Latent cervical virus infection as a possible cause of early abortion]

Cervical smears of 50 women who had an abortion were examined by dot-blot hybridization for human papillomavirus (HPV), herpes simplex virus (HSV) types 1 and 2, and cytomegalovirus (CMV) DNA. HPV DNA type 16 or 18 positivity was shown in 17.6% of the cases; in the aborted material, however, it amounted to 30.8%. IgM-positive titres were present in a few cases. In cervical smears of intact pregnancies, positivity for HPV DNA types 6 and 11 was detected in 9.5% and for the HSV DNA types 1 and 2 and CMV DNA in 48.0% of the cases. In this group of patients mostly positive IgM and IgG titers were present.     

Age at first pregnancy and the viral etiology of cervical neoplasia

In a retrospective study of cervical neoplasia, the relative risk estimate (with 95% confidence limits) of a first pregnancy before 22 years of age was 2.6 (1.41;5.12), with regard to the herpes simplex virus (HSV) infection 6 (2.05;23.81) and with regard to the cytomegalovirus (CMV) infection 2 (1.07;3.85). There was no relation between gravidity and cervical neoplasia. After eliminating the confounding effect of the HSV and the CMV infection, the relative risk for cervical neoplasia of a first pregnancy before 22 years of age was estimated to be 2.17 (1.24; 3.80). There was no evidence of a tumor-promoting role of low age at first pregnancy in the possible neoplastic outcome of the HSV and CMV infections. The association between low age at first pregnancy and cervical neoplasia presumably results from the association between a low age at first pregnancy and the occurrence of a causal infectious agent other than HSV and CMV.     

Seroprevalence, incidence of prenatal infections and reliability of maternal history of varicella zoster virus, cytomegalovirus, herpes simplex virus and parvovirus B19 infection in South-Western Finland

Objective   To study seroprevalence and incidence and fetal transmission of varicella zoster virus (VZV), cytomegalovirus (CMV), herpes simplex virus (HSV) types 1 and 2 and parvovirus B19 infections during pregnancy and to evaluate the reliability of maternal past history of VZV, HSV and parvovirus infections.
Design   Prospective study of parturient women.
Setting   South-Western Finland.
Participants   Five hundred and fifty-eight parturient women.
Methods   IgG and IgM antibodies against VZV, CMV, HSV-1 and -2, and parvovirus B19 were measured from maternal serum in the first trimester and at delivery and from cord serum, mother's own information of her past infections was compared with her serological status.
Main outcome measures   Seroprevalence, seroconversions and fetal transmission of VZV, CMV, HSV and parvovirus B19, reliability of maternal history of VZV, HSV and parvovirus B19.
Results   Seroprevalences were 96.2% for VZV, 56.3% for CMV, 54.3% for HSV, 46.8% for HSV-1, 9.3% for HSV-2 and 58.6% for parvovirus B19. Parity was associated with CMV seropositivity, maternal age differed only between HSV-2 seropositive and seronegative women, while area of residence (urban or rural) had no effect. Six seroconversions were observed: two VZV, one CMV and three parvovirus infections. No cases of primary HSV infections occurred. Fetal transmission was observed in two cases of parvovirus infection. No infants with anti-CMV IgM antibodies were born to CMV immunised women. False positive history of chickenpox was given only by 1.5% of the women, history of herpes infections was less reliable, and history of parvovirus infection was unreliable.
Conclusions   Seroprevalence and the risk of viral infections during pregnancy cannot be extrapolated from one pregnant population to another.     

Cell-mediated and humoral immune responses to chlamydial and herpesvirus antigens in patients with cervical carcinoma

Herpes simplex virus (HSV) and Chlamydia trachomatis are both discussed in the etiology of cervical carcinoma. In this study the antibody titers and the T-cell proliferative responses to chlamydial and HSV antigens in patients with cervical intraepithelial neoplasia (CIN) and invasive cervical cancer, have been investigated and compared. The patients with CIN and invasive cancer showed approximately the same degree of immune responses to chlamydial and HSV antigens. Of the patients, 58% showed proliferative T-cell responses to C. trachomatis antigen, 87% to HSV antigens. Chlamydial antibodies were detected in 65% of the patients, while 81% had a positive HSV serology. Our results show a lack of correlation between levels of antibody titer and T-cell responses. It is concluded that patients with CIN and invasive cervical cancer have intact cellular immune responses to both chlamydial and HSV antigens. The eventual role of these infections in the etiology remains unclear.     

