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Increased rates of sexually transmitted infections (STIs) are reported among men who have sex with men (MSM) and new interventions are needed. We aimed to assess whether post-exposure prophylaxis (PEP) with doxycycline could reduce the incidence of chlamydia or syphilis (or both) and whether the meningococcal group B vaccine (4CMenB) could reduce the incidence of gonorrhoea in this population. ANRS 174 DOXYVAC is a multicentre, open-label, randomised trial with a 2 × 2 factorial design conducted at ten hospital sites in Paris, France. Eligible participants were MSM aged 18 years or older, HIV negative, had a history of bacterial STIs within the 12 months before enrolment, and who were already included in the ANRS PREVENIR study (a cohort of MSM using pre-exposure prophylaxis with tenofovir and emtricitabine for HIV prevention). Participants were randomly assigned (2:1) to doxycycline PEP (two pills of 100 mg each orally within 72 h after condomless sex, with no more than three doses of 200 mg per week) or no PEP groups and were also randomly assigned (1:1) to the 4CMenB vaccine (GlaxoSmithKline, Paris, France; two intramuscular injections at enrolment and at 2 months) or no vaccine groups, using a computer-generated randomisation list with a permuted fixed block size of four. Follow-up occurred for at least 12 months (with visits every 3 months) up to 24 months. The coprimary outcomes were the risk of a first episode of chlamydia or syphilis (or both) after the enrolment visit at baseline for the doxycycline intervention and the risk of a first episode of gonorrhoea starting at month 3 (ie, 1 month after the second vaccine dose) for the vaccine intervention, analysed in the modified intention-to-treat population (defined as all randomly assigned participants who had at least one follow-up visit). This trial is registered with ClinicalTrials.gov, NCT04597424 (ongoing). Between Jan 19, 2021, and Sept 19, 2022, 556 participants were randomly assigned. 545 (98%) participants were included in the modified intention-to-treat analysis for the doxycycline PEP and no PEP groups and 544 (98%) were included for the 4CMenB vaccine and no vaccine groups. The median follow-up was 14 months (IQR 9–18). The median age was 40 years (34–48) and all 545 participants were male. There was no interaction between the two interventions (p≥0·1) for the primary outcome. The incidence of a first episode of chlamydia or syphilis (or both) was 8·8 per 100 person-years (35 events in 362 participants) in the doxycycline PEP group and 53·2 per 100 person-years (80 events in 183 participants) in the no PEP group (adjusted hazard ratio [aHR] 0·17 [95% CI 0·12–0·26]; p<0·0001). The incidence of a first episode of gonorrhoea, starting from month 3 was 58·3 per 100 person-years (103 events in 274 participants) in the 4CmenB vaccine group and 77·1 per 100 person-years (122 events in 270 participants) in the no vaccine group (aHR 0·78 [95% CI 0·60–1·01]; p=0·061). There were no deaths during the study. One drug-related serious adverse event (fixed-drug eruption) occurred in the doxycycline PEP group. Six (2%) participants in the doxycycline group discontinued doxycycline PEP because of gastrointestinal adverse events. Doxycycline PEP strongly reduced the incidence of chlamydia and syphilis in MSM, but we did not show efficacy of the 4CmenB vaccine for gonorrhoea. Doxycycline PEP should be assessed in other populations, such as heterosexual men and women, and its effect on antimicrobial resistance carefully monitored. ANRS Maladies Infectieuses Emergentes. For the French translation of the abstract see Supplementary Materials section.

In an open-label, randomized study involving men who have sex with men, doxycycline use after high-risk sexual exposure reduced the incidence of sexually transmitted infections (chlamydia, gonorrhea, and syphilis).

The resurgence of syphilis and subsequent risk for newborns has been described worldwide; however, European data on this congenital infection is lacking. We report the activity of a multidisciplinary specialized unit assisting a large area in the Southern Italy. A retrospective cohort study has been conducted at the Perinatal and Pediatric Infectious Diseases Units of the Federico II University of Naples, enrolling all newborns and children referred from January 2010 to June 2022 exposed to Treponema pallidum in utero and/or congenitally infected. A total of 323 patients were included in the analysis. Twenty (6.2%) received a diagnosis of confirmed congenital syphilis (CS) and one died. Fifteen CS cases had typical clinical features. Since 2017, the number of referred neonates tripled while the rate of late maternal diagnoses did not significantly differ. When compared with mothers of exposed infants, mothers of CS cases were younger (25 ± 7.2 vs 29.9 ± 6 years, p  =  0.041 ), had less previous pregnancies (0.64 vs 1.11, p  =  0.044 ), and received a diagnosis of syphilis at a later stage of pregnancy (86% vs 20%, from third trimester or later on; p  < 0.001). Appropriate maternal therapy was protective against vertical transmission (− 1.2; − 1.4, − 1 95% CI; p  < 0.001). Paternal syphilis status was known in 36% of cases. Conclusion : CS has still a significant impact. Prevention should be implemented towards specific maternal risk profiles. A specialized unit is the preferable model to improve surveillance and healthcare for this neglected population. What is Known: • The resurgence of syphilis and subsequent risk for newborns has been described worldwide. • European data on this congenital infection is lacking. What is New: • Congenital syphilis has a significant impact still in Europe and prevention should be implemented towards specific maternal risk profiles.  • A specialized unit is the preferable model to improve surveillance and healthcare for this neglected population.

