Viruses of relevance to dentistry

VIRUSES OF RELEVANCE TO

DENTISTRYDr. Hadeel Almasri

Orthodontics Resident

Lecture’s Outlines Human papillomavirus Herpesviruses Mumps virus Coxsackieviruses

Human papillomavirus

DNA virus.

mainly causes skin warts (verrucae); it is also associated with a number of lesions including oral papillomas, oral verrucous carcinomas and focal epithelial hyperplasia.

There are more than 70 serological types of HPV, some of which are more closely associated with lesions (both benign and cancerous) than others.


Skin warts:

Clinical features: warts typically are benign epithelial tumours. Specific serological types of HPV are associated with anogenital warts (condylomata acuminata) and are seen in all cervical biopsies that show precancerous change.

Epidemiology: warts are generally more common in children than in adults. The virus is likely to be transmitted by direct contact or autoinoculation.


Oral infections with HPV :

Over 40% of healthy individuals have HPV in the normal oral mucosa, suggesting that this is a reservoir of the virus.

Oral squamous papillomas and warts Clinical features: most are single, small (1 cm),

pedunculated, exophytic lesions. They rarely, if ever, progress to carcinomas.

Epidemiology: occur mainly in the third to fifth decade of life, with a male preponderance.

Verrucous carcinoma

Herpesviruses There are a range of different human herpesviruses, currently

numbered 1–8 .

All of them are structurally similar (enveloped, icosahedral with double-stranded DNA) and infect both humans and animals.

They are the most common causes of human viral infections.

All have the important property of remaining latent, with the ability to reinfect the host a variable period after the primary infection.

Important human pathogens include herpes simplex virus types 1 and 2 (HSV-1 and HSV-2), varicella-zoster virus (VZV), cytomegalovirus (CMV) and Epstein–Barr virus (EBV)

Herpesviruses Structure:

180–200 nm in diameter and contain a linear dsDNA molecule.

unstable at room temperature and are rapidly inactivated by lipid solvents such as alcohol.

During reproduction, maturation of the progeny begins in the nucleus of the host cell, which buds through the nuclear membrane and acquires the viral envelope. Typical and highly pathognomonic intranuclear inclusions are therefore found in cells that have undergone active virus replication.

Herpesviruses Structure:

As many herpesviruses can fuse with the cells they infect, polykaryocytes or giant cells readily appear in tissue lesions. This is a hallmark of herpetic infections.

Herpesviruses HSV (human herpesviruses 1 and 2) :

They can be differentiated by serotyping, by DNA homology and, to some extent, by clinical disease pattern.

Clinical disease: can be either a primary infection, due to first

encounter with the virus, or a reactivation or recurrent infection, due to activation of the latent virus.

Herpesviruses Primary infection:

There is an incubation period of 2–20 days, depending upon the infected site and the infecting strain of virus.

The lesions include:

primary gingivostomatitis with lesions on the lips and mouth; very common

genital herpes: vesicular eruption of the genitalia, mostly due to HSV-2 (but up to a third of the cases may be due to HSV-1)

herpetic whitlow: infection of the fingers, acquired by dentists and nurses as a result of contamination of the hands by virus-laced saliva or other secretions.

conjunctivitis and keratitis: less commonly, HSV infections involve the eyes, sometimes leading to blindness.

encephalitis: a result of either primary or recurrent infection; may lead to permanent defects or death.

Herpesviruses Recurrent infections:

Recurrence or reactivation of HSV entails activation of the non-infectious form of the latent virus residing in the neurons of either the trigeminal ganglion or the sacral ganglia.

Reactivation is provoked by menstruation, stress, sunlight (possibly ultraviolet rays), local trauma.

The lesions tend to recur at the site of the primary lesion.

HSV has been implicated in Bell’s palsy.

Herpesviruses Epidemiology:

Humans are the only known reservoir for HSV-1 and HSV-2.

As the virus is highly labile, most primary infections are acquired through direct contact with a lesion or contaminated secretions.

In general, HSV-1 causes orofacial lesions or lesions ‘above the belt’, while HSV-2 causes lesions ‘below the belt’, i.e. genital herpes.

