Use of Home-Based Self-Collected Dried Blood Spots to Test for Syphilis, Human Immunodeficiency Virus, Hepatitis C and B Virus Infections and Measuring Creatinine Concentration.

INTRODUCTION: Home-based self-collected dried blood spot (DBS) sampling could simplify sexual health and preexposure prophylaxis care and reduce sexually transmitted infections (STIs) clinic visits for men who have sex with men (MSM). We compared the performance of DBS to venipuncture collected blood samples to test four STIs and creatinine concentration. METHODS: We invited MSM clients of the Amsterdam STI clinic to participate. Routinely collected peripheral blood was tested for syphilis treponemal antibody, HIV (HIV Ag/Ab), HCV (antibodies), HBV (HBsAg) and creatinine concentration. Participants received a home kit for DBS sampling, a return envelope and a questionnaire to evaluate the acceptability, feasibility and usability of DBS, measured on 5-point Likert scales, 1 representing complete disagreement and 5 complete agreement. We assessed sensitivity and specificity of DBS versus peripheral blood-based testing. RESULTS: In 2020 to 2021, we included 410 participants; 211 (51.5%) returned a completed DBS card, 117 (28.5%) returned a partially filled card and 82 (20.0%) did not return a card. The sensitivity for syphilis was 90.8% and the specificity 84.3%. For both HIV Ag/Ab and HBsAg, the sensitivity and specificity were 100.0%. The sensitivity for HCV antibody was 80.0%, and the specificity was 99.2%. The DBS creatinine concentration was a mean of 5.3 µmol/L higher than in venipuncture obtained plasma. Participants' median willingness to take a future DBS was 4 (interquartile range, 3-5). DISCUSSION: Dried blood spot may be an acceptable method among MSM for STI testing and creatinine follow-up during preexposure prophylaxis use. However, collecting enough blood on DBS cards was a challenge, and sensitivities for syphilis and HCV serology were too low.

Characteristics of mpox positive, versus mpox negative, and mpox unsuspected clients from the Centre of Sexual Health, Public Health Service of Amsterdam, 20 May to 15 September 2022.

BACKGROUND: In May 2022, an outbreak of mpox (monkeypox) in men-who-have-sex-with-men (MSM) emerged and quickly affected over 100 countries. In the early stages of the outbreak, overlap in symptoms with sexually transmitted infections (STI) made triage for mpox testing challenging. More information was needed on whom to screen and the main route of transmission. OBJECTIVES: We aimed to identify characteristics of mpox cases to further strengthen case definitions. We also compared Cycle threshold (Ct) values of the DNA positive mpox samples as a proxy for viral load by body location. METHODS: From 20 May 2022 to 15 September 2022, we tested all MSM who presented with malaise, and/or ulcerative lesions, and/or proctitis and/or a papular-vesicular-pustular eruption attending the Centre of Sexual Health in Amsterdam, the Netherlands, for mpox, with a PCR test. In the same period, 6932 MSM mpox unsuspected clients were not tested. We compared those tested positive for mpox with those tested negative and those unsuspected for mpox. RESULTS: Of the 374 MSM tested, 135 (36%) were positive for mpox. The mpox-positive MSM were older (median age, respectively, 36, 34 and 34 years, p = 0.019) and more often lived with HIV (30% vs. 16% and 7%, p < 0.001). Furthermore, mpox-positive patients more often reported receptive anal sex without a condom, sexualized drug use, more sex partners, and were more often diagnosed with bacterial STI (p < 0.001). Systemic symptoms and anogenital lesions were associated with mpox infection. For mpox-positive patients, anal samples (p = 0.009) and lesional samples (p = 0.006) showed significantly lower median mpox Ct values compared to throat samples. CONCLUSIONS: Mpox-positive patients more often reported receptive anal sex without a condom, had more sex partners and more often lived with HIV. Our results suggest that in the current mpox outbreak among MSM, sexual transmission is the main route.

Detection of Treponema pallidum DNA During Early Syphilis Stages in Peripheral Blood, Oropharynx, Ano-Rectum and Urine as a Proxy for Transmissibility.

