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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