Chapter 10 Orofacial viral infections
It has been estimated that 90% of adults harbour viruses that have been acquired as a result of infection during earlier life. Many viruses have the property of latency and may reside in the tissues asymptomatically for the remainder of the patient’s life. The oral tissues are a frequent site for symptomatic primary infection and also reactivation of latent viruses. The presence of these viruses often becomes apparent at times when the host immune defence is compromised. This may range from short episodes of localized symptoms in otherwise healthy individuals to widespread prolonged problems in HIV positive patients.
Viruses, which are some of the smallest microorganisms (100–300 nm), consist of a core (genome) containing either DNA or RNA surrounded by a protein shell (capsid) (Fig. 10.1), can cause a range of important human diseases. Certain viruses also possess an outer lipoprotein coat derived from infected host cells. Viruses are obligate intracellular parasites in that they require the protein synthesizing apparatus (ribosomes) of the host cell. Viral replication is a complex process but comprises a number of recognized steps including, adsorption/penetration into the host cell, uncoating, transcription, synthesis of viral components, assembly and finally, release of new virions (Fig. 10.2).
Knowledge of the different steps in viral replication has been the principle basis for the development of the antiviral drugs that are presently available. Relatively few antiviral agents have been developed when compared to the number of antibacterial drugs that are available. The intracellular nature of infection and the ability of viruses to establish latent forms have contributed to the difficulty in designing effective antiviral drugs.
The development of aciclovir was a milestone in antiviral therapy, representing the first true specific antiviral agent, recognized by the award of the Nobel Prize for Medicine. Aciclovir is a nucleoside analogue drug that has activity against members of the herpes group of viruses, in particular herpes simplex virus type 1 (HSV-1) and herpes simplex virus type 2 (HSV-2). Viral enzymes, within HSV-infected cells, phosphorylate aciclovir to monophosphate and the agent becomes cell bound. Subsequent further phosphorylation to aciclovir triphosphate produces an analogue to deoxyguanosine triphosphate that inhibits viral DNA synthesis and prevents further viral replication.
Since aciclovir acts by blocking viral replication, a decision to provide the drug should be made at an early stage, preferably within 48 hours of the onset of acute symptoms in herpes simplex or varicella zoster infections. Antiviral therapy started later than this time is unlikely to produce any significant clinical benefit, and therefore is not justified unless the patient is otherwise medically compromised.
Aciclovir may be applied topically or given systemically in severe infection. Other antiviral agents used for orofacial herpes simplex and varicella zoster infections include valaciclovir (which is given systemically and has a longer intracellular half-life than aciclovir), penciclovir (available only in topical form) and famciclovir (the oral pro-drug of penciclovir). These agents act essentially in the same way as aciclovir. Docosanol, an agent that alters the cell membrane to prevent viral entry, is also available for topical application for orofacial herpes simplex infections. Ganciclovir and foscarnet are two other antiviral agents that are used in specialist units for treatment of infections due to cytomegalovirus.
A variety of laboratory methods have been developed for the detection, isolation and identification of viruses within clinical samples (Table 10.1). These techniques involve microscopy, culture, serology and nucleic acid amplification. However, the most appropriate method of sampling depends on the nature of the suspected infection.
|Electron microscopy of vesicular fluid||Easy sampleRapid result||InsensitiveNot specific|
|Light microscopy of lesional smear||Easy sample of smear Widely availableRapid result||Not specific|
|Light microscopy of lesional smear with immunofluorescence||Easy sampleRapid resultSpecific||Not routinely available|
|Culture of swab of lesion||Easy sampleCan be specificWidely available||Result may not be available for up to 10 days|
|Antibody titre in venous blood||Requires paired venous samples||Two haematological samples required.Result not available for at least two weeks|
|PCR amplification of vesicular fluid or swab of lesion||Easy sampleRapid result||Not widely available|
Electron microscopy can be used to provide a provisional identification based on the morphological appearance of viral particles but this approach has low specificity and requires additional tests. Routine light microscopy can be used in conjunction with immunofluoresence and monoclonal antibodies to detect the presence of specific viruses (Fig. 10.3). This is a relatively rapid method giving a result within 30 minutes but the technique is not widely available.
Viruses can be grown in tissue culture usually involving baby hamster or monkey kidney fibroblasts. A swab of the lesion should be placed in viral transport medium, which contains at least two antibiotics, usually penicillin and streptomycin, to prevent bacterial growth, combined with an antifungal, such as amphotericin, to eliminate any fungal contamination. The transport medium should also contain serum and a buffer to maintain virus viability. The specimen should be sent to the laboratory promptly although it will not be processed for 24 hours to allow the antimicrobials mentioned above time to have an effect. The first stage of processing is inoculation into a monolayer of tissue culture. The presence of virus is determined in the laboratory by detection of a cytopathic effect, which is seen as the development of multinucleate giant cells (Fig. 10.4). This may take up to 10 days although the cytopathic effect occurs more rapidly in the presence of high numbers of virus particles.
Fig. 10.4 (A) Monolayer of baby hamster kidney fibroblasts inoculated with swab specimen at day 1. (B) Same monolayer at day 7 showing cytopathic effect as destruction of architecture and development of multinucleate cells.
Alternatively, diagnosis may be confirmed retrospectively by the detection of a four-fold rise in antibody titre between acute and convalescent sera taken from the patient. However, this technique has limited clinical benefit in diagnosis due to the prolonged time involved in obtaining a result. Molecular methods are being used increasingly to detect virus DNA or mRNA and in the future it is likely that these will provide a rapid diagnosis.
The name herpes comes from the Greek word ‘herpein’ which means to creep (chronic, recurrent). While more than 100 herpes viruses have been isolated in nature, only eight herpes viruses have been described in humans and these are classified according to their biological properties into three sub-families: Alphaherpesvirinae, Betaherpesvirinae and Gammaherpesvirinae (Table 10.2), all of which may be encountered in orofacial tissues.
|Human herpesvirus 1||Herpes simplex virus 1||HSV-1|
|Human herpesvirus 2||Herpes simplex virus 2||HSV-2|