Anti-BP180 IgG antibody ELISA values correlate with adverse pregnancy outcomes in pemphigoid gestationis.

BACKGROUND: Adverse pregnancy outcomes (APO) occur in 35% of patients with pemphigoid gestationis (PG). No biological predictor of APO has been established yet. OBJECTIVES: To assess a potential relationship between the occurrence of APO and the serum value of anti-BP180 antibodies at the time of PG diagnosis. METHODS: Multicentre retrospective study conducted from January 2009 to December 2019 in 35 secondary and tertiary care centres. INCLUSION CRITERIA: (i) diagnosis of PG according to clinical, histological and immunological criteria, (ii) ELISA measurement of anti-BP180 IgG antibodies determined at the time of PG diagnosis with the same commercial kit and (iii) obstetrical data available. RESULTS: Of the 95 patients with PG included, 42 had one or more APO, which mainly corresponded to preterm birth (n = 26), intrauterine growth restriction (IUGR) (n = 18) and small weight for gestational age at birth (n = 16). From a ROC curve, we identified a threshold of 150 IU ELISA value as the most discriminating to differentiate between patients with or without IUGR, with 78% sensitivity, 55% specificity, 30% positive and 91% negative predictive value. The threshold >150 IU was confirmed using a cross-validation based on bootstrap resampling, which showed that the median threshold was 159 IU. Upon adjusting for oral corticosteroid intake and main clinical predictors of APO, an ELISA value of >150 IU was associated with the occurrence of IUGR (OR = 5.11; 95% CI: 1.48-22.30; p = 0.016) but not with any other APO. The combination of blisters and ELISA values higher than 150 IU led to a 2.4-fold higher risk of all-cause APO (OR: 10.90; 95% CI: 2.33-82.3) relative to patients with blisters but lower values of anti-BP180 antibodies (OR of 4.54; 95% CI 0.92-34.2). CONCLUSION: These findings suggest that anti-BP180 antibody ELISA value in combination with clinical markers is helpful in managing the risk of APO, in particular IUGR, in patients with PG.

Oropharyngeal samples versus lesion specimens at diagnosis in patients infected with monkeypox virus in Northern France.

The ongoing outbreak of monkeypox virus (MPXV) is the largest one in historically non-endemic countries. Early reports described atypical epidemiological and clinical presentations. We investigated MPXV DNA detection in oropharyngeal samples (OPS), and compared the viral load to that in lesion samples at diagnosis in patients infected with MPXV. We retrospectively included patients suspected to have monkeypox in Northern France, who underwent a MPXV PCR in the Virology Laboratory, University Hospital of Lille, from May 23 to August 18, 2022. Overall, a total of 228 patients (376 samples) were included. A positive result in at least one sample was found in 138 patients (60.5%). We compared PCR results between OPS and lesion samples (i.e., cutaneous or anal/rectal samples) in patients with both samples. A positive result in OPS was observed in 54 out of 60 patients (90%). The viral load in OPS (median Ct value = 29.5; interquartile range [IQR] = 24.7-34) was significantly lower than that in lesion samples (median Ct  value = 17.8; IQR = 16.3 and 19.7) (p < 0.0001). This report shows that pharyngeal sampling does not bring additional information for the initial diagnosis in patients presenting with typical lesions.

A rare case of invasive non-typeable Haemophilus influenzae spondylodiscitis and periprosthetic joint infection.

A non-typeable Haemophilus influenzae (NTHi) was responsible for an invasive infection including bacteremia, spondylodiscitis with epidural abscess, and periprosthetic hip infection in a 79-year-old woman, triggered by a superinfected ethmo-orbital mucocele. Surgical drainage and antibiotic therapy allowed recovery. PET-scan full cartography of NTHi infection dissemination enabled the discovery of spondylodiscitis. This rare cause of spondylodiscitis and periprosthetic joint infection suggests a complete work-up is unavoidable.

Ceftriaxone compared with benzylpenicillin in the treatment of neurosyphilis in France: a retrospective multicentre study.

