ArticlePDF Available

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

Springer Nature
Scientific Reports
Authors:

Abstract and Figures

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.
This content is subject to copyright. Terms and conditions apply.
1
Scientific RePoRtS | (2018) 8:2752 | DOI:10.1038/s41598-018-21058-w
www.nature.com/scientificreports
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
Content courtesy of Springer Nature, terms of use apply. Rights reserved
www.nature.com/scientificreports/
2
Scientific RePoRtS | (2018) 8:2752 | DOI:10.1038/s41598-018-21058-w
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).
Content courtesy of Springer Nature, terms of use apply. Rights reserved
www.nature.com/scientificreports/
3
Scientific RePoRtS | (2018) 8:2752 | DOI:10.1038/s41598-018-21058-w
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.
Content courtesy of Springer Nature, terms of use apply. Rights reserved
www.nature.com/scientificreports/
4
Scientific RePoRtS | (2018) 8:2752 | DOI:10.1038/s41598-018-21058-w
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.
Content courtesy of Springer Nature, terms of use apply. Rights reserved
www.nature.com/scientificreports/
5
Scientific RePoRtS | (2018) 8:2752 | DOI:10.1038/s41598-018-21058-w
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.
Content courtesy of Springer Nature, terms of use apply. Rights reserved
www.nature.com/scientificreports/
6
Scientific RePoRtS | (2018) 8:2752 | DOI:10.1038/s41598-018-21058-w
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.
References
1. Global, regional, and national life expectancy, all-cause mortality, and cause-specic mortality for 249 causes of death, 1980–2015:
a systematic analysis for the Global Burden of Disease Study 2015. Lancet 388, 1459–1544 (2016).
2. Paules, C. & Subbarao, . Inuenza. Lancet 390, 697–708 (2017).
3. Cowling, B. J. et al. Aerosol transmission is an important mode of inuenza A virus spread. Nat Commun 4, 1935 (2013).
4. Yu, I. T. et al. Evidence of airborne transmission of the severe acute respiratory syndrome virus. N Engl J Med 350, 1731–1739 (2004).
5. Pai, M. et al. Tuberculosis. Nat ev Dis Primers 2, 16076 (2016).
6. Hollaender, A., du Buy, H. G., Ingraham, H. S. & Wheeler, S. M. Control of air-borne microorganisms by ultraviolet oor irradiation.
Science 99, 130–131 (1944).
7. owalsi, W. J. Ultraviolet Germicidal Irradiation Handboo: UVGI for Air and Surface Disinfection, (New Yor: Springer).
8. Wells, W. F. & Fair, G. M. Viability of B. Coli Exposed to Ultra-Violet adiation in Air. Science 82, 280–281 (1935).
9. Conner-err, T. A., Sullivan, P. ., Gaillard, J., Franlin, M. E. & Jones, . M. e eects of ultraviolet radiation on antibiotic-
resistant bacteria in vitro. Ostomy Wound Manage 44, 50–56 (1998).
10. Budowsy, E. I., Bresler, S. E., Friedman, E. A. & Zheleznova, N. V. Principles of selective inactivation of viral genome. I. UV-induced
inactivation of inuenza virus. Arch Virol 68, 239–247 (1981).
11. Setlow, . B., Grist, E., ompson, . & Woodhead, A. D. Wavelengths eective in induction of malignant melanoma. Proc Natl Acad
Sci USA 90, 6666–6670 (1993).
12. Balasubramanian, D. Ultraviolet radiation and cataract. J Ocul Pharmacol er 16, 285–297 (2000).
13. Buonanno, M. et al . 207-nm UV light - a promising tool for safe low-cost reduction of surgical site infections. I: in v itro studies. PLoS
One 8, e76968 (2013).
14. Buonanno, M. et al. 207-nm UV Light-A Promising Tool for Safe Low-Cost eduction of Surgical Site Infections. II: In-Vivo Safety
Studies. PLoS One 11, e0138418 (2016).
15. Buonanno, M. et al. Germicidal Ecacy and Mammalian Sin Safety of 222-nm UV Light. adiat. es. 187, 483–491 (2017).
16. Matafonova, G. G., Batoev, V. B., Astahova, S. A., Gómez, M. & Christo, N. Eciency of rCl excilamp (222 nm) for inactivation
of bacteria in suspension. Lett. Appl. Microbiol. 47, 508–513 (2008).
