Syphilis testing in blood donors, France, 2007 to 2022.

BackgroundSyphilis in blood donors (BD) has increased in many countries.AimWe aimed to describe trends in syphilis seroposivity in BD in France, to identify risk factors and assess if a non-treponemic test (NTT) could define BD having recovered from syphilis for more than 1 year.MethodsThe analysis covered the period 2007 to 2022 and 45,875,939 donations. Of the 474 BD syphilis-positive in 2022, 429 underwent additional investigations with an NTT. History of syphilis was obtained at the post-donation interview or based on serology results for repeat donors.ResultsUntil 2021, positivity rates remained stable (mean: 1.18/10,000 donations, range: 1.01-1.38). An increased rate was observed in 2022 (1.74/10,000; p = 0.02). Over the whole study period, prevalence was 2.2 times higher in male than in female BD (4.1 times higher in 2022). The proportion of males with an identified risk factor who have sex with men increased from 16.7% in 2007 to 64.9% in 2022. Based on NTT, 79 (18%) of the donors who were seropositive in 2022 were classified as having been infected in the previous year. History of syphilis was available for 30 of them. All had an infection within the previous 3 years. Among seven donors with a syphilis < 12 months before testing, one had an NTT titre ≥ 8, three a titre between 1 and 4, three were negative.ConclusionSyphilis seropositivity increased considerably in BDs in 2022, mostly in males, notably MSM. Available data did not allow appropriate evaluation of the NTT to distinguish recent from past infection.

Specific detection of Treponema pallidum in clinical samples: validation of a qPCR assay combining two genomic targets.

OBJECTIVES: We evaluated a real-time quantitative PCR (qPCR) for detection of the Treponema pallidum (TP) genome in clinical samples through simultaneous detection of two genomic targets. METHODS: We performed qPCR with TaqMan technology using two TP genes, polA and tpp47, as targets, with an internal positive control. The qPCR assay was compared with syphilis diagnosis based on a combination of clinical examination, serological results and inhouse nested PCR (nPCR). Samples were analysed at the National Reference Center for STIs at Cochin Hospital in Paris. RESULTS: In total, from October 2010 to December 2016, 320 documented clinical samples (mucosal and cutaneous swabs) were collected from patients with or without syphilis attending STI centres in France. The qPCR had an overall sensitivity of 89% (95% CI 85.1% to 92.1%), a specificity of 100%, a positive predictive value of 100% and a negative predictive value of 88% (95% CI 84.3% to 91.5%). The agreement between qPCR and nPCR results was 94% (κ=0.88, 95% CI 0.83 to 0.93). Calibration of the qPCR assay, by cloning both the polA and tpp47 genes, defined the detection threshold as 1 copy/µL of DNA elution. CONCLUSIONS: We validated a new qPCR for detecting the TP genome in clinical samples with excellent sensitivity and specificity. The cloning of polA and tpp47 genes for calibration would be interesting in the evaluation of bacterial loads in samples.

Severe Scabies: A French Multi-centre Study Involving 95 Patients with Crusted and Profuse Disease and Review of the Literature.

The aim of this multi-centre French retrospective study was to identify severe, i.e. crusted and profuse, scabies patients. Records were retrieved from 22 Dermatology or Infectious Diseases departments in the Ile-de-France from January 2009 to January 2015 to characterize epidemiology, demography, diagnosis, contributing factors, treatment features, and outcomes in severe scabies. A total of 95 inpatients (57 crusted and 38 profuse) were included. A higher number of cases was observed among elderly patients (>75 years), mostly living in institutions. Thirteen patients (13.6%) reported a history of previously treated scabies. Sixty-three patients (66.3%) had been seen by a previous practitioner for the current episode (up to 8 previous visits). Initial misdiagnosis (e.g. eczema, prurigo, drug-related eruptions, psoriasis) was documented in 41 patients (43.1%). Fifty-eight patients (61%) had already received 1 or more previous treatments for their current episode. Forty percent received corticosteroids or acitretin for an initial diagnosis of eczema or psoriasis. Median time from the onset of symptoms to the diagnosis of severe scabies was 3 months (range 0.3-22). Itch was present in all patients at diagnosis. Most patients (n=84, 88.4%) had comorbidities. Diagnostic and therapeutic approaches varied. Complications occurred in 11.5% of cases. To date, there is no consensus for diagnosis and treatment, and future standardization of is required for optimal management.

