RRTM 12 153
RRTM 12 153
RRTM 12 153
Tesfaye Kassa Abstract: Orf virus (ORFV) is the etiologic agent of Orf or ecthyma contagiosum in humans
but primarily affects different domestic and wild animals. The disease mostly affects sheep, goats
School of Medical Laboratory Science,
Institute of Health, Jimma University, and other small wild ruminants and spreads to humans through direct contact with infected
Jimma, Ethiopia animals or by way of contaminated fomites worldwide. ORFV is taxonomically classified as a
member of the genus Parapoxvirus. It is known to have tolerance to inactivation in a drier
environment, and it has been recovered from crusts after several months to years. Among
immunocompetent people, the lesions usually resolve by its natural course within a maximum
of 8 weeks. In immunosuppressed patients, however, it needs the use of various approaches
including antiviral, immune modifier or minor surgical excisions. The virus through its associa
tion with divergent host ranges helps to develop a mechanism to evade the immune system. The
relative emergence of Orf, diagnosed on clinical ground among human cases, in unusual
frequencies in southwest Ethiopia between October 2019 and May 2020, was the driver to
write this review. The objective was to increase health care providers’ diagnostic curiosity and to
bring the attentiveness of public health advisors for prevention, control and the development of
schemes for surveillance of Orf zoonosis in a similar setting like Ethiopia.
Keywords: Orf, Orf virus, ecthyma contagiosum, zoonosis, human, Ethiopia
Background
Orf or ecthyma contagiosum (EC) is primarily a zoonosis affecting the skin of
humans.1 The disease is caused by Orf virus (ORFV) which is a member of the
genus Parapoxvirus.2 The virus is communicable to humans from infected small
ruminants predominantly sheep and goats. Less commonly, it has been described
transmissible from contaminated fomites and environments besides a rare human-
to-human transmission or auto-infection has also been defined.3
ORFV has a worldwide endemicity among livestock herds.1,4 The virus manifests
among infected animals as proliferative skin or mucous membrane lesions named
ecthyma contagiosum, contagious pustular dermatitis, infectious labial dermatitis,
scabby mouth, or sore mouth with the lesions often appearing on the parts of lips,
muzzle, ears, eyelids, nostrils, and, less commonly in udders, genitalia, and feet of the
infected animals.5,6 In humans, the lesions manifest often on the exposed parts of the
skin that can contact animals especially on the hands, fingers, and forearms.7
Ethiopia, in the sub-Saharan and horn of Africa region, has a sizable livestock
Correspondence: Tesfaye Kassa
Jimma University, PO Box 6 788, Jimma, resource, and most of them are owned by small scale farmers and pastoralists in the
Ethiopia rural areas of the country. According to the Central Statistical Agency of Ethiopia in
Tel +251931057195
Email ktes36@gmail.com; 2019, the estimated count of sheep and goats are approximately 72.0 million among
which 33.02 million and 38.96 million are sheep and Thus, the objective of the current study is to provide an
goats, respectively.8 These categories of animals alone, increased curiosity for health professionals and public
excluding other small wild and domestic ruminants in the health officials in Jimma, Ethiopia as well as in many
geographic location, can greatly increase the risk of human other low income settings of the potential importance of
exposure to the virus. Also, human employment status is this virus. Different literature sources were examined to
another known associated factor for increasing the occur review the disease and the virus, respectively.
rence of the infections in urban areas such as among Furthermore, this review offers an update on clinical find
veterinarians, slaughterhouse workers, butcher, farmwor ings of human Orf cases in Ethiopia and equally, it may
kers, zookeepers, and others.9–11 Still the largest propor sensitize the health sectors in other African countries to
tion of the Ethiopian population (~78%) lives in rural areas consider the potential importance of this virus in their
on small hold farms.8 clinical settings. The information considered in this review
There are few published works available on the sub suggests it is important to recognize orf as the disease is a
stantial morbidity of Orf or EC among animals in common infection of ruminant animals in most parts of
Ethiopia.12–15 This author searched published studies and Africa18 where per capita health spending is relatively low
no studies were found describing Orf or EC infections of and advanced diagnostic tools are inaccessible to support
humans in Ethiopia. Recently, a series of cases clinically diagnosis. Before the virus extends its affliction among
suspected as Orf have been observed among patients at a susceptible hosts, there is a need for confirmatory diag
dermatology clinic in Jimma University Medical Center as nostic tools to rule out and employ a one health approach
well as cases arising in the community in Jimma town for epidemiologic surveillance, prevention and control of
since October 2019 until the mid of 2020. Typical clinical the disease.
dermatologic appearances of the lesions were used to
record suspected cases of ORFV infections despite the Search Methods
absence of mechanisms to confirm the virus from biopsied A literature search was made to find published studies
material (Figure 1) using histology, molecular amplifica reporting on Orf and Orf virus with particular focus to
tion techniques, or electron microscopy.16,17 For some of African countries. Emphasis was given on the burden of
the visiting cases, the base of the lesions were opened and the virus in human morbidity as well as its distribution in
swabbed for bacterial culture and all remained negative source animals with particular attention to sheep and goats
after one week of incubation at 37 ºC (data not shown). published in the English language, mainly in recent years.
Figure 1 A 45 year old woman patient representative of the characteristic single Orf lesion on the second (A) and eighth (B) weeks of orf/EC appearance, from Jimma
town, Ethiopia.
ORFV, in the same manner as other poxviruses, repli that also play roles in viral pathogenesis.29,34,35 These
cates in the cytoplasm of infected host cells and therefore include an interleukin (IL)-10 homologue, a chemokine-
encodes its own machinery for DNA replication and tran binding protein (CBP), a vascular endothelial growth fac
scription. The DNA is a linear double-stranded molecule tor homologue (VEGF), interferon-resistance (IFNr) pro
and has a size of 134 kb to 140 kb in length. It encodes tein, and a cytokine-binding protein (CBP).36–38 The IFNr
about 132 genes and is assumed to have the smallest gene is present in the “CORE‟ region which is a relatively
genome length among poxvirus members.29,30 The gen conserved one with a high G+C content. IFNr plays a role
ome consistes of a central region (Core) and inverted in the viral replication and morphogenesis.32
terminal repeats (ITR) at both ends of the DNA molecule
(Figure 3). The core region of the genome encodes factors Virulence Factors
for the virus genetic transcription and replication. The The major virulence factors identified in ORFV as indi
transcription process is followed by the translation of cated above include an IL-10 homologue, CBP, VEGF
different proteins for the construction of new virus parti homologue, granulocyte-macrophage colony-stimulating
cles in the cytoplasm of infected cells. Instead, the term factor (GIF), apoptosis inhibitor, IFNr and inhibitors of
inal regions of the ORFV genome encode for different NF-κB.36–38 The discovery of an IL-10 homologue gene in
accessory factors that also provide the parapoxvirus a poxvirus was first reported in ORFV.23 Mammalian IL-
group many of its unique features playing a role in patho 10 is a multipurpose cytokine that has suppressive effects
genesis. The virus expresses about 35 virus specific pro on inflammation, anti-viral responses and T-helper type 1
teins with molecular weights ranging between 10 and 220 (Th1) effector function. The inhibition of a Th1 response
kDa on the surface of the virus particle as a virulence happens indirectly through abating the function of antigen-
factor or usable as a candidate for vaccine development presenting macrophages and dendritic cells.32 In addition,
since some of them are capable of inducing an immune IL-10 has co-stimulatory functions on T lymphocytes
response.31 associated with Th2 responses, mast cells and B cells.
