Download viral infection

Oral viral infections
Prof. Elsanousi M Taher
BDS, MSc., FFDRCSI
LIMU Dental School
Email: [email protected]
Virus structure
The nature of viruses
• small size (10-300 nm)
• obligate intracellular parasites ( lacks ribosomes
for protein synthesis ): on entry into a susceptible
host the virus NA transcribed into - or itself acts
as- virus specific messenger RNA
• nucleic acid: DNA or RNA as a single or double
stranded
• shape variation
Structure of viruses
– Nucleic acid core ( genome): of either
DNA or RNA
– Capsid: consist of small subunits called
capsomeres
– Envelop: (in some viruses) consist of
lipoproteins
• most of envelop viruses like herpes viruses
are more susceptible to physiochemical
agents
Viral replications process
•
•
•
•
•
•
Attachment
Penetration
Viral synthesis
Virion assembly and replication
Release
Invasion of another cells or tissue
and replicate
Classification of viruses
No generally accepted classification
a.
RNA VIRUSES:
1. Picorna virues:
2.
3.
hepatitis A
enteroviruses: coxackie, polio ...etc
rhinoviruses
Myxoviruses:
 orthomyxoviruses: influenza
 paramyxoviruses: measeles, mumps,
parainfluenza
Retroviruses:
 HIV



b.DNA VIRUSES:
1. Herpes viruses ( 8 types)
2.Hepadana virus: hepatitis B virus
3.Papovirus: human papiloma virus
(HPV)
4.Pox viruses: smallpox, molluscum
contagiosum
Modes of viral infection
•
acute infection:
•
latent infection:
•
chronic infection: CMV, HBV
•
oncogenic virus:
•
benign as HPV
•
malignant as some viruses that cause certain
lymphomas and leukemias
Laboratory investigations for virus infection
I. Detection of the virus or its components
(antigens or nucleic acids) "foot prints"
1. Electron microscopy
•
–
diagnosis can be made within minutes
Disadvantages:



insensitive
only morphological diagnosis can be made
not very useful for clinical purposes
2. Direct antigen detection by
o
o
immunofluorescence or immune assay:
Enzyme linked immunosorbant assay (ELIZA)
Radio-immune assay (RIA)

Can be done on cells, serum or other body fluids
2.Detection of viral nucleic acid
by using nucleic acid hybridization and
polymerase chain reactions (PCR) in
clinical specimens
3.Detection of virus inclusion bodies:
• too non specific to be useful in clinical diagnosis
4.Culture of the virus:
–Lab. animals: rabbits, mice,
monkeys (less commonly used
nowadays)
–Chick emberyonated eggs
– Tissue cultures:
Tissue cultures:
• most cultures can be propagated in cultures of
suitable cells
• depends on preparation of single layer (monolayer) of
actively metabolizing cells adherent to glass surface
in a test tube or Petri plates)
• for continuous cell line, human rhabdomyosarcoma is
used
• almost all virus isolation is nowadays done by tissue
culture
• the diagnosis is made by detection of cytopatheic
effect (CPE)
• once the virus in cell culture is recognized, its
identity has to be confirmed
The main disadvantages of tissue culture:
• the time taken by most viruses to grow to
detectable levels (4 days for HSV & 3-4
weeks for CMV)
• some viruses can't yet be cultured routinely
in lab. like HPV, HBV, HAV
II.Serological investigation:
• Detection of the antibodies is by far the most
commonly used method for virological diagnosis in
clinical practice
– Paired serum sample is taken:
• acute stage sample
• convalescent stage sample
• A fourfold rise in the titre of serum antibodies is
indicative of infection
• Detection of IgM (the earliest antibodies to
appear is only present if there is a recent
infection with the virus)
• Limitation: retrospective
V. Detection of cytopathic changes in
the infected tissue
•
Cytopathic effect or cytopathogenic effect
(abbreviated CPE) refers to degenerative
changes in cells, especially in tissue culture,
and may be associated with the multiplication
of certain viruses.
•
Cytopathic effects have been shown in
conjunction with non-viral infections as well,
such as those changes seen in fibroblasts
during the early lesion of periodontal diseases.
