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Epidemiology, Diagnosis, and Control of Monkeypox Disease: A comprehensive Review

Authors:
  • Narayan Consultancy on Veterinary Public Health and Microbiology Anand India

Abstract

Human monkeypox is an emerging viral zoonotic disease, which is caused by monkey pox virus. The disease occurs mostly in the rain forests of central and western Africa. People living in or near the forested areas may have indirect or low-level exposure, possibly leading to subclinical infection. However, the disease recently emerged in the United States in imported wild rodents from Africa. Monkeypox has a clinical presentation like ordinary forms of smallpox, including flulike symptoms, fever, malaise, back pain, headache, and characteristic rash. In view of the eradication of smallpox, such symptoms in a monkepox endemic region should be carefully diagnosed. Primarily, monkey pox transmission to humans is believed to occur through direct contact with infected animals or possibly by ingestion of inadequately cooked flesh. Infection by inoculation through contact with cutaneous or mucosal lesions on the animal, especially when the skin barrier is compromised secondary to bites, scratches, or other trauma is a possibility. Laboratory diagnosis is imperative because it is clinically indistinguishable from other pox-like illnesses. There are no licensed therapies to treat human monkey pox viral infection; however, the smallpox vaccine can protect against the disease. The discontinuation of general vaccination in the 1980s has given rise to increasing susceptibility to monkey pox virus infection in the human population. This has led to fears that monkey pox virus could be used as a bioterrorism agent. Effective prevention relies on limiting the contact with infected patients or animals and limiting the respiratory exposure to infected patients.
American Journal of Infectious Diseases and Microbiology, 2017, Vol. 5, No. 2, 94-99
Available online at http://pubs.sciepub.com/ajidm/5/2/4
©Science and Education Publishing
DOI:10.12691/ajidm-5-2-4
Epidemiology, Diagnosis, and Control of Monkeypox
Disease: A comprehensive Review
Mahendra Pal1, Fisseha Mengstie1, Venkataramana Kandi2,*
1College of Veterinary Medicine, Addis Ababa University, Debre Zeit, Ethiopia
2Prathima Institute of Medical Sciences, Karimnagar, Telengana, India
*Corresponding author: ramana_20021@rediffmail.com
Abstract Human monkeypox is an emerging viral zoonotic disease, which is caused by monkey pox virus. The
disease occurs mostly in the rain forests of central and western Africa. People living in or near the forested areas
may have indirect or low-level exposure, possibly leading to subclinical infection. However, the disease recently
emerged in the United States in imported wild rodents from Africa. Monkeypox has a clinical presentation like
ordinary forms of smallpox, including flulike symptoms, fever, malaise, back pain, headache, and characteristic
rash. In view of the eradication of smallpox, such symptoms in a monkepox endemic region should be carefully
diagnosed. Primarily, monkey pox transmission to humans is believed to occur through direct contact with
infected animals or possibly by ingestion of inadequately cooked flesh. Infection by inoculation through contact
with cutaneous or mucosal lesions on the animal, especially when the skin barrier is compromised secondary to
bites, scratches, or other trauma is a possibility. Laboratory diagnosis is imperative because it is clinically
indistinguishable from other pox-like illnesses. There are no licensed therapies to treat human monkey pox
viral infection; however, the smallpox vaccine can protect against the disease. The discontinuation of general
vaccination in the 1980s has given rise to increasing susceptibility to monkey pox virus infection in the human
population. This has led to fears that monkey pox virus could be used as a bioterrorism agent. Effective prevention
relies on limiting the contact with infected patients or animals and limiting the respiratory exposure to infected
patients.
Keywords: monkeypox, public health, virus, zoonosis
Cite This Article: Mahendra Pal, Fisseha Mengstie, and Venkataramana Kandi, Epidemiology, Diagnosis,
and Control of Monkeypox Disease: A comprehensive Review.” American Journal of Infectious Diseases and
Microbiology, vol. 5, no. 2 (2017): 94-99. doi: 10.12691/ajidm-5-2-4.
1. Introduction
Monkeypox is a smallpox-like viral infection caused by
a virus of zoonotic origin, which belongs to the genus
Orthopoxvirus, family Poxviridae, and sub-family
Chordopoxvirinae. It was first isolated in 1958 from a
group of sick monkeys (Macaca cynomolgus). Human
infection with Monkeypox virus was first described in
central Africa in 1970 in a 9-month old child from Zaire
[1,2,3]. The disease is endemic in the Congo basin
countries of Africa and, possibly, West Africa as well with
majority of human cases being reported from countries in
the Congo basin [4,5,6].
Smallpox is a serious, contagious, and sometimes fatal
infectious disease and the name is derived from the Latin
word for “spotted” and refers to the raised bumps that
appear on the skin of face and body of an infected person.
Smallpox outbreaks have occurred from time to time for
thousands of years, but the disease is now eradicated after
a successful worldwide vaccination program. The last
naturally occurring case in the world was in Somalia in
1977. After the disease was eliminated from the world,
routine vaccination against smallpox among the public
was stopped because it was no longer necessary for
prevention. In 1970, when smallpox was nearly eradicated,
a previously unrecognized orthopoxvirus named monkey
pox was identified in humans. The first known human
case occurred in the Equateur province of Zaire (now
known as the Democratic Republic of Congo (DRC) when
a 9-year-old boy developed smallpox like illness, which
was eventually confirmed as human monkey pox by the
World Health Organization [4]. Retrospectively, similar
cases occurring in 1970-1971 from the Ivory Coast,
Liberia, Nigeria, and Sierra Leone were attributed to
monkeypox infection.
Monkeypox virus was discovered in 1958, when it was
isolated from the lesions of a generalized vesiculo-
pustular disease among captive monkeys at the State
Serum Institute, Copenhagen [7]. The close resemblance
between smallpox and monkeypox in captive primates
focused attention on monkey pox virus as a potential
threat to smallpox eradication.
Prior to 1970, monkey pox, a disease caused by the
Orthopoxvirus, monkeypox virus (MPXV), was
recognized only in non-human hosts. Between 1970 and
1986, 10 cases of human monkey pox were reported from
Western African countries (Sierra Leone, Nigeria, Liberia
and Côte d'Ivoire) and 394 cases were reported from the
95 American Journal of Infectious Diseases and Microbiology
Congo Basin countries of Cameroon, Central African
Republic and Zaire (now Democratic Republic of the
Congo) [8].
Monkeypox was limited to the rain forests of central
and western Africa until 2003, when the first cases in the
Western Hemisphere were reported. In late spring 2003,
multiple persons were identified in the Midwestern United
States who had developed fever, rash, respiratory
symptoms, and lymphadenopathy following exposure to
ill pet prairie dogs (a rodent of Cynomys species) infected
with the monkeypox virus [9].
