Distribution of Chlamydia trachomatis ompA genovars and the new variant of C. trachomatis in the Göteborg area, Sweden.

The aims of this study were to assess the proportion of the new variant of Chlamydia trachomatis (nvCT) and the distribution of ompA genovars among C. trachomatis-positive patients in the Göteborg area, Sweden. Consecutive urine samples positive for C. trachomatis using BD ProbeTec ET (177 patients, 88 men and 89 women) were collected. An nvCT-specific real-time polymerase chain reaction (PCR) assay was used to investigate the nvCT prevalence. To identify the genovars, a 990-bp ompA DNA segment from 105 specimens was sequenced. Seventeen percent (30/177) of all specimens contained nvCT. Nine different genovars were identified. About 50% were of genovar E, followed by F 16%, G 11%, K 8%, and D 5%, representing about 90% of the specimens in Göteborg. The occurrence of nvCT and the dominance of genovar E in Göteborg is similar to those in other areas of Sweden. To cover about 90% of the C. trachomatis infections in Sweden, the serovars D, E, F, G, and K should be included in future vaccines based on the major outer membrane protein.

Viral and bacterial aetiologies of male urethritis: findings of a high prevalence of Epstein-Barr virus.

Male urethritis is one of the most common sexually transmitted infections (STIs). However, the aetiology is still unclear in many cases. In this study the prevalences of Epstein-Barr virus (EBV), herpes simplex virus type 1 (HSV-1), HSV-2, cytomegalovirus (CMV), adenovirus, Chlamydia trachomatis, Mycoplasma genitalium and Ureaplasma urealyticum (including subtyping) were investigated. Samples from 112 male STI attendants with microscopically verified urethritis and from a control group of 103 men without clinical or microscopic signs of urethritis were analysed. Prevalences in the urethritis group compared with the controls were as follows: EBV 21%, 6% (P < 0.01); C. trachomatis 15%, 3% (P < 0.01); M. genitalium 6%, 1% (P = 0.067) and U. urealyticum 10%, 10% (ns). The results for HSV-1, HSV-2, CMV and adenovirus were negative in patients, and therefore not analysed in the controls. EBV was shown to be an independent predictor of urethritis and may play a role in its pathogenesis.

The microenvironment of vulvar skin in women with symptomatic and asymptomatic herpes simplex virus type 2 (HSV-2) infection.

BACKGROUND: It is not known why some individuals infected with herpes simplex virus type 2 (HSV-2), experience frequent recurrences, while most of those infected have a completely silent infection. OBJECTIVE: We wanted to study if local factors in the skin could explain this difference. DESIGn 21 HSV-2 seropositive patients, 10 with history of >8 clinical recurrences a year (symptomatics) and 11 without symptoms of genital herpes (asymptomatics) were included. All had to answer a questionnaire. With standardised methods, the skin temperature, pH, and the skin barrier function, expressed as transepidermal water loss (TEWL) and skin capacitance, were measured on labium majus and perineum. Culture for bacteria was performed from the same regions. RESULTS AND CONCLUSION: No significant differences in terms of pH and skin barrier function were registered between symptomatic and asymptomatic patients. Asymptomatic patients had a tendency (0.06) to a higher colonisation with lactobacilli on labium majus than symptomatic patients.

Characterization of T-cell reactive epitopes in glycoprotein G of herpes simplex virus type 2 using synthetic peptides.

We have previously shown that the CD4+ T-cell response to herpes simplex virus type 2 glycoprotein G-2 is type-specific and can thus be used to evaluate herpes simplex virus type 2-specific T-cell responses in individuals with a concomitant herpes simplex virus type 1 infection. In this study we have followed the glycoprotein G-2-specific T-cell responses over time, and also tried to identify T-cell epitopes in the membrane bound portion and the secreted portion of glycoprotein G-2 using synthetic peptides spanning the whole amino acid sequence of glycoprotein G-2. We found that the magnitude of the glycoprotein G-2-specific response varied considerably in infected individuals over time, even though all patients responded to at least one of the two glycoproteins at all time-points examined. We could also document strong T-cell responses to synthetic peptides from the secreted glycoprotein G-2 but only low responses to synthetic peptides corresponding to sequences from the heavily glycosylated membrane-bound glycoprotein G-2. We were able to map an immunogenic region (amino acid 31-125) within the secreted glycoprotein G-2. This region of the glycoprotein induced proliferative responses in 47% of the herpes simplex virus type 2-infected individuals. However, we were not able to identify any universal T-cell epitope.