Comparison of molecular and serological assays on cerebrospinal fluid for the diagnosis of neurosyphilis.

BACKGROUND: Many assays are available on cerebrospinal fluid (CSF) for the diagnosis of neurosyphilis (NS) but there is no 'gold standard'. OBJECTIVES: The aim of this study was to evaluate different molecular and serological assays used in NS. METHODS: We evaluated two PCR assays and three serological techniques in parallel on CSF samples collected between 2019 and 2020 from patients suspected of NS. RESULTS: The study included 143 patients comprising 30 early NS, 7 late NS and 106 patients without a diagnosis of NS. All patients with NS were symptomatic and had either neurological (67.6%) or ophthalmological signs (54.1%). The qPCR and nPCR assays had overall sensitivities (Se) of 41% and 27%, respectively; with each an overall specificity (Sp) of 100%. VDRL had a Se of 51% and a Sp of 92%. Immunoblot had a Se of 62% and a Sp of 85%. Finally, treponemal tests (TT) had a Se of 96% and a Sp of 69%. CONCLUSIONS: Our study confirms the excellent specificity of molecular techniques allowing to avoid overdiagnosis of NS, and thus, unjustified intensive antibiotic therapy protocols. CSF TT, although not very specific, has an excellent Se confirming that there is almost never NS with negative CSF TT. VDRL and immunoblot tests have better overall diagnostic performance. However, none of these techniques has sufficient diagnostic performance to represent a 'gold standard'. Thus, the diagnosis of NS relies on a combination of clinical and biological parameters with the association of PCR with serology, associating VDRL and immunoblot, in CSF.

Bartonella and Coxiella infections presenting as systemic vasculitis: case series and review of literature.

OBJECTIVES: Coxiella and Bartonella spp. display particular tropism for endothelial or endocardial tissues and an abnormal host response to infections with induced autoimmunity. We aimed, through a case series combined with a comprehensive literature review, to outline characteristics of Coxiella and Bartonella infections presenting as systemic vasculitis. METHODS: We retrospectively included cases of definite Coxiella and Bartonella infections presenting with vasculitis features and performed a comprehensive literature review. RESULTS: Six cases of Bartonella infections were added to 18 cases from literature review. Causative pathogens were mainly B. henselae. Bartonella infection mimicked ANCA-associated vasculitis in 83% with PR3-ANCA and presented as cryoglobulinaemic vasculitis in 8%. GN was present in 92%, and 88% had endocarditis. Complement fractions were low in 82% and rheumatoid factor positive in 85%. Kidney biopsies showed cell proliferation, mostly crescentic, with pauci-immune GN in 29%. Outcome was favourable, with the use of antibiotics alone in one-third. Five cases of Coxiella infections were added to 16 from literature review. Sixteen had small-vessel vasculitides, mainly cryoglobulinaemia vasculitis in 75%. One patient had polyarteritis nodosa-like vasculitis and four large-vessel vasculitis. Outcome was good except for one death. A highly sensitive next generation sequencing analysis on three Coxiella- and two Bartonella-related vasculitides biopsies did not find any bacterial DNA. CONCLUSION: Coxiella and Bartonella are both able to induce vasculitis but display distinct vasculitis features. Bartonella mimics PR3-ANCA-associated vasculitis in the setting of endocarditis, whereas Coxiella may induce vasculitis involving all vessel sizes.

Sweet-like syndrome and multiple COVID arm syndrome following COVID-19 vaccines: 'specific' patterns in a series of 192 patients.

