herpes simplex viral infection - dr sanjana ravindra
TRANSCRIPT
Seminar no: 09
Dr Sanjana RavindraOral Medicine and radiologyRajarajeswari Dental CollegeBangalore
CONTENTS
VIRUS BASICS
Introduction
History
General Characteristics
Viral replication
Pathogenesis
Routes of entry
Classification and
Nomenclature
Antiviral Drugs
HERPES VIRUS
Introduction
History
Morphology
Classification
HERPES SIMPLEX
VIRUS
Introduction
Epidemiology
Pathophysiology
Clinical features
Types
Complications
Diagnosis
Differential Diagnosis
Management
Conclusion
TERMINOLOGIES
TERMINOLOGIES
Lynch MA. Ulcerative, Vesicular, and Bullous Lesions. In: Lynch MA, Brightman VJ, Greenberg MS eds. Burket's Oral Medicine: Diagnosis
and Treatment. 8th ed. USA: JB Lippincott Company; 1984. 50-89
Vesicles. These are elevated blisters containing clear fluid that are less than 1 cm in diameter
Bullae. These are elevated blisters containing clear fluid that are greater than 1 cm in diameter
Erosions. These are red lesions often caused by the rupture of vesicles or bullae or trauma and are generally moist on the skin
Ulcers. These are well-circumscribed, often depressed lesions with an epithelial defect that is covered by a fibrin clot, causing a yellow-white appearance
INTRODUCTION
INTRODUCTION
“Submicroscopic entities which reproduce within the specific living cells”
. . .
The word virus in Latin refers to poison and other noxious substances.
Norrby E . Nobel Prizes and the emerging virus concept. Arch Virol 2008 153 (6): 1109–23.
HISTORY
HISTORY
Louis Pasteur and Edward Jenner developed the first vaccines to protect against viral infections he did not know that viruses existed.
The first evidence of the existence of viruses came from experiments with filters that had pores small enough to retain bacteria.
In 1892, the Russian biologist Dmitry Ivanovsky (1864–1920) used a Chamberland filter to study what is now known as the tobacco mosaic virus. His experiments showed that crushed leaf extracts from infected tobacco plants remain infectious after filtration.
Oldstone MBA (2009). Viruses, Plagues, and History: Past, Present and Future. Oxford University Press, USA. p. 306.
HISTORY
.
THE FIRST ANIMAL VIRUSES
The second virus discovered was what is now known as Foot and mouth disease virus (FMDV) of farm and other animals, in 1898 by the German scientists Friedrich Loeffler and Paul Frosch
The FIRST HUMAN VIRUS described was the agent which causes yellow fever: this probably originated in Africa, but was spread along with its mosquito vector Aedesaegyptii to the Americas and neighbouring islands by the slave trade.
Oldstone MBA (2009). Viruses, Plagues, and History: Past, Present and Future. Oxford University Press, USA. p. 306.
GENERAL
CHARACTERISTICS
CHARACTERISTICS OF VIRUS
Samaranayake L. Virus and Prions. In: Essential Microbiology. 4th ed. Churchill livingstone.2011.P. 28-68.
Small, obligate, intracellular parasites.
Do not have a cellular organization.
Contain only one type of nucleic acid, either DNA or RNA but never both.
Cannot replicate on their own.
Must infect and take over a host cell in order to replicate.
Lack the enzymes necessary for protien & nucleic acid synthesis.
Multiply by a complex process and not by binary fission.
Unaffected by antibiotics
MORPHOLOGY
Size
• Much smaller than bacteria
• Filterability: ability to pass through filters that can hold back bacteria – thus known as filterable virus
• Largest virus : pox virus - 300nm
• Smallest virus : parvovirus – 20nm
William Boyd A Textbook of Pathology- Structure and Function in Disease; 8th edition.
MORPHOLOGY
Structure and Shape
VIRAL PARTICLE
COVERING
CAPSID(protein)
ENVELOPE (not found in all
viruses)
INNER CORE
NUCLEIC ACID-DNA/RNA
VARIOUS PROTEINS (enzymes)
Cann A.J. Particles. In: Principles of Molecular Virology. 4th ed. Elsevier Saunders, USA. 2005.
