1. Oral viral infections Prof. Elsanousi M Taher BDS, MSc., FFDRCSI
LIMU Dental School

2. Virus structure

3. 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

4. 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

5. Viral replications process
Attachment
Penetration
Viral synthesis
Virion assembly and replication
Release
Invasion of another cells or tissue and replicate

6. Classification of viruses
No generally accepted classification
RNA VIRUSES:
Picorna virues:
hepatitis A
enteroviruses: coxackie, polio ...etc
rhinoviruses
Myxoviruses:
orthomyxoviruses: influenza
paramyxoviruses: measeles, mumps, parainfluenza
Retroviruses:
HIV

7. DNA VIRUSES:
Herpes viruses ( 8 types)
Hepadana virus: hepatitis B virus
Papovirus: human papiloma virus (HPV)
Pox viruses: smallpox, molluscum contagiosum

8. 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

9. Disadvantages: Laboratory investigations for virus infection
Detection of the virus or its components
(antigens or nucleic acids) "foot prints"
Electron microscopy
diagnosis can be made within minutes
Disadvantages:
insensitive
only morphological diagnosis can be made
not very useful for clinical purposes
Direct antigen detection by immunofluorescence or immune assay:
Enzyme linked immunosorbant assay (ELIZA)
Radio-immune assay (RIA)
Can be done on cells, serum or other body fluids

10. Detection of viral nucleic acid
by using nucleic acid hybridization and polymerase chain reactions (PCR) in clinical specimens
Detection of virus inclusion bodies:
too non specific to be useful in clinical diagnosis

11. Lab. animals: rabbits, mice, monkeys (less commonly used nowadays)
Culture of the virus:
Lab. animals: rabbits, mice, monkeys (less commonly used nowadays)
Chick emberyonated eggs
Tissue cultures:

12. 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

13. 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

14. 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

15. 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.

16. Herpes viruses

17. 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

18. 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

19. Primary herpetic gingivostomatitis Recurrent herpetic lesions:
HERPES SIMPLEX VIRUS
CLINICAL CLASSIFICATION OF ORAL HERPETIC INFECTION
Primary herpetic gingivostomatitis
Recurrent herpetic lesions:
Recurrent herpes labialis
Recurrent intra oral herpes

20. 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

21. 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

28. HSV 2 cause genital lesion in both males in females

29. D.D Acute necrotizing gingivitis HZV infection Erythema multiforme
Herpengina & HFMD
Aphthous ulceration

30. 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

31. 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

32. 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

33. Complications of HSV infection:
Herpetic whitlow
Herpetic keratoconjuctivitis
Herpetic encephalitis
Eczematous herpeticum

34. Herpetic whitlow

35. Herpetic keratoconjuctivitis

36. 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

37. 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

42. D.D: Impetigo: Traumatic ulcers EM
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

43. imptigo

44. 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

45. 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

47. 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

48. Face and distal extremities are less commonly involved
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

49. 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

52. Chickenpox (oral lesions)

53. Secondary infection (zoster or shingles)
Predisposing factors:
Old age
Immunosuppression medication
HIV
Radiation
Others

54. 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 pre-eruptive 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

55. 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

61. 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

62. Treatment of orofacial shingles
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)

63. 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

64. as above in addition to:
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

66. 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

67. Post-herpetic neuralgia
Occurs in 9-15 % of patients with shingles
Tricyclic antidepressant (amitriptyline)
Phenothiazines
Combined treatment of carbamazepine ( mg/day) or phenytoin sodium ( mg) 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
Postherpetic neuralgia is thought to be nerve damage caused by herpes zoster. The damage causes nerves in the affected dermatomic area of the skin to send abnormal electrical signals to the brain. These signals may convey excruciating pain, and may persist or recur for months, years or for life.
Signs and symptoms
Symptoms:
With resolution of the HZ eruption, pain that continues for 3 months or more is defined as PHN.
Pain is variable from discomfort to very severe and may be described as burning, stabbing, or gnawing.
Signs:
Area of previous HZ may show evidence of cutaneous scarring.
Sensation may be altered over involved areas, in the form of either hypersensitivity or decreased sensation.
In rare cases, the patient might also experience muscle weakness, tremor or paralysis — if the nerves involved also control muscle movement.

68. 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

69. Epstein -Barr virus
This virus is being associated with many conditions:
infectious mononucleosis
Burkitt's lymphoma
Nasopharyngeal carcinoma
Hairy leukoplakia

70. 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 ( days)

71. 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

72. 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)

73. Skin rash on ampicillin administration

74. Palatal petechiae in 30 % of cases

75. Blood film: large atypical nononuclear lymphocytes

76. Complications of infectious mononucleosis:
Hairy leukoplakia
Burkitt’s lymphoma
Nasopharyngeal carcinoma
Chronic infection and persistent malaise

77. Infectious mononucleosis
D.D:
CMV mononucleasis
diphtheria
HIV infection
acute lymphonodular pharyngitis
leukemia

78. 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)

79. Infectious mononucleosis
Management:
Supportive
Acyclovir is of little benefit
SYSTEMIS steroids if there is pharyngeal oedema severe enough to compromise the airway

80. 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

81. 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

82. 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

83. Coxsackie viruses RNA viruses group A type is responsible for:
Herpangina
Hand, foot and mouth disease
Acute lymphonodular pharyngitis

84. Herpangina
Epidemic & contiguous disease usually seen among school children
Transmitted by contaminated saliva and fecal-oral 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)

85. Oral lesions of herpangina

86. 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

87. 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