BACKGROUND: Syphilis diagnosis may be challenging, especially in the asymptomatic and early clinical stages. We evaluated the presence of Treponema pallidum DNA (TP-DNA) in various sample types to elucidate transmissibility during various syphilis stages. METHODS: The study was conducted at the Amsterdam Centre for Sexual Health. We included adult men who have sex with men (MSM), who were suspected of having syphilis. The 2020 European guidelines definitions were followed for the diagnosis and staging of syphilis. Using a polymerase chain reaction (PCR) targeting the polA gene of Treponema pallidum (TP-PCR), we tested the following study samples on TP-DNA: peripheral blood, oropharyngeal swab, ano-rectal swab, and urine. RESULTS: From November 2018 to December 2019 we included 293 MSM. Seventy clients had primary syphilis, 73 secondary syphilis, 86 early latent syphilis, 14 late latent syphilis, 23 treated syphilis, and 27 had no syphilis. TP-DNA was detected in at least 1 study sample in 35/70 clients with primary syphilis (2/70 peripheral blood, 7/70 oropharynx, 13/70 ano-rectum, and 24/70 urine); in 62/73 clients with secondary syphilis (15/73 peripheral blood, 47/73 oropharynx, 37/73 ano-rectum, and 26/73 urine); and in 29/86 clients with early latent syphilis (5/86 peripheral blood, 21/86 oropharynx, 11/86 ano-rectum, and 6/86 urine). TP-DNA was not detected in clients with late latent syphilis or treated syphilis, nor in clients without syphilis. CONCLUSIONS: TP-DNA was frequently detected in various sample types in the absence of lesions. This is in line with the high transmission rate of syphilis and opens diagnostic opportunities for early presymptomatic syphilis stages.

2021 European Guideline on the management of proctitis, proctocolitis and enteritis caused by sexually transmissible pathogens.

This guideline intents to offer guidance on the diagnosis and management of patients with gastrointestinal symptoms and a suspected sexually transmitted cause. Proctitis is defined as an inflammatory syndrome of the anal canal and/or the rectum. Infectious proctitis can be sexually transmitted via genital-anal mucosal contact, but some also via digital contact and toys. Neisseria gonorrhoeae, Chlamydia trachomatis (including lymphogranuloma venereum), Treponema pallidum and herpes simplex virus are the most common sexually transmitted anorectal pathogens. Shigellosis can be transferred via oral-anal contact and may lead to proctocolitis or enteritis. Although most studies on these infections have concentrated on men who have sex with men (MSM), women having anal intercourse may also be at risk. A presumptive clinical diagnosis of proctitis can be made when there are symptoms and signs, and a definitive diagnosis when the results of laboratory tests are available. The symptoms of proctitis include anorectal itching, pain, tenesmus, bleeding, constipation and discharge in and around the anal canal. The majority of rectal chlamydia and gonococcal infections are asymptomatic and can only be detected by laboratory tests. Therefore, especially when there is a history of receptive anal contact, exclusion of anorectal infections is generally indicated as part of standard screening for sexually transmitted infections (STIs). Condom use does not guarantee protection from STIs, which are often spread without penile penetration. New in this updated guideline is: (i) lymphogranuloma venereum proctitis is increasingly found in HIV-negative MSM, (ii) anorectal Mycoplasma genitalium infection should be considered in patients with symptomatic proctitis after exclusion of other common causations such N. gonorrhoeae, C. trachomatis, syphilis and herpes, (iii) intestinal spirochetosis incidentally found in colonic biopsies should not be confused with syphilis, and (iv) traumatic causes of proctitis should be considered in sexually active patients.

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.

Grading immunohistochemical markers p16INK4a and HPV E4 identifies productive and transforming lesions caused by low- and high-risk HPV within high-grade anal squamous intraepithelial lesions.

