Genital herpes (GH) is a chronic lifelong viral infection caused by herpes simplex virus (H SV) infection. Herpes simplex virus type 2 (HSV-2) primarily causes genital herpes, and in rare cases H SV-1 causes genital herpes. Almost all HSV-2 infections are sexual, seen in perianal and genital infections, and HSV-1 infections are seen in perianal, genital, and oral-lip infections.
Most patients with H SV-2 infection are not diagnosed with genital herpes. In patients with mild or undetermined infections, many genital tracts intermittently discharge the virus. The majority of genital herpes infections are transmitted through unconscious or asymptomatic carriers of the patient, and more attention should be paid to the management of patients with genital HSV infection in the intra-onset phase.
1. Diagnostic considerations
The clinical diagnosis of genital herpes lacks sensitivity and specificity. Many H SV infections lack the typical painful multiple blisters or ulcerative lesions. Most first-episode genital herpes is caused by H SV-1, but recurrent and subclinical shedding is often H SV-2 infection, and determining the type of herpes virus causing genital herpes can affect patient prognosis and counseling. Laboratory testing is necessary for the clinical diagnosis of genital herpes.
Viral typing based on virologic or serologic testing determines the management of patients with sexually transmitted disease (STD) or patients at high risk for STD.
HSV is detected by culture of tissue or cells from genital ulcers or other mucous membranes and lesions, but the sensitivity of culture is low, and even lower in patients with recurrent infection. Polymerase chain reaction (PCR) is more sensitive for detecting herpesvirus DNA and has been used instead of viral culture, especially for diagnosing HSV infection of the central nervous system. The sensitivity and specificity of herpesvirus infection based on cell smears is low and is not a reliable basis for the diagnosis of HSV infection.
Because of the intermittent nature of detoxification in infected patients, a negative culture or PCR test does not necessarily mean that infection is not present.
The sensitivity of serologic antibodies for the diagnosis of herpesvirus infection is
The sensitivity of serological antibodies for the diagnosis of herpesvirus infection is 80% to 98%, and the specificity is >96%. Herpes virus serologic testing is used primarily for: (1) recurrent genital herpes or atypical genital herpes and negative herpes virus cultures; (2) clinical diagnosis of genital herpes without laboratory confirmation; and (3) partnered genital herpes. Some experts recommend that STD testing for patients at high risk for H IV infection, such as multiple partners, human immunodeficiency virus (H IV) infection, and men who have sex with men (M SM), should include H SV testing. Screening for HSV-1 and H SV-2 in the general population is not required.
2. Treatment
Antiviral therapy is beneficial for most patients with clinical symptoms and is the mainstay of management of genital herpes. It has been shown to control signs and symptoms during the onset of infection and to prevent recurrence by suppressing the virus in recurrent infections. Systemic antivirals are used for the first clinical episode and recurrence, or as daily viral suppression therapy to partially control the signs and symptoms of herpes attacks.
However, these drugs neither eradicate the underlying virus nor do they have a significant effect on the risk, frequency, or severity of recurrence when discontinued. Three antiviral drugs, acyclovir, valacyclovir, and famciclovir, have been shown to be clinically effective in genital herpes in randomized trials. Valacyclovir is the valine ester of acyclovir and has an increased oral absorption rate. Oral bioavailability of famciclovir is also high. The clinical benefit of topical antivirals is small and their use is not recommended.
2 1 Confirmed HSV-2 infection Almost all patients with a first symptomatic episode of genital HSV-2 infection are followed by a recurrence of genital herpes; recurrences after a first H SV-1 infection are less common. H SV-2 infected patients and those with long-standing clinical or asymptomatic infection have intermittent asymptomatic detoxification. Antiviral therapy for recurrent genital herpes may be suppressive to reduce recurrence or intermittent to improve or shorten the course of the disease. Antiviral therapy is also beneficial in some patients with mild or few recurrences, and suppressive therapy can reduce the risk of transmission of H SV-2 between partners.
2 2 First episode of genital herpes Recommended regimen:
Acycloguanosine, 400 m g, 3 times/d, orally for 7 to 10 d;
or acycloguanosine, 200 m g, orally, 5 times/d, 7-10 d; or famciclovir, 250 m g, 3 times/d, orally, 7-10 d; or valacyclovir, 1 g, 2 times/d, orally, 7-10 d. If not completely cured, the treatment course may exceed 10 d.
Treatment of recurrent genital herpes: Treatment of patients with recurrent genital herpes should be started on the first day of recurrent lesions to shorten the duration and remission of the disease.
Recommended regimen:
Acycloguanosine, 400 m g, 3 times/d, orally, 5 d; or acycloguanosine, 800 m g, 2 times/d, orally, 5 d; or acycloguanosine, 800 m g, 3 times/d, orally, 2 d; or famciclovir, 125 m g, 2 times/d, orally, 5 d; or famciclovir, 1 g, 2 times/d, orally, 1 d; or famciclovir, 500 m g, 2 times/d, orally, 3 d; or famciclovir, 1 g, 1 time/d, orally, 5 d.
2 4 Viral suppression therapy Viral suppression therapy for recurrent genital herpes may
reduce the recurrence rate of genital herpes in patients with frequent recurrences (6 times/year) by 70% to 80%. This treatment is also effective in preventing recurrence in patients with infrequent genital herpes. It also improves the quality of life of patients. Over time, the patient’s psychological adjustment to the disease may also change, and many patients experience less frequent recurrences of genital herpes. Continued changes in the treatment cycle (e.g., once a year) can be discussed.