17. Sosnin, E. A., Avdeev, S. M., uznetzova, E. A. & Lavrent’eva, L. V. A Bactericidal Barrier-Discharge rBr Excilamp. Instruments and
Experimental Techniques 48, 663–666 (2005).
18. Wang, D., Oppenländer, T., El-Din, M. G. & Bolton, J. . Comparison of the Disinfection Eects of Vacuum-UV (VUV) and UV
Light on Bacillus subtilis Spores in Aqueous Suspensions at 172, 222 and 254 nm. Photochem and Photobiol 86, 176–181 (2010).
Content courtesy of Springer Nature, terms of use apply. Rights reserved
www.nature.com/scientificreports/
7
Scientific RePoRtS | (2018) 8:2752 | DOI:10.1038/s41598-018-21058-w
19. McDevitt, J. J., udnic, S. N. & adonovich, L. J. Aerosol Susceptibility of Inuenza Virus to UV-C Light. Appl. Environ. Microbiol.
78, 1666–1669 (2012).
20. Bec, S. E., Hull, N. M., Poepping, C. & Linden, . G. Wavelength-Dependent Damage to Adenoviral Proteins Across the Germicid al
UV Spectrum. Environ. Sci. Technol. (2017).
21. Bec, S. E. et al. Comparison of UV-Induced Inactivation and NA Damage in MS2 Phage across the Germicidal UV Spectrum.
Appl. Environ. Microbiol. 82, 1468–1474 (2016).
22. eed, N. G. e history of ultraviolet germicidal irradiation for air disinfection. Public Health ep 125, 15–27 (2010).
23. Nardell, E., Vincent, . & Sliney, D. H. Upper-room ultraviolet germicidal irradiation (UVGI) for air disinfection: a symposium in
print. Photochem Photobiol 89, 764–769 (2013).
24. udnic, S. N. et al. Spatial distribution of uence rate from upper-room ultraviolet germicidal irradiation: Experimental validation
of a computer-aided design tool. HVAC& esearch 18, 774–794 (2012).
25. ahmani, B., Bhosle, S. & Zissis, G. Dielectric-Barrier-Discharge Excilamp in Mixtures of rypton and Molecular Chlorine. IEEE
Trans Plasma Sci 37, 546–550 (2009).
26. Sosnin, E. A., Avdeev, S. M., Taraseno, V. F., Saun, V. S. & Schitz, D. V. rCl barrier-discharge excilamps: Energy characteristics
and applications. Instrum Exp Tech 58, 309–318 (2015).
27. eez, M. M. & Sattar, S. A. A new ozone-based method for virus inactivation: preliminary study. Phys. Med. Biol. 42, 2027 (1997).
28. Welch, D., anders-Pehrson, G., Spotnitz, H. M. & Brenner, D. J. Unlaminated Gafchromic EBT3 Film for Ultraviolet adiation
Monitoring. adiat. Prot. Dosim. 176, 341–346 (2017).
29. Welch, D., Spotnitz, H. M. & Brenner, D. J. Measurement of UV Emission from a Diusing Optical Fiber Using adiochromic Film.
Photochem and Photobiol 93, 1509–1512 (2017).
30. Drobny, J. G. Dosimetry and adiometry. In adiation Technology for Polymers, Second Edition 215–231 (CC Press, 2010).
31. rins, A., Bolsée, D., Dörschel, B., Gillotay, D. & nusche, P. Angular Dependence of the Eciency of the UV Sensor Polysulphone
Film. adiat. Prot. Dosim. 87, 261–266 (2000).
32. Mendez, I., Peterlin, P., Hudej, ., Strojni, A. & Casar, B. On multichannel lm dosimetry with channel-independent perturbations.
Med Phys 41, 011705 (2014).
33. o, G., First, M. W. & Burge, H. A. Inuence of relative humidity on particle size and UV sensitivity of Serratia marcescens and
Mycobacterium bovis BCG aerosols. Tubercle and Lung Disease 80, 217–228 (2000).
34. Lai, . M., Burge, H. A. & First, M. W. Size and UV Germicidal Irradiation Susceptibility of Serratia marcescens when Aerosolized
from Dierent Suspending Media. Appl. Environ. Microbiol. 70, 2021–2027 (2004).
35. McDevitt, J. J. et al. Characterization of UVC Light Sensitivity of Vaccinia Virus. Appl. Environ. Microbiol. 73, 5760–5766 (2007).
36. Chao, C. Y. H. et al. Characterization of expiration air jets and droplet size distributions immediately at the mouth opening. J.