Mannan-binding lectin modulates the response to HSV-2 infection.

Viruses have developed numerous strategies to escape recognition by the immune system. However, some viruses such as herpes simplex virus-2 (HSV-2) are recognized by initiators of the complement system, e.g. mannan-binding lectin (MBL). To study the effects of MBL deficiency during viral infection we have chosen a model of generalized HSV-2 infection. We infected MBL-A and MBL-C double knock-out mice (DKO) with HSV-2 via the intraperitoneal (i.p.) route. DKO mice cleared HSV-2 from the liver less efficiently than the comparable wild-type animals. The impairment to effectively neutralize HSV-2 correlated with compromised liver function as measured by increased plasma levels of alanine-amino transferase. No differences in the viral burden were found in other organs such as spleen or brain. Thus, MBL-mediated protection was limited to the effects of preservation of liver homeostasis. Reconstitution with recombinant human MBL before and during the HSV-2 infection dramatically lowered the viral titres in the liver. Taken together, the data show that MBL modulates the response to HSV-2 in mice by affecting neutralization of the virus. To analyse if MBL plays a role in establishment and progression of human HSV-2 infection we analysed MBL levels in the serum samples from asymptomatic (virus-exposed people who have never displayed symptoms of HSV-2 infection) and symptomatic HSV-2 patients (people with recurrent HSV-2 infections). We found that the frequency of the MBL deficiency (<100 ng/ml) was higher in the symptomatic group and significantly different from that in the asymptomatic group (P = 0.0369). This suggests that lack of MBL-mediated complement activation increases susceptibility to viral infection.

Recurrent genital herpes in a population attending a clinic for sexually transmitted diseases.

Patients with recurrent genital herpes attending a sexually transmitted disease clinic were studied and transmission of the infection was elucidated by evaluating serostatus in their partners. Of 84 patients attending for recurrent genital herpes, 94% had a herpes simplex virus type 2 (HSV-2) infection and only 6% (5 patients) a type 1 infection. The mean age of the patients was 36 years and the duration of their infection was up to 37 years (median 4 years). In most patients the number of recurrences had not decreased between the first year and the last year. About half had experienced a more severe first episode infection. Of the patients, 64% were not aware of asymptomatic shedding and the risk of sexual transmission without clinical symptoms. Of 67 steady partners of patients with genital HSV-2, 15% had a history of genital herpes. By HSV serology, HSV-2 antibodies (indicating subclinical genital herpes) were demonstrated in more than half of the partners. The duration of the relationship or condom use did not seem to influence the frequency of transmission to the partner, which may indicate an individual susceptibility for acquiring a genital HSV-2 infection. Eleven per cent of the patients were on suppressive antiviral therapy, while 39% had no experience of antiviral therapy. Type-specific HSV serology was found to be of value in counselling partners of patients with genital herpes.

First episodes of genital herpes in a Swedish STD population: a study of epidemiology and transmission by the use of herpes simplex virus (HSV) typing and specific serology.

OBJECTIVES: To determine the proportion of herpes simplex virus type 1 (HSV-1) and HSV type 2 (HSV-2) in first episodes of genital herpes. To evaluate the use of HSV specific serology for classifying first episodes of genital herpes and for defining HSV serostatus in the patients' sexual partners. METHODS: 108 consecutive patients with first episodes of genital herpes seen at three STD clinics in Sweden from 1995 to 1999 were included in the study. HSV culture and typing were performed and serum was tested for antibodies against a type common HSV antigen and a type specific HSV-2 antigen, glycoprotein G2 (gG2). A structured interview including questions about sexual behaviour and sexual partners was taken. "Steady" partners were offered a blood test for HSV serology and counselling. RESULTS: Of 108 patients, 11 had a negative HSV culture. Of the 97 who were HSV culture positive, 44% (43/97) were typed as HSV-1 and 56% (54/97) as HSV-2. For 86 of these 97 patients, HSV serology from the initial visit was available. Of 52 primary infections, thus initially seronegative, 64% were HSV-1 infections and of 19 female primary infections 16 (84%) were HSV-1. In 17% the first episode of genital herpes corresponded to the first clinical recurrence of an infection acquired earlier in life. There was a significant correlation between having orogenital sex and being infected with HSV-1 and also a history of labial herpes in the partner. Only 20% of partners of patients with an HSV-2 infection had a history of genital herpes. CONCLUSIONS: Almost half of first episodes of genital herpes are caused by HSV-1. In young women with a primary genital infection, HSV-1 is much more frequent than HSV-2. Besides HSV typing, we found specific HSV serology of value for classifying first episodes and for diagnosing a subclinical HSV-2 infection in partners. Anamnestic data supported the suggestion that the orogenital route of transmission was common in genital HSV-1 infections.

