Anal Squamous Intraepithelial Lesions (SILs) in Human Immunodeficiency Virus-Positive Men Who Have Sex With Men: Incidence and Risk Factors of SIL and of Progression and Clearance of Low-Grade SILs.

BACKGROUND: Human immunodeficiency virus (HIV)-positive men who have sex with men (MSM) are at risk of anal squamous cell carcinoma. Data are limited on the natural history of the precursor to this carcinoma, anal squamous intraepithelial lesions (SILs). METHODS: HIV-positive MSM were screened for histopathological SILs by means of high-resolution anoscopy (HRA). For participants without SILs at baseline, we estimated the cumulative incidence and risk factors for SILs. For those with low-grade SILs (LSILs) at baseline, the risk of progression to high-grade SILs (HSILs) and the clearance rate were estimated at the lesion level. RESULTS: Of 807 men without SILs at baseline, 107 underwent follow-up HRA between 1 to 4.5 years later. At the second visit 18 men (16.8%) showed LSIL, and 25 (23.4%) HSIL. Age was associated with incident LSILs (adjusted odds ratio [aOR], 2.10 per 10-year increase in age; P = .01). Of 393 men with LSILs at baseline, 114 underwent follow-up HRA 0.5 to 2.5 years later. Of the 177 LSILs found at baseline, 87 (49.2%) had cleared at the second visit, and 29 (16.4%) had progressed to HSILs. CONCLUSION: Incident LSILs and HSILs were common during follow-up among HIV-positive MSM without dysplasia at baseline. Among men with LSILs at baseline, nearly half of these lesions cleared, and a small portion progressed.

[Syphilis epidemic and an increase of the number of HIV infections among homosexual men attending the Amsterdam venereal disease clinic]. / Syfilisepidemie en stijging van het aantal HIV-infecties onder homoseksuele mannen op de Amsterdamse SOA-polikliniek.

The registered number of cases of early infectious syphilis and of (ano)genital gonorrhoea among the attendees of the outpatient clinic for sexually transmitted diseases of the Amsterdam municipal health service shows a strong increase for both diagnoses in the period 1990-2001, notably in the last few years. Nearly all of this increase is accounted for by homosexual men. Syphilis increased mostly among men aged 35 years and over, gonorrhoea mostly among younger men. The population of older men also showed a distinct increase since 1997 in HIV incidence.

[Increased Neisseria gonorrhoeae quinolone resistance in Amsterdam]. / Toename van chinolonresistentie bij Neisseria gonorrhoeae in Amsterdam.

In addition to a rise in the number of cases of gonorrhoea, the susceptibility of Neisseria gonorrhoeae to antibiotics is also a cause for concern. After a period of high resistance rates to penicillin and tetracycline between 1985 and 1995, resistance rates have dropped considerably in recent years, probably due to changes in treatment regimens. However, recently we have seen an increasing number of quinolone-resistant N. gonorrhoeae isolates in Amsterdam, the Netherlands, a development that has previously been reported in other parts of the world. Some form of national resistance monitoring for gonococci is therefore urgently required to allow timely detection of changes in N. gonorrhoeae resistance.

Patients' perspectives on the burden of recurrent genital herpes.

The purpose of this study was to quantify the impact of recurrent genital herpes (RGH) on health-related quality of life, healthcare resource and workplace productivity. This was a cross-sectional survey conducted in 5 countries (Australia, Denmark, Italy, The Netherlands and UK). Patients with a confirmed history of RGH completed the MOS 36-Item Short Form Health Survey (SF-36) and the Recurrent Genital Herpes Quality of Life questionnaire (RGHQoL). Questionnaires addressing frequency of access to healthcare services and workplace productivity were also completed and patients' medical history was obtained. Scores for 6 of the 8 domains of the SF-36 were significantly lower (P<0.001) i.e. worse, compared with scores for the normal population. The RGHQoL score was significantly lower in patients experiencing more frequent or more severe recurrences. Forty-five per cent of patients estimated that their work effectiveness was reduced by between 25% and 50% due to genital herpes symptoms.

Comparison between the LCx Probe system and the COBAS AMPLICOR system for detection of Chlamydia trachomatis and Neisseria gonorrhoeae infections in patients attending a clinic for treatment of sexually transmitted diseases in Amsterdam, The Netherlands.

