Introduction
Traditionally, the epidemiological control of most viral infections depends on the
isolation of cases, quarantine of contacts, personal protection by infection control
measures, and mass vaccination, because specific antiviral treatment is generally
not available for most viral infections (Table 1
). This scenario is rapidly changing with the increasing availability of rapid diagnostic
tests that use nucleic acid amplification and the development of increasing number
of effective antiviral agents. Common acute viral diseases such as respiratory, diarrheal,
exanthematous, or neurological infections can overlap with each other and appear as
seasonal epidemics that peak in incidence every few years and coincide with the accumulation
of sufficient number of nonimmune hosts in the young population. Arboviral disease
activity often coincides with arthropod vector activity such as mosquito breeding
in hot rainy seasons that are associated with increased incidence of hemorrhagic fever
or neurological diseases such as dengue hemorrhagic fever, West Nile virus, or Japanese
encephalitis in Southeast Asia. Many chronic blood-borne viral illnesses such as human
immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV)
are still taking a major toll in certain geographic regions due to specific human
behaviors or vertical transmission. Some of these chronic viral infections such as
HBV, HCV, HIV, polyomaviruses, and papillomaviruses are also linked to the genesis
of cancers. Over 70% of emerging viral infections such as the Ebola virus, severe
acute respiratory syndrome (SARS) coronavirus, and Middle East respiratory syndrome
(MERS) coronavirus are associated with acute explosive outbreaks after the virus jumps
the species barrier from bats or other animals to human (Table 2
). This chapter will focus on the prevention and control of viral infections, while
other article in this book will cover information on specific viruses.
Table 1
Common human viral infections
Major viral families
Viruses within the family
Modes of transmission
Major clinical syndrome
Diagnostic methods
Antiviral treatment
Vaccine prevention
Herpesviridae
HSV-1, HSV-2VZVEBVCMVHHV-6, HHV-7HHV-8
Contact/dropletsAirborne (VZV)
Oral/genital herpesChickenpox/shinglesInfectious mononucleosisRoseola infantumKaposi's
sarcomaEncephalitis (HSV, VSV)
Viral culture/PCR/serologyCMVpp65
Acyclovir, valacyclovir (HSV, VZV, HHV-8)Ganciclovir, valganciclovir, foscarnet, cidofovir
(CMV, HHV-8)Imiquimod (HHV-8)
Varicella (VZV) vaccine
Orthomyxoviridae
Influenza AInfluenza BInfluenza C
Contact/droplets
Upper respiratory tract infectionPneumoniaPneumonitisEncephalitisPericarditis/myocarditis
Viral culture/PCR/serologyImmunofluorescent staining
Neuraminidase inhibitors (oseltamivir, zanamivir, peramivir) for influenza A or BM2
inhibitors (amantadine, rimantadine)Favipiravir
Seasonal trivalent or quadrivalent influenza vaccine (e.g., H1N1, H3N2, B)Monovalent
influenza vaccine (H5N1, H7N9)
Filoviridae
EbolavirusMarburgvirus
Contact
Viral hemorrhagic fever
Viral culture/PCR/serology
None
Ebola vaccine (phase II/III trial)
Picornaviridae
Enterovirus
Droplets
Hand, foot, and mouth disease, respiratory illness, aseptic meningitis, and myocarditis
Viral culture/PCR/serology
None
None
Hepatovirus
Hepatitis A infection
Hepatitis A vaccine
Poliovirus
Poliomyelitis
Oral polio vaccine
Rhinovirus
Upper respiratory tract infection
None
Rhabdoviridae
Rabies virus
Contact
Rabies
Viral culture/PCR/serology
Human rabies immunoglobulin
Rabies vaccine
Flaviviridae
Dengue virusJapanese encephalitis virusSt. Louis encephalitis virusTick-borne encephalitis
virusWest Nile virusYellow fever virusHepatitis C virus
ArthropodBlood-to-blood contact (hepatitis C)
Hemorrhagic feverAcute and chronic hepatitis (HCV)
Viral culture/PCR/serology
NonePolymerase/protease inhibitors/ribavirin/pegylated interferon (HCV)
Dengue vaccine (phase III)Yellow fever vaccine
Paramyxoviridae
Measles virusMumps virusHuman parainfluenza virusHuman metapneumovirus
Droplets
MeaslesMumpsUpper respiratory tract infectionPneumonia
Viral culture/PCR/serology
None
MMR vaccine (measles, mumps)
Togaviridae
Rubella virusChikungunya virusEquine encephalitis virus
DropletsArthropod (Chikungunya virus/equine encephalitis virus)
RubellaChikungunya disease