Aerosol Sci 40, 122–133 (2009).
37. Papineni, . S. & osenthal, F. S. e Size Distribution of Droplets in the Exhaled Breath of Healthy Human Subjects. J. Aerosol Med
10, 105–116 (1997).
38. Morawsa, L. et al. Size distribution and sites of origin of droplets expelled from the human respiratory tract during expiratory
activities. J. Aerosol Sci 40, 256–269 (2009).
39. Flint, S. J., acaniello, V. ., Enquist, L. W. & Sala, A. M. Principles of virology, Volume 2: pathogenesis and control, (ASM press,
2009).
40. eene, O. N. e log transformation is special. Sta t Med 14, 811–819 (1995).
41. Ihaa, . & Gentleman, . : a language for data analysis and graphics. J. Comp. Graph. Stat. 5, 299–314 (1996).
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.
Publisher's note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and
institutional aliations.
Open Access This article is licensed under a Creative Commons Attribution 4.0 International
License, which permits use, sharing, adaptation, distribution and reproduction in any medium or
format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Cre-
ative Commons license, and indicate if changes were made. e images or other third party material in this
article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the
material. If material is not included in the article’s Creative Commons license and your intended use is not per-
mitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the
copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
© e Author(s) 2018, corrected publication 2021
Content courtesy of Springer Nature, terms of use apply. Rights reserved
1.
2.
3.
4.
5.
6.
Terms and Conditions
Springer Nature journal content, brought to you courtesy of Springer Nature Customer Service Center GmbH (“Springer Nature”).
Springer Nature supports a reasonable amount of sharing of research papers by authors, subscribers and authorised users (“Users”), for small-
scale personal, non-commercial use provided that all copyright, trade and service marks and other proprietary notices are maintained. By
accessing, sharing, receiving or otherwise using the Springer Nature journal content you agree to these terms of use (“Terms”). For these
purposes, Springer Nature considers academic use (by researchers and students) to be non-commercial.
These Terms are supplementary and will apply in addition to any applicable website terms and conditions, a relevant site licence or a personal
subscription. These Terms will prevail over any conflict or ambiguity with regards to the relevant terms, a site licence or a personal subscription
(to the extent of the conflict or ambiguity only). For Creative Commons-licensed articles, the terms of the Creative Commons license used will
apply.
We collect and use personal data to provide access to the Springer Nature journal content. We may also use these personal data internally within
ResearchGate and Springer Nature and as agreed share it, in an anonymised way, for purposes of tracking, analysis and reporting. We will not
otherwise disclose your personal data outside the ResearchGate or the Springer Nature group of companies unless we have your permission as
detailed in the Privacy Policy.
While Users may use the Springer Nature journal content for small scale, personal non-commercial use, it is important to note that Users may
not:
use such content for the purpose of providing other users with access on a regular or large scale basis or as a means to circumvent access
control;
use such content where to do so would be considered a criminal or statutory offence in any jurisdiction, or gives rise to civil liability, or is
otherwise unlawful;
falsely or misleadingly imply or suggest endorsement, approval , sponsorship, or association unless explicitly agreed to by Springer Nature in
writing;
use bots or other automated methods to access the content or redirect messages
override any security feature or exclusionary protocol; or
share the content in order to create substitute for Springer Nature products or services or a systematic database of Springer Nature journal
content.
In line with the restriction against commercial use, Springer Nature does not permit the creation of a product or service that creates revenue,
royalties, rent or income from our content or its inclusion as part of a paid for service or for other commercial gain. Springer Nature journal
content cannot be used for inter-library loans and librarians may not upload Springer Nature journal content on a large scale into their, or any
other, institutional repository.
These terms of use are reviewed regularly and may be amended at any time. Springer Nature is not obligated to publish any information or
content on this website and may remove it or features or functionality at our sole discretion, at any time with or without notice. Springer Nature
may revoke this licence to you at any time and remove access to any copies of the Springer Nature journal content which have been saved.
To the fullest extent permitted by law, Springer Nature makes no warranties, representations or guarantees to Users, either express or implied
with respect to the Springer nature journal content and all parties disclaim and waive any implied warranties or warranties imposed by law,
including merchantability or fitness for any particular purpose.
Please note that these rights do not automatically extend to content, data or other material published by Springer Nature that may be licensed
from third parties.
