Clinical outcomes of syphilis in HIV-negative and HIV-positive MSM: occurrence of repeat syphilis episodes and non-treponemal serology responses.

OBJECTIVES: HIV-positive men who have sex with men (MSM) may be at a higher risk of repeat syphilis, have different clinical manifestations and have a different serological response to treatment compared with HIV-negative MSM. The objective of this study was to assess whether HIV-negative and HIV-positive MSM with infectious syphilis (primary, secondary or early latent) differed in history of previous syphilis episodes, disease stage and non-treponemal titre of initial and repeat episodes, and the titre response 6 and 12 months after treatment. Furthermore, determinants associated with an inadequate titre response after treatment were explored. METHODS: This retrospective analysis used data of five longitudinal studies (four cohorts; one randomised controlled trial) conducted at the STI clinic in Amsterdam, the Netherlands. Participants were tested for syphilis and completed questionnaires on sexual risk behaviour every 3-6 months. We included data of participants with ≥1 syphilis diagnosis in 2014-2019. Pearson's χ² test was used to compare HIV-negative and HIV-positive MSM in occurrence of previous syphilis episodes, disease stage of initial and repeat syphilis episode and non-treponemal titre treatment responses. RESULTS: We included 355 participants with total 459 syphilis episodes. HIV-positive MSM were more likely to have a history of previous syphilis episodes compared with HIV-negative MSM (68/90 (75.6%) vs 96/265 (36.2%); p<0.001). Moreover, HIV-positive MSM with repeat syphilis were less often diagnosed with primary syphilis (7/73 (9.6%) vs 36/126 (28.6%)) and more often diagnosed with secondary syphilis (16/73 (21.9%) vs 17/126 (13.5%)) and early latent syphilis (50/73 (68.5%) vs 73/126 (57.9%)) (p=0.005). While not significantly different at 12 months, HIV-negative MSM were more likely to have an adequate titre response after 6 months compared with HIV-positive MSM (138/143 (96.5%) vs 66/74 (89.2%); p=0.032). CONCLUSIONS: In repeat syphilis, HIV infection is associated with advanced syphilis stages and with higher non-treponemal titres. HIV infection affects the serological outcome after treatment, as an adequate titre response was observed earlier in HIV-negative MSM.

High incidence of HCV in HIV-negative men who have sex with men using pre-exposure prophylaxis.

BACKGROUND & AIMS: HCV has emerged as a sexually transmitted infection (STI) among HIV-positive men who have sex with men (MSM). We evaluated HCV incidence and its risk factors among HIV-negative MSM using HIV pre-exposure prophylaxis (PrEP). METHODS: Participants of the Amsterdam PrEP project were tested for HCV antibodies or HCV-RNA every 6 months. Participants used daily or event-driven PrEP and could switch regimens during follow-up. We calculated incidence rates (IRs) for overall HCV infection and separately for primary and re-infection. A univariable Bayesian exponential survival model was used to identify risk factors associated with incident HCV infection. The HCV NS5B gene fragment (709 bp) was sequenced and compared to HCV isolates from HIV-positive MSM and other risk groups (n = 419) using phylogenetic analysis. RESULTS: Among 350 participants contributing 653.6 person-years (PYs), we detected 15 HCV infections in 14 participants (IR = 2.30/100PY). There were 8 primary infections (IR = 1.27/100PY) and 7 re-infections (IR = 27.8/100PY). IR was 2.71/100PY in daily and 1.15/100PY in event-driven PrEP users. Factors associated with incident HCV infection were higher number of receptive condomless anal sex acts with casual partners (posterior hazard ratio [HR] 1.57 per ln increase; 95% credibility interval [CrI] 1.09-2.20), anal STI (posterior HR 2.93; 95% CrI 1.24-7.13), injecting drug use (posterior HR 4.69; 95% CrI 1.61-12.09) and sharing straws when snorting drugs (posterior HR 2.62; 95% CrI 1.09-6.02). We identified robust MSM-specific HCV clusters of subtypes 1a, 4d, 2b and 3a, which included MSM with and without HIV. CONCLUSIONS: HIV-negative MSM using PrEP are at risk of incident HCV infection, while identified risk factors are similar to those in HIV-positive MSM. Regular HCV testing is needed, especially for those with a previous HCV infection and those reporting risk factors. LAY SUMMARY: We report that hepatitis C virus infections are frequently acquired among HIV-negative men who have sex with men (MSM) using pre-exposure prophylaxis to prevent HIV infection. New infections occurred more frequently in those reporting receptive anal sex without using condoms, having an anal sexually transmitted infection, injecting drugs, and sharing straws when snorting drugs. The viruses found in HIV-negative men using pre-exposure prophylaxis are genetically similar to those in HIV-positive men, but not in other hepatitis C risk groups, suggesting that (sexual) transmission is occurring between HIV-positive MSM and HIV-negative MSM using pre-exposure prophylaxis. CLINICAL TRIAL NUMBER: Dutch trial registration number NTR5411.

