Epidemiology and transmission
Herpes simplex virus 1 and 2 (HSV-1 and HSV-2), also known as human herpes virus 1 and 2 (HHV-1 and HHV-2), are two members of the herpes virus family, herpesviridae, that infect humans. HSV-1 and HSV-2 share 85% of genetic homology. The envelope glycoprotein G determines type-specificity of the virus.
Both HSV-1 and HSV-2 are highly contagious and affect people worldwide. Virus transmission occurs horizontally via mucosa and skin or through wounds during close contact with infected persons who are shedding the virus in saliva, genital secretions or from virus filled blisters and lesions. Both viruses may also be transmitted vertically from mother to child during delivery.

Prevalence
HSV-1 infections are acquired by almost all people worldwide. Globally, 60-90% prevalence of HSV-1 antibodies has been reported.
According to WHO estimates in 2008 the global seroprevalence of HSV-2 infection in 2003 was 16% in both sexes being higher in females (19% than in males (13%). The number of infected individuals increased with age and was higher in developing than in developed countries.

Incidence
The estimated number of new HSV-2 infections among 15–49 year olds worldwide in 2003 was 23.6 million (0.7%), of whom 12.8 million (0.8%) were women and 10.8 million (0.6%) were men. The number of new infections was highest in the youngest age groups, and declined thereafter due to a decline in the number of susceptibles with increased prevalence.

Primary HSV infections and clinical pictures
HSV-1 is usually acquired during childhood and manifests as oro-facial infection, but may also be sexually transmitted. HSV-2 is predominantly a sexually transmitted infection and manifests as genital herpes. However, type-specific localization of infection is not obligatory, each of the virus types may cause infections in both body regions. In immunocompetent patients in most of the cases the infections are asymptomatic. Symptomatic primary attacks present as gingivostomatitis, a serious infection of the lips and the mucous membranes in the mouth, of the tongue, the gums and the pharynx. A herpes infection may also occur on the cheeks or in the nose, but facial herpes is not common. For patients who experience symptoms due to genital infections, the first outbreak usually occurs in or around the genital area and is characterized by bilateral lesions, inguinal lymophadenopathy and dysuria. Symptomatic primary (initial) infections can be very painful.
In newborns or immuno-compromised adults, the infection may involve visceral organs (e.g., lungs, liver), produce encephalitis or fatal disseminated disease with a mortality rate of >70%. About half of the survivors may develop neurological impairment.

Latency
Once a patient has become infected by herpes virus, the infection remains for life. The initial infection may be followed by latency notably in neuronal cells with subsequent reactivation. After primary infection HSV spreads from mucosa / skin via sensory nerves to the sacral ganglia (genital infection) or trigeminal ganglia (oro-facial infection) where it stays latent for a variable period of time. Both types of HSV can also persistently infect macrophages and lymphocytes.

Reactivation of primary HSV infections and clinical pictures
Most cases of herpes simplex recur. The site on the body and the type of virus influence how often it comes back. On average, about one-third of all reactivations are subclinical, they neither cause sores or other visible skin blemishes nor symptoms. These subclinical reactivations, accompanied by virus shedding, are an important cause of unnoticed transmission and, thus, further spread of the viruses. Symptomatic reactivations of HSV-1 feature mainly the clinical picture of herpes labialis (cold sores or fever blisters). Symptomatic recurrence of HSV-2 feature mainly the same clinical picture as primary infections. Recurrent infections usually tend to be milder and briefer than primary infections.

Diagnosis
The diagnosis of symptomatic primary and reactivated HSV infections normally bases on the clinical picture. In unclear cases isolation of the pathogens in cell culture, direct fluorescence assays (DFA) or PCR may be used for direct detection of the pathogen. Moreover, specific laboratory diagnosis is carried out in cases of exanthema of unclear origin, suspected herpes encephalitis, generalised infections in immunocompromised patients and newborns, and in females with genital infections during pregnancy.
Specific antibody detection is preferably performed for identification of the immune status as well as for differentiation of infection stages (early phase of infection versus recurrence).


For information about indications for the diagnosis with the medac HSV serology please refer to HSV serology in this section.