Viral culture/PCR/serology
None
MMR vaccine (rubella)
Retroviridae
HIV-1, HIV-2
Body fluid/blood contact
Acquired immune deficiency syndrome
Viral culture/PCR/serology
HAART
None
Hepadnaviridae
Hepatitis B virus
Body fluid/blood contact
Acute and chronic hepatitis B
Viral culture/PCR/serology
Nucleoside and nucleotide analogHepatitis B immunoglobulin
Hepatitis B vaccine
Hepeviridae
Hepatitis E virus
Fecal–oral route
Acute hepatitis E
Viral culture/PCR/serology
None
None
Reoviridae
Rotavirus
Fecal–oral route
Gastroenteritis
Viral culture/PCR
None
Rotavirus vaccine
Coronaviridae
Human coronavirus
Droplets
Upper respiratory tract infection, pneumonia
Viral culture/PCR
None
None
Papillomaviridae
Human papillomavirus
Contact
Warts
Viral culture/PCR
Imiquimod
HPV vaccine
Table 2
Examples of outbreaks of emerging viral infections with bats as the most likely natural
reservoir
Viral agent
Intermediate or amplification hosts
At-risk population
Epicenter for animal to human transmission
Reference
SARS-CoV
Palm civets
Wet market workers
Wet markets (healthcare facilities and household)
Guan et al. (2003) and Lau et al. (2005)
MERS-CoV
Dromedary camels
Close contact with camel
Camel farm (healthcare facilities and household)
(Woo et al., 2014)
Ebola virus
Nonhuman primates
Bush meat hunters, healthcare workers, and family/community members with exposure
Forests (healthcare facilities and household)
Feldmann et al. (2003)
Nipah virus
Pigs
Pig farmers and abattoir workers
Pig farms and abattoirs (healthcare facilities)
Goh et al. (2000)
Hendra virus
Horses
Close contact with horses
Horse farms
Halpin et al. (2000) and Hooper et al. (2000)
Rabies virus
Nil (direct bat to human transmission)
Scientists and personnel handling bats
Rural residents with contact with bats (organ transplantation)
Dietzschold and Koprowski (2004) and Kusne and Smilack (2005)
Diagnostic Approaches for Viral Illness
Unlike bacteria, fungi, and parasites, viruses are too small to be visible under light
microscopy. Moreover, viruses are obligate intracellular pathogens and do not grow
in artificial culture medium. Collecting the correct clinical specimens during the
peak of viral shedding in appropriate viral transport medium is crucial for accurate
diagnosis. Electron microscopy is not sensitive and has a limited role in the examination
of feces from viral gastroenteritis and vesicular fluid from skin lesions caused by
herpesviruses and poxviruses. Virus isolation in cell lines or chick embryo is the
gold standard for virological diagnosis but seldom alters clinical management due
to its long turnaround time. Viral antigen detection by immunofluorescence, enzyme
immunoassay, and point-of-care rapid lateral flow immunochromatographic assays has
significant impact on therapeutic and infection control strategies.
The most important rapid virological tests are nucleic acid amplification tests such
as real-time or multiplex reverse transcription-polymerase chain reaction (RT-PCR)
assays that are useful for accurate diagnosis and subsequent viral load monitoring
during antiviral treatment. Genotyping by nucleic acid amplification and sequencing
for detection of mutations associated with antiviral resistance directly from clinical
specimens is now available for many antiviral agents and is routine for antiretroviral
drugs used to treat HIV infection. Though nucleic acid amplification tests still have
practical limitations in the field settings of developing areas, such tests are now
routine in most hospitals in developed countries. Antibody testing by enzyme immunoassay
for IgM in acute infection, IgG for immune status of exposed individuals, and retrospective
diagnosis by the presence of rising antibody titers in paired acute and convalescent
sera of symptomatic patients is useful for making clinical and epidemiological decisions.
Antibody screening is especially important in antenatal visits of expectant mothers,
blood donors, and organ donor and recipients before transplantation. Next-generation
sequencing performed directly on clinical specimens may revolutionize virological
diagnosis in the coming decade. The timely and accurate diagnosis of viral infections
has important implications for effective epidemiological control in the community
and infection control for hospital outbreaks.
