Viral Zoonosis: A Comprehensive Review
Zoonoses are human diseases caused by animal pathogens
or animal diseases that are transmissible to humans. Zoonotic pathogens
identified are mostly viral origin and are emerging and reemerging. Zoonotic
viral infections are grouped based on the type of infection they produce
in natural host. Some are associated with encephalitis/hemorrhages and
others may cause only local lesions like rashes and arthalgia. Transmission
of these viruses usually involves arthropod vectors, which sometime act
either as mechanical and/or biological vectors. Some zoonotic agents may
be transmitted directly through animal bite or close contact with infected
animals or fomites. The zoonotic microbes continue to evolve and adapt
with tremendous acceleration and expansion of global trade, human movement
and population explosion for efficient adaptation in new host and ecosystem
results in catastrophic effects. They continue to cause health hazards
in most parts of world and are economically important and public health
concern. Control of zoonotic diseases and protection of public health
are challenging tasks as the world population is increasing proportionately.
The prevention of these infections depends on improved diagnosis and highly
effective therapeutics/prophylactics. The collective effort of professionals
from medical and veterinary and others is necessary to combat these zoonotic
infections. In this review most important zoonotic infections along with
their specific etiology, transmission (role of wild-life) manifestations
and epidemiology and control/preventive measures are described, so as
to create awareness to the scientific/public health community.
Zoonosis (zoo-e-no-sis) is an infectious disease that may be transmitted from
animals (wild and domestic) to humans or from humans to animals. The word zoonosis
is derived from the Greek, zoon (animal) (pronounced as zoo-on) and nosos
(disease). Of the 1415 microbial diseases affecting humans, 61% are zoonotic
(Taylor et al., 2001) and among emerging infectious
diseases, 75% are zoonotic with wildlife being one of the major sources of infection
(Daszak et al., 2001). A new virus has been
emerging almost every year since last two decades (Woolhouse
and Sequeria, 2005). Of 534 zoonotic viruses (belonging to 8 families) identified
120 cause human illnesses with or without the involvement of intermediate host/vectors.
In the past 15 years, many zoonotic viral infections are of emerging and re-emerging
in nature (Wilke and Hass, 1999) and haemorrhagic fever
causing viruses transmitted by insect vectors (arboviruses i.e., yellow fever
virus) (Khan et al., 1988), rodents i.e., Hanta
viruses (Peters and Khan, 2002) and also by direct contact
i.e., Filoviruses (Payling, 1996). Thus, they pose a
great challenge to both veterinary and public health professionals. It is essential
to investigate the complex interactions between pathogens, host, vectors and
environment to curtail these infections. This review focuses on description
of the important zoonotic viral infections with especially the recently emerging
and reemerging diseases and their causes, transmission, clinical manifestations,
distribution and preventive measures, to abreast the knowledge on zoonoses.
Zoonotic viruses are transmitted to humans either directly or indirectly.
Direct transmission involves contact between the infected and susceptible individual
(orf), bite (rabies) and handling of the affected animal's tissues or materials
(Orf). Indirect transmission involves transmission through the bite of a hematophagous
(blood-sucking) arthropod after replicating in the reservoir animal host (Japanese
encephalitis, yellow fever). Most viral zoonoses require blood-sucking arthropods
for their transmission to humans. Among them, mosquitoes (Equine encephalitis
complex) are the most common followed by ticks (Powassan virus), sand flies
(Vesicular stomatitis) and midges (bluetongue). The arthropod vector becomes
infected when it feeds the blood of a viraemic animal. In most of the cases,
virus replicates in the arthropod tissues and reaches their salivary glands.
The arthropod then transmits the virus to a new susceptible host when it injects
infective salivary fluid while taking a blood meal. The extrinsic incubation
period (time between ingestion and transmission of the virus) is usually 8 to
12 days. This period depends on the virus, the environment and the vector species
involved (Hubalek and Halouzka, 1999). Arthropod-borne
viruses generally remain undetected until humans encroach on the natural enzootic
focus or until the virus escapes the primary cycle via a secondary vector or
vertebrate host. Wild birds are important to public health as they carry various
zoonotic pathogens and they either act as reservoir hosts or help in disseminating
the infected arthropod vectors (Reed et al., 2003).
In addition, bird migration provides a mechanism for the establishment of new
endemic foci of disease at great distances from where an infection was acquired
(avian influenza). There has been a change in the transmission pattern especially
in the occurrence and incidence of diseases due to broadening of host range
(Monkey pox and Nipah viruses), high mutation rate (avian influenza, FMD) and
anthropogenic environmental changes viz., ecological imbalance and change in
agricultural practices (Wilke and Haas, 1999).