Herpes viruses
Herpes viruses include:
– HSV: 1 & 2
– HZ VARICELLA : chicken box & Shingles
– EBV: infectious mononucleosis & others
– Cytomegalovirus: salivary infection
– Human herpes viruses 6 and 7: skin
rashes
– Human herpes viruses 8: Kaposi sarcoma
Herpes simplex virus (HSV) infection
• HVs are double stranded DNA
viruses:
– Transmitted in saliva
– Encountered early in life
– Characterized by latency
– Reactived by Immunosuppression
• Has two subtypes:
• HSV- 1: causes oral, skin above waist
• HSV-2 : causes genital, skin below waist and
newborn babies
HERPES SIMPLEX VIRUS
CLINICAL CLASSIFICATION OF ORAL HERPETIC
INFECTION
– Primary herpetic gingivostomatitis
– Recurrent herpetic lesions:
a. Recurrent herpes labialis
b. Recurrent intra oral herpes
Primary herpetic gingivostomatitis
Clinical features:
–
Caused by HS1 USUALLY but in teenagers may be due to
HSV2 transmitted sexually
–
route of transmission: direct contact with saliva and body
fluids
–
incubation period 2-20 days (usually 4 days)
–
most cases are subclinical (50%) or mild to be considered
as teething process
–
self limiting (10-14 days ) but may be fatal in
immunocompromised host
–
prodromal signs & symptoms (pyrexia, headache and
cervical lymphadenopathy)
–
Single episode of vesiculobullous oral lesion
–
acute marginal gingivitis with edema and ulceration
–
Ulcerations of oral mucosa
–
excessive salivations
–
Bilateral Cervical lymphadenopathy (jugolodigastric
specially)
–
Usually no hepatosplenomegally
–
after primary infection, the virus reside in the
dorsal root & trigeminal ganglion (neuroinvasive)
and at local neural tissue to be reactivated later
HSV 2 cause genital lesion in both males in
females
D.D
–
Acute necrotizing gingivitis
–
HZV infection
–
Erythema multiforme
–
Herpengina & HFMD
–
Aphthous ulceration
Special investigations: diagnosis is mainly
clinical
– Cytology smear: rarely used nowdays
– HSV isolation
– Serology: fourfold rise in antibody titer in acute
and convalescent stages
– Electron microscopy: not always available
– PCR for HSV-DNA: sensitive, rapid and
expensive
– culture of the virus: takes days
• The culture and serology take about
10 days to provide the result so they
are of limited clinical value
• Chair side kits that can rapidly (within
minutes) prove the presence of the
HSV in a lesional smear using
immunoflurosecence are available but
their routine use is limited due to
high cost
Management:
–
•
•
•
•
•
•
•
–
Supportive measures
Reduce fever and pain: paracetamol and
ibuprofen elixir
Maintain hydration
Soft diet
Reduce secondary infection
Rest
Local antseptic (0.2% CHLORHEXIDINE mouth
wash)
Antiviral : in severe or immunocompromised cases
(200 mg acyclovir five times a day for 5 days)
Reassure the parents of the affected child
about the nature and self limiting feature
of the disease
Complications of HSV infection:
– Herpetic whitlow
– Herpetic keratoconjuctivitis
– Herpetic encephalitis
– Eczematous herpeticum
Herpetic whitlow
Herpetic keratoconjuctivitis
HSV latency and reactivation
(Recurrent herpes labialis)
Predisposing factors:
–
Common cold & febrile infection
–
Exposure to sun light
–
Menstruation
–
–
–
Local irritation e.g. Dental treatment
Emotional upset
Immunosuppression
Clinical features:
–
–
Adults mainly affected
paraesthesia or burning & erythema
–
Macular papular vesicles and ulcer appear
1-2 hours later at the mucocutaneuos
junction of lip
–
–
rupture of vesicles after 2 days &
appearance of new vesicles
Healing
–
the whole cycle may take about 10 days
–
secondary bacterial infection may induce
impetiginous lesion
D.D:
• Impetigo:
• contagious superficial skin infection among kids
infection generally caused by Staphylococcus
aureus or Streptococcus pyogenes, usually
produces blisters or sores on the face, neck,
hands, and diaper area.
