I. Overview
Genital Herpes (GH) is a chronic, recurrent, incurable STD caused by herpes simplex virus (HSV) infection of the genital and perianal skin and mucous membranes, which occurs in young and middle-aged people and is mainly transmitted through sexual contact, but can also be transmitted from mother to child.
Second, the pathogenesis
HSV belongs to the family Herpesviridae, which has more than 100 members and is a group of medium-sized double-stranded DNA viruses. According to its physicochemical properties, herpes viruses can be divided into three subfamilies: α, β and γ. HSV belongs to the α herpesvirus subfamily, with a diameter of 150-200 nm, containing a double-stranded DNA nucleus with a diameter of 75 nm, surrounded by a nuclear capsid of 162 polypeptides with a diameter of 100-150 nm, and a lipid periplasm outside the capsid, which contains a variety of virus-specific glycoproteins, including gB , gC, gD and gG.
These glycoproteins are antigens that induce neutralizing antibodies and cellular immune responses. HSV1 and HSV2-related glycoproteins are basically similar in structure except for HSV1gG and HSV2gG, which have specific antigenic determinants, respectively; however, HSV1 and HSV2 have significant differences in biology, natural history and immune response.
HSV-II is the main pathogen of genital herpes, and humans are the only host of herpes viruses, which die when they leave the body, and can be inactivated by ether, ultraviolet light and general disinfectants.
Electron micrograph of HSV
III. Pathogenesis
HSV1 is transmitted through saliva, mainly causing orofacial herpes, and after infection the virus is latent in the trigeminal nerve root and superior cervical ganglion; HSV2 is transmitted mainly through sexual contact, and during sexual contact the virus invades the epithelial cells with body fluids through the broken mucosa or skin and replicates, causing the host cells to rupture and die, causing inflammation and immune response. When the lesion subsides, the virus enters the ganglion along the nerve axon and lurks in the sacral nerve root area.
When the immune function of the body decreases or is stimulated by certain factors, such as menstrual flow, hot sunlight, frequent intercourse, sensitization, exertion or use of immunosuppressive drugs, HSV proliferation can be triggered, and the virus is released from the latently infected posterior root ganglion, mainly invading the adjacent tissues of ectodermal origin, including skin, mucosa and nerve tissue, causing infection of skin, mucosa and nerve tissue, resulting in clinical or subclinical manifestations.
Histopathology of genital herpes
Intraepidermal blisters, caused by ballooning and reticular degeneration of cells, are seen within the blisters with spindled loosening cells and multinucleated epithelial giant cells. The dermal papillae are edematous, with extravasated erythrocytes and varying degrees of inflammatory cell infiltration in the dermis, with neutrophilic leukocytes and lymphocytes.
V. Clinical manifestations
The main symptoms of genital herpes usually start 4 to 5 days after infection, and the clinical symptoms are a burning sensation in the affected area of the vulva, followed by clusters of papules, which can be one or more clusters, followed by the formation of blisters. After a few days, it evolves into pustules, and after breaking down, it forms vesicles or shallow ulcers, which are painful and finally heal themselves with scabs. The lesions are mostly found on the foreskin, glans, coronal sulcus and penis in men, and occasionally on the urethra; in women, they are mostly found on the labia, clitoris, mons pubis, cervix, and also on the urethra. Primary genital herpes is often associated with systemic symptoms such as general malaise, low-grade fever, headache, and local lymph node enlargement.
The clinical manifestations of genital herpes are diverse and are clinically divided into three types of genital herpes: primary, recurrent, and subclinical. Other infections include genital herpes in pregnant women, subclinical infections, and neonatal herpes virus infections. The severity of clinical manifestations and frequency of recurrence are influenced by factors such as virus type and host immune status.
(a) Primary genital herpes: incubation period of 3 days to 14 days, clinical manifestations are clusters or scattered small blisters around the external genitalia or anus, breaking down to form vesicles or ulcers in 2 to 4 days, self-conscious pain, finally crusting and self-healing, duration of the disease 2 weeks to 3 weeks. The lesions are mostly found on the glans coronalis and penis of the foreskin in men, and on the labia majora and minora, mons pubis, clitoris and uterus in women. It is often accompanied by inguinal lymph node enlargement, pressure pain, fever, headache, malaise and other systemic symptoms.
(b) Recurrent genital herpes: primary genital herpes recurs within 1 month to 4 months after the lesions have subsided, and recurrent infections usually occur at the original site, recurrent genital herpes has lighter systemic symptoms and lesions than primary genital herpes, and has a shorter course.