Immunological and microbiological studies of midtrimester amniotic fluid

Midtrimester amniotic fluids (MAF) from 73 women undergoing an amniocentesis were studied. The mean immunoglobin G (IgG) level was 34 +/- 14 mg/dl, which is higher than that reported in the third trimester. The maternal serum:MAF IgG ratio was 29 suggesting the blood:MAF barrier is less restrictive than others like the blood:cerebrospinal fluid barrier. Antibodies to herpes simplex virus (HSV) type 1 were detected in 78% of the MAF and the maternal serum:MAF HSV antibody titer ratio was 33. Antibodies to cytomegalovirus (CMV) were found in 84% of the MAF and the maternal serum:MAF CMV antibody titer ration was 40. Whenever either antibody was detected in the maternal serum it was also found in the MAF. No viruses, bacteria, mycoplasma, fungi and chlamyidae were isolated from MAF.     

Cervical and serum IgA and serum IgG antibodies to Chlamydia trachomatis and herpes simplex virus in threatened abortion: a prospective study

The aetiological role of Chlamydia trachomatis (CT) and herpes simplex virus (HSV) was investigated in 189 patients with threatened abortion. Assessment of infection was based on isolation, and on determination of serum immunoglobulin (Ig)G and IgA antibodies as well as cervical IgA antibody levels with new sensitive radioimmunoassay (RIA) techniques. One third of the women were delivered of a healthy infant and two thirds aborted, but the two groups were otherwise clinically similar. By isolation, only 2.7% of the patients were CT-positive, but increased cervical IgA antibody level to CT was detected in 41.3%. The mean level of these local antibodies was similar in both study groups, but the mean levels of serum IgA and IgG antibodies were somewhat higher in the patients who aborted although the difference was not significant. None of the cervical specimens was positive for HSV by isolation but the cervical IgA antibody level to HSV was raised in 47.1% of the patients. Both cervical and serum IgA antibody levels to HSV were significantly raised among the patients who aborted, but there were no differences between the patients with spontaneous abortion and those with a blighted ovum. There was no clear association between CT and abortion, but an association between HSV and abortion is possible. The incidence of raised levels of both CT and HSV IgA antibodies in the cervix was surprisingly high in both groups and the significance of this finding remains to be investigated.     

Cervical and serum IgA and serum IgG antibodies to Chlamydia trachomatis and herpes simplex virus in threatened abortion: a prospective study

Summary. The aetiological role of Chlamydia trachomatis (CT) and herpes simplex virus (HSV) was investigated in 189 patients with threatened abortion. Assessment of infection was based on isolation, and on determination of serum immunoglobulin (Ig)G and IgA antibodies as well as cervical IgA antibody levels with new sensitive radioimmunoassay (RIA) techniques. One third of the women were delivered of a healthy infant and two thirds aborted, but the two groups were otherwise clinically similar. By isolation, only 2.7% of the patients were CT-positive, but increased cervical IgA antibody level to CT was detected in 41.3%. The mean level of these local antibodies was similar in both study groups, but the mean levels of serum IgA and IgG antibodies were somewhat higher in the patients who aborted although the difference was not significant. None of the cervical specimens was positive for HSV by isolation but the cervical IgA antibody level to HSV was raised in 47.1% of the patients. Both cervical and serum IgA antibody levels to HSV were significantly raised among the patients who aborted, but there were no differences between the patients with spontaneous abortion and those with a blighted ovum. There was no clear association between CT and abortion, but an association between HSV and abortion is possible. The incidence of raised levels of both CT and HSV IgA antibodies in the cervix was surprisingly high in both groups and the significance of this finding remains to be investigated.     

Chlamydia trachomatis and herpes simplex virus IgA antibodies in cervical secretions of patients with cervical atypia

The association of Chlamydia trachomatis (CT) and herpes simplex virus (HSV) with malignant or premalignant changes in the cervix uteri was studied by determining immunoglobulin A (IgA) antibodies in the cervical secretions of 28 women with inflammatory, 28 with dysplastic, 7 with malignant changes of the uterine cervix, and 26 healthy controls. In cervical secretions IgA antibodies to CT were found in 24 of 35 (69%) patients with malignant or premalignant changes, in 11 of 28 (39%) with cervicitis and in 3 of 26 (12%) controls. IgA antibodies to HSV were found in 10 of 35 (28%) patients with malignant atypic or dysplasia but in none of the women with cervicitis or the controls. The highest frequency of antibodies was found in the patients with cervical carcinoma. Serum IgA antibodies to CT and HSV were found equally on the patients and the controls. Our results suggest that in patients with cervical atypic, local IgA CT antibody production occurs. Whether this association is aetiological or coincidental can not be concluded from this study.     