Two assays for the detection of Chlamydia trachomatis and Neisseria gonorrhoeae were compared: the LCx Probe system (the LCx system; Abbott Diagnostic Laboratories, North Chicago, Ill.) and the COBAS AMPLICOR C. trachomatis/N. gonorrhoeae system (the COBAS AMPLICOR system; Roche Diagnostic Systems, Branchburg, N.J.). Endocervical swab specimens, male urethral swab specimens, and female and male urine specimens were collected from 503 female and 498 male visitors attending a sexually transmitted diseases clinic in Amsterdam, The Netherlands. Prevalences for C. trachomatis were 12.5% (63 of 503) and 10.0% (50 of 498) in females and males, respectively. The prevalences for N. gonorrhoeae were 1.2% (6 of 503) and 4.2% (21 of 498) in females and males, respectively. Both assays showed high values for sensitivity and specificity with regard to the detection of C. trachomatis in endocervical swab specimens, male urethral swab specimens, and female and male urine specimens. The sensitivities for the LCx system were 92.1, 90.0, 88.9, and 94.0% for each type of specimen, respectively; and the sensitivies for the COBAS AMPLICOR system were 96.8, 98.0, 82.5, and 92.0% for each type of specimen, respectively. Specificities ranged between 98.4 and 100%. The sensitivity of the LCx system for the detection of N. gonorrhoeae was 100% for female cervical swab and urine specimens and male urethral swab specimens, while for male urine specimens the sensitivity was 95.2%; the specificity was 100% for all types of specimens. For the detection of N. gonorrhoeae by the COBAS AMPLICOR assay, the sensitivity for female cervical swab and male urethral swab specimens was 100%, that for female urine specimens was 66.7%, and that for male urine specimens was 95.2%. However, the predictive values of a positive test for female cervical swab specimens and urine specimens were 31.6 and 36.4%, respectively. Sequence analysis of the amplimers obtained by an in-house 16S rRNA PCR of the solely COBAS AMPLICOR system-positive swab specimens revealed neither N. gonorrhoeae nor other Neisseria spp. The COBAS AMPLICOR assay was considered not suitable for screening for infections with N. gonorrhoeae. If this assay is used for detection of N. gonorrhoeae, confirmation of positive results by a reliable test is mandatory.

Diagnosing genital ulcer disease in a clinic for sexually transmitted diseases in Amsterdam, The Netherlands.

The most common etiologic agents of genital ulcer disease (GUD) are herpes simplex virus type 1 (HSV-1), HSV-2, Treponema pallidum, and Haemophilus ducreyi. In an outpatient clinic for sexually transmitted diseases in Amsterdam, The Netherlands, specimens from 372 patients with GUD were collected from February to November 1996. Sera were collected at the time of the symptoms and, for most patients, also during follow-up visits. Swabs in viral transport medium were used for HSV culture and for detection of DNA. The most prevalent pathogen found was HSV-2, which was detected by culture in 35% of the patients and by PCR in 48% of the patients. Also, HSV-1 infection was more often detected by PCR (7.8%) than by culture (5.6%). Evidence for an active infection with T. pallidum was found in 1.9% of the patients, using serological tests. A multiplex PCR for simultaneous T. pallidum and H. ducreyi DNA detection was positive for T. pallidum in 3.3% of the samples and for H. ducreyi in only 0.9% (3 out of 368) of the samples. The sensitivity of the PCR was superior to that of culture for HSV detection and to that of serology for T. pallidum detection. Specific H. ducreyi immunoglobulin G antibodies were detected in sera of 5.2% of the patients, with no concordance between serology and PCR. In 37% of the cases, none of the tested microorganisms was detected. Performance of PCR in addition to conventional techniques significantly improved the diagnosis of GUD.

Comparison of a monoclonal antibody-blocking enzyme-linked immunoassay and a strip immunoblot assay for identifying type-specific herpes simplex virus type 2 serological responses.

