were rarely useful to diagnosis and not routinely used in clinical practice. the older igm serologic assay could not differentiate between antibodies generated in response to hsv-1 or hsv-2 infection. however, a glycoprotein g-specific (igg) hsv test introduced in the 1980s is more than 98% specific at discriminating hsv-1 from hsv-2. differential diagnosis it should not be confused with conditions caused by other viruses in the herpesviridae family such as herpes zoster, which is caused by varicella zoster virus. the differential diagnosis includes hand, foot and mouth disease due to similar lesions on the skin. lymphangioma circumscriptum and dermatitis herpetiformis may also have a similar appearance. prevention barrier protection, such as a condom, can reduce the risk of herpes transmission. as with almost all sexually transmitted infections, women are more susceptible to acquiring genital hsv-2 than men. on an annual basis, without the use of antivirals or condoms, the transmission risk of hsv-2 from infected male to female is about 8–11%. this is believed to be due to the increased exposure of mucosal tissue to potential infection sites. transmission risk from infected female to male is around 4–5% annually. suppressive antiviral therapy reduces these risks by 50%. antivirals also help prevent the development of symptomatic hsv in infection scenarios, meaning the infected partner will be seropositive but symptom-free by about 50%. condom use also reduces the transmission risk significantly. condom use is much more effective at preventing male-to-female transmission than vice versa. previous hsv-1 infection may reduce the risk for acquisition of hsv-2 infection among women by a factor of three, although the one study that states this has a small sample size of 14 transmissions out of 214 couples. however, asymptomatic carriers of the hsv-2 virus are still contagious. in many infections, the first symptom people will have of their own infections is the horizontal transmission to a sexual partner or the vertical transmission of neonatal herpes to a newborn at term. since most asymptomatic individuals are unaware of their infection, they are considered at high risk for spreading hsv. in october 2011, the anti-hiv drug tenofovir, when used topically in a microbicidal vaginal gel, was reported to reduce herpes virus sexual transmission by 51%. barrier methods condoms offer moderate protection against hsv-2 in both men and women, with consistent condom users having a 30%-lower risk of hsv-2 acquisition compared with those who never use condoms. a female condom can provide greater protection than the male condom, as it covers the labia. the virus cannot pass through a synthetic condom, but a male condom's effectiveness is limited because herpes ulcers may appear on areas not covered by it. neither type of condom prevents contact with the scrotum, anus, buttocks, or upper thighs, areas that may come in contact with ulcers or genital secretions during sexual activity. protection against herpes simplex depends on the site of the ulcer; therefore, if ulcers appear on areas not covered by condoms, abstaining from sexual activity until the ulcers are fully healed is one way to limit risk of transmission. the risk is not eliminated, however, as viral shedding capable of transmitting infection may still occur while the infected partner is asymptomatic. the use of condoms or dental dams also limits the transmission of herpes from the genitals of one partner to the mouth of the other (or vice versa) during oral sex. when one partner has a herpes simplex infection and the other does not, the use of antiviral medication, such as valaciclovir, in conjunction with a condom, further decreases the chances of transmission to the uninfected partner. topical microbicides that contain chemicals that directly inactivate the virus and block viral entry are being investigated. antivirals antivirals may reduce asymptomatic shedding; asymptomatic genital hsv-2 viral shedding is believed to occur on 20% of days per year in patients not undergoing antiviral treatment, versus 10% of days while on antiviral therapy. pregnancy the risk of transmission from mother to baby is highest if the mother becomes infected around the time of delivery (30% to 60%), since insufficient time will have occurred for the generation and transfer of protective maternal antibodies before the birth of the child. in contrast, the risk falls to 3% if the infection is recurrent, and is 1–3% if the woman is seropositive for both hsv-1 and hsv-2, and is less than 1% if no lesions are visible. women seropositive for only one type of hsv are only half as likely to transmit hsv as infected seronegative mothers. to prevent neonatal infections, seronegative women are recommended to avoid unprotected oral-genital contact with an hsv-1-seropositive partner and conventional sex with a partner having a genital infection during the last trimester of pregnancy. mothers infected with hsv are advised to avoid procedures that would cause trauma to the infant during birth (e.g. fetal scalp electrodes, forceps, and vacuum extractors) and, should lesions be present, to elect caesarean section to reduce exposure of the child to infected secretions in the birth canal. the use of antiviral treatments, such as aciclovir, given from the 36th week of pregnancy, limits hsv recurrence and shedding during childbirth, thereby reducing the need for caesarean section. aciclovir is the recommended antiviral for herpes suppressive therapy during the last months of pregnancy. the use of valaciclovir and famciclovir, while potentially improving compliance, have less-well-determined safety in pregnancy. management no method eradicates herpes virus from the body, but antiviral medications can reduce the frequency, duration, and severity of outbreaks. analgesics such as ibuprofen and paracetamol (acetaminophen) can reduce pain and fever. topical anesthetic treatments such as prilocaine, lidocaine, benzocaine, or tetracaine can also relieve itching and pain. antiviral the antiviral medication aciclovir several antiviral drugs are effective for treating herpes, including aciclovir (acyclovir), valaciclovir, famciclovir, and penciclovir. aciclovir was the first discovered and is now available in generic. valaciclovir is also available as a generic and is slightly more effective than aciclovir for reducing lesion healing time. evidence supports the use of aciclovir and valaciclovir in the treatment of herpes labialis as well as herpes infections in people with cancer. the evidence