Sexually transmitted diseases and sexual behavior in men attending an outpatients' clinic for gay men in Gothenburg, Sweden.

The prevalence of sexually transmitted diseases (STDs) diagnosed in men attending an outpatients' clinic for gay men from 1983 to 1997 and the results from a questionnaire survey concerning sexual behaviour conducted in 1994-96 are reported. The prevalence of gonorrhoea and chlamydia has decreased during the period, although in 1997 there was a micro-epidemic of gonorrhoea in gay men in Gothenburg. The results indicate that the reservoir of syphilis and hepatitis B in the gay population was eradicated during the early 1980s. Of altogether 1,808 HIV tests performed, 3.0% (n=55) were positive. In the questionnaire, the majority claimed they had sufficient knowledge on how HIV is transmitted, while 11.3% stated that they lacked that knowledge. Half of the patients stated that they had a steady sexual partner. Starting a new relationship was the most common reason (69%) for HIV screening. The use of condoms in anal and oral sex was 88% and 31%, respectively. Of those practising anal sex, 4% stated that they never used a condom. The prevalence of STDs has decreased in this period of time and safer sex is fairly well accepted, but the results also tell us that there is still a need for dedicated clinics like ours.

Occurrence and treatment of Mycoplasma genitalium in patients visiting STD clinics in Sweden.

Two hundred and thirty-three men and 85 women visiting STD clinics in western Sweden between April 1997 and March 1998 were examined for Mycoplasma genitalium and Chlamydia trachomatis. The bacteria were identified by the polymerase chain reaction (PCR) technique. Three women (3.5%) and 18 men (7%) were positive for M. genitalium. Seventeen (14%) of the 115 men with urethritis were infected but only one of the men was without urethritis. After treatment with tetracyclines for 10 days, one woman and 8 of the 13 men still harboured M. genitalium. M. genitalium-infected men did not have more life-time partners than other men visiting STD clinics. More men positive for M. genitalium gave a history of previous urethritis but the difference was not significant.

[Bone marrow depression after azathioprine. New discoveries on an old drug]. / Benmärgshämning efter azatioprin. Nya rön om ett gammalt läkemedel.

Azathioprine, a cytostatic and immunosuppressive drug in use for some 30 years, can give rise to life-threatening neutropenia and thrombocytopenia. This may be caused by unexpectedly high concentrations of cytotoxic metabolites due to abnormally slow inactivation of 6-mercaptopurine (6-MP) by thiopurine S-methyltransferase (TPMT) and/or xanthine oxidase. Low TPMT activity may be due to genetic polymorphism or interaction with drugs such as salicylic acid derivatives, while xanthine oxidase may be inhibited by allopurinol. High TPMT activity, on the other hand, may hamper cytostatic treatment. Safer and more effective treatment with azathioprine and its metabolite 6-MP becomes possible with new laboratory methods for pharmacotherapy monitoring.

Glycoprotein G of herpes simplex virus type 1: identification of type-specific epitopes by human antibodies.