MORPHOLOGY
Structure and Shape
CAPSID
Virion consists of mainly nucleic acid
surrounded by a protein coat
Cann A.J. Particles. In: Principles of Molecular Virology. 4th ed. Elsevier Saunders, USA. 2005.
MORPHOLOGY
Structure and Shape
CAPSID
Protect the nucleic acid from inactivation by nucleases and other
deleterious agents in the environment
Introduce the viral genome into host cells by adsorbing
readily to cell surface
FUNCTION
Cann A.J. Particles. In: Principles of Molecular Virology. 4th ed. Elsevier Saunders, USA. 2005.
MORPHOLOGYStructure and Shape
CAPSIDICOSAHEDRAL (CUBICAL)
Icosahedral polygon with 12 vertices (corners), 20 facets (Sides)
Each facet is in shape of a equilateral triangle
Capsomeres in icosahedral symmetry are of two types
Pentagonal capsomeres at the vertices
Hexagonal capsomeres in the facets
HELICAL
Nucleic acid and capsomeres are wound together to form a Helical tube
Rod like with capsid proteins winding around the core in a spiral
COMPLEX
Polyhedral capsid attached to a helical tail.
Eg: Pox virus
.
.
.
Kapil A. Virology. In: Ananthanarayan and Paniker’s Textbook of Microbiology. 9th ed. United press, Hyderabad. P. 427-588.
MORPHOLOGY
Structure and Shape
VIRAL PARTICLE
COVERING
CAPSID(protein)
ENVELOPE (not found in all
viruses)
INNER CORE
NUCLEIC ACID-DNA/RNA
VARIOUS PROTEINS (enzymes)
Cann A.J. Particles. In: Principles of Molecular Virology. 4th ed. Elsevier Saunders, USA. 2005.
MORPHOLOGYStructure and Shape
ENVELOPE
Enveloped virus Non enveloped
( Naked Virus)
Derived from host cell while budding
Made up of lipoproteins
Lipid from host + protein coded by virus
Protein subunits projecting from the surface
Peplomers
Virus may carry more than one type of peplomers
E.g – Influenza virus
Triangular spike – Haemagglutinin spike
Mushroom shaped structure –
Neuraminidase
Envelope : Chemical , Antigenic & Biological
properties
Kapil A. Virology. In: Ananthanarayan and Paniker’s Textbook of Microbiology. 9th ed. United press, Hyderabad. P. 427-588.
ENVELOPE
Structure and Shape MORPHOLOGY
Kapil A. Virology. In: Ananthanarayan and Paniker’s Textbook of Microbiology. 9th ed. United press, Hyderabad. P. 427-588.
ENVELOPE
Structure and Shape MORPHOLOGY
Kapil A. Virology. In: Ananthanarayan and Paniker’s Textbook of Microbiology. 9th ed. United press, Hyderabad. P. 427-588.
MORPHOLOGY
Structure and Shape
VIRAL PARTICLE
COVERING
CAPSID(protein)
ENVELOPE (not found in all
viruses)
INNER CORE
NUCLEIC ACID-DNA/RNA
VARIOUS PROTEINS (enzymes)
Cann A.J. Particles. In: Principles of Molecular Virology. 4th ed. Elsevier Saunders, USA. 2005.
Chemical properties
NUCLEIC ACID
PROTEINS
LIPIDS
Kapil A. Virology. In: Ananthanarayan and Paniker’s Textbook of Microbiology. 9th ed. United press, Hyderabad. P. 427-588.
Resistance
Mostly heat labile
• Destroyed in seconds @56°C
• Destroyed in minutes @37°C
• Destroyed in days @4°C
Stable at lower temperatures
For long term storage store at
– 70°C
Better method –Lyophilization/
freeze drying
Bordenave G . "Louis Pasteur (1822–1895)". Microbes and Infection / Institut Pasteur. 20035 (6): 553–60.