The two clinico-pathological patterns are 'Sweet-like syndrome' and 'Multiple COVID-Arm'. 'Sweet-like syndrome' presents clinically as erythematous and oedematous papules or plaques, sometimes developing vesiculation or bullae. Histology shows classical Sweet syndrome with a diffuse dermal neutrophilic infiltrate, or an infiltrate of histiocyte-like immature myeloid cells consistent with a histiocytoid Sweet syndrome. 'Multiple COVID-arm' is characterized by multiple large inflammatory plaques with histological analyses showing a perivascular and interstitial inflammatory infiltrate with eosinophils.

Cluster analysis reveals eosinophilia and fibrosis as poor prognostic markers in 128 patients with eosinophilic fasciitis.

BACKGROUND: Eosinophilic fasciitis (EF) is an extremely rare disease with polymorphic presentation and prognosis. OBJECTIVE: To further investigate EF features. METHODS: We performed a retrospective multicentre study of EF patients from 2013 to 2019, clustered patients using multivariate correspondence analysis, and sought prognosis factors. RESULTS: One hundred twenty-eight patients were included. Sixty-nine (50%) patients had skin sclerosis, and eosinophil count was increased in 71 (55%) patients. Multivariate correspondence analysis identified 3 clusters: a "mild," a "late-onset and hypereosinophilic," and a "fibrotic" cluster. Of 109 patients who followed up for more than 1 year, 49 (45%) presented a relapse, and 48 (44%) had sequelae. Multivariate analysis revealed that eosinophilia (hazard ratio = 1.56; P = .02) and fibrosis (hazard ratio = 4.02; P = .002) were predictive factors of relapse, whereas edema (odds ratio = 0.31; P = .03), relapse (odds ratio = 3.00; P = .04) and fibrosis (odds ratio = 1) were predictive factors of sequelae. Following relapse, treatment modifications consisted of an increase in glucocorticoids in 40 (82%) patients and the addition of methotrexate in 31 (63%) patients. These modifications led to clinical improvement and glucocorticoid withdrawal in 37 (76%) and 22 (45%) patients. LIMITATIONS: Retrospective study. CONCLUSION: EF patients can be divided into 3 homogenous clusters, which, along with fibrosis and eosinophilia, are prognosis factors of relapse and sequelae.

Bullous pemphigoid: Three main clusters defining 3 outcome profiles.

BACKGROUND: Bullous pemphigoid (BP) is the most common autoimmune blistering disorder. Its presentation is polymorphic. OBJECTIVE: To investigate different clinical and biological profiles of BP. METHODS: We conducted a retrospective 2-center study including all BP patients seen between January 1, 2015, and February 28, 2021. We performed hierarchical clustering on principal components. RESULTS: Three clusters were identified. Patients in cluster 1 (n = 155) were older than those in clusters 2 (n = 89) and 3 (n = 35; P < .0001), more frequently presented pauci-bullous BP (n = 63 [41%] vs 14 [16%] and 2 [6%], respectively; P < .0001) and had anti-BP230 antibodies in 87% of cases. More than 100 blisters were observed in 14 patients (40%) from cluster 3, versus 3 (2%) from cluster 1 and 0 (0%) from cluster 2 (P < .0001). Frequency of mucosal involvement was higher in cluster 3 (n = 32 [91%, including epiglottis in 40%] vs 11 [7%] and 34 [38%]; P < .0001). In clusters 2 and 3, 70% and 74% of patients had antibodies targeting only BP180. Those in cluster 3 received more lines of systemic treatment and experienced more relapses. LIMITATIONS: Retrospective study without immunoelectron microscopy. CONCLUSION: We identified 3 different BP clusters, including one corresponding to severe BP180+ BP230- BP with features common to mucous membrane pemphigoid.

Efficacy and safety of treatments in cutaneous polyarteritis nodosa: A French observational retrospective study.