If you would like to use or distribute our Springer Nature journal content to a wider audience or on a regular basis or in any other manner not
expressly permitted by these Terms, please contact Springer Nature at
onlineservice@springernature.com
... UVC blocks airborne and droplet-transmission respiratory tract viruses through space disinfection. UVC can efficiently disinfect viruses present in aerosol, such as coronaviruses and influenza (13,14). Previous studies have shown that UVC radiation with a wavelength of 222 nm can effectively inactivate a wide range of microbial pathogens. ...
... We confirmed the effectiveness of 222 nm UVC irradiation in disinfecting clinical antibiotic-resistant bacteria on various surfaces. Previous studies have primarily focused on the effectiveness of 222 nm UVC irradiation in deactivating respiratory pathogens that are airborne or transmitted through droplets present in aerosol, including coronavi ruses, seasonal and pandemic influenza, and tuberculosis (14,18). However, the effectiveness of 222 nm UVC irradiation against equipment-mediated bacterial diseases has not been adequately examined. ...
Article
Full-text available
In recent years, there has been a gradual increase in the prevalence of drug-resistant bacteria, primarily attributed to the widespread use of antibiotics. This has resulted in heightened mortality rates, morbidity, and exorbitant healthcare costs associated with antibiotic-resistant bacterial infections. In order to mitigate the spread of antibiotic-resistant bacteria, environmental disinfection plays a crucial role. Ultraviolet radiation C (UVC) light disinfection has emerged as a potent technique to limit the transmission of nosocomial pathogens and prevent healthcare-associated infections. Different types of high-touch surfaces were used. A serial disinfected experiment with different 222 nm UVC dosages was conducted on clinically isolated antibiotic-resistant bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus species (VRE), carbapenem-resistant Escherichia coli (CREC), carbapenem-resistant Klebsiella pneumonia (CRKP), carbapenem-resistant Acinetobacter baumannii (CRAB), and carbapenem-resistant Pseudomonas aeruginosa (CRPA) on different material surfaces. The bactericidal efficacy was evaluated by The Clinical & Laboratory Standards Institute (CLSI) guidelines. 222 nm UVC irradiation had a potent bactericidal efficacy on clinical antibiotic-resistant bacteria on different high-touch surfaces that are commonly found in the environment and healthcare facilities. 222 nm UVC irradiation time was tested from 10 s to 1 h. Different surfaces affect the efficiency of 222 nm UVC. The more adsorptive a material is, the higher the dosage of 222 nm UVC irradiation energy is required for effective disinfection. The use of 222 nm UVC lamps for disinfection on different materials has been shown to be a useful method. However, it is crucial to pay attention to the energy required for effective sterilization. IMPORTANCE This study is crucial, providing compelling evidence on Far-ultraviolet radiation C (Far-UVC) light’s efficacy against clinically significant antibiotic-resistant bacteria—a pressing issue in microbiology and infection control. Our research employs antibiotic-resistant strains from clinically isolated bacteria, emphasizing real-world relevance. Simultaneously, we assess Far-UVC light (222 nm) across diverse material surfaces commonly found in clinical settings. This dual approach ensures practical applicability and broad relevance. Our comprehensive setup and rigorous methodologies unequivocally demonstrate Far-UVC light’s potency in combating antibiotic-resistant bacteria. Since 222 nm far-UVC has a disinfection capability and is harmless to mammalian cells, this dual effectiveness positions Far-UVC as a secure tool for infection control, with potential applications in healthcare settings, mitigating antibiotic-resistant bacteria spread, and reducing healthcare-associated infections.
... Criscuolo et al. (2021) inactivated >94.4% of SARS-CoV-2 by irradiating surfaces of various materials, including glass, plastic, gauze, and wool, with 254-nm ultraviolet radiation (d = 200 mm, 1.8 mW/cm) for 15 min. Moreover, exposure to either 222-nm UVC (d = 300 mm, 48 mJ/cm 2 ) for >10 min or UVB for 14 h (90 μW/cm) has been noted to effectively inactivate influenza viruses (Sutton et al., 2013;Welch et al., 2018;Xie et al., 2022). ...
