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.

Lymphogranuloma Venereum-Serovar L2b Presenting With Painful Genital Ulceration: An Emerging Clinical Presentation?

These 5 cases of atypical inflammatory lymphogranula venereum (LGV) serovar L2b presenting initially with edema and persistent painful ulceration illustrate that clinical manifestations of LGV in the current outbreak in men who have sex with men reflect the influence of both the serovars virulence and the host immune system and are not confined to proctitis. L2b serovar could have a particular high virulence profile, and the need for awareness of LGV as a cause of genital ulceration is crucial.

Did L Strains Responsible for Lymphogranuloma Venereum Proctitis Spread Among People With Genital Chlamydia trachomatis Infection in France in 2013?

We retrospectively analyzed 1802 nonrectal Chlamydia trachomatis-positive specimens to determine if the L strains responsible for rectal Lymphogranuloma venereum in men who have sex with men could spread to the heterosexual population. No evidence for Lymphogranuloma venereum transmission among heterosexuals in France was observed in 2013. L2b strains seem to be restricted to the men who have sex with men population.

Recalcitrant pseudotumoral anogenital herpes simplex virus type 2 in HIV-infected patients: evidence for predominant B-lymphoplasmocytic infiltration and immunomodulators as effective therapeutic strategy.

BACKGROUND: In patients with human immunodeficiency virus (HIV) infection, genital herpetic lesions may be extensive and tend to persist for longer periods; in addition, atypical hypertrophic, ulcerative, or pseudotumor forms have been reported, frequently showing resistance to acyclovir (ACV) treatment. METHODS: Between 2003 and 2011, 10 HIV-1-infected patients presenting with chronic pseudotumoral anogenital herpes simplex type 2 (HSV-2) infections were studied. RESULTS: All patients developed chronic, hypertrophic HSV-2 anogenital lesions with multilesional presentation in 7 cases and involvement of 2 anatomical sites in 6 of them. At the time of diagnosis, the median CD3(+)CD4(+) absolute blood count was 480.5 cells/µL (range, 165-632 cells/µL), whereas the plasma HIV load was undetectable in all cases. Histopathologic analysis of lesion biopsies showed a moderately dense dermal polytypic plasma cell infiltrate. Detection of HSV-2 by culture and/or polymerase chain reaction was positive for all patients, with evidence for ACV-resistant strains in 6 of 8 cases. In addition, viral resistance to ACV was found only in HSV-2 isolated from ulcerative lesions, whereas purely pseudotumoral ones harbored sensitive strains. Durable control was observed with HSV DNA polymerase inhibitors in only 2 cases, and the immunomodulators imiquimod and thalidomide allowed 5 patients to reach sustained complete response. CONCLUSIONS: HSV-2-related pseudolymphoma in HIV-infected patients is characterized by a predominant polyclonal lymphoplasmacytic infiltration, and is frequently refractory to antiherpetic drugs. Immunomodulatory therapeutic strategies using thalidomide showed consistent efficacy, and should be considered early during the course of disease.

Molecular subtyping of Treponema pallidum in Paris, France.

Two major Treponema pallidum subtypes, 14 d/g and 14 d/f, were identified in a population of 119 patients with syphilis in Paris, France, characterized by a high proportion of men who have sex with men. A new subtype named 11 q/j was characterized, and a reinfection case was determined in 1 patient having consecuitve syphilis infection at 19-month interval.

Treatment of late syphilis with 2.4 million units benzathine penicillin G (BPG): tolerance of single versus divided doses.

Although there is no data in the literature, some textbooks recommend fractioning the injection of benzathine penicillin G (BPG) for alleviating the pain. In a monocentric study done in 50 consecutive patients with late syphilis. Patients were assigned to receive 1 dose of 2.4 million units BPG intramuscularly the first week and 2 doses of 1.2 million units BPG in each buttock the second week. In the third week, patients were asked to choose between the 2 options. It was demonstrated that the 2 techniques were equally well tolerated and equally preferred by patients.

Absence of community-acquired methicillin-resistant Staphylococcus aureus carriage or infection in a cohort of 300 men who have sex with men attending an inner-city sexually transmitted disease clinic in Paris, France.

