Herpes Simplex – Types, Diagnosis, Vaccine & Cures

What is Herpes Simplex?

Herpes virus infection is caused by the herpes simplex viruses type I (oral herpes) and type II (genital herpes), which cause characteristic lesions on the skin, the mucous membranes, most often on the face or the genital area.

Herpes viruses are widespread and can be easily transmitted from person to person.

Herpes simplex infection is spread all around the world and is showing a progressive increase in frequency.

According to WHO (World Health Organisation) „More than 3.7 billion people under the age of 50 – or 67% of the population – are infected with herpes simplex virus type 1 (HSV-1)” and „417 million people aged 15-49 years have Herpes Simplex Virus – 2 infection, which causes genital herpes. Taken together, the estimates reveal that over half a billion people between the ages of 15-49 years have a genital infection caused by either HSV-1 or HSV-2.”[1]

The herpes simplex virus is present in two variants – type I and type II.

They can be distinguished by laboratory diagnostics as well as by a physical examination – based on the localization of the clinical manifestations.

 

Herpes Simplex Type I
Herpes Simplex Type I
Source: https://commons.wikimedia.org

The infection occurs from person to person through an exudation (the escape of fluid, cells, or cellular debris from blood vessels and deposition in or on the tissue), saliva, tears, excrements, directly by kissing, sexual intercourse or indirectly by air or by contact with contaminated objects.

The infection can be transmitted even during a child birth or until the end of the first year of the newborn.

Herpes infections, including latent infections, are spread all over the world. They are transmitted from person to person through the saliva, the tears, the feces or a physical contact of the sick and the carriers and “the receiver”.

The infection can occur even during childbirth and is transmitted by the genital pathways of mothers carrying the viruses.

50 to 100% of children become infected the first year after birth. Genital HSV can cause potentially fatal infections in babies. If a woman has active genital herpes during delivery, a cesarean sectio is usually performed.

The infection is transmitted directly, for example, by kissing, by sexual contact or indirectly by the air or through contaminated objects.

There is a tendency for more common infections spreading around the world, especially caused by herpes simplex II. There are severe and widespread cases, often fatal, which can be caused by immunosuppression.

The epidemiological significance is attributed to the carcinogenic effect of herpes virus, which is experimentally proven.


Disseminated Primary Herpes Simplex Virus Type 2 Infection in a 22-Year-Old male. Disseminated vesicles on erythematous bases at the time of presentation (A). Note clustering of some vesicles (B). The patient provided written consent to use his photographs.
Source: https://openi.nlm.nih.gov

The herpes simplex virus belongs to alphaherpesviruses of the family Herpesviridae, in which more than 70 species have been identified so far, causing various diseases in different animal species. After penetration into the cells, the viral elemental particles lose their outer envelope.

Only the viral species under the influence of which degrades the viral nucleocapsids that form clumps, detectable microscopically in the form of intracutaneous inclusions, pass through the nucleus.

After leaving the depleted nucleus, viral particles receive outer envelopes from the transformed nuclear and cytoplasmic membrane.

The primary herpes simplex infection cannot be clinically detectable in 99% of all cases. This is usually done by the presence of antibodies in the serum.

It is assumed that the primary spread of infection from the first outbreak can be accomplished by passing the viral particles from a cell to another, blood, or nerve cells.

After the clinical recovery, the virus remains in latent state and is suppressed by the humoral immunity.

In a case of immune degradation, under the influence of bacterial and various viral infections, in connection with intoxications, gastrointestinal, neurogenic disorders or external chemical, physical and neurological stimuli found in latent phase viruses, the virus can be activated and cause recurrences.

The anti-herpetic immunity is humoral and cellular. Humoral antibodies are detected 1 to 3 weeks after the infection. Some of them pass through the placenta and are detected in the first months after birth.

The most important are the virus-neutralizing antibodies. Cytotoxic and cytological circulating antibodies damage and lyse the infected cells.

The clinical manifestations after the healing of the virus, leave it in a latent state, suppressed by humoral immunity. When immune decreases, viruses are activated and cause recurrent infections.

The anti-viral immunity that is being developed can be humoral and cellular [7]. Humoral antibodies (The humoral response or antibody‐mediated response involves B-cells that recognize antigens or pathogens that are circulating in the lymph or blood) are demonstrated 1 to 3 weeks after the infection has passed. Cellular immunity is mediated by T-lymphocytes, macrophages, and other immune cells.

For laboratory diagnosis of herpes simplex infections, cell cultures are most commonly used, given that the herpes simplex virus produces cytopathogenic effects on various cell cultures, such as fibroblasts, kidney, and others. Inoculation of experimental animals can also confirm the diagnosis.

Diagnostic significance also includes serological tests: viral neuritis [2], complement fixation [3], passive haemagglutination [4], direct and indirect immunofluorescence [5]. Cell-mediated immunity by blast transformation of lymphocytes, rosette test, skin test, lymphocyte migration inhibition response was determined.