Viral Transmission and Infection Control Prevention for Blood-Borne Viruses Including
HIV, HBV, and HCV
Transmission of blood-borne viruses can result from sexual intercourse and maternal–fetal
transmission in the community setting and needlestick injury and other exposure-prone
procedures in the healthcare setting. In a study from the United States, the annual
death rate of healthcare workers from occupational events was estimated to be 17–57
per 1 million workers, and most of these deaths resulted from infection-related complications
of blood-borne viruses (Sepkowitz and Eisenberg, 2005). The overall risk of transmission
of blood-borne viruses by hollow needlestick injury is 33%, 3%, and 0.3% if the source
is a hepatitis carrier with positive HBe antigen or high viral load, hepatitis C carrier
with RNAaemia, and HIV, respectively. Compliance with standard precautions including
wearing gloves when handling blood during patient care practice, disposing sharp and
needles into puncture-resistant box, and avoidance of recapping needles remains the
most important way to prevent nosocomial acquisition of blood-borne viruses (Garner,
1996).
Active immunization for HBV can protect healthcare workers from HBV infection with
an efficacy of 80–95% (Dienstag et al., 1984, Sabido et al., 2007, Shim et al., 2011).
Postimmunization anti-HBs antibody level should be measured at 4–8 weeks after completion
of the 3-dose immunization regimen given at baseline, 1 month, and 6 months. A good
responder is defined as a person whose anti-HBs antibody level is > 100 IU l− 1. If
the hepatitis B antibody level is between 10 and 100 IU l− 1, a booster dose of vaccine
should be given. For nonresponders whose anti-HBs antibody is < 10 IU l− 1, another
course of HBV vaccine should be given. The response rate is about 61% in repeated
HBV vaccination by the same route as the initial vaccination (Struve et al., 1994).
Alternatively, immunization with high-dose intradermal recombinant HBV vaccine, given
in up to four doses, can achieve immunity in 88% of healthcare workers who failed
to respond to intramuscular vaccination and boosters (Levitz et al., 1995). The anti-HBs
titer was persistently higher than the protective level for at least 10 years after
primary HBV vaccination (Floreani et al., 2004).
When a healthcare worker sustains a needlestick injury, he or she should be advised
to rinse the wound with tap water and allow natural bleeding. The source patient's
blood is collected to check for the presence of HIV, HBV, and HCV. If the status of
blood-borne viruses of the source patient is positive or unknown, postexposure prophylaxis
(PEP) should be offered according to current guidelines (Kuhar et al., 2013). The
exposed healthcare worker will be closely followed up for counseling, baseline, and
HIV testing and monitored for drug toxicity. If a newer fourth-generation combination
HIV p24 antigen–HIV antibody test is utilized for follow-up HIV testing, HIV testing
may be concluded 4 months after exposure. Otherwise, follow-up HIV testing is performed
6 months after the exposure (Kuhar et al., 2013). For HBV, PEP with hepatitis B immune
globulin (HBIG) and/or HBV vaccination should be considered for occupational exposures
after evaluation of the HBsAg status of the source and the vaccination and vaccine-response
status of the exposed person (2001). For HCV, PEP is not currently recommended. However,
an open-label pilot trial was conducted to determine the safety, tolerability, and
acceptance of peginterferon alfa-2b as PEP. Among 213 healthcare workers exposed to
an HCV antibody-positive source, 51 HCWs enrolled in the study and 44 (86%) elected
to undergo peginterferon alfa-2b as the study group. Seven subjects elected not to
undergo PEP were treated as the control group. In this pilot study, peginterferon
alfa-2b was proved to be safe without serious adverse side effects. However, the lack
of HCV transmission in both the study and control groups did not support the routine
use of PEP in healthcare workers after HCV exposure (Corey et al., 2009). It is likely
that the new polymerase and protease inhibitors used in the treatment of HCV infection
will result in new strategies for PEP of HCV exposures.
Blood-borne viruses can also be transmitted from healthcare workers to patients, especially
during exposure-prone procedures in dental and cardiothoracic operations. The most
well-known example involved an HIV-positive dentist working in Florida, the United
States, who infected five of his patients after performing invasive dental procedures
on them (Ciesielski et al., 1992). Sequencing of the HIV proviral envelope gene showed
that the viruses infecting the dentist and the five patients were closely related
(Ou et al., 1992). However, the overall risk for transmission of HIV from a healthcare
worker to a patient is very small. In a study conducted by the Centers for Disease
Control and Prevention (CDC) of 22 171 patients being cared by 51 HIV-positive healthcare
workers, 113 (0.5%) patients became HIV-positive. Epidemiological investigation did
not implicate healthcare workers as the source of infection in any of these patients
(Robert et al., 1995). In contrast, transmission of HBV and HCV from healthcare workers
to patients was more frequently documented. Between August 1991 and July 1992, 19
of 144 (13%) patients who were operated on by a thoracic surgeon with acute HBV infection
became HBV-infected. Sequencing of 160 bases in the core region of HBV showed an indistinguishable
pattern among the strains of the surgeon and nine infected patients (Harpaz et al.,
1996). Subsequently, numerous healthcare worker-to-patient transmissions of HBV and
HCV were reported. Among all these reported cases, the viral loads of the index healthcare
workers were more than 106 genome copies per milliliter (Buster et al., 2003, Gunson
et al., 2003). In this connection, the Society for Healthcare Epidemiology of America
(SHEA) issued a guideline for the management of healthcare workers who are infected
with HIV, HBV, and HCV to impose restriction on different categories of exposure-prone
procedures according to the viral load (Henderson et al., 2010).