BACKGROUND: Community-acquired methicillin-resistant Staphylococcus aureus (caMRSA) skin and soft-tissue infections are a major cause for concern. Communities of men who have sex with men (MSM) in the USA being prone to caMRSA epidemics, we investigated whether MSM attending our sexually transmitted disease clinic were carriers of or infected by caMRSA. METHODS: 300 MSM were prospectively recruited, interrogated and examined. Swabs of their nares and of their pubic and perineal skin were taken and cultured. RESULTS: No evidence of carriage or infection by caMRSA was found. Nasal carriage of methicillin-sensitive S. aureus was within French estimates. Perineal carriage significantly correlated with the number of sexual partners. CONCLUSION: Although caMRSA carriage or infection does not seem to affect Paris MSM, prospective sampling may not be the best method to monitor them. The correlation between number of partners and perineal carriage suggests that thorough hygiene after intercourse could limit the spread of S. aureus in MSM with multiple partners.

Remission of severe CD8(+) cytotoxic T cell skin infiltrative disease in human immunodeficiency virus-infected patients receiving highly active antiretroviral therapy.

BACKGROUND: A CD8 cutaneous lymphoinfiltrative disease has been described in human immunodeficiency virus (HIV)-infected patients presenting with a severe erythroderma. The true nature of this severe skin infiltrative disorder is still elusive. Although some clinical features of this syndrome have raised the hypothesis of its malignant nature in initial observations, several studies have provided stronger support to the hypothesis that it is a reactive pseudotumoral process. METHODS: From 1995 through 2008, 8 HIV type 1 (HIV-1)-infected patients presenting with a chronic skin eruption, diagnosed as CD8 T cell infiltration of the skin, were studied. RESULTS: All patients showed diffuse infiltrated skin with superficial lymphadenopathy. A profound CD4(+) lymphocytopenia and eosinophilia were other major features. Histological and immunostaining analysis revealed a predominant dermal and epidermal infiltration by CD8(+) T cells belonging to the cytotoxic lineage, without evidence for a monoclonal status by polymerase chain reaction-based molecular analysis of lesional skin. A remission of skin symptoms occurred in all cases following highly active antiretroviral therapy, which paralleled the decrease of HIV-1 RNA load and the increase of CD4(+) peripheral blood absolute count. CONCLUSIONS: Altogether, these results emphasize the reactive, nonmalignant nature of this syndrome and strongly support the coupling between HIV-induced immune deficiency and uncontrolled CD8 activation.

Etiology of genital ulcer disease. A prospective study of 278 cases seen in an STD clinic in Paris.

OBJECTIVES: The goal of this study was to identify the causes and factors associated with genital ulcer disease (GUD) among patients attending a sexually transmitted disease (STD) clinic in Paris. METHODS: This study was a prospective investigation of GUD cases. Data were collected from 1995 to 2005. In each case, a Dark Field Examination (DFE), Gram stain, inoculation onto Thayer Martin agar, Columbia agar and chocolate agar with 1% isovitalex and 20% fetal calf serum, PCR Chlamydia trachomatis (Amplicor Roche), culture for herpes simplex virus (HSV) on MRC 5 cells and PCR HSV (Argene Biosoft) were obtained from the ulceration. First Catch Urine (FCU) PCR for Chlamydia trachomatis and syphilis, HIV, HSV, and HBV serologies were also performed. RESULTS: A total 278 cases of GUD were investigated, 244 (88%) in men and 34 (12%) in women. Primary syphilis accounted for 98 cases (35%), genital herpes for 74 (27%), chancroid for 8 (3%), other infections for 12 (5%). In 91 (32%) patients, no identifiable microorganism was documented. Primary syphilis was more prevalent in MSMs (P < 0.0001), while genital herpes and chancroid were significantly associated with heterosexuality (both P < 0.0001). A high level of HIV infection (27%) was found, particularly in patients with primary syphilis (33%). In the univariate analysis, no statistical difference was found between syphilis and herpes according to clinical presentation, pain being the only item slightly more frequent in herpes (P = 0.06). In the multivariable model syphilis was associated with being MSM (OR: 51.3 [95% CI: 14.7-178.7], P < 0.001) and with an ulceration diameter >10 mm (OR: 9.2 [95% CI: 2.9-30.7], P < 0.001). Genital herpes was associated with HIV infection in the subgroup of MSWs (OR: 24.4 [2.4-247.7], P = 0.007). We did not find significant differences in the clinical presentation of the ulcers according to HIV status. CONCLUSION: The profound changes of the epidemiology of GUD during the decade, due to disappearance of chancroid and reemergence of infectious syphilis have led to a new distribution of pathogens, genital herpes, primary syphilis and GUD from unknown origin, accounting each for one third of cases. No clinical characteristic is predictive of the etiology, underlining the importance of performing a thorough microbiologic evaluation. Close association with HIV is still a major public health problem.