– Traumatic ulcers
– EM
imptigo
Management:
–
Prophylactic
–
Symptomatic:
• immunocmopetent: topical 5%
•
acyclovir cream may be applied at
early stage of the disease to reduce
its duration and severity
immunocompromised: systemic
acyclovir
Recurrent intra-oral herpes
–
–
–
–
Rare
Seen more commonly in
immunocompromised patients as in HIV
infection
The hard palate is a common site
In immunocompromised patients,
systemic antiviral is given with
supportive treatment
Varicella zoster virus infection
Primary infection ( chickenpox)
• The virus is acquired by inspiration of
contaminated droplets
• During the two weeks incubation period the virus
proliferate within the macrophages with subsequent
viraemia and dissemination into the skin and other
organs including nerve ganglia in which it reside in
latent form
• In children, it is preceded by little (malaise and
fever) or no prodromal symptoms which are more
severe in adults
– The appearance of cough, dyspnea or chest pain within
2-5 days after the onset of the rash is indicative of severe
pulmonary involvement
• Pruritus is the primary and most annoying feature
of chickenpox and patient’s scratching contributes
to secondary bacterial infections and scarring
• Abrupt discrete erythematous macules and papules
over the chest, scalp and mucous membrane that
appear in crops
• Face and distal extremities are less commonly
involved
• Irritability and anorexia
• Mouth ulcers are indistinguishable from HSV BUT
it doesn’t involve gingiva
Varicella zoster virus infection
– The macules progress to clear, tense fragile
vesicles which may rupture and become crusted
– Varicella lesions appear in 3 -5 distinct crops
for up to 5 day period and lesions in all stages
of development may be seen within one area
( an important difference from smallpox)
– The disease is highly contagious
Chickenpox (oral lesions)
Secondary infection
(zoster or shingles)
Predisposing factors:
•
Old age
•
Immunosuppression medication
•
HIV
•
Radiation
•
Others
Secondary infection
(zoster or shingles)
•
•
Zoster is latin for belt (belt like distribution)
Is due to reactivation of latent virus in sensory
ganglion
•
The lesions are preceded by mild severe preeruptive itch, tenderness or severe pain; the
last may be generalized over the entire nerve
segment or localized to part of it, or referred
•
The pain in the facial area mimic and be
confused with toothache
•
Neurological changes like hypo, hyperesthesia or
dysthesia may be reported or detected
– The interval between pain and the appearance of
eruptions may be as long as 10 days but on average is
3-5 days
– Lesions are usually unilateral and involve face and/or
oral cavity along the distribution of v cranial nerve
and doesn’t cross the mid line
– The pain usually subsided in several weeks with scar
formation
– Rarely the eruption may be bilateral
– Lesion on the tip of the nose may herald involvement
of trigeminal nerve
– Trigeminal nerve is affected in about 15% of cases of
shingles (most lesions are in thoracic area)
– May be complicated by post-herpetic neuralgia
Secondary infection
(zoster or shingles)
Investigations:
– cytological smear of the vesicle may
show T zank cells
– viral culture
– antibody titre
– Electron microscopy examination
– investigate for underlying disease
Treatment of orofacial shingles
I.
Healthy patient:
–
maintain good OH
–
painting of the lesions with tincture benzoin
–
analgesics like opiates
–
topical 5% acyclovir (early in the course)
–
systemic acyclovir if severe (400 mg tds/ 10
days)
–
ocular involvement should be evaluated and
managed by an ophthalmologist
–
it may treated with topical steroid and the
lesion must be distinguished from herpes simplex
keratitis where the steroid is contraindicated
–
systemic antibiotic if secondarily infected arise
II. In immunocompromised patient:
– as above in addition to:
• systemic acyclovir (800 mg IV tds)
• zoster immunoglobulin
• acyclovir: reduce duration of pain, time of healing,
post-herpatic neuralgia
• systemic steroid for a short period appear to reduce
the post-herpatic neuralgia. It should be started
early after skin eruption
Complications of shingles:
• Ophthalmic: corneal ulcers and scarring &
blindness
• Motor palsy: may result from spread of the
lesion from the posterior horn into the ant. horn
of spinal cord
• Disseminated HZ: in immunocompromised patients
and cause gangrenous and necrotic lesions,
varicella pneumonia and encephalitis are
potentially fatal
• post-herpatic neuralgia
Post-herpetic neuralgia
–
Occurs in 9-15 % of patients with shingles
–
Tricyclic antidepressant (amitriptyline)
–
Phenothiazines
–
Combined treatment of carbamazepine (600-800
mg/day) or phenytoin sodium (300-400 mg) + 50-100
mg nortryptaline
–
Intralesional or subcutaneous injection of triamcinolone
0.2 mg/ml into the affected dermatome
–
Repeated cryosurgery of the area affected with by
postherpatic neuralgia is reported to cause long-term
relief of pain
–
Transcutaneous electrical stimulation may be useful in
patients with intractable pain
Ramsay Hunt syndrome
is the reactivation syndrome of herpes zoster in
the geniculate ganglion. It has variable
presentation which may include a lower motor
neuron lesion of the facial nerve, deafness,
vertigo and pain.