Viral Transmission and Infection Control Prevention for Droplet and Airborne Agents
Including All Respiratory Viruses, Chickenpox, and Measles
Epidemiologically important respiratory viruses such as influenza A virus are predominantly
transmitted by the droplet route. By definition, the virus can spread within 1 m from
the index case. However, individuals infected with influenza A virus may produce as
many as 40 000 droplets of 0.5–12 μm in size and expel them at a velocity of 100 m s− 1
upon sneezing (Tang et al., 2006). Droplet nuclei of < 3 μm may suspend in air and
do not settle onto the ground (Knight, 1980). Therefore, an explosive outbreak with
high clinical attack rate as a result of aerosol transmission may occur under special
conditions. In a jet airliner with nonfunctioning ventilation system, 72% of 54 passengers
developed influenza-like illness within 72 h after being kept on ground for 3 h due
to delay in flight time (Moser et al., 1979). As the virus may survive on inanimate
surfaces for 12–48 h and on the surface of hands for 10–15 min (Kampf and Kramer,
2004, Kramer et al., 2006), influenza virus can be transmitted indirectly by contact
with hands from the contaminated environment to the pharyngeal mucosa. Symptomatic
influenza may develop after intranasal inoculation of one TCID50 of influenza A virus
(Tellier, 2006). Hand hygiene is always the core component of infection control measures
in both community and hospitals to prevent the transmission of influenza A virus.
Wearing face masks by either the index case as source control or the healthcare workers
as contacts has shown to be equally effective in the control of nosocomial transmission
of pandemic influenza A H1N1 (Cheng et al., 2010). Hand hygiene and face masks have
been shown to prevent household transmission of influenza virus when implemented within
36 h of the index patient's symptom onset (Cowling et al., 2009). Oseltamivir PEP
halted an outbreak of pandemic influenza A H1N1 in a secondary school (Asiedu-Bekoe
et al., 2012), but not in nursing homes (van der Sande et al., 2014).
Prevention of nosocomial transmission of influenza A virus requires multiple actions.
Early identification of symptomatic cases by direct antigen detection from nasopharyngeal
specimens and initiation of droplet precautions by wearing surgical masks, along with
staff education, could achieve reductions in nosocomial pandemic influenza to near
zero (Cheng et al., 2010), while a similar protocol was also effective in minimizing
the risk of nosocomial transmission of avian influenza A/H7N9 virus (Cheng et al.,
2014). To ensure hand hygiene compliance, directly observed hand hygiene was adopted
to control the spread of respiratory viruses in hospitals (Cheng et al., 2007b, Cheng
et al., 2010). Alcohol-based hand rub is delivered to every healthcare worker and
conscious patient once every 2–3 h in the clinical areas, which may further reduce
the spread of respiratory viruses.
Varicella zoster virus (VZV) and measles are predominantly transmitted by aerosols
and deposited in distal airways (Roy and Milton, 2004). The exact mechanism of airborne
transmission remains to be elucidated. However, an early study demonstrated that nosocomial
outbreak of VZV occurred even when the index case was strictly isolated in a single
room (Gustafson et al., 1982). There was a lack of nosocomial spread of VZV when all
index cases were placed in negative-pressure airborne infection isolation rooms (Anderson
et al., 1985). Measles virus can survive in the air for at least 1 h, as shown in
an outbreak where three susceptible children who contracted measles were never in
the same room with the source patient and one of the three arrived at the office 1 h
after the source patient had left (Bloch et al., 1985). A massive community outbreak
of measles occurred in a modern suburban elementary school in New York in spring,
1974, when the index case produced 28 secondary cases in 14 different classrooms.
The epidemic subsided after two subsequent generations when 60 children had been infected.
From estimates of major physical and biological factors, it was possible to calculate
that the index case produced ~ 93 units of airborne infection (quanta) per minute,
which was higher than that of patients with laryngeal tuberculosis (Riley et al.,
1962, Riley et al., 1978). Early recognition and placement in airborne infection isolation
room of index case of VZV and measles may reduce the risk of nosocomial outbreaks.