Vaginal herb use and Chlamydia trachomatis infection: cross-sectional study among women of various ethnic groups in Suriname.

OBJECTIVE: Vaginal steam baths with herb leaves (herb use) is practised by some Surinamese women. We assessed herb use among women from the five most prevalent ethnic groups, and if herb use is associated with Chlamydia trachomatis infection. SETTING: Participants were recruited at a sexually transmitted infection (STI) clinic and a family planning clinic (FP) in Paramaribo, Suriname. PARTICIPANTS: 1040 women were included subsequently, comprising the following ethnic groups: Creole (26.7%), Hindustani (24.6%), Javanese (15.7%), Maroon (13.3%) and mixed descent (19.7%). METHODS: Nurses collected a questionnaire and vaginal swabs for nucleic acid amplification C. trachomatis testing. PRIMARY OUTCOMES: Determinants of vaginal herb use and C. trachomatis infection via univariable and multivariable logistic regression. RESULTS: Herb use was most common among Maroon (68.8%) and Creole women (25.2%). In multivariable analysis including only Maroon and Creole women, determinants significantly associated with vaginal herb use were (OR; 95% CI): Maroon ethnic descent (5.33; 3.26 to 8.71 vs Creole), recruitment at the STI clinic (2.04; 1.24 to 3.36 vs FP), lower education levels (3.80; 1.68 to 8.57 lower vs higher, and 2.02; 0.90 to 4.51 middle vs higher). Lower age and recruitment at the STI clinic were associated with C. trachomatis infection, but not vaginal herb use. CONCLUSION: In Suriname, vaginal herb use is common among Maroon and Creole women. Education, ethnic group and recruitment site were determinants for herb use. Vaginal herb use was not a determinant of C. trachomatis infection. Future research should focus on the effect of herb use on the vaginal microbiome and mucosal barrier.

Spontaneous Clearance of Pharyngeal Gonococcal Infections: A Retrospective Study in Patients of the Sexually Transmitted Infections Clinic; Amsterdam, the Netherlands; 2012 to 2015.

INTRODUCTION: Pharyngeal Neisseria gonorrhoeae infections are mostly asymptomatic, yet sustain ongoing gonococcal transmission. We assessed the proportion of pharyngeal gonorrhea that spontaneously clears and identified determinants of clearance. METHODS: At the sexually transmitted infections clinic Amsterdam, at-risk women and men who have sex with men were routinely screened for pharyngeal N. gonorrhoeae using an RNA-based nucleic acid amplification test (NAAT; Aptima Combo 2).We retrospectively examined medical records of pharyngeal gonorrhea patients (January 2012-August 2015). We included patients who returned for antibiotic treatment and had a new sample taken for NAAT before treatment. Spontaneous clearance was defined as a negative NAAT result at the follow-up visit. RESULTS: During the study period, 1266 cases with a pharyngeal gonorrhea were not treated at the first consultation and returned for a follow-up visit. Median (interquartile range) time between the first consultation and follow-up was 10 (7-14) days. Spontaneous clearance was found in 139 cases (11.0%) and was associated with age at least 45 years (vs. 16-24 years; adjusted odds ratio, 2.02 [95% confidence interval, 1.09-3.75]) and with time from the first consultation to follow-up (adjusted odds ratio, 1.08 [1.06-1.10], per extra day). CONCLUSIONS: Eleven percent of pharyngeal gonorrhea cases cleared spontaneously. Spontaneous clearance of pharyngeal gonorrhea was more often seen among older patients.

Molecular epidemiology of Neisseria gonorrhoeae strains circulating in Indonesia using multi-locus variable number tandem repeat analysis (MLVA) and Neisseria gonorrhoeae multi-antigen sequence typing (NG-MAST) techniques.

