Ebola virus (EV) is a filovirus which causes viral haemorrhagic fever (VHF) in humans
(World Health Organization (WHO), 2014a). Fruit bats of the family Pteropodidae are
thought to be the natural reservoir and humans are thought to acquire the disease
through direct contact with non-human primates (NHP) (Leroy et al., 2005). The first
cases of Ebola virus disease (EVD) were reported in 1976 in the Democratic Republic
of Congo and since then sporadic cases and small scale outbreaks have occurred in
central African countries (World Health Organization, 2014d, World Health Organization,
2014e, World Health Organization, 2014f). There are five strains of EV but the Zaire
strain is the most severe, with a case-fatality rate up to 90% (World Health Organization
(WHO), 2014a). The unprecedented scale of the current outbreak of EVD in Sierra Leone,
Guinea, Liberia and Nigeria, led to the World Health Organization, 2014d, World Health
Organization, 2014e, World Health Organization, 2014f declaring an international public
health emergency on August 8th 2014. The outbreak has since spread to Senegal, and
a reportedly unrelated outbreak has since occurred in the Democratic Republic of Congo
(World Health Organization (WHO), 2014b). As of 22nd August 2014, the West African
outbreak has resulted in 2615 cases and 1427 deaths and is unprecedented because it
has continued for more than double the length of time of the largest previous outbreak
in Uganda in 2000 (3 months vs. 8 months), has resulted in more than six times as
many cases (425 cases vs. 2615 cases), and has for first time occurred in more than
one country simultaneously and in capital cities (Okware et al., 2002, World Health
Organization, 2014d, World Health Organization, 2014e, World Health Organization,
2014f). Among the total cases, 1251 have been laboratory confirmed, and genetic sequencing
has showed that the similarity of the virus to the Zaire EV is 97% (Baize et al.,
2014). Unlike past outbreaks, the current outbreak of EVD has not been contained and
has resulted in social unrest, breakdown in law and order, shortages of personal protective
equipment (PPE) and depletion of the healthcare workforce, with over 240 healthcare
workers (HCWs) becoming infected and 120 HCW deaths as of 25th August 2014 (World
Health Organization (WHO), 2014c). The inability to contain this outbreak has been
blamed variously on lapses in infection control, shortages of PPE and other supplies,
myths and misconceptions about EVD, and the fact that it is occurring in large cities
rather than small villages.
HCWs, many of whom are nurses, are on the frontline of the response, and their occupational
health and safety is critical to control of the outbreak and maintenance of the health
workforce during a crisis. The WHO, the US Centers for Disease Control (1998) and
several other countries recommend surgical masks for HCWs treating Ebola (Centers
for Disease Control and Prevention, 2014a, Centers for Disease Control and Prevention,
2014b, Centers for Disease Control and Prevention, 2014c, World Health Organization,
2014d, World Health Organization, 2014e, World Health Organization, 2014f) whilst
other countries (The Department of Health UK, 2014) and Médecins Sans Frontières (MSF)
have recommend the use of respirators (Sterk, 2008) (Table 1
). We question the recommendations for surgical masks and outline evidence on the
use of respiratory protection for HCWs, and the issues that must be considered when
selecting the most appropriate type of protection.
Table 1
Recommendations around the use of mask/respirators to protect healthcare workers from
Ebola Virus Disease (EVD).
Organization/country
Developed by/year
Type of HCWs
Recommendation
WHO
World Health Organization (World Health Organization, 2014d, World Health Organization,
2014e, World Health Organization, 2014f)
Hospital HCWs
Routine care - Medical masksAGPs – N95 respirators or powered air purifying respirators
(PAPRs).
World Health Organization (World Health Organization, 2014d, World Health Organization,
2014e, World Health Organization, 2014f)
Lab workers
N95 respirators or powered air purifying respirators (PAPRs).
