Introduction
Herpes Simplex Virus (HSV) is a common and contagious infection that causes painful blisters and ulcers on the skin. It is not curable but treatable. HSV has two types, HSV-1 and HSV-2, which can cause various diseases including cold sores and genital herpes. The virus can be transmitted through skin-to-skin contact, childbirth, and contact with infected areas. Most infections are asymptomatic. Treatment includes antiviral medications and managing symptoms. Complications can include increased risk of HIV infection, severe disease in immunocompromised individuals, and neonatal herpes. Precautions include avoiding contact during outbreaks and using condoms. Testing for HSV includes viral culture, serological tests, and molecular techniques.
Symptoms
- Most people with herpes have no symptoms or only mild symptoms.
- painful, recurring blisters or ulcers. New infections may cause fever, body aches and swollen lymph nodes.
- symptoms often begin with tingling, itching or burning near where the sores will appear.
- Common oral herpes symptoms include blisters (cold sores) or open sores (ulcers) in or around the mouth or lips.
- Common genital herpes symptoms include bumps, blisters, or open sores (ulcers) around the genitals or anus.
- These sores and blisters are typically painful. Blisters may break open, ooze and then crust over.
During their first infection, people may experience:
- fever
- body aches
- sore throat (oral herpes)
- headache
- swollen lymph nodes near the infection.
Cycles of Herpes Simplex Virus
Primary Infection: The Lytic Cycle
HSV infects its host through both lytic and latent infection, and replication of HSV occurs within 15 hours after infection. In the lytic cycle, HSV infects epithelial cells located in the mucosa, replicates, and causes epithelial cell death.
HSV-1 most frequently invades oral and ocular epithelial cells while HSV-2 infects the genital areas, but both strains have the ability to cause infection in either area of the body (Herbst-Kralovetz et al. 2006).
In order to infect epithelial cells, glycoproteins (namely gB, gC, and gD) on the surface of HSV fuse with entry receptors on the host cell membrane. One study demonstrated that when the virion lacks gC, the virus loses some function in binding to host cells, and the infectivity of the virus is decreased by a factor of 10. Also, gC-negative virions did bound to host cells required much more time to penetrate the host cell compared to controls (Herold et al. 1991).
gD has also been found to be necessary for fusion between the host cell membrane and the virus envelop and for entry of viral particles into the host cell (Spear et al. 2004).
- There are three known types of entry receptors located on the host cell that bind to HSV during cell infection and fusion.
- Heparan sulfate is a glycosaminoglycan (GAG), and it binds to gB and gC (Spear et al. 2004).
- Another entry receptor is herpesvirus entry mediator (HVEM), which is a member of TNF receptor family. This receptor is expressed at high levels on NK-T cells and naïve CD8+ cells and at weaker levels on CD4+ cells and dendritic cells. HVEM is also expressed on B cells, epithelial cells, and fibroblasts, so HSV has the potential to infect any of these cell types.
- The third receptors are nectin-1 and nectin-2, which are members of the immunoglobulin superfamily, and these receptors are expressed in epithelial cells, fibroblasts, and neurons. HSV-1 and 2 both bind to HVEM and nectin-1, while HSV-1 also uses heparan sulfate and HSV-2 uses nectin-2 (Spear et al. 2004).
Latency
In order to establish latency, the virus enters sensory neurons, which are non-dividing, and replicates infrequently (Smiley et al. 2004).
Latency-associated transcripts (LAT) are the only mRNAs that are expressed during latency, and these proteins serve to help the neuron survive initial infection. LAT are also required to establish and maintain viral latency and for the virus to be reactivated from latency (Bystricka and Russ 2005).
Although the adaptive immune response is present, the virus is occasionally reactivated and when this occurs, it anterogradely travels back to epithelial cells to form herpetic lesions (Spear et al. 2004).
Reactivation can be caused by numerous factors, including stress, ultraviolet light, heat, fever, hormonal changes, menstruation, and physical trauma to the neuron (Jenkins and Turner 1996).
Epidemiology
- Almost 3.7 billion people under age of 50 years which accounts for almost 67% people globally have herpes simplex virus type 1 (HSV-1) infection, the main cause of oral herpes
- As estimated 491 million people aging 15-49 years accounting 13% worldwide have herpes simplex virus type 2 (HSV-2) infection, the main cause of genital herpes.
- Most HSV infections are asymptomatic or unrecognised, but symptoms of herpes include painful ulcers or blisters that can occur and recur over time.
- The risk of transmitting and acquiring HIV infection also increases with HSV-2 infection
Transmission
- HSV-1 is mainly transmitted via contact with the virus in sores, saliva or surfaces in or around the mouth. Less commonly, HSV-1 can be transmitted to the genital area through oral-genital contact to cause genital herpes.
