VENEREALLY ACQUIRED HERPES VIRUS HOMINIS (HVH)
by Maj. M. P. Vora, M.B.B.S., D.V.D.
Former Hon. Senior Venereologist,
St. George’s Hospital, Bombay.
Current Medical Practice
A monthly journal devoted to Modern Medicine and Surgery.
Volume No. – 21, Number – 1 of January 1977.
Page No. 17 to 20.
Only a few years ago, genital herpes as a virus infection was little known and not even considered as a venereally acquired disease. Prior to 1965, it was generally not seen nor was it considered for differential diagnosis. It is estimated that some percentage of the population does suffer from HVH at one time or other. It is more frequently seen now than before, though its true incidence can never be determined precisely; for, some of these infections are totally silent or asymptomatic and do not require the sufferer to seek medical relief. In 1967, the herpes virus hominis and its association with other venereal diseases became known for the first time. In a group of 15 patients of average age under 20, from whom the virus was isolated, 5 had gonorrhoea within 1 or 2 months before or after the herpes virus diagnosis, 2 were re-infected with gonorrhoea shortly after the first infection was treated and 1 had syphilis. In 4 of the others, beta- streptococci were cultured from their cervical specimens. This latter infection is now being seen more frequently and is related to venereal contact. 5 percent of the patients in prenatal clinics harbour this pathogen, leading to primary salpingitis and neonatal pathology. Only now more light is thrown on the genital herpes virus infections, which were unheard of a decade ago.
There are two antigenic groups of herpes virus hominis i.e. HVH-1 and HVH-2, formerly known as herpes simplex virus, which show diverse relation with man. Acute disseminated primary infection, recurrent or chronic infection occur. Virus multiplies within lymphocytes and produces antibodies. An infected cell produces 1000 virus particles, with or without envelops, but only 5 to 10 per cent are infectious. 9 to 24 distinct virus proteins have been identified. An unique feature is that HVH produces infection and also reproduces itself in the presence of significant antibody level. This is precisely the cause of great confusion as to whether a primary or recurrent infection is present. Herpes virus antibody complexes may be infectious. Of the two types, type 1 causes classic “cold sores” or “fever blisters”, commonly known as herpes simplex, herpes genitals, herpes labialis. Type 2 HVH is generally acquired venereally and is responsible for nearly 90 per cent of female genital infections. It is frequently associated with other venereal diseases, primarily gonorrhoea and is responsible for disseminated herpes virus infection in the new-born, - a frequently a fatal disease. It has also been very probably associated with cervical cancer, though no definite etiologic relationship between the two has yet been established. Women with either positive culture or positive cytosmear for herpes virus are ten times more likely to have an abnormal cervical cytologic smear indicating premalignant or malignant cervical lesions. Women with herpes virus cervicitis are clearly at risk and need to be identified early and also in pregnancy too.
Biologic characters: Type 1 strains are recovered from the nasopharynx, the skin and the brain. Type 2 strains are uniformly related to the adult genital tract. Isolates have been recovered from the penis, the cervix, endocervix, vagina, vulva, the skin, the spinal fluid and in the infection of the new-born from its brain, liver, lung and adrenals. Virus isolation takes place in rabbit or baby hamster kidney and human foreskin tissue cultures. A characteristic cytopathic effect is evident within 72 hours after the inoculation. These consist of an inclusion of Cowdry, an eosinophilic mass surrounded by a halo in a nucleus with marginated chromatin. Besides, the site of recovery, a number of other properties separate type 1 from type 2 HVH. The type 2 HVH produces:
Immunology: After primary exposure to HVH, humoral antibodies appear, peak during the acute phase of primary infection with HVH-1 and fall during convalescence. Complement enhances the immunoaggregation of herpes virus. In early immune serum, 1gM and 1gG antibodies to type 1-HVH, complement- requiring antibody behaves like monovalent antibody. Each virus- antibody- complement aggregate functions as a single infectious unit. Late immune serum is polyvalent and convalescent serum alone neutralizes virus. Several strains of HVH-2 have been tested but they do not stimulate homotypic neutralizing antibodies. After initial exposure, immunoglobulin M antibodies appear in the serum within a week. Seven days after infection, IgG antibodies appear and anti-herpes virus 1gM synthesis decreases. Complement-fixing antibodies may be measured. Low titers of heterologous antibodies to HVH-1 and HVH-2 are found by tests. HVH-1 1gA complexes are non-infectious while HVH-1 1gC complexes are infectious.