BACKGROUND: Cutaneous polyarteritis nodosa is a form of medium-sized vessel vasculitis. Despite a disabling and prolonged course, data on treatment efficacy and safety remain scarce. OBJECTIVES: We aimed to describe treatment efficacy and safety in patients with cutaneous polyarteritis nodosa. METHODS: This multicenter retrospective, observational study, recorded clinical and biologic data together with treatments received. The primary outcome was the rate of complete response at month 3. Secondary outcomes assessed drug survival and safety. RESULTS: We included 68 patients who received a median of 2 therapeutic lines (interquartile range, 1-3). Overall, complete response was achieved in 13 of 42 (31%) patients with colchicine, 4 of 17 (23%) with dapsone, 11 of 25 (44%) with glucocorticoids (GCs) alone, 1 of 9 (11%) with nonsteroidal anti-inflammatory drugs, 11 of 13 (84%) with GCs+azathioprine, and 7 of 15 (47%) with GCs+methotrexate. GCs+azathioprine had the best drug survival (median duration, 29.5 months; interquartile range, 19.5-36.0). Response at month 3 was decreased with peripheral neurologic involvement (odds ratio, 0.19; 95% confidence interval, 0.03-0.81; P = .04). Overall, the rate of treatment-related adverse events was 18%, which led to the discontinuation of treatment in 7% of patients. LIMITATION: Retrospective study. CONCLUSION: Colchicine seems to confer good benefit-risk balance in cutaneous polyarteritis nodosa without peripheral sensory neuropathy. GCs+azathioprine seem the best treatment in the event of relapse.

Use of healthcare reimbursement data to monitor bacterial sexually transmitted infection testing in France, 2006 to 2020.

BackgroundDiagnoses of bacterial sexually transmitted infections (STIs) have increased in France since the 2000s. The main strategy to control STI transmission is recommending/facilitating access to condom use, testing, and antibiotic treatments.AimThis study analyses the evolution of STI testing in the private sector in France from 2006 to 2020.MethodsNational health insurance reimbursement data were used to determine numbers and rates of individuals aged ≥ 15 years tested for diagnoses of chlamydia, gonorrhoea and syphilis in the private sector in France and to describe their evolution from 2006 to 2020.ResultsUpward tendencies in testing were observed from 2006 to 2019 for all three STIs. The highest testing rates were identified in people aged 25‒29-years old. The observed testing-increase from 2017 to 2019 was twice as high in young people (< 25 years old) as in older people. In 2019, chlamydia, gonorrhoea and syphilis testing rates were respectively 45.4 (+ 21% since 2017), 41.3 (+ 60%), and 47.2 (+ 22%) per 1,000 inhabitants. For all STIs combined, the number of tested individuals decreased by 37% between March and April 2020 during the first COVID-19 epidemic wave and lockdown in France.ConclusionImprovements found in STI testing rates may have resulted from better awareness, especially among young people and health professionals, of the importance of testing, following prevention campaigns. Nevertheless, testing levels remain insufficient considering increasing diagnoses. In 2020, the COVID-19 pandemic had a considerable impact on STI testing. Partner notification and offering diverse testing opportunities including self-sampling are essential to control STI epidemics particularly in exposed populations.

Characterization of a Cutibacterium acnes Camp Factor 1-Related Peptide as a New TLR-2 Modulator in In Vitro and Ex Vivo Models of Inflammation.

Cutibacterium acnes (C. acnes) has been implicated in inflammatory acne where highly mutated Christie-Atkins-Munch-Petersen factor (CAMP)1 displays strong toll like receptor (TLR)-2 binding activity. Using specific antibodies, we showed that CAMP1 production was independent of C. acnes phylotype and involved in the induction of inflammation. We confirmed that TLR-2 bound both mutated and non-mutated recombinant CAMP1, and peptide array analysis showed that seven peptides (A14, A15, B1, B2, B3, C1 and C3) were involved in TLR-2 binding, located on the same side of the three-dimensional structure of CAMP1. Both mutated and non-mutated recombinant CAMP1 proteins induced the production of C-X-C motif chemokine ligand interleukin (CXCL)8/(IL)-8 in vitro in keratinocytes and that of granulocyte macrophage-colony stimulating factor (GM-CSF), tumor necrosis factor (TNF)-α, IL-1ß and IL-10 in ex vivo human skin explants. Only A14, B1 and B2 inhibited the production of CXCL8/IL-8 by keratinocytes and that of (GM-CSF), TNF-α, IL-1ß and IL-10 in human skin explants stimulated with rCAMP1 and C. acnes. Following pretreatment with B2, RNA sequencing on skin explants identified the 10 genes displaying the strongest differential expression as IL6, TNF, CXCL1, CXCL2, CXCL3, CXCL8, IL-1ß, chemokine ligand (CCL)2, CCL4 and colony stimulating factor (CSF)2. We, thus, identified a new CAMP1-derived peptide as a TLR-2 modulator likely to be a good candidate for clinical evaluation.