Detection of herpes simplex virus type 2 (HSV-2)-specific antibodies by a monoclonal antibody (MAb)-blocking enzyme-linked immunoassay (EIA) was compared with detection by a strip immunoblot assay (SIA) in a sexually transmitted disease (STD) clinic population. The study population consisted of 1,683 genitourinary medicine clinic attendees (582 women and 1,101 men). Sera were tested for the presence of HSV-2 antibody by use of the blocking EIA, in which binding of the MAb AP-1 to HSV-2 glycoprotein G-2 (gG-2) is blocked by HSV-2-specific antibody. The Chiron RIBA HSV-1 and -2 strip immunoassay (SIA) utilizes HSV-1- and HSV-2-specific or cross-reactive antigens immobilized on nitrocellulose strips (HSV gB-1 and HSV gG-1 peptide bands specific for HSV-1 antibody, HSV-2 gG-2 band specific for HSV-2 antibody, and HSV gD-2 band cross-reactive for HSV-1 and HSV-2 antibodies). A total of 1,612 sera were tested by MAb-blocking EIA for HSV-2 antibody and by SIA for HSV-1 and HSV-2 antibodies. By EIA, 541 (33.6%) sera were positive for HSV-2 antibody and 1,068 sera were negative for HSV-2 antibody; 3 sera gave equivocal results. HSV-2 antibody was detected in 555 (34.4%) sera by SIA; 144 (26%) of these sera possessed only HSV-2 antibody, and 411 (74%) sera contained both HSV-1 and HSV-2 antibodies. SIA detected HSV-1 antibody in 1,155 (71.6%) sera; 744 (64%) of these sera contained HSV-1 antibody alone. Sixteen sera contained antibody against HSV but could not be typed by SIA. A total of 512 sera were positive for HSV-2 antibody by both the EIA and SIA. We concluded that the blocking EIA and SIA showed a high level of agreement in detecting HSV-2 antibody in this population. In contrast to the SIA, the blocking EIA is a useful tool for large epidemiological studies, though the SIA proved to be slightly more sensitive once sera with discrepant results were further tested.

[Substantial increase in gonorrhea and syphilis among clients of Amsterdam Sexually Transmitted Diseases Clinic]. / Sterke toename van gonorroe en syfilis onder bezoekers van de Amsterdamse SOA-polikliniek.

In the Sexually Transmitted Diseases (STD) clinic of the Amsterdam Municipal Health Service standardized data are collected about all visitors, which makes it possible to gain insight into the STD trends. In 1999, 706 new cases of gonorrhoea and 76 new cases of infectious syphilis were diagnosed, increases of 46% and 111% respectively compared with 1998. The largest increase was seen among men who had sex with men. In this group the number of diagnosed cases of anorectal gonorrhoea in 1999 was twice as high as in 1998 (186 versus 94) and the number of infectious syphilis cases four times as high (40 versus 9). These data indicate an increase in unsafe sexual behaviour, possibly because of a change in attitudes about AIDS, now that effective antiretroviral treatment is available.

[Positive results from serologic screening for syphilis in pregnancy in the Amsterdam region, 1991-1995]. / Het nuttig effect van serologische screening op syfilis in de zwangerschap in de regio Amsterdam, 1991-1995.

OBJECTIVE: To evaluate the results of screening of pregnant women for syphilis in the region of Amsterdam, the Netherlands. DESIGN: Descriptive study and cost-benefit analysis. METHODS: In the period 1991-1995, physicians and midwives from the Amsterdam region sent serum samples of pregnant women to the Regional Public Health Laboratory of the Municipal Health Service (GG & GD) to be screened for syphilis. All physicians who had sent in specimens with a positive result of the Treponema pallidum haemagglutination assay (TPHA) and a confirming test result were asked, in the year of the screening, by telephone or in writing, what diagnosis they had made in the woman in question. Collection of these data was handled by the social nursing staffs of the outpatient clinics for sexually transmitted diseases in Amsterdam. The costs of laboratory tests and follow-up of the children were compared with the positive effects of special treatment and education avoided by antibiotic treatment. RESULTS: 54,344 serum samples were sent in. In the city of Amsterdam the coverage was 87.4%. In 81 women (0.15%) all the serological tests for syphilis were positive. From this group, 37 women had already been treated and 24 women were treated as a result of this screening programme (most of them had a foreign nationality), 10 for early syphilis and 14 for syphilis of unknown duration, preventing the birth of an estimated five to six children with congenital syphilis. The cost-benefit ratio was 1:15. CONCLUSION: Continuation of screening for syphilis during pregnancy in the Amsterdam region remains useful.

HIV surveillance among sexually transmitted disease clinic attenders in Amsterdam, 1991-1996.