OBJECTIVES: Because current guidelines recognise high-grade anal squamous intraepithelial lesions (HSILs) and low-grade SILs (LSILs), and recommend treatment of all HSILs although not all progress to cancer, this study aims to distinguish transforming and productive HSILs by grading immunohistochemical (IHC) biomarkers p16INK 4a (p16) and E4 in low-risk human papillomavirus (lrHPV) and high-risk (hr)HPV-associated SILs as a potential basis for more selective treatment. METHODS: Immunostaining for p16 and HPV E4 was performed and graded in 183 biopsies from 108 HIV-positive men who have sex with men. The causative HPV genotype of the worst lesion was identified using the HPV SPF10-PCR-DEIA-LiPA25 version 1 system, with laser capture microdissection for multiple infections. The worst lesions were scored for p16 (0-4) to identify activity of the hrHPV E7 gene, and panHPV E4 (0-2) to mark HPV production and life cycle completion. RESULTS: There were 37 normal biopsies, 60 LSILs and 86 HSILs, with 85% of LSILs caused by lrHPV and 93% of HSILs by hrHPV. No normal biopsy showed E4, but 43% of LSILs and 37% of HSILs were E4 positive. No differences in E4 positivity rates were found between lrHPV and hrHPV lesions. Most of the lesions caused by lrHPV (90%) showed very extensive patchy p16 staining; p16 grade in HSILs was variable, with frequency of productive HPV infection dropping with increasing p16 grade. CONCLUSIONS: Combined p16/E4 IHC identifies productive and nonproductive HSILs associated with hrHPV within the group of HSILs defined by the Lower Anogenital Squamous Terminology recommendations. This opens the possibility of investigating selective treatment of advanced transforming HSILs caused by hrHPV, and a 'wait and see' policy for productive HSILs. What's already known about this topic? For preventing anal cancer in high-risk populations, all patients with high-grade squamous intraepithelial lesions (HSILs) are treated, even though this group of lesions is heterogeneous, the histology is variable and regression is frequent. What does this study add? By adding human papillomavirus (HPV) E4 immunohistochemistry to p16 INK4a (p16), and grading expression of both markers, different biomarker expression patterns that reflect the heterogeneity of HSILs can be identified. Moreover, p16/E4 staining can separate high-risk HPV-associated HSILs into productive and more advanced transforming lesions, providing a potential basis for selective treatment.

Effects of an over-the-counter lactic-acid containing intra-vaginal douching product on the vaginal microbiota.

BACKGROUND: Over-the-counter intra-vaginal lactic-acid containing douches are marketed as vaginal hygiene products that support optimal vaginal pH balance. We report the effect of a commercially available douche (Etos®) on the vaginal microbiota (VM) in a prospective study. RESULTS: Twenty-five healthy women were recruited through advertisements in 2015-2017 (ethical approval: METC-2014_413) and followed over three menstrual cycles. The participants had a median age of 24 years [IQR: 22-29], were mostly Dutch-Caucasian (88%), and 60% used combined oral contraceptives. All participants douched three times a week during the second cycle, starting on the first day of that cycle. Participants completed a questionnaire at baseline, kept a daily diary to report douching, menses, and sexual activity, self-collected vaginal swabs every other day during the first and third cycle and daily during the second cycle, and measured vaginal pH mid-cycle. A median of 44 vaginal swabs [inter-quartile range (IQR): 41-50] were assessed per participant by 16S rRNA gene (V3-V4 region) sequencing and a Candida albicans PCR was done at four time-points. At baseline, 21 participants (84%) had Lactobacillus-dominated VM (Lactobacillus crispatus (n = 14), L. iners (n = 6), or diverse Lactobacillus species (n = 1) and 4 participants (16%) had VM consisting of diverse anaerobes. In multinomial logistic regression models, a trend towards increased odds were observed for having diverse anaerobic VM in the second and third cycle, compared to the first cycle, after adjusting for menses [odds ratio (OR) = 1.4 (95% CI: 0.9-2.1) and OR = 1.7 (95% CI: 0.9-3.1), respectively] (p = 0.376). Douching did not affect vaginal pH. Menses increased the odds for having VM consisting of diverse anaerobes almost two-fold (OR = 1.7; 95% CI: 1.0-2.8), while douching during menses increased the odds 2.6 fold (OR = 2.6; 95% CI: 1.0-6.5), compared to not menstruating (p = 0.099). Participants were more likely to test positive for C. albicans after cycle 2, compared to cycle 1 [OR = 3.0 (95% CI: 1.2-7.2); p = 0.017]. CONCLUSION: The Etos® douche did not significantly affect the vaginal pH or VM composition, although increased odds for having diverse anaerobic VM was observed, especially when douching during menses. Furthermore, douching may promote C. albicans infections.