ORFV is not different from other poxviruses in its The molecular mass of IL-10 homologue protein is 21.7
possession of at least two categories of genes that play kDa (185 amino acids sequence) making the ORFV IL-10s
roles in the virus life. These are early genes transcribed in slightly larger than their mammalian counterparts which is
the infection process and those transcribed in later periods ~18.6 kDa. The amino acid sequence identity of the virus
(intermediate and late genes). It is doubtful whether more IL-10 with human IL-10 is known to be 67% in the
than one protein is produced from the early transcription C-terminal two thirds of the polypeptide, although the
of mRNAs.33 Most of the genes of ORFV in the terminal relatedness at the nucleotide level is less apparent.
regions are unique and encode factors that play in the virus Curiously, the N-terminal region of the IL-10 like contains
pathogenicity by modulating the immune system for the little similarity to that of mammalian IL-1023,32 and this
induction of inflammation, innate immune responses and may help to deduce that the viral IL-10 polypeptide is
the expansion of acquired immunity.34 These terminal larger than the mammalian counterpart.
regions of the genome typically encode other proteins CBP is another known virulence factor among pox
that also interact with components of the immune system viruses. Normally, chemokines are a large family of
molecules that recruit and activate immune cells at sites of and abrasions. The virus is reported to remain viable on
inflammation and infection.39 CBP has been described in the wool and hides of animals for approximately one
ORFV and is thought to interact with the chemokine month after the lesions have healed.7 ORFV is very resis
families with strong affinity and results in anti-inflamma tant to inactivation in the environment, and has been
tory process.38 recovered from dried crusts after several months to years
ORFV VEGF gene encoding a polypeptide that is in the laboratory, with one account of survival recorded for
homologous to mammalian VEGF. The viral VEGF homo up to 12 to 15 years.4 This viral property of resistance to
logue is likely to contribute to the widespread expansion inactivation can bring unexpected widespread public
of vascular endothelial cells and enlargement of blood health significance among animals and humans in the
vessels and dermal bumps seen in typical EC lesions. future.
The viral VEGF through its capacity to induce vascular Humans can also become exposed to the virus by
permeability results in the development of broad scabs. exposure to vaccines containing live ORFV that is applic
This property is linked to VEGF because the lesions able for animals.42 However, human to human transmis
induced by the VEGF-gene deleted ORFV resulted in no sion has not been clarified well. Most published articles do
scab formation.37 The presence of the scab affords protec not agree with the virus transmissibility being transmissi
tion of the virus from external factors knocked down in the ble between humans.43 While still others reported direct
lesions. On the other hand, the scab material which drops contact with ORFV contaminated fomites resulted in very
from Orf lesions contains an extensive number of infec
rare cases of human infection.3,44 Nosocomial transmis
tious virus particles that easily contaminate different envir
sion has also been documented for one epidemic in the
onments and contribute to the virus persistence. The virus
burn ward.7,45
in the process can remain viable for approximately a year
Once the virus reaches the skin, Orf or EC develops
retaining the capacity to infect naïve hosts.34
after a 3 to 7 days incubation period. The clinical pathol
ORFV is unaffected by type 1 and type 2 interferon
ogy observed at the sites of infection is typically the
because of an IFNr factor in the virus.33 The virus also
creation of pustules and scabs. Orf lesions are normally
demonstrates anti-apoptosis and anti-interferon properties
benign; however, more serious complications can arise
due to a protein called E3L.39 The NF-κB, is a family of
with secondary bacterial infections or due to misdiagnosis
transcription factors that plays an essential role in directing
or over-treatment.1,46 ORFV infection in humans remains
the immune response by modifying the progression of
localized as foci unlike in animals where it is usually
numerous biological pathways ranging from immune reg
proliferative lesions. The progression of Orf from infection
ulation, inflammation, stress response to apoptosis.
to resolution has been categorized sequentially into six
Inhibitors of NF-κB encoded by ORFV help the virus to
evade the host immune responses.40 stages each stage taking roughly one week.1
GIF (protein inhibitor of Granulocyte-Macrophage The first stage of ORFV infection is termed as the
Colony-Stimulating Factor and Interleukin-2) is encoded maculopapular stage which is distinguished by vacuoliza
by ORFV and expressed in the late stage of the infection. It tion of the cells of the upper epidermis. A target stage
has the dual activity of inhibiting host Granulocyte- follows and is characterized by having a macroscopically
Macrophage Colony-Stimulating Factor and IL-2, thus visual red center bounded by a white ring of maculopap
inhibiting host immune activity.41 Knowledge of the var ular stage cells developing, which is further encircled by a
ious virulence factors and the mechanism of ORFV red halo of inflammation. This is followed by an acute
immune evasion apparatus can be beneficial. This may stage where the epidermis disappears and in certain areas
direct the way to develop new and efficient vaccines or hair follicles are dilated and become full of pycnotic cells.
drugs to respond to the outbreaks among humans as well In a regenerative stage in the fourth week, the epithelium
as in animals around the world. is regenerating and the lesion becomes drier with a yellow
crust and black center on the surface. In the fifth week, a
Transmission and Pathogenesis papilloma stage is distinguished by a raised epidermal
The ORFV primarily originates from skin lesions and lesion with finger-like projections of epidermis extending
scabs of various animals. The virus from infected animals downward into the dermis. Finally, the course enters into a
is assumed to reach the human skin through minute cuts regressive phase (in the sixth and later weeks) wherein the
skin returns to its normal thickness and appearance, often spontaneous regression.49,51 This type of lesion can take
without scarring.47 extended time or may fail to resolve naturally. In some
Since immunity against the virus is short-lived, even in cases, ORFV infections can cause complications such as
immunocompetent animals or humans, reinfection can erythema multiforme reactions and presents with rashes on
take place at a lower degree of severity, remain unnotice the back of hands, legs and ankles. A swan-neck or a
able or heal quickly.43,48 Large, highly vascularized, flexion of the base of index finger deformity has also
tumor-like lesions of the skin called giant orf have been been reported.43,49,50 Very rare outcomes of Orf have
noted in immunocompromised persons. In such people, a been described including papular and vesicular rashes
severe progressive disease can develop and present with and bullous pemphigoid‒like eruptions.54 Most published
multiple lesions. The lesions are typically larger than usual studies showed that Orf in humans is misdiagnosed and
dimensions (>5 cm), with multiple and recurrent patients are usually exposed to overtreatment and
lesions.49,50 unwanted costs as can be viewed in Table 1.
Other manifestations important for differential diagno
Clinical Features in Humans sis in humans includes: cowpox and pseudocowpox (milk
ORFV infection is mostly limited to the epidermal parts of er's nodule) – both are a member of poxviruses naturally
the skin. Viral ecthyma or nodules typically (one to a few affecting cattle; herpetic whitlow (caused by herpes sim
in number) develop on exposed parts of the human body plex viruses); furuncle; pyoderma; pyogenic granuloma;
including fingertips, hands, forearms, or face.51,52 The cat scratch disease (associated with a bacterial etiology
lesions originate as trivial papules that in due course including Bartonella henselae); atypical mycobacterial
grow into ulcerative lesions. The original lesion is a infections; syphilitic chancre; deep seated fungal infec
small, firm, red to blue papule at the site of ORFV entry, tions; sporotrichosis; squamous cell carcinoma; keratoa
typically on a finger or hand. The papule develops into a canthoma type; primary inoculation tuberculosis;
hemorrhagic pustule or bulla, which can quickly produce a tularemia; acute febrile neutrophilic dermatosis (sweet
central crust and bleed. During later stages, the lesion syndrome); ecthyma gangrenosum; erysipeloid (caused
transforms into a nodule that can weep fluid and leak by Gram positive non-sporing bacilli); insect bites, or
blood, often surrounded by a thin crust and eventually, it anthrax.1,51,75 ORFV zoonotic infection shares similar
becomes coated with a thick crust. The skin lesions may clinical manifestations and exposure risks with etiologies
be associated with low-grade fever, which usually lasts that may have potentially life threatening outcome. As a
just a few days with moderate lymphadenopathy, erythema result, suspect orf cases may necessitate the availability of
multiforme, or lymphangitis.53 confirmatory diagnostic arrangements especially in places
The majority of infections will be uncomplicated disor where little or no attention has been given to this virus.
ders, with the lesion usually resolving naturally within a 3 to
6 week period and sometimes can extend up to 8 weeks. Host Immune Response
Secondary bacterial infections can happen at the skin open The interface of the ORFV particle with the infected host's
ings. Possible complications include poisonous erythema, immune system has been a subject of research for decades
erythema multiforme and a bullous pemphigoid-like condi and most of the discoveries appear from findings in
tion; an Orf-induced immunobullous disease.54,55 animals.31,75 Although both cell-mediated and humoral
Orf lesions that pass through the various pathogenesis immune responses have been confirmed in sheep and
and clinical stages generally have a dimension of greater human ORFV infections, cell-mediated immunity plays
than 1 to 3 cm in diameter but can rarely extend to be as the major role against the virus.75,76 Antibodies do not
big as 5 cm. The lesions can be painful but usually resolve appear to confer protective immunity to ORFV although
without the need for treatment.56 IgG2 isotype might be important in defense against the
Lesions can appear as a generalized vesiculopapular virus. IgG2 is not transported in the milk of ruminants
rash on the skin and mucosa.7 ORFV infections rarely which might explain why colostral antibodies are not
involve the eyes, though it has been reported to cause protective in lambs and kids.34,77 Since immunity against
blindness when it emerges on the eye.57 ORFV is short-lived, both animals and humans remain
In immunocompromised persons, giant Orf lesions can susceptible to reinfection.20,75 So far, there is no available
develop with continued progression in size instead of protective vaccine for human use.