Herpes simplex virus causes diseases with a different clinical picture.

Gingivostomatitis herpetica is an infection in children between 1 and 5 years of age, characterized by acute leakage, an involvement of the mucous membrane and joint manifestations.

Redness and swelling of the suppository with sharply defined ulceration
Source: https://de.wikipedia.org

Gingivostomatitis herpetica is actually the primary herpetic gingivostomatitis or orolabial herpes) which is a combination of gingivitis and stomatitis, or an inflammation of the oral mucosa and gingiva. Herpetic gingivostomatitis is often the initial presentation during the first herpes simplex infection.

After an incubation period (the time from the arrival of the virus to the first clinical signs) for 2-7 days, the oral mucosa and the half-mucosa are red, swollen, and blooming with bubbles of 1-2 mm to 1 cm.

There are painful and bleeding erosions. They are accompanied by over salivation and unpleasant breath of the mouth. Regional lymph nodes are painful and enlarged. The body temperature is rising. Loss of appetite combined with painful erosions greatly hinders eating, even taking fluids.

The most common complications caused by the infection are bacterial or fungal infections of the mucous membranes, bacterial inflammation of the lymph nodes and the formation of abscesses in them.

The herpetic rash spreads in the throat and the esophagus, the skin of the lips, the adjacent skin areas, the genital organs, the fingers of the hands. Rare complications are the herpetic meningoencephalitis (inflammation of the cerebral envelopes and the cerebrum).

Immunostimulants, vitamins, and antivirals are used to treat the disease. To prevent the bacterial infection (as well as its complications), antibiotics, antiseptics – both for internal and topical application- are used. Anti-fungal agents for a general and topical application can also be used.

Causes

Genital herpes simplex infections are caused by Herpes Simplex II. It occurs in the form of a proficial balanitis (inflammation of the head of the male sex organ) and vulvovaginitis (inflammation of the vulva and the vagina).

When it develops in childhood, it is accompanied by regional inflammation of the lymph nodes and has also joint manifestations.

In adulthood, primary genital infection is transmitted from a sexual partner to recurrent genital herpes.

Treatment is symptomatic.

Eczema herpeticum is a severe form of primary herpes simplex infection. It develops most often in children with pre-existing itchy dermatoses as well as a reduced immune status, and the infection is caused by already existing gingivitis or other virus carriers.

The incubation period is 5-10 days. The general condition gets worse, the temperature rises, the patients are often depressed, intoxicated, dehydrated, especially in the presence of vomiting and/or diarrhea.

Scattered, sometimes clustered bubbles appear, most often on the face, neck, upper limbs. For 2-3 days, the bubbles become puss-filled and expand peripherally. This condition may last for 5-6 weeks.

Herpes sepsis (Systemic inflammatory response syndrome due to an infectious cause) in the newborn is transmitted by the mother and the infection occurs during the delivery. Exceptionally, the source of the infection may be the medical staff (if they carry the infection).

The incubation period is 3-6 days. The beginning is very acute with a fever, shortness of breath and jaundice. The liver and the spleen are increased.

The worsened general condition is combined with a herpetic rash on the skin and mucous membranes – there are a herpetic stomatitis and vulvovaginitis with a tendency of bleeding. The central nervous system is affected by meningoencephalitis. Usually, within 5-6 days the illness ends fatally.

If a woman has an active outbreak at the time of delivery, the safest course is a Cesarean section to prevent the baby from coming into contact with the virus in the birth canal.

Complications of herpes simplex infections are bacterial and candidal superficial infections of the mucous membranes, bacterial lymphadenitis with redness and abscessation of the lymph nodes.

In children with severely impaired immunity, the herpetic rash spreads to the throat, the esophagus, the trachea and may be secondary to infection, and sometimes the infection is disseminated. Herpes labialis infection can spread to other parts of the face, such as around the eyes. A very rare complication is the herpetic meningoencephalitis.

Diagnosis

The diagnosis of herpes is usually based solely on the appearance of the lesions. Less often, tests are used to help diagnose herpes.

Blister scraping, in the attempt to cultivate the virus in the laboratory, can be effective only in the first 48 hours and before the lesion crust over.

Blood tests are usually less effective, as the presence of antibodies to herpes means that the body has been exposed to this virus at some point in the past.

If the diagnosis is in doubt, the best approach is to encourage a visit to a doctor at the earliest signs of pain .

Herpes Simplex Type II Vaccine

Scientists at the University of Pennsylvania [6] have developed a new vaccine against genital herpes. The first vaccine has successfully undergone preclinical trials. The preparation suggests three consecutive injections, which should be administrated within 6 months. This is the most reliable formula created to combat genital herpes HSV2 so far.

The new formula has provided reliable protection against genital herpes in laboratory animal studies. Scientists explain that in the coming months the specialists will test the preparation with people. The drug increases

The drug increases the number of antibodies against three different parts of the virus. It includes two key components that, under normal conditions, help HSV2 avoid attacks on the immune system. This is a completely new strategy that has produced positive results.