A longitudinal study to investigate previous Chlamydia trachomatis infection as a risk factor for subsequent anorectal infection in men who have sex with men (MSM) and women visiting STI clinics in the Netherlands.

Although anorectal Chlamydia trachomatis (CT) infections are frequently diagnosed in men who have sex with men (MSM) and women, the reason for this infection often remains unexplained, as anal sex is not always reported. Oropharyngeal infections inoculating the gastrointestinal (GI) tract may contribute to anorectal-CT infections, as evidence in animals suggests that chlamydia bacteria undergo GI passage; however, no evidence exists in humans. Longitudinal patient clinic-registry data from MSM (n = 17 125) and women (n = 4120) from two Dutch sexually transmitted infection clinics were analysed. When adjusting for confounding socio-demographics, co-infections and risk behaviour, previous (from 3 weeks up to 24 months) oropharyngeal CT was not a risk factor for subsequent anorectal CT in women (odds ratio (OR) 0.46; 95% confidence interval (CI) 0.18-1.18; P = 0.11) and MSM (OR 1.33; 95% CI 0.86-2.07; P = 0.204). Despite the large dataset, the numbers did not allow for the estimation of risk in specific subgroups of interest. The role of the GI tract cannot be excluded with this epidemiological study, but the impact of preceding oropharyngeal CT on anorectal-CT infection is likely limited.

2019 European guideline on the management of lymphogranuloma venereum.

New or important issues in this updated version of the 2013 European guideline on the management of lymphogranuloma venereum (LGV): EPIDEMIOLOGY: Lymphogranuloma venereum continues to be endemic among European men who have sex with men (MSM) since 2003. Lymphogranuloma venereum infections in heterosexuals are extremely rare in Europe, and there is no evidence of transmission of LGV in the European heterosexual population. AETIOLOGY AND TRANSMISSION: Chlamydia trachomatis serovars/genovars L2b and L2 are the causative strains in the majority of cases in Europe. CLINICAL FEATURES: Among MSM, about 25% of the anorectal LGV infections are asymptomatic. Genital infections among MSM are rare; the ratio of genital vs. anorectal LGV infections is 1 in 15. DIAGNOSIS: To diagnose LGV, a sample tested C. trachomatis positive with a commercial nucleic acid amplification test (NAAT) platform should be confirmed with an LGV discriminatory NAAT. TREATMENT: Doxycycline 100 mg twice a day orally for 21 days is the recommended treatment for LGV. This same treatment is recommended also in asymptomatic patients and contacts of LGV patients. If another regimen is used, a test of cure (TOC) must be performed.

Neisseria gonorrhoeae Sequence Typing for Antimicrobial Resistance, a Novel Antimicrobial Resistance Multilocus Typing Scheme for Tracking Global Dissemination of N. gonorrhoeae Strains.

A curated Web-based user-friendly sequence typing tool based on antimicrobial resistance determinants in Neisseria gonorrhoeae was developed and is publicly accessible (https://ngstar.canada.ca). The N. gonorrhoeae Sequence Typing for Antimicrobial Resistance (NG-STAR) molecular typing scheme uses the DNA sequences of 7 genes (penA, mtrR, porB, ponA, gyrA, parC, and 23S rRNA) associated with resistance to ß-lactam antimicrobials, macrolides, or fluoroquinolones. NG-STAR uses the entire penA sequence, combining the historical nomenclature for penA types I to XXXVIII with novel nucleotide sequence designations; the full mtrR sequence and a portion of its promoter region; portions of ponA, porB, gyrA, and parC; and 23S rRNA sequences. NG-STAR grouped 768 isolates into 139 sequence types (STs) (n = 660) consisting of 29 clonal complexes (CCs) having a maximum of a single-locus variation, and 76 NG-STAR STs (n = 109) were identified as unrelated singletons. NG-STAR had a high Simpson's diversity index value of 96.5% (95% confidence interval [CI] = 0.959 to 0.969). The most common STs were NG-STAR ST-90 (n = 100; 13.0%), ST-42 and ST-91 (n = 45; 5.9%), ST-64 (n = 44; 5.72%), and ST-139 (n = 42; 5.5%). Decreased susceptibility to azithromycin was associated with NG-STAR ST-58, ST-61, ST-64, ST-79, ST-91, and ST-139 (n = 156; 92.3%); decreased susceptibility to cephalosporins was associated with NG-STAR ST-90, ST-91, and ST-97 (n = 162; 94.2%); and ciprofloxacin resistance was associated with NG-STAR ST-26, ST-90, ST-91, ST-97, ST-150, and ST-158 (n = 196; 98.0%). All isolates of NG-STAR ST-42, ST-43, ST-63, ST-81, and ST-160 (n = 106) were susceptible to all four antimicrobials. The standardization of nomenclature associated with antimicrobial resistance determinants through an internationally available database will facilitate the monitoring of the global dissemination of antimicrobial-resistant N. gonorrhoeae strains.