[Gonococcal infections]. / Infections à gonocoques.

Gonococcal infections as well as other sexually transmited diseases have been increasing for several years. Short incubation period and rich symptomatology of gonococcal urethritis in man, make it an epidemiological indicator of high-risk sexual behavior. In women, cervicitis is often asymptomatic. Anorectitis is a classical form of gonococcal infection especially in men who have sex with men. Sepsis and conjunctivitis, while rare, are to be diagnosed as quickly as possible because of their severity. To limit the spread of gonococcal infections, prevention of sexually transmitted diseases must be strengthened, the screening of asymptomatic subjects can be improved by using the polymerase chain reaction technique and finally the latest therapeutic guidelines taking into account gonococcal antibiotic resistances must be applied.

An unusual bipolar primary herpes simplex virus 1 infection.

We describe an atypical primary HSV 1 genital infection with bilateral palmar involvement. Two routes of dissemination of HSV are discussed, self-inoculation and blood dissemination. This case highlights the role of HSV 1 in extragenital pustules in the context of sexually transmitted diseases.

Multi-locus sequence typing of Treponema pallidum subsp. pallidum present in clinical samples from France: Infecting treponemes are genetically diverse and belong to 18 allelic profiles.

Treponema pallidum subsp. pallidum, the causative agent of sexually transmitted syphilis, detected in clinical samples from France, was subjected to molecular typing using the recently developed Multilocus Sequence Typing system. The samples (n = 133) used in this study were collected from 2010-2016 from patients with diagnosed primary or secondary syphilis attending outpatient centers or hospitals in several locations in France. Altogether, 18 different allelic profiles were found among the fully typed samples (n = 112). There were five allelic variants identified for TP0136, 12 for TP0548, and eight for TP0705. Out of the identified alleles, one, seven, and three novel alleles were identified in TP0136, TP0548, and TP0705, respectively. Partial allelic profiles were obtained from 6 samples. The majority of samples (n = 110) belonged to the SS14-like cluster of TPA isolates while 7 clustered with Nichols-like isolates. Patients infected with Nichols-like samples were more often older (p = 0.041) and more often diagnosed with secondary syphilis (p = 0.033) compared to patients infected with SS14-like samples. In addition, macrolide resistance caused by the A2058G mutation was found to be associated with allelic profile 1.3.1 or with strains belonging to the 1.3.1 lineage (p<0.001). The genetic diversity among TPA strains infecting the European population was surprisingly high, which suggests that additional studies are needed to reveal the full genetic diversity of TPA pathogens infecting humans.

Human Treponema pallidum 11q/j isolate belongs to subsp. endemicum but contains two loci with a sequence in TP0548 and TP0488 similar to subsp. pertenue and subsp. pallidum, respectively.