- It can be transmitted from oral or skin surfaces that appear normal; however, the greatest risk of transmission is when there are active sores. People who already have HSV-1 are not at risk of reinfection, but they are still at risk of acquiring HSV-2.
- HSV-2 is mainly transmitted during sex through contact with genital or anal surfaces, skin, sores or fluids of someone infected with the virus. HSV-2 can be transmitted even if the skin looks normal and is often transmitted in the absence of symptoms.
- In rare circumstances, herpes (HSV-1 and HSV-2) can be transmitted from mother to child during delivery, causing neonatal herpes.
Symptoms
- Most people are asymptomatic during the course while they are in infected stage.
- The first herpes outbreak usually starts about two to 20 days after you contract the infection.
- Severity: Cold sores and genital herpes tend to cause more noticeable and extensive symptoms during the first infection. Generally, recurrences are milder
- Sites where watery blisters occur
- In the skin
- Mucous membrane of the
mouth - Lips
- Genitals
- Eyes- when herpes affects eyes its known as Herpes simplex keratitis
- Healing- healing occurs with a scab formation, which is a characteristic of herpetic disease.
- Warning signs of reactivation: Pain, tingling, or burning can occur prior to a recurrent episode of herpes. This is due to inflammation and irritation of the nerves in the infected area. These warning signs of another outbreak (often referred to as prodromal symptoms) mean that you are very contagious even if you do not have any visible sores.
HSV Sign and Symptoms
Investigations for HSV
- Viral culture
- A swab test takes a sample of fluid from a sore, which may be used to do:
- A viral culture. For this test, cells from your sample are grown in a lab and then checked for HSV.
- A polymerase chain reaction (PCR) test. This test looks for genetic material from HSV in your sample.
- A swab test takes a sample of fluid from a sore, which may be used to do:
- Serological test
- A blood test looks for HSV antibodies in a blood sample. HSV antibodies are proteins that your immune system makes fight the virus. Your body makes different antibodies for HSV-1 and HSV-2. This test can be done when you don’t have sores.
- Molecular techniques
- done by nucleic acid amplification
by PCR and LAMP. This is extremely sensitive test
- done by nucleic acid amplification
Stages of HSV
Precautions
- People with symptoms of oral herpes should avoid oral contact with others (including oral sex) and sharing objects that touched saliva. Individuals with symptoms of genital herpes should abstain from sexual activity while experiencing symptoms. Both HSV-1 and HSV-2 are most contagious when sores are present but can also be transmitted when no symptoms are felt or visible.
- For sexually active people, consistent and correct use of condoms is the best way to prevent genital herpes and other STIs. Condoms reduce the risk; however, HSV infection can still occur through contact with genital or anal areas not covered by the condom. Medical male circumcision can provide life-long partial protection against HSV-2 infection, as well as against HIV and human papillomavirus (HPV).
- People with symptoms suggestive of genital herpes should be offered HIV testing.
- Pregnant women with symptoms of genital herpes should inform their health care providers. Preventing acquisition of HSV-2 infection is particularly important for women in late pregnancy when the risk for neonatal herpes is greatest
Treatment
- Medicines are often used to treat first or recurrent episodes of herpes. They can decrease how long symptoms last and how severe they are, but they can’t cure the infection.
- Treatment for recurrent episodes is most effective when started within 48 hours of when symptoms begin.
- Antiviral medicines commonly given include
- acyclovir, famciclovir and valacyclovir. Taking a lower daily dose of one of these medicines can also decrease how often symptoms occur (‘outbreaks’).
- Treatment is often recommended for people who get very painful or frequent recurrent episodes or who want to lower the risk of giving herpes to someone else.
- Medicines to help with pain related to sores include
- paracetamol (acetaminophen), naproxen or ibuprofen.
- Medicines that can be applied to numb the affected area include
- benzocaine and lidocaine.
- Herpes simplex virus lives inside of nerve cells and alternates between being inactive and active.
- Certain triggers can make the virus active including:
- illness or fever
- sun exposure
- menstrual period
- injury
- emotional stress
- surgery.
- For people whose oral herpes is activated by sunlight, avoiding sun exposure and wearing sunscreen can lower the risk of recurrences.
- To decrease symptoms of oral herpes, people can:
- drink cold drinks or suck on popsicles
- use over-the-counter pain medicines.
- For genital herpes, people can:
- sit in a warm bath for 20 minutes (without soap)
- wear loose fitting clothes
- use over-the-counter pain medicines.
- There are ways to lower the risk of spreading herpes including:
- talk to your partner about having herpes
- don’t have sex if you have symptoms and always wear a condom
- don’t share items that touched saliva (oral herpes).
- Talk to your healthcare provider if you are pregnant, because there is a risk of passing herpes to your baby.