Article
Full-text available
We reviewed research on SARS-CoV-2 and influenza virus detection on surfaces, their persistence under various conditions, and response to disinfectants. Viral contamination in community and healthcare settings was analyzed, emphasizing survival on surfaces influenced by temperature, pH, and material. Findings showed higher concentrations enhance survivability at room temperature, whereas stability increases at 4°C. Both viruses decline in low pH and high heat, with influenza affected by salinity. On various material surfaces, SARS-CoV-2 and influenza viruses demonstrate considerable variations in survival durations, and SARS-CoV-2 is more stable than influenza virus. On the skin, both virus types can persist for ≥2 h. Next, we delineated the virucidal efficacy of disinfectants against SARS-CoV-2 and influenza viruses. In daily life, exposure to ethanol (70%), isopropanol (70%), bleach (10%), or hydrogen peroxide (1–3%) for 15–30 min can effectively inactive various SARS-CoV-2 variants. Povidone-iodine (1 mg/mL, 1 min) or cetylpyridinium chloride (0.1 mg/mL, 2 min) may be used to inactive different SARS-CoV-2 variants in the mouth. Chlorine disinfectants (500 mg/L) or ultraviolet light (222 nm) can effectively inhibit different SARS-CoV-2 variants in public spaces. In conclusion, our study provides a scientific basis and practical guidance for reduction of viral persistence (retention of infectivity) on surfaces and environmental cleanliness.
... This technology uses filtered krypton chloride light sources that emit light at 222 nm, with the filter blocking residual emissions outside the 222 nm peak [6]. Far-UVC irradiation has been shown to inactivate bacteria, viruses, and fungi [7][8][9], including pathogens such as influenza viruses [10] and SARS-CoV2 [11], which pose significant global health risks, particularly to the elderly [12,13]. Beyond its germicidal capabilities, far-UVC has been demonstrated to be safe for skin [14][15][16] and eyes [17,18] when applied within regulatory limits. ...
Research
Full-text available
A protocol for a controlled, phase II, multi-arm, parallel-group, superiority, six-month trial comparing the effectiveness of far-UVC (222 nm) in two experimental arms against standard care in preventing viral and bacterial infections in long-term care facilities.
Chapter
The effective use of disinfection and sterilization procedures is important in patient care and laboratory settings. Inadequate disinfection and sterilization procedures may lead to health care‐associated and laboratory‐acquired infections. This chapter also discusses international consensus standards related to disinfection and sterilization in the health care environment. Cleaning is often an essential prerequisite to disinfection or sterilization to ensure the optimal activity of the antimicrobial effects of disinfectants or sterilization processes, as well as ensuring the lack of residual materials that may have other negative impacts. There are two major considerations in the use of any disinfection or sterilization product or process: antimicrobial expectations and safety. These safety practices include cleaning and disinfection of laboratory surfaces, sterilization, and hand hygiene. The chapter considers the most widely used sterilization method for clinical laboratory applications that is heat sterilization along with a brief explanation of alternative sterilization methods.
Article
Full-text available
Maintaining the stability of environmental organisms is crucial for their survival, yet it face significant challenges due to climate change, particularly ultraviolet (UV) radiation. UV radiation can cause severe damage to DNA, and lead to morphological changes, deformities, and even death. This damage can be mitigated through the use of protective creams manufactured using nanotechnology. In this work, we investigate the effects of UV‐C radiation on earthworms, with a focus on their skin damage response. We employed histological examination and electron microscopy to study these effects in detail. Our findings reveal that earthworms display extreme sensitivity when exposed to UV‐C light. As an initial defensive response, they produce a subterranean fluid post‐autopsy. However, increased doses of UV‐C lead to tissue inflammation and subsequent death. Notably, when TiO2 nanoparticles were applied before UV‐C exposure, they effectively protected the worms from UV‐induced damage. This study provides valuable insights into the impact of UV radiation on earthworms and highlights the potential of nanotechnology in offering protection.
Article
Decontamination of the clinical working environment and reprocessing of reusable dental instruments and devices are key components of modern infection control. This narrative review, which is part of a special issue devoted to contemporary infection control practices, highlights the latest evidence and the potential role of emerging technologies. The underpinning concepts of environmental decontamination and reprocessing have remained unchanged for many years, and key principles such as cleaning before disinfection or sterilisation remain true to the present day. What has changed in recent years are the range of options available, most notably for no-touch decontamination as an adjunct to regular environmental cleaning methods, including vapourised hydrogen peroxide, hydroxyl radicals, and ultraviolet C irradiation. In the realm of sterilisation, newer approaches include solar autoclaves and hydrogen peroxide gas plasma sterilisation. With all new and emerging technologies, greater attention is now being paid to safety as well as effectiveness, with stronger consideration of environmental impacts. This is especially relevant to the use of fully disposable surgical instruments vs reusable instruments. Because dental clinics have many configurations and sizes, each clinic needs to undertake local risk assessments to inform their decisions regarding suitable decontamination and reprocessing methods.