Manifestations of HVH-1: Primary infection with HVH-1 causes acute gingiostomatitis, rhinitis, keratoconjunctivities, meningoencephalitis, eczema herpeticum, whitlow and generalised herpes simplex. The incubation period varies from 2 to 12 days, the average being 6 to 7 days. The route of infection is respiratory. During the acute stage, there is fever, irritability, red swollen gums, a patch of tiny, tense vesicular eruption on the mucous membrane or the skin and the regional non-suppurative lymphadenitis. Viremia may occur or a generalised vesicular eruption may follow usually in crops. Vesicles are small, tense with clear fluid and surrounded by red areola; they rapidly collapse, ulcerate to round or oval, descrete or confluent ulcers, flush with surrounding skin and have grey-white floor. Secondary infection is common. A smear taken from the opened vesicle shows syncytial giant cells undergoing ballooning degeneration. Intranuclear inclusions are seen. Virus can be isolated from the fluid but no bacteria are seen or cultured. Infected secretion from the patient can contaminate others. Herpetic whitlow is an example.
Clinical types: Herpes simplex, follicular conjunctivitis, herpes genitalis, inclusion conjunctivitis, herpes labialis, facial neuralgia, and encephalitis. Persons with pre-existing neutralizing antibodies in serum may suffer from recurrent attacks of herpes. Glans penis, shaft of the penis, the subpreputial mucosa and the urethral mucosa are common sites in the male; while the labia, perineum, vulva, vagina and the cervix are usual sites in the female. The involvement of the cervix and upper vagina is commonly asymptomatic while the involvement of the vulva, perineum and lower vagina is symptomatic and forces patients to seek medical aid. Primary genital herpes virus infection is caused by venereal contact with an infected partner. However, the infection can recur unrelated to venereal or other kinds of contacts. Factors associated with recurrence are changes in temperature, stress, emotion, tension, trauma, menstruation and contraceptive pills. The primary infection is rather severe, longer in duration and is frequently associated with fever, malaise and non-suppurative regional lymphadenitis. The recurrent infection may be similar and confusing. The epidemiology, symptomatology, therapy and association with cervical cytologic change are basically the same for both. Clinically, the genital herpes virus infection resembles that of an oral herpes virus and has an incubation period from 3 to 6 days. Typical vesicular lesions appear at the sites mentioned above. There may be some pruritus, vesicles form and ulcerate. It is the ulcerative stage that prompts the patient to seek medical advice. The scrapings from the base show clusters of epithelial giant cells, intraepithelial multinucleated giant cells and eosinophilic intra-nuclear inclusions in spreads. HVH-1 can be cultured and isolated. The typical cytological changes of the infection with HVH, recognizable with a Papanicolaou preparation occur. Neutralizing antibodies to HVH-2 are found in 35.7 per cent of the patients, of whom some females are likely to develop subsequently carcinoma of the cervix. If the initial infection occurs during pregnancy, transplacental infection of the foetus may ensue. If the cervix or vulva is infected at the time of delivery, prenatal infection of the infant during it transit through the birth canal is likely, and the new-born infant may show signs of fatal viremia by the 4 th to 7 th day of life.