Number of (Suspect) Orf Occupation of the Cases Main Clinical Picture, Sign and Methods Employed to Confirm Support and Management Given Orf case Reference
Cases Symptom Orf to the Cases Country
of Origin#
58
231 suspect cases from Orf suspect cases were from 18 In 95% of orf cases, the lesions Electron microscopy Nothing given Not found
slaughtering units. lambs and sheep slaughtering units. appeared on hands.
The chief risk of contracting orf was From 119 lesion samples collected,
related to handling skins or wools. 85% (n=100) of them were positive
for ORFV.
59
A 34-year-old man The person has history of contact The case visited health facility with Complete blood count (CBC) and Analgesic, wound care with the use of Turkey
with sheep mildly painful 4 lesions on the tip and X-ray graph were normal. The povidone iodine & mupirocin cream.
the dorsa of his fingers (one on right characteristic lesion, its course and
hand). The lesions measured history of contact with sheep was
60
4 cases of orf (complicated Each of the case are described below Four complicated cases of orf as each In all cases, clinical evidence and All the patients were given the Turkey
cases) described below history of animal contact were used. following as the lesions fail to regress
naturally. Topical imiquimod cream
was applied in all cases twice daily for
five to ten days resulting in rapid
regression of orf and associated
lesions.
60
1. A 25-year-old woman She had a history of injury on her The case had pruritic, erythematous, Topical corticosteroids. Turkey
hand with a knife while cutting sheep centrally darker macules and papules
meat. (target lesions) on the hands and feet.
60
2. A 56-year-old woman. The case had fed a sheep with a sore The case had a nodule circumscribed Topical corticosteroids and oral Turkey
mouth. with an erythematous border on her antihistamines.
left thumb.
60
3. A 45-year-old Diabetic The case slaughtered sheep during The case developed a giant, target-like Antiseptics and wet dressings for the Turkey
(type-2) man. the Feast of Sacrifice. orf nodule of about 4.5cm on his right patient finger lesion were applied.
index finger complicated with axillary
adenitis.
60
4. A 42-year-old woman The case had transported carcasses She has had a painful, weeping and She had been unsuccessfully treated Turkey
during the Feast of Sacrifice. crusting nodular lesion on her left with oral and topical antibiotics
DovePress
https://doi.org/10.2147/RRTM.S306446
thumb for 4 weeks. She has severe before she was managed with various
and recurrent edema of the eyelids. oral antihistamines.
(Continued)
Kassa
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Table 1 (Continued).
160
Kassa
Number of (Suspect) Orf Occupation of the Cases Main Clinical Picture, Sign and Methods Employed to Confirm Support and Management Given Orf case Reference
Cases Symptom Orf to the Cases Country
of Origin#
DovePress
43
Nine orf cases aged 33 to 58 Three of the cases were teachers and Clinical diagnosis was made based on Electron microscopy was used in five One case received treatment for Turkey
years old. the other six were housewives. All the history, appearance and location case biopsies. anthrax. Lesion of another case was
were not exposed occupationally to of orf lesion and clinical course. All CBC was normal in all. Bacterial incised for drainage while in a third
animals but orf developed after the the lesions appeared on the hands. culture was done in six cases and all patient, lesion was excised totally. In
Feast of Sacrifice. The lesion was seen on the dorsal was negative. Histopathology was all cases, adequate analgesics and
https://doi.org/10.2147/RRTM.S306446
Six out of nine were females. parts of left hands in eight cases and used in five cases. conservative wound care was given
right hand in one. In two cases giant with povidone-iodine and keeping the
orf developed and patients feared of lesion dry. All but one case resulted in
having cancer. Stiffness of finger joints, healing without any complications.
swan-neck deformity and paresthesia Three cases received overtreatment.
developed in one case with giant orf.
61
A seven-year-old girl child There was a history of contact with The child presented with an orf of the Clinical The lesion was incised and drained USA
sheep. hand. and healed spontaneously within 5
weeks.
62
Two cases of orf from Milan (a The two cases had contact with lamb In both patients, typical orf lesions On clinical grounds. Not stated Italy
34-year-old Muslim man from meat and were acquired during happened on the left hand fingers.
Tunisia, & a 57-year-old Jewish religious practices “Feast of Sacrifice”
man) and “Kosherization”.
63
Seven men cases aged between All had been infected 2–3 weeks after In all patients, clinical diagnosis was In all patients, clinical diagnosis was Not stated Italy
18 and 61 years of age were they slaughtered lambs for the Feast made mainly on clinical supported by histologic examinations.
Moroccan, Tunisian or Egyptian of Sacrifice (Eid al-Adha). One of the characteristics.
origin during 2015–2018 seven was a butcher. ● Aged 34, lesion on left hand,
periods, in Italy. In all the patients, one hand and/or erythematous, & ulcerated nodule
fingers were affected. ● Aged 42, lesion appeared on back
Generally, 4 of the patients, presented of right hand, erythematous
with erythematous pustules; while pustule.
ulcerated nodules in the other 3 ● Aged 44, lesion on the back of right
cases. hand, and erythematous pustule.
● Aged 18, lesion on back of second
right finger, ulcerated nodule.
● Aged 21, lesions appeared on the
palm of right hand, 3 erythematous
pustules.
● Aged 44, lesion appeared on the
back of the second left finger,
erythematous pustule.
● Aged 61, lesion on third right finger
and ulcerated nodule.
the emergency department. (year), sex and location of the lesions bacterial culture. All were negative to the later facility. All the others did
The patients were relatives to each are described below. for B.anthracis. CBC and C-reactive not take antimicrobials.
other living in a farm in three families. ● 19/male, upper lip protein levels were normal. Biopsies The lesions healed spontaneously in 4
Prior to the illness, these families ● 29/male, dorsal side of the third were performed from one patient to 7 weeks.
purchased many goats and sheep for finger of the right hand lesion for histopathology examination Wound care with povidone-iodine
profit making. Anthrax like outbreak ● 19/male, dorsal side of the thumb, and molecular amplification testing. was given and keeping the lesion dry.
led to the deaths among kids and the 2nd and 3rd fingers in the right
lambs in the same herds. hand (3 lesions), ventral side of the
thumb in the left hand & left flank
area.
● 17/male, dorsal side of the third
finger in the left hand.
65
27 confirmed cases reported to All experienced animal contact to Initially almost all were diagnosed as Confirmation was made using real- No data was found for treatment Georgia
Georgia’s national surveillance sheep and cows. Common livelihood cutaneous anthrax. The most time polymerase chain reaction (PCR) regimens administered in the majority
system from January 2016 reported was housewife (48%), common presentations were as was run in Tbilisi, Georgia. of cases.
through January 2017. Their age followed by farmer (15%), pustules (52%) and ulcers (37%); five Culture for anthrax whenever No specific treatment was used in
ranged between 15 and 65 year unemployed (11%) & students (7%). patients (19%) required performed was negative. three of four cases but antibiotics was
old and 15 out of 27 cases were hospitalization and no deaths were prescribed in one case.
females. reported.
Lesions were primarily located on
hands and fingers; most patients had a
single lesion although, unusually, up to
7 to 8 were observed in some; lesions
presented both as painful and painless
in equal measure; the lesions typically
measures between 10 and 25 mm in
diameter and rarely exceeded this
size; some of the most frequently
described accompanying symptoms
were itchiness around the lesion,
fever and lymphadenopathy; and
patients did not have other systemic
DovePress
https://doi.org/10.2147/RRTM.S306446
signs or symptoms of illness.