Article
Air pollution poses the greatest risk of death for humans and has become a global cause of concern. The global population spends an average of 90% of their time indoors; therefore, the significance of indoor air quality (IAQ) on human health comes to the forefront. Most households, offices, restaurants, and other indoor places, whether in rural or urban areas, are facing the problem of indoor air pollution (IAP). This review begins by elucidating the health impact analysis of IAP and drawing parallels and distinctions between outdoor and indoor air pollution. This paper synthesizes a critical examination of existing commercial indoor air purifiers and sheds light on their limitations and drawbacks through a comprehensive review of the literature. The review then pivots toward the exploration of new technologies poised to revolutionize indoor air purification. From advanced filter manufacturing techniques to regenerating photocatalytic oxidation, this review outlines the possibilities to shape next-generation indoor air purifiers. Simultaneously, it discusses challenges holding back the integration of these technologies into commercial applications.
Article
Guidance on maximal limits for ultraviolet (UV) exposure has been developed by national and international organizations to protect against adverse effects on human skin and eyes. These guidelines consider the risk of both acute effects (i.e., erythema and photokeratitis) and delayed effects (e.g., skin and ocular cancers) when determining exposure limits, and specify the dose a person can safely receive during an 8‐h period without harmful effects. The determination of these exposure limits relies on the action spectra of photobiological responses triggered by UV radiation that quantify the effectiveness of each wavelength at eliciting each of these effects. With growing interest in using far‐UVC (200–235 nm) radiation to control the spread of airborne pathogens, recent arguments have emerged about revisiting exposure limits for UV wavelengths. However, the standard erythema action spectrum, which provides some of the quantitative basis for these limits, has not been extended below 240 nm. This study assists to expand the erythema action spectrum to far‐UVC wavelengths using a hairless albino mice model. We estimate that inducing acute effects on mouse skin with 222 nm radiation requires a dose of 1162 mJ/cm ² , well above the current ACGIH skin exposure limit of 480 mJ/cm ² .
Article
Full-text available
We have previously shown that 207-nm ultraviolet (UV) light has similar antimicrobial properties as typical germicidal UV light (254 nm), but without inducing mammalian skin damage. The biophysical rationale is based on the limited penetration distance of 207-nm light in biological samples (e.g. stratum corneum) compared with that of 254-nm light. Here we extended our previous studies to 222-nm light and tested the hypothesis that there exists a narrow wavelength window in the far-UVC region, from around 200-222 nm, which is significantly harmful to bacteria, but without damaging cells in tissues. We used a krypton-chlorine (Kr-Cl) excimer lamp that produces 222-nm UV light with a bandpass filter to remove the lower- and higher-wavelength components. Relative to respective controls, we measured: 1.in vitro killing of methicillin-resistant Staphylococcus aureus (MRSA) as a function of UV fluence; 2. yields of the main UV-associated premutagenic DNA lesions (cyclobutane pyrimidine dimers and 6-4 photoproducts) in a 3D human skin tissue model in vitro; 3. eight cellular and molecular skin damage endpoints in exposed hairless mice in vivo. Comparisons were made with results from a conventional 254-nm UV germicidal lamp used as positive control. We found that 222-nm light kills MRSA efficiently but, unlike conventional germicidal UV lamps (254 nm), it produces almost no premutagenic UV-associated DNA lesions in a 3D human skin model and it is not cytotoxic to exposed mammalian skin. As predicted by biophysical considerations and in agreement with our previous findings, far-UVC light in the range of 200-222 nm kills bacteria efficiently regardless of their drug-resistant proficiency, but without the skin damaging effects associated with conventional germicidal UV exposure.
Article
Full-text available
Tuberculosis (TB) is an airborne infectious disease caused by organisms of the Mycobacterium tuberculosis complex. Although primarily a pulmonary pathogen, M. tuberculosis can cause disease in almost any part of the body. Infection with M. tuberculosis can evolve from containment in the host, in which the bacteria are isolated within granulomas (latent TB infection), to a contagious state, in which the patient will show symptoms that can include cough, fever, night sweats and weight loss. Only active pulmonary TB is contagious. In many low-income and middle-income countries, TB continues to be a major cause of morbidity and mortality, and drug-resistant TB is a major concern in many settings. Although several new TB diagnostics have been developed, including rapid molecular tests, there is a need for simpler point-of-care tests. Treatment usually requires a prolonged course of multiple antimicrobials, stimulating efforts to develop shorter drug regimens. Although the Bacillus Calmette-Guérin (BCG) vaccine is used worldwide, mainly to prevent life-threatening TB in infants and young children, it has been ineffective in controlling the global TB epidemic. Thus, efforts are underway to develop newer vaccines with improved efficacy. New tools as well as improved programme implementation and financing are necessary to end the global TB epidemic by 2035. © 2016 Macmillan Publishers Limited, part of Springer Nature. All rights reserved.
