Introduction
Herpes comes from the Greek word meaning “to creep” and is used to describe two distinct but antigenically related serotypes of herpes simplex virus. Herpes simplex virus type 1 (HSV-1) is most commonly associated with oropharyngeal disease, and herpes simplex virus type 2 (HSV-2) is most closely associated with genital disease; however, each virus is capable of causing infections clinically indistinguishable in both anatomic areas. (1) , (2)
Humans are the sole known reservoir for HSV. Infection is transmitted via inoculation of virus from infected secretions onto mucosal surfaces (e.g., urethra, oropharynx, cervix, conjunctivae) or through abraded skin. (3) The virus can exist for a limited time on environmental surfaces, suggesting possible transfer by means other than the venereal route.
Infections of herpes simplex occur in cycles. The first stage is primary mucotaneous infection. Exposure at mucosal surfaces or abraded skin permits entry of the virus and replication in cells of the epidermis and dermis. Initial infection is often subclinical. Whether clinical, or subclinical, sufficient viral replication occurs to cause infection of either sensory or autonomic nerve endings. This is followed by infection of the ganglia and establishment of latency. The time period involved from mucosal inoculation to transport and replication in the ganglion is unknown. The virus may then spread to distant locations through peripheral sensory nerves. At some point, the disease is reactivated causing recurrent infection. It is unclear what factors occur that cause or maintain latency, and what factors trigger reactivation. It is believed, however, that physical and emotional stresses contribute to reactivation of latent virus.
Host responses to infection with HSV influence the acquisition of the disease, the severity of infection, resistance to the development of latency, the maintenance of latency, and the frequency of recurrences. (4) While both cell-mediated immunity and antibody-mediated immunity are important, immunocompromised patients with defects in cell-mediated immunity appear to have a greater recurrence and greater severity of HSV disease than those with deficits in humoral immunity, such as gammaglobulinemia.
First episode primary infections are classified as infections occurring in persons lacking antibody to either type of HSV. (5) First episode infections are typically more severe than recurrent infections and include systemic as well as local symptoms. Many patients experience flu-like symptoms of fever, myalgia, headache, and malaise, in addition to pustular or ulcerative local lesions. Both subtypes can cause oral-facial or genital lesions that are clinically indistinguishable. However, the frequency of reactivation of infection is influenced by anatomic site and virus type. Genital HSV-2 infection is twice as likely to reactivate and recurs eight to 10 times more frequently than genital HSV-1 infection. Conversely, oral-labial HSV-1 infection recurs more frequently than oral-labial HSV-2 infection. (6) First episodes of genital herpes in patients who have had prior HSV-1 infection are associated with faster healing of lesions and less frequent systemic symptoms than in primary genital herpes.
Other herpes infections include herpetic whitlow, or HSV infection of the finger. This may occur as a complication of primary oral or genital herpes via a break in the epidermal surface, or it may occur by direct exposure to the hand through occupational or other exposure. Herpes gladitorum has been most frequently described in association with wrestlers. HSV may infect any area of the skin. Mucotaneous infection of the thorax, ears, face, and hands is facilitated by trauma to the skin sustained during wrestling. Prompt diagnosis and treatment should be obtained to prevent the spread of infection.
HSV infection of the eye is a frequent cause of corneal blindness in the United States, and HSV is the most commonly identified cause of acute sporadic viral encephalitis. Visceral infections may result from viremia, and multiple organ involvement may occur.
Neonates have the highest frequency of visceral and/or CNS involvement of any HSV infected population. Transmission is most frequent in mothers who acquire primary genital herpes during the third trimester of pregnancy, and occurs when the baby comes in contact with infected genital secretions during delivery. If not treated, neonatal herpes undergoes dissemination or develops into CNS infection in >70 percent of cases. Without therapy, the overall death rate from neonatal herpes is 65 percent; fewer than 10 percent of neonates with CNS infection develop normally. (7)
Statistic
International Herpes Alliance (IHA), 2001.
- Worldwide 1 in 7 to 1 in 5 people have been exposed to and infected by genital herpes simplex virus (HSV).
- Only about 20% of people infected with the herpes simplex virus are diagnosed.
The New Zealand Herpes Foundation, 2004.
- Genital herpes affects 1 in 5 people in New Zealand.
World Health Organization, 2004.