The manifestations are clusters of small blisters around the external genitalia or anus, which break down to form vesicles or shallow ulcers, with mild self-conscious symptoms and a self-healing course of 7 to 10 days. It recurs after an interval of 2 to 3 weeks or months, and recurs after a year of infection. Male homosexuals may develop anorectal HSV-II infection, which is clinically manifested by anorectal pain, constipation, increased discharge, urgency, and herpetic ulcers around the anus, and sigmoidoscopy reveals mucosal congestion, bleeding, and ulceration in the lower rectum.
(c) Subclinical genital herpes: asymptomatic genital herpes, generally 50% HSV-Ⅰ and 70%-80% HSV-II infections are clinically asymptomatic. It is not that the subclinical type is truly asymptomatic, but that the rash is atypical, and the lack of recognition of minor fissures and ulcers in the genital area is ignored, making them asymptomatic HSV carriers. The subclinical type of genital herpes is the main source of infection for this disease, and latent HSV-II is more likely to be stimulated to cause disease than latent HSV-Ⅰ.
(iv) Other infections
1. Genital herpes in pregnant women
Pregnant women with HSV infection are more serious, and in addition to skin and mucous membrane damage, they are prone to disseminated infections of internal organs, such as hepatitis and pneumonia, etc.; and they also have some effect on the fetus. The infection rate of the fetus of a pregnant woman with primary genital herpes is 20% to 50%; a pregnant woman with recurrent genital herpes has neutralizing antibodies in her blood, and the rate of intrauterine infection is lower, about 0-8%. HSV infection in early pregnancy can cause miscarriage, stillbirth, stillbirth and premature birth; infection via the birth canal and premature rupture of the amniotic membrane can cause neonatal herpes virus infection.
2.Herpesvirus infection in newborns
Most often seen in premature infants, their skin, mucous membranes and internal organs can be involved; if the central nervous system is involved, microcephaly, cerebral edema and encephalitis will occur; if not treated in time, the mortality rate is up to 50% and the sequelae are serious.
VI. Diagnosis
1.History of unclean sexual intercourse or spousal infection.
2, the clinical manifestations of primary, recurrent, subclinical genital herpes.
To further confirm the diagnosis, the following tests should be done.
1. cytological examination (Tzank smear)
2.Viral antigen test
3. Viral culture
1.Cytological examination (Tzank smear)
Take a sterilized slide to make a herpetic bottom print, stain it with Wright stain or Giemsa stain and then examine it microscopically.
2.Viral antigen detection
Herpes simplex virus antigen can be detected by direct immunofluorescence with monoclonal antibodies or by enzyme-linked immunosorbent assay (ELISA) from the lesion.
3.Virus culture
Herpes simplex virus and cytopathic lesions can be diagnosed if the specimen is collected from the lesion for virus culture.
Differential diagnosis
1.Contact dermatitis
2. Leukoplakia
3.Hard chancre
4.Soft chancre
5. Perianal herpes zoster
1. Contact dermatitis.
There is a history of contact with allergens and no history of unclean sexual intercourse. The skin of the skin is not only a good source of blood, but also a good source of blood.
3. Leukoplakia.
It can be accompanied by oral ulcers, eye lesions, joint symptoms or nodular erythema of the lower legs.
4.Hard chancre
(1) Mostly develops 2~3 weeks after unclean sexual intercourse;
(2) No pain, no itching;
(3) Early damage is red or dark red papules, which later break down to form hard nodular ulcers with a hard base like cartilage;
(4) In men, the lesions are usually found in the coronal sulcus, glans, inner plate of the foreskin and the prepuce; in women, the labia, clitoris and urethra are often involved;
(5) Syphilis spirochetes can be detected in the basal or marginal exudate of the damage.
5. Soft chancre
(1) Onset is usually 1~6 days after unclean sexual intercourse;
(2) Self-perceived pain in the affected area of varying degrees;
(3) The early damage is painful red macules, papules or small pustules, which later break down to form painful superficial ulcers with a soft base and easy bleeding when touched;
(4) In males, the lesions are found in the coronal groove, penile body, inner foreskin plate and prepuce tether; in females, they are found in the labia, labial tether and anus;
(5) Haemophilus ducreyi can be detected in the basal or marginal exudate of the ulcer foci.
6. Perianal herpes zoster
Herpes zoster is caused by varicella-zoster virus, usually with prodromal symptoms and clusters of blisters in the genital area, with local burning and neuralgia, mostly invading unilateral nerves, the blisters can erode and crust, and rarely recur after healing. There is no history of impure sexual intercourse.