A direct contact or exposure with ill, prairie dogs (a
group of herbivorous burrowing rodents), showing signs
of profuse nasal and ocular discharge, dyspnoea,
lymphadenopathy, and muco-cutaneous lesions was noted
among the cases reported. Another interesting observation
noted among those cases was the presence of a common
animal distributor where prairie dogs were housed or
transported along with African rodents from Ghana.
Reports have later confirmed that most cases of
monkeypox were associated with exposure to these
rodents, the local Gambian rats, which were known
reservoirs of monkeypox in their native habitat of Africa.
After an exposure, and an average incubation period of 12
days, the animal became ill and has a potential to transmit
the virus to humans, when present in close proximity.
Human-to-human, disease transmission leading to an
outbreak was reported from DRC during 1996-1997 [6].
Studies reported from this outbreak suggested that within
households, monkeypox virus was secondarily transmitted
to 8-15% of human contacts. Prior to this, monkey pox
was not identified as an important worldwide health
problem because human infection rates were either not
known or were undermined to play a significant role in the
pathogenesis. Analysis of the 2003 US outbreak
implicates animal-to-animal and animal-to-human
transmission as the significant modes of transmission.
Genomic sequencing of monkeypox strains isolated
from the America, western and central Africa’s, has noted
the existence of two distinct clades of the virus. The
isolates from the United States were found to be identical
with the western African strains. The clinical course of the
disease among people infected with the western African
strain was observed to be milder with minimum
human-to-human transmission as compared to those
infected with isolates from central African region [10]. In
2010, a dosage comparison using a prairie dog animal
model
re-confirmed that the Congo Basin strain of monkeypox
virus was more virulent than the West African strain of
monkeypox virus [11]. This communication presents a
comprehensive review on the epidemiology, diagnosis and
control of monkeyox, an emerging viral zoonosis, which
attracted the attention of public health authorities.
2. Classification and Characterization of
Monkeypox Virus
The monkeypox virus belongs to Poxviridae family,
which also includes cowpox, vaccinia, and variola
(smallpox) viruses. Poxviruses are the largest vertebrate
viruses known, infecting humans, and other vertebrates
(species of sub-family Chondropoxvirinae), and
arthropods (species of sub-family Entemopoxvirinae).
There are around 70 known species of pox viruses
spread among 28 genera and two sub-families (the
Chordopoxvirinae and the Entomopoxvirinae). The
virions contain a linear double-stranded deoxyribonucleic
acid (dsDNA) genome and enzymes that synthesize
messenger ribonucleic acid (mRNA). They multiply in the
cytoplasm of the host cells.
The Chordopoxvirinae consists of around ten genera
including the genera which are genetically and
antigenetically related. The genus Orthopoxvirus
comprises camelpox, cowpox, ectromelia, monkeypox,
racoonpox, skunkpox, taterapox, Uasin Gishu (pox virus
of Horse), vaccinia, variola and volepox. African swine
fever viruses were also known to share some properties of
the poxviruses. Many poxviruses are associated with a
specific vertebrate species, which indicates that the
transmission of these viruses occurs preferentially among
a specific vertebrate species. Although accidental
transmission in to a different vertebrate species can occur,
there was no resultant clinico- pathological condition
noted in the infected host to be further maintained in this
'aberrant' species [12]. The orthopoxviruses which can
infect humans include variola, vaccinia, cowpox and
monkeypox viruses. Variola virus is a virus which only
infects humans and the Vaccinia virus is a vaccine strain
that does not exist in nature and is used to treat small pox.
Vaccinia virus has originated in the 18th Century from an
unknown vertebrate species. Cowpox is a rodent virus that
may infect cats, cows and zoo animals and could transmit
infection to humans.
Monkeypox is also a rodent virus, which occurs mostly
in West and Central Africa. The identification of
monkeypox virus is based on biological characteristics
and endonuclease patterns of viral DNA. In contrast to
smallpox, monkeypox virus can infect rabbit skin and can
be transmitted serially by intracerebral inoculation of mice.
The four orthopoxviruses that may infect man produce
macroscopically characteristic lesions on the inoculated
chorioallantoic membrane of an embryonated chicken egg
[8]. The maximum or 'ceiling' temperature at which the
viruses can proliferate in the chorioallantoic membrane
differs for monkeypox and smallpox. These viruses differ
also in the ability to multiply in different tissue culture
cells. However, at present the clearest results are obtained
by the endonuclease restriction patterns of the virus DNA
[13]. Some genetic variability has been noted between
monkeypox viruses isolated from West and Central
African regions. Genome studies have revealed strong
evidence regarding monkeypox virus being a non-
ancestral to variola virus. This may be important in view
of the fear expressed by some researchers that variola
might again evolve from monkeypox virus. In the pre-
molecular era, significant efforts were made to distinguish
the four viruses by serological reactions. These were
delicate studies, since the viruses share most antigens [14].
Some results were obtained using absorbed sera in agar
gel diffusion tests, but they were rapidly superseded by the
studies on biological characteristics and DNA restriction
patterns. The development of relatively specific antigens
has been extremely useful for serological surveys in
human and animals. In the field, rapid presumptive
American Journal of Infectious Diseases and Microbiology 96
diagnosis of infection caused by viruses belonging to the
orthopoxvirus group is necessary, as is differentiation
from chickenpox, as confusion is possible on clinical
grounds. For this purpose, it is recommended that scabs of
the lesions are sent, without transport medium, to the
diagnostic laboratory. Electron microscopic examination
of this material will allow the differentiation of Orthopox
and Herpes viruses. Poxviruses can be detected in more
than 95% of the scabs, whereas varicella-zoster virus
could be detected in only half of the material from cases
of chickenpox, meaning that electron microscopy negative
specimens are very unlikely to be monkeypox [8,15,16].
3. Epidemiology
3.1. Occurrence
People living in or near the forested areas may have
indirect or low-level exposure, possibly leading to
subclinical infection [17]. The disease is rare and only
known to be indigenous to the rain forests of western and
central Africa. It was first recognized in humans in 1970
after the eradication of smallpox, possibly because of the
subsequent unmasking of the infection. Surveillance
reports from 1981-1986 documented 338 cases in the
DRC (out of a 1982 estimated population of 5 million). In
the 1996-1997 outbreaks in the DRC, the attack rate was
22 cases per 1000 population. Human infection with
monkey pox has not been reported in West Africa since
1978. However, monkeypox continues to exhibit a robust
emergence in the DRC, with sporadic occurrences of
disease in neighboring countries. In 2003, 11 cases and 1
death were reported from the DRC and 10 cases with no
deaths were reported from Sudan in 2005 [18]. In United
States, no cases occurred until the late spring 2003
outbreak in the Midwestern states. Between May 16 and
June 20, 2003, 71 suspected cases of monkeypox were
investigated [19].