- Sub-Saharan Africa prevalence of HSV-2 among women is as high as 75%.
National Institute of Dental Research, 2000.
- Eight out of every 10 American adults are infected with the herpes simplex virus, or HSV.
- Eight of 10 people with first-time HSV infections–and a few with recurrences–also contract viral meningitis.
Medline Plus Health Information, 2002.
While statistics vary, research shows that 90% of the population has been exposed to HSV-1, “oral herpes”, and 25% of the population aged 25-45 years old in the United States has been exposed to infection with HSV-2, “genital herpes”.
Signs and Symptoms
The following list does not insure the presence of this health condition. Please see the text and your healthcare professional for more information.
During the first episode HSV-1 Oral-facial infections the most frequent clinical manifestations are
gingivostomatitis, pharyngitis, fever, malaise, myalgias, inability to eat, irritability and cervical adenopathy. Lesions involving the lip, tongue, facial area, gingival, soft, or hard palate are likely present. These symptoms may last from three to fourteen days and may be clinically difficult to distinguish from bacterial pharyngitis, Mycoplasma pneumoniae, or pharyngeal ulcerations from non-infectious sources such as Stevens-Johnson syndrome.
Genital infections is characterized by fever, headache, malaise, myalgias, dysuria, vaginal discharge, pain and itching. Tender inguinal lymphadenopathy and widely spaced bilateral lesions of external genitalia in varying stages (vesicles, pustules, erythematous ulcers) can be present.
Eye infections involve blurry vision, conjunctivitis, chemosis, pain and characteristic dendritic lesions of the cornea.
Herpetic whitlow present with edema, erythema, localized tenderness and vesicular or pustular lesions of the fingertip. Fever, lymphadenitis, and epitrochlear and axillary lymphadenopathy are common.
Herpes infections in the CNS, such as HSV encephalitis, are often difficult to distinguish from other viral encephalitides. The same may be true of visceral HSV infections, and laboratory analysis may be necessary to confirm diagnosis.
General
- Symptoms are the worst during the first episode of HSV-1
- Skin eruptions occur 2-12 days after exposure on various infected parts of the body
- Flu-like symptoms may be present
- Headache
Treatment Options
Conventional
Goals of therapy include relief of symptoms, prevention of complications and recurrences, shortening of clinical course, and decrease in disease transmission. The pain and discomfort of genital herpes usually respond to warm saline baths or the use of analgesics or antipruritics. Good genital hygiene can prevent bacterial superinfection.
Although the CDC recommendations for the treatment of genital herpes include only acyclovir, two related antiviral agents, valacyclovir and famciclovir, have been marketed for the management of HSV. (8) Dosage recommendations for acyclovir include: for a first clinical episode of genital herpes, acyclovir, 200mg orally five times daily for seven to 10 days or until clinical resolution occurs. Alternatively, if the patient’s symptoms or complications are severe enough to warrant hospitalization, acyclovir, 5-10mg/kg IV every eight hours for five to seven days or until clinical resolution occurs. Recurrent infections may be treated with acyclovir, 200mg orally five times daily, or 400mg orally three times daily.
The recommended dosage of valacyclovir in first-episode genital HSV is 1 gram twice daily for 10 days. The usual dose of famciclovir to treat first-episode infections has ranged from 250-750mg three times daily for five days. Although the valacyclovir and famciclovir dosage regimens are more convenient and offer the potential for greater patient compliance when compared to acyclovir, no therapeutic advantages over acyclovir are apparent at this time. (9)
Several topical agents are available for use in HSV eye infections: idoxuridine, trifluorothymidine, topical vidarabine, and more recently, cidofovir. Oral-labial infection of HSV may be treated with oral acyclovir, 200mg four to five times daily. For recurrent episodes, topical penciclovir cream is effective in speeding the healing of oral-labial HSV. Oral acyclovir has minimal benefit.