HSV-1 is acquired early in life, while HSV-2 appears after the onset of sexual activity.

As recurrent infection is common in the presence of high antibody titres, circulating antibodies appear to be unhelpful in controlling HSV infection. One reason for this may be the contiguous cell-to-cell spread of the virus, which cannot be prevented by antibody. Reactivation is not accompanied by a rise in herpes antibody titre.

Herpesviruses Diagnosis:

Diagnosis is usually achieved clinically; laboratory diagnosis is useful to confirm infection, especially in compromised patients.

This entails: direct demonstration of viral antigens in vesicular fluid or

scrapings by electron microscopy or immunofluorescence. demonstration of characteristic multinuclear giant cells in

scrapings from lesions – simple but not always successful. propagation of virus in tissue culture.

However, the foregoing traditional techniques are now supplanted by polymerase chain reaction-based rapid diagnostic methods.

Herpesviruses Prevention:

Control is difficult because of the high frequency of asymptomatic infection. It is important to avoid contact with acute herpetic lesions and contaminated body fluid (e.g. saliva) by routine wearing of gloves. No vaccine is available.

Treatment:

The course of primary infection can be altered significantly with drugs that interfere with viral DNA synthesis, such as aciclovir and vidarabine, but these should be administered in the early prodromal phase of the disease for best results.

Herpesviruses Varicella-zoster virus (human herpesvirus

3):

This organism causes both varicella (chickenpox); the primary infection, and herpes zoster (shingles); the reactivation of illness.

Herpesviruses Varicella (chickenpox) :

A common childhood fever, varicella is mild and selflimiting. The disease is more severe if contracted in adulthood.

After a 2-week incubation period, fever develops, followed by a papular rash of the skin and mucous membranes, including the oral mucosa.

The papules rapidly become vesicular and itchy but painless (in contrast to the rash in zoster).

Herpesviruses herpes zoster (shingles):

Occurs primarily as a reactivation of the virus in dorsal root or cranial nerve (usually trigeminal) ganglia.

The disease usually affects adults, and the virus is reactivated despite circulating antibodies.

Zoster is triggered by trauma, drugs, neoplastic disease or immunosuppression.

The virus remains latent in ganglionic nerve cells and, after activation, travels back along the nerve fibre to the skin.

Thoracic nerves supplying the chest wall are most often affected, and the lesion presents as a unilateral, painful vesicular rash, which extends in a horizontal strip from the middle of the back around the side of the chest wall (‘belt of roses from hell’).

Herpesviruses herpes zoster (shingles):

Fever and malaise accompany the lesion.

The rash may last for 2–4 weeks, with pain (post-herpetic neuralgia) persisting for weeks or months.

The trigeminal nerve is affected in about 15% of cases, with involvement of the ophthalmic, maxillary and mandibular divisions (in that order of precedence).

Severe localized oral pain precedes the rash and may be easily confused with toothache.

Ramsay Hunt syndrome is a rare manifestation of zoster, with a vesicular rash on the tympanic membrane and the external auditory canal, together with unilateral facial nerve palsy.


Shingles is primarily a disease of older adults and immunocompromised persons; it is rare in children.

It is a highly contagious infection in a host not previously exposed to the virus.

Transmission occurs by direct contact with skin lesions or droplet infection from infectious saliva.

Herpesviruses Diagnosis:

The clinical picture is pathognomonic, as the lesion distribution overlaps and accurately maps the distribution of the sensory nerve.

Serology, if needed, entails detecting a fourfold rise in antibody titre in paired sera.

Prevention:

Passive immunization with varicella-zoster immune globulin (VZIG) may be indicated for persons at high risk of severe infection. A vaccine for chickenpox is now available.

Herpesviruses Treatment:

Chickenpox is self-limiting and requires symptomatic treatment, if any.

Disseminated zoster in immunocompromised patients requires antiviral drugs (e.g. aciclovir, vidarabine), which interfere with herpesvirus DNA replication.

Varicellazoster virus is less sensitive to aciclovir than is HSV, and hence, a higher dosage is required; therapy should start within 72 h of onset.