Viral Transmission and Infection Control Prevention for Viral Agents Spread by Contact
Standard and transmission-based precautions are important to prevent the spread of
respiratory and gastrointestinal viral infection (Table 3
). Some of the respiratory viruses such as respiratory syncytial virus (RSV), parainfluenza
virus, and the gastrointestinal viruses, norovirus, and rotavirus are predominantly
spread by direct contact. As an illustrative example, RSV is the most frequent cause
of nosocomial infection in pediatric wards and causes lower respiratory tract disease
in 40% of young children. Prolonged shedding of RSV for 3–11 days has been observed
in immunocompetent children (Hall, 2000), and the virus can survive on inanimate surfaces
for 6 h (Kramer et al., 2006). All these factors contribute to fomite-mediated transmission
of RSV in the hospital. The risk of nosocomial RSV transmission was not related to
age or underlying disease, but to length of hospitalization (Hall et al., 1975). Contact
precautions with cohort nursing and wearing gloves and gowns during patient care resulted
in a significant reduction in nosocomial transmission of RSV in three consecutive
winters (Madge et al., 1992). In another study, the incidence of nosocomial acquisition
of RSV was significantly decreased after implementation of wearing gloves and gowns
and isolation of case events though the duration of RSV shedding remained unchanged
before and after the intervention (Leclair et al., 1987).
Table 3
Infection control measures for transmission-based precautions in resource-poor areas
Transmission-based precautions (example)
Infection control measures in developed areas
Infection control measures modified in resource-poor areas
Contact precautions (norovirus)
Patient placement: single room isolation or cohort nursingPatient care practice: hand
hygiene with alcohol-based hand rub or soap and water if the hands are visibly soiled;
personal protective equipment with glove and gown; use of dedicated medical equipmentEnvironment
disinfection: frequent disinfection with sodium hypochlorite (1000 ppm) to the high-touch
surfaces and terminal disinfection after patient discharge from isolation facilities
Intrinsic limitation: single room isolation facilities, personal protective equipment,
and dedicated medical equipment are not sufficient or not availablePossible solution:
nursed in the open cubicle or cohort nursing, performing regular hand hygiene round
by designated healthcare workers at 2–3 h interval to all patients and healthcare
workers; directly observed hand hygiene to conscious patients before meals and medications
to reduce the risk of nosocomial transmission
Droplet precautions (influenza A virus H3N2, H1N1)
Patient placement: cohort nursing with spatial separation of at least 1 m between
bedsPatient care practice: hand hygiene with alcohol-based hand rub or soap and water
if the hands are visibly soiled; personal protective equipment with surgical mask
when caring patients within 1 mEnvironment disinfection: frequent disinfection with
sodium hypochlorite (1000 ppm) to the high-touch surfaces and terminal disinfection
after patient discharge from isolation facilities
Infection control requirement of droplet precautions should be able to perform in
resource-limited setting
Airborne precautions (SARS-CoV)
Patient placement: airborne infectious isolation room with negative pressure of at
least 12 air change per hoursPatient care practice: hand hygiene with alcohol-based
hand rub or soap and water if the hands are visibly soiled; personal protective equipment
with N95 respirator when caring patients within 1 mEnvironment disinfection: frequent
disinfection with sodium hypochlorite (1000 ppm) to the high-touch surfaces, and terminal
disinfection after patient discharge from isolation facilities
Intrinsic limitation: lack of airborne infectious isolation room and N95 respiratorPossible
solution: natural ventilation in open space at tent shelter hanged up by tall post
to ensure free air circulation from any wind directions; or in buildings with large
windows opened to increase the air change per hour; or large extraction fans if electricity
available; provide surgical mask to patient for source control
For the gastrointestinal viruses, norovirus is the most famous agent to cause outbreaks
in the community and hospital. Transmission is predominantly by the fecal–oral route.
Numerous community outbreaks of norovirus have been reported in restaurants, resorts,
cruise ships, schools, and nursing homes (Arvelo et al., 2012, Britton et al., 2014,
Kuo et al., 2009, Lai et al., 2013, Wikswo et al., 2011). The emergence of new variant
of norovirus, genogroup II, type 4 (GII.4), in Australia, Europe, and North America
associated with increased acute gastroenteritis activity has been reported since 2006
(Bruggink and Marshall, 2010, Hasing et al., 2013, Kanerva et al., 2009, Yen et al.,
2011).
Norovirus is a nonenveloped RNA virus that is relevantly resistant to common disinfectants.