(Continued)
Kassa
161
162
Kassa
DovePress
Table 1 (Continued).
Number of (Suspect) Orf Occupation of the Cases Main Clinical Picture, Sign and Methods Employed to Confirm Support and Management Given Orf case Reference
Cases Symptom Orf to the Cases Country
https://doi.org/10.2147/RRTM.S306446
of Origin#
66
A 19-year-old Caucasian male Shepherd Patient had a necrotic lesion at the Typically established based on clinical No treatment was given to the Greece
patient. dorsal surface of his left hand. The presentation and history of animal patient but local antiseptics. Strongly
lesion regressed within a month exposure. advised to wear gloves and practice
period. The patient had noticed proper hand hygiene when handling
similar lesions located at the lips and his animals.
the breast of his sheep.
67
a 45-year-old Moroccan-born The man butchered a sheep to The man presented with 3 skin Investigations including erythrocyte Incision and drainage of the lesion USA
man in Louisiana celebrate the Muslim holiday, Eid al- lesions on his fingers overlying the sedimentation rate, C-reactive were attempted but produced no
Adha, a week ago before he dorsal surface of joints. The lesions protein, white blood cell count & HIV discharge. Trimethoprim-
developed skin lesions. were painful erythematous, testing did not reveal problems. sulfamethoxazole
The sheep he purchased had pimple- violaceous plaques on his hands. Vital An X -ray of the right hand was noted 960 mg tablets twice daily and
like lesions on its lips. signs were normal. On physical to have mild soft tissue swelling. itraconazole 100 mg twice daily for
examination, the case revealed No organisms grew on culture for empiric treatment of suspected
bilateral, tender axillary bacteria, acid fast bacilli, and fungi. nocardiosis/Sporotrichosis but later
lymphadenopathy. There were no Exposure history, histopathology, and discontinued.
abnormal cardiovascular, pulmonary, classic skin lesions were used to
or abdominal examination findings. establish diagnosis of orf.
68
65-year-old woman She reported contact with a sheep The case had 3 painless well-delimited The virus was isolated from finger The patient was given antiseptic and France
during the Aïd-el-Fitr festival in erythematous nodules on her fingers nodules. The diagnosis was confirmed local antimicrobial drug therapy (2%
France during 2017. with an erythematosus halo. from biopsy specimens using fusidic acid cream) to prevent
histologic analysis and PCR. bacterial super-infection.
Electron microscopy also confirmed All skin lesions healed in 3 weeks.
the presence of virions in cells from
cell culture. The genome was
sequenced.
France lamb during Eid al-Adha. He appearing papule on his finger after he Mechanisms of orf-induced The orf lesion disappeared in 6
developed ulceration on his finger. had slaughtered a lamb 10 days ago autoimmune diseases may include weeks. Then in later weeks, the case
and the lesion evolved to a central viral mimicry of host proteins developed a severe tense blistering
ulceration. A diagnosis of orf was (“molecular mimicry”) or alteration eruption associated with mucous
made clinically although no viral of basement membrane proteins by membrane erosions.
confirmatory analysis was performed the virus (increasing immunogenicity). Epidermolysis bullosa acquisita:
at that time. treatment with topical steroids was
Dermatological examination revealed effective with disappearance of the
tense blisters on non-inflamed skin, bullous lesions in a few days, leaving
affecting the whole body, including the scars but not bumps formation. There
face and the scalp. Mucous membrane was no relapse after 3 months of
erosions were present in the oral follow-up.
cavity and the nostrils. Epidermolysis
54
A 36-year-old woman. The case has a history of contact with A 36 year-old woman was diagnosed Histologic finding of skin biopsy Prednisone Iran
dead sheep having had a typical orf with orf on the basis of her typical revealed subepidermal bulla which
lesion. history of contact with sheep and contains fibrin and inflammatory cells
typical lesion, concomitant with composed of eosinophils, some
erythema multiforme and bullous lymphocytes, and neutrophils. The
pemphigoid-like eruptions as dermis showed edema and
complications of orf disease. These perivascular infiltration of
have been associated with rare lymphocytes, neutrophils, and
complications of orf disease. They are eosinophils. The findings were
usually characterized by tense blister consistent with bullous pemphigoid.
eruptions with or without mucosal
involvement.
3
A 16-year-old girl and the girl’s The girl had lesion on her face. Her The girl was admitted with a few fast Based on the clinical features, medical No specific treatment was given. The Turkey
father (his age not indicated) father had developed a similar lesion growing, reddish nodules and facial history and histopathological findings, lesions resolved within 2 weeks of the
on right hand after making contact swelling. The targetoid lesions on the the lesions were diagnosed as orf. examination.
with a lamb during the Feast of frontotemporal region (0.7 to 2 cm in The father was believed to be the
Sacrifice. The father tried to drain his diameter) as well as with periorbital source of infection to the girl.
lesion using tweezers. His daughter edema.
used the same tweezers to squeeze On the other hand, the father had a
acne lesions on her face. centrally crusted, erythematous
nodular lesion measuring about 1cm
in size and was observed on the
palmar aspect of the right hand.
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(Continued)
Kassa
163
164
Kassa
Table 1 (Continued).
Number of (Suspect) Orf Occupation of the Cases Main Clinical Picture, Sign and Methods Employed to Confirm Support and Management Given Orf case Reference
Cases Symptom Orf to the Cases Country
DovePress
of Origin#
70
A 38-year-old man The person had slaughtered a lamb The patient presented with a 5 week This diagnosis was on the basis of Crohn’s disease was suspected & the Belgium
for a religious ceremony two months history of a slightly tender, erosive history of sheep handling and clinical patient was given azathioprine 100mg/
prior to his current presentation. lesion between the thumb and index examination as well as day. Then he was given flucloxacillin
https://doi.org/10.2147/RRTM.S306446
finger of the right hand. histopathological findings. 500mg 3 times/day and topical
Three weeks later, multiple povidone-iodine 10% twice per day
asymptomatic, well circumscribed, for the clinical suspicion of bacterial
erythematous, papulonodular lesions infection. The lesions regressed
appeared on his right lower jaw that completely within 8 weeks.
had developed over several weeks.
71
A 61-year-old woman The woman owned sheep. She visited a clinic for lymphangitis Diagnosis of orf was made on clinical The patient was treated for the The
One week earlier to her lesion, she appearing on her lower forearm as grounds. A wound culture showed bacterial infection with flucloxacillin Netherlands
had suffered two wounds whilst well as a painless lesion on the dorsal secondary bacterial infection. intravenously for 1 day and then orally
walking in the woods. site of the middle of her left little for 1 week. Three weeks later, the
finger. lesion had healed without any scarring
On further examination, she has no or loss of function.
palpable axillary lymph nodes.
46
A 67-year-old Canadian man The person has his own goats and The case developed painful blisters on The diagnosis of orf was made based Analgesic and 500 mg of cephalexin Canada
sheep farm in rural Ontario the third and fourth digits of both on the history of exposure to goats orally 4 times daily for 7 days for
hands after taking care of goats and and sheep, as well as the appearance secondary cellulitis.
sheep in the farm. The blisters were of the typical cutaneous lesions. One month later the lesions resolved
tender and swollen and their centers Biopsy material from blisters was completely without residual scarring.
became ulcerated and crusted. On checked for histology, and bacterial
examination, he was not febrile and culture.
vital signs were within normal ranges.
The nodules were similar in
appearance and measured about
1.5cm in diameter.
72
A 48-year-old woman The woman had fed lambs from a The woman presented with a papulo- Diagnosis of orf was made on clinical The self-maintained local application Switzerland
neighboring farm property bullous cutaneous lesion on the ground. Material from the lesion was of antiseptics did not improve
extensor surface of her right index confirmed by using histological and recovery before her visit. No specific
finger. She did not remember any real-time rt-PCR tests. treatment was initiated after
trauma. She had no fever, evaluation. Three weeks after the
lymphedema, pain or tenderness. initial evaluation the lesion healed
without scar.