BACKGROUND: Treponema pallidum subsp. endemicum (TEN) is the causative agent of endemic syphilis (bejel). An unusual human TEN 11q/j isolate was obtained from a syphilis-like primary genital lesion from a patient that returned to France from Pakistan. METHODOLOGY/PRINCIPAL FINDINGS: The TEN 11q/j isolate was characterized using nested PCR followed by Sanger sequencing and/or direct Illumina sequencing. Altogether, 44 chromosomal regions were analyzed. Overall, the 11q/j isolate clustered with TEN strains Bosnia A and Iraq B as expected from previous TEN classification of the 11q/j isolate. However, the 11q/j sequence in a 505 bp-long region at the TP0488 locus was similar to Treponema pallidum subsp. pallidum (TPA) strains, but not to TEN Bosnia A and Iraq B sequences, suggesting a recombination event at this locus. Similarly, the 11q/j sequence in a 613 bp-long region at the TP0548 locus was similar to Treponema pallidum subsp. pertenue (TPE) strains, but not to TEN sequences. CONCLUSIONS/SIGNIFICANCE: A detailed analysis of two recombinant loci found in the 11q/j clinical isolate revealed that the recombination event occurred just once, in the TP0488, with the donor sequence originating from a TPA strain. Since TEN Bosnia A and Iraq B were found to contain TPA-like sequences at the TP0548 locus, the recombination at TP0548 took place in a treponeme that was an ancestor to both TEN Bosnia A and Iraq B. The sequence of 11q/j isolate in TP0548 represents an ancestral TEN sequence that is similar to yaws-causing treponemes. In addition to the importance of the 11q/j isolate for reconstruction of the TEN phylogeny, this case emphasizes the possible role of TEN strains in development of syphilis-like lesions.

First case of chancroid in 14 years at the largest STI clinic in Paris, France.

We report the first case of chancroid seen at our clinic in 14 years. It was diagnosed by nuclear acid amplification test in a male patient returning from Madagascar. Although the disease is considered on the verge of disappearance even in tropical countries, its real potential for reemergence - due to new strains of Haemophilus ducreyi, underreporting and a lack of widespread use of molecular testing - could be underestimated.

First HSV-1 non primary genital herpes in two patients.

First HSV-1 genital episodes in HSV-2 infected patients however, had never been demonstrated until the 2 cases we observed. This scarcity could reflect the lower impact of HSV-2 on western populations but questions the existence of cross-protection between viral types.

[Discovery of Chlamydia trachomatis in the throat during diagnosis of secondary syphilis in an HIV+ patient]. / Découverte de Chlamydia trachomatis dans la gorge lors d'un diagnostic de syphilis secondaire chez un sujet VIH +

INTRODUCTION: Chlamydia trachomatis (CT) pharyngitis has rarely been described in the literature. Studies in the last decade have shown a prevalence of less than 5%, with more women than men infected in the pharynx. Among homosexual men, only one study, conducted more than 5 years ago, detected the presence of CT in the throat (in one patient out of 13 tested). OBSERVATION: A 33 year-old homosexual man consulted for cutaneous lesions on the palms and the chest. Infected by HIV, he was taking antiretroviral therapy but no antibiotic prophylaxis. He admitted practising unprotected (insertive and receptive) fellatio with unknown partners. The lesions were those of secondary syphilis but the location of the chancre remained unknown. An enlarged screening for sexually transmitted infections detected the presence, through molecular amplification, of CT in the throat without further localisation (urethra, anus). After intramuscular injection of Extencillin and an 8-day-regimen of cycline, CT was no longer detected in the throat. The course of HIV infection did not appear modified by this infectious episode. COMMENTS: According to a review of the literature, the 4 most recent studies have not revealed CT in the throat of homosexuals although the bacteria was detected in the urethra of 3 to 4% of them. Chlamydia trachomatis is more frequently detected in the genital tract rather than the pharynx of women also screened in various localisations. These results must be tempered by the participant recruitment methods, diagnostic methods used, sample size and history of recent antibiotherapy. The pharyngeal mucosa might be less receptive to CT than the urethral mucosa. Association of CT pharyngitis with syphilis or its occurrence during HIV infection are not documented. The molecular amplification technique detects CT in the throat with sensitivity and specificity. A one-week regimen of cycline can cure this pharyngitis. Cost-effectiveness of screening for pharyngeal CT has not yet been assessed in persons 'at risk'.

[Syphilis: clinical, biological and therapeutical aspects]. / Syphilis: aspects cliniques, diagnostiques et thérapeutiques.

Syphilis is a STI. The present epidemic is related to the relapse into unsafe sexual behaviour. HIV has not modified clinical aspects and the great simulator implies to perform TPHA and VDRL in various circumstances. Treatment is simple and consensual in early syphilis. Treatment of late syphilis is dependent upon indications of CSF control, to be discussed by specialists, particularly in HIV+ patients.