CDC US
Centers for Disease Control and Prevention (CDC) August 2014 (Centers for Disease
Control and Prevention (CDC))
Hospital HCWs
Routine care – Medical masks Fit-tested AGPs – N95 filtering face piece respirators
or higher (e.g., powered air purifying respiratory or elastomeric respirators)
Centers for Disease Control and Prevention (CDC) August 2014 (Centers for Disease
Control and Prevention (CDC))
Lab workers
Appropriate respirators or a full body suit
WHO/CDC
World Health Organization and Centers for Disease Control and Prevention (CDC) December
1998 (Centers for Disease Control and Prevention and World Health Organization)
Hospital HCWs and Lab workers
Respirators were recommended for HCWs. Medical and cloth masks were also recommended
in cases respirators were not available
MSF
Médecins Sans Frontières (MSF) 2007 (Sterk, 2008)
Hospital HCWs and Lab workers
High Efficiency Particulate filtration (HEPA) masks
Australia
The Department of Health, August 2014 (The Department of Health. Australia 2014)
Hospital HCWS
Routine care – Medical masksAGPs - P2 (N95) respirators
Department of Health, September 2005 (The Department of Health Australia, 2014)
Lab workers
P2 (N95) respirators
United Kingdom (UK)
Department of Health August 2014 (The Department of Health UK, 2014)
Hospital HCWs and Lab workers
Low possibility of VHF infection – Medical masksHigh possibility of VHF infection
but patient does NOT have extensive bruising, active bleeding, uncontrolled diarrhoea,
uncontrolled vomiting – Medical masksHigh possibility of VHF infection but patient
does have extensive bruising, active bleeding, uncontrolled diarrhoea, uncontrolled
vomiting – FFP3 respiratorsConfirmed VHF infection or AGPs in any situation – FFP3
respirators
Canada
Public Health Agency of Canada, August 2014 (Public Health Agency of Canada, 2014b)
Hospital HCWS
Medical masks; fit-tested respirators (seal-checked NIOSH approved N95 at a minimum)
for AGPs
Public Health Agency of CanadaAugust 2014 (Public Health Agency of Canada, 2014a)
Lab workers
Particulate respirators (e.g., N95, or N100) or powered air purifying respirators
(PAPRs)
Belgium
Superior Health Council July 2014 (Superior Health Council, Belgium 2014)
Hospital HCWs and Lab workers
Patients categorized as ‘possibility of EMD – Surgical mask for routine care and FFP3
respirator or EN certified equivalent for AGPsPatients categorized as ‘high possibility’
or ‘confirmed EMD’ – FFP3 respirators
South Africa
Department of Health (Draft guidelines) August 2014 (Department of Health, South Africa
2014)
Hospital HCWS
Preferably N95 respirators
CDC = Centers for Disease Control; HCW = Health Care Workers; MSF = Médecins Sans
Frontières; WHO = World Health Organization.
1
Background controversy about face masks
There is ongoing debate and lack of consensus around the use of respiratory protection
for HCWs for respiratory diseases, including influenza, which is reflected in inconsistencies
between policies and guidelines across healthcare organizations and countries (Chughtai
et al., 2013). In the healthcare setting facemasks (medical/surgical masks) are generally
used to protect wearers from splashes and sprays of blood or body fluids and to prevent
spread of infection from the wearer, while a respirator is intended for respiratory
protection (Siegel et al., 2007). The mode of disease transmission is one factor which
influences the selection of facemasks or respirators – for example, facemasks are
recommended for infections transmitted through contact and droplets, while respirators
are recommended for airborne infections. Such guidelines are based on often tenuous
theoretical principles informed by limited experimental evidence, given the lack of
data drawn from the complex clinical environment. Transmission is not fully elucidated
for many infections, spread can occur by multiple modes and the relative contribution
of each mode may not be precisely quantified. Further, host related factors can mediate
the severity of the disease. Some diseases exclusively transmit through the airborne
route in natural setting (e.g. tuberculosis), while other diseases mainly transmit
through the droplet or contact modes but short range respiratory aerosols are generated
during high risk procedures which increases the risk of infection transmission (Roy
and Milton, 2004). For example, the primary mode of influenza transmission is thought
to be droplet (reflected in guidelines which largely recommend surgical masks), but
there is increasing evidence that it is also spread by short-range respiratory aerosols
(Bischoff et al., 2013, Tellier, 2009). For Severe Acute Respiratory Syndrome (SARS),
data supported both droplet and airborne transmission (Centers for Disease Control
and Prevention, 2014a, Centers for Disease Control and Prevention, 2014b, Centers
for Disease Control and Prevention, 2014c, Yu et al., 2004). Airborne precautions
have even been recommended for measles and varicella-zoster viruses despite a lack
of data (Siegel et al., 2007).