Resistance to acids – VarySusceptible to alkaline
conditions
Inactivated by Sunlight, UV rays and ionizing radiation More resistant to chemical
disinfectants – Some of them act as preservatives
for virus
Killed by oxidizing agents
• Hydrogen peroxide
• Potassium permagnate
• hypochlorites
Formaldehyde & BPL are actively virucidal
Ether, chloroform (Lipid solvents) active on enveloped viruses
Resistance
Bordenave G . "Louis Pasteur (1822–1895)". Microbes and Infection / Institut Pasteur. 20035 (6): 553–60.
Cann A.J. Particles. In: Principles of Molecular Virology. 4th ed. Elsevier Saunders, USA. 2005.
VIRUS REPLICATION
VIRUS MULTIPLICATION
Adsorption / Attachment
Penetration/Entry
Replication
Assembly
Release
Cann A.J. Particles. In: Principles of Molecular Virology. 4th ed. Elsevier Saunders, USA. 2005.
Contact by random collision but
adsorption takes place only if
there is affinity between the two
Cell surface contain specific
receptors for attachment of virus
ATTACHMENT/ADSORPTION PENETRATION/ ENTRY
• Bacteria have thick cell wall ,
viruses cannot penetrate so , only
nucleic acid is introduced
• Animal cells do not have rigid cell
walls so the whole virus gets in
Virus DNA/RNA uses ribosomes to make virus proteins
Virus proteins created by transcription/ translation
REPLICATION ASSEMBLY
New virus proteins are
assembled in the cytoplasm
Virus enzyme causes cell membrane to lyse (burst)
Viruses are released
Cycle repeats
RELEASE
Attachment
Entry
Replication
& Assembly
Release
PATHOGENESIS
OF VIRAL
INFECTION
PATHOGENESIS OF VIRAL INFECTION
Inapparentinfections
(subclinical)
Apparent (clinical) infections which
may be acute, subacute or chronic
Latent infections –Recurrent, Persistent
RECURRENT
Clinical manifestations appear after prolonged periods of
quiescence during which the viruses remain hidden in the
nerve root ganglion
PERSISTENT
Occurs when the virus is readily demonstrable in the
tissues of the host but neither disease nor immune response
develops
Virus latency (or viral latency) is the ability of a pathogenic virus to lie dormant (latent) within a cell, denoted as the lysogenic part of the viral life cycle.
Latent viral infection is a type of persistent viral infection which is distinguished from a chronic viral infection.
ROUTES OF
ENTRY
ROUTES OF ENTRY
Sexual
Inhalation
Inoculation
BloodOrgan transplant
Ingestion
Congenital / vertical
CLASSIFICATION
AND
NOMENCLATURE
OF VIRUS
ANTIVIRAL
DRUGS
Either block viral entry into or exit from the cell or be active inside the host cell
Inhibit virus specific directed nuclei rather than host cell directed nucleic acid
Optimal efficacy- used as prophylactic
Drugs can potentially target in the replication steps, so antiviral drugs have to be specific for different viral mechanisms.
ANTIVIRAL DRUGS
NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS
(NRTIS)Zidovudine (AZT)
DidanosineStavudine,
Lamivudine
NONNUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS (NNRTIS)
NevirapineDelavirdine
PROTEASE INHIBITORSRitonavirIndinavirNelfinavirLopinavir
AmantadineRimantadine
Ribavirin, Lamivudine
AdefovirDipivoxil
Interferon A
Idoxuridine
Acyclovir
Valacyclovir
Famciclovir,
Ganciclovir
Foscarnet
Based on their therapeutic use
HERPES VIRUS
INTRODUCTION
INTRODUCTION
Characterised by ability to establish latent infections, enabling the virus to persist indefinetly within infected
hosts and to undergo periodic reactivation
HISTORY
HISTORYHippocrates is known to have described the cutaneous spreading of herpes simplex lesions
Scholars of greek civilization define the greek word "herpes" to mean "to creep or crawl" in reference the spreading nature of the herpetic skin lesions
1919- lowenstein confirmed experimentally the infectious nature of HSV that shakespeare had only suspected.(It is believed that shakespeare mentioned oral herpes in romeo and juliet)
1920-1930: found that HSV not only infects the skin, but also the central nervous system.
1930: the property of HSV - latency
More recent research has focused on antiviral research, differences between HSV strains, and using HSV vectors for use in vaccines.