Ocular Safety Profile of BRAF and MEK Inhibitors: Data from the World Health Organization Pharmacovigilance Database.

PURPOSE: BRAF inhibitors (BRAFi) and MEK inhibitors (MEKi) significantly improved metastatic melanoma prognosis. Ocular adverse effects (OAEs) represent an uncommon but disabling toxicity of these drugs. We aimed to characterize the ocular safety profile of BRAFi or MEKi and to detect possible safety signals. METHODS: We performed a retrospective, observational, pharmacovigilance study using VigiBase, the World Health Organization global safety database. Ocular adverse effects were classified according to the eye segments and the inflammatory pattern based on the Standardization of Uveitis Nomenclature. Associations among BRAFi monotherapy, MEKi monotherapy, and BRAFi+MEKi combination therapy and OAE reporting were assessed using disproportionality analysis. Results were expressed with the reporting odds ratio (ROR) and its 95% confidence interval (CI). RESULTS: From January 2010 to October 2019, 1568 OAE cases were reported with BRAFi or MEKi. Among them, 1006 cases with sufficient data were included, corresponding to 310 (30.8%), 124 (12.3%), and 572 (56.9%) cases reported with BRAFi, MEKi, or BRAFi+MEKi combination therapy, respectively. BRAF inhibitor monotherapy was significantly associated with the reporting of iris and ciliary body abnormalities (ROR, 8.7; 95% CI, 6.0-12.5), diffuse abnormalities (ROR, 7.1; 95% CI, 5.4-9.4), anterior uveitis (ROR, 8.6; 95% CI, 6.0-12.1), and panuveitis (ROR, 7.1; 95% CI, 5.4-9.4). MEK inhibitor monotherapy was associated with the reporting of retinal and choroid abnormalities (ROR, 9.5; 95% CI, 7.4-12.2), diffuse abnormalities (ROR, 2.5; 95% CI, 1.1-6.1), and panuveitis (ROR, 2.5; 95% CI, 1.1-6.1). Combinations of BRAFi and MEKi therapies were associated with OAEs from both drugs, with a possible synergistic or additive effect for diffuse abnormalities and panuveitis. CONCLUSIONS: Our study characterizes the ocular safety profile of BRAFi and MEKi. We identify possible safety signals for several OAEs not previously reported with BRAFi and MEKi. Our data provide the rationale for a personalized management of OAE in patients with BRAFi+MEKi combination therapy according to the type of ocular reaction.

Oral forms of secondary syphilis: An illustration of the pitfalls set by the great imitator.

INTRODUCTION: Syphilis is reemerging in certain populations, such as in men who have sex with men in particular. Oral manifestations are not uncommon and can render diagnosis difficult, particularly if occurring in isolation. MATERIALS AND METHODS: We recovered clinical data for all patients receiving a diagnosis of secondary syphilis who were referred to the National Reference Center for Syphilis in Paris, France, from January 2000 to July 2019. We selected patients presenting oral symptoms only and analyzed their general characteristics, time to diagnosis, and clinical presentations. RESULTS: Secondary syphilis was diagnosed in 206 patients, 38 of whom (18%) presented oral manifestations, which were isolated in 14 patients (37%). The main oral manifestations were subacute erosive or ulcerative lesions (55%), mucous patches on the tongue (53%), and nodular (10%) and leukokeratotic lesions (5%). Mean time to diagnosis was 4.5 months, but was significantly longer for patients with isolated oral symptoms (8.8 vs 1.8 months; P = .02). CONCLUSION: Oral presentations of secondary syphilis are frequent and challenging for diagnosis, even in patients with epidemiologic risk factors. Clinicians confronted with subacute oral lesions in such patients should bear in mind the possibility of this contagious, curable, and sometimes severe disease.