Outbreaks of syphilis among men who have sex with men attending STI clinics between 2007 and 2015 in the Netherlands: a space-time clustering study.

OBJECTIVES: Infectious syphilis (syphilis) is diagnosed predominantly among men who have sex with men (MSM) in the Netherlands and is a strong indicator for sexual risk behaviour. Therefore, an increase in syphilis can be an early indicator of resurgence of other STIs, including HIV. National and worldwide outbreaks of syphilis, as well as potential changes in sexual networks were reason to explore syphilis trends and clusters in more depth. METHODS: National STI/HIV surveillance data were used, containing epidemiological, behavioural and clinical data from STI clinics. We examined syphilis positivity rates stratified by HIV status and year. Additionally, we performed space-time cluster analysis on municipality level between 2007 and 2015, using SaTScan to evaluate whether or not there was a higher than expected syphilis incidence in a certain area and time period, using the maximum likelihood ratio test statistic. RESULTS: Among HIV-positive MSM, the syphilis positivity rate decreased between 2007 (12.3%) and 2011 (4.5%), followed by an increasing trend (2015: 8.0%). Among HIV-negative MSM, the positivity rate decreased between 2007 (2.8%) and 2011 also (1.4%) and started to increase from 2013 onwards (2015: 1.8%). In addition, we identified three geospatial clusters. The first cluster consisted of MSM sex workers in the South of the Netherlands (July 2009-September 2010, n=10, p<0.001). The second cluster were mostly HIV-positive MSM (58.5%) (Amsterdam; July 2011-December 2015; n=1123, p<0.001), although the proportion of HIV-negative MSM increased over time. The third cluster was large in space (predominantly the city of Rotterdam; April-September 2015, n=72, p=0.014) and were mostly HIV-negative MSM (62.5%). CONCLUSIONS: Using SaTScan analysis, we observed several not yet recognised outbreaks and a rapid resurgence of syphilis among known HIV-positive MSM first, but more recently, also among HIV-negative MSM. The three identified clusters revealed locations, periods and specific characteristics of the involved MSM that could be used when developing targeted interventions.

Trichomonas vaginalis and Mycoplasma genitalium: age-specific prevalence and disease burden in men attending a sexually transmitted infections clinic in Amsterdam, the Netherlands.

BACKGROUND: Men are not routinely tested for Trichomonas vaginalis (TV) and Mycoplasma genitalium (MG) in the Netherlands and, therefore, very few studies have looked into their prevalence and/or role in urogenital complaints in the Dutch male population. OBJECTIVE: To describe the age-specific prevalence and disease burden of TV and MG, and their co-occurrence with Chlamydia trachomatis (CT), in men attending the sexually transmitted infections (STI) clinic in Amsterdam, the Netherlands. METHODS: Urine samples and clinical data were collected from 526 men who have sex with women (MSW) and 678 men who have sex with men (MSM) attending the STI clinic. To investigate age as a risk factor, we oversampled older men. Urine samples were tested for TV and MG using molecular tests. RESULTS: The overall prevalence was 0.5% (6/1204) for TV and 3.1% (37/1204) for MG. Four out of the six TV cases were older than 40 years and all TV cases were MSW. No age trend was observed for MG, nor did MG prevalence differ between MSW and MSM. Co-infections between TV or MG and CT were rare. TV infection did not associate with urogenital symptoms, whereas 5.9% of men reporting urogenital symptoms were infected with MG. CONCLUSIONS: TV infection was rare in men, asymptomatic and was limited to the heterosexual network. MG infection was relatively common and equally prevalent among MSW and MSM of all ages. Most MG infections remained asymptomatic, however, our results suggest that up to 6% of urogenital complaints could be explained by MG infection.

