Download - 1. Herpesviridae-Unimal.ppt
1. HERPES SIMPLEKS VIRUS TYPE 1
2. HERPES SIMPLEKS VIRUS TYPE 2
3. VARICELLA ZOSTER VIRUS
4. EPSTEIN BARR VIRUS
5. CYTOMEGALO VIRUS
6. HUMAN HERPES VIRUS TYPE 6
7. HUMAN HERPES VIRUS TYPE 7
8. HUMAN HERPES VIRUS TYPE 8
1. HERPES SIMPLEKS VIRUS TYPE 1
2. HERPES SIMPLEKS VIRUS TYPE 2
3. VARICELLA ZOSTER VIRUS
4. EPSTEIN BARR VIRUS
5. CYTOMEGALO VIRUS
6. HUMAN HERPES VIRUS TYPE 6
7. HUMAN HERPES VIRUS TYPE 7
8. HUMAN HERPES VIRUS TYPE 8
HERPES VIRUSES
Mengandung bbp patogen yg paling penting pd manusia
Dikharakteristikkan dgn adanya infeksi latent yg diikuti infeksi primer
Masa latent menghasilkan gejala-gejala rekurent yang tetap persisten sepanjang kehidupan individu yang terinfeksi
Adalah “ubiquitous” pada manusia, misal hampir semua individu telah terinfeksi dengan HSV type-1
KEY CONCEPS
HERPES VIRUSES
Kebanyakan infeksi adalah asymptomatikSecara klinik :
Memperlihatkan suatu spektrum dr penyakit
Bbp memp. host yg luas, sedangkan yg lain memp. host yg sempit
Kemampuannya utk tetap sbg infeksi yg persisten sepanjang hidup dan mengalami reaktivasi secara periodeik
Dapat diobati dgn antiviral, namun antiviral tak dpt mencegah rekurent
Terakhir, vaksin vericella telah tersedia
HERPES VIRUSESKEY CONCEPS
Subfamily Virus Abbreviation
Alphaherpesvirinae Human herpes virus 1 Herpes simplex type 1 HSV-1Human herpes virus 2 Herpes simplex type 2 HSV-2Human herpes virus 3 Varicella-zoster virus VZV
Gammaherpesvirinae Human herpes virus 4 Epstein-Barr virus EBVHuman herpes virus 8 Kaposi’s sarcoma HHV-8
related virus
BetaherpesvirinaeHuman herpes virus 5 Cytomegalovirus CMVHuman herpes virus 6 Herpes lymphotropic virus HHV-6Human herpes virus 7 Human herpes virus 7 HHV-7
HERPES VIRUSESCLASSIFICATION FAMILY HERPESVIRIDAE
VIRUS MEANS OF PORTAL OF ENTRY INITIALTRANSMISSION TARGET CELLS
HSV-1 Direct contact Mucous membrane, skin EpithelialHSV-2 Direct contact Mucous membrane, skin EpithelialVZV Inhalation, Respiratory tract Epithelial direct contact mucous membranes ? CMV Saliva, blood, Blood stream, Neutrophils, urine ? mucous membranes monocytes, Semen ? othersEBV Saliva, blood Mucous membranes, B lymphocytes,
blood stream salivary glandsHHV-6 Respiratory, ? T lymphocytes close contact ?HHV-7 ? ? T lymphocytesHHV-8 Saliva ? ?