To date, only four randomized controlled clinical trials (RCTs) and five papers on
the clinical efficacy of facemasks in the healthcare setting have been published (Jacobs
et al., 2009, Loeb et al., 2009, MacIntyre et al., 2011, MacIntyre et al., 2013, MacIntyre
et al., 2014b). One of these had only 32 subjects (Jacobs et al., 2009), and one had
446 subjects (Loeb et al., 2009). The largest RCTs conducted (by authors CRM, HS and
colleagues) on N95 respirators and masks, with 1669 and 1441 subjects, respectively,
showed a benefit associated with using N95 respirators and failed to show any benefit
of surgical masks (MacIntyre et al., 2011, MacIntyre et al., 2013). In one of the
trials, the majority of laboratory confirmed infections were with respiratory syncytial
virus and influenza, neither of which are thought to be predominantly airborne (MacIntyre
et al., 2013). These data support the concept that transmission of viruses is multimodal
and caution against dogmatic paradigms about pathogens and their transmission, particularly
when the disease in question has a high case-fatality rate and no proven pharmaceutical
interventions.
Respirators are designed for respiratory protection and are indicated for infections
transmitted by aerosols (MacIntyre et al., 2011, MacIntyre et al., 2013). However,
this is based purely on the fact that they have superior filtration capacity, and
can filter smaller particles. The guidelines fail to consider that respirators offer
the additional benefit of being fitted, therefore creating a seal around the face.
It is also possible that the seal achieved by a respirator may be an additional benefit
over and above the superior filtration that they offer. Respirators are not regulated
by fit however, only on filtration capacity (with filtration of airborne particles
being the sole consideration in guidelines), but the seal offered by a respirator
adds to the protection when compared to other mask types. The risk of infection with
respiratory pathogens increases three-fold during aerosol-generating procedures (AGPs)
such as intubation and mechanical ventilation (MacIntyre et al., 2014a). Respirators
are generally recommended in these situations for diseases that are known to be transmitted
though the droplet route such as influenza and SARS (Chughtai et al., 2013), so the
fact that they are not recommended more broadly for a disease with a much higher case-fatality
rate such as EVD, is concerning.
2
Modes of transmission of Ebola
The inability to control the West African Ebola outbreak has led to debate around
the mode of transmission of EV, with some public health agencies suggesting aerosol
transmission (Murray et al., 2010). Current evidence suggests that human to human
transmission occurs predominantly though direct contact with blood and body secretions,
(World Health Organization (WHO), 2014a) and this is the basis of the WHO and the
CDC recommendations for facemasks to protect HCWs from EVD.
However, like influenza and SARS, there is some evidence of aerosol transmission of
EVD. In an observational study from The Democratic Republic of Congo, of the 19 EVD
cases who visited the home of an EVD patient, 14 had contact with the infected case
while the remaining five had no history of any contact, which points to transmission
through some other mode (Roels et al., 1999). There is some evidence from experimental
animal studies that EVD can be transmitted without direct contact; however these studies
generally do not differentiate between droplet and airborne transmission (Dalgard
et al., 1992, Jaax et al., 1995, Johnson et al., 1995). In one study, six monkeys
were divided into three groups and each group was exposed to low-dose or high-dose
aerosolized EV and aerosolized uninfected cell culture fluid (control), respectively.
All four monkeys exposed to EV developed infection (Johnson et al., 1995). Jaax et
al. found that two of three control monkeys caged in the same room as monkeys with
EVD, 3 m apart, died of EVD (Jaax et al., 1995).