OBJECTIVE: To determine trends in HIV prevalence among attenders of a clinic for sexually transmitted diseases (STD), with emphasis on heterosexuals who did not have a history of injecting drug use. METHODS: Anonymous unlinked HIV surveys with individual consent, conducted each half year from 1991 to 1996 (except 1993) among STD clinic attenders who came for evaluation of a possible new STD episode. RESULTS: Of 10,940 eligible attenders 10,046 (92%) accepted HIV testing. Of all tested attenders, 312 (3.1%) were HIV-infected. Overall HIV prevalence decreased significantly from 4.6% in 1991 to 2.8% in 1996. HIV prevalence among heterosexual men and women who were not injecting drug users was less than 1% in all but one survey period. Except for one woman, none of the 48 HIV-infected heterosexuals was aware of their current serostatus. Among HIV-infected heterosexuals, 21 out of 28 males (75%) and 18 out of 20 females (90%) were of non-Dutch origin. HIV prevalence was 16% among all homosexual men, and 12% among young homosexual men aged < 30 years. HIV prevalence among young homosexual men decreased significantly over time. Among HIV-infected homosexual men, 58% of older men and 59% of younger men were not aware of their current HIV infection. Rates of current STD were generally significantly higher among HIV-infected participants compared with non-HIV-infected participants. CONCLUSIONS: Although HIV prevalence among heterosexual clinic attenders is low, there is a clear potential for ongoing sexual HIV transmission. Most heterosexually acquired HIV infections are found in non-Dutch persons. This observation suggests migration of HIV-infected heterosexuals or the separation of Dutch and non-Dutch heterosexual networks. Awareness of serostatus is almost non-existent among HIV-infected heterosexuals, and is low among male homosexual clinic attenders. To increase awareness of current HIV serostatus and possibly decrease risk behaviour, HIV counselling and testing should be offered actively to all clinic attenders.

[Imported skin diseases]. / Importhuidziekten.

In two Dutch subjects who had been on holiday in the tropics, a woman aged 32 and a man of Surinam descent aged 52 years, and in two men aged 21 and 38 years who had arrived from the tropics in the Netherlands, one recently and one 15 years previously, import skin diseases were diagnosed: larva migrans cutanea, cutaneous leishmaniasis, mycetoma and lobomycosis. The diagnosis was based on the anamnesis, the clinical picture and histopathological findings. The patients were cured by administration of antimicrobial agents and (or) excision. When travellers or immigrants from the tropics present with skin lesions, an imported skin disease should be considered.

Expression of the T-cell activation antigens CD27 and CD28 in normal and psoriatic skin.

Activated T lymphocytes are thought to be involved in the pathogenesis of psoriasis. From studies with peripheral blood T lymphocytes it is known that T cells show a decrease in membrane expression of CD27 molecules during continuous antigenic stimulation. The T-cell activation molecule CD28 is thought to be involved in the transduction of an antigen-non-specific costimulatory signal. Therefore, in order to elucidate further the pathogenesis of psoriasis we studied the expression of CD27 and CD28, together with CD4, CD8 and CD45RA in this benign inflammatory dermatological disease. We used immunohistochemical techniques to determine absolute numbers of T lymphocytes and expression of these T-cell activation and T-subset-specific molecules in normal (n = 7), uninvolved perilesional (n = 7) and lesional psoriatic (n = 7) skin. We found that not only lesional but also clinically uninvolved perilesional skin showed an increased number of T cells. Further, immunohistochemical studies showed that CD27 is expressed by a minority of normal skin T cells, while in lesional psoriatic skin, expression was even lower, and almost absent in perilesional skin sections. In contrast to normal skin, both perilesional and lesional psoriatic skin contained no CD28 positive T cells. In lesional psoriatic skin, however, T cells showed predominantly the CD4 phenotype, while in perilesional skin CD8 positive T cells were dominant. Two conclusions were reached: first, the absolute number of T cells, their CD27, CD28 and CD45RA expression, and the influx of CD8 positive T cells, indicate that perilesional psoriatic skin is different from normal and lesional psoriatic skin; and secondly, the data on CD27 and CD28 suggest that not only lesional but also perilesional psoriatic skin is subject to continuous antigenic stimulation, thus leading to decreased CD27 and CD28 expression on skin T cells.

Differential in situ hybridization for herpes simplex virus typing in routine skin biopsies.

A herpes simplex virus (HSV) type 2 specific recombinant plasmid probe designated pH2S3 was constructed from non-HSV-1 crossreactive regions of the HSV-2 genome. DNA in situ hybridization on in vitro reconstructed tissue samples of sheep collagen matrix impregnated with herpes virus-infected human cells was used to demonstrate absence of crossreactivity of the pH2S3 probe with HSV-1 and varicella zoster virus under stringent posthybridization washing conditions. It was demonstrated that DNA in situ hybridization with pH2S3 allows specific detection of HSV-2 in routine formalin-fixed, paraffin-embedded patient material.

Solitary erythema migrans: a clinical, laboratory and epidemiological study of 77 Dutch patients.