Update on oncogenesis and therapy for Kaposi sarcoma.

PURPOSE OF REVIEW: This review is an update of the recent findings on pathophysiology of Kaposi sarcoma, the role of HHV-8 in Kaposi sarcoma pathogenesis and to summarize the recent advances in the treatment of Kaposi sarcoma and the role of immunity to control the disease. RECENT FINDINGS: The causal agent of Kaposi sarcoma is HHV-8 and the mechanism by which HHV-8 drives the tumor development is unique. HHV-8 is not a classic oncogenic virus and the disease is an opportunistic tumor responding to immune restoration when it is possible. SUMMARY: Five epidemiologic types of Kaposi are recognized and HHV-8 is associated to all epidemiologic forms of Kaposi. HHV-8 is a virus favoring both angiogenesis and cellular proliferation, which are the two main histological features of Kaposi sarcoma. Although in many cases, treatment of Kaposi sarcoma is not necessary, specific chemotherapy, immunomodulation and immune stimulation are the tools for treating Kaposi sarcoma. Monochemotherapy has been shown to be as efficient as polychemotherapy and less toxic. Immune checkpoint inhibitors gave some promising results, which should be confirmed by prospective studies.

Mastocytosis onset in a patient with treated hairy cell leukemia: Just a coincidence?

Mastocytosis is a mast cell disease caused by functionally defective infiltrating mast cells and CD34+ mast cell precursors. The heterogeneous group of mast cell disorders is categorized into five variants in the updated 2017 World Health Organization (WHO) classification among those systemic mastocytosis with an associated neoplasm (SM-AHN). Except for myeloid neoplasia, lymphoproliferative disorders associated to SM-AHN are more scarce. Here, we report the second case ever described of associated mastocytosis and hairy-cell disease. A 38-year-old female patient without any specific medical history was diagnosed a hairy cell leukemia and BRAFV600E mutation was found in hairy cells. Since purine-analogs were avoided to prevent prolonged myelosuppression, she was treated with vemurafenib and rituximab. Despite early discontinuation due to vemurafenib-induced agranulocytosis, a partial response was observed. Strikingly, bone marrow biopsy performed one month after vemurafenib discontinuation revealed a nodular infiltration by 30% tumoral mastocytes. Along with elevated tryptase level, KITD816V mutation on mastocytes and clinical exam, the patient was diagnosed with systemic mastocytosis with an associated hematological neoplasm (SM-AHN). No BRAFV600E mutation was found on mastocytes. The physiopathology of this association is not known and might be only a coincidence or a common genetic driver mutation enhancing mast and hairy cells.

Partial response in hairy cell leukemia with vemurafenib despite early discontinuation due to agranulocytosis.

Vemurafenib is an oral BRAF kinase inhibitor approved since 2012 for the treatment of patients with unresectable or metastatic melanoma with BRAF mutations. Vemurafenib also demonstrated efficacy for patients with hairy cell leukemia genetically characterized by BRAF mutation. Here, we report the case of a 38-year-old female patient without any previous medical history who experienced agranulocytosis associated with erythrodermia after vemurafenib initiation for the treatment of hairy cell leukemia. Agranulocytosis was confirmed with bone marrow examination. Vemurafenib was considered the most probable drug responsible for this agranulocytosis and was thus stopped. We observed a full neutrophils recovery 10 days after vemurafenib cessation without any haematopoietic growth factors. A bone marrow biopsy performed 1 month after aplasia ending showed a good partial response with less than 5% of hairy cells remaining. To our knowledge, this is the first case ever described by vemurafenib-induced agranulocytosis. Thus, physicians should be warned about this risk given the growing number of patients treated with vemurafenib.

Surveillance of Antibiotic Resistance Genes in Treponema Pallidum Subspecies Pallidum from Patients with Early Syphilis in France.