Vaginal high-risk human papillomavirus infection in a cross-sectional study among women of six different ethnicities in Amsterdam, the Netherlands: the HELIUS study.

OBJECTIVE: In the Netherlands the incidence of cervical cancer is higher among ethnic minority populations compared with the general Dutch population. We investigated the prevalence of, and risk factors associated with, vaginal high-risk human papillomavirus (hrHPV) infection in women of six different ethnicities living in Amsterdam. METHODS: For this cross-sectional study we selected women aged 18-34 years old of six ethnicities from the large-scale multiethnic HEalthy LIfe in an Urban Setting study. Self-collected vaginal swabs were tested for HPV DNA and genotyped using a highly sensitive PCR and reverse line blot assay (short PCR fragment (SPF)10-PCR DNA enzyme immunoassay/LiPA25-system version-1, delft diagnostic laboratory (DDL)). Participants completed a questionnaire regarding demographics and sexual behaviour. Logistic regression using generalised estimating equations was used to assess risk factors of hrHPV, and to investigate whether prevalence of hrHPV differed among ethnicities. RESULTS: The study population consisted of 592 women with a median age of 27 (IQR: 23-31) years. Dutch and African Surinamese women reported the highest sexual risk behaviour. HrHPV prevalence was highest in the Dutch (40%) followed by the African Surinamese (32%), Turkish (29%), Ghanaian (26%), Moroccan (26%) and South-Asian Surinamese (18%). When correcting for sexual risk behaviour, the odds to be hrHPV-positive were similar for all non-Dutch groups when compared with that of the Dutch group. CONCLUSIONS: We found an overall higher hrHPV prevalence and higher sexual risk behaviour in the native Dutch population. Further research is needed to unravel the complex problem concerning cervical cancer disparities, such as differences in participation in the cervical cancer screening programme, or differences in clearance and persistence of hrHPV.

Low- and high-risk human papillomavirus genotype infections in intra-anal warts in HIV-positive men who have sex with men.

BACKGROUND: Anogenital warts are often presumed to represent nondysplastic or low-grade anal intraepithelial neoplasia (LGAIN). We previously demonstrated that up to 20% of intra-anal warts in HIV-positive men who have sex with men (MSM) contain regions of high-grade AIN (HGAIN). OBJECTIVES: To determine the causative human papillomavirus (HPV) types of low- and high- grade dysplastic areas in warts from HIV-positive MSM. METHODS: A total of 42 intra-anal warts from 41 HIV-positive MSM were graded as nondysplastic, LGAIN or HGAIN. Whole-tissue sections (WTS) were analysed with the SPF10 polymerase chain reaction/LiPA25 HPV genotyping system. If the WTS contained multiple HPV types, dysplastic regions were isolated by laser capture microdissection (LCM) for HPV genotyping. RESULTS: Overall, 38 of 42 (91%) WTS tested positive for HPV DNA. Of these, 23 (61%) contained a single HPV type and 15 (39%) contained multiple HPV types. All LCM-selected regions contained no more than one HPV type. Ten of 42 (24%) WTS contained HGAIN disease, of which six (60%) were associated with a high-risk HPV (hrHPV) genotype. Twenty-three of 42 WTS contained LGAIN disease, of which two (9%) were associated with hrHPV. AIN lesions containing hrHPV types were identified using p16 staining. CONCLUSIONS: LGAIN lesions can be caused by high-risk HPV genotypes and vice versa. We therefore recommend routine follow-up and treatment of all dysplastic intra-anal warts for HIV-positive MSM.

Monitoring the response of patients with cutaneous leishmaniasis to treatment with pentamidine isethionate by quantitative real-time PCR, and identification of Leishmania parasites not responding to therapy.