Role of Wildlife in Zoonosis
The significance of wild life as animal reservoir for zoonotic viruses has
been traced long back with two important ancient diseases such as rabies and
West Nile virus and represent as large spectrum of transmission mode (Marr
and Calisher, 2003). Of the total emerging diseases, 75% are considered
zoonotic with wild life as a major source of reservoir. Recent emerging viral
diseases which moved into new species such as AIDS, SARS and avian influenza
have a strong evidence of wild life origin due to human encroachment and changed
international trade and travel patterns. Commonly the pattern of moving of viral
agents from wild animal species to human occurs either as actual transmission
being rare (HIV, Influenza A, Ebola and SARS) but will be maintained and has
potential of man to man transmission or direct/indirect manner through animal
bite and arthropod vectors (rabies, Nipah, West Nile virus and hantavirus) (Bengis
et al., 2004). Many zoonoses with a wildlife origin are spread through
insect vectors (Rift Valley fever, equine encephalitis and Japanese encephalitis),
whereas, rabies by animal bite and hantaviruses by contact with rodent excreta
is common. The outcome in the form of clinical manifestation in humans depends
on the transmission pattern of the agent causing the disease. Direct contact
and vector bite lead to the formation of rashes and ulcers, whereas, intake
of contaminated meat/water lead to digestive tract problems and diseases transmitted
by inhalation of infected foci of dust cause pneumonia like illness (Kruse
et al., 2004). Wild life are basically involved in epidemiology of
the disease which is influenced by other factors such as change in agro-climatic
conditions, host abundance, movement of pathogens/vector/animal host including
migratory birds and anthropogenic factors. For example, increase in transmission
and subsequent spread of Sin Nombre Hantavirus causing Hantavirus Pulmonary
Syndrome (HPS) to humans is due to increase in heavy rainfall and host abundance
in USA. Increase in the emergence of some wild life diseases result in high
potential of emergence of human pathogens as in the case of West Nile virus
spread in USA. A potential threat to human health, animal welfare and species
conservation from domesticated and wild life is presented equally by emergence
of human and wild life pathogens.
Manifestations of Viral Zoonoses
Zoonotic infections are broadly grouped in to (1) diseases causing no illness,
(2) nonspecific viral syndrome and (3) severe illness. The third category of
infections is further classified in to (1) hemorrhagic fever, (2) encephalitis
and/or rash arthralgia, (3) emerging and reemerging and (4) rare zoonotic infections.
The major viral zoonoses, which are associated with encephalitis, are listed
in Table 1. They are arthropod borne and belong mostly to
five viral families (Rhabdoviridae, Flaviviridae, Togaviridae, Reoviridae and
Bunyaviridae). Most of them are transmitted through mosquito or tick bites,
except a few which are transmitted through bite of an infected host (rabies).
Mosquitoes and ticks are major vectors for this category of infections. They
cause symptoms like fever, vomition, encephalitis, headache and neurological
disorders. Some of these infections are confined to a particular country (Colorado
tick fever), while others are distributed worldwide (rabies). Prophylactic/therapeutic
measures are available for some of the infections, while for others vector elimination
is the only means of control. Intense research is required towards the development
of vaccines including conventional as well as recombinant. Specific diagnosis
of this group of infections is done employing serological tests like Hemagglutination-Inhibition
(HI), Complement Fixation (CF) and Virus Neutralization (VN).
Most of the viral zoonoses causing haemorrhagic fevers are reported to be
of emerging and reemerging in nature (Murphy, 1998).
There are more than 16 zoonotic infections in this category (Table
2) belong mainly to four viral families (Arenaviridae, Bunyaviridae, Flaviviridae,
Filoviridae). These infections are often associated with extensive bleeding
in human (Lacy and Smego, 1996). Most of them are transmitted
upon vector bite. The common vectors are mosquitoes and ticks. Vaccines are
not available for majority of the infections and therefore, control relies on
supportive treatment. Control of vector is the main means of control. Chemotherapy
is available for some of the infections (Crimean-Congo haemorrhagic fever) with
a limited success.
||Zoonotic infections causing encephalitis
|EEE: Eastern equine encephalitis, WEE: Western equine encephalitis;
VEE: Venezuelan encephalitis; R: Reservoir host. *Man to man transmission
#Potential for bioterrorism
||Viral zoonotic infections causing haemorrhagic fevers
|*Potential for man to man and nosocomial transmission. #Potential
for bioterrorism; R: Reservoir host
Though some of these infections have local importance (Kyasanur forest disease),
others have global impact (Dengue, Yellow fever). Specific laboratory diagnosis
of hemorrhagic fevers usually requires special serological or virological tests
like enzyme-linked immunosorbent assays (ELISAs) to detect virus-specific immunoglobulin.