Regional variations in the clinical spectrum of Lyme borreliosis have been described previously. These may be related to strain variations, or reflect selection bias. We compared the clinical and epidemiological profiles of Dutch patients presenting with solitary erythema migrans alone, with the profiles in other European studies, and studies from the U.S.A., and cultured Borrelia burgdorferi from erythema migrans to identify the genospecies. Seventy-seven consecutive patients with a final diagnosis of erythema migrans were admitted into the study. Various clinical and epidemiological data were obtained, and serum was evaluated for antibodies to Borrelia burgdorferi with an enzyme-linked immunosorbent assay. Skin biopsy specimens were taken from the border of the erythema migrans and cultured in modified Kelly's medium. The different genospecies of Borrelia burgdorferi were identified by reactivity with monoclonal antibodies H3TS, LA-26, LA-31 and D6, and by rRNA gene restriction patterns. Patients were treated with tetracycline or doxycycline, and were seen for follow-up 6 weeks after treatment. Long-term follow-up was by telephone interview. A tick bite had been noticed by 45% of the patients. The onset of erythema migrans occurred in 97% of these patients within 3 months of the tick bite. Erythema migrans was present for 1-319 days (median 2 months). No concomitant manifestations were spontaneously reported. Borrelia burgdorferi was cultured from 52 (84%) of 62 skin biopsy specimens. Fifty isolates (96%) were identified as Borrelia burgdorferi group VS461. No therapy failures occurred among patients treated with tetracycline (follow-up 1-4 years, median 27 months) or doxycycline (follow-up 6-31 months, median 19 months).(ABSTRACT TRUNCATED AT 250 WORDS)

Isolation of Borrelia burgdorferi from biopsy specimens taken from healthy-looking skin of patients with Lyme borreliosis.

Erythematous skin lesions due to infection with Borrelia burgdorferi will often disappear without antibiotic treatment. The aim of the study was to assess whether after disappearance of the erythematous skin lesion B. burgdorferi is still present in the healthy-looking skin of untreated patients. In six patients, a skin biopsy specimen was taken at the site of a previous erythematous skin lesion 1 to 6 months after disappearance of the lesion. Four of them presented with early disseminated Lyme borreliosis. In one additional patient with early disseminated Lyme borreliosis, the site of a previous tick bite was biopsied. None of these patients had been treated with antibiotics before presentation. The cultures of the skin biopsy specimens of the seven patients showed growth of Borrelia species. By rRNA gene restriction analysis and genospecies-specific PCR, six isolates were classified as Borrelia garinii and one as Borrelia group VS461. These results show that B. burgdorferi can still be cultured from the skin after disappearance of the erythematous skin lesion or at the site of a previous tick bite.

T-cell receptor gamma delta bearing cells in normal human skin.

T-cell antigen receptors (TCR) are divided into common alpha beta and less common gamma delta types. In the murine skin, TCR gamma delta+ cells have been reported to form the great majority of epidermal T lymphocytes. We have examined the relative contribution of TCR alpha beta+ and TCR gamma delta+ cells to the T-cell population in normal human skin. Serial sections of freshly frozen skin specimens were acetone fixed, incubated with anti-CD3, beta F1 (anti-TCR alpha beta), anti-TCR gamma delta-1 and anti-TCR delta 1 (anti-TCR gamma delta) monoclonal antibodies (MoAb), and stained with a highly sensitive method. Over 90% of the T cells of normal human skin are localized around the postcapillary venules of the dermis, while less than 5% are present within the epidermis. In papillary dermis, TCR gamma delta+ cells formed on average 7% (anti-TCR gamma delta-1) or 9% (anti-TCR delta 1) of the total number of CD3+ cells, while TCR alpha beta+ cells constituted up to 80%. In epidermis, these percentages were 18% and 29% for TCR gamma delta+ cells, and up to 60% for TCR alpha beta+ cells. It is concluded that there is no preferential immigration or in situ expansion of TCR gamma delta+ T cells in normal human skin, because the relative percentages found for the TCR alpha beta+ and TCR gamma delta+ populations in skin are comparable to those found in lymphoid organs and peripheral blood. However, the percentage of TCR gamma delta+ cells in epidermis seemed on average higher than in papillary dermis. Therefore, there may still be a difference in migration patterns of TCR gamma delta+ v TCR alpha beta+ cells, but this does not result in their preferential localization in human epidermis. The hypothesis that TCR gamma delta+ T cells have a specialized function in immunosurveillance of epithelia may thus not be valid for human epidermis.