3.2. Mortality/Morbidity
Rash burden, hospitalization rates and illness severity (a
global score incorporating degree of incapacitation, need
for nursing care and rash burden) were used to define
human disease
Morbidity during a monkeypox infection. Monkeypox
case-fatality rates in Democratic Republic of the
Congo were ~10% among non-vaccinated individuals as
compared to those people who were vaccinated against
smallpox, and the vaccinated group was noted to have
fewer lesions and generally less severe disease [8].
The disease was generally self-limited, with resolution
in 2-4 weeks, depending on the severity of the illness.
However, a small subset of patients, most commonly
pediatric patients, had a more severe course, with several
patients requiring ICU care [20]. Complications reported
from African outbreaks include pitted scars, deforming
scars, secondary bacterial infection, bronchopneumonia,
respiratory distress, keratitis, corneal ulceration, blindness,
septicemia, and encephalitis.
African cases have mortality rates of 1-10%, with the
highest rates occurring in children and individuals without
vaccination. In general, the prognosis is related to the
amount of exposure to the virus, host immune response,
comorbidities, vaccination status, and severity of
complications. Poxvirus infections have no racial
predilection and the incidence is equal in males and
females.
In the African epidemics, 90% of the patients were
children younger than 15 years [21]. In the recent US
outbreak, of the confirmed cases in 2003 (n = 35), 11
patients were younger than 18 years and 24 were older.
Although the highest age-specific incidences and the
greatest number of cases occur among persons younger
than 15 years, a trend toward increasing incidence among
persons aged 15-30 years has been seen in recent years. It
has been hypothesized that cessation of smallpox
vaccination may be a factor in the increasing incidence in
this age group, but this theory fails to account for why the
disease has not re- emerged in countries where the disease
was seen previously, such as West Africa [18]. An annual
crude incidence rate of human monkey pox of 0.63/10,000
population was inferred. Those at high risk were young
unvaccinated children (especially boys) and adult women.
Approximately one third of the infections were estimated
to be sub-clinical [22]. The increase in cases was ascribed
to the effect of the civil war which had led to increased
hunting for forest animals that carry monkey pox,
particularly squirrels. With changes in lifestyle due to
increasing urbanization, and intensified agricultural
activities replacing hunting and trapping, the chances of
contracting monkey pox, either from the primary reservoir
or intermediate hosts, will decrease and monkey pox will
become a disappearing disease.
3.3. Transmission
It is a zoonotic virus with primary transmission
believed to occur through direct contact with infected
animals or possibly by ingestion of their inadequately
cooked flesh. Inoculation may be from cutaneous or
mucosal lesions on the animal, especially when the skin
barrier is compromised secondary to bites, scratches, or
trauma. Transmission can also occur from animal
reservoirs from Western Africa (prairie dogs, rabbits, rats,
mice, squirrels, dormice, monkeys, porcupines, gazelles).
Additionally, direct cutaneous (skin-to-skin) or respiratory
contact with an animal or person who is infected can
transmit the infection.
3.4. Hosts and Reservoirs
Although rodents are believed to be the major reservoir
in Africa, A 2010 study reaffirmed that several species of
forest-dwelling rodents are at risk of developing
Orthopoxvirus (including monkey pox) infection [23,24].
Serological surveys suggest that many animals are
infected with MPV under natural conditions, including
squirrels, non-human primates, and rats. Several
epidemiological studies from the Democratic Republic of
Congo have implicated squirrels (especially Funisciurus
anerythrus) inhabiting agricultural areas as primary
candidates to sustain viral transmission among people in
nearby settlements [24]. In one environmental survey,
Funisciurus spp. squirrels had a higher rate of MPV
97 American Journal of Infectious Diseases and Microbiology
seropositivity (24%) than other animals that were tested,
including Heliosciurus spp. squirrels (15%) and primates
(8%). A subsequent seroprevalence study done as part of
the investigation of the outbreak in February 1997, in the
Democratic Republic of Congo showed even higher
positivity rates in these squirrels (3950% in Funisciurus
spp. and 50% in Heliosciurus spp. squirrels) [6]. In
addition, 16% of Gambian giant rats tested in this study
had serological evidence of MPV exposure. The infection
of a rabbit (family Leporidae) after exposure to a diseased
prairie dog at a veterinary clinic confirmed the
transmissibility of the virus between mammal species
common in North America. Little is known about
coinfection with MPV and HIV [25].
4. Clinical Presentation
The clinical presentation of human monkeypox was
described primarily among children and adolescents
identified in central and West African regions. The disease
was characterized as a viral prodrome fever with chills,
headache, myalgias, and back pain lasting for 13 days,
followed by a maculopapular exanthematous eruption.
The rash was predominantly monomorphic with a
centrifugal distribution, progressing to vesicular, pustular,
and finally developing crusts during a 23-week period
[21,26].
Monkeypox viral infection can cause a syndrome
clinically like smallpox but was noted to be less infectious
and clinically milder. The incubation period averages 12
days, ranging from 4-20 days. In the prodrome or pre-
eruptive stage (lasts 1-10 days), fever could be the first
symptom (usually 38.5-40.5°C). The febrile illness may
often be accompanied by chills, drenching sweats, severe
headache, backache, myalgia, malaise, anorexia,
prostration, pharyngitis, shortness of breath, and cough
(with or without sputum). Lymphadenopathy might appear
within 2-3 days after the fever in most cases. In the 2003
outbreak, 47% of patients had cervical lymphadenopathy,
with nodes measuring several centimeters in diameter. In
the exanthematous stage, most infected people develop a
rash within 1-10 days after the onset of fever. The rash
often starts on the face and then spreads to the rest of the
body, and could persist for 2-4 weeks until all lesions have
turned to crusts. Encephalitis with immunoglobulin M
(IgM) was observed in the cerebrospinal fluid as reported
in a previous research [27].
In the exanthematous stage, within a body region,
lesions evolve synchronously over 14-21 days, like the
development of lesions with smallpox. However, unlike
smallpox, skin lesions may appear in crops. In contrast to
smallpox, the lesions do not have a strong centrifugal
distribution. Lesions progress from macules to papules to
vesicles and pustules; the face, the trunk, the extremities,
and the scalp are involved. Lesions may appear both in
covered and uncovered areas. Lesions may be seen on the
palms and the soles. Necrosis, petechiae, and ulceration
may be features and pruritus may also occur. Pain is
unusual, and, if it occurs, it is often associated with
secondary bacterial infection. In patients who have been
previously vaccinated against smallpox, a milder form of
disease occurs. In children, the lesions may appear as
nonspecific, erythematous papules that are 1-5 mm in
diameter and suggestive of arthropod bite reactions. The
lesions of monkeypox need to be differentially diagnosed
with that of small pox and chicken pox, technically only
chicken pox as small pox has been eradicated [28].
