Herpes


Introduction

Common recurrent, lifelong STD with no cure caused by herpes simplex virus.


Aetiology

Herpes simplex virus (HSV):

HSV are linear, double stranded DNA viruses capable of establishing latency in humans. They belong to the family of Herpesviridae and more specifically to the sub-family of Alphaherpesvirinae. There are two sub-types: HSV-1 and HSV-2 that are closely related but differ slightly in tissue tropism and antigenic properties.

90% of all people worldwide have one or both viruses

  • Herpes simplex virus type 1 (HSV-1) (65% prevalence)
  • Herpes simplex virus type 2 (HSV-2) (15-80% prevalence)
Electron micrograph of HSV-1 (×105,000) showing the composition of the virus: nucleocapsid with high density surrounded by the tegument with low density and the envelope with high density. | HSV-1, herpes simplex virus type 1. | Image courtesy of the Institute of Virology and Antiviral Therapy, Jena University Hospital, Friedrich-Schiller University of Jena, Germany.

Risk factors:

  • Sexual activity at ≤ 17 years
  • History of STDs
  • History of undiagnosed genital lesions or discharge
  • HIV infection
  • Multiple sex partners
  • Multiple lifetime sex partners
  • Partner diagnosed with genital HSV infection

Pathophysiology

Natural history of infection:

Natural history of HSV infection includes acute or subclinical first-episode mucocutaneous infection, establishment of viral latency, and subsequent reactivation.

The herpes virus enters the body through the skin or mucous membranes by direct sexual contact with the secretions or mucosal surfaces of an infected person. The virus multiplies at the epithelial layer and then ascends along the sensory nerve roots to the dorsal root ganglion, where it becomes latent. With reactivation, the virus travels from the dorsal root ganglion back down the nerve root to create a mucocutaneous outbreak, or it may produce no detectable symptoms.

Schematic of Primary Infection and Reactivation: Primary infection occurs when a host is exposed to the virus for the first time. When a person is exposed to HSV, the virus infects the epithelial cells. Depending on the immune system of the host, lytic infection leads to virus shedding that can cause symptoms such as ulcers or remain asymptomatic. After lytic infection, the virions reach the nerve endings and through a retrograde transport, reach the sacral ganglion where it establishes latency till the life of the host. Recurrent infections occur when the virus gets reactivated due to stress, environmental conditions and other unknown factors. Reactivation causes the virus from the sacral ganglion to travel to the site of primary infection or high nerve endings via an anterograde fashion where virus shedding can cause symptoms or remain asymptomatic depending on the host immune system. | Jaishankar, D., & Shukla, D. (2016). Genital Herpes: Insights into Sexually Transmitted Infectious Disease. Microbial cell (Graz, Austria), 3(9), 438–450. https://doi.org/10.15698/mic2016.09.528
  • Initial primary infection: First virus exposure in anti-HSV-1/2 IgG-negative persons
  • Initial nonprimary infection: First HSV-1/HSV-2 infection in persons having IgG antibodies against the other virus type than the one causing acute infection
    • Due to cross-reaction of HSV-1 and HSV-2 antibodies, initial nonprimary genital infections cause milder symptoms than initial primary infections.

Clinical features

Herpes is predominantly transmitted through sexual contact. Viral transmission by oro-genital contact is mostly HSV-1 and therefore the number of genital HSV-1 cases is on the rise. Virus shedding is more predominant in sites like mouth and mucosal surfaces such as the vagina. Contact with any one of these increases the risk of being infected with HSV.

Prodrome:

Lasting 2-24 hours characterized by localized/regional pain, tingling, and burning. Patients also may have constitutional symptoms such as headache, fever, inguinal lymphadenopathy, anorexia, and malaise.

Primary herpes:

Primary genital infections caused by HSV-1 or HSV-2 are mostly not associated with clinical symptoms and remain asymptomatic

Classic clinical picture:

  • Mucous membrane lesions appearing as maculae and papules, followed by vesicles, pustules, and ulcers
  • Duration: Arise within 4–7 days after sexual exposure and last up to 3 weeks
  • Symptoms: Pain, itching, burning, and dysuria
  • Site: Mostly presenting on external genitalia characterized by bilateral clusters
    • Women: Introitus, urethral meatus, labia, and perineum.
    • Men: Shaft/glans of penis
    • Both: Perianal area, thighs, or buttocks
  • Associated features: Lymphadenopathy, fever, cervicitis (women), and proctitis (homosexual men).

Recurrent herpes:

Following the primary eruption the virus establishes lifelong latency in sensory neural ganglions; in the case of primary genital infection the sacral ganglions are mainly involved. From here the virus can reactivate, causing recurrent infection. Viral reactivation is common in the presence of immunogenetic predisposition, though reactivations decrease with increasing age. Numerous physiological and environmental factors such as fever, UV light, menstruation, stress or trauma can function as triggers. Endogenous viral reactivations may manifest as recurrent herpes genitalis.

Compared to primary infection, symptoms of recurrence are much less severe and the clinical course shorter.

  • Prodromal symptoms: Neuralgic symptoms, dysaesthesia or lumbosacral dermatome pain 1–2 days before skin and mucosal lesions erupt

Asymptomatic genital viral shedding:

Majority of cases endogenous viral reactivation is characterised by asymptomatic genital viral shedding.

Complications:

Immunocompromised patients including neonates are susceptible to additional systemic infections including debilitating consequences of nervous system inflammation.
Different HSV-1 and HSV-2 diseases and their localization. | HSV-1, herpes simplex virus type 1; HSV-2, herpes simplex virus type 2. | Sauerbrei A. (2016). Optimal management of genital herpes: current perspectives. Infection and drug resistance, 9, 129–141. https://doi.org/10.2147/IDR.S96164

Diagnosis

  • Polymerase chain reaction (PCR): Viral DNA detection
  • Viral cultivation in cell cultures, detection/typing using monoclonal antibodies for virus isolation
  • Immunofluorescence test with monoclonal antibodies: Viral antibody detection
  • Enzyme-linked immunosorbent assay (ELISA): Detection of type-specific and non-type-specific antibodies
  • Indirect immunofluorescence antibody test (IFAT): Detection of non-type-specific antibodies
  • Immunoblot: Detection of type-specific antibodies
Recommended viral diagnostic algorithm for herpes genitalis. | PCR – polymerase chain reaction, TK – thymidine kinase. | Sauerbrei A. (2016). Herpes Genitalis: Diagnosis, Treatment and Prevention. Geburtshilfe und Frauenheilkunde, 76(12), 1310–1317. https://doi.org/10.1055/s-0042-116494

Management

Currently prescribed medications, mostly nucleoside analogs, only reduce the symptoms caused by an active infection, but do not eliminate the virus or reduce latency. Therefore, no cure exists against genital herpes and infected patients suffer from periodic recurrences of disease symptoms for their entire lives.

  • Acyclovir, Valacyclovir, Famciclovir, Foscarnet

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