Nutritional Supplementation
Lysine
Several studies report that lysine is effective in the treatment of herpes. In one double-blind, placebo-controlled trial, patients given 1,000mg of lysine 3 times daily for 6 months experienced fewer herpes outbreaks, had a substantial reduction in the severity of symptoms, and a shortened healing time. (10) Another study surveyed 1,543 individuals who suffer from either cold sores, or genital herpes. 88 percent of those surveyed considered supplemental lysine an effective form of treatment for herpes infection. (11) A third study was a double-blind, placebo-controlled trial examining whether or not lysine (1,000 mg/day) would be effective prophylactically in the treatment of herpes simplex labialis. Most of the 26 subjects reported significantly fewer lesions than the control group. Similarly, a majority of the subjects who were taken off lysine supplementation experienced a significant increase in the frequency of herpes events. (12)
It has been suggested that the herpes virus utilizes the amino acid arginine to replicate itself. (13) Since lysine and arginine competitively inhibit each other, high doses of lysine may reduce the frequency and severity of herpes.
Vitamin C
In vitro tests have shown that solutions of vitamin C are able to inactivate the herpes simplex virus, types 1 and 2. (14) Short-term topical treatment with an ascorbic acid-containing pharmaceutical formulation (Ascoxal) resulted in statistically significant clinical and antiviral effects in the treatment of patients with recurrent mucocutaneous herpes outbreaks. In this randomized double-bind, placebo-controlled clinical trial, patients treated with the ascorbic acid solution reported a significantly smaller cumulative number of days with scab, or with any remaining symptoms and significantly fewer occasions of worsening of any symptom after the treatment. Reports from nurse’s records indicated that the persistence of scabs was significantly shorter in the active treatment group (mean 3.4 vs 5.9 days). Also, virus culture after the first day of treatment yielded herpes simplex virus significantly less frequently in the active treatment group than in the placebo group. (15) It has also been reported that a topically applied vitamin C-paste has been found very effective in the treatment of herpes simplex. (16)
Zinc
It has been reported that various zinc salt compounds including zinc gluconate, zinc lactate, zinc acetate, or zinc sulfate were able to inactivate the herpes simplex virus by 0 to 55%. (17)
In one study, it was reported that various low concentrations of zinc sulphate solution provide a preventive effect in recurrent herpes simplex of the skin and oral mucous membrane. Treatment with zinc sulphate solution of the skin at the site of the infection was also effective in the prevention of relapses of post-herpetic erythema multiforme. Concentrations of zinc sulfate used were 0.025-0.05% for the skin, and, 0.01-0.025% for the oral mucous membranes. (18)
Another study tested the effectiveness of a 4% zinc sulfate solution in water on 18 patients experiencing episodes of recurrent herpes simplex skin infections. All patients reported that pain, tingling and burning stopped completely within the first 24 hours of zinc therapy. Crusting occurred within 1-3 days and no adverse effects were observed. (19)
Orally, 100 mg of zinc sulfate, providing 25 mg of elemental zinc, along with 250 mg of vitamin C twice daily have also been shown to be helpful in the treatment of genital herpes infections. (20)
Zinc monoglycerolate powder was evaluated in 102 patients with oral herpes (cold sores) while 56 patients with oral herpes were treated with zinc oxide powder. Patient progress and results were documented by photographs. By the thirteenth day, 70% of the lesions had healed in the patients receiving zinc monoglycerolate compared to only 9% of those receiving zinc oxide. The authors suggest that zinc ions inhibit the synthesis of viral DNA in the cells that are infected with the herpes virus. The authors note that zinc monoglycerolate could be the most effective method of delivering zinc other than by intravenous route. (21)
Eicosapentaenoic Acid (EPA)
One author reported that the long-chain omega-3 fatty acid known as eicosapentaenoic acid is effective as an anti-viral agent for the herpes virus family. Patients were given EPA, at doses between 180 mg. and 350 mg (depending upon body weight) 4 times a day for 2 to 6 weeks, without prescribing the common anti-viral agent Acyclovir. The author reported that this EPA fatty acid protocol often eliminated the symptoms due to viral infection including all well-known types of the herpes viruses. (22)