5. Clinical and Laboratory Diagnosis
The geographic location of the patient is important in
the diagnosis of monkeypox, as the disease usually occurs
in remote villages in the tropical African rain forests.
Differentiation from chickenpox is important; the latter
appears in successive crops so that lesions at various
stages of development are visible at any time. In contrast
with smallpox, the distribution of chickenpox is
'centripetal' with more lesions on the trunk than on the
face and extremities. For definitive diagnosis, scabs can
be forwarded to a reference laboratory where electron
microscopy may confirm the presence of an
Orthopoxvirus and differentiate this virus from varicella
virus. The virus can be cultured in tissue culture and
identified by DNA restriction analysis.
A viral culture should be obtained from an
oropharyngeal or nasopharyngeal swab. A skin biopsy
specimen of the vesiculopustular rash or a sample of the
roof of an intact vesiculopustule should be analyzed.
Tissue for PCR of DNA sequence-specific for the
monkeypox virus may be obtained. Paired sera for acute
and convalescent titers may be analyzed. Serum collected
more than 5 days for IgM detection or serum collected
more than 8 days after rash onset for IgG detection was
most efficient for the detection of the monkeypox virus
infection [29]. A Tzanck smear can help differentiate
monkeypox from other nonviral disorders in the
differential diagnosis. However, a Tzanck smear does not
differentiate a monkeypox infection from smallpox or
herpetic infections.
Monkey pox cases were confirmed based on virus
isolation or detection of the virus by polymerase chain
reaction (PCR) from a clinical specimen (skin biopsy or
throat culture). Individuals who presented with fever and
rash within 21 days of exposure to monkey pox and had
serum positive for orthopox immunoglobulin M (IgM),
but did not have culture- or PCR- positive clinical
specimens, were classified as having a probable case of
infection [29,30]. The most reliable clinical sign
differentiating monkeypox from smallpox and chickenpox
is enlarged lymph nodes, especially the submental,
submandibular, cervical, and inguinal nodes. Regarding
exanthema, nonspecific lesions and inflammation of the
pharyngeal, conjunctival, and genital mucosae have been
observed [28].
5.1. Histological Findings
Histological examinations of papular lesions could
show the presence of acanthosis, individual keratinocyte
necrosis, and basal vacuolization, along with a superficial
and deep perivascular, lymphohistiocytic infiltrate in the
dermis. Lesions in the vesicular stage could show
spongiosis with reticular and ballooning degeneration.
Multinucleated epithelial giant cells can be another
American Journal of Infectious Diseases and Microbiology 98
significant observation. Pustular lesions might show
epidermal necrosis with numerous eosinophils and
neutrophils, many displaying karyorrhexis. Necrosis may
extend through full-thickness epidermis with sharp lateral
demarcation from adjacent intact epidermis. The
associated perivascular infiltrate may include eosinophils
and neutrophils in addition to lymphocytes and histiocytes
and petechial lesions can demonstrate secondary vasculitis.
Amphophilic intranuclear structures suggestive of viral
inclusions may also be seen in keratinocytes [28].
Immunohistochemistry staining for Orthopox viral
antigens is available and can be performed in select
reference laboratories. Electron microscopic observation
can reveal intracytoplasmic, round-to-oval inclusions
with sausage-shaped structures centrally, measuring
approximatrely 200-300 µm. These Inclusions were noted
to be consistent with Orthopox viruses, permitting
differentiation from Parapox and Herpes viruses [28].
6. Treatment
The Centers for Disease Control and Prevention (CDC)
recommended smallpox vaccination within 2 weeks,
ideally before 4 days, after a significant, unprotected
exposure to a diseased animal or a confirmed human case
[31]. Data from the African outbreaks suggest that prior
smallpox vaccination confers 85% protection from
monkeypox viral infection. Efficacy of vaccination was
noted to be prolonged with protection noted even several
years after vaccination, and the incidence of complications
being reduced [8].
Since human infection with monkeypox virus is a rare
disease, no benefit would be derived from vaccination
with Vaccinia virus. Furthermore, smallpox vaccination
cannot be undertaken in populations with high prevalence
of HIV infection because of the risk of serious
complications. Antiviral chemotherapeutic treatment is not
a viable option in those remote places where the disease is
likely to appear. The treatment would have to be
administered in the very early stages of the disease and it
is unlikely that the treatment could be made available in
time. In addition, the treatment is not devoid of side
effects [32].
7. Prevention and Control
Improved infection control measures, including the
regular screening, and isolation of newly infected animals
will certainly help in preventing outbreaks among animals.
Better hygiene habits are warranted to avoid spreading of
the virus on fomites which then become a source for
newer infections. Vaccination with vaccinia virus could be
choice to protect animals. Because infections have been
reported in Asian monkeys mixed with primates from
Africa, care must be taken to house these species
separately. Anyone who has been exposed to monkeypox
virus should avoid contact with animals, particularly
rodents and non-human primates, to stop transmitting the
virus [32].
During an outbreak, monkeypox viral spread may be
controlled by quarantining (at least for 6 weeks from the
date of the last exposure) the infected animals and tracing
of their contacts. Areas where these animals have been
kept should be cleaned and disinfected thoroughly.
Adherence to specific instructions from the state or local
health department or the CDC Web site is required.
8. Recent Advances in the Knowledge
of Monkeypox Virus
A recent study has observed that the presence of a gene
coding for Golgi-associated retrograde protein (GARP)
complex in an infecting monkeypox virus strain could
contribute to serious infection. The same study has also
noted that it is important to identify the host target cells
which are required for viral multiplication could pave the
way for development of anti-viral therapy [33]. Another
report recently noted that it was not exactly known as to
how the monkepox virus spreads to humans. The same
research study has suggested that, although there is no
known reservoir for monkeypox virus, a close association
with wild animals leading to bites, and consumption of
bush meat could be potential risk factors to acquire
monkepox virus infection [32]. Immunization with highly
attenuated smallpox strain proved to be beneficial in
human giving a protection for up to 6 weeks after
vaccination. The same study has observed that such highly
attenuated smallpox vaccine could provide longer
protection for more than a year as observed in monkeys
[33]. Identification of infection with monkeypox virus is
complex due to its similarities between smallpox virus,
and, varicella-zoster viruses. Recently a study has
evaluated utility of two methods that included the real-
time quantitative polymerase chain reaction (PCR) assay,
and the more automated GeneXpert MPX/OPX technique
in the laboratory diagnosis of monkeypox [35,36].