BACKGROUND: Leishmania (Viannia) guyanensis is believed to be the principal cause of cutaneous leishmaniasis (CL) in Suriname. This disease is treated with pentamidine isethionate (PI), but treatment failure has increasingly been reported. AIM: To evaluate PI for its clinical efficacy, to compare parasite load, and to assess the possibility of treatment failure due to other infecting Leishmania species. METHODS: Parasite load of patients with CL was determined in skin biopsies using real-time quantitative PCR before treatment and 6 and 12 weeks after treatment. Clinical responses were evaluated at week 12 and compared with parasite load. In parallel, molecular species differentiation was performed. RESULTS: L. (V.) guyanensis was the main infecting species in 129 of 143 patients (about 90%). PI treatment led to a significant decrease (P < 0.001) in parasite counts, and cured about 75% of these patients. Treatment failure was attributable to infections with Leishmania (Viannia) braziliensis, Leishmania (Leishmania) amazonensis and L. (V.) guyanensis (1/92, 1/92 and 22/92 evaluable cases, respectively). There was substantial agreement beyond chance between the parasite load at week 6 and the clinical outcome at week 12, as indicated by the κ value of 0.61. CONCLUSIONS: L. (V.) guyanensis is the main infecting species of CL in Suriname, followed by L. (V.) braziliensis and L. (L.) amazonensis. Furthermore, patient response to PI can be better anticipated based on the parasite load 6 weeks after the treatment rather than on parasite load before treatment.

Tuberculids: cutaneous indicator diseases of Mycobacterium tuberculosis infection in young patients.

BACKGROUND: In the past years the incidence of tuberculosis has dropped significantly in most parts of Europe and the presentation of symptomatic tuberculosis cases have become increasingly rare. With the recent influx of refugees in Europe coming from tuberculosis endemic areas like the Middle East and Africa, it is expected that the incidence of tuberculosis will increase. OBJECTIVES: Cutaneous symptoms are important hallmarks that can be of aid for the correct diagnosis of an underlying disease, like tuberculosis. METHODS: We describe 2 young patients with tuberculids, respectively lichen scrofulosorum and papulonecrotic tuberculids, caused by a systemic Mycobacterium tuberculosis infection. RESULTS: Tuberculids are cutaneous immunological reactions triggered by a Mycobacterium tuberculosis infection elsewhere in the body. The three main manifestations of cutaneous tuberculids are: lichen scrofulosorum, papulonecrotic tuberculids and erythema induratum of Bazin. Whereas the latter is more common, the first two presentations are rare. CONCLUSION: It is of importance that clinicians, including dermatologists, are aware of the spectrum of clinical presentations of tuberculosis to halt this destructive and highly contagious disease early in its course.

Point-of-care management of urogenital Chlamydia trachomatis via Gram-stained smear analysis in male high-risk patients. Diagnostic accuracy and cost-effectiveness before and after changing the screening indication at the STI Clinic in Amsterdam.

OBJECTIVES: To measure the effect of changing the point-of-care (POC) testing algorithm of urogenital chlamydia for all male high-risk patients to those with only symptoms with respect to: diagnostic accuracy, loss to follow-up, correctly managed consultations and costs. METHODS: Retrospective comparison of the diagnostic accuracy and cost-effectiveness of Gram-stained urethral smear analysis for the POC management of urogenital Chlamydia trachomatis infections. Between 2008 and 2009 Gram-stained urethral smear analysis was offered to all men irrespective of symptoms; between 2010 and 2011 only to those with symptoms. The Aptima CT assay was the reference diagnostic test. RESULTS: The number of examined Gram-stained smears in the two periods was respectively 7185 (2008-2009 period) and 18,852 (2010-2011 period). The sensitivity of the Gram stain analysis was respectively 83.8% (95% CI 81.2% to 86.1%) and 91.0% (95% CI 89.5% to 92.3%) (p<0.001). The specificity was respectively 74.1% (95% CI 73.0% to 75.2%) and 53.1% (95% CI 51.8% to 54.4%) (p<0.001). The positive predictive value was low in both periods, respectively 31.7% (95% CI 29.8% to 33.6%) and 35.6% (95% CI 34.1% to 37.1%) (p=0.002), whereas the negative predictive value was high, respectively 97.0% (95% CI 96.4% to 97.4%) and 95.4% (95% CI 94.6% to 96.1%) (p=0.002). The loss to follow-up rate between 2008-2009 and 2010-2011 was, respectively, 1.8% (95% CI 1.0% to 2.9%) vs 2.3% (95% CI 1.7% to 3.0%) (p=0.36). There was a small difference in overtreatment, 68.0% (95% CI 66.0% to 69.8%) vs 64.1% (95% CI 62.6% to 65.5%) (p=0.001). The cost per correctly managed consultation was 14.3% lower in the 2010-2011 period (€94.31 vs €80.82). The percentage of delayed treated infections was significantly lower in the 2008-2009 period (10.5%) compared with the 2010-2011 period (22.8%) (p<0.001). CONCLUSIONS: With a high sensitivity in male high-risk patients, the Gram-stained urethral smear is a useful POC test to detect urogenital C. trachomatis. When offered only to men with urogenital symptoms the specificity decreases but the cost per correctly managed consultation is reduced with 14.3% without a significant difference in loss to follow-up but with a significantly higher rate of delayed treatment.