VIII. Treatment
(a) Treatment principles
1, timely and adequate use of antiviral drugs to reduce symptoms, shorten the course of the disease and control the infection and recurrence of herpes;
2. Keep the wound surface clean and dry to prevent secondary infection;
3. Enhance the immunity of the body to reduce and prevent recurrence;
Antispasmodic and pain relief.
4, should pay attention to rest, avoid drinking alcohol and transitional sexual life; avoid sexual life when clinical symptoms appear.
(II) Treatment plan
1.Systematic antiviral therapy
(1) Primary genital herpes
Can be treated with one of the following regimens.
(1) Acyclovir: 200mg orally 5 times a day or 400mg 3 times a day for 7 to 10 days;
(ii) Vaciclovir: orally, 300 mg twice daily for 7-10 days;
(3) Famciclovir: 250mg orally 3 times a day for 7-10 days.
(2) Recurrent genital herpes
It is best to treat with one of the following regimens within 24 hours of the onset of prodromal symptoms or damage.
(1) Acyclovir: orally, 200 mg 5 times a day or 400 mg 3 times a day for 5 days;
②Vaciclovir: orally, 300 mg twice daily for 5 days;
(3) Famciclovir: orally, 250mg per dose, 3 times daily for 5 days.
(3) Frequent genital herpes (more than 6 recurrences in a year)
①Acyclovir: orally, 400mg twice a day for 4 months to 6 months;
②Vaxilovir: oral, 300mg per dose, 1 time daily, usually for 4 months to 6 months;
(3) Famciclovir: orally, 125-250mg twice daily for 4 months to 6 months.
(4) Severe infection
Refers to those with severe primary symptoms or widespread lesions, and may be treated with one of the following regimens.
① Acyclovir: 5~10 mg per kg of body weight per dose, intravenous, every 8 hours for 5~7 days or until clinical symptoms subside;
② Ganciclovir: 5 mg per kg of body weight per time, intravenous infusion, once a day, for 5-7 days or until the clinical symptoms subside.
2.Local therapy
(1) Keep the wound surface clean and dry to prevent secondary infection.
Use saline or 3% boric acid water wet compress for 15-30 minutes each time, 2-3 times a day; avoid rubbing the wall of the herpes; if the wall of the herpes is broken, apply antimicrobial ointment or cream.
(2) Topical antiviral therapy.
Topical application of 3% ~ 5% acyclovir cream, 1% penciclovir cream or phthalamide cream can be applied 2 ~ 3 times a day until the blisters disappear.
(3) Antispasmodic and pain relief
For primary genital herpes with significant pain, apply 2% lidocaine gel or 5% lidocaine ointment topically.
3.Immune-enhancing therapy
Recurrent genital herpes can be treated with the following regimen to reduce the number of recurrences or prevent recurrence.
(1) Levamisole: 50 mg orally, 3 times daily, for 3 days every 1~2 weeks; forbidden for those whose total peripheral blood leukocyte count is below 40,000/L;
(2) Thymic factor D: 10 mg per injection, every other day, 1 ~ 3 months as a course of treatment;
(3) BCG polysaccharide nucleic acid injection: 1 mg per intramuscular injection, once every other day, for 1 month as a course of treatment;
(4) Multi-Anti-Methylation Injection: 5 mg per injection, once every other day, one month as a course of treatment.
IX. Precautions during treatment
1. Patients should check whether there are other local infections.
2. Patients should pay attention to rest during treatment. In particular, attention should be paid to mental relaxation, avoiding excessive tension, fatigue, avoiding strain, and strengthening nutrition.
3, the patient’s daily necessities should be used separately. Patients’ daily necessities, especially towels and basins, should be used separately and disinfected at the same time to prevent infection.
4, abstinence during treatment. If you are suffering from genital herpes, it is forbidden to have sex when the herpes has not completely subsided, to prevent aggravation of the disease, and if the symptoms of herpes have subsided for a month after treatment, you should use condoms to prevent infection when you have sex.
Slide 45
5. Patients should check if they have other STDs. For people who suffer from genital herpes, it should be necessary to check for other STDs. If you don’t pay attention to the presence of other STDs, these diseases often increase the chances of herpes disease recurrence.
6. Patients should pay attention to the relevant situation of their sexual partners or spouses. If necessary, the sexual partner or spouse should also go to the hospital together to check if they are also suffering from the disease, to conduct a comprehensive examination, once found should be treated accordingly to prevent cross-infection.
7. There should be an understanding of the patient’s general condition. The patient should be further checked if he has other diseases, and if he has other diseases, he should be actively treated to avoid medication inducing drug reflection of other diseases during the treatment.