39
A mother and a son from Gansu The patients bred 84 Boer goats. The Ten days after contact with the goats, From patients, pathological biopsy In both patients surgical excision was The
province. The son was a 31- mother and her son’s hands become their hands swelled and showed and blood samples were collected. done. People’s
year-old man, and his mother wounded while transporting hay for tender painful injuries. Antibody neutralization test, electron The patients were then treated with Republic of
was a 53-yearold woman. the goats. They cared Orf infected The male case had a fever and a lesion microscopy, virus isolation using amoxicillin. Subsequently the lesions China
suckling lambs without any on his left thumb with no local ovine-epithelial cells, and PCR was regressed in 2 weeks, with no scarring
protection. complications observed. conducted to confirm ORFV. observed.
The mother had a fever, and the
73
A 58-year-old man The patient reported contacts with A painful ulcer on the left hand A biopsy specimen of the lesion was NA France
sheep in a slaughterhouse as a risk second finger developed as well as a used for transmission electron
factor. palpable olecranal lymph node microscopy at low and higher
swelling. The rest of his examination magnification.
was unremarkable. At a low magnification, extreme
swelling of infected cells was seen,
resulting in degeneration. The
parapoxvirus particles was identified
under electron microscopy, presumed
to be ORFVs
74
A 34-year-old man A farmer manages livestock on his He came to hospital with a painful Lesion swabs were sent for PCR assay The patient was treated USA
farm. The rash began a few days after rash with purulent-appearing papules and confirmed ORFV. conservatively with routine wound
a sheep bit his left hand. He had on his hands. His physical examination care and antibiotic agents for possible
recognized that multiple animals on was unremarkable. Initial differential bacterial superinfection. The lesions
his farm had “sore mouth disease.” diagnosis included herpetic whitlow, resolved completely over a period of
He did not wear gloves while feeding cutaneous anthrax, methicillin- 3 weeks. To prevent recurrent
on hand. resistant Staphylococcus aureus infection, the patient was advised to
infection, and poxvirus infection. use gloves when he handled animals
or any potentially contaminated
equipment.
Note: #There were no published case studies found from African countries on human Orf.
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Kassa Dovepress
needed. Sometimes if the lesion appears on a finger, it may in patients with nonhealing or proliferative lesions, and
be important to immobilize the affected finger and anti immunocompromised.87 Interferon alpha-2a is another
biotics may be recommended to prevent bacterial immune response modifier used rarely in Orf cases. It
infections. has antiviral, antiproliferative, and antiangiogenic proper
Orf has been reported resolving with only supportive ties and by so doing, it may stimulate the immune defense
care in burn patients.45 Cryotherapy using liquid nitrogen mechanism.48,95
facilitates recovery from Orf.87 Mortality from Orf has not
been reported in humans.7 Epidemiology
For diagnostic as well as therapeutic purposes, shave Orf or EC is particularly distributed in all sheep and goat
excision technique may be employed to remove portions raising countries worldwide.18,35 The virus further affects
of Orf lesions. For large, out-growing lesions, surgical a wide range of animals including dogs, cats, horses,
dissection from the underlying dermis has been camels and other wild animals.15,75 The wide host ranges
described.88 If the lesion is persistent and refractory, help the virus remain endemic in areas where the animals
curettage and electro-desiccation can be employed as are prevalent, implying an opportunity for the virus and
curative operations.7 In severe Orf cases on the fingers, host interaction dynamicity remain predominant.34 It
amputation may be performed. However, it is only affects all ages of animals but easily manifest in small
advised as a last chance remedy.43 In certain instances, aged ruminants and results in high fatality.7 ORFV infec
the lesion is outsized with ulceration and necrosis that tion in kids of goats and lambs can lead to severe out
may become refractory to treatments and require comes as it interferes with their feeding desire and they
amputation.48,89 Recurrences and delayed healing have become debilitated. Moreover, secondary microbial infec
been reported after surgical treatment.90 Generally, surgi tions due to bacteria and/or fungi through the damaged
cal procedures are usually reserved for immunocompro skin or mucous membranes become a reason for more than
mised patients who do not have the capacity to respond to 90% mortality among one week aged lambs and kids.31
more conservative measures.91 The epidemiology of ORFV among sheep, goats and
As ORFV is a DNA virus, it has a DNA dependent other ruminant animals has been characterized in most
RNA polymerase. This enzyme serves as a target of anti parts of Africa including in Ethiopia.17,18,96,97 However,
viral drugs such as cidofovir. Cidofovir is a nucleotide the incidence of human ORFV infection remains unre
analog that selectively inhibits viral DNA production in ported or unknown in Ethiopia. This is probably because
cytomegalovirus and other herpes viruses. The drug has the majority of Orf cases do not seek medical attention or
been found almost ubiquitously used as a first-line anti are misdiagnosed.
viral therapy, along with mechanical excision of the Orf Orf in humans was chiefly described in the 20th cen
lesion.51 Cidofovir in cream and intravenous preparations tury:1934 by Newson and Cross.5 ORFV is known to
were used in severe Orf cases, even though it is not infect all age groups in humans but the incidence is com
approved for this use.80 The apparently successful use of monly seen among adults with a history of exposure to
cidofovir to treat a giant non-resolving ORFV infected animals. Those people involved in animal businesses such
lesion has been reported in an immunocompromised as farm workers, abattoir workers, veterinarians, students
patient.48,92 The use of topical cidofovir cream has also in animal science, petting zoos and others working with
been described due to its apparent benefit, despite the lack animals are at increased risk of acquiring the virus.9,98
of controlled clinical trials to support this.93 There is no racial preference reported for Orf although
Other reports described that Orf has been successfully the disease is more commonly reported among men. This
treated with topical imiquimod application80,88 including is owing to the fact that men are more likely to have
in immunocompromised cases with very large Orf occupational exposure while serving as sheep breeders,
lesions.93 However, imiquimod, which is an immune goat or sheep dealers, slaughter workers, etc.90 As most
response modifier, is not approved for treating ORFV Orf cases have been attributed to religious observances
infections. The product may induce secretions of inter such as sacrificial feasts,56 there was a widespread custom
feron alpha and other cytokines where the mechanisms of slaughtering small ruminates in backyards during Eid
of action are not well elucidated.94 Generally, topical al-Adha.1,18,43,63,99–101 The virus is known to survive in
cidofovir or imiquimod have been particularly employed different conditions for weeks to months and even to years
as described above in the Transmission and Pathogenesis livestock herds as well as humans4,96 that may be because
section. It was also demonstrated that some chronically many people who had contact with animals recognize Orf
infected animals are known to carry the virus without lesions and they did not seek medical attention. A series of
visible lesions.1,35 In humans, ORFV re-infection was Orf suspected human cases were attended in Jimma town
noted57 and infected individuals must be advised to mini between the months of October 2019 and May 2020. This
mize auto-inoculation, spread of infection to contacts period encompasses the drier seasons in most parts of
including animals or should not handle animals without Ethiopia.
