruses produced via human coughing and breathing. e chamber operated at a relative humidity of 55%
which resulted in a particle size distribution of 87% between 0.3 µm and 0.5 µm, 11% between 0.5 µm and 0.7 µm,
and 2% > 0.7 µm. A comparison to published ranges of particle size distributions is shown in Table1. Aerosolized
viruses were eciently transmitted through the system as evidenced from the control (zero exposure) showing
clear virus integration (Fig.1, top le).
Experimental protocol. e virus solution in the nebulizer consisted of 1 ml of Dulbecco’s Modied Eagle’s
Medium (DMEM, Life Technologies, Grand Island, NY) containing 108 focus forming units per ml (FFU/ml) of
inuenza A virus [A/PR/8/34 (H1N1)], 20 ml of deionized water, and 0.05 ml of Hank’s Balanced Salt Solution
with calcium and magnesium (HBSS++). e irradiation chamber was operated with aerosolized virus particles
owing through the chamber and the bypass channel for 15 minutes prior to sampling, in order to establish
the desired RH value of ~55%. Sample collection initiated by changing air ow from the bypass channel to the
BioSampler using the set of three way valves. e BioSampler was initially lled with 20 ml of HBSS++ to capture
the aerosol. During each sampling time, which lasted for 30 minutes, the inside of the irradiation chamber was
Figure 4. Photograph of the custom UV irradiation chamber. e experimental setup shows many of the
necessary components while some elements, such as pumps, lters, and lamps, were omitted to better depict the
overall setup.
Particle Size Distribution
<1.0 µm>1.0 µm
Papineni 199740 Coughing 83–91% 9–16%
Mouth Breathing 83–95% 4–16%
Nose Breathing 83–100% 0–16%
Talking 77–88% 11–22%
0.3–0.5 µm 0.5–0.7 µm>0.7 µm
is work 87% 11% 2%
Table 1. Example particle size distributions from humans during various activities are given along with the
measured values for this work.
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exposed to 222 nm far-UVC light through the UVC semi-transparent plastic window. Variation of the far-UVC
dose delivered to aerosol particles was achieved by inserting additional UVC semi-transparent plastic lms, iden-
tical to the material used as the chamber window, between the lamps and the chamber window. e extra plastic
lms uniformly reduced the power entering the chamber. e three test doses of 0.8, 1.3 and 2.0 mJ/cm2, were
achieved by adding two, one, or no additional plastic lms, respectively. Zero-dose control studies were con-
ducted with the excimer lamps turned o. Experiments at each dose were repeated in triplicate. A newly sterilized
BioSampler was used for each experimental run to prevent unwanted contamination. Negative controls, where
virus was omitted from the nebulizer mixture, were run intermittently and showed no virus collection in the
BioSampler. Aer the sampling period was completed the solution from the BioSampler was used for the virus
infectivity assay.
Virus infectivity assay. We measured viral infectivity with a focus forming assay that employs standard u-
orescent immunostaining techniques to detect infected host cells and infectious virus particles39. Briey, aer run-
ning through the irradiation chamber for 30 minutes, 0.5 ml of virus suspension collected from the BioSampler
was overlaid on a monolayer of Madin-Darby Canine Kidney (MDCK) epithelial cells routinely grown in DMEM
supplemented with 10% Fetal Bovine Serum (FBS), 2 mM L-alanyl-L-glutamine, 100 U/ml penicillin and 100 μg/
ml streptomycin (Sigma-Aldrich Corp. St. Louis, MO, USA). Cells were incubated with the virus for 45 minutes,
washed three times with HBSS++ and incubated overnight in DMEM. Infected cells were then xed in 100% ice
cold methanol at 4 °C for 5 minutes and labeled with inuenza A virus nucleoprotein antibody [C43] (Abcam
ab128193, Cambridge, MA) 1:200 in HBSS++ containing 1% bovine serum albumin (BSA; Sigma-Aldrich Corp.