MORPHOLOGY
MORPHOLOGY
The herpes virus capsid is icosahedral, composed of
162 capsomere and enclosing the core of linear
double stranded DNA genome.
The envelope carries surface spikes about 8nm long
Between envelope and the capsid is an amorphous
structure called the tegument, containing
several proteins.
CLASSIFICATION
CLASSIFICATION
CLASSIFICATION
HERPES SIMPLEX
INFECTION
INTRODUCTION
Herpes Simplex Virus (HSV) Infection
• Human Simplex Virus occurs naturally only in humans
• Can produce experimental infection in many lab animals
HSV-1 : usually located from lesions
in and around the mouthTransmitted by direct contact or droplet
spread from cases/carrers
HSV-2 : majority of genital herpes
infectionsTransmitted venereally
As a general rule, HSV1 produces ‘above the waist’ and HSV2 ‘below the waist’
Primary infection
acquired in early childhood : 2-5 years of age
Hosts - Humans
Source of infection: Saliva, Skin lesions or Respiratory secretions
EPIDEMIOLOGY
EPIDEMIOLOGY
HSV has a worldwide distribution and is endemic in all human population groups
examined.
The rate of infection and the timing of primary infection differs for hsv-1 and hsv-2,
reflecting the differences in the major modes of transmission of the two viruses.
Overall prevalence of hsv-1 rates of 70% or lower are often reported among 30–40 year-
old adults
The frequency of HSV-2 infection (up to 60%) is higher than that observed in HSV-1
A single recurrence of ophthalmic infection is observed in 20–30% of atients within 2
years of the first infection
The rate of recurrence is believed to be slightly higher in men than in women, with
rates of up to 2.7 and 1.9 episodes per 100 patient-days, respectively.
PATHOPHYSIOLOGY
CLINICAL
FEATURES
CLINICAL FEATURES
Cutaneous infections
Cheeks
Chin
Around the mouth
Forehead
buttocks in infants (napkin
rash)
Typical lesion – ‘fever blister’ or ‘herpes febrilis’
(caused by viral reactivation in febrile patients)
In some sensitive persons, very minor stimuli, like the common cold, exposure to
sun or stress
Eczema herpeticum:
Generalized eruption caused
by herpes infection in children
suffering from eczema
Herpetic whitlows, can infect patients and have led to outbreaks of infection in hospitals and among patients in
dental practices.
Now that gloves are universally worn when giving dental treatment, such cross-infections should no longer
happen.
In immunodeficient patients, such infections can be dangerous but aciclovir has dramatically improved the prognosis in such cases and may be given on suspicion.
Mothers applying antiherpetic drugs to children's lesions should wear gloves.
HERPETIC CROSS-INFECTIONS
Herpetic whitlow
Cutaneous infections
CLINICAL FEATURES
Mucosal infections
Buccal mucosa is most commonly affected site followed by hard palate, gingiva, dorsum surface of tongue
Acute gingivostomatitis is a selflimiting disease and resolution begins abruptly. The lesions become painless and inflammation subsides.