Other tests like Haemagglutination Inhibition (HI), Complement Fixation Test
(CFT) and Virus Neutralization (VNT) have to be carried out on paired serum
samples collected on two occasions i.e., acute and convalescent phases of illness.
Rashes and Arthralgia
A very few viruses are associated with local rashes and arthralgia and almost
all belong to Togaviridae family (Table 3). Most of
them are transmitted to humans through infected mosquito bites. These vectors
are mainly from Aedes and Culex families. No specific treatment
is available and control depends on the elimination of vectors. EU countries
appear to be free, while other continents are endemic for these infections.
Emerging and Reemerging Zoonoses
The complex interaction between environment/ecology, social, health care,
human demographics and behavior influences the emergence and re-emergence of
zoonotic viral diseases. Periodic discovery of new zoonoses suggest that the
known viruses are only a fraction of the total number that exist in nature.
The RNA viruses are capable of adapting to changing environmental conditions
rapidly and are among the most prominent emerging pathogens (Ludwig
et al., 2003). Mutations are more common in RNA viruses (Influenza)
than DNA viruses (Pox). The common mutations are point (insertion/deletion),
drift (minor) and shift (major). In addition to these, movement of population,
birds, vectors, pathogens and trade contribute to the global spread of emerging
infectious diseases (influenza, severe acute respiratory syndrome). Other factors
viz., human migration, change in land use pattern, mining (disturbance of ecosystem),
coastal land degradation, wetland modification, construction of buildings, habitat
fragmentation, deforestation, expansion of agents host range, human intervention
in wild life resources like hiking, camping and hunting also influence on acquiring
zoonotic infections from wildlife (Daszak et al.,
2001; Bengis et al., 2004; Patz
et al., 2004). Cessation of vaccination against smallpox since 1980s,
emergence of some genetically related orthopoxviruses has been reported throughout
the world i.e., monkey pox (Nalca et al., 2005),
buffalo pox (Singh et al., 2007) and Bovine Vaccinia
(BV) infections (Fernandes et al., 2009).
Despite successful eradication of some viral diseases (small pox and almost
polio in humans and rinderpest in cattle) due to intensive research and dedicated
coordinated efforts, modern medicine has failed to control many infectious diseases
resulting from emerging and reemerging viruses (Table 4).
Some infectious agents already known to be pathogenic have gained increasing
importance in recent decades due to change in disease patterns. Several previously
unknown infectious agents with a high pathogenic potential have also been identified
(Manojkumar and Mrudula, 2006). Several infectious viral
agents (DNA and RNA viral families) have been emerged as zoonotic agents (Table
4). They are associated with flu-like signs (Alkhumra virus infection, influenza
A) to respiratory (SARS), pox lesions mostly localized distributed over hairless
parts of body namely udder, teats, ears and tail (in buffaloes) and fingers
and hands (in humans) due to buffalopox (Fig. 1a) and Orf
virus infections in affected goats (Fig. 1b), hepatitis (hepatitis
E virus), haemorrhagic fevers (Ebola, Marburg and hanta virus infections) and
encephalitis (Henipa virus complex). Treatment/prophylaxis is not available
to many of these infections. But some of antiviral compounds, which are under
trial, are found to be effective.
||Viral zoonotic infections causing rashes and arthralgia
||Emerging and re-emerging zoonotic infections
|*Potential of man to man transmission. #Potential
tool for bioterrorism
||Rare zoonotic infections
||(a) Buffalo pox infection in human particularly milkers showing
characteristic localized ulcerative and vesicular skin lesions on hand and
fingers and (b) Orf virus infection in goats showing characteristic proliferative
skin lesions on mouth, lips and nose
For example Ebola and Marburg viruses are inhibited in vitro by Carbocyclic-3-deazaadenosine,
a first compound to cure these virus infections (Huggins
et al., 1999).