to support the use of aciclovir in primary herpetic gingivostomatitis is weaker. topical a number of topical antivirals are effective for herpes labialis, including aciclovir, penciclovir, and docosanol. alternative medicine evidence is insufficient to support use of many of these compounds, including echinacea, eleuthero, l-lysine, zinc, monolaurin bee products, and aloe vera. while a number of small studies show possible benefit from monolaurin, l-lysine, aspirin, lemon balm, topical zinc, or licorice root cream in treatment, these preliminary studies have not been confirmed by higher-quality randomized controlled studies. prognosis following active infection, herpes viruses establish a latent infection in sensory and autonomic ganglia of the nervous system. the double-stranded dna of the virus is incorporated into the cell physiology by infection of the nucleus of a nerve's cell body. hsv latency is static; no virus is produced; and is controlled by a number of viral genes, including latency-associated transcript. many hsv-infected people experience recurrence within the first year of infection. prodrome precedes development of lesions. prodromal symptoms include tingling (paresthesia), itching, and pain where lumbosacral nerves innervate the skin. prodrome may occur as long as several days or as short as a few hours before lesions develop. beginning antiviral treatment when prodrome is experienced can reduce the appearance and duration of lesions in some individuals. during recurrence, fewer lesions are likely to develop and are less painful and heal faster (within 5–10 days without antiviral treatment) than those occurring during the primary infection. subsequent outbreaks tend to be periodic or episodic, occurring on average four or five times a year when not using antiviral therapy. the causes of reactivation are uncertain, but several potential triggers have been documented. a 2009 study showed the protein vp16 plays a key role in reactivation of the dormant virus. changes in the immune system during menstruation may play a role in hsv-1 reactivation. concurrent infections, such as viral upper respiratory tract infection or other febrile diseases, can cause outbreaks. reactivation due to other infections is the likely source of the historic terms 'cold sore' and 'fever blister'. other identified triggers include local injury to the face, lips, eyes, or mouth; trauma; surgery; radiotherapy; and exposure to wind, ultraviolet light, or sunlight. the frequency and severity of recurrent outbreaks vary greatly between people. some individuals' outbreaks can be quite debilitating, with large, painful lesions persisting for several weeks, while others experience only minor itching or burning for a few days. some evidence indicates genetics play a role in the frequency of cold sore outbreaks. an area of human chromosome 21 that includes six genes has been linked to frequent oral herpes outbreaks. an immunity to the virus is built over time. most infected individuals experience fewer outbreaks and outbreak symptoms often become less severe. after several years, some people become perpetually asymptomatic and no longer experience outbreaks, though they may still be contagious to others. immunocompromised individuals may experience longer, more frequent, and more severe episodes. antiviral medication has been proven to shorten the frequency and duration of outbreaks. outbreaks may occur at the original site of the infection or in proximity to nerve endings that reach out from the infected ganglia. in the case of a genital infection, sores can appear at the original site of infection or near the base of the spine, the buttocks, or the back of the thighs. hsv-2-infected individuals are at higher risk for acquiring hiv when practicing unprotected sex with hiv-positive persons, in particular during an outbreak with active lesions. epidemiology main article: epidemiology of herpes simplex worldwide rates of either hsv-1 and/or hsv-2 are between 60 and 95% in adults. hsv-1 is more common than hsv-2, with rates of both increasing as people age. hsv-1 rates are between 70% and 80% in populations of low socioeconomic status and 40% to 60% in populations of improved socioeconomic status. an estimated 536 million people or 16% of the population worldwide were infected with hsv-2 as of 2003 with greater rates among women and in those in the developing world. rates of infection are determined by the presence of antibodies against either viral species. in the us, 58% of the population is infected with hsv-1 and 16% are infected with hsv-2. among those hsv-2-seropositive, only 19% were aware they were infected. during 2005–2008, the prevalence of hsv-2 was 39% in black people and 21% in women. the annual incidence in canada of genital herpes due to hsv-1 and hsv-2 infection is not known (for a review of hsv-1/hsv-2 prevalence and incidence studies worldwide, see smith and robinson 2002). as many as one in seven canadians aged 14 to 59 may be infected with herpes simplex type 2 virus and more than 90 per cent of them may be unaware of their status, a new study suggests. in the united states, it is estimated that about 1,640,000 hsv-2 seroconversions occur yearly (730,000 men and 910,000 women, or 8.4 per 1,000 persons). in british columbia in 1999, the seroprevalence of hsv-2 antibody in leftover serum submitted for antenatal testing revealed a prevalence of 17%, ranging from 7% in women 15–19 years old to 28% in those 40–44 years. in norway, a study published in 2000 found that up to 70–90% of genital initial infections were due to hsv-1. in nova scotia, 58% of 1,790 hsv isolates from genital lesion cultures in women were hsv-1; in men, 37% of 468 isolates were hsv-1. history herpes has been known for at least 2,000 years. emperor tiberius is said to have banned kissing in rome for a time due to so many people having cold sores. in the 16th century romeo and juliet, blisters "o'er ladies' lips" are mentioned. in the 18th century, it was so common among prostitutes that it was called "a vocational disease of women". the term 'herpes simplex' appeared in richard boulton's a system of rational and practical chirurgery in 1713, where the terms 'herpes miliaris' and 'herpes exedens' also appeared. herpes was not found to be a virus until the 1940s. herpes antiviral therapy began in the early 1960s with the experimental use of medications that interfered with viral replication called deoxyribonucleic acid (dna) inhibitors. the original use was against normally fatal or debilitating illnesses such as adult