In young children the skin around the mouth is frequently involved
Hard palate Attached gingiva
Tongue
GENITAL
In men, the lesions occur mainly on the urethra causing urethritis
In women, the cervix, vagina, vulva and perineum are affected
When only cervix is involved, the infection is usually asymptomatic
The primary infection is usually more serious, accompanied by systemic features like fever and malaise
Both types of HSV may cause genital lesions, though HSV2 is responsible more frequently and causes more
recurrences
TYPES
PRIMARY HERPES SIMPLEX INFECTION
Acute herpetic gingivo-stomatitis Herpes labialis Fever blister Cold sore Infectious stomatitis
Occurs in patients with HSV-1
HSV reaches nerve ganglion supplying the affected area, along nerve pathways and remains latent until reactivated
Usual ganglion involved – trigeminal for HSV-1 and lumbosacral for HSV-2
Primary Herpes Simplex Infection
AGE
Develops in both, children and young adults
INCUBATION PERIOD
5-7 days
PRODORMAL SYMPTOMS
Precede local lesion by 1 to 2 days and includes fever, headache, malaise, nausea, vomiting and subsequently painful
Irritability, pain upon swallowing and regional lymphadenopathy Hard palate Attached gingiva
Tongue Skin
LOCATION
Primary Herpes Simplex Infection
AP
PE
AR
AN
CE
• Small vesicles- thin walled -surrounded by inflammatory base
• They rupture quickly leaving small, shallow, oval shaped discrete ulcers
SIZ
E
• Individual ulcer : 2-6 mm
• As disease progresses, several lesions may coalesce-forming larger, irregular lesions
BA
SE
• Grayish white or yellow plaque M
AR
GIN
S
• Uneven and are accentuated by bright red rimmed, well demarcated, inflammatory halos
Primary Herpes Simplex Infection
LIPS: In severe cases, excoriation involving the lips may become hemorrhagic and matted with
serosanguinous fibrin- like exudate and parting of the lips during mastication
and speech may become difficult
ACUTE MARGINAL GINGIVITIS : entire gingiva is edematous and swollen
Small gingival ulcers are seen
PHARYNX: inflammation causing difficulty in swallowing
LYMPH NODES: cervical and submandibular
HEALING: self limiting- begin healing 7-10 days- leave no scar
Primary Herpes Simplex Infection
Histopathological Findings
Lipschutz bodies,Presence of multinucleated
gaint cells, ballooning degeneration of cells.
Recurrent or Secondary Herpes Simplex Infection
Herpes Simplex Virus may be latent in epithelium-main cause
HSV reactivated at the latent site it moves centrally to the mucosa
When reactivation is triggered, they spread along the nerves to different sites on the oral mucosa and skin
Destroy the epithelial cells and induce the typical inflammatory response
Recurrent or Secondary Herpes Simplex Infection
TYPES
Recurrent Herpes Labialis
Recurrent intraoral herpes
simplex infection
Recurrent or Secondary Herpes Simplex Infection
SURGERY
• Which involve trigeminal ganglion, recurrent infections with herpes can occur (since herpes remains latent in T.ganglion)
IMMUNITY
• Low serum IgA, decreased cell mediated immunity, decreased anti-herpes activity and depression of Antibody dependent cellular cytotoxicity and interleukin-2 caused by prostaglandin release in skin can precipitate the attack
TRAUMA
• Trauma to lips, dental extraction
INFECTION
• Upper respiratory tract infection can trigger the herpes infection
OTHERS
• Fever, emotional upset, sunburns, fatigue, menstruation, pregnancy and allergy may precipitate
Precipitating Factor
Recurrent or Secondary Herpes Simplex Infection
Clinical Features
OC
CU
RA
NC
E
Every month in some patients to about once a pear or even less than that
PR
OD
OM
AL
SY
MP
TO
MS
Lesion is preceded by tingling and burning sensation and feeling of tautness, swelling or slight soreness subsequent to development of vesicles
SIG
NS
Edema at the site of lesion, followed by formation of clusters of small vesicles
Recurrent or Secondary Herpes Simplex Infection
Clinical Features
RECURRENT HERPES LABIALIS
These gray or white vesicles rupture quickly leaving small red ulcerations
Slightly erythematous halo on lip covered by brownish crust on lips
Sizes: 1-3mm to 1-2 cm
Sometimes large enough to cause disfigurement
RECURRENT INTRAORAL HERPES
Vesicles break rapidly to form small red ulcerations, sometimes erythematous
halo
Size: 1-2 mm in diameter
Site: gingivae, tongue, palate and alveolar region
Recurrent or Secondary Herpes Simplex Infection
Clinical Features
COMPLICATIONS:Extra-genital lesionsCNS complications
Vaginal fungal super infections
HEALING: within 7-10
days and leaves no scars
Herpes Simplex Virus in Immunocompromised Patient
Appears mainly as herpes labialis and recurrent intraoral herpes
HERPES LABIALIS: vesicles on an
erythematous base that heals within 7-10 days
RECURRENT INTRAORAL HERPES:
more widespread as compared to lesions in
non HIV patients
TREATMENT: systemic acyclovir 30mg/kg/dayIn acyclovir resistant patient- Foscarnet is advised
COMPLICATIONS
HERPES AND PREGNANCY
Pregnant women who are infected with either herpes simplex virus 2 (HSV-2) or
herpes simplex virus 1 (HSV-1)
genital herpes have a higher risk for miscarriage, premature labor, retarded
fetal growth, or transmission of the herpes infection to the infant while in the
uterus or at the time of delivery.