St. Louis, MO, USA) at room temperature for 30 minutes with gentle shaking. Cells were washed three times
in HBSS++ and labeled with goat anti-mouse Alexa Fluor-488 (Life Technologies, Grand Island, NY) 1:800 in
HBSS++ containing 1% BSA at room temperature for 30 minutes with gentle shaking. Following three washes
in HBSS++, the cells were stained with Vectashield containing DAPI (4,6-diamidino-2-phenylindole) (Victor
Laboratories, Burlingame, CA) and observed with the 10× and 40× objectives of an Olympus IX70 uorescent
microscope equipped with a Photometrics PVCAM high-resolution, high-eciency digital camera. For each
sample, at least three elds of view of merged DAPI and Alexa-488 images were acquired. Image-Pro Plus 6.0
soware (Media Cybernetics, Bethesda, MD) was used to analyze the 10× images to measure the FFUUV as the
ratio of cells infected with the virus divided by the total number of cells.
Data analysis. e surviving fraction (S) of the virus was calculated by dividing the fraction of cells that
yielded positive virus growth at each UV dose (FFUUV) by the fraction at zero dose (FFUcontrols): S = FFUUV/
FFUcontrols. Survival values were calculated for each repeat experiment and natural log (ln) transformed to bring
the error distribution closer to normal40. Linear regression was performed using these normalized ln[S] values
as the dependent variable and UV dose (D, mJ/cm2) as the independent variable. Using this approach, the virus
survival (S) was tted to rst-order kinetics according to the equation7:
=− ×kDln[S], (1)
where k is the UV inactivation rate constant or susceptibility factor (cm2/mJ). e regression was performed
with the intercept term set to zero, which represents the denition of 100% relative survival at zero UV dose.
Bootstrap 95% condence intervals for the parameter k were calculated using R 3.2.3 soware41. e virus inac-
tivation cross section, D95, which is the UV dose that inactivates 95% of the exposed virus, was calculated as
D95 = ln[1 0.95]/k.
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Acknowledgements
is work was supported by the Shostack Foundation and also NIH grant 1R41AI125006–01. We thank Dr. Rea
Dabelic from the Department of Environmental Health Sciences, Mailman School of Public Health at Columbia
University for her expertise and training with viral cell culture.
Author Contributions
D.W., M.B. and V.G. designed and performed experiments, analyzed the data, and wrote the manuscript; I.S.
analyzed the data; C.C. and A.W.B. designed the irradiation chamber; G.W.J. constructed the irradiation chamber;
D.J.B and G.R.-P. supervised, contributed conceptual advice, and wrote the manuscript. All authors discussed the
results and commented on the manuscript.
Additional Information
Competing Interests: The authors G.R.-P., D.J.B. and A.B. have a granted patent entitled ‘Apparatus, method
and system for selectively affecting and/or killing a virus’ (US10780189B2), that relates to the use of filtered
222 nm UV light to inactivate viruses. In addition, D.J.B. has an ongoing non-financial collaboration with
Eden Park Illumination, and the authors’ institution, Columbia University, has licensed aspects of UV light
technology to USHIO Inc.