Selenium
A study in China reported that cervical cancer mortality rates were positively and significantly correlated with antibodies to the type 2 herpes simplex virus, while being correlated negatively and significantly with serum levels of selenium. (23)
Herbal Supplementation
Echinacea
Echinacea is reported to have a wide level of antimicrobial activity on bacteria, fungi, and viruses, such as the herpes viruses. (24) It has been used externally for a wound wash, eczema, burns, herpes, canker sores, and abscesses, as well as other conditions. (25)
There are several mechanisms that could explain echinacea’s activity. Echinacea (more prominently E. angustifolia) inhibits the enzyme hyaluronidase. (26) The active constituents in Echinacea inhibit the breakdown of collagen ground substance and stimulate fibroblasts to make more of the ground substance. Echinacea reportedly stimulates an alternate pathway for the immune system. (27) Inulin is the component responsible for this activity. Echinacea is claimed to activate and increase white blood cell activity and cell-mediated immunity. (28) The components of white blood cells most affected by this are T-lymphocytes, macrophages and killer cells. Cell-mediated immunity provides resistance to a variety of pathogens and guards against the development of arthritis, allergies and other potential pathologies. Echinacea is reported to increase interferon, tumor necrosis factor and interleukin-1 production through stimulation of macrophage activity. (29)
Lemon Balm/Melissa
There have been several reports of melissa topical extract (70:1w/v) being useful in the treatment of herpes labialis. (30) , (31) , (32) , (33) A recent double-blind, placebo-controlled, randomized trial was carried out with the aim of proving efficacy of standardized melissa cream for the therapy of herpes simplex labialis. (34) In addition to shortening the healing period, melissa extract aided in the prevention of spreading the infection and had an effect on typical symptoms of herpes like itching, tingling, burning, stabbing, swelling, tautness, and erythema. Authors concluded that the different mechanism of antiviral action of the melissa extract rules out the development of resistance of the herpes virus. Some indication exists that the intervals between periods with herpes might be prolonged with melissa cream treatment. Another study reported virucidal and antiviral effects of melissa extracts with respect to Herpes simplex virus type 1 (HSV-1) (35) . Of interest is that melissa has also been reported to have anti-HIV-1 activity in vitro. (36) Melissa also has reported antibacterial and antifungal activity in vitro. (37)
Cat’s Claw
Cat’s claw reportedly affects the immune system and acts as a potent free radical scavenger. (38) Cat’s claw has glycosides which reportedly reduce inflammation and edema. (39) The anti-inflammatory effects of cat’s claw are considered to be due to the sum total of the plant’s constituents, but the sterols have demonstrated anti-inflammatory activity in animal studies. The glycosides are also reported to enhance and stimulate phagocytosis, which if true would be a key part of cat’s claw’s immune function activity. (40) Isopteridine, an alkaloid which has been isolated, is claimed to have immuno-stimulatory properties. Triterpenoid alkaloids and quinovic acid glycosides have been isolated and studied for antiviral activity, possibly inhibiting replications of some DNA viruses. (41) , (42)
Olive Leaf
Olive leaf extract has been reported to be an effective antimicrobial agent against a wide variety of pathogens, including Salmonella typhi, Vibrio parahaemolyticus and Staphylococcus aureus (including penicillin-resistant strains), Klebsiella pneumonia and Eschericha coli, causal agents of intestinal or respiratory tract infections in man. (43) The component usually associated with olive leaf’s antimicrobial properties is oleuropein. (44) , (45) Oleuropein also has been reported to directly stimulate macrophage activation in laboratory studies. (46)
Olive leaf extract has reported antiviral activity, reportedly caused by the constituent calcium elenolate, a derivative of elenolic acid. (47) , (48) As an antifungal and antiviral agent, olive leaf extract is currently used as a supportive agent in maintaining bowel flora, beneficial in problems such as Crohn’s disease. (49) Recent laboratory studies in laboratory animals reported hypoglycemic and hypolipidemic activity. (50) , (51) The constituent with the activity was reported to be oleuropein, with a proposed mechanism of action being: (1) potentiation of glucose-induced insulin release, and (2) an increase in peripheral blood glucose uptake.