Serological diagnosis of herpes simplex virus (HSV) infections requires assays based on antigens that expose type-specific determinants. This study was designed to outline the B-cell epitopes of the type-specific glycoprotein G-1 (gG-1) of HSV type 1 (HSV-1), by investigating the reactivity of human anti-gG-1 antibodies, purified from 21 HSV-1-isolation-proven patient sera, to cellulose-bound synthetic peptides spanning the entire gG-1 sequence. The epitope mapping demonstrated that these antibodies bound preferentially to antigenic determinants that localized to regions with a high degree of amino acid similarity to the corresponding glycoprotein in HSV-2, gG-2. In spite of this, the purified anti-gG-1 antibodies were found to be non-reactive to native gG-2 antigen, as well as to overlapping gG-2 peptides, thus supporting the role of gG-1 as a prototype HSV-1 type-specific antigen. One immunodominant region, delimited by amino acids 112-127, reacted with all purified anti-gG-1 antibodies and may be of interest for the further development of a peptide-based HSV-1 type-specific seroassay.

PCR detection of Epstein-Barr virus, herpes simplex virus and human papillomavirus from the anal mucosa in HIV-seropositive and HIV-seronegative homosexual men.

This study aimed to examine the prevalence of the Epstein-Barr virus (EBV), herpes simplex virus (HSV) and human papillomavirus (HPV) in the anal and oral mucosa of homosexual men with and without HIV infection and to correlate these findings to CD4+ count and anal cytology. Anal and oral cell samples from 20 HIV-infected and 14 non-infected homosexual men attending the STD clinic at Sahlgrenska University Hospital, Goteborg were examined for EBV, HSV and HPV by the polymerase chain reaction (PCR) technique. Proctoscopy was performed in all patients and swabs for cytology were taken. EBV was demonstrated in 32% (6/19) of anal cell samples from the HIV-positive group but in none from 13 HIV-negative men. Asymptomatic shedding of HSV type 2 from the anus was detected in 3 of 19 HIV-positive men, all with low CD4+ counts and abnormal cytology. No patient in the HIV-negative group shed HSV from the anus. HPV was demonstrated in 16 of 17 anal cell samples in the HIV-infected group and in 7 of 13 HIV-negative men. More than one HPV type was detected in 7 HIV-infected men. Five (29%) of 17 HIV-positive patients exhibited abnormal cytology whereas none did so in the HIV-negative group. Those with abnormal cytology all had CD4+ counts below 0.35 and were infected with multiple HPV types including HPV 16/18. In conclusion, our results demonstrate an enhanced expression of HPV as well as EBV from the anus in HTV-infected homosexual men. In this small number of patients EBV was not related to low CD4+ count or to abnormal cytology.

Changes in sexual behaviour focusing on condom use in STD clinic attenders in Göteborg, Sweden, from 1989 to 1994--a questionnaire survey.

During the 4 years from 1989/1990 to 1994 an increase in the use of condoms was registered. A high frequency of condom failures was reported and probably reflects inappropriate use. More efforts should be made to educate people how to use the condom. The impact of alcohol intake as a risk factor for unsafe sex seems to be significant and should also be stressed in educational safer sex programmes. STD patients are a well-motivated group for information about safer sex and condom use. Health workers in STD clinics have an important task in this context.

Are acetowhite lesions of the cervix correlated to the presence of Epstein-Barr virus DNA?

The purpose of this study was to investigate whether Epstein-Barr virus (EBV) is associated with acetowhite lesions of the portio cervix, demonstrating koilocytosis and/or cervical intraepithelial neoplasia (CIN) I-III. The study group comprised 37 women admitted to the Department of Gynaecology and Obstetrics, Sahlgrenska University Hospital, Göteborg because of pathological colposcopy or cytology of the portio cervix. Colposcopically, all exhibited acetowhite lesions of the portio cervix. Cells were sampled with a cytobrush for examination for EBV and human papillomavirus (HPV) DNA by polymerase chain reaction (PCR) and a biopsy was taken for histopathology. Biopsies from 5 patients positive for EBV by PCR in cervical cell samples were examined by an in situ hybridization technique for EBER (Epstein-Barr virus encoded RNA), RNAs expressed in latent EBV infection. The control group consisted of women attending the Department of Dermato-Venereology at the same hospital for STD check-up. These had a normal cytology and no signs of acetowhiteness of the portio cervix. In the study group, EBV DNA was found in 30% and HPV DNA in 51%. In the control group 57% exhibited EBV DNA and 23% HPV DNA. EBV was not found to be a predictive factor in the development of koilocytosis and/or CIN I-III. HPV was a predictive factor in acetowhite, koilocytotic lesions. No expression of EBER was found in the 5 biopsies examined by in situ hybridization.