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We also expanded the database of vital registration, survey, and census data to 14 294 geography-year datapoints. For GBD 2015, eight causes, including Ebola virus disease, were added to the previous GBD cause list for mortality. We used six modelling approaches to assess cause-specific mortality, with the Cause of Death Ensemble Model (CODEm) generating estimates for most causes. We used a series of novel analyses to systematically quantify the drivers of trends in mortality across geographies. First, we assessed observed and expected levels and trends of cause-specific mortality as they relate to the Socio-demographic Index (SDI), a summary indicator derived from measures of income per capita, educational attainment, and fertility. Second, we examined factors affecting total mortality patterns through a series of counterfactual scenarios, testing the magnitude by which population growth, population age structures, and epidemiological changes contributed to shifts in mortality. Finally, we attributed changes in life expectancy to changes in cause of death. We documented each step of the GBD 2015 estimation processes, as well as data sources, in accordance with Guidelines for Accurate and Transparent Health Estimates Reporting (GATHER). Findings: Globally, life expectancy from birth increased from 61·7 years (95% uncertainty interval 61·4-61·9) in 1980 to 71·8 years (71·5-72·2) in 2015. Several countries in sub-Saharan Africa had very large gains in life expectancy from 2005 to 2015, rebounding from an era of exceedingly high loss of life due to HIV/AIDS. At the same time, many geographies saw life expectancy stagnate or decline, particularly for men and in countries with rising mortality from war or interpersonal violence. From 2005 to 2015, male life expectancy in Syria dropped by 11·3 years (3·7-17·4), to 62·6 years (56·5-70·2). Total deaths increased by 4·1% (2·6-5·6) from 2005 to 2015, rising to 55·8 million (54·9 million to 56·6 million) in 2015, but age-standardised death rates fell by 17·0% (15·8-18·1) during this time, underscoring changes in population growth and shifts in global age structures. The result was similar for non-communicable diseases (NCDs), with total deaths from these causes increasing by 14·1% (12·6-16·0) to 39·8 million (39·2 million to 40·5 million) in 2015, whereas age-standardised rates decreased by 13·1% (11·9-14·3). Globally, this mortality pattern emerged for several NCDs, including several types of cancer, ischaemic heart disease, cirrhosis, and Alzheimer's disease and other dementias. By contrast, both total deaths and age-standardised death rates due to communicable, maternal, neonatal, and nutritional conditions significantly declined from 2005 to 2015, gains largely attributable to decreases in mortality rates due to HIV/AIDS (42·1%, 39·1-44·6), malaria (43·1%, 34·7-51·8), neonatal preterm birth complications (29·8%, 24·8-34·9), and maternal disorders (29·1%, 19·3-37·1). Progress was slower for several causes, such as lower respiratory infections and nutritional deficiencies, whereas deaths increased for others, including dengue and drug use disorders. Age-standardised death rates due to injuries significantly declined from 2005 to 2015, yet interpersonal violence and war claimed increasingly more lives in some regions, particularly in the Middle East. In 2015, rotaviral enteritis (rotavirus) was the leading cause of under-5 deaths due to diarrhoea (146 000 deaths, 118 000-183 000) and pneumococcal pneumonia was the leading cause of under-5 deaths due to lower respiratory infections (393 000 deaths, 228 000-532 000), although pathogen-specific mortality varied by region. Globally, the effects of population growth, ageing, and changes in age-standardised death rates substantially differed by cause. Our analyses on the expected associations between cause-specific mortality and SDI show the regular shifts in cause of death composition and population age structure with rising SDI. Country patterns of premature mortality (measured as years of life lost [YLLs]) and how they differ from the level expected on the basis of SDI alone revealed distinct but highly heterogeneous patterns by region and country or territory. Ischaemic heart disease, stroke, and diabetes were among the leading causes of YLLs in most regions, but in many cases, intraregional results sharply diverged for ratios of observed and expected YLLs based on SDI. Communicable, maternal, neonatal, and nutritional diseases caused the most YLLs throughout sub-Saharan Africa, with observed YLLs far exceeding expected YLLs for countries in which malaria or HIV/AIDS remained the leading causes of early death. Interpretation: At the global scale, age-specific mortality has steadily improved over the past 35 years; this pattern of general progress continued in the past decade. Progress has been faster in most countries than expected on the basis of development measured by the SDI. Against this background of progress, some countries have seen falls in life expectancy, and age-standardised death rates for some causes are increasing. Despite progress in reducing age-standardised death rates, population growth and ageing mean that the number of deaths from most non-communicable causes are increasing in most countries, putting increased demands on health systems. Funding: Bill & Melinda Gates Foundation.
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