BACKGROUND: Control of gonorrhea in resource-limited countries, such as Indonesia, is mostly unsuccessful. Examining Neisseria gonorrhoeae (Ng) transmission networks using strain typing might help prioritizing public health interventions. METHODS: In 2014, urogenital Ng strains were isolated from clients of sexually transmitted infection clinics in three Indonesian cities. Strains were typed using Multiple-Locus Variable Number Tandem Repeat (VNTR) Analysis (MLVA) and Ng Multi-Antigen Sequence Typing (NG-MAST) at the Public Health Service, Amsterdam, the Netherlands, and compared to Dutch strains collected from 2012 to 2015. Minimum spanning trees (MSTs) were constructed using MLVA profiles incorporating demographics and NG-MAST genogroups. A cluster was defined as ≥5 strains differing in ≤1 VNTR locus. The concordance between MLVA and NG-MAST was examined with the adjusted Wallace coefficients (AW). RESULTS: We collected a total of 78 Indonesian strains from Yogyakarta (n = 44), Jakarta (n = 25), and Denpasar (n = 9). Seven MLVA clusters and 16 non-clustered strains were identified. No cluster was specific for any geographic area, risk group or age group. Combined with 119 contemporary Dutch strains, 8 MLVA clusters were identified, being four clusters of Indonesian strains, two of Dutch strains, and two of both Indonesian and Dutch strains. Indonesian strains (79.5%) were more often clustered compared to Dutch strains (24.3%). The most prevalent NG-MAST genogroups among Indonesian strains was G1407 (51.3%) and among Dutch strains was G2992 (19.3%). In Indonesian strains, the AW [95% confidence interval] for MLVA to NG-MAST was 0.07 [0.00-0.27] and for NG-MAST to MLVA was 0.03 [0.00-0.12]. CONCLUSION: Indonesian Ng strains are more often clustered than Dutch strains, but show no relation with geographical area, risk group, or age group, suggesting a more clonal Ng epidemic in Indonesia. Some similar Ng strains circulate in both Indonesia and the Netherlands.

Persistence after treatment of pharyngeal gonococcal infections in patients of the STI clinic, Amsterdam, the Netherlands, 2012-2015: a retrospective cohort study.

INTRODUCTION: Infection of Neisseria gonorrhoeae in the pharynx (pharyngeal Ng) is associated with gonococcal transmission and development of antimicrobial resistance. We assessed proportion of and determinants for persistence after treatment of pharyngeal Ng. METHODS: At the STI clinic of Amsterdam, the Netherlands, females-at-risk and men who have sex with men are routinely screened for pharyngeal Ng using an RNA-based nucleic acid amplification test (NAAT; Aptima Combo 2). Patients with pharyngeal Ng were invited for a test-of-cure (TOC) 7 days after treatment with a 500 mg ceftriaxone intramuscularly. We retrospectively examined medical records of patients with pharyngeal Ng (January 2012-August 2015) who returned for a TOC 7-28 days after treatment. Persistence was defined as a positive NAAT at TOC. RESULTS: Out of 2204 pharyngeal Ng cases recorded in the study period, 781 cases (median time between first treatment and TOC of 8 (IQR 7-12) days) were included in the analysis. Persistence after treatment was found in 36 (4.6%) and was less likely among patients who received ceftriaxone in combination with other antibiotics (vs monotherapy) (adjusted OR (aOR) 0.36, 95% CI 0.12 to 1.04) and with longer time from treatment to TOC (aOR 0.74, 95% CI 0.60 to 0.90, per extra day). In those with a TOC 15-28 days after treatment, Ng persisted in only 1.0% (1/105 cases). CONCLUSION: A small proportion of pharyngeal Ng persists despite appropriate treatment. Combining ceftriaxone with other antibiotics appears to lead to faster clearance. A TOC for pharyngeal Ng 7 days after treatment may be too soon.

Gonorrhea in Indonesia: High Prevalence of Asymptomatic Urogenital Gonorrhea but No Circulating Extended Spectrum Cephalosporins-Resistant Neisseria gonorrhoeae Strains in Jakarta, Yogyakarta, and Denpasar, Indonesia.

BACKGROUND: Little is known about the epidemiology of asymptomatic urogenital gonorrhea and antimicrobial susceptibility of Neisseria gonorrhoeae (NG) strains circulating in Indonesia. We studied these issues in 3 large Indonesian cities. METHODS: In 2014, participants were recruited from sexually transmitted infection clinics and through outreach in Jakarta, Yogyakarta, and Denpasar. Neisseria gonorrhoeae detection in genital specimens was performed with NG-qPCR at the Public Health Service in Amsterdam. Antimicrobial susceptibility was investigated using the Etest. RESULTS: Among 992 participants, 781 were asymptomatic and included in the risk factors analysis: 439 (56.2%) men, 258 (33.0%) women, and 84 (10.8%) transwomen. They differed significantly in age and were mostly men who have sex with men (35.2%) and female sex workers (29.3%).Overall, 175 (22.4%) asymptomatic participants had a positive NG-qPCR result. Factors positively associated with asymptomatic urogenital gonorrhea were being recruited through outreach (vs clinic-based), inconsistent condom use, and being divorced/widowed (vs single).Among 79 urogenital cultured isolates derived from 27 symptomatic and 52 asymptomatic participants, all isolates were susceptible to ceftriaxone and cefixime, and 98.7% of isolates were susceptible to azithromycin. In contrast, resistance to doxycycline (98.7%) and ciprofloxacin (97.4%) was common. CONCLUSIONS: Prevalence of asymptomatic urogenital gonorrhea among Indonesian key populations is very high. Little to no resistance against extended spectrum cephalosporins and azithromycin was observed. However, almost all isolates were resistant to doxycycline and ciprofloxacin. Strengthening outreach sexually transmitted infections services, composing guidelines to screen asymptomatic individuals, and implementing periodical antimicrobial resistance surveillance are recommended.