Grapefruit Seed
Grapefruit seed extract has been reported to be a broad-spectrum antimicrobial both in vitro and in vivo. Studies indicate that the antimicrobial activity of grapefruit seed extract exists in the cytoplasmic membrane of the invading bacteria, where the uptake of amino acids is prevented, there is disorganization of the cytoplasmic membrane and leakage of low molecular weight cellular contents ultimately resulting in inhibition of cellular respiration and death. (52)
Grapefruit seed extract also inhibits the growth of H. pylori and C. jejuni, both causative agents in gastrointestinal ulcers. (53) By inhibiting causative agents of bowel dysbiosis (the imbalance of normal bacterial flora in the GIT) including Candida sp. In vivo, grapefruit seed extract is a useful agent in maintaining bowel integrity. (54) In this human study, an improvement in constipation, flatulence, abdominal distress and night rest were noticed after 4 weeks of therapy. Most clinicians now agree on the importance of maintaining homeostatis of the microflora in health and disease. (55)
Acupuncture & Acupressure
Qin Hong Xia, et al. used a Mei Hua (plum-flower) needle to treat 26 cases of herpes simplex. After routine sterilization, the affected skin was tapped with the plum-flower needle until the area was flushed and blood slightly seeped from skin. The procedure was done once a day. Points at and near the affected area could be tapped according to the condition of the disease. 1-7 sessions resulted in full recovery in all cases. (56)
Mao Lei Yong pricked Ying Xiang (LI20) for bloodletting to treat 45 cases of lip herpes simplex. After local sterilization, Ying Xiang (LI20) (on affected side or both sides) was swiftly pricked with a 3-square needle 2-3 times. The needle was then inserted 1-2 inches deep. The skin around Ying Xiang (LI20) was pressed until 4-8 drops of blood seeped out. Niu Huang Jie Du Pian (a classical formula) was also taken orally, 2-4 tablets each time, twice a day. After 1-2 sessions, 31 cases were resolved. After 2-3 sessions, 11 cases showed significant improvement and decreased the course of the disease, and little improvement was seen in 3 cases. (57)
Combined treatment of acupuncture and herbs
Shi Ting used the combination of acupuncture and Chinese herbs to treat 57 eyes out of 34 cases of herpes simplex viral keratitis. The herbal formula consisted of Chai Hu (Bupleurum), Huang Qin (Scutellaria), Long Dan Cao (Gentiana Root), Pu Gong Yin (Dandelion), Bo He (Mentha), Jin Yin Hua (Lonicera Flower), and Quan Xie (Scorpion). For patients with relapses, Huang Qi (Astragalus Root), Bai Zhu (White Atractylodes), Fang Feng (Siler), and other ingredients that strengthen the body resistance were added accordingly. The decoction was taken orally as one dose a day in 2 separate administrations. The following acupoints were used: Feng Chi (GB20), Cheng Chi (St 1), Can Zhu (UB 2), Tai Yang (Extra), Wai Kuan (SJ 5), and He Gu (LI 4). 3-4 points were used each session. He Gu (LI 4) was used with purgation and Tai Yang (Extra) was used for bloodletting. The needles were retained for 20 minutes. This was applied once a day. Bear bile eye drops were used once every 2 hours. During the treatment, other drugs were not used. 1% atropine was used for combined iridocyclitis. 10 sessions constituted one course of treatment. The results showed that 30 eyes significantly improved, 21 eyes somewhat improved, and 6 eyes had no improvement. The effectiveness rate was 89.5%. (58)
Aromatherapy
Aromatherapy for Herpes Simplex
Topical application of essential oils may provide relief from discomfort as well as promote healing through specific antiviral activities. In a study done at the University of Heidelberg, Germany, Australian tea tree oil (Melaleuca alternifolia) and eucalyptus oil (Eucalyptus globules) were evaluated for their antiviral effects against herpes simplex. The results of the study indicated that both oils affect the virus and are capable of exerting a direct antiviral effect on HSV. (59)
When using either of these oils, they should be diluted with a carrier oil to prevent skin irritation.
Caution: Essential Oil therapies should not be used during pregnancy or lactation unless under the guidance of an experienced aromatherapist or practitioner.
Traditional Chinese Medicine
Herpes Simplex
Extensive information regarding the treatment of this health condition using Traditional Chinese Medicine is available through the link above.
Clinical Lab Assessment
Some of the following laboratory testing can provide information necessary for diagnosis and treatment. In addition, the tests listed may also give insight to functional metabolism and functional nutrient status in the body.
Herpes Cytology Specimen
Herpes Simplex 1 and 2 are similar viruses differing slightly in structure. The presence of the herpes virus is seen as multinucleated epithelial cells with enlarged atypical nuclei. This may be performed as a Pap smear and has an average sensitivity of 45-50%.
Herpes Virus Antigen
This test is used if herpes is suspected but cytology findings are negative.
Varicella-Zoster Virus Serology
Herpes Zoster may be misdiagnosed as Herpes Simplex.
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