8, the patient to maintain local cleanliness, clean, dry. Patients should diligently wash the lesion local, keep the local clean, dry, local available hot water sitz bath or soak. The patient’s underwear should be loose and well ventilated (breathable).
X. Management and prevention
(i) Management
Cases diagnosed with genital herpes for the first time should be reported as an outbreak.
(ii) Prevention
1. Strictly abide by monogamy, do not engage in extramarital relationships, and oppose prostitution and prostitution;
2. Sexual intercourse is prohibited during the attack period, and those who want to have sex before the remission period is confirmed to be cured should reasonably use condoms to reduce the chance of infection;
3, frequent recurrence of cases, in the prodromal symptoms appear oral acyclovir, valacyclovir or famciclovir can reduce the disease or prevent recurrence
4, sexual partners with treatment, sexual partners of one party suffering from genital herpes, should mobilize the other party to timely examination, with clinical or subclinical manifestations of infection, should be treated at the same time.
Research progress of genital herpes treatment
I. Gene phagocytosis immune enhancement therapy
l The treatment achieves its effect through the following steps: the first step is strong sterilization. The unique drug factor of the “gene phagocytosis immune enhancement therapy” series of drugs has a strong penetrating effect, reaching the lesion, quickly and accurately identifying the germs, using the international advanced gene technology, so that the drug quickly reaches an effective therapeutic concentration, completely killing the germs latent in the blood, the basal layer of the skin, the cells of the hair layer and the ganglia; The second step is comprehensive detoxification. Through metabolism, the virus and DNA debris are excreted, preventing the reorganization of debris;
The third step of systemic repair. “Gene phagocytosis immune enhancement therapy” is to promote the drug rich in mucosal repair factors to quickly repair the diseased tissues and damaged cells, eliminate metabolic disorders, correct immune deficiencies, completely restore the body function; the fourth step to activate the immune. The fourth step is to stimulate the body’s immune mechanism to produce protective immunity to prevent the virus from reinfection and completely eliminate the recurrence of warts and herpes virus.
It is a broad-spectrum antiviral drug, mainly by changing the lipid composition of the host cell membrane and inhibiting the fusion of the viral envelope with the host cell membrane, the possibility of virus resistance is very small, and the drug does not affect the synthesis of DNA, no potential teratogenic and mutagenic effects, so it has a broad application prospect in the field of antiviral. Antiviral drugs can shorten the course of GH, reduce viral emission, promote lesion healing, and inhibit herpes recurrence, but they do not prevent the establishment of latent infection or change the frequency and characteristics of recurrence. There is no effective solution to the problem of recurrence of HSV infection. Long-term suppressive therapy with ACV, FCV and VCV has been shown to have good immediate efficacy, but the effect on disease recurrence after drug withdrawal needs to be further evaluated.
Slide 54
It is now generally accepted that the tendency of genital herpes to recur and not be easily cured is related to cellular immune dysfunction in patients. Research on the cellular immunity of genital herpes has progressed quite rapidly in recent years, and since the onset and recurrence are related to the low cellular immune function of the organism, treatment over the years has mostly focused on antiviral and immunomodulation. Initially, immunotherapy was mainly based on the application of non-specific immunomodulatory drugs such as levamisole, transfer factor, thymidine and polymyxin. In recent years, with the in-depth understanding of the mechanism of low cellular immunity in patients and the development of genetic engineering technology, new immunomodulatory agents have been continuously applied to the treatment of genital herpes.
However, neither non-specific immunomodulators nor new immunomodulators can control its occurrence and recurrence, so the development of herpes virus vaccine has become the key to prevent genital herpes infection and has become a hot spot for research in recent years. With the development of genetic engineering technology, HSV vaccine has also entered the era of genetic engineering vaccine from the initial research of inactivated virus vaccine. Currently, there are more researched live vector vaccines, live attenuated vaccines, replication-restricted vaccines, DISC vaccines, subunit vaccines, DNA vaccines, etc. Although these vaccines have good effect in immunized animals, clinical trials are not as satisfactory as they should be.
Since infection is a complex process, the vaccine HSV obtained so far does not completely stop the infection, but may reduce the occurrence of the disease and decrease the infectiousness. A large number of experiments have shown that anti-HSV infection requires the participation of humoral immunity and cellular immunity of the organism, and replication-restricted vaccines and DNA vaccines have more advantages than other vaccines, and with the continuous development of genetic engineering technology, coupled with the easy manipulation of DNA DNA vaccines will probably have a broader application prospect.