Development of an on-site laboratory diagnostic test
which can be used both in humans and animals was
recently reported. It is an immune-filtration technique
called as ABICAP (Antibody Immuno Column for Analytical
Processes). This works on a gravity-driven flow-through
antigen capture ELISA, different from the traditional
enzyme linked immunosorbent assays (ELISAs), and the
lateral flow Immunochromatographic tests [37,38].
9. Conclusion
Among the group of pox viruses, the smallpox virus has
been declared as non-existent in the wild many years back.
Although Varicella-Zoster virus/Chicken pox virus, the
causative agent of chicken pox is prevalent among humans,
it is a self-limiting infection. The cause of concern now is
the presence and potential spread of other hither to less
known pox viruses, including the monkeypox in humans.
It has been observed that the newer pox viruses could be
like the eradicated smallpox virus which causes a
potentially life threatening infection in humans. In the era
of globalization, there is a frequent mobility of human,
carrying a potential for spread of monkeypox. Cross
border transport of animals also provides an imminent
threat of spread of infection. Biological warfare and potential
threat of bioterrorism cannot be ruled out; therefore, a
99 American Journal of Infectious Diseases and Microbiology
better understanding of monkeypox virus and similar
microorganisms could contribute to better management of
emergency situations.
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... This is thought to occur due to the decreasing number of smallpox vaccines as the disease is eradicated in several countries. 9,12, 14,17,18 Some groups included in the vulnerable group are pregnant women, children, and immunocompromised patients. Research conducted by the New England Journal of Medicine recently showed that 98% of monkeypox cases diagnosed in 16 countries between April and June occurred in men who had sex with other men. ...
... Clothes, bedding, towels or eating utensils/plates contaminated with the virus from an infected person can also infect others. 14 In addition, animal-to-person transmission can also occur. Contact with blood, body fluids or skin lesions of infected animals can transmit Monkeypox. ...
... The differential diagnosis includes syphilis, cancroid, varicella zoster, herpes simplex, hand-foot-and-mouth disease, molluscum contagious and cryptococcus. 1,3,5,6,8,12,14 The definition of Monkeypox cases can be divided into four classifications of suspected (suspected), confirmed, probable and possible diagnoses. The Monkeypox case definitions are divided into four classifications: suspected, confirmed, probable and possible diagnoses. ...
Article
Monkeypox disease (monkey smallpox) is a disease that has never been found in Indonesia since it was first discovered in humans in the Congo in 1970. So if there is one positive confirmed event, then the disease is an Extraordinary Event (KLB). This disease has become a global concern because since May 13, 2022, WHO has received reports of Monkeypox cases from non-endemic countries. It has expanded to 4 WHO regions: Europe, America, Eastern Mediterranean, and Western Pacific. Until now, further investigations and studies are still being carried out to understand more about the epidemiology, sources of infection, and transmission patterns in non-endemic countries that have reported new cases, such as Indonesia. Until now, no specific treatment has been proven to treat Monkeypox infection. Currently, the therapy used is symptomatic support. The antiviral tecovirimat, or TPOXX, developed by the European Medicines Agency (EMA) as a Monkeypox therapy in 2022 based on research, has not been marketed freely. In addition, antivirals such as cidofovir and brincidofovir have been shown to be effective against orthopox virus in vitro and in animal studies. However, the effectiveness of this drug against monkeypox in humans is not yet known. However, this disease can be prevented by vaccination. In Indonesia, the Modified Vaccinia Ankara-Bavarian Nordic (MVA-BN) vaccine is recommended to prevent Monkeypox disease. The existence of the outbreak report is important to discuss, explore, and understand more about the disease and its management and prevention.
... 6 Monkeypox virus is classified into the Orthopox virus (OPXV) genus, the Chordopoxvirinae subfamily, and the Poxviridae family. 1 It was first isolated in 1958 from a species of diseased monkey called Macaca cynomolgus that was brought from Africa to Denmark, and the first human infection with the virus was reported in 1970 from Zaire in central Africa. 7 Since that year, most of the reported cases have been related to the two endemic regions of Congo basin countries of Africa and West Africa, as well as a few sporadic cases in the United States, Nigeria, and the United Kingdom who acquired the infection by travelling to the endemic areas. 7 The recent outbreak of the virus outside of Africa has raised concerns among global health organisations. ...
... 7 Since that year, most of the reported cases have been related to the two endemic regions of Congo basin countries of Africa and West Africa, as well as a few sporadic cases in the United States, Nigeria, and the United Kingdom who acquired the infection by travelling to the endemic areas. 7 The recent outbreak of the virus outside of Africa has raised concerns among global health organisations. Up-to-date Monkeypox Outbreak Global Map by CDC announced 73,288 confirmed cases (72,428 in countries that have not historically reported monkeypox and 860 in countries that have historically reported monkeypox) of virus infection by 14 Oct 2022. ...
... 18,19 A rash appears shortly after the prodromal phase that begins to grow and disseminate throughout the body. 7 Lesions will develop in four stages_ macular, papular, vesicular and pustular __ before scaling and healing. 7 This process occurs in 2-3 weeks (Table 1). ...
Article
The multi-country outbreak of monkeypox virus (MPXV) infection, while the coronavirus disease 2019 pandemic is still an ongoing issue, has caused a new challenge. The re-emergence of MPXV and the rising incidence in non-endemic countries is turning into an upcoming threat to global health. Hence, rapid identification of the virus with appropriate methodology with the lowest false results plays a critical role in estimating the global extent of the crisis and providing preventive measures. This review summarised the main applicable strategies for primary detection and confirmation of MPXV and highlighted available data in biosafety, requirements, standard operating procedures, specimen collection, transportation and storage of clinical samples, and waste disposal of the viral agent. Also, various assays including molecular techniques, immunoassays, histopathological methods, electron microscopy, genomic sequencing, and cell culture have been illustrated. Moreover, we reflected on current knowledge of the advantages and disadvantages of each approach.
... Although other nations in Central and West Africa have also recorded cases of monkeypox in people, the first human MPX case was reported in 1970 in the Democratic Republic of the Congo (DRC), where the disease is endemic [1]. The USA and Sudan both reported outbreaks of this disease in the early 2000s with a recent outbreak in the USA due to imported wild rodents from Africa [3]. Case fatality rates in Democratic Republic of Congo were around 10% among non-vaccinated individuals as compared to the smallpox vaccinated population [3]. ...
... The USA and Sudan both reported outbreaks of this disease in the early 2000s with a recent outbreak in the USA due to imported wild rodents from Africa [3]. Case fatality rates in Democratic Republic of Congo were around 10% among non-vaccinated individuals as compared to the smallpox vaccinated population [3]. In 2022, an outbreak was witnessed in the UK, originating from a British resident who went to Nigeria [4]. ...