HERPES VIRUSESTRANSMISSION OF HUMAN HERPES VIRUSES
Sangat tersebar luas dlm populasi Memperlihatkan host yg luas, mampu
bereplikasi dlm banyak tipe sel Tumbuh dgn cepat dan sifat cytolytic
yg tinggi Bertanggungjawab pd penyakit-
penyakit : gingivostomatitis keratoconjunctivitis encephalits genital herpes infections of newborn
Seringkali latent dlm sel syaraf
HERPES SIMPLEX VIRUSHERPES SIMPLEX VIRUS
Kedua virus berbeda dalam Kedua virus berbeda dalam cara transmisinya :cara transmisinya : HSV-1 disebarkan mel. kontak, HSV-1 disebarkan mel. kontak,
biasanya melibatkan saliva yg biasanya melibatkan saliva yg terinfeksiterinfeksi
HSV-2 ditransmisikan mel. HSV-2 ditransmisikan mel. hubungan seksual atau dari ibu hubungan seksual atau dari ibu yang terinfeksi pada genitalnya yang terinfeksi pada genitalnya ke bayinyake bayinya
HERPES SIMPLEX VIRUSHERPES SIMPLEX VIRUS
TRANSMISI
HERPES SIMPLEX VIRUSHERPES SIMPLEX VIRUS
Infection Predominant Frequency AgeInfection Predominant Frequency Age Usual Usual RecurrenceRecurrence virus typevirus type group outcome group outcome
INFECTIONS ASSOCIATED WITH HERPES SIMPLEX VIRUS
Ocular herpes Ocular herpes 1 1 Common Common AllAll Resolution Resolution YesYes visual impairmentvisual impairment
Oral herpesOral herpes 1 1 >> 2 2 Very common Very common AllAll Resolution Resolution YesYesGenital herpes 2 Genital herpes 2 >> 1 1 Common Common Adolescence, ResolutionAdolescence, Resolution
YesYes adultsadults
Neonatal herpes 2 Neonatal herpes 2 >> 1 1 Very rare Very rare 0 – 4 weeks Developmental0 – 4 weeks Developmental NoNoimpairmentimpairment
Meningo-Meningo- 2 2 Un Un Adolescence, ResolutionAdolescence, ResolutionNoNo
encephalitisencephalitis common common adults adultsEncephalitisEncephalitis 1 1 Very rare Very rare AllAll Severe neurologic Severe neurologic NoNo
impairmentimpairmentDisseminated Disseminated 1 1 >> 2 2 Rare Rare AllAll Resolution or Resolution or NoNoherpesherpes death death
HERPES SIMPLEX VIRUSHERPES SIMPLEX VIRUS
CLINICAL FINDINGSCLINICAL FINDINGS
Vesicular eruption at the skin or mucous membrane
Incubation period is short : 3 – 5 days, with a range of 2 – 12 days Clinical manifestation 2 categoriesPrimary infectionReactivation
HSV-1 : oropharyngeal areaHSV-2 “ genital
CLINICALCLINICAL HSV-1HSV-1 HSV-HSV-22
Primary infectionGingivostomatitis + -Pharyngotonsilitis + -Keratoconjunctivitis + -Neonatal infections ± +
HERPES SIMPLEX VIRUSHERPES SIMPLEX VIRUS
CLINICAL FINDINGSCLINICAL FINDINGS
Recurrent infection
Cold sores, fever blisters + -
Keratitis + -
Primary or recurrent infectionCutaneous herpes
Skin above the waist + -Skin below the waist - +Hands or arms + +
Herpetic whitlow + +Eczema herpeticum + -Genital herpes ± +Herpes encephalitis + -Herpes meningitis + +
HERPES SIMPLEX VIRUSHERPES SIMPLEX VIRUS
CLINICAL FINDINGSCLINICAL FINDINGS
• Oropharyngeal disease : cluster of vesicles, most commonly localized at the border of the lip, painful, 4 – 5 days
• Keratoconjunctivitis : common & appear as dendritic keratitis or corneal ulcers or vesicles on the eyelids
• Genital herpes : common & tend to be mild, a limited number of vesicles, heal in 10 days
RECURRENT INFECTION
HERPES SIMPLEX VIRUSHERPES SIMPLEX VIRUS
Reactivation
Provocation :• Common cold
– UV• Underlying disease
– Stress• Hormonal (menstrual cycle)
HSV-2 : Oncogenic virus Ca-cervix & vulva
transformation of cell cultureinoculation of animal tumor
HERPES SIMPLEX VIRUSHERPES SIMPLEX VIRUS
IMMUNITY
• Many newborns acquire passively transferred maternal Abs, lost during 6 months, not totally protected against infection of newborns
• During primary infections, IgM Abs appear transiently, and followed by IgG & IgA that persist for long period
• Abs do not prevent reinfection or reactivation of latent virus, but maybe subsequent disease
HERPES SIMPLEX VIRUSHERPES SIMPLEX VIRUS
LABORATORY DIAGNOSIS
• ISOLATION & IDENTIFICATIONSpecimens : swab or vesicle fluidHSV has a wide host range ------------- many cell culture system are susceptible Appearance of CPE in cell cultures in 2 – 3 days identified by Nt test or immunofluorescence staining Hybridization using DNA probes & DNA
amplification
• SEROLOGY Abs appear in 4 – 7 days after infection, reach a peak after 2 – 4 weeks
can be measured by Nt, CF, ELISA, RIA, IF
HERPES SIMPLEX VIRUSHERPES SIMPLEX VIRUS
TREATMENT
• Inhibitors of viral DNA synthesis
• The drugs inhibits virus replication & suppress clinical manifestation
• HSV remain latent in sensory ganglia
• Acyclovir (acycloguanosine) : topical, intravenous, oral