In 2007 the World Health Organization (WHO) launched the global initiative to eliminate mother-to-child transmission of syphilis (congenital syphilis, or CS). To assess progress towards the goal of <50 CS cases per 100,000 live births, we generated regional and global estimates of maternal and congenital syphilis for 2016 and updated the 2012 estimates. Maternal syphilis estimates were generated using the Spectrum-STI model, fitted to sentinel surveys and routine testing of pregnant women during antenatal care (ANC) and other representative population data. Global and regional estimates of CS used the same approach as previous WHO estimates. The estimated global maternal syphilis prevalence in 2016 was 0.69% (95% confidence interval: 0.57-0.81%) resulting in a global CS rate of 473 (385-561) per 100,000 live births and 661,000 (538,000-784,000) total CS cases, including 355,000 (290,000-419,000) adverse birth outcomes (ABO) and 306,000 (249,000-363,000) non-clinical CS cases (infants without clinical signs born to un-treated mothers). The ABOs included 143,000 early fetal deaths and stillbirths, 61,000 neonatal deaths, 41,000 preterm or low-birth weight births, and 109,000 infants with clinical CS. Of these ABOs- 203,000 (57%) occurred in pregnant women attending ANC but not screened for syphilis; 74,000 (21%) in mothers not enrolled in ANC, 55,000 (16%) in mothers screened but not treated, and 23,000 (6%) in mothers enrolled, screened and treated. The revised 2012 estimates were 0.70% (95% CI: 0.63-0.77%) maternal prevalence, and 748,000 CS cases (539 per 100,000 live births) including 397,000 (361,000-432,000) ABOs. The estimated decrease in CS case rates between 2012 and 2016 reflected increased access to ANC and to syphilis screening and treatment. Congenital syphilis decreased worldwide between 2012 and 2016, although maternal prevalence was stable. Achieving global CS elimination, however, will require improving access to early syphilis screening and treatment in ANC, clinically monitoring all women diagnosed with syphilis and their infants, improving partner management, and reducing syphilis prevalence in the general population by expanding testing, treatment and partner referral beyond ANC.

The World Health Organization initiative to eliminate mother-to-child transmission of syphilis aims for ≥ 90% of pregnant women to be tested for syphilis and ≥ 90% to receive treatment by 2015. We calculated global and regional estimates of syphilis in pregnancy and associated adverse outcomes for 2008, as well as antenatal care (ANC) coverage for women with syphilis. Estimates were based upon a health service delivery model. National syphilis seropositivity data from 97 of 193 countries and ANC coverage from 147 countries were obtained from World Health Organization databases. Proportions of adverse outcomes and effectiveness of screening and treatment were from published literature. Regional estimates of ANC syphilis testing and treatment were examined through sensitivity analysis. In 2008, approximately 1.36 million (range: 1.16 to 1.56 million) pregnant women globally were estimated to have probable active syphilis; of these, 80% had attended ANC. Globally, 520,905 (best case: 425,847; worst case: 615,963) adverse outcomes were estimated to be caused by maternal syphilis, including approximately 212,327 (174,938; 249,716) stillbirths (>28 wk) or early fetal deaths (22 to 28 wk), 91,764 (76,141; 107,397) neonatal deaths, 65,267 (56,929; 73,605) preterm or low birth weight infants, and 151,547 (117,848; 185,245) infected newborns. Approximately 66% of adverse outcomes occurred in ANC attendees who were not tested or were not treated for syphilis. In 2008, based on the middle case scenario, clinical services likely averted 26% of all adverse outcomes. Limitations include missing syphilis seropositivity data for many countries in Europe, the Mediterranean, and North America, and use of estimates for the proportion of syphilis that was \"probable active,\" and for testing and treatment coverage. Syphilis continues to affect large numbers of pregnant women, causing substantial perinatal morbidity and mortality that could be prevented by early testing and treatment. In this analysis, most adverse outcomes occurred among women who attended ANC but were not tested or treated for syphilis, highlighting the need to improve the quality of ANC as well as ANC coverage. In addition, improved ANC data on syphilis testing coverage, positivity, and treatment are needed. Please see later in the article for the Editors' Summary.