Systemic aciclovir may reduce the duration of the early infective phase and the associated pain. In addition, it may reduce the prevalence of post-herpetic neuralgia.

Herpesviruses EBV (human herpesvirus 4):

The virus persists in latent form within lymphocytes after primary infection (lymphotrophic, unlike HSV and varicella-zoster virus, which are neurotrophic).

The genome resides in a latent form in B cells.

It causes a number of diseases:

Infectious mononucleosis (glandular fever) Burkitt’s lymphoma and other B cell lymphomas nasopharyngeal carcinoma (especially in southern Chinese

populations) oral hairy leukoplakia post-transplant lymphoproliferative diseases.

Herpesviruses Infectious mononucleosis:

An acute infection affecting lymphoid tissue throughout the body.

commonly seen in teenagers, with a peak incidence at 15–20 years of age.

The organism is present in saliva and is postulated to be transmitted during kissing – hence, it is called the ‘kissing disease’.

Incubation is 4–7 weeks; possibly shorter (10–40 days) in young children.


Signs and symptoms:

Low-grade fever with generalized lymphadenopathy and abnormal lymphocytes in the blood.

tonsillitis and fatigue. many patients have splenomegaly. Lymphocytosis is a characteristic feature, hence the term

‘mononucleosis’. Chronic, persistent or reactivated EBV infection; less

common than acute mononucleosis characterized by persistent fatigue, with or without physical or laboratory findings.


Epidemiology:

humans are its only known host. Spread of EBV is via respiratory secretions,

primarily through oral contact. Those from lower socioeconomic classes are

exposed to EBV at an early age and typically develop asymptomatic infections, while in higher socioeconomic classes, primary infection is usually delayed to adolescence or young adulthood.


Diagnosis:

Indirect immunofluorescence is used to detect EBVspecific immunoglobulin M (IgM); the antibody is directed against both the capsid antigen and a noncapsid early antigen.

Haematology: a blood film is useful for demonstrating atypical lymphocytosis in infectious mononucleosis.

Heterophile antibody (non-specific): infectious mononucleosis is characterized by the appearance of heterophile antibodies in the patient’s serum, which agglutinate sheep or horse red blood cells. This property is made use of in the Paul–Bunnell diagnostic test.

Treatment : Infectious mononucleosis is generally mild and self-limiting; hence, therapy

is usually symptomatic.

Herpesviruses Burkitt’s lymphoma:

is a highly malignant tumour that spreads rapidly, with widespread metastases.

common in African children.

The disease is common in areas of Africa with endemic malaria. Hence, it is thought that the effect of the malarial parasite on the reticuloendothelial system could cause an abnormal response to infection with EBV.

Under these conditions, the EBV may become frankly oncogenic, producing a malignant transformation in lymphoid tissue (lymphoma) instead of the benign proliferation seen in infectious mononucleosis.

Herpesviruses Nasopharyngeal carcinoma:

A tumour with a remarkable geographic and probably racial distribution, it is particularly common among the southern Chinese. EBV DNA is regularly present in the malignant epithelial cells of the tumour.

Herpesviruses Hairy leukoplakia:

The term ‘hairy leukoplakia’ is given to raised, white areas of thickening, particularly on the lateral border of the tongue.

The DNA of EBV is present in the epithelial cells of hairy leukoplakia.

Demonstration of EBV in biopsy tissue of hairy leukoplakia is essential for a definitive diagnosis.

Herpesviruses CMV (human herpesvirus 5):

CMV rarely causes disease unless other precipitating factors, such as immunocompromising states, are present. However, it can infect the foetus during pregnancy.

Clinical disease :

Symptomless infection. Post-natal infection.

Herpesviruses Symptomless infection:

The majority of infants show no signs of infection, and diagnosis is made by serology.

Although a large proportion of the infants are unharmed, a significant number of neonates with congenital infection show neurological sequelae, such as deafness and mental retardation, later in life.

A minority develop a severe, often fatal illness associated with infection of the salivary glands, brain, kidneys, liver and lungs.

Herpesviruses Post-natal infection:

Later in life, the virus may be activated by pregnancy, multiple blood transfusions or immunosuppression.