See Facial Pain
Epstein -Barr virus
This virus is being associated with many conditions:
• infectious mononucleosis
•
Burkitt's lymphoma
• Nasopharyngeal carcinoma
•
Hairy leukoplakia
•
Transmitted by saliva, blood
transfusion and may become latent in
B-lymphocytes and pharyngeal
epithelial cells
•
Infected lymphocytes appear in
peripheral blood as atypical
lymphocytes
•
It has relatively long incubation period
(30- 50 days)
Infection with EBV
–
–
•
EBV is present in pharyngeal epithelium
and appears in saliva of patient with
infectious mononucleosis and for several
months after recovery
Close contact transmit the disease
(kissing disease)
sub clinical (asymptomatic)
•
acute (infectious mononucleosis)
•
chronic infection
Infectious mononucleosis
–
Common in adolescents & young adults
–
Fever and Malaise
–
Sore throat
–
Tonsillar exudates that mimic diphtheria
–
Cervical lymphadenopathy
–
Hepatomegally and abnormal liver function tests
–
Splenomegally
–
Palatal petechiae in 30 % of cases
–
Oral ulceration
–
Skin rash on ampicillin administration (non allergic type)
Skin rash on ampicillin administration
Palatal petechiae in 30 % of cases
Blood film: large atypical nononuclear
lymphocytes
Complications of infectious mononucleosis:
– Hairy leukoplakia
– Burkitt’s lymphoma
– Nasopharyngeal carcinoma
– Chronic infection and persistent malaise
Infectious mononucleosis
D.D:
• CMV mononucleasis
• diphtheria
• HIV infection
• acute lymphonodular pharyngitis
• leukemia
Infectious mononucleosis
Investigations:
– CBC with lymphocytosis
– Blood film: large atypical nononuclear
lymphocytes
– Serology:
• Paul-Bunnel or monospot test (positive
heterophil antibody test)
• Antibody to EBV viral capsid antigen (VCA)
Infectious mononucleosis
Management:
– Supportive
– Acyclovir is of little benefit
– SYSTEMIS steroids if there is
pharyngeal oedema severe enough to
compromise the airway
Cytomegalovirus infection
•
About 80% of adults by the age of 40 are CMV
seropositive
•
The prevalence of CMV in homosexuals, IVDA, is
almost 100% where it is present in all body fluids
Contracted from infected saliva, urine and body
fluids, blood transfusion, can cross the placenta
20-40 days incubation periods
•
•
•
The virus is usually latent in salivary gland, kidney,
liver and lung
•
The CMV can cause:
• congenital CMV: abortion, mental retardation and physical
defects and expels the virus in urine for months or years
(reservoir for virus)
•
CMV mononucleosis
CMV mononucleosis
• Infection usually subclinical
• In healthy individuals it Cause CMV
mononucleosis syndrome:
–
–
–
–
Headache
Sore throat
Back and abdominal pain
Atypical Lymphocytosis but Paul- Bunnell test is
negative
• Lymphadenopathy are not conspicuous
feature as in EBV
• In immunocompromised (HIV and kidney transplant)
patients infection or activation of latent virus may
be very serious as it cause opportunistic infections
in:
– Lung and Liver
– GIT
– CNS
– EYE
• Treatment is asymptomatic but Ganciclovir is
active against CMV AND INDICATED FOR
IMMUNOCOMPROMISED patients
Coxsackie viruses
• RNA viruses
• group A type is responsible for:
– Herpangina
– Hand, foot and mouth disease
– Acute lymphonodular pharyngitis
Herpangina
•
Epidemic & contiguous disease usually seen
among school children
•
Transmitted by contaminated saliva and fecaloral routes
•
Affect mainly children and young adults
•
May present with low grade fever, anorexia,
sore throat or dysphagia
•
Orally 4-6 ulcers are predominantly affect
post. Part of the oral cavity and soft palate
•
Lymphadenopathy is less common
•
Self limiting ( lasts for few days)
Oral lesions of herpangina
D.D:
–
–
–
–
HSV
HZV
herpetiform aphthous ulceration
The main D.D is herpetic gingivostomatitis
but in herpengina:
–
occurs in epidemics
–
milder & ulcers are less painful
–
the gingiva is not affected
–
affect post. part of oropharyngeal cavity
–
the smear doesn't show cythopatic changes
Hand, Foot and Mouth disease
(HFM)
clinical features are similar to herpangina but:
–
Has painful maculo-papular and vesicular lesions on
dorsum of palm of hands and soles of feet and between
digits and mucosa of the pharynx, soft palate and
tongue
•
Diagnosis and management is as herpangina
•
Self limiting disease
•
Foot & mouth disease (of cattle) is quite
different rhinovirus infection which rarely affect
humans