BACKGROUNDIncident syphilis infections continue to be especially prevalent among a core group of HIV-infected men who have sex with men (MSM). Because of synergy between syphilis and HIV infections, innovative means for controlling incident syphilis infections are needed. METHODSThirty MSM who had syphilis twice or more since their HIV diagnosis were randomized to receive either daily doxycycline prophylaxis or contingency management (CM) with incentive payments for remaining free of sexually transmitted diseases (STDs). Participants were tested for the bacterial STDs gonorrhea (Neisseria gonorrhoeae), chlamydia (Chlamydia trachomatis) and syphilis at weeks 12, 24, 36, and 48 and completed a behavioral risk questionnaire during each visit to assess number of partners, condom use, and drug use since the last visit. Generalized linear mixed models were used to analyze differences between arms in STD incidence and risk behaviors at follow-up. RESULTSDoxycycline arm participants were significantly less likely to test positive for any selected bacterial STD during 48 weeks of follow-up (odds ratio, 0.27; confidence interval, 0.09–0.83) compared with CM arm participants (P = 0.02).There were no significant self-reported risk behavior differences between the doxycycline and CM arms at follow-up. CONCLUSIONSDaily doxycycline taken prophylactically was associated with a decreased incidence of N. gonorrhoeae, C. trachomatis, or syphilis incident infections among a core group of HIV-infected MSM at high risk for these infections. Safe and effective biomedical tools should be included in the efforts to control transmission of syphilis, especially in this population. A randomized clinical trial should be conducted to confirm and extend these findings.

Background The impact of untreated syphilis during pregnancy on neonatal health remains a major public health threat worldwide. Given the high prevalence of syphilis during pregnancy in Zambia and Democratic Republic of Congo (DRC), the Preventive Congenital Syphilis Trial (PCS Trial), a cluster randomized trial, was proposed to increase same-day screening and treatment of syphilis during antenatal care visits. To design an accepted and feasible intervention, we conducted a qualitative  formative research. Our objective was to identify context-specific  barriers and facilitators to the implementation of antenatal screening and treatment during pregnancy. Methods Qualitative research included in-depth semi-structured interviews with clinic administrators, group interviews with health care providers, and focus groups with pregnant women in primary care clinics (PCCs) in Kinshasa (DRC) and Lusaka (Zambia). Results A total of 112 individuals participated in the interviews and focus groups. Barriers for the implementation of syphilis testing and treatment were identified at the a) system level: fragmentation of the health system, existence of ANC guidelines in conflict with proposed intervention, poor accessibility of clinics (geographical and functional), staff and product shortages at the PCCs; b) healthcare providers’ level: lack of knowledge and training about evolving best practices, reservations regarding same-day screening and treatment; c) Pregnant women level: late enrollment in ANC, lack of knowledge about consequences and treatment of syphilis, and stigma. Based on these results, we developed recommendations for the design of the PCS Trial intervention. Conclusion This research allowed us to identify barriers and facilitators to improve the feasibility and acceptability of a behavioral intervention. Formative research is a critical step in designing appropriate and effective interventions by closing the “know-do gap”.

