Download Molluscum Contagiosum

POXVIRIDAE
Introduction
• Poxviruses are the largest and most complex of viruses that
infect vertebrates.
• They are large enough to be seen under the light microscope.
• Smallpox, the great success story in the fight against
infectious disease
• This provides at least three ‘firsts’:
• the first vaccine,
• the first disease to be totally eradicated by immunization,
• and the first virus infection against which chemotherapy was
clinically effective.
2
Introduction
• Poxviridae contains two subfamilies:
• The Chordopoxvirinae,
• the poxviruses of vertebrates, and
• Entomopoxvirinae,
• the poxviruses of insects.
• Chordopoxvirinae are placed in eight genera, the
following table enumerate those that can infect human
• Viruses are distinguished on the basis of morphology,
genome structure, growth characteristics and serological
reactions
• There is cross-reaction between genera
3
Poxviruses that infect humans
Genus
Orthopoxvirus
Virus
Primary host(s)
Variola
Man
Smallpox
Vaccinia
Man
Vesicular vaccination lession
Cowpox
Cattle, cats, rodents
Monkey,
squirrels
Lesions on hands
Monkeypox
Parapoxvirus
Pseudocowpox
Cattle
Yatapoxvirus
Orf
Sheep, goats
Tanpox
Monkeys
Yabapox
Monkeys
Molluscum
contagiosum
Man
Molluscipoxvirus
Clinical features in humans
Resembles smallpox
Localized nodular lesions
(milkers’ nodes)
Localized vesiculo.
Granulomatous lesions
Vesicular skin lesions and febrile
illness
Human infections very rare and
accidental; localized skin tumors
Multiple small skin nodules
4
General Characteristics
• The largest viruses of all
• They measure 230x270 nm
• Orthopoxviruses are brick-shaped, Orf and molluscum
contagiosum are ovoid
• When stained, can be seen with ordinary microscope
• DNA is double-stranded
• Molecular weight of the genome is about 108
• The genome codes for more than 100 polypeptides, including
DNA-dependent RNA polymerase and other enzymes, there is a
common internal family antigen in the core
5
6
General Characteristics
• Propagation on chorioallantoic membrane of chick embryos
producing lesions (pocks) and in tissue culture.
• Unlike most DNA viruses, the poxviruses replicate only in the
cytoplasm, in which they form inclusion bodies; eosinophilic
cytoplasmic inclusions (Guarnieri bodies).
• Preference for epidermal cells.
• Vaccine is prepared by infecting calves with vaccinia virus,
scrapings of lesions are used as intradermal.
• In 1977, World Health Organization (WHO) announced that
smallpox was eradicated worldwide.
• Immunity develops 8-10 days after vaccination
7
Epidemiology
• Transmission
• Smallpox: respiratory droplets, contact with virus on fomites
• Other poxviruses: direct contact or fomites
• At risk or risk factors
• Molluscum contagiosum: sexual contact
• Pet owners, animal handlers (contact with lesion)
• Distribution
• Worldwide
• No seasonal incidence
• Vaccines or antiviral drugs
• Attenuated vaccine against smallpox (vaccinia virus)
8
Epidemiology
• Smallpox and molluscum contagiousum are strictly
human viruses.
• In contrast, the natural hosts for the other poxviruses
important to humans are vertebrates other than humans
(e.g., cow, sheep, goats).
• The viruses infect humans only through accidental or
occupational exposure (zoonosis).
9
Pathogenesis
• After being inhaled, smallpox virus
replicates in the upper respiratory
tract.
• Dissemination occurs via lymphatic
and cell-associated viremic spread.
• Internal and dermal tissues are
inoculated after a second viremia,
causing the simultaneous eruption
of the characteristic pocks.
• Molluscum contagiosum and the
other poxviruses, however, are
acquired through direct contact with
lesions.
10
Replication
• It takes place in cytoplasm
1. Phagocytosis
2. Transcription of early mRNA by the action of viral RNA
polymerases:
•
Enzymes degrading viral core
3. Uncoating
4. DNA replication
5. Late transcription:
•
Structural proteins
6. Assembly of viral DNA into inner viral membrane
7. Enclosure of viral core and lateral bodies by outer membrane
8. Release from host cell
11
1
4
3
5
2
7
6
8
12
Variola and Vaccinia Viruses
• Variola viruses:
• The variola virus is the causative agent of smallpox
• Variola has a narrow host range
• Smallpox used to occur in two distinct clinical varieties:
• Variola major or classical smallpox:
• The complicated, highly fatal disease typically seen in Asia.
• Variola minor or alastrim:
• The mild, nonfatal disease (alastrim) typically seen in Latin America.
13
Variola and Vaccinia Viruses
• Vaccinia virus:
• Vaccinia virus, the agent used for smallpox vaccination, is a
distinct species of Orthopoxvirus.
• Vaccinia has a broad host range that includes rabbits and mice.
• At some time after Jenner’s original use of “cowpox” virus, the
vaccine virus became “vaccinia virus”.
• Vaccinia virus is unique in that it is an ‘artificial virus’ and
does not occur in nature as such.
• It may be the product of genetic recombination, a new species
derived from cowpox virus or variola virus by serial passage.
14
Diagnosis
• Clinical picture
• Detection of viral antigen from skin
scrapings
• Tissue culture, or on chorioallantoic
membrane of chick embryo “pocks and
Guarnieri bodies”
• Detection of specific antibodies
• Hemagglutinin inhibition
15
Control
• Vaccination-intradermal
• Chemotherapy
• Istatin-β-thiosemicarbazone (IBT):
• Inhibits translation of late mRNA
• Methisazone:
• inhibits morphogenesis
• Rifampin:
• inhibits morphogenesis
• Cidofovir:
• inhibits viral DNA polymerase
16
Cowpox and Monkeypox
• Cowpox
• Cowpox is, a zoonosis.
• Cowpox lesions are seen on the
udder and teats of cows and may be
transmitted to humans during
milking.
• The lesions in humans usually
appear on the hands or fingers.
• The natural reservoir of cowpox
seems to be a rodent.
17
Cowpox and Monkeypox
• Monkeypox
• This orthopoxvirus zoonosis causes an
illness in humans very similar to
smallpox.
• Squirrels seem to be the main reservoir
of infection, and the infection is seen
mainly in children who may acquire it
from playing with captive animals
18
Orf
• Orf (contagious pustular
dermatitis or sore Mouth)
• Orf is a disease of sheep and goats
transmitted to human beings by
contact.
• It is an occupational disease of sheep
handlers.
• In humans, the disease occurs as a
single papulovesicular lesion with a
central ulcer usually on the hand,
forearm, or face.
19
Tanapox
• This virus takes its name from the Tana River in Kenya, where it
was first diagnosed.
• It is prevalent in monkeys and appears to be spread by insect
bites.
• Monkeys are the only animals susceptible.
• There is usually only one vesicular lesion but its appearance is
preceded by fever and quite severe malaise.
• Recovery is uneventful.
20
Molluscum Contagiosum
• The result of the infection is usually a benign, mild skin disease
characterized by lesions (growths) that may appear anywhere on
the body.
• Within 6-12 months, Molluscum contagiosum typically resolves
without scarring but may take as long as 4 years.
21