Herpes in newborn babies (neonatals) can be a very serious condition.
The reported incidence of neonatal herpes varies from extremes of 1 case in 2500 live births (Alabama, USA; Whitley, 1993) to 1.65 per 100 000 live births reported in a UK survey (Tookey
and Peckham, 1996).
Most commonly, infection is acquired during passage through an infected birth canal and
disease is evident 3–21 days (mean 12 days) post-delivery.
Infection can also occur as a result of transmission of oral herpes from the mother, her relatives or hospital staff in the immediate post-
delivery period.
In this situation disease may appear up to 28 days post-partum.
NEONATAL HERPES
Symptoms at presentation can range from the very severe, associated with high mortality, to the relatively mild, which nonetheless can be a cause of significant residual morbidity
OPHTHALMIC
The normal course of the disease is 3 weeks but if ulcers are large, healing can be slow.Mild systemic disturbances, blepharitis and circumocular herpetic dermatitis are commonly
present during the primary infection.
Most common cause of corneal blindness
There are several forms of recurrent ophthalmic infection that may occur in combination.
Dendritic or larger ‘geographic’ ulcers are usually the first
manifestation of recurrence, with the patient complaining of ocular irritation, lacrimation, photophobia and sometimes
blurring of vision.
Infection is usually confined to the superficial layers of the
cornea and stromal involvement is absent or only
relatively mild
Days or weeks after the recurrent infection, the corneal
epithelium may ulcerate to form a nondescript ovoid ulcer,
known as post-infectious or metaherpetic keratitis
The early symptoms of herpes keratitis are of a unilateral or bilateral conjunctivitis, with
pre-auricular lymphadenopathy.
Acute keratoconjunctivitis may occur by itself or by extension
from facial herpes
Acute retinal necrosis caused by HSV-1, or less commonly by
HSV-2, is a severe ocular inflammatory syndrome
associated with a poor (visual) prognosis.
Ophthalmic disease associated with intrauterine and neonatal infection with HSV can present as keratoconjunctivitis or later as chorioretinitis.
VISCERAL
HSV esophagitis may cause dysphagia,
substernal pain and weight loss
It may involve the respiratory tract, causing
tracheobronchitis and pneumonitis
NERVOUS SYSTEM
HSV encephalitis HSV
meningitis
HSV encephalitis –rare – is most
common sporadic acute viral
encephalitis in most parts of the world
It has an acute onset, with fever and focal
neurological symptoms
HSV meningitis is a self limiting disease, usually resolving in about a week
HSV can cause sacral autonomic dysfunction
and also rarely transverse myelitis or the Guillian-
Barre syndrome
HSV has been implicated in the causation of Bell’s palsy
Herpes Simplex Dermatitis; Zosteriform Herpes Simplex; Herpes
Gladiatorum
HERPETIC DERMATITIS is a
complication of primary infection. Perioral or
periorbital herpes simplex regularly accompanies more severe primary gingivostomatitis or
primary/initial herpes keratitis.
A distinct form of cutaneous infection,
‘ZOSTERIFORM HERPES simplex’, is an
infrequent presentation of herpes simplex but is recognised when the distribution of HSV
lesions accords with a dermatome and otherwise
resembles zoster.
HERPES GLADIATORUM and
‘scrum pox’ are conditions spread among wrestlers
through bites or ‘mat burns’, and among rugby players through bites and
facial scraping. The appearance of herpetic
vesicles at ‘unusual’ sites can sometimes be
explained by an inquiry into the individual’s
athletic pursuits!