• Vidarabine : more toxic
Virus Syndrome Frequency Age group Tissue Usual involved outcome
INFECTIONS ASSOCIATED WITH OTHER HERPES VIRUSESINFECTIONS ASSOCIATED WITH OTHER HERPES VIRUSES
Cytomegalo Congenital Common Newborn Brain, eye, Developmental virus infection liver, spleen, problems,
other death Mononucleosis Common Adolescent, Lymph Resolution
adult nodes, liver
Hepatitis Uncommon Adolescent Liver Resolution adult
Pneumonia Common in All Lung Death immunosuppressed patients
Retinitis Common in All Eye Blindness immunosuppressed patients
Virus Syndrome Frequency Age group Tissue Usual involved outcome
INFECTIONS ASSOCIATED WITH OTHER HERPES VIRUSESINFECTIONS ASSOCIATED WITH OTHER HERPES VIRUSES
Epstein- Mononucleosis Very common All Lymph ResolutionBarr nodes, liver,virus spleen
Lymphomas Very rare All Lymph Death nodes, liver, spleen, brain
VZV Chickenpox Very common All Skin, others Resolution, uncommon rarely death
Shingles Common Older Skin, nerves Resolution, (Zoster) adults others chronic pain,
uncommon rarely deathHHV-6 Roseola Very common Infants Skin Resolution
Febrile Common Infants Brain Resolution, convulsions developmental
problems
Virus Syndrome Frequency Age group Tissue Usual involved outcome
INFECTIONS ASSOCIATED WITH OTHER HERPES VIRUSESINFECTIONS ASSOCIATED WITH OTHER HERPES VIRUSES
HHV –7 RoseolaHHV –7 Roseola Common Common Infants SkinInfants Skin Resolution Resolution
Kaposi’s Kaposi’s CommonKaposi’s Kaposi’s Common AdultsAdults Skin Death Skin Death
Sarcoma sarcoma ? in immuno-Sarcoma sarcoma ? in immuno- “metastatic” “metastatic”Associated suppressedAssociated suppressedVirus patientsVirus patients
(HHV-8) Lymphomas Uncommon Adults Body(HHV-8) Lymphomas Uncommon Adults Body Death Death in immuno-in immuno- cavities cavities suppressedsuppressed patientspatients
– Varicella (chickenpox) :Varicella (chickenpox) :a mild, highly contagious disease a mild, highly contagious disease
chiefly in childrenchiefly in children characterized clinically by a characterized clinically by a
generalized vesicular eruption of the generalized vesicular eruption of the
skin & mucous membranesskin & mucous membranes– The disease may be severe in adults & The disease may be severe in adults &
immunocompromised childrenimmunocompromised children
VARICELLA-ZOSTER VIRUS (VZV)VARICELLA-ZOSTER VIRUS (VZV)
Zoster (shingles) a sporadic, incapacitating disease of
adults or immunocompromised individuals
characterized by rash limited to distribution to the skin innervated by a single sensory ganglion
lesions similar to those of varicella
VARICELLA-ZOSTER VIRUS (VZV)VARICELLA-ZOSTER VIRUS (VZV)
Varicella : route of infection is the mucosa of the upper respiratory tract or conjunctiva
blood multiple cycle of replication
skin
VARICELLA-ZOSTER VIRUS (VZV)VARICELLA-ZOSTER VIRUS (VZV)
PATHOGENESIS
Zoster skin lesion histopathologicaly identical to
varicella
acute inflammation of the sensory nerve & ganglia
often only a single ganglion may be involved
as a rule the distribution of lesions in the skin corresponds closely to the areas of innervation from an individual dorsal root ganglion
VARICELLA-ZOSTER VIRUS (VZV)VARICELLA-ZOSTER VIRUS (VZV)
Varicella Herpes Zoster Varicella Herpes Zoster
VARICELLA-ZOSTER VIRUS (VZV)VARICELLA-ZOSTER VIRUS (VZV)
• Previous infection with varicella is believe to confer lifelong immunity to varicella
• However, zoster can occur in the presence of relatively high level of Nt Ab to varicella
VARICELLA-ZOSTER VIRUS (VZV)VARICELLA-ZOSTER VIRUS (VZV)
IMMUNITY
VARICELLA-ZOSTER VIRUS (VZV)VARICELLA-ZOSTER VIRUS (VZV)
Laboratory diagnosis
Stained smear of scraping or swabs of the base vesicles :multinucleated giant cells
Virus isolated from vesicle fluid using culture of human cells 3 – 7 days
Cytopathic effects develop more slowly
VARICELLA-ZOSTER VIRUS (VZV)VARICELLA-ZOSTER VIRUS (VZV)
Treatment
Gamma globulin of high VZV Ab titer (VZ Ig) can be used to prevent the development of the illness of immunocompromised patients exposed to varicella
It has no therapeutic value once varicella has started
Antiviral : acyclovir, valacyclovir, vidarabine
INTRODUCTIONINTRODUCTIONThe largest & most complex of viruses knownSmallpox first appeared in China and the Far East at least 2000 years ago.The family encompasses a large group of agents,
morphologically similar, share a common nucleoprotein
antigenThe group includes variola virus
etiologic agent of smallpox, disease has most affected humans throughout the worldrecorded history until elimination in 1977