Demonstration of Epstein-Barr virus DNA and human papillomavirus DNA in acetowhite lesions of the penile skin and the oral mucosa.

Oral hairy leukoplakia (OHL), thought to be caused by Epstein-Barr virus (EBV), shows similar histological and clinical features to human papillomavirus (HPV)-related acetowhite lesions of the vulva. We thus aimed to investigate the role of both HPV and EBV in men with acetowhite lesions of the penis. HPV but not EBV was significantly associated with penile acetowhite lesions showing koilocytosis compared with normal penile skin (12/20 versus 5/20, P < 0.02). HPV (5/20) and EBV (6/20) was detected in oral mucosa of some of these individuals. These results confirm an aetiological association between HPV and acetowhite penile lesions showing koilocytosis. HPV and EBV carriage in the oral mucosa is relatively common in young sexually active men.

Prevalence of Epstein-Barr virus and human papillomavirus in cervical samples from women attending an STD-clinic.

A group of 91 women attending the STD-clinic, Department of Dermatovenereology, Sahlgrenska Hospital, Gothenburg, were screened for EBV DNA and HPV DNA of the cervix with the PCR-technique. Presence of EBV DNA was demonstrated in 35 (38%) women and HPV DNA in 30 (33%) women. Fourteen (15%) women had both EBV DNA and HPV DNA present. Without the colposcope 20 of these women had macroscopic signs of HPV infection on the vulva and/or vagina and 71 had no signs of infection. Presence of EBV DNA was not correlated to clinical signs of HPV infection.

Human papilloma virus infection among women attending an STD clinic correlated to reason for attending, presence of clinical signs, concomitant infections and abnormal cytology.

The purpose of this study was to demonstrate the prevalence of cervical human papilloma virus (HPV) infection correlated to reason for attending an STD clinic, presence of clinical signs of HPV infection, concomitant infection and abnormal cytology. Samples from the cervical canals of 588 consecutive women attending the STD clinic, Department of Dermato-Venereology, Sahlgrenska Hospital, Gothenburg, were taken with a Cytobrush for detection of HPV DNA with the dot blot/Southern-blot technique. Visible condylomata, i.e. filiform or papular condylomata, were registered. Acetic acid test and colposcopy were not routinely performed. Cytological examination was performed as well as isolation of Chlamydia trachomatis on Mc Coy's cells and culture on Sabouraud agar for Candida albicans. The prevalence of HPV DNA was 8% (48/588). In the group of 233 women attending because of concern about HPV infection, 94 (40%) had visible signs of HPV infection and 30 (13%) were positive for HPV DNA in the cervix. In 355 women attending for other reasons, such as discharge, pruritus or STD check-up, 4 (1%) had visible signs of HPV infection and 18 (5%) were HPV DNA positive. Of 98 women with visible signs of vulvar/vaginal HPV infection, 33 (34%) were HPV-positive in the cervix with a commercial Southern-blot test. Of 490 patients without visible signs of HPV infection, 15 (3%) were HPV-positive in the cervix. In the group of HPV-positive women a positive culture for Candida was demonstrated in 26% (11/43), Compared to 16% (79/504) of the HPV-negative women.(ABSTRACT TRUNCATED AT 250 WORDS)

Demonstration of Epstein-Barr virus DNA in acetowhite lesions of the vulva.

Acetowhite lesions in the vulva disclosing koilocytosis have been related to infection by human papilloma virus (HPV). Because of the clinical resemblance of these lesions to oral hairy leukoplakia (OHL), and EBV-manifestation, 23 women with acetowhite koilocytotic lesions in the vulva were examined. The PCR-technique was used to detect EBV DNA as well as HPV DNA in 17% of 23 patients examined. In a control group of 19 patients EBV DNA was detected in 11% and HPV DNA in 42% of cell samples from normal vulvar mucosa. EBV DNA has not previously been demonstrated in the vulvar mucosa, and this virus might be related to subclinical acetowhite lesions.