Studies have also shown that pigs may transmit EV though direct contact or respiratory
aerosols (Kobinger et al., 2011). In one study, monkeys without direct contact contracted
EBV from infected pigs in separate enclosures (Weingartl et al., 2012). It was not
clear whether transmission was due to respiratory aerosols or large droplets. The
first infection occurred in a monkey caged near the air ventilation system and positive
air samples identified through real time polymerase chain reaction (PCR), which raised
the possibility of airborne transmission. However, pigs cough and sneeze more than
humans and thus have more capacity to generate aerosols. Furthermore, in pigs EVD
mainly affects the lungs while in primates, it mainly affects the gastrointestinal
tract and is excreted in the faeces. As with influenza, the transmission characteristics
of EVD may also change due to temperature and humidity, and it should be noted that
the experimental studies on EV transmission were conducted at low temperature and
humidity, which might have favoured aerosol transmission. A recent study has shown
that nonhuman primate to nonhuman primate transmission is mainly through contact,
with airborne transmission being unlikely (Alimonti et al., 2014).
Finally it must be emphasized that EV transmission in high-risk situations is not
well studied, particularly during AGPs, in the handling of human remains or exposure
to surgical smoke due to new surgical technologies like laser or diathermy. Although
the CDC does recommend a respirator during AGPs for EVD patients, aerosols may be
created in the absence of aerosol-generating procedures. Evidence suggests that aerosols
from vomitus can transmit norovirus, and SARS was likely transmitted via faecal aerosols
(Barker et al., 2004, Marks et al., 2003, McKinney et al., 2006, Yu et al., 2004).
Staff contacts of two HCWs infected with Ebola in 1996, who were treated in South
Africa, took universal precautions, with respirators used for high-risk procedures,
and no further cases occurred in 300 potential contacts (Richards et al., 2000). The
report of this outbreak (by author GAR) has been cited in support of the WHO and CDC
guidelines (Klompas et al., 2014), however in South Africa one HCW contracted EBV
when using normal surgical attire during placement of a central line in a patient
with undiagnosed EBV. This occurred despite no obvious lapse in infection control.
In contrast, once EBV had been diagnosed in the HCW, respirators, impermeable one-piece
suits and visors were used (according to South African guidelines), and no further
infections occurred despite procedures such as intubation, mechanical ventilation,
dialysis, central line placement and the insertion of a Swan Ganz catheter (Richards
et al., 2000).
3
Factors to consider in guidelines
When determining recommendations for the protection of HCWs, guidelines should not
be based solely on one parameter, the presumed mode of transmission. A risk-analysis
approach is required that takes into account all relevant factors which could impact
on the occupational health and safety of HCWs (Fig. 1
). The severity of the outcome (case-fatality rate and disease severity) must be considered.
Any level of uncertainty around modes of transmission must also be evaluated, particularly
if the disease has a high case-fatality rate. In addition, the availability of pre-
and post-exposure prophylaxis or treatment must be considered. The immune status and
co-morbidities in HCWs should also be considered, as some HCWs may be innately more
vulnerable to infection. As the ageing of the nursing workforce occurs in developed
countries, there is likely to be a high proportion of HCWs with chronic conditions.
In this case, facemasks have been recommended for HCWs by CDC and WHO because of the
assumption that EV is not transmitted via the airborne route. However, there is uncertainty
about transmission, the consequences of EVD infection are severe, there is no proven
treatment, vaccine or post-exposure prophylaxis. Recommending a surgical mask for
EVD has much more serious implications than for influenza, which has a far lower case-fatality
rate and for which there are easily accessible vaccines and antiviral therapy. Further,
numerous HCWs have succumbed to EVD during this epidemic, including senior physicians
experienced in treating EVD and presumably less likely to have suffered lapses in
infection control (World Health Organization, 2014d, World Health Organization, 2014e,
World Health Organization, 2014f). Aside from these factors, it is also important
to consider the perspectives of the staff member. In this highly stressful situation,
staff members will want to be reassured that they are using the highest level of protection
and are not putting themselves and their families/colleagues at risk. This is especially
important if the outbreak escalates and additional staff members are required to assist.
Staff may refuse to treat patients unless they feel adequately protected.