protective precautions.80
Until recently, only the clinical symptoms and history Prevention and Control
of animal contacts were used in the suspicion of human orf Since animals are essentially reservoirs and sources of
lesions unlike in animals where a sign of ORFV infection ORFV infection in humans, the principal preventive mea
on skin and mucous membrane is important in Jimma sure must be to target animals for vaccination.111 There are
town, Ethiopia. Suspect human cases with a minimum live attenuated ORFV vaccine candidates for sheep and
age of 9 years have been found among visiting patients goats.34 Care must be taken while handling this vaccine
at Jimma University medical center originating from the product or from vaccinated animals as the virus can pose
town. There were no confirmatory laboratory tests avail an infection risk to humans.4 There are reports of the
able at the facility to identify ORFV or perform specific vaccine used for ORFV resulting in human infection.112,113
molecular characterization assays from biopsied It is recommended that infected or vaccinated animals
materials.14 should be put in isolation away from human and healthy
Orf or EC appears to be neglected among animals animals to prevent contact, potentially leading to transmis
owing to its minimal impact on the animal production sion. Wearing non-permeable gloves or regular hand wash
and economic loss.102 Different studies have shown the ing practice with warm soapy water or by using hand
phylogenetic relatedness of ORFV isolates from diverse sanitizer for 20 seconds after handling sheep or goats is
animal sources.103,104 The findings help to predict and recommended to minimize the risk of human infections.1
assess the extent of the risk to human health. While con Patients who are particularly immunosuppressed must
siderable information on animal and human Orf is avail avoid contact with animals as they have an increased
able from other regions of the world, such as in Europe, susceptibility to potentially severe ORFV infection. To
Asia and the USA, only very few studies on animals have aid in preventing transmission to humans, any visible (or
been conducted in Africa.105 So far, some molecular stu invisible) cuts or abrasions on the skin should be covered
dies on ORFV infections among small ruminants have to avoid contact exposure to animal scabs or animal pro
been reported from Ethiopia, Gabon, South Africa, and ducts like meat, wool or hides, the use of non-porous
Egypt.5,14,99,106,107 The disease has also been reported gloves is recommended for this purpose.7
infecting camels in Africa.56 Several others also confirmed It is important to provide health information about the
ORFV infections from sheep, goats and camel in different virus routes of transmission and its disease manifestations
African countries including Kenya, Somalia, Sudan, to farmers and people who handle animals or animal
Tanzania, Cameroon, Nigeria and Zambia.5,18,97,107–109 products. People should also be informed of the potential
There are some additional published reports that orf dis recurrences of infection due to repeated exposure to the
ease in animals was diagnosed on the basis of clinical virus.1 In endemic locations, confirmation of the presence
findings.12,63,82,99,110 of the virus from human or animal lesions, surveillance
In recent times, the increasing trend of Orf infections is implementations, and infection control measurements are
noticeable due to the emergence of the virus in new geo important to employ by integrating the public health inter
graphic locations. This may be associated with the expan face of both human and animal sectors.
sion in interspecies infection as well as the possibility of
reinfection in previously infected animals.5,18 Different Conclusion
studies showed a high incidence rate (ranging from 75– Orf, ecthyma contagiosum or contagious ecthyma is an
90%) of Orf among animal herds throughout the dry exanthematic debilitating disease of sheep and goats with
season in parts of the central African region. The actual zoonotic potential to affect humans but is largely a
prevalence may be significantly underestimated among neglected disease in developing countries. It is caused by
17. Kusiluka L, Kambarage D; VETAID, Great Britain, Animal 35. Fleming SB, Mercer AA. Genus Parapoxvirus. In: Mercer AA,
Health Programme. Diseases of Small Ruminants: A Handbook Schmidt A, Weber O editors. Poxviruses. Birkhäuser Basel;
: Common Diseases of Sheep and Goats in Sub-Saharan Africa. 2007:127–165. doi:10.1007/978-3-7643-7557-7_7.
VETAID; 1996. 36. Lyttle DJ, Fraser KM, Fleming SB, Mercer AA, Robinson AJ.
18. CABI. contagious ecthyma. November 25, 2019. Available from: Homologs of vascular endothelial growth factor are encoded by
https://www.cabi.org/isc/datasheet/88087#tooverview Accessed the poxvirus orf virus. J Virol. 1994;68(1):84–92.
October 1, 2020. 37. Savory LJ, Stacker SA, Fleming SB, Niven BE, Mercer AA. Viral
19. Etymologia: orf. Emerg Infect Dis. 2013;19(1):105. doi:10.3201/ vascular endothelial growth factor plays a critical role in orf virus
eid1901.ET1901 infection. J Virol. 2000;74(22):10699–10706.
20. CDC C. Poxvirus. CDC.2020. Available from: https://www.cdc. 38. Fleming SB, McCaughan C, Lateef Z, et al.. Deletion of the
gov/poxvirus/index.html. Accessed October 13, 2020. chemokine binding protein gene from the parapoxvirus orf virus
21. ICTV. International Committee on Taxonomy of Viruses. ICTV; reduces virulence and pathogenesis in sheep. Front Microbiol.
2019. Available from: https://talk.ictvonline.org/taxonomy/p/taxo 2017;8. doi:doi:10.3389/fmicb.2017.00046
nomyhistory?taxnode_id=201904780. Accessed September 6, 39. Zhang K, Liu Y, Kong H, Shang Y, Liu X. Human Infection with
2020. Orf Virus from Goats in China, 2012. Vector Borne Zoonotic Dis.
22. Baxby D. Poxviruses. In: Baron S, editor. Medical Microbiology. 2014;1(1):3. doi:10.1089/vbz.2013.1445
4th ed. University of Texas Medical Branch at Galveston; 1996. 40. Diel DG, Delhon G, Luo S, Flores EF, Rock DL, Novel A.
Available from: http://www.ncbi.nlm.nih.gov/books/NBK8364/. Inhibitor of the NF-κB signaling pathway encoded by the para
Accessed September 6, 2020. poxvirus orf virus. J Virol. 2010;84(8):3962–3973. doi:10.1128/
23. Fleming SB, Wise LM, Mercer AA. Molecular genetic analysis of JVI.02291-09
orf virus: a poxvirus that has adapted to skin. Viruses. 2015;7 41. Deane D, McInnes CJ, Percival A, et al. Orf virus encodes a novel
(3):1505–1539. doi:doi:10.3390/v7031505 secreted protein inhibitor of granulocyte-macrophage colony-sti
24. Delhon G, Tulman ER, Afonso CL, et al. Genomes of the mulating factor and Interleukin-2. J Virol. 2000;74(3):1313–1320.
Parapoxviruses Orf virus and bovine papular stomatitis virus. doi:10.1128/JVI.74.3.1313-1320.2000
JVI. 2004;78(1):168–177. doi:10.1128/JVI.78.1.168177.2004 42. Monath TP. Vaccines against diseases transmitted from animals to
25. Likos A, Goldsmith C. Details; Public Health Image Library humans: a one health paradigm. Vaccine. 2013;31(46):5321–
(PHIL). United States Centers for Disease Control and 5338. doi:10.1016/j.vaccine.2013.09.029
Prevention; 2020. Available from: https://phil.cdc.gov/Details. 43. Uzel M, Sasmaz S, Bakaris S, et al. A viral infection of the hand
aspx?pid=8434. Accessed November 29, 2020. commonly seen after the feast of sacrifice: human orf (orf of the
26. Spehner D, Carlo SD, Drillien R, et al. Appearance of the bona hand). Epidemiol Infect. 2005;133(4):653–657. doi:10.1017/
fide spiral tubule of orf virus is dependent on an intact 10-kilo s0950268805003778
dalton viral protein. J Virol. 2004;78(15):8085–8093. 44. Rajkomar V, Hannah M, Coulson IH, Owen CM. A case of
doi:10.1128/JVI.78.15.8085-8093.2004 human to human transmission of orf between mother and child.
27. Nashiruddullah N, Pathak DC, Barman NN, et al. In vitro and in Clin Exp Dermatol. 2016;41(1):6063. doi:10.1111/ced.12697
vivo assessment of orf virus (ORFV) by electron microscopy. 45. Midilli K, Erkılıç A, Kuşkucu M, et al. Nosocomial outbreak of
Veterinarski Arhiv. 2018;88(6):847–861. doi:10.24099/vet. disseminated orf infection in a burn unit, Gaziantep, Turkey,
arhiv.0229 October to December 2012. Eurosurveillance. 2013;18:11.
28. Groves RW, Wilson-Jones E, MacDonald DM. Human orf and doi:10.2807/ese.18.11.20425-en
milkers’ nodule: a clinicopathologic study. J Am Acad Dermatol. 46. Ginzburg VE, Liauchonak I. Human orf. Can Fam Physician.
1991;25(4):706–711. doi:10.1016/0190-9622(91)70257-3 2017;63(10):769–771. Available from: https://www.ncbi.nlm.nih.