DIAGNOSIS
DIAGNOSIS
History
Typical C/F
Microscopy
Serology
Virus isolation
DIAGNOSIS
Negative past history of recurrent herpes labialis and a positive history of close contact with a patient with primary or recurrent HSV
Generalised symptoms followed by eruption of oral vesicles and acute marginal gingivitis and does not have history of recurrent herpes
HISTORY TYPICAL CLINICAL FEATURES
Serological methods are useful in diagnosis of primary infection
Antibodies developed within a few days of infection and rise in titre of antibodies may be demonstrated by
ELISA, neutralisation or complement fixation test
In recurrent or re-infection herpes, there may be little change in titre
SEROLOGY
VIRUS ISOLATION
1. Primary cells - Monkey Kidney
2. Semi-continuous cells - Human embryonic kidney and skin fibroblasts
3. Continuous cells - HeLa, Vero, Hep2, LLC-MK2, MDCK
Primary cell culture are widely acknowledged as the best cell culturesystems available since they support the widest range of viruses.However, they are very expensive and it is often difficult to obtain areliable supply. Continuous cells are the most easy to handle but therange of viruses supported is often limited.
MicroscopyT
ZA
NC
K S
ME
AR
Smears are taken from base of vesicle
Stained with 1% aqueous solution of toluidine blue – 15 sec
Multinucleated gaint cells with faceted nuclei and homogeneously stained ‘ground glass’ chromatin “Tzanck cells” constitute positive smear
GIE
MS
A-
ST
AIN
ED
SM
EA
RS
Intranuclear type A inclusion bodies
FL
UR
OS
CE
NT
AN
TIB
OD
Y
TE
CH
NIQ
UE
Fluorescent antibody test on brain biopsy specimen provides reliable and speedy diagnosis in encephalitis
DIFFERENTIAL
DIAGNOSIS
Differential Diagnosis
RECURRENT HERPES SIMPLEX INFECTION
HERPES ZOSTER
Prodomal symptoms: tension, burning, itching
Prodomal symptoms: fatigue,hyperesthesia, pain
Development: vesiculoerosive lesion in crops and clusters, but not limited to dermatome
Development: edema and erythema, papulovesicular then vesiculopapularlesions and erosions
Crosses midline Does not crosses midline
Moderate pain Severe pain
Fast healing without any consequences Longer course- post zoster neuralgia
Recurrent appearances No recurrences
Differential Diagnosis
HAND- FOOT AND MOUTH DISEASE
Not clustered
Gingiva is not affected
Prominently seen on feet and hand
HERPANGINA
Oropharyngeal and soft palate involvement is more prominent
Affects children in late summar and early monsoon
CHRONIC RECURRING APHTHAE
No stomatitis
No general systemic symptoms and lesions
Less numerous
More often seen in adults
MANAGEMENT
Management
Primary herpes simplex infection
Symptomatic
PAIN CONTROL MEASURES
• Topical anesthetics like 2% lidocaine
• 0.1% dicloninehydrochloride
• 0.5% benzocaine hydrocholride
TOPICAL ANTI-INFECTIVE
AGENTS
Given to prevent secondary infection
0.2% chlorhexidinegluconate
Tetracycline mouthwash / diphenylhydramine
SUPPORTIVE CARE
• Fluid is given to maintain proper hydration and electrolyte balance
• Antipyretics can be given to control fever
GOOD ORAL HYGIENE
To avoid any secondary infection
Management
Primary herpes simplex infection
Specific
ACYCLOVIR
• It inhibits DNA replication in HSV infected cells reducing the duration of illness but with few side-effects
• 1000-1600 mg daily for 7-10 days
• 15mg/kg 5 times a day
VALACYCLOVIR
• Prodrug of acyclovir
• Better biocompatibility than acyclovir
• Should be used in combination with famicyclovir
Management
Recurrent Herpes Simplex Infection
MIN
IMIZ
ED
OB
VIO
US
T
RIG
GE
R Applying sunscreen lotion to lip
TO
PIC
AL
AN
TIV
IRA
L
ME
DIC
AT
ION
5% acyclovir cream
3% penciclovircream
10% docosanolcream
3-6 times daily
SY
ST
EM
IC A
NT
IVIR
AL
M
ED
ICA
TIO
N
Valacyclovir / Famiclovir(500-1000 mg 3 times daily)
TO
PIC
AL
CA
RB
ON
O
XO
LO
NE
In herpetic gingivostomatitis
Management
Herpes Simplex Infection in Immunocompromised patients
The primary pathogen for herpes encephalitis and herpes pneumonitis is HSV-1
For patients undergoing hematopoietic stem cell transplantation, antiviral therapy at suppressive doses should be initiated for all patients who are HSV seropositive.