INTRODUCTIONINTRODUCTIONEradication & vaccination all over the world started by WHO (1967)Smallpox has been declared eradicated from the world (May 1980) after an extensive campaign coordinated by WHOVaccinia virus is under intensive study as a vector for introducing active immunizing genes as live-virus vaccines for a variety of viral diseases of humans & domestic animals
POXVIRUSES CAUSING DISEASE IN HUMANSPOXVIRUSES CAUSING DISEASE IN HUMANS
Genus Virus Primary Disease
hostOrthopoxvirus Variola Humans Small pox (now extinct)
Vaccinia Humans Localized lesion, usedfor smallpox vaccination
Buffalopox Water buffalo Human infection rare, local
Monkeypox Monkeys Human infection rare,general
Cowpox Cows Human infection rare, local
Parapoxvirus Orf Sheep Human infection rare, local
Pseudocowpox Cows Milkers’ nodes
Bovine papular Cows
stomatitis
Molluscipoxvirus Molluscum Humans Many benign skin nodules
contagiosum
Yatapoxvirus Tanapox Monkeys Human infection rare, local
Yabapox Monkeys Human infection very rare, accidental, localized skin tumor
Subfamily: Genus: Members:
Chordopoxvirinae
Avipoxvirus fowlpox virus
Capripoxvirus sheeppox virus
Leporipoxvirus myxoma virus
Molluscipoxvirus Molluscum contagiosum
Orthopoxvirus vaccinia virus
Parapoxvirus orf virus
Suipoxvirus swinepox virus
Yatapoxvirus Yaba monkey tumor virus
Entomopoxvirinae
Entomopoxvirus AMelolontha melolontha entomopoxvirus
Entomopoxvirus B Amsacta moorei entomopoxvirus
Entomopoxvirus CChironomus luridus entomopoxvirus
VIRUS REPLICATIONVIRUS REPLICATION Multiplication cycle takes place in the
cytoplasm, in which they form inclusion bodies
Nuclear factors involved in transcription and virion assembly
Propagation in the laboratory :most poxviruses can be propagated on the chorioallantoic membrane of the 10 – 12 days old chick embryo, form
circumscribed pocks, Ø 2 - 3 mm or in cell cultures
Molluscum contagiosum virus has not so far been grown in the laboratory
POXVIRUS INFECTIONS IN POXVIRUS INFECTIONS IN HUMANS : VACCINIA & VARIOLAHUMANS : VACCINIA & VARIOLA
Control & eradication of smallpox :Control & eradication of smallpox : Edward Jenner (1798) introduced
vaccination with live cowpox virus In 1967 WHO introduced a worldwide
campaign to eradicate smallpox The last Asiatic case occurred in
Bangladesh (1975) The last natural victim was diagnosed
in Somalia (1977)
The main reasons for outstanding The main reasons for outstanding success of vaccination & eradication ;success of vaccination & eradication ;
The vaccine was easily prepared, stable, safe and effective
It could be given simply by personnel in the field
Humans are the only natural host
Only I type of smallpox virus
Comparison of vaccinia & variola virus :Comparison of vaccinia & variola virus :
Vaccinia virus :Vaccinia virus :
Used for smallpox vaccine
Has a broad host range
Nucleotide sequences 192 kb
Variola virus :Variola virus :
Has narow host range
Nucleotide sequences 186 kb
PATHOGENESIS & PATHOLOGY OF PATHOGENESIS & PATHOLOGY OF SMALLPOXSMALLPOX
Portal of entry : mucous membranes of respiratory tract
1. Primary multiplication in lymphoid tissue draining the site of entry
2. Transient viremia & infection of RE cells throughout the body
3. Secondary phase of multiplication4. Secondary & more intense viremia5. Clinical disease
Smallpox was transmitted by respiratory route Smallpox was transmitted by respiratory route from lesions in the respiratory tract of patients from lesions in the respiratory tract of patients in the early stage of the disease. in the early stage of the disease. During the 12 day incubation period, the virus During the 12 day incubation period, the virus was distributed initially to the internal organs was distributed initially to the internal organs and then to the skin. and then to the skin. Variola major caused severe infections with Variola major caused severe infections with 20-50% mortality, variola minor with <1% 20-50% mortality, variola minor with <1% mortality. mortality. Management of outbreaks depended on the Management of outbreaks depended on the isolation of infected individuals and the isolation of infected individuals and the vaccination of close contacts.vaccination of close contacts. The vaccine was highly effective. If given The vaccine was highly effective. If given during the incubation period, it either during the incubation period, it either prevented or reduced the severity of clinical prevented or reduced the severity of clinical symptoms. symptoms.