Rare Viral Zoonoses
Several viral infections cause nonspecific febrile illness in humans and
occur rarely (Table 5). Many of them are animal pathogens,
but often they produce nonspecific febrile illnesses in humans, though, humans
are not the primary hosts. However, there is an increasing trend of occurrence
of such infections in recent times (Table 5). Transmission
of these infections have been reported upon direct contact of human objects
with infected animal (FMD particularly serotypes O followed by C and rarely
A, buffalo pox, Orf), handling of such organisms in the laboratory (bluetongue,
Newcastle disease), sexual contact (simian immuno deficiency (SID) virus), bite/
scratch (monkey B virus), vectors (semliki forest virus, African horse sickness
and louping ill) and food and water (calici viruses such as swine vesicular
exanthema, feline calicivirus and rabbit haemorrhagic disease virus (Thiel
and Konig, 1999) causing vomition and diarrohoea. Recently, animal rotaviruses
and Eyach virus related to Colorado tick fever virus and Oropouche fever virus,
an arbovirus (Nunes et al., 2005) similar to
dengue fever in Trinidad are reported to cause mild infections in humans. Treatment
is not available for most of the human infections, while some of them can be
treated with nucleoside analogues like acyclovir or gancyclovir.
Prion diseases are caused by scrapie associated prion protien (PrPsc),
which are proteinacious infectious agents common in animals and humans. Some
of the animal prion diseases are scrapie of sheep, Bovine Spongiform Encephalopathy
(BSE) and goats and mink spongiform encephalopathy. Human prion diseases are
Creutzfeldt-Jakob Disease (CJD), Kuru, Gertsmann Straussler Schienker Syndrome
(GSS) and fatal familial insomnia. The human disease variant (vCJD) is believed
to be a zoonotic disease caused by BSE agent and recently an emerging disease
as well (Murphy, 1998). The route of transmission of
vCJD is not yet fully proven but it is generally transmitted through exposure
to food contaminated by the bovine BSE agent (Will, 2003).
Human prion diseases can be classified as sporadic, hereditary or acquired.
Acquired form i.e., vCJD is caused by the transmission of infection from human
to human or, as a zoonosis, from cattle to human. Transmission of infectious
agents between species through xenotransplantation called xenosis (Takeuchi
and Weiss, 2000) is another way of introducing viruses from animal to human
(porcine endogenous retroviruses). No specific treatment and vaccine is available.
Prevention is by avoiding consumption of BSE contaminated or half cooked meat.
Prevention, Control Measures and Perspectives
Effective prevention and control measures can be achieved through proper
diagnostics and prophylactic aids to curtail further spread in most of zoonotic
viral diseases. Improved sanitary conditions such as proper treatment and disposal
of human waste, higher standards for public water supplies, improved personal
hygiene procedures and sanitary food preparation are vital to strengthen the
control measures. A clear understanding of epidemiology of the diseases with
wild life as reservoir namely the virulence and transmissibility of many diseases
(human monkey pox, Tana pox and Yaba pox) could help in understanding the severity
and thereby to take appropriate measures in eradication of such dreadful diseases.
Research should focus on molecular biology of these viruses so as to develop
diagnostics and prophylactics in a modern way to combat these infections in
short time. To safeguard the public health from pathogens of zoonotic infections,
application of skills, knowledge and resources of veterinary public health is
essential. It is time to combat viral zoonoses with a combined effort of veterinary
and public health specialists. A better understanding of avian migration patterns
and their infectious diseases would be useful to forecast disease outbreaks
due to emerging zoonotic infections like avian influenza. Further, the control
measures for emerging and re-emerging viral pathogens are demanding, as there
is population explosion. Novel, highly sensitive and specific techniques comprising
genomics and proteomics along with conventional methods would be useful in the
identification of emerging and re-emerging viruses, thereby; therapeutic/prophylactic/preventive
measures would be applied on time. The first line of measure to control any
disease is the surveillance. Control and prevention strategies should be designed
based on transmission pattern and characteristics of virus, involvement of vectors,
environment and epidemiology of the disease. The European Union (EU) has established
a net work termed as Med-Vet-Net to develop a network of excellence for the
integration of medical, veterinary and food scientists in order to develop food
safety measures and to improve research on the prevention and control of zoonoses,
including food-borne diseases. The network will also consider the concerns of
consumers and other stakeholders throughout the food chain. Another system the
Hazard Analysis and Critical Control Point (HACCP), which is regulated under
FDA and it aims at analyzing hazards associated with food and identify preventive
and control measures to check spread of food-borne diseases including viral
pathogens. Similarly, sanitary and phyto-sanitary measures (SPS) measures, which
are set out with WTO are to be strictly followed to have safe food in order
to conserve the health of animal, human and plants due to zoonotic agents.
The authors are grateful to the Director of the Indian Veterinary Research Institute for providing the facilities to carry out this work. This study was supported by grants from the Ministry of Forest and Environment (MOFE), Government of India, under the All India Coordinated Project on the Taxonomy capacity building of poxviruses (AICOPTAX).
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