Benzathine penicillin G (BPG) is the reference treatment for early syphilis, but shortages have recently been reported, highlighting a need for the validation of alternative treatments. The aim of this study was to evaluate the genomic resistance of Treponema pallidum subspecies pallidum (TPA) to macrolides and doxycycline in France. Swabs from genital, anal, oral and cutaneous lesions were obtained from 146 patients with early syphilis in France. They were screened for mutations conferring resistance to macrolides and doxycycline by nested PCR and sequencing. Resistance to macrolides was detected in 85% of the isolates, but no point mutations conferring doxycycline resistance were detected. These findings confirm that, in France, resistance to macrolides is widespread. Moreover, we confirmed the absence of genomic resistance to doxycycline in the TPA strains. Therefore, doxycycline could be safely recommended as an alternative to BPG for the treatment of early syphilis.

Trends and determinants of condomless sex in gonorrhoea patients diagnosed in France through the sentinel surveillance network ResIST, 2005-2014.

BACKGROUND: Gonorrhoea is increasing in France since its resurgence in the late 1990's. Understanding trends of condomless sex is a requirement to tailor prevention toward most exposed individuals. This study aims to analyse trends and determinants of condomless penetrative sex (PS) in MSM and heterosexuals diagnosed with gonorrhoea in France. METHODS: A standardized self-administered questionnaire filled by 3453 patients was used to monitor condomless sex through the sentinel surveillance network ResIST between 2005 and 2014. Trends were used to describe consistent condom use for penetrative sex (PS). A logistic regression model analysed patients' characteristics associated with condomless PS. RESULTS: Between 2005 and 2014, condomless PS increased regardless of sexual orientation. Condomless PS was particularly common among HIV positive men who have sex with men (MSM (65%)). People living in metropolitan regions outside Paris area (adjusted odds-ratio (AOR) [95% CI] =1.33[1.12-1.58]) were more likely to engage in condomless PS. Conversely, MSM (AOR [95% CI] =0.21 [0.16-0.29]), HIV seronegative patients (AOR [95% CI] =0.68 [0.51-0.89]), patients diagnosed in hospital (AOR [95% CI] = 0.66 [0.45-0.97]) and multi-partners (≥ 10 partners, AOR [95% CI] = 0.54 [0.40-0.74]) were more likely to use condoms. CONCLUSIONS: These findings highlight a decreasing use of condom in MSM and heterosexuals diagnosed with gonorrhoea. Prevention strategies should take in account drivers of condomless sex in a context of uncontrolled STI epidemics.

iNKT and memory B-cell alterations in HHV-8 multicentric Castleman disease.

Human herpesvirus 8 (HHV-8) is the causative agent of Kaposi sarcoma (KS) and multicentric Castleman disease (MCD), a life-threatening, virally induced B-cell lymphoproliferative disorder. HHV-8 is a B-lymphotropic γ-herpesvirus closely related to the Epstein-Barr virus (EBV). Invariant natural killer T (iNKT) cells are innate-like T cells that play a role in antiviral immunity, specifically in controlling viral replication in EBV-infected B cells. Decline of iNKT cells is associated with age or HIV infection, both situations associated with HHV-8-related diseases. We analyzed iNKT cells in both blood (n = 26) and spleen (n = 9) samples from 32 patients with HHV-8 MCD and compared them with patients with KS (n = 24) and healthy donors (n = 29). We determined that both circulating and splenic iNKT cell frequencies were markedly decreased in patients with HHV-8 MCD and were undetectable in 6 of them. Moreover, iNKT cells from patients with HHV-8 MCD displayed a proliferative defect after stimulation with α-galactosylceramide. These iNKT cell alterations were associated with an imbalance in B-cell subsets, including a significant decrease in memory B cells, particularly of marginal zone (MZ) B cells. Coculture experiments revealed that the decrease in iNKT cells contributed to the alterations in the B-cell subset distribution. These observations contribute to a better understanding of the complex interactions between HHV-8 and immune cells that cause HHV-8-related MCD.