Fig. 1
Factors to consider in making recommendations for respiratory protection of health
workers*. *Cost, supply and logistics may affect implementation of guidelines, but
should not drive recommendations for best practice.
We feel the recommendations for masks do not apply risk analysis methods appropriately,
and are solely based on the low probability of non-contact modes of EV spread. Previous
guidance provided by the WHO and CDC for “Infection Control for Viral Haemorrhagic
Fevers in the African Health Care Setting” in 1999 were more conservative, with both
organizations recommending the preferred use of respirators first line and surgical
masks and cloth masks as a last option (Centers for Disease Control, 1998). Why then,
during the worst outbreak of EVD in history, with the most virulent EV strain and
with hundreds of HCWs succumbing to the disease is it considered adequate for them
to wear surgical masks? The high case-fatality rate warrants the use of better protection
such as a respirator and full body suit with face shield, where it can be provided.
4
Consistency of guidelines
There appears to be a double standard in recommendations for laboratory scientists
working with EV, who must adhere to the highest level of biocontainment (BSL4) when
working with the virus. (Centers for Disease Control and Prevention, 2014a, Centers
for Disease Control and Prevention, 2014b, Centers for Disease Control and Prevention,
2014c, Department of Health and Aging Australia, 2007) Further, in contrast to HCWs,
laboratory workers are exposed to the virus in a highly controlled, sterile environment
in which there is less risk of transmission than in the highly unstable, contaminated
and unpredictable clinical environment. The perceived inequity inherent in these inconsistent
guidelines may also reduce the willingness of HCWs to work during an EVD outbreak.
Table 1 shows recommendations of the selected organizations and countries regarding
the use of masks/respirators for EVD for HCWs and laboratory workers. Only the UK
and South African guidelines have consistent guidelines for HCWs and laboratory scientists,
with respirators recommended for confirmed cases of Viral Haemorrhagic Fever (including
EVD) (Department of Health, 2014, Superior Health Council, 2014, The Department of
Health UK, 2014). Among healthcare organizations, only MSF recommends respirators
for EVD, and notably, in contrast to other international agencies including WHO, no
MSF worker has developed EVD during the West African outbreak (Thomson, 2007).
In conclusion, whilst EV is predominantly spread by contact with blood and body fluids,
there is some uncertainty about the potential for aerosol transmission. There is RCT
evidence for respirators (but not masks) providing protection against non-aerosolised
infections, (MacIntyre et al., 2013) and an abundance of evidence that transmission
of pathogens in the clinical setting is rarely unimodal. Where uncertainty exists,
the precautionary principle (that action to reduce risk should not await scientific
certainty) should be invoked and guidelines should be consistent and err on the side
of caution. Moreover, a clear description of risk should be provided to HCWs (Jackson
et al., 2014). Given the predominant mode of transmission, every HCW death from Ebola
is a potentially preventable death. It is highly concerning that a recent commentary
suggests HCWs do not need a mask at all “to speak with conscious patients, as long
as a distance of 1–2 metres is maintained”(Martin-Moreno et al., 2014). This fails
to consider the changeability and unpredictability of the clinical environment and
disregards the rights of the HCW. It is also unrealistic to believe a HCW can constantly
keep track of their distance from a patient in the hectic acute care setting. We accept
that cost, supply and logistics may, in some settings, preclude the use of respirators,
but guidelines should outline best practice in the ideal setting, with discussion
about contingency plans should the ideal recommendation be unfeasible. Importantly,
in the absence of sufficient evidence, recommendations should be conservative and
estimation of risk considered. Recommendations should be developed using a risk analysis
framework, with the occupational health and safety of HCWs being the primary consideration.
Conflict of interest statement
CR MacIntyre has conducted several investigator-driven trials of respirators vs face
masks, one of which was funded by an Australian Research Council Linkage Grant, where
the industry partner was 3M, a manufacturer of PPE. 3M also provided supplies of surgical
masks and respirators for the investigator-driven trials in health workers in China.
H Seale was also involved in this research as a co-investigator. A Chugtai has had
filtration testing of masks for his PhD thesis conducted by 3M Australia.