Low prevalence of methicillin-resistant Staphylococcus aureus among men who have sex with men attending an STI clinic in Amsterdam: a cross-sectional study.

OBJECTIVE: Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) is common among men who have sex with men (MSM) in the USA. It is unknown whether this is also the case in Amsterdam, the Netherlands. DESIGN: Cross-sectional study. SETTING: Sexually transmitted infection outpatient low-threshold clinic, Amsterdam, the Netherlands. PARTICIPANTS: Between October 2008 and April 2010, a total of 211 men were included, in two groups: (1) 74 MSM with clinical signs of a skin or soft tissue infection (symptomatic group) and (2) 137 MSM without clinical signs of such infections (asymptomatic group). PRIMARY OUTCOME MEASURES: S aureus and MRSA infection and/or colonisation. Swabs were collected from the anterior nasal cavity, throat, perineum, penile glans and, if present, from infected skin lesions. Culture for S aureus was carried out on blood agar plates and for MRSA on selective chromagar plates after enrichment in broth. If MRSA was found, the spa-gene was sequenced. SECONDARY OUTCOME MEASURES: Associated demographic characteristics, medical history, risk factors for colonisation with S aureus and high-risk sexual behaviour were collected through a self-completed questionnaire. RESULTS: The prevalence of S aureus colonisation in the nares was 37%, the pharynx 11%, the perianal region 12%, the glans penis 10% and in skin lesions 40%. In multivariable analysis adjusting for age, anogenital S aureus colonisation was significantly associated with the symptomatic group (p=0.01) and marginally with HIV (p=0.06). MRSA was diagnosed in two cases: prevalence 0.9% (95% CI 0.1% to 3.4%)). Neither had CA-MRSA strains. CONCLUSIONS: CA-MRSA among MSM in Amsterdam is rare. Genital colonisation of S aureus is not associated with high-risk sexual behaviour.

Anorectal and inguinal lymphogranuloma venereum among men who have sex with men in Amsterdam, The Netherlands: trends over time, symptomatology and concurrent infections.

OBJECTIVES: To examine lymphogranuloma venereum (LGV) trends over time among men who have sex with men (MSM) visiting the Amsterdam sexually transmitted infection (STI) clinic; to investigate anal LGV symptomatology; and to examine the positivity and characteristics of anorectal and inguinal LGV. METHODS: We included MSM consultations from whom a swab (from anorectum, bubo or an genital ulcer) was taken for Chlamydia trachomatis (Ct) screening. Anorectal swabs were taken from all MSM who reported receptive anorectal intercourse in the preceding 6 months. Ct positive samples were further tested with a pmpH PCR to identify L-genovars. Patient symptoms, clinical and anoscopic inflammatory signs, and STI co-infections were noted; Gram-stained anorectal mucosal smears were examined. RESULTS: Between January 2005 and June 2012, 48 570 consultations among MSM were conducted. In 3628/35 650 visits, anorectal Ct infections were diagnosed, including 411 anal LGV (1.2%). Moreover, 65/1649 genital ulcer swabs were Ct positive; 10 were inguinal LGV (0.6%) Since January 2011 a significant increase in the positivity of LGV occurred (p<0.0001). 89 (27.2%) anorectal LGV cases were asymptomatic. HIV prevalence among anorectal LGV cases was significantly higher (p=0.008) than among inguinal LGV cases. STI co-morbidity in anorectal LGV cases remained invariably high during the study period. CONCLUSIONS: Since January 2011, LGV positivity in MSM consultations in Amsterdam has risen significantly. The great majority comprise anal LGV; inguinal LGV is rare. Anal LGV is asymptomatic in a quarter of cases. In all MSM with anal Ct infections LGV should be excluded, irrespective of symptoms or inflammatory signs.