Recommended regimen:
Acyclovir, 400 m g, orally, 2 times /d;
or famciclovir, 250 m g, orally, 2 times/d; or valacyclovir, 500 m g, orally, 1 time/d; or valacyclovir, 10 g, orally, 1 time/d.
For very frequent recurrences of genital herpes (10/year), valacyclovir 500 m g orally once/d is less effective than either the valacyclovir or acyclovir regimens.
2 5 Severe infections HSV severe infections or complications require hospitalization. Disseminated infections such as pneumonia, hepatitis, meningitis, or encephalitis require intravenous acyclovir at the recommended dose of 5-10 m g/kg IV every 8 h for 2-7 days or until clinical improvement, followed by oral therapy for a total duration of at least 10 days.
3. Counseling
Objectives of the counseling service:
( 1) To help patients cope with infection;
(2) To prevent sexual and perinatal transmission.
4. Management of sexual partners
Evaluation and counseling of sexual partners. Evaluate and treat partners with clinical signs and symptoms (same as patient). Ask asymptomatic partners if they have any previous history of genital herpes, and do serological examination.
5. Special considerations
Allergy, intolerance and adverse reactions to acyclovir, famciclovir and famciclovir are rare. Acyclovir allergy can be treated by desensitization.
H SV infection is more common, severe and atypical in patients with H IV infection. Oral antiviral therapy is often effective. Oral antiviral therapy is often effective and includes treatment of HSV infection during the flare-up phase and treatment of H SV infection during the non-flare-up phase to suppress the virus.
Onset treatment:
Recommended regimen:
Acyclovir, 400 m g, orally, 3 times/d, 5-10 d; or Famciclovir, 500 m g, orally, 2 times/d, 5-10 d; or Valacyclovir, 10 g, orally, 2 times/d, 5-10 d. Viral suppressive therapy:
Recommended regimen:
Acyclovir, 400-800 mg, orally, 2 to 3 times /d;
or famciclovir, 500 m g, orally, 2 times /d;
or valacyclovir, 500 m g, orally, 2 times/d.
The recommended doses of acyclovir, famciclovir, and famciclovir are safe for immunodeficient inpatients. For severe herpesvirus infections, treatment is initiated with acyclovir 5-10 m g/kg intravenously every 8 h. If the herpes virus recurs during the course of treatment, viral resistance should be suspected. All acyclovir-resistant patients are resistant to vaxilovir and most are resistant to famciclovir. Fosfomycin is often effective in acyclovir-resistant patients at a dose of 40 mg/kg intravenously every 8 h. Antiviral therapy should be continued until the first day of treatment.
Antiviral therapy should be continued until clinical symptoms are resolved. Cidofovir 5 mg/kg administered intravenously once weekly is also effective. Imiquimod cream is a topical drug that, like topical cidofovir 1% gel, is not available on the market and must be prepared over the counter. These topical medications are applied to the lesions once daily for 5 days.
6. Genital herpes in pregnancy
Most mothers of infants with neonatal herpes lack a history of genital herpes, and the risk of genital herpes infection in newborns near delivery is 30% to 50%. The risk of neonatal infection with genital herpes in mothers with recurrent genital herpes infections during pregnancy is < 1%. However, due to the high number of genital herpes infections during pregnancy, neonatal infections caused by recurrent genital herpes infections during pregnancy still account for the majority of neonatal herpes infections.
The prevention of neonatal herpes is centered on the prevention of fetal infection during pregnancy and the prevention of neonatal infection during delivery. Pregnant women known not to have genital herpes are advised to avoid sexual intercourse with an infected or suspected infected partner in late pregnancy, and pregnant women known not to have orofacial herpes are advised to avoid oral-genital contact with an infected or suspected orofacial herpes partner in late pregnancy.
Serologic testing can help identify pregnant women at high risk for H SV infection and counsel them about the risks involved. These tests are even more important for counseling when the pregnant woman’s sexual partner is infected with HSV.
All pregnant women should be asked about their history of genital herpes and, at the time of delivery, about the presence of genital herpes symptoms (including prodromal signs), with vaginal delivery possible in the absence of herpes lesions and prodromal signs.
To prevent herpes infection in the newborn, cesarean delivery should be chosen for those with recurrent genital herpes lesions at the time of delivery. However, cesarean delivery does not completely exclude the risk of transmission of herpes virus to the infant. The safety of systemic acyclovir, famciclovir, and famciclovir in the treatment of pregnant women has not been fully established. The use of acyclovir during early pregnancy did not increase birth defects compared with the general population. Oral acyclovir may be used for the first episode of genital herpes or severe recurrent herpes during pregnancy.
Severe infections may be treated with intravenous administration. To prevent HSV infection in the newborn, cesarean section should be used to terminate the pregnancy for the first episode of genital herpes in late pregnancy. The use of acyclovir in late pregnancy may reduce the rate of cesarean delivery by reducing the recurrence of genital herpes during pregnancy. There is no data to support the need for beneficial antiviral therapy for pregnant women with H SV infection without a history of genital herpes.
7. Neonatal herpes
Neonates presumed to have been exposed to HSV at delivery by virologic testing or clinical observation should be followed closely and viral surveillance should be performed in these neonates to detect H SV infection before the onset of clinical signs. Acyclovir treatment of these infants has also been recommended. All newborns with signs of herpesvirus infection should be evaluated promptly and treated with acyclovir, i.e., acyclovir 20 mg/kg intravenously every 8 h for 21 d if the infection is disseminated to the central nervous system or 14 d if the infection is confined to the skin and mucous membranes.