Most of the vaccines available so far have been directed to glycoprotein GD2, coated with sugar-like molecules. The glycoprotein helps the virus to penetrate the body and attack the cells. However, in clinical trials, vaccines have been unable to block the virus.

The new vaccine is targeted to attack two other glycoproteins gC2 and gE2, suppressing the immune system. That’s what distinguishes it from all the previous methods.

The new vaccine will allow one of the most common sexually transmitted diseases to be controlled.

Treatment

If you successfully avoid unlocking factors such as sunburn and stress, you can help prevent further Herpes Simplex Virus outbreaks. There are established treatments that can help reduce the healing time, the pain associated with the lesion, and, in specific cases, lead to suppression of the recurrence of the virus.

Home Remedies

Frequent hand washing will help reduce the spread of the virus to other parts of the body or to other people.

Also, the use of cool and wet compresses applied on the lesion can reduce the pain and prevent skin dryness and cracking.

Over-the-counter remedies:

Most products only provide symptomatic relief, they do not reduce the treatment time. The use of topical anesthetics that contain benzocaine (5% -20%), lidocaine (0.5% -4%), tetracaine (2%) or dibucaine (0.25% -1%) will help to ease the burning sensation, as well as the itching and the pain.

Lipactin and Zilactin products are most often recommended. It is important to keep in mind that these anesthetics have a short duration of action, usually about 20-30 minutes. For skin protection – allantoin, vaseline and dimethicone containing products, help keep the lesion moist and prevent its cracking. Sun-protecting lip products can also help prevent further outbreaks.

For further pain relief, aspirin, ibuprofen (Advil) or acetaminophen (Tylenol)  are often used. These products should be used according to the instructions on the package.

Docosanol 10% Cream (Abreva) is the only non-prescription product known to reduce treatment time when given at the first signs of reoccurrence (for example, after a pre-existing symptom or feeling of tingling). Docosanol is administered five times a day until the lesion heals completely. Common side effects include rash and itching at the application area.

Prescription drugs: Treatment with topical acyclovir (Zovirax 5% cream) or penciclovir (Denavir 1% cream) will reduce healing time by about half a day and reduce the pain associated with the lesion.

Local treatment has a limited effectiveness because of the insufficient penetration. Acyclovir cream should be applied five times a day for four days and Penciclovir cream should be applied every two hours for four days.

Oral Drugs: Oral antiviral medicines used to treat herpes simplex virus are acyclovir, valacyclovir (Valtrex) and famciclovir (Famvir). Famciclovir is not tested in children with herpes.

These oral drugs reduce the duration of the outbreak when their intake has begun during the preceding symptoms before the actual condition has visible symptoms. These drugs are usually well tolerated with very few side effects.

The most common side effects include a headache, nausea, and diarrhea. Treatment with valacyclovir and famciclovir lasts only one day. Valacyclovir is given 2 g orally every 12 hours for one day and 1500 mg famciclovir orally per dose.

Acyclovir is taken per 400 mg orally five times a day for five days. Acyclovir, valacyclovir, and famciclovir are considered to be relatively safe and effective when used during pregnancy, although topical treatment is highly recommended. Acyclovir and valacyclovir may be used during lactation. However, pregnant women and breastfeeding mothers should contact their doctor or pharmacist before using such medicines.

People with more than two herpes within four months should consider chronic therapy.

Other treatment options: Lysine, citrus bioflavonoids, Lactobacillus Acidophilus and Bulgaricus and vitamins C, E and B12 have also been identified as agents for the treatment of herpes simplex virus, but there is insufficient clinical evidence regarding their positive effect.

References

  1. http://www.who.int/mediacentre/news/releases/2015/herpes/en/
    Globally, an estimated two-thirds of the population under 50 are infected with herpes simplex virus type 1
  2. http://vestibular.org/labyrinthitis-and-vestibular-neuritis
    Labyrinthitis and Vestibular Neuritis: INFECTIONS OF THE INNER EAR
  3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2323744/
    THE MECHANISM OF COMPLEMENT FIXATION
  4. http://jcm.asm.org/content/27/1/179.full.pdf
    Passive Hemagglutination Test for Detection of Antibodies to Human Immunodeficiency Virus Type 1 and Comparison of the Test with Enzyme-Linked Immunosorbent Assay and Western Blot (Immunoblot) Analysis
  5. http://www.abcam.com/secondary-antibodies/direct-vs-indirect-immunofluorescence
    Direct vs indirect immunofluorescence
  6. https://www.pennmedicine.org/news/news-releases/2017/january/new-genital-herpes-vaccine-candidate-provides-powerful-protection-in-preclinical-tests
    New Genital Herpes Vaccine Candidate Provides Powerful Protection in Preclinical Tests
  7. http://theydiffer.com/difference-between-humoral-and-cell-mediated-immunity/
    Difference between Humoral and Cell-Mediated Immunity

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