Preprint
In 2022, Monkey pox disease was declared as a Global Health Emergency. With the emergence of an epidemic such as this, it becomes imperative that accurate information is imparted to all the individuals. However, as seen in the case of Covid-19 pandemic, it is evident that people consume most of the information through social media platforms such as Instagram, Facebook, Twitter and others. With this, there is a possibility of an increase in dissemination of misinformation which was very well noted in case of Covid-19 Pandemic. Aims: To analyse the information that is available on Instagram regarding Monkey Pox disease and to determine its accuracy. Methodology: A cross-sectional, observational type of study where total of 522 posts were analysed over a period of two days was done. Top 90 posts from the top six monkey pox related hashtags were analysed on the basis of a proforma made of pre-selected questions via the platform google docs and accordingly the results were calculated. Results showed that, most of the posts are descriptive in nature, and only a few(11.65%) were posted by doctors. Most of them were posted by news or other agencies. Some of the posts were from unverified sources as well(27.65%). Discussion: As witnessed in Covid 19, there is prevalent misinformation when a global health emergency is concerned, attributed to vast access to social media platforms. In order to combat this dissemination of false information, such platforms should be regulated and should operate under guidelines of WHO.
... Thus, laboratory confirmation is crucial since MPXV can induce illness that is clinically identical to other pox-like illnesses. WHO lists smallpox, varicella, chickenpox, measles, bacterial skin diseases, scabies, drug allergies, and syphilis among the possible differential diagnoses [37]. ...
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With the recent increased prevalence of human outbreaks, monkeypox has been recognized for decades as an infectious disease with substantial pandemic potential. The majority of cases of this virus have been observed in the European region (11,865), with few cases in the Western Pacific (54). Various governing health agencies are striving to restrain the fatal monkeypox virus (MPXV). Health practitioners around the world are learning about the many clinical manifestations of this infection, and its potential therapies. Despite the plethora of new evidence and rising cases, the essential questions remain unsolved. Thus, in this review, we have modernized the outlook for monkeypox, which will be helpful for various medical practitioners. In the light of continuing outbreaks around the world, we have also presented our assessment of the readiness of India against this outbreak, with a special focus on its effects on oral health.
... It is caused by monkeypox virus, a member of the family Poxviridae's Orthopoxvirus genus (2)(3)(4). The clinical syndrome is characterized by fever, rash, headache, flu and lymphadenopathy (5). Complications of monkeypox can include pneumonitis, encephalitis, sight-threatening keratitis, and secondary bacterial infections (6). ...
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Monkeypox is a viral etiological agent with hallmarks analogous to those observed in smallpox cases in the past. The ongoing outbreak of Monkeypox viral infection is becoming a global health problem. Multi-valent peptide based next generation vaccines provides us a promising solution to combat these emerging infectious diseases by eliciting cell-mediated and humoral immune response. Considering the success rate of subtractive proteomics pipeline and reverse vaccinology approach, in this study, we have developed a novel, next-generation, multi-valent, in silico peptide based vaccine construct by employing cell surface binding protein. After analyzing physiochemical and biological properties of the selected target, the protein was subjected to B cell derived T cell epitope mapping. Iterative scrutinization lead to the identification of two highly antigenic, virulent, non-allergic, non-toxic, water soluble, and Interferon-gamma inducer epitopes i.e. HYITENYRN and TTSPVRENY. We estimated that the shortlisted epitopes for vaccine construction, roughly correspond to 99.74% of the world’s population. UK, Finland and Sweden had the highest overall population coverage at 100% which is followed by Austria (99.99%), Germany (99.99%), France (99.98%), Poland (99.96), Croatia (99.93), Czech Republic (99.87%), Belgium (99.87), Italy (99.86%), China (97.83%), India (97.35%) and Pakistan (97.13%). The designed vaccine construct comprises of 150 amino acids with a molecular weight of 16.97242 kDa. Molecular docking studies of the modelled MEMPV (Multi-epitope Monkeypox Vaccine) with MHC I (PDB ID: 1I1Y), MHC II (PDB ID: 1KG0), and other immune mediators i.e. toll like receptors TLR3 (PDB ID: 2A0Z), and TLR4 (PDB ID: 4G8A) revealed strong binding affinity with immune receptors. Host immune simulation results predicted that the designed vaccine has strong potency to induce immune responses against target pathogen in the form of cellular and antibody-dependent immunity. Our findings suggest that the hypothesized vaccine candidate can be utilized as a potential therapeutic against Monkeypox however experimental study is required to validate the results and safe immunogenicity.
... However, their efficacy against the monkeypox virus is unknown [51]. Scientific data reveals that the smallpox vaccination offers more than 80% protection from Monkeypox infection [52]. JYNNEOSTM vaccine (also known as Imvanex or Imvamune), has been licensed in the US to prevent monkeypox and smallpox [53]. ...
Article
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Currently, Monkeypox is a threatening viral disease terminology around the world that worries the global community after the Coronavirus pandemic. Beyond the woods of central Africa, where cases were first discovered, the geographic distribution of monkeypox cases has extended to other parts of the world including India, where cases have been imported. Under these circumstances, public confusion is noticed between Monkeypox and Monkey fever across southern parts of India. Monkeypox and Monkey fever (Kyasanur Forest Disease) are categorized as potential emerging or re-emerging Zoonotic diseases of humans and are fundamentally having clear-cut differentiation in their causative agent, clinical symptoms, and pathogenesis. Hence, it is important to clarify and eliminate the confusions which would have tremendous and dangerous public health impacts. As defined by the Global Burden of Disease Study, Emerging Infections (EIs) are those that have recently appeared in a population or previously existed but are now gaining in prevalence or geographic spread rapidly. A disease emerges from the interactions between rapidly evolving infectious agents and the environmental changes and changes in human behavior that provide these agents with favorable ecological niches. This review attempts to differentiate between the two emerging infections - Monkeypox and Monkey fever which are affecting a significant group of the population worldwide and provides a comparative picture of both diseases towards developing adequate awareness among the public and expects to complement the community-based future control measures.
... The causative agent was first isolated in a captive monkey in Denmark, but the virus is naturally transmitted among small rodents and mammals in African countries. Evidence shows that squirrels (especially Funisciurusanerythrus) inhabiting agricultural areas in the DRC are considered primary candidates to sustain viral transmission among people in nearby settlements [12]. ...