Infection in immunocompromised patients can be severe and involve many organs, such as the lungs, liver, gastrointestinal tract and eyes.


Infection appears to increase during the perinatal period and during early adulthood; patients with neoplastic disease or AIDS and transplant recipients often have local and disseminated CMV disease. The route of CMV transmission is not clear.

Diagnosis and treatment:

Diagnosis is by viral isolation in human embryonic fibroblast tissue cultures; it is confirmed using immunofluorescence and DNA hybridization. There are no proven regimens for therapy and prevention of CMV infections.

Herpesviruses Human herpesvirus 6:

A DNA virus closely related to CMV.

The virus shows affinity for T and B cells in particular.

common in childhood, and most primary infections are asymptomatic followed by latency.

The pathogenicity of HHV-6 is as yet unclear. Recently, it has been found in active plaques in patients with multiple sclerosis.

Herpesviruses Human herpesvirus 6:

Exanthem subitum (roseola infantum) is A common childhood disorder characterized by mild fever and a facial rash, and appears to be associated with HHV-6 infection.

Mononucleosis with cervical lymphadenopathy is a febrile illness in adults with bilateral cervical lymphadenopathy, somewhat like glandular fever; thought to be a primary infection with HHV-6.

Herpesviruses HHV-6 and the oral cavity:

The virus is present in the saliva of most healthy adults, and it can also be demonstrated in ductal and alveolar epithelium of major salivary glands.

There are no specific oral lesions reported for HHV-6, though erythematous papules seen in soft palate and uvula (Nagayama’s spots) and in the pharynx are thought to be due to this organism.

No occupational hazard from HHV-6 has been proved in dentistry, but the virus may well be transmitted in saliva.

Herpesviruses Human herpesviruses 7 and 8:

These viruses have been recently identified.

(HHV-7) is a T-lymphotrophic virus and is implicated in rashes.

(HHV-8) is the agent responsible for Kaposi’s sarcoma, a vascular endothelial tumour commonly seen in HIV disease it is also implicated in sarcoidosis.

Mumps virus A common childhood fever.

typically causes parotitis (mumps) of acute onset involving one or both parotid glands.

The attenuated form of the mumps virus, incorporated in the combined measles–mumps–rubella (MMR) vaccine, leads to the development of antibody in 95% of vaccinees.

Coxsackieviruses Coxsackieviruses are subdivided into two major groups, A and B.

Each group also has several serologically distinct subgroups.

Most human coxsackievirus infections are mild and frequently asymptomatic.

Serious infection, although rare, results in severe disease.

Two diseases caused by group A coxsackieviruses are of particular dental interest: herpangina, and hand, foot and mouth disease.

the greatest epidemic spread occurs in the summer and autumn.

Viral transmission is by the faecal–oral route and from nasal and pharyngeal secretions.

Coxsackieviruses Herpangina:

is common in children but may affect any age group.

characterized by fever, headache, sore throat, dysphagia, anorexia and occasionally a stiff neck.

herpes-like oropharyngitis, where the ulceration is predominantly on the tonsil, soft palate and uvula.

The small, papulovesicular lesions are about 1–2 mm in diameter, with a greyish-white surface surrounded by red areolae.

The disease is self-limiting and lasts for 3–4 days.

Coxsackieviruses Hand, foot and mouth disease:

a relatively common infection in children.

easily diagnosed because of its classic distribution in the hands, feet and mouth.

The incubation period is about 3–5 days and resolution occurs within a week.

The disease may begin with facial pain, with tenderness along the course of the parotid duct and a few vesicles around the duct orifice.

Coxsackieviruses Hand, foot and mouth disease:

The onset of the oral and skin eruptions is accompanied by headache, malaise and sore throat, but in many, there is little systemic upset.

The oral lesions are generally bright-red macules, which later form oval or grey vesicles with red areolae.

The plantar surface of the feet and the palmar surface of the hands are affected.

These skin lesions are bright-red macules with pale centres, which develop into thin-walled bullae or small ulcers with surrounding erythema.

The lesions in the mouth, and on the hands and feet, are not always seen.

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Health & Medicine

Viruses of relevance to dentistry