As norovirus is unculturable, feline calicivirus has been used as a surrogate for
in vitro and in vivo testing for different preparations of disinfectants (Gehrke et
al., 2004, Lages et al., 2008). In the WHO formulation alcohol-based hand rub (AHR),
formula I preparation contains ethanol (80% v/v) that, based on the aforementioned
studies, may possess reasonable virucidal activity for norovirus when the contact
time is prolonged for up to 30 s. Successful control of nosocomial outbreaks of norovirus
by directly observed hand hygiene has been reported, especially during high-risk nursing
care practices such as changing napkins and feeding (Cheng et al., 2009). A proactive
infection control approach with the provision of ‘added test’ was implemented to prevent
the occurrence of nosocomial outbreak when the new variant of norovirus, genogroup
II, type 4 (GII.4), was circulating in Hong Kong (Cheng et al., 2011). RT-PCR for
norovirus was performed as an ‘added test’ by the microbiology laboratory for all
fecal specimens that were requested for bacterial culture, Clostridium difficile culture
or cytotoxin, and rotavirus antigen detection without a request for norovirus detection.
During the study period, almost 50% of newly diagnosed norovirus infections were detected
by the added test. Timely implementation of infection control measures by single room
isolation of index case with strict contact precautions significantly reduced the
incidence of hospital-acquired norovirus infection from 131 (baseline) to 16 cases
per 1000 potentially infectious patient-days (P
< 0.001) (Cheng et al., 2011).
Management of an Acute Emerging Infectious Disease Outbreak Such as SARS, Pandemic
Influenza, and Ebola
SARS
The outbreak of SARS in 2003 was the first emergence of an important human pathogen
in the twenty-first century. SARS emerged as an outbreak of atypical acute community-acquired
pneumonia in the late 2002. The epidemic may have started when a bat SARS coronavirus
jumped into caged palm civets in a wildlife market and became adapted and amplified
to jump from civet to human. Infected chefs and animal handlers transmitted the adapted
virus to healthcare workers and then the epidemic became amplified into the community.
The epidemic was rapidly and globally disseminated when a ‘super-spreader’ of SARS,
who was a medical professor from a teaching hospital in Guangzhou, went to Hong Kong
on 21 February 2003. During his stay in hotel M, he transmitted SARS-CoV to other
residents, and the secondary cases spread the disease to hospitalized patients in
Hong Kong and to other countries including Vietnam, Singapore, and Canada. Eventually,
a total of 8096 patients were infected in over 30 countries among 5 continents and
774 (9.5%) of them died (Cheng et al., 2007a). Nosocomial outbreaks were reported
in many parts of the world including Toronto, Hong Kong, Guangzhou, Kaohsiung, Singapore,
and Vietnam during the SARS epidemic. There were a total of 716 secondary and tertiary
cases of SARS as a result of the admission of infected index patients. Healthcare
workers constituted 410 (52.3%) of the secondary and tertiary cases (Cheng et al.,
2013). As there were no known effective antiviral agents and vaccine for the treatment
and prevention of SARS, infection control measures and extensive tracing to quarantine
the contact person became the most important interventions for SARS control. The longitudinal
follow-up of SARS patients revealed that the viral load gradually increased on day
5 after symptom onset and peaked at day 10. Early isolation of source patients can
prevent ongoing transmission of SARS in the community. In hospitals, temporary suspension
of clinical services in both inpatient and outpatient settings was adopted (Gopalakrishna
et al., 2004, Liu et al., 2006, Nishiura et al., 2005, Reynolds et al., 2006), while
home quarantine of healthcare workers who had contact with SARS patients was also
mandated in some centers (Dwosh et al., 2003).
Provision of personal protective equipment (PPE) such as N95 respirators, gloves,
gowns, and goggles and placement of suspected or confirmed cases of SARS in airborne
infection isolation rooms were enforced when resources were available. The appropriate
use of PPE was also important for staff protection. Many healthcare workers apparently
lacked a clear understanding of how best to remove PPE without contaminating themselves.
Little information about the appropriate sequence of removing PPE was available at
that time (Puro and Nicastri, 2004).
Ebola Virus
Infection control measures are particularly important for emerging viral infections
without effective antiviral therapy and vaccine. Recently, the largest outbreak of
Ebola virus disease (EVD) in West Africa (Guinea, Sierra Leone, Liberia, Nigeria,
and Equateur province of Democratic Republic of the Congo) has already resulted in
a total of 27988 cases and 11299 deaths as of 16 August 2015.