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Monkeypox (MPX) is a zoonotic disease caused by the monkeypox virus (MPXV) belonging to the Orthopoxvirus genus. It results in a smallpox-like disease in humans. Recently, MPX has been declared a public health emergency of international concern. The disease is characterized by fever, muscle ache, malaise, and pustules. The presence of characteristic significant lymphadenopathy helps it to be differentiated from other similar illnesses. Early detection of cases and effective contact tracing is necessary for breaking the chain of transmission. Diagnosis can be confirmed by polymerase chain reaction (PCR) testing of the lesions or by demonstrating the virus in other body fluids. There is no specific treatment for monkeypox, although the smallpox vaccine is thought to have high levels of protection. In this review, we have tried to collect all relevant information about the current outbreak, including epidemiological data, modalities of diagnosis, and treatment options
... 28 Surprisingly, the most frequent animal seized in the traps around the affected individual's residences was a mouse (Mus sp.). 18,24 The virus transmission between mammalian species was established by inoculating a rabbit (family Leporidae) with the MonkeyPox virus following exposure to an infected prairie dog at a veterinary facility. 28 Table 2 3.2. ...
Article
Full-text available
Monkeypox virus was named so because of its detection in monkeys in 1958. It belongs to the same family as smallpox and chickenpox viruses. There had been numerous outbreaks of this malady initially in the African continent and other parts of the world. The simultaneous spread in nineteen countries in 2022 has raised some serious concerns. Monkeypox is no more a rare disease and has the potential for bioweapon use. We discuss the various ways to prevent its spread, treatment options available, diagnosis, and differentiation from other closely related diseases. We also discuss if the present outbreak could be a bioattack or if this disease is here to stay. The literature suggests that we can effectively manage Monkeypox because of the availability of drugs and vaccination against smallpox. There is also a need for active surveillance against the new resistant recombinant viral strains. The possibility of this outbreak being a bioattack seems remote, although there are questions about the transmission which still need to be answered.
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Monkeypox virus, a member of the Orthopoxvirus family, is the etiological agent that causes sporadic human infections in Central and West Africa's forested areas. Human infection was first described in Central Africa in 1970. Monkeypox is the most common Orthopoxvirus in humans, at least in endemic regions, and maybe worldwide. Currently Monkeypox virus is known to exist in two separate clades, the West African clade is known to exist from western Cameroon to Sierra Leone, but the Congo Basin clade has been discovered from central and southern Cameroon to the Democratic Republic of the Congo. The most prevalent routes of infection for humans include respiratory, and permucosal percutaneous exposures to infected monkeys, prairie dogs, zoo animals, and humans. This review also elucidates the epidemiology, morphology and genomic organization, transmission, clinical recognition, the possible diagnostic tests, prevention, control and medical countermeasures, and the clinical stages of the monkeypox.
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Human monkeypox is a zoonotic disease resulting from the monkeypox virus (MPXV). During the coronavirus disease (COVID-19) pandemic, MPXV has become a global concern. From 1 January to 22 June of the current year, the World Health Organization (WHO) received reports of 3413 confirmed cases and one death. The most common cases (98%) have been recorded since May of this year (2022). The ongoing outbreak is largely affecting men who have sex with men (MSM). Most of the confirmed cases (86%, n=2933) have occurred in the WHO European countries. Other confirmed cases have been documented from the Americas (11%, n=381), Africa (2%, n=73), Western Pacific (less than 1%, n=11), and Eastern Mediterranean (less than 1%, n=15) regions. It is too early to decide whether the monkeypox outbreak is an independent phenomenon or has been exacerbated by the COVID-19 pandemic. Therefore, global healthcare organizations should apply precautionary measures to stop this outbreak.
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This article reviews the different types of poxvirus infections. Smallpox, although eradicated, must continue to be monitored because of the potential risk of accidental or voluntary (by bioterrorism) reintroduction. Monkeypox and cowpox viruses are considered to be emergent today ; their high risk of dissemination is due to the increase in international transport as well as trends for new animals as pets and the loss of vaccinal protection against smallpox. Molluscum contagiosum (molluscipoxvirus) causes mild infections, is particularly frequent in children ; in adults it is a marker of the risk of sexually transmitted infections and can, in cases with profuse lesions, reveal AIDS.
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Monkeypox virus (MPXV) is a human pathogen that is a member of the Orthopoxvirus genus, which includes Vaccinia virus and Variola virus (the causative agent of smallpox). Human monkeypox is considered an emerging zoonotic infectious disease. To identify host factors required for MPXV infection, we performed a genome-wide insertional mutagenesis screen in human haploid cells. The screen revealed several candidate genes, including those involved in Golgi trafficking, glycosaminoglycan biosynthesis, and glycosylphosphatidylinositol (GPI)-anchor biosynthesis. We validated the role of a set of vacuolar protein sorting (VPS) genes during infection, VPS51 to VPS54 (VPS51-54), which comprise the Golgi-associated retrograde protein (GARP) complex. The GARP complex is a tethering complex involved in retrograde transport of endosomes to the trans-Golgi apparatus. Our data demonstrate that VPS52 and VPS54 were dispensable for mature virion (MV) production but were required for extracellular virus (EV) formation. For comparison, a known antiviral compound, ST-246, was used in our experiments, demonstrating that EV titers in VPS52 and VPS54 knockout (KO) cells were comparable to levels exhibited by ST-246-treated wild-type cells. Confocal microscopy was used to examine actin tail formation, one of the viral egress mechanisms for cell-to-cell dissemination, and revealed an absence of actin tails in VPS52KO- or VPS54KO-infected cells. Further evaluation of these cells by electron microscopy demonstrated a decrease in levels of wrapped viruses (WVs) compared to those seen with the wild-type control. Collectively, our data demonstrate the role of GARP complex genes in double-membrane wrapping of MVs necessary for EV formation, implicating the host endosomal trafficking pathway in orthopoxvirus infection.
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Monkeypox virus (MPXV), a close relative of Variola virus, is a zoonotic virus with an unknown reservoir. Interaction with infected wildlife, bites from peri-domestic animals, and bushmeat hunting are hypothesized routes of infection from wildlife to humans. Using a Risk Questionnaire, performed in monkeypox-affected areas of rural Democratic Republic of the Congo, we describe the lifestyles and demographics associated with presumptive risk factors for MPXV infection. We generated two indices to assess risk: Household Materials Index (HMI), a proxy for socioeconomic status of households and Risk Activity Index (RAI), which describes presumptive risk for animal-to-human transmission of MPXV. Based on participant self-reported activity patterns, we found that people in this population are more likely to visit the forest than a market to fulfill material needs, and that the reported occupation is limited in describing behavior of individuals may participate. Being bitten by rodents in the home was commonly reported, and this was significantly associated with a low HMI. The highest scoring RAI sub-groups were ‘hunters’ and males aged ≥ 18 years; however, several activities involving MPXV-implicated animals were distributed across all sub-groups. The current analysis may be useful in identifying at-risk groups and help to direct education, outreach and prevention efforts more efficiently.