At least 9 different poxviruses cause disease in humans, but variola virus (VV) and vaccinia are the best known. VV strains are divided into variola major (25-30% fatalities) and variola minor (same symptoms but less than 1% death rate).
"Variolation" = the administration of material from known smallpox cases (hopefully variola minor!!!) to protect recipients - practiced for at least 1000 years (Chinese) but risky - Jenner was nearly killed by variolation in 1756!
IMMUNITYIMMUNITYAn attack of smallpox complete protection against re-infectionVaccination with vaccinia induced immunity against variola virus at least 5 years & sometimes longerNeonates of vaccinated, immune mother receive maternal antibody transplacentally, persists for several months. After that time, artificial immunity can be produced by vaccination
Molluscum contagiosum virusMolluscum contagiosum virus Molluscum contagiosum is a specifically human disease of worldwide distribution. The incubation period varies from 1 week to 6 months.
The lesion begins as a small papule and gradually grows into a discrete, waxy, smooth, dome-shaped, pearly or flesh-coloured nodule. Usually 1-20 lesions but occasionally they may be present in
hundreds. In children, the lesions are found on the trunk and the proximal extremities. In adults they tend to occur on the trunk, pubic area
and thighs. Individual lesions persist for about 2 months, but the disease usually lasts 6 to 9
months. Constitutional disturbance is rare.
Molluscum contagiosum virusMolluscum contagiosum virusThe disease occurs world-wide and is spread by direct contact or fomites. In general it tends to occur in children. The disease by may transmitted from skin to skin after sexual intercourse. A diagnosis can usually be made on clinical appearance
alone. The diagnosis can be supported by EM. Unlike other poxviruses, molluscum have not been demonstrated to grow in cell culture. Infection is usually benign and painless, with spontaneous recovery in most cases. Where treatment is required for cosmetic reasons, various procedures are available such as curretage, cryotherapy with liquid nitrogen, silver nitrate etc. which are routinely used for the removal of warts.
SYMPTOMSSYMPTOMS
Molluscum contagiosum is a superficial skin infection.
The virus invades the skin causing the appearance of firm, flesh-colored, doughnut-shaped bumps, about 2-5 mm in diameter.
Their sunken centers contain a white, curdy-type material. The bumps can occur almost anywhere on the body including the buttocks
CAUSECAUSE
Molluscum contagiosum is caused by a virus belonging to the poxvirus family. Close physical contact is usually necessary
for transmission; indirect transmission from shared towels, swimming pools, etc., may also be responsible for
infection. The incubation period varies from several weeks to several months. Shaving or scratching may cause the infection to spread.
COMPLICATIONS
If scratched, the bumps can become infected with bacteria.
DIAGNOSIS
The diagnosis is based on the typical appearance of the bumps.
No diagnostic test for this virus is available.
TREATMENTAvoid shaving infected areas. Treatment is done for aesthetic reasons and to
prevent spread of the virus. The goal of treatment is to remove the soft center, after which the bump goes away. Your health care provider may use a curette (sharp, spoon-shaped instrument) to remove the
centers. Freezing the lesion with liquid nitrogen or nitrous
oxide is an alternative treatment.
RISKS OF TREATMENT
There is a slight risk of minimal scarring.
Observe for signs of infection that include redness, swelling, pus-like drainage, or increased
soreness at the site.