Ebola virus is transmitted via contact with contaminated body fluid or the contaminated
environment, and therefore, the practice of contact precautions with appropriate PPE
is of utmost importance when handling suspected or confirmed EVD cases. Healthcare
workers should preferably work in pairs so as to mutually observe against breaks in
infection control measures. They are required to put on the PPE in the following sequence:
N95 respirator, water-repellent cap or hood, full-length shoe cover or boot, water-resistant
gown, face shield, and finally long nitrile gloves. If the patient has hemorrhagic
symptoms, double nitrile gloves should be worn. In view of the high virulence and
mortality, patients suspected to have EVD should be isolated in airborne isolation
rooms, although the WHO allows cohorted nursing in designated areas with dedicated
instruments, where access should be restricted in developing countries with limited
isolation facilities.
Degowning remains the most critical procedure for healthcare workers. The most contaminated
PPE should be removed first, starting with the long nitrite gloves, water-resistant
gown, full-length shoe cover or boot, face shield, water-repellent cap or hood, and
finally N95 respirator. Hand hygiene with alcohol-based hand rub should be performed
in each step of degowning. When the hand is visibly soiled, it should be washed with
soap and water. Healthcare workers must be well trained and audited for the proper
procedure of gowning and degowning.
When the suspected or confirmed case of EVD dies, the healthcare and mortuary workers
are required to wear PPE as described earlier. The dead body is placed in double bags
with leakproof characteristic of no < 150 mm thick. Absorbent material should be put
under the body and placed in the first bag. The surface of each body bag is wiped
with 10 000 ppm sodium hypochlorite solution. The bags are sealed and labeled with
the indication of highly infectious material (category 3) and moved to the mortuary
immediately. Viewing in funeral parlor, embalming and hygienic preparation are not
allowed. The dead body should not be removed from the body bag and should be sent
to cremation as soon as possible.
In August 2014, WHO declared the EVD outbreak in West Africa a public health emergency
of international concern. Preparedness and response plans were made available by health
authorities in nearly all countries worldwide. The aim was to detect the first imported
case for early isolation in order to prevent local transmission in the community and
healthcare settings. Therefore, risk assessment at ports, emergency rooms, and outpatient
clinics for any patient fulfilling both clinical and epidemiological criteria for
EVD is important. For the clinical definition, patient suffering from elevated body
temperature or subjective fever or symptoms including severe headache, fatigue, muscle
pain, vomiting, diarrhea, abdominal pain, or unexplained hemorrhage should be alerted,
while the epidemiological definition includes close contact with a confirmed or probable
case of EVD or resided in or history of travel to an affected area or countries (Guinea,
Liberia, Sierra Leone) within 21 days before symptom onset. Healthcare workers working
in volunteer medical services or nongovernment organization, who have direct contact
with patients in the affected areas or countries, should also perform medical surveillance
or be placed in quarantine for at least 21 days after leaving the affected areas or
countries. Medical evaluation should be sought promptly if there are any symptoms
of fever, diarrhea, vomiting, or bleeding during quarantine or medical surveillance.
Control of Viral Outbreak in the Community
With reference to the experience in the community spread of pandemic influenza A virus
infection, nonpharmacological interventions with social distancing, such as school
closures, have been evaluated in previous modeling and epidemiological studies (Bell
et al., 2009, Bootsma and Ferguson, 2007, Ferguson et al., 2006, Markel et al., 2007).
During the influenza pandemic in 2009, school closures were practiced in the United
States and Australia (Borse et al., 2011, Effler et al., 2010), because school closures
were associated with a 65% reduction in the mean total number of contacts for each
student as reported in a retrospective questionnaire survey in the United Kingdom
(Jackson et al., 2011). In Hong Kong, kindergartens and primary schools were closed
when local transmission of influenza A virus was identified in 2009, followed shortly
afterward by secondary school closures for summer vacations. Influenza A virus transmission
was estimated to be reduced by 25% (Wu et al., 2010). Home quarantine was also shown
to reduce the incidence of pandemic influenza A in the workplace (Miyaki et al., 2011).
In fact, home quarantine has been used to control the community spread of SARS in
Beijing, Taiwan, Singapore, and Toronto (2003; Cava et al., 2005, Hsu et al., 2006).
Home quarantine can be considered for the control of the spread of Ebola virus in
affected countries although in resource-limited settings, effectively implementing
these strategies can be challenging. The local government and health authorities have
already implemented home quarantine for 3 days as an urgent infection control measure.
However, if it is technically and politically feasible, home quarantine may be extended
for up to 21 days (one incubation period) for EVD. However, public health staff is
expected to face unprecedented challenges in implementing an extensive quarantine
policy, as they have a dual role of monitoring compliance and providing support to
people in quarantine. Countries in close proximity to the affected areas require implementing
border control measures to screen for any suspected case of Ebola virus, or even considering
closing the border for 21 days. Although these measures may adversely affect international
travel and local economies, it may be worthwhile to implement such strict measures
to control this reemerging infectious disease with high mortality and psychological
fear in a timely manner.