Herpes virus hominis-2: Infection with HVH-2 is, as a rule, a venereally acquired infection. 7 out of 8 female contacts of men with penile herpetic infection showed evidence of Current HVH genital infection. Similarly, 63 of 64 HVH isolates from male genitalia and 155 out of 162 from the female genital tract were HVH-2. This infection is the most common cause of genital vesicles or ulcers found in women and is second only to primary syphilitic chancre in males, as the cause of genital ulcers in males. Teenagers make up ¼ to ½ of patients with genital herpes infection. Neutralizing antibodies to HVH-2 are reported to be present in 35.7 per cent of patients who subsequently develop malignancy of the cervix, but are found in 7.1 per cent in matched controls. However, no etiologic relation between the carcinoma of the cervix and infection with HVH-2 is as yet established. A definite epidemiologic relationship between the viral infection and abnormal Papanicolaou smears and its frequent association with cytologic changes in the cervix are noted. A survey of over 300,000 patients showed some 170 positive smears for virus, giving an incidence of 0.05 per cent. More than half of these had an evidence of premalignant changes or cytologic smears, suggesting that atypical cervical cells may be more susceptible to virus infection. Hence it is necessary to follow such patient closely to determine early the presence of other venereal disease or premalignant changes in cytologic smears of the cervix. The possibility of a serious neonatal infection is a real one. Pregnant woman with herpes virus lesions should be studied carefully to decide the best route of delivery.
In the male, there may be a patch of tiny vesicles on the glans, shaft or prepuce, giving rise to burning, urgency frequency, watery discharge per urethra. During primary infection, fever, malaise, nonsuppurative lymphadenopathy are present. Viremia or benign aseptic meningitis may follow. Virus can be cultivated from the vesicular fluid. In the female, there are tiny vesicles on the labia minora, the inner surface of the labia majora and the cervix. They rapidly ulcerate. The ulcers are tender and do not bleed when scraped. The typical cytologic changes of the infection with herpes simplex virus occur. If the initial infection occurs during pregnancy, transplacental infection of the foetus may follow. In the pregnant state, the disease is more severe and longer in duration than that in the non-pregnant women. In a severe case of vulvovaginitis, there is painful ulceration of the labia, perenium and the vagina; marked oedema of the labia minora, and the clitoris at times cause retention of urine. Secondary infection with streptococcus and monilia is common. This clinical picture of genital herpes virus infection can be easily recognised. Recurrent attacks are likely. Infection of the cervix or vulva at the time of delivery may cause prenatal infection of the infant during its passage through birth canal, and the new-born may suffer from viremia, often fatal. Cutaneous vesicles, affections of lungs, liver, adrenals and the brain are noted.
Diagnosis: Its firm diagnosis in a pregnant woman is imperative. A simple diagnostic test is to scrape the typical lesion, collect the exudate from the ulcer and prepare a standard papanicolaou stained smear. Under microscope, multinucleated giant cells and nuclear inclusion bodies, characteristic of virus herpes hominis can be seen and identified, even in an asymptomatic patient. The most accurate diagnostic technic is to isolate the virus on tissue culture cells by inoculation. Primary rabbit kidney cells or human lung fibroblast cells are commonly used. HVH produces a characteristic cytopathic efforts, which can be recognised in less than 48 hours. This can be further confirmed when an appropriate antiherpes virus serum inhibits this cytopathic effect on the tissue culture. The detection of virus infection thus depends on:
To determine the frequency of virus isolation, some 135 consequent specimens were taken from ulcerative genital lesions of patients diagnosed clinically as HVH. In general virus isolation rate of 50% was noted in these patients. This poor or low rate was attributed to several factors such as delay in inoculation, inexperience, poor techinc etc. Better results could be possible with a little care and experience.
Treatment: Neither killed or attenuated vaccine is shown to be effective. The clinical manifestations, epidemiology, and circumstances of transmission have been now clearly defined and attention has been directed to find out appropriate therapy. Where there is a history of recurrent herpetic virus vulvovaginitis, coupled with clinical exacerbations at term, delivery by cesarean section must be considered. If primary herpes virus vulvovaginitis is detected during gestation, the foetus may be infected during the mother’s viremia and the indication for cesarean section is less clear and certain. Idoxuridine (IDV) is effective tropically; 0.1 per cent solution or 0.5 per cent ointment, frequently applied to the lesions is recommended. For vulvovaginitis, frequent sitz baths containing 100µg I.D.U. per ml in water are suggested. In case of viremia, I.D.U. intravenous infusion 60 mg per kilo body weight per day for 5 days is advised; the drug is dissolved in 5 per cent glucose solution. No more than 20 g be given to a patient. Side reactions are common and need a careful watch.