Low syphilis testing uptake is a major public health issue among men who have sex with men (MSM) in many low- and middle-income countries. Syphilis self-testing (SST) may complement and extend facility-based testing. We aimed to evaluate the effectiveness and costs of providing SST on increasing syphilis testing uptake among MSM in China. An open-label, parallel 3-arm randomized controlled trial (RCT) was conducted between January 7, 2020 and July 17, 2020. Men who were at least 18 years of age, had condomless anal sex with men in the past year, reported not testing for syphilis in the last 6 months, and had a stable residence with mailing addresses were recruited from 124 cities in 26 Chinese provinces. Using block randomization with blocks of size 12, enrolled participants were randomly assigned (1:1:1) into 3 arms: standard of care arm, standard SST arm, and lottery incentivized SST arm (1 in 10 chance to win US$15 if they had a syphilis test). The primary outcome was the proportion of participants who tested for syphilis during the trial period and confirmed with photo verification and between arm comparisons were estimated with risk differences (RDs). Analyses were performed on a modified intention-to-treat basis: Participants were included in the complete case analysis if they had initiated at least 1 follow-up survey. The Syphilis/HIV Duo rapid test kit was used. A total of 451 men were enrolled. In total, 136 (90·7%, 136/150) in the standard of care arm, 142 (94·0%, 142/151) in the standard of SST arm, and 137 (91·3%, 137/150) in the lottery incentivized SST arm were included in the final analysis. The proportion of men who had at least 1 syphilis test during the trial period was 63.4% (95% confidence interval [CI]: 55.5% to 71.3%, p = 0.001) in the standard SST arm, 65.7% (95% CI: 57.7% to 73.6%, p = 0.0002) in the lottery incentivized SST arm, and 14.7% (95% CI: 8.8% to 20.7%, p < 0.001) in the standard of care arm. The estimated RD between the standard SST and standard of care arm was 48.7% (95% CI: 37.8% to 58.4%, p < 0.001). The majority (78.5%, 95% CI: 72.7% to 84.4%, p < 0.001) of syphilis self-testers reported never testing for syphilis. The cost per person tested was US$26.55 for standard SST, US$28.09 for the lottery incentivized SST, and US$66.19 for the standard of care. No study-related adverse events were reported during the study duration. Limitation was that the impact of the Coronavirus Disease 2019 (COVID-19) restrictions may have accentuated demand for decentralized testing. Compared to standard of care, providing SST significantly increased the proportion of MSM testing for syphilis in China and was cheaper (per person tested). Chinese Clinical Trial Registry: ChiCTR1900022409.

Background. Syphilis infection may potentiate transmission of human immunodeficiency virus (HIV). We sought to determine the extent to which HIV acquisition was associated with syphilis infection within an HIV preexposure prophylaxis (PrEP) trial and whether emtricitabine/tenofovir (FTC/TDF) modified that association. Methods. The Preexposure Prophylaxis Initiative (iPrEx) study randomly assigned 2499 HIV-seronegative men and transgender women who have sex with men (MSM) to receive oral daily FTC/TDF or placebo. Syphilis prevalence at screening and incidence during follow-up were measured. Hazard ratios for the effect of incident syphilis on HIV acquisition were calculated. The effect of FTC/TDF on incident syphilis and HIV acquisition was assessed. Results. Of 2499 individuals, 360 (14.4%) had a positive rapid plasma reagin test at screening; 333 (92.5%) had a positive confirmatory test, which did not differ between the arms (FTC/TDF vs placebo, P = .81). The overall syphilis incidence during the trial was 7.3 cases per 100 person-years. There was no difference in syphilis incidence between the study arms (7.8 cases per 100 person-years for FTC/TDF vs 6.8 cases per 100 person-years for placebo, P = .304). HIV incidence varied by incident syphilis (2.8 cases per 100 person-years for no syphilis vs 8.0 cases per 100 person-years for incident syphilis), reflecting a hazard ratio of 2.6 (95% confidence interval, 1.6–4.4; P < .001). There was no evidence for interaction between randomization to the FTC/TDF arm and incident syphilis on HIV incidence. Conclusions. In HIV-seronegative MSM, syphilis infection was associated with HIV acquisition in this PrEP trial; a syphilis diagnosis should prompt providers to offer PrEP unless otherwise contraindicated.

Male circumcision has been shown to reduce the acquisition of the human immunodeficiency virus (HIV) in circumcised men. In two studies in Uganda involving 3393 adolescent boys and men who were seronegative for HIV and for herpes simplex virus type 2 (HSV-2), circumcision reduced the acquisition of HSV-2 and the prevalence of high-risk human papillomavirus (HPV) infection but not the acquisition of syphilis. In two studies in Uganda, circumcision reduced the acquisition of herpes simplex virus type 2 (HSV-2) and the prevalence of high-risk human papillomavirus (HPV) infection but not the acquisition of syphilis. Herpes simplex virus type 2 (HSV-2) and human papillomavirus (HPV) infections and syphilis are common sexually transmitted infections. HSV-2 infection and syphilis are two of the main causes of genital ulceration 1 – 3 and have been associated with an increased risk of human immunodeficiency virus (HIV) infection in observational studies. 1 , 2 , 4 The prevalence of HPV is significantly increased in developing nations. 5 HPV infection can cause genital warts, and high-risk HPV genotypes are associated with penile and anal cancer, as well as with cervical cancer in female partners. 5 , 6 Three randomized trials and multiple observational studies showed that male circumcision significantly . . .