Antiviral and Convalescent Plasma Treatment in the Control of Viral Outbreaks
Currently available antiviral against influenza A include the adamantanes (amantadine
and rimantadine), neuraminidase inhibitors (oseltamivir, zanamivir and peramivir),
and a pyrazinecarboxamide derivative (favipiravir). Only the neuraminidase inhibitors
and pyrazinecarboxamide derivatives are active against currently circulating influenza
A viruses. Oseltamivir and favipiravir are available orally. Zanamivir is available
either as dry powders and delivered by oral inhalation, or recently, intravenous formulation
is available. Peramivir is only available in the intravenous formulation. Randomized
controlled trial in patients with seasonal influenza suggested that the use of neuraminidase
inhibitor can shorten the duration of illness by ~ 1 day. A recent meta-analysis had
demonstrated that early neuraminidase inhibitor treatment (within 2 days of symptom
onset) was associated with a reduction in mortality (Muthuri et al., 2014). Two prospective
clinical trials have demonstrated that treatment with convalescent plasma or hyperimmune
intravenous immunoglobulin for patients with severe influenza infection was associated
with lower viral load, cytokine level, and reduced mortality (Hung et al., 2011, Hung
et al., 2013).
Clinical trials on various antiviral treatments against EVD are underway. These agents
include BCX4430 (a novel nucleoside analog) (Julander et al., 2014), brincidofovir,
favipiravir, TKM-Ebola, and ZMapp (a chimeric monoclonal antibody) in Guinea, Sierra
Leone, and Liberia (Bishop, 2015).
Importance of Vaccination in the Control of Viral Outbreaks
When there is no highly effective antiviral for the treatment of a severe viral illness,
especially in patients at the extremes of age or with medical comorbidities, and infection
control measures are difficult to implement or comply with, vaccination is the final
option to prevent massive outbreaks. Influenza vaccine is the most widely used annual
vaccine in the community and healthcare setting to protect at risk or any person to
develop influenza-related complications and prevent institutional outbreaks. Seasonal
influenza-related excess hospitalization and death were estimated to be 10 000 and
1100 per year in Hong Kong, a subtropical city (Chiu et al., 2002, Wong et al., 2004,
Wong et al., 2006). In a meta-analysis assessing influenza vaccine efficacy and effectiveness
in elderly patients, the inactivated influenza vaccine could reduce the risk of hospitalization
as a result of pneumonia by 21–38% and cardiovascular disease by 18–30% and all cause
of mortality by 39–56% (Nichol, 2008).
Control of virus disease outbreak by vaccination is particularly valuable for exposed
individuals, when the viral diseases have a long enough incubation period so that
the exposed individuals have sufficient time to develop protective immune responses
before symptomatic disease set in. Measles (incubation period of 7–18 days), mumps
(incubation period of 12–25 days), rubella (incubation period of 14–23 days), and
varicella (incubation period of 10–21 days) are relevant examples. Reactive vaccination
for measles outbreak has been shown to be an effective measure to reduce the scale
of outbreaks. In the Democratic Republic of Congo, weekly reported cases reduced,
respectively, by 89.3% and 68.9% in the 3 weeks following mass vaccination campaigns
(Alberti et al., 2010). Similarly, nationwide mass vaccination interrupted the transmission
of paralytic poliomyelitis in Albania. In 1996, a total of 138 paralytic cases occurred
with an attack rate of 10 per 100 000 population among adults aged 19–25 years. The
epidemic was controlled by two rounds of mass vaccination with trivalent oral poliovirus
vaccine targeted to persons aged 0–50 years (Prevots et al., 1998).
Conclusion
While routine laboratory diagnostic tests and specific antimicrobial agents are generally
available for the treatment of bacterial, fungal, and parasitic infections, we are
just entering the stage when rapid nucleic acid tests and a greater array of antiviral
agents are available for tackling viral infections. The broad array of viruses worldwide
causes substantial morbidity and mortality, ranging from respiratory viruses, arthropod-related
viruses, to the most deadly blood-borne viruses. Novel emerging or reemerging viruses
are causing major epidemics from time to time especially in densely populated areas
where human populations have close contact with wild animals (wildlife markets) and
food animals (wet markets and abattoirs). Such epidemics such as the EVD can be explosive
in countries with failed governance and poor health infrastructures. Currently, there
is a lack of antiviral treatment for most of these infections. Therefore, prevention
by implementing effective infection control and vaccination is of utmost importance
to contain these viruses.