29. Mercer A, Fleming S, Robinson A, Nettleton P, Reid H. gov/pmc/articles/PMC5638474/. Accessed, 2020.
Molecular genetic analyses of parapoxviruses pathogenic for 47. Teshale A. Contagious Ecthyma and its Public Health Significance.
humans. In: Kaaden O-R, Czerny C-P, Eichhorn W editors. JDVS. 2018;7:3. doi:10.19080/JDVS.2018.07.555711
Viral Zoonoses and Food of Animal Origin. Springer; 1997:25– 48. Lederman ER, Green GM, DeGroot HE, et al. Progressive orf
34. doi:10.1007/978-37091-6534-8_3. virus infection in a patient with lymphoma: successful treatment
30. Mercer A, Ueda N, Friederichs S-M, et al. Comparative analysis using imiquimod. Clin Infect Dis. 2007;44(11):e100–e103.
of genome sequences of three isolates of Orf virus reveals unex doi:10.1086/517509
pected sequence variation. Virus Res. 2006;116(12):146–158. 49. Ata N, Gögüs HE, Giant KS. Orf on the Nose. J Craniofacial
doi:10.1016/j.virusres.2005.09.011 Surg. 2017;28(3):e234. doi:10.1097/SCS.0000000000003441
31. Zhang K, Liu Y, Shang Y, Liu X, Cai X. Major virulence factors 50. Geerinck K, Lukito G, Snoeck R, et al. A case of human Orf in an
of orf virus and their mechanism for immune evasion. Austin J immunocompromised patient treated successfully with cidofovir
Infect Dis. 2014;(1):1. https://austinpublishinggroup.com/infec cream. J Med Virol. 2001;64(4):543–549. doi:10.1002/jmv.1084
tious-diseases/fulltext/ajid-v1-id1005.php. Accessed, 2020. 51. Faridi W, Ahmed K. Orf Disease. In: StatPearls. StatPearls
32. Wang R, Luo S. Orf virus: a new class of immunotherapy drugs. Publishing. Available from: http://www.ncbi.nlm.nih.gov/books/
In: Systems Biology. IntechOpen;2018: 17. Available from: NBK562191/. 2020. Accessed September 30, 2020.
https://www.intechopen.com/books/systems-biology/orf-virus-a- 52. Taghipour M, Babamahmoodi F, Arashnia P, Taghipour S. Orf
new-class-ofimmunotherapy-drugs. Accessed September 29, Virus Infection in Human (EchtymaContagiosum): a report of
2020 eight cases in the North of Iran. Int J Med Invest. 2015;4(1):4.
33. McInnes CJ, Wood AR, Mercer AA. Orf Virus Encodes a Homolog of 53. Mourtada I, Le Tourneur M, Chevrant-Breton J, Le Gall F.
the Vaccinia Virus Interferon-Resistance Gene E3L | springerLink. [Human orf and erythema multiforme]. Ann Dermatol Venereol.
Virus Genes. 1998;17:9. doi:10.1023/A:1026431704679 2000;127(4):397–399.
34. Hosamani M, Scagliarini A, Bhanuprakash V, McInnes CJ, Singh 54.. Alian S, Ahangarkani F, Arabsheybani SA. Case of orf disease
RK. Orf: an update on current research and future perspectives. complicated with erythema multiforme and bullous pemphigoid-
Expert Rev Anti Infect Ther. 2009;7(7):879–893. doi:10.1586/ like eruptions. Case Rep Infect Dis. 2015;2015. doi:10.1155/
eri.09.64 2015/105484.
55. Joseph RH, Haddad FA, Matthews AL, Maroufi A, Monroe B, 77. Sahu BP, Majee P, Singh RR, Sahoo A, Nayak D. Comparative
Reynolds M. Erythema multiforme after orf virus infection: a analysis, distribution, and characterization of microsatellites in
report of two cases and literature review. Epidemiol Infect. Orf virus genome. Sci Rep. 2020;10(1):13852. doi:10.1038/
2015;143(2):385–390. doi:10.1017/S0950268814000879 s41598-020-70634-6
56. Al-Qattan MM. Orf Infection of the Hand. J Hand Surg Am. 78. Chan K-W, Hsu W-L, Wang C-Y, et al. Differential diagnosis of
2011;36(11):1855–1858. doi:10.1016/j.jhsa.2011.08.019 orf viruses by a single- step PCR. J Virol Methods. 2009;160
57. Cubells JRE, Braverman I, Kashgarian M, Lazova R. A 65-year- (1):85–89. doi:10.1016/j.jviromet.2009.04.025
old female from connecticut with orf infection. Dermatopathology 79. Margaret R, Ayman AH Orf. 2019. Available from: https://www.
(Basel). 2016;3(2):55–60. doi:10.1159/000447125 pathologyoutlines.com/topic/skinnontumororf.html Accessed
58. Orf virus infection of workers in the meat industry. N Z Med J. September 7, 2020.
1983;96(725):81–85. 80. Hoover A, Milroy M Orf treatment & management: medical care,
59. Sasmaz S, Uzel M, Ucmak H Rare presentation of human orf as surgical care, prevention.2019. https://emedicine.medscape.com/
multiple lesions. 2010. Available from: https://login.research4life. article/1133450-treatment Accessed September 22, 2020.
org/tacsgr1onlinelibrary_wiley_com/doi/full/10.1111/j.13468138. 81. Wang G, Yanhua W, Qi J, et al.. Comparison of the sensitivity of
2010.01082.x. Accessed January 6, 2021. three cell cultures to ORFV. 2019:8.
60. Erbağci Z, Erbağci İ, Tuncel AA. Rapid improvement of human 82. Wang X, Zhang J, Hao W, et al. Isolation and characterization of
orf (ecthyma contagiosum) with topical imiquimod cream: report monoclonal antibodies against a virion core protein of orf virus
of four complicated cases. J Dermatol Treat. 2005;16(5–6):353– strain NA1/11 as potential diagnostic tool for orf viruses.
356. doi:10.1080/09546630500375734 Monoclon Antib Immunodiagn Immunother. 2015;34(4):233–
61. Waldram MA. A seven-year-old girl with orf of the hand. J Hand 245. doi:10.1089/mab.2014.0101
Surg. 1986;11(3):467–468. doi:10.1016/0266-7681(86)90186-5 83. Ivanov L, Hristov M, Peshev R. STUDIES ON CULTURAL
62. Veraldi S, Nazzaro G, Vaira F, Çuka E. Presentation of orf (ecthyma CHARACTERISTICS OF CONTAGIOUS ECTHYMA (ORF)
contagiosum) after sheep slaughtering for religious feasts. Infection. VIRUS. Bulg J Vet Med. 2016;19(4):308–316. doi:10.15547/
2014;42(4):767–769. doi:10.1007/s15010-014-0591-7 bjvm.933
63. Veraldi S, et al. Feast of Sacrifice and Orf, Milan, Italy, 84. Scagliarini A, Gallina L, Dal Pozzo F, et al. Diagnosis of orf virus
2015-2018. Emerg Infect Dis. 2019;25(8):1585–1586. infection in humans by the polymerase chain reaction. New
doi:10.3201/eid2508.181063 Microbiol. 2004;27(4):403–405.
64. Bayindir Y, Bayraktar M, Karadag N, et al. Investigation and 85. Wang G, Shang Y, Wang Y, Tian H, Liu X. Comparison of a loop-
analysis of a human orf outbreak among people living on the mediated isothermal amplification for orf virus withquantitative
same farm. New Microbiol. 2011;34:8. real-time PCR. Virol J. 2013;10(1):138. doi:10.1186/1743-422X-
65. Chakhunashvili G, Carlson BF, Power L, et al. Parapoxvirus 10-138
infections in the country of Georgia: a case series. Am J Trop 86. Tsai S-M, Chan K-W, Hsu W-L, Chang T-J, Wong M-L, Wang C-
Med Hyg. 2018;98(6):1870–1875. doi:10.4269/ajtmh.17-0874 Y. Development of a loop-mediated isothermal amplification for
66. Koufakis T, Katsaitis P, Gabranis I. Orf disease: a report of a case. Braz rapid detection of orf virus. J Virol Methods. 2009;157(2):200–
J Infect Dis. 2014;18(5):568–569. doi:10.1016/j.bjid.2014.04.001 204. doi:10.1016/j.jviromet.2009.01.003
67. Vellucci A, Manolas M, Jin S, et al. Orf virus infection after Eid 87. Degraeve C, De Coninck A, Senneseael J, Roseeuw D. Recurrent
al-Adha. IDCases. 2020;21:e00854. doi:10.1016/j.idcr.2020. contagious ecthyma (Orf) in an immunocompromised host suc
e00854 cessfully treated with cryotherapy. Dermatology (Basel).