The use of antiviral drugs during the neonatal period

Parenteral therapy of viral infections of the newborn and infant began with vidarabine (adenine arabinoside) for the treatment of neonatal herpes simplex virus (HSV) infections in the early 1980s. Acyclovir has become the treatment of choice for neonatal HSV infections and a variety of other herpesvirus infections. Ganciclovir is beneficial for the treatment of congenital cytomegalovirus (CMV) infections involving the central nervous system (CNS). This article reviews the use of acyclovir and ganciclovir in the treatment of neonatal HSV and congenital CMV infections. A brief summary precedes a detailed discussion of available established and alternative therapeutics.     

Is there an association between fetal viral infection and fetal malformation? I. Detection of specific IgM antibodies in the serum of malformed fetuses

Determinations of IgG and IgM antibodies specific for cytomegalovirus (CMV), herpes simplex virus (HSV1), herpes simplex virus (HSV2), varicella-zoster virus (VZV), rubella, echo, Coxsackie and morbilli viruses were performed in 20 sera from malformed fetuses. Demonstration of a fetal infection by increased fetal serum IgM permits linkage to a detected fetal malformation. In parallel, 14 maternal sera and 17 amniotic fluid samples were examined. Laser nephelometry (a quantitative method) was used for the determination of IgM and IgG class immunoglobulins. None of the fetal sera were found to contain IgM class antibodies specific for the viral antigens studies. While IgM CMV-specific antibodies were present in one maternal serum, the specific IgM was absent in the fetus. The absence of specific IgM antibodies appears to warrant the conclusion that the malformed fetuses were uninfected by any of the above viruses. IgM antibodies were detected in two fetal sera by quantitative methods. The IgM antibodies present in two fetuses probably were generated in response to some other introduced antigen.     

Human papillomavirus screening for women with atypical Papanicolaou smears.

A study was undertaken to evaluate the utility of human papillomavirus (HPV) DNA screening and colposcopy in the management of women whose Papanicolaou smears demonstrated atypia less than dysplasia. Fifty patients whose initial Papanicolaou smears were interpreted as showing atypia less than dysplasia were evaluated for the presence of HPV 16 DNA in exfoliated cervicovaginal cells and for histologic findings on biopsy. Those 50 patients were compared to two groups of patients: one consisting of 124 patients with biopsy-documented cervical intraepithelial neoplasia (CIN) and another of 112 patients with normal Papanicolaou smears. The presence of HPV 16 DNA was confirmed with Southern analysis in 46% of patients with atypical Papanicolaou smears, 46% with confirmed CIN and 11.6% with normal Papanicolaou smears. The 50 patients with atypical smears underwent colposcopically directed cervical biopsies, revealing the following results: 14 (28%) had normal histology, 29 (58%) had koilocytosis without dysplasia, and 7 (14%) had CIN. HPV 16 DNA was present in exfoliated cervicovaginal cells from a large percentage of patients from each category (50% of patients with normal histology, 41.2% with koilocytosis and 57% with CIN). HPV 16 DNA screening did not predict which patients with atypical smears had underlying CIN. Colposcopically directed biopsy remains the evaluation method of choice.     

Isolation of herpes simplex virus from the genital tract during symptomatic recurrence on the buttocks

OBJECTIVE: To estimate the frequency of isolation of herpes simplex virus (HSV) from the genital tract when recurrent herpes lesions were present on the buttocks. METHODS: Data were extracted from a prospectively observed cohort attending a research clinic for genital herpes infections between 1975 and 2001. All patients with a documented herpes lesion on the buttocks, upper thigh or gluteal cleft ("buttock recurrence") and concomitant viral cultures from genital sites including the perianal region were eligible. RESULTS: We reviewed records of 237 subjects, 151 women and 86 men, with a total of 572 buttock recurrences. Of the 1,592 days with genital culture information during a buttock recurrence, participants had concurrent genital lesions on 311 (20%, 95% confidence interval [CI] 14-27%) of these days. Overall, HSV was isolated from the genital region on 12% (95% CI 8-17%) of days during a buttock recurrence. In the absence of genital lesions, HSV was isolated from the genital area on 7% (95% CI 4%-11%) of days during a buttock recurrence and, among women, from the vulvar or cervical sites on 1% of days. CONCLUSION: Viral shedding of herpes simplex virus from the genital area is a relatively common occurrence during a buttock recurrence of genital herpes, even without concurrent genital lesions, reflecting perhaps reactivation from concomitant regions of the sacral neural ganglia. Patients with buttock herpes recurrences should be instructed about the risk of genital shedding during such recurrences. LEVEL OF EVIDENCE: II-2.     