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Monkeypox virus (MPXV) causes human monkeypox (human MPX), which is a similar disease with smallpox in humans. A previous study showed that a single vaccination of monkeys with LC16m8, a highly attenuated smallpox vaccine, protected them from MPX at 4-5 weeks after vaccination. In the present study, we evaluated the long-term efficacy of a single vaccination with LC16m8 in a nonhuman primate model of MPXV infection. The monkeys were inoculated with LC16m8, Lister (parental strain of LC16m8), or mock and then challenged with MPXV via the subcutaneous route at 6 and 12 months after vaccination, which we compared with either Lister or mock vaccination. The LC16m8-monkeys exhibited almost no MPX-associated symptoms, whereas most of the naïve monkeys died. LC16m8 generated the protective memory immune response against MPXV, suggested from the immediate viremia reduction and the response of IgG antibody. The results demonstrate that the vaccination of monkeys with a single dose of LC16m8 provided durable protection against MPXV for longer than 1 year after immunization. Our results suggest that the vaccination of humans with LC16m8 could induce long-term protection against MPXV infection.
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Monkeypox virus (MPXV), a zoonotic orthopoxvirus (OPX), is endemic in the Democratic Republic of Congo (DRC). Currently, diagnostic assays for human monkeypox (MPX) focus on real-time quantitative polymerase chain reaction (qPCR) assays, which are typically performed in sophisticated laboratory settings. Herein, we evaluate the accuracy and utility of a multiplex MPXV assay using the GeneXpert platform, a portable rapid diagnostic device that may serve as a point-of-care test to diagnose infections in endemic areas. The multiplex MPX/OPX assay includes a MPX-specific qPCR test, OPX-generic qPCR test, and an internal control qPCR test. In total, 164 diagnostic specimens (50 crusts and 114 vesicular swabs) were collected from suspected MPX cases in Tshuapa District, DRC, under national surveillance guidelines. The specimens were tested with the GeneXpert MPX/OPX assay and an OPX qPCR assay at the Institut National de Recherche Biomedicale (INRB) in Kinshasa. Aliquots of each specimen were tested in parallel with a q-specific MPX qPCR assay at the Centers for Disease Control and Prevention. The results of the MPX qPCR were used as the gold standard for all analyses. The GeneXpert MPX/OPX assay performed at INRB had a sensitivity of 98.8% and specificity of 100%. The GeneXpert assay performed well with both crust and vesicle samples. The GeneXpert MPX/OPX test incorporates a simple methodology that performs well in both laboratory and field conditions, suggesting its viability as a diagnostic platform that may expand and expedite current MPX detection capabilities.
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Full-text available
Background The rapid and reliable detection of infectious agents is one of the most challenging tasks in scenarios lacking well-equipped laboratory infrastructure, like diagnostics in rural areas of developing countries. Commercially available point-of-care diagnostic tests for emerging and rare diseases are particularly scarce. ResultsIn this work we present a point-of-care test for the detection of Orthopoxviruses (OPV). The OPV ABICAP assay detects down to 1 × 104 plaque forming units/mL of OPV particles within 45 min. It can be applied to clinical material like skin crusts and detects all zoonotic OPV infecting humans, including Vaccinia, Cowpox, Monkeypox, and most importantly Variola virus. Conclusions Given the high sensitivity and the ease of handling, the novel assay could be highly useful for on-site diagnostics of suspected Monkeypox virus infections in areas lacking proper laboratory infrastructure as well as rapid on-site testing of suspected bioterrorism samples.
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Orthopoxvirus species like cowpox, vaccinia and monkeypox virus cause zoonotic infections in humans worldwide. Infections often occur in rural areas lacking proper diagnostic infrastructure as exemplified by monkeypox, which is endemic in Western and Central Africa. While PCR detection requires demanding equipment and is restricted to genome detection, the evidence of virus particles can complement or replace PCR. Therefore, an easily distributable and manageable antigen capture enzyme-linked immunosorbent assay (ELISA) for the detection of orthopoxviruses was developed to facilitate particle detection. By comparing the virus particle binding properties of polyclonal antibodies developed against surface-exposed attachment or fusion proteins, the surface protein A27 was found to be a well-bound, highly immunogenic and exposed target for antibodies aiming at virus particle detection. Subsequently, eight monoclonal anti-A27 antibodies were generated and characterized by peptide epitope mapping and surface plasmon resonance measurements. All antibodies were found to bind with high affinity to two epitopes at the heparin binding site of A27, toward either the N- or C-terminal of the crucial KKEP-segment of A27. Two antibodies recognizing different epitopes were implemented in an antigen capture ELISA. Validation showed robust detection of virus particles from 11 different orthopoxvirus isolates pathogenic to humans, with the exception of MVA, which is apathogenic to humans. Most orthopoxviruses could be detected reliably for viral loads above 1 × 103 PFU/mL. To our knowledge, this is the first solely monoclonal and therefore reproducible antibody-based antigen capture ELISA able to detect all human pathogenic orthopoxviruses including monkeypox virus, except variola virus which was not included. Therefore, the newly developed antibody-based assay represents important progress towards feasible particle detection of this important genus of viruses.
Article
During the course of the recently concluded smallpox eradication program, a new human orthopoxvirus infection was discovered which is caused by monkeypox virus. The disease occurs sporadically in remote villages within tropical rain forests of West and Central Africa. The disease is rare; only 155 cases having been reported from 1970 to 1983. The symptoms and signs of human monkeypox resemble those of smallpox, differing significantly only in the occurrence of lymphadenopathy with human monkeypox disease. Of 155 cases, some 80% are believed to have resulted from infection from an as yet unknown animal reservoir; the rest occurred among unvaccinated close contacts among whom a secondary attack rate of 15% was observed. Although person-to-person spread appears to have occurred in some instances, few cases were observed in the third or fourth generation of transmission and none thereafter. Since 1982, the incidence of human monkeypox infections in Zaire has increased concomitant with an intensified surveillance program. Additional reasons which might explain the increased incidence are discussed. Further surveillance and research of this primarily zoonotic infection are warranted and are in progress.
Article
A method of one-stage rapid detection and differentiation of epidemiologically important variola virus (VARV), monkeypox virus (MPXV), and varicella-zoster virus (VZV) utilizing multiplex real-time TaqMan PCR assay was developed. Four hybridization probes with various fluorescent dyes and the corresponding fluorescence quenchers were simultaneously used for the assay. The hybridization probes specific for the VARV sequence contained FAM/BHQ1 as a dye/quencher pair; MPXV-specific, JOE/BHQ1; VZV-specific, TAMRA/BHQ2; and internal control-specific, Cy5/BHQ3. The specificity and sensitivity of the developed method were assessed by analyzing DNA of 32 strains belonging to orthopoxvirus and herpesvirus species.