Article
Full-text available
Background: Improving survival and extending the longevity of life for all populations requires timely, robust evidence on local mortality levels and trends. The Global Burden of Disease 2015 Study (GBD 2015) provides a comprehensive assessment of all-cause and cause-specific mortality for 249 causes in 195 countries and territories from 1980 to 2015. These results informed an in-depth investigation of observed and expected mortality patterns based on sociodemographic measures. Methods: We estimated all-cause mortality by age, sex, geography, and year using an improved analytical approach originally developed for GBD 2013 and GBD 2010. Improvements included refinements to the estimation of child and adult mortality and corresponding uncertainty, parameter selection for under-5 mortality synthesis by spatiotemporal Gaussian process regression, and sibling history data processing. 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.
Article
Full-text available
Background: UVC light generated by conventional germicidal lamps is a well-established anti-microbial modality, effective against both bacteria and viruses. However, it is a human health hazard, being both carcinogenic and cataractogenic. Earlier studies showed that single-wavelength far-UVC light (207 nm) generated by excimer lamps kills bacteria without apparent harm to human skin tissue in vitro. The biophysical explanation is that, due to its extremely short range in biological material, 207 nm UV light cannot penetrate the human stratum corneum (the outer dead-cell skin layer, thickness 5-20 μm) nor even the cytoplasm of individual human cells. By contrast, 207 nm UV light can penetrate bacteria and viruses because these cells are physically much smaller. Aims: To test the biophysically-based hypothesis that 207 nm UV light is not cytotoxic to exposed mammalian skin in vivo. Methods: Hairless mice were exposed to a bactericidal UV fluence of 157 mJ/cm2 delivered by a filtered Kr-Br excimer lamp producing monoenergetic 207-nm UV light, or delivered by a conventional 254-nm UV germicidal lamp. Sham irradiations constituted the negative control. Eight relevant cellular and molecular damage endpoints including epidermal hyperplasia, pre-mutagenic UV-associated DNA lesions, skin inflammation, and normal cell proliferation and differentiation were evaluated in mice dorsal skin harvested 48 h after UV exposure. Results: While conventional germicidal UV (254 nm) exposure produced significant effects for all the studied skin damage endpoints, the same fluence of 207 nm UV light produced results that were not statistically distinguishable from the zero exposure controls. Conclusions: As predicted by biophysical considerations and in agreement with earlier in vitro studies, 207-nm light does not appear to be significantly cytotoxic to mouse skin. These results suggest that excimer-based far-UVC light could potentially be used for its anti-microbial properties, but without the associated hazards to skin of conventional germicidal UV lamps.
Article
Full-text available
Polychromatic ultraviolet (UV) irradiation is a common method of pathogen inactivation in the water treatment industry. To improve its disinfection efficacy, more information is necessary on the mechanisms of ultraviolet inactivation on microorganisms at wavelengths throughout the germicidal UV spectrum, particularly below 240 nm. This work examined UV inactivation of the bacteriophage MS2, a common surrogate for enteric pathogens, as a function of wavelength. The bacteriophage was exposed to monochromatic UV irradiation from a tunable laser at wavelengths between 210 nm and 290 nm. To evaluate the mechanisms of UV inactivation throughout this wavelength range, RT-qPCR (Reverse Transcription quantitative Polymerase Chain Reaction) was performed to measure genomic damage for comparison with genomic damage at 253.7 nm. The results indicate that the rates of RNA damage closely mirror the loss of viral infectivity across the germicidal UV spectrum. This demonstrates that genomic damage is the dominant cause of MS2 inactivation from exposure to germicidal UV irradiation. These findings contrast those of adenovirus, for which MS2 is used as a viral surrogate when validating polychromatic UV reactors.