A cyclovir and valacyclovir suppress HSV reactivation in such patients.
Acyclovir-resistant HSV is most frequently seen in this group of patients, where the virally derived thymidine kinase that activates acyclovir is mutated.
In such cases, foscarnet is the drug of choice.
The dosage of the acyclovir family of drugs should be adjusted for age and renal health.
CONCLUSION
CONCLUSION
CONCLUSION
CONCLUSION
REFERENCES
1. Oldstone MBA (2009). Viruses, Plagues, and History: Past, Present and Future. Oxford University Press,
USA. p. 306.
2. Norrby E (2008). "Nobel Prizes and the emerging virus concept". Archives of Virology. 153 (6): 1109–
23.
3. Teri Shors (2008). Understanding Viruses. Sudbury, Mass: Jones & Bartlett Publishers. pp. 76–77
4. Bordenave G (May 2003). "Louis Pasteur (1822–1895)". Microbes and Infection / Institut
Pasteur. 5 (6): 553–60.
5. Cawson R.A., Odell E.W. Soft Tissue Diseases. In: Cawson’s Essentials in Oral Pathology and Oral
medicine. 7th Ed. Churchill livingstone.2011.P. 179-214.
6. Lynch MA. Ulcerative, Vesicular, and Bullous Lesions. In: Lynch MA, Brightman VJ, Greenberg MS eds.
Burket's Oral Medicine: Diagnosis and Treatment. 8th ed. USA: JB Lippincott Company; 1984. 842-848.
7. Cumming CG. Ulcerative, Vesicular, and Bullous Lesions. In: Lynch MA, Brightman VJ, Greenberg MS eds.
Burket's Oral Medicine: Diagnosis and Treatment. 9th ed. USA: JB Lippincott Company; 1994. 607-614.
8. Mealey B. Ulcerative, Vesicular, and Bullous Lesions. Greenberg MS, Glick M eds. Burket's Oral Medicine.
10th ed. Spain: BC Decker Inc; 2003. 563-577.
9. Johnson RE, Nahmias AJ, Magder LS, et al. A seroepidemiologic survey of the prevalence of herpes
simplex virus type 2 infection in the United States. N Engl J Med 2011;321:7–12.
10. Ward PL, Roizman B. Herpes simplex genes: the blueprint of a successful pathogen. Trends Genet
2004;10:267–74.
11. Rajendran R, Sivapathasundaram. Shafer’s textbook of Oral Pathology. 6th ed. India: Elsevier; 2009.
12. Preshaw PM. Periodontal diseases. In: Warnakulasuriya S, Tilakaratne WM. Oral Medicine and
Pathology A Guide to Diagnosis and Management. New Delhi: Jaypee Brothers Medical Publishers (P)
Ltd; 2014.p. 72.
13. Maitra A, Abbas AK. Oral and Gastrointestinal cavity. In Kumar Abbas Fustao eds. Robbins and Cotran
Pathologic Basis of Disease. 7th ed. Elsevier Saunders, China 2005.
14. William Boyd A Textbook of Pathology- Structure and Function in Disease; 8th edition.
15. ZuckermanA.J., Banatvala J.E., Pattison J.R. Herpes Simplex. In: Clinical Virology. 5th ed. John Wiley
& Sons. 2004.p.23-81.
16. Cann A.J. Particles. In: Principles of Molecular Virology. 4th ed. Elsevier Saunders, USA. 2005.
17. Samaranayake L. Virus and Prions. In: Essential Microbiology. 4th ed. Churchill livingstone.2011.P.
28-68.
18. Kapil A. Virology. In: Ananthanarayan and Paniker’s Textbook of Microbiology. 9th ed. United press,
Hyderabad. P. 427-588.