Clinical course and diagnosis of genital herpes simplex virus infection and evaluation of topical surfactant therapy.

A prospective study of 37 men and 32 women with culture-proved genital herpes simplex virus (HSV) infection was undertaken to characterize the clinical manifestations of the disease and effects of topical therapy with Nonoxynol 9, a nonionic surfactant active in vitro against HSV. The duration of pain, lesions, and virus shedding was significantly longer in initial than in recurrent genital HSV infection. Cervical HSV shedding occurred in 11 of 13 initial infections versus two of 19 recurrences (p less than 0.001). Type 1 HSV caused seven of 29 initial and none of 40 recurrent infections (p less than 0.01). Clinical recurrences within six weeks were detected more often in men than in women and were unrelated to the menstrual cycle. The influence of coitus on recurrence is unclear. Papanicolaou smears were transiently abnormal (Class II) in four (12.5 per cent) of 32 female patients. Evidence of herpesvirus was detected cytologic smears from only 28 (41 per cent) of 69 culture-proved external lesions and three (23 per cent) of 13 culture-positive cervices. Serology was also of limited diagnostic value except in testing paired sera from initial infections. The topical therapy had no beneficial effect.     

自然流产孕妇巨细胞病毒与单纯疱疹病毒感染的研究

目的:探讨自然流产孕妇中巨细胞病毒与单纯疱疹病毒感染的状况。方法:留取132例自然流产孕妇及113例因计划外妊娠行人工流产者(对照组)的绒毛组织,用荧光定量多聚酶链反应技术检测绒毛组织标本中巨细胞病毒和单纯疱疹病毒的基因数量。结果:自然流产组孕妇中巨细胞病毒阳性率为16.67％(22/132),对照组阳性率为1.91％(2/113),差异有显著性(P<0.005)。自然流产组孕妇单纯疱疹病毒阳性率为17.42％(23/132),对照组阳性率为2.65％(3/113),差异有显著性(P<0.005)。两者皆为阳性者自然流产组孕妇有12例,占9.09％,对照组均为阴性。治疗后复查巨细胞病毒和单纯疱疹病毒阴性的妇女再次妊娠成功。结论:巨细胞病毒和单纯疱疹病毒均可导致孕妇发生自然流产,且巨细胞病毒及单纯疱疹病毒易合并存在,因此,对自然流产孕妇应同时检测巨细胞病毒及单纯疱疹病毒,针对病因进行治疗,提高下一次妊娠成功率。     

女性下生殖道感染细胞病理学诊断的价值

目的：评价女性下生殖道感染细胞学诊断的标准和意义，方法：1997年5月至2001年5月Papnet辅助宫颈细胞学检查98317例，按TBS诊断标准进行细胞病理学诊断。重点病毒感染，细菌性感染，滴虫性感染和念珠菌性感染进行分析总结。结果：疱疹病毒感染20例，HPV感染2564例（2．6％），滴虫感染3349例（3．4％），念珠菌性感染4925例（5．0％），细菌性感染3519例（3．6％）。结论：宫颈涂片细胞病理检查方法为女性下生殖道感染诊断主要方法，具有肯定诊断价值。     

Characteristics and management of pregnancy in women with genital herpes simplex virus infection

The natural history of genital herpes simplex virus (HSV) infections was investigated in 83 pregnancies in 78 women, and the information was used to determine the need for cesarean section in these women. We studied 163 recurrent episodes with HSV cultures from the cervix and from vulvar lesions every 1 to 3 days. Cervical HSV cultures were obtained weekly from asymptomatic women beginning at 32 weeks' gestation, and 14/462 (3.03%) of these cultures were positive. Cervical cultures obtained during culture-positive vulvar recurrences demonstrated concomitant cervical HSV shedding in 25/165 (15.2%) cultures. Mean duration of 26 genital HSV recurrences was 4.6 +/- 2.8 days with a range of 1 to 13 days. The mean interval between culture-positive HSV recurrences was 59.2 +/- 42.1 days, but many (14/76 = 18%) intervals were less than 21 days. Viral cultures were already positive in 92.3% of cases after 4 days' incubation, so they could be used effectively to determine route of delivery. Following a cautious set of criteria for vaginal delivery in these women, 69.1% were delivered of their infants vaginally and no neonatal morbidity caused by HSV was encountered. Information about the natural history of genital HSV infections obtained from frequent third-trimester viral cultures can be used to manage pregnancy and will reduce the need for cesarean section while avoiding neonatal HSV morbidity.     