Article
Public health concerns such as multi- and extensive drug-resistant tuberculosis, bioterrorism, pandemic influenza, and severe acute respiratory syndrome have intensified efforts to prevent transmission of infections that are completely or partially airborne using environmental controls. One such control, ultraviolet germicidal irradiation (UVGI), has received renewed interest after decades of underutilization and neglect. With renewed interest, however, come renewed questions, especially regarding efficacy and safety. There is a long history of investigations concluding that, if used properly, UVGI can be safe and highly effective in disinfecting the air, thereby preventing transmission of a variety of airborne infections. Despite this long history, many infection control professionals are not familiar with the history of UVGI and how it has, and has not, been used safely and effectively. This article reviews that history of UVGI for air disinfection, starting with its biological basis, moving to its application in the real world, and ending with its current status.
Article
Adenovirus, a waterborne pathogen responsible for causing bronchitis, pneumonia, and gastrointestinal infections, is highly resistant to UV disinfection and therefore drives the virus disinfection regulations set by the U.S. Environmental Protection Agency. Polychromatic UV irradiation has been shown to be more effective at inactivating adenovirus and other viruses than traditional monochromatic irradiation emitted at 254 nm; the enhanced efficacy has been attributed to UV-induced damage to viral proteins. This research shows UV-induced damage to adenoviral proteins across the germicidal UV spectrum at wavelength intervals between 200 and 300 nm. A deuterium lamp with bandpass filters and UV light emitting diodes (UV LEDs) isolated wavelengths in approximate 10 nm intervals. SDS-PAGE (sodium dodecyl sulfate polyacrylamide gel electrophoresis) and image densitometry were used to detect signatures for the hexon, penton, fiber, minor capsid, and core proteins. The greatest loss of protein signature, indicating damage to viral proteins, occurred below 240 nm. Hexon and penton proteins exposed to a dose of 28 mJ/cm2 emitted at 214 nm were approximately four times as sensitive, and fiber proteins approximately three times as sensitive, as those exposed to a dose of 50 mJ/cm2 emitted at 254 nm. At 220 nm, a dose of 38 mJ/cm2 reduced the hexon and penton protein quantities to approximately 33% and 31% of the original amount, respectively. In contrast, a much higher dose of 400 mJ/cm2 emitted at 261 nm, and 278 nm reduced the original protein quantity to between 66 - 89%, and 80 - 93% respectively. No significant damage was seen by 400 mJ/cm2 at 254 nm. This research directly correlates enhanced inactivation at low wavelengths with adenoviral protein damage at those wavelengths, adding fundamental insight into the mechanisms of inactivation of polychromatic germicidal UV irradiation for improving UV water disinfection.
Article
Analysis of the emission pattern from optical diffuser tips is vital to their usage in biomedical applications, especially as they find growing functionality beyond established phototherapy techniques. The use of ultraviolet radiation with diffuser tips increases the need to accurately characterize these devices, both for effective application and to avoid potentially dangerous exposure conditions. This work presents a new method to capture the diffusion pattern at a high resolution through the use of radiochromic film. The film is positioned in a cylinder around the diffuser, light is emitted from the diffuser onto the film, and the film expresses a color change relative to the exposure amount. The resulting emission map shows the distribution of power from the diffuser in all direction. This method, which is both quick and inexpensive, generates high resolution data much simpler than previously published works which required precise goniometric positioning. This article is protected by copyright. All rights reserved.
Article
Measurement of ultraviolet (UV) radiation is important for human health, especially with the expanded usage of short wavelength UV for sterilization purposes. This work examines unlaminated Gafchromic EBT3 film for UV radiation monitoring. The authors exposed the film to select wavelengths in the UV spectrum, ranging from 207 to 328 nm, and measured the change in optical density. The response of the film is wavelength dependent, and of the wavelengths tested, the film was most sensitive to 254 nm light, with measurable values as low as 10 µJ/cm2. The film shows a dose-dependent response that extends over more than four orders of magnitude. The response of the film to short wavelength UV is comparable to the daily safe exposure limits for humans, thus making it valuable as a tool for passive UV radiation monitoring.
Article
Influenza is an acute respiratory illness, caused by influenza A, B, and C viruses, that occurs in local outbreaks or seasonal epidemics. Clinical illness follows a short incubation period and presentation ranges from asymptomatic to fulminant, depending on the characteristics of both the virus and the individual host. Influenza A viruses can also cause sporadic infections or spread worldwide in a pandemic when novel strains emerge in the human population from an animal host. New approaches to influenza prevention and treatment for management of both seasonal influenza epidemics and pandemics are desirable. In this Seminar, we discuss the clinical presentation, transmission, diagnosis, management, and prevention of seasonal influenza infection. We also review the animal–human interface of influenza, with a focus on current pandemic threats.