Background Information

For more information, see the management guidelines and monograph:

	The medical Importance of Genital HSV Infection
	Genital and Orofacial Herpes Simplex Virus Infections - Clinical Implications of Latency

Under-diagnosis of genital HSV infection is a problem. Serological studies show that the infection is common, but questionnaire studies of primary health-care physicians suggest that they never see it – they rarely make the diagnosis or recognize the disease.
On first clinical presentation in primary health-care settings, approximately 50% of patients with HSV infection appear to be misdiagnosed with Candida or other causes of vulvitis.

Culture

• Any patient presenting for the first time with suspected genital HSV infection should have a swab taken for virus culture

• Physicians must recognize that a swab may give a false-negative for HSV and so a negative test result does not rule out genital HSV infection

• Every patient with genital herpes, including those with classic symptoms, should receive a laboratory-confirmed diagnosis, regardless of whether it is the first episode or not

• In a presentation of first episode genital herpes, the virus should be typed because this gives important prognostic information

• If the first test is negative, the patient should be invited to return for another swab/culture as soon as possible when they next have symptoms in case it leads to a diagnosis of genital HSV

• Serial swabs may be useful for monitoring an immunocompromised patient.

Serology

• Serological testing may also be useful in the patient who has chronic recurrent genitourinary symptoms for which there is no apparent aetiology, and also where there is a concern about transmission in discordant couples

• Serological screening will not be useful in areas where there is a high prevalence of HSV-1 genital infection. If serology is used to confirm a diagnosis of genital herpes in a culture-negative person, there is a possibility that they will be HSV-1 seropositive and HSV-2 seronegative, so the test will not be able to confirm that genital lesions were due to HSV

• Serological tests for HSV-2 can be valuable, particularly in selected patient settings such as pregnant women.

HSV Encephalitis

• For cases of suspected HSV encephalitis, it is strongly recommended that the physician obtain a sample of cerebrospinal fluid (CSF) and ask for a polymerase chain reaction (PCR) analysis as quickly as possible

• If PCR is not available or until PCR results are obtained, the infection can be confirmed by antibody assay; all patients with a positive PCR sample are recommended to be treated with aciclovir (i.v.). The patient should be treated empirically until the test confirms the diagnosis

• If the PCR sample is negative, but the physician feels that clinically the patient has encephalitis, empirical treatment should be continued

• CSF can be taken 1 week after the initiation of aciclovir therapy as 80-85% of patients still have a CSF sample that is HSV-positive

• If the PCR is negative, the CSF sampling should be repeated. If it is negative twice, and if there is an alternative diagnosis, aciclovir treatment can be stopped; if there is not an alternative diagnosis, repeat the CSF sampling and consider other diagnoses.

Ocular HSV

• It is recommended that a patient who presents with suspected ocular HSV should have diagnosis confirmed by a swab although it can be difficult to culture the virus. Taking a culture should be the first step in referral to an ophthalmologist.

Orolabial HSV

• For labial HSV infections and primary gingivostomatitis, the diagnosis can usually be made by inspection. Cultures should be obtained from those who have atypical or problematic recurrent orolabial lesions, and where the diagnosis is uncertain

• With gingivostomatitis in children, the differential diagnosis includes Coxsackie virus infection. A swab may be particularly helpful in atypical or difficult cases of gingivostomatitis

• For pharyngitis, which paediatricians and medical practitioners dealing with adolescents see frequently, herpes is rarely considered as a diagnosis. The only way to establish this diagnosis is by culture. The symptoms associated with herpes pharyngitis can last weeks and should be treated

• Classic cases of orolabial HSV should be swabbed for culture only in immunocompromised patients.

For more information, see the management guidelines and monograph:

Management of Varicella

• Taking swabs from an otherwise healthy child who presents with classic varicella is appropriate only if the child has been vaccinated; they have a history of having had varicella zoster virus (VZV) or if the presentation is atypical. In these cases the test of choice is immunofluorescence

• In patients with a history of vaccination, culture is important to establish whether lesions are due to a reactivation of the vaccine virus, or if it is a wild type infection. Serology is less useful in patients with a history of VZV infection

• If an immunocompromised patient presents with widespread vesicular lesions which the clinician believes are due to VZV infection, the diagnosis should be confirmed. In these patients, cases may present which appear to be typical varicella, but which may be a result of drug reactions

• Lesion culture may assist in diagnosis of atypical presentations of herpes zoster or disseminated lesions in the elderly immunocompetent patient.

Herpes simplex virus

• There are two vaccination strategies for HSV: immunotherapeutic and prophylactic. As yet, however, there is no proven effective immunotherapeutic or immunoprophylactic vaccine. New technology and understanding of the molecular biology of HSV suggest a number of encouraging approaches

• A vaccine for HSV would offer great potential for the individual and in public health terms. This is a major challenge for HSV researchers

• There is a need to explore further the immune response to HSV to identify new approaches and targets

• A number of subunit vaccines are in development.

Varicella zoster virus

• Varicella zoster virus (VZV) vaccine is derived from the Oka strain of VZV

• Varicella vaccine has an excellent safety profile and no serious adverse events have been reported

• The efficacy of varicella vaccine is approximately 80-90% in healthy populations, with pre-adolescent children being the most responsive

• The intensity of immune response and protective efficacy is correlated with the titre of the vaccine. A high titre of infectious virus is associated with a greater likelihood of seroconversion

• Antibodies and cell-mediated immune responses to VZV persist for up to 20 years following vaccination

• Varicella vaccine can also be used to boost the cell-mediated immunity to VZV in individuals who have been previously exposed to natural varicella

• Vaccination strategies include: universal vaccination of young children or of children at 12 years of age; a catch-up strategy, which is a combination of the two universal approaches; and targeted vaccination of those individuals at risk of severe or complicated varicella

• A wider uptake of immunization is needed. Current estimates suggest that an immunization rate of greater than 90% of children is required to control the spread of VZV optimally. Present levels of immunization are approximately 20% in Japan and below 20% in the USA

• It has been suggested that herpes zoster develops because VZV-specific cell-mediated immunity falls below a certain level. The Oka strain vaccine can stimulate cell-mediated immunity in children and adults and restoration of this immunity may reduce the frequency and severity of herpes zoster and its complications.