68. Andreani J, Fongue J, Khalil JYB, et al. Human Infection with 1999;198(2):162–163. doi:10.1159/000018095
Orf Virus and Description of Its Whole Genome, France, 2017 - 88. Barraviera SRCS. Diseases caused by poxvirus - orf and milker’s
Volume 25, Number 12—December 2019 - Emerging Infectious nodules: a review. J Venomous Animals Toxins Including Trop
Diseases journal - CDC. EID. 2019;25:12. doi:10.3201/ Dis. 2005;11(2):102108. doi:10.1590/S1678-9199200
eid2512.181513 5000200002
69. Zuelgaray E, Salle de Chou C, Gottlieb J, et al. Human orf 89. Rørdam OM, Ø G, Spigset O, Ryggen K. Giant orf with pro
complicated by epidermolysis bullosa acquisita. Br J Dermatol. longed recovery in a patient with psoriatic arthritis treated with
2018;178(2):547–550. doi:10.1111/bjd.15496 etanercept. Acta Derm Venereol. 2013;487–488. doi:10.2340/
70. Duchateau NC, Aerts O, Lambert J. Autoinoculation with Orf 00015555-1514
virus (ecthyma contagiosum). Int J Dermatol. 2014;53(1):e60– 90. Caravaglio JV, Khachemoune A. Orf virus infection in humans: a
e62. doi:10.1111/j.1365-4632.2012.05622.x review with a focus on advances in diagnosis and treatment. J
71. Friebel TR, van der Werff JFA. The orf virus: a case report. J Drugs Dermatol. 2017;16(7):684–689.
Hand Surg. 2013. doi:10.1177/1753193413516403 91. Ü G, Günde S, Melek Ü. Human Orf: echtyma contagiosum
72. Meier R, Sommacal A, Stahel A, Grünert J, Hoffmann M. Orf – report of five cases. Turk J Med Sci. 2002;32(2):3.
an orphan disease?. JRSM Open. 2015;6(6). doi:10.1177/ 92. Kilic SS, Puel A, Casanova J-L. Orf infection in a Patient with
2054270415593718 Stat1 gain-of-function. J Clin Immunol. 2015;35(1):80–83.
73.. Roingeard P, Machet L. Orf skin ulcer. N Engl J Med. 1997;337 doi:10.1007/s10875-014-0111-7
(16):1. 93. Uluğ M. A viral infection of the hands: orf. Jmid. 2013;03
74. Thurman RJ, Fitch RW, Contagious Ecthyma. N Engl J Med. (01):41–44. doi:10.5799/ahinjs.02.2013.01.0078
2015;372(8):1. doi:10.1056/NEJMicm1304779 94. Anon. Imiquimod - an overview | scienceDirect Topics. Cancer
75. Haig DM. Orf virus infection and host immunity. Curr Opin Immunother. 2016. Available from: https://www.sciencedirect.
Infect Dis. 2006;19(2):127–131. doi:10.1097/01. com/topics/medicine-and-dentistry/imiquimod..
qco.0000216622.75326.ef 95. Ertekin SS, Gurel MS, Erdemir AVT, Leblebici C. Systemic
76. Muhsen M, Protschka M, Schneider LE, Müller U, Köhler G, interferon alfa injections for the treatment of a giant orf. Cutis.
Magin T. Orf virus (ORFV) infection in a three-dimensional 2017;99(5):E19–E21.
human skin model: characteristic cellular alterations and interfer 96. Nfi A. Soremouth in sheep and goats at the Mankon Animal
ence with keratinocyte differentiation. PLoS ONE. 2019;14(1):22. Research Station, Cameroon. Revue Elev Méd vét Pays trop.
doi:10.1371/journal.pone.0210504 1991;44(2):2.
97. Africa. HANDISTATUS II Multiannual animal disease status. 107. Mwanandota J, Macharia M, Car. M-N, Sallu R, Yongolo M,
2004. Available from: https://web.oie.int/hs2/sit_mald_freq_pl. Holton T. Phylogenetic Analysis of ORF virus from goats in
asp?c_cont=1&c_mald=152 Accessed October 26, 2020. Tanzania: short communication. Universal Journal of
98. Hasheminasab SS, Mahmoodi A, Mahmoodi P, Maghsood H. Orf Agricultural Research. 2016;4(5):165–169. doi:10.13189/
virus infection in human ecthyma contagiosum: a report of two ujar.2016.040501
cases in the West of Iran. Virusdisease. 2016;27(2):209–210. 108. Munz E, Schillinger D, Reimann M, Mahnel H. Electron
doi:10.1007/s13337-016-0304-1 Microscopical Diagnosis of Ecthyma contagiosum in Camels
99. Scagliarini A, Piovesana S, Turrini F, Savini F, Sithole F, (Camelus dromedarius) First Report of the Disease in Kenya. J
McCrindle CM. Orf in South Africa: endemic but neglected. Vet Med Series B. 1986;33(1–10):73–77. doi:10.1111/j.1439-
Onderstepoort J Vet Res. 2012;79(1):8. doi:10.4102/ojvr. 0450.1986.tb00007.x
v79i1.499 109. Simulundu E, Mtine N, Kapalamula TF, et al. Genetic character
100. Saade D, Higham C, Vashi N. A case series of orf infection after ization of orf virus associated with an outbreak of severe orf in
the religious sacrifice feast Eid al-Adha. JAAD Case Rep. 2018;4 goats at a farm in Lusaka, Zambia (2015). Arch Virol. 2017;162
(5):489–492. doi:10.1016/j.jdcr.2018.01.007 (8):2363–2367. doi:10.1007/s00705-017-3352-y
101. Ozkan B, Uysal CA, Uner H, Ertas NM. Sacrifice feast disease:
110. Mahmoud M, Abdelrahman K, Soliman H. Molecular and viro
orf. Turkish J Plastic Surg. 2020;28(3):195. doi:10.4103/tjps.
logical studies on contagious pustular dermatitis isolates from
tjps_73_19
Egyptian sheep and goats. Res Vet Sci. 2010;89(2):290–294.
102. Bala JA, Balakrishnan KN, Abdullah AA, et al. An association of
doi:10.1016/j.rvsc.2010.02.019
Orf virus infection among sheep and goats with herd health
111. Mombeni EG, Mousavi MB, Ranjbaran I, et al.. Prevention and
programme in Terengganu state, eastern region of the peninsular
treatment of contagious ecthyma in sheep and goat by goat-pox
Malaysia. BMC Vet Res. 2019;15(1):250. doi:10.1186/s12917019-
vaccine in Khuzestan Province, Iran. 2012;1:4.
1999-1
112. Demiraslan H, Doganay GD . An Overwiev of ORF Virus
103. Arens M. Methods for Subtyping and Molecular Comparison of
Infection in Humans and Animals. Recent Patents on Anti-
Human Viral Genomes. Clin Microbiol Rev. 1999;12(4):612–626.
doi:10.1128/CMR.12.4.612 Infective Drug Discovery. 2017. Accessed October21, 2020.
104. Chi X, Zeng X, Hao W, et al. Heterogeneity among Orf Virus https://www.eurekaselect.com/152874/article
Isolates from Goats in Fujian Province, Southern China.. PLOS 113. Bass JM Human Orf Virus Infection from Household Exposures
ONE. 2013;8(10):e66958. doi:10.1371/journal.pone.0066958 — united States, 2009–2011. 2012. Available from: https://www.
105. Bala JA, Balakrishnan KN, Abdullah AA. The re-emerging of orf cdc.gov/mmwr/preview/mmwrhtml/mm6114a3.htm Accessed
virus infection: a call for surveillance, vaccination and effective September 28, 2020.
control measures.. Microb Pathog. 2018;120:9. doi:10.1016/j.
micpath.2018.04.057
106. Selim A, Elhaig M, Höche J, Gaede W. BMTW_Molecular detec
tion and analysis of Sheeppox and Orf viruses isolated from sheep
from Qalubia, Egypt. Berliner und Münchener Tierärztliche
Wochenschrift. (Berliner und Münchener Tierärztliche
Wochenschrift 129, Heft 7/8 (2016), Seiten 310–317).
2016;310–317. doi:10.2376/0005-936615076