2013 European guideline on the management of lymphogranuloma venereum.

WHAT IS NEW IN THIS UPDATED GUIDELINE?: This is the update version of the 2010 European guideline on the management of lymphogranuloma venereum (LGV). New issues are: EPIDEMIOLOGY: Based on clonal relatedness of prevalent LGV strains there is evidence that the LGV epidemic among men who have sex with men (MSM) in the Western world prevailed already in the United States in the 1980s and was introduced into Europe by the end of the last century. AETIOLOGY AND TRANSMISSION: A new LGV variant causing severe proctitis was unveiled and designated L2c. The L2b LGV variant causing the vast majority of infections among MSM is now also found among a few heterosexual women. MANAGEMENT: Apart from HIV and STI screening, Hepatitis C Virus (HCV) testing should be offered to all LGV patients. To exclude reinfections, STI screening during a follow-up visit 3 months after an LGV diagnosis should be offered.

Comparison of two Gram stain point-of-care systems for urogenital gonorrhoea among high-risk patients: diagnostic accuracy and cost-effectiveness before and after changing the screening algorithm at an STI clinic in Amsterdam.

OBJECTIVES: To compare point-of-care (POC) systems in two different periods: (1) before 2010 when all high-risk patients were offered POC management for urogenital gonorrhoea by Gram stain examination; and (2) after 2010 when only those with symptoms were offered Gram stain examination. METHODS: Retrospective comparison of a Gram stain POC system to all high-risk patients (2008-2009) with only those with urogenital symptoms (2010-2011) on diagnostic accuracy, loss to follow-up, presumptively and correctly treated infections and diagnostic costs. Culture was the reference diagnostic method. RESULTS: In men the sensitivity of the Gram stain was 95.9% (95% CI 93.1% to 97.8%) in 2008-2009 and 95.4% (95% CI 93.7% to 96.8%) in 2010-2011, and in women the sensitivity was 32.0% (95% CI 19.5% to 46.7%) and 23.1% (95% CI 16.1% to 31.3%), respectively. In both periods the overall specificity was high (99.9% (95% CI 99.8% to 100%) and 99.8% (95% CI 99.7% to 99.9%), respectively). The positive predictive value (PPV) and negative predictive value (NPV) before and after 2010 were also high: PPV 97.0% (95% CI 94.5% to 98.5%) and 97.7% (95% CI 96.3% to 98.6%), respectively; NPV 99.6% (95% CI 99.4% to 99.7%) and 98.8% (95% CI 98.5% to 99.0%), respectively. There were no differences between the two time periods in loss to follow-up (7.1% vs 7.0%). Offering Gram stains only to symptomatic high-risk patients as opposed to all high-risk patients saved €2.34 per correctly managed consultation (a reduction of 7.7%). CONCLUSIONS: The sensitivity of the Gram stain is high in men but low in women. When offered only to high-risk patients with urogenital symptoms, the cost per correctly managed consultation is reduced by 7.7% without a significant difference in accuracy and loss to follow-up.