Prevalence of antibodies to herpes simplex virus and frequency of HLA antigens in patients with preinvasive and invasive cervical cancer

Previous herpes simplex virus type 2 (HSV-2) infections are known to predispose women for the development of cervical cancer, but causal relationship between the virus and the cancer has never been proven. Forty-six patients with cervical carcinoma (13 with preinvasive lesions and 33 with various stages of invasive disease) were selected for the present study. Among the patients 96% were seropositive for the presence of antibodies to herpes simplex virus compared to 87% of the 30 controls. Antibodies specific for HSV-2 were found in the sera from 24% of the patients and 17% of the controls by the use of an immunoblotting test. Patients and controls were typed for HLA-A,B,C and D/DR antigens, but no significant associations were found.     

Genital herpes simplex virus infections: laboratory confirmation in diverse patient groups

The laboratory diagnosis of genital herpes simplex virus (HSV) infections in various patient groups with diverse clinical manifestations including asymptomatic pregnant women with history of genital herpes and in a high prevalence group consisting of male patients with recurring genital ulcerations is described. HSV was detected by conventional cell culture and also by a CPE-enhancement technique using human embryonic lung fibroblasts (MRC-5) and Vero cells with subsequent typing of isolate by HSV type-specific monoclonal antibodies. A definite improvement in HSV diagnosis was noted by the use of the CPE-enhancement technique with the reduction of turn-around time to 24 h at which 61.1% and 50% isolation rates were detected in MRC-5 cells in comparison to 38.9% and 16.6% by conventional cell culture in the high prevalence patient population and asymptomatic pregnant women, respectively. Delayed development of CPE and reduced isolation rates were detected using Vero cells. Follow-up sampling of subsequent episodes of genital ulcerations in those with history of recurrence but an initial negative cell culture result, increased the isolation rate substantially and enabled the confirmation of diagnosis of genital HSV infection.     

Herpes simplex virus and human papillomavirus infection in cervical disease in Argentine women.

The aim of the present study was to determine that prevalence of herpes simplex virus (HSV) type 1 and 2 in cervical samples from Argentine women and to assess the role of HSV-2 in cervical cancer. A sample of 79 normal and 200 neoplastic cervical tissues (35 invasive cervical carcinomas, 75 high-grade squamous intraepithelial lesions, 79 low-grade squamous intraepithelial lesions and 11 abnormal squamous cells of undermined significance) was analyzed for herpes simplex and human papillomavirus DNA using the polymerase chain reaction method. Viral genotyping was performed by single strand conformation polymorphisms and restriction fragment length polymorphisms. The overall prevalence of HSV was 21.5% in controls and 29% in cases. Among women with normal cytology, herpes simplex prevalence in HPV positive (20.8%) women was approximately the same as in negative (21.8%) women. HPV- and age- adjusted ORs of high-grade squamous intraepithelial lesions and invasive cervical carcinomas for HSV-2 were 1.4 (p = 0.6) and 1.6 (p = 0.5), respectively. The obtained results indicated that herpes simplex virus may not be involved in cervical cancer development. Future investigations are needed to provided conclusive evidence on the role of this pathogen in cervical cancer.     

Cytologic evidence of the association of different infective lesions with dysplastic changes in the uterine cervix.

Cervical smears from 4055 women were examined and classified as per WHO criteria. 873 (21.53%) smears revealed dysplastic changes. The dysplastic smears were further examined cytologically for the presence of Chlamydia trachomatis, Herpes simplex virus type-2, Human papilloma virus, Trichomonas vaginalis and Candida albicans. Chlamydia was found to be the commonest micro-organism associated with cervical dysplasia followed by Herpes simplex virus type-2 and Human papilloma virus. The association of Trichomonas and Candida with cervical dysplasia was found to be insignificant. Cervical dysplasia associated with Herpes simplex virus type-2 commonly occurred in the early reproductive life. The data observed in this study provide useful baseline information for detecting the subjects harbouring the infective microbes in the cervical epithelium.