BACKGROUND: Intravenous benzylpenicillin is the gold-standard treatment for neurosyphilis, but it requires prolonged hospitalisation. Ceftriaxone is a possible alternative treatment, the effectiveness of which remains unclear. We aimed to assess the effectiveness of ceftriaxone compared with benzylpenicillin in the treatment of neurosyphilis. METHODS: We did a retrospective multicentre study including patients with neurosyphilis who were treated at one of eight tertiary care centres in France, from Jan 1, 1997, to Dec 31, 2017. We defined neurosyphilis as positive treponemal and non-treponemal tests and at least one of otic syphilis, ocular syphilis, either neurological symptom with a positive result on cerebrospinal fluid (CSF)-VDRL or CSF-PCR tests, or more than five leukocytes in a CSF cell count. Patients with neurosyphilis were identified from the medical information department database of each centre and assigned to one of two groups on the basis of the initial treatment received (ie, benzylpenicillin group or ceftriaxone group). The primary outcome was the overall clinical response (ie, proportion of patients with a complete or partial response) 1 month after treatment initiation. The secondary endpoints were proportions of patients with a complete response at 1 month and serological response at 6 months, and length of hospital stay. FINDINGS: Of 365 patients with a coded diagnosis of neurosyphilis in one of the eight care centres during 1997-2017, 208 were included in this study (42 in the ceftriaxone group and 166 in the benzylpenicillin group). The mean age of patients was 44·4 years (SD 13·4), and 193 (93%) were men. We observed 41 instances of overall clinical response (98%) in the ceftriaxone group versus 125 (76%) in the benzylpenicillin group (crude odds ratio [OR] 13·02 [95% CI 1·73-97·66], p=0·017). After propensity score weighting, overall clinical response rates remained different between the groups (OR 1·22 [95% CI 1·12-1·33], p<0·0001). 22 (52%) patients in the ceftriaxone group and 55 (33%) in the benzylpenicillin group had a complete response (crude OR 2·26 [95% CI 1·12-4·41], p=0·031), with no significant difference after propensity score weighting (OR 1·08 [95% CI 0·94-1·24], p=0·269). Serological response at 6 months did not differ between the groups (21 [88%] of 24 in the ceftriaxone group vs 76 [82%] of 93 in the benzylpenicillin group; crude OR 1·56 [95% CI 0·42-5·86], p=0·50), whereas hospital stay was shorter for patients in the ceftriaxone group than for those in the benzylpenicillin group (mean 13·8 days [95% CI 12·8-14·8] vs 8·9 days [5·7-12·0], p<0·0001). No major adverse effects were reported in either group. INTERPRETATION: Our results suggest that ceftriaxone is similarly effective to benzylpenicillin for the treatment of neurosyphilis, potentially decreasing the length of hospital stay. Randomised, controlled trials should be done to confirm these results. FUNDING: None.

A disseminated Mycobacterium marinum infection in a renal transplant HIV-infected patient successfully treated with a bedaquiline-containing antimycobacterial treatment: A case report.

BACKGROUND: Disseminated Mycobacterium marinum infections occur rarely, in immunocompromised patients. Treatment with a prolonged multi-drug regimen exposes patients to drug-drug interactions and side effects. CASE REPORT: We report a case of disseminated M. marinum infection in a 54-year-old renal transplant, HIV-infected woman. Manifestations of the infection were cutaneous and subcutaneous nodules, mediastinal lymph nodes and left pulmonary infiltrate. Empirical treatment for non-tuberculous mycobacteria was initiated with rifabutin, ethambutol and azithromycin. After identifying M. marinum in sputum, due to unfavourable clinical evolution and severe drug-related adverse events, treatment was changed to doxycycline and rifabutin. Digestive and haematologic side effects motivated a change in antimycobacterial treatment to a combination of moxifloxacin and bedaquiline. Tolerance was satisfactory, and the patient was cured after 12 months of treatment. CONCLUSION: We report (to the authors' knowledge) the first case of disseminated M. marinum infection successfully treated with a bedaquiline-containing regimen. Bedaquiline could be an alternative to recommended antimicrobial regimens in cases of non-tuberculous mycobacterial disease, including M. marinum infection.

Bacterial sexually transmitted infections in France: recent trends and patients' characteristics in 2016.

Diagnoses of bacterial sexually transmitted infections (STI) have been increasing in France since their resurgence in the late 1990s. This article presents recent epidemiological trends until 2016 and the patients' characteristics. STI surveillance relies on sentinel networks: a clinician-based network RésIST (clinical, biological and behavioural data for early syphilis and gonorrhoea), the lymphogranuloma venereum (LGV) network (clinical, biological and behavioural data for rectal LGV, and the laboratory networks Rénachla and Rénago (demographic and biological data for chlamydial infections and gonorrhoea, respectively). Here we describe trends between 2014 and 2016, using data from diagnostic centres which participated regularly during the study period. The number of early syphilis, gonorrhoea and LGV diagnoses increased between 2014 and 2016, particularly in men who have sex with men. An increase in syphilis and gonorrhoea cases was also observed in heterosexuals. Nevertheless, we observed a drop in 2016 for syphilis and chlamydial infections after two decades of increases. Under-reporting and shortage of benzathine penicillin in 2016 may explain this latest evolution. Regular screening of patients and partners, followed by prompt treatment, remains essential to interrupt STI transmission in a context where human immunodeficiency virus (HIV) prevention has expanded towards biomedical prophylaxis.

Clinical and virological features of acute hepatitis A during an ongoing outbreak among men who have sex with men in the North of France.

OBJECTIVES: Since February 2017, an increase of acute hepatitis A (AHA) cases has been notified in North of France. We aimed to report clinical and virological features of 49 cases treated in three hospitals in Lille European Metropolis (LEM). METHODS: All adult patients treated for AHA in 3 LEM hospitals between 20 February and 5 July 2017 were included. Demographic characteristics, exposure risk factors to hepatitis A virus (HAV), AHA manifestations and concomitant sexually transmitted infections (STI) were retrospectively recorded. RESULTS: Forty-nine cases of AHA were diagnosed among which 34 (69%) were hospitalised. Severe AHA occurred in 7 (14%) patients. The median age of cases was 36 years. All cases except 1 were men and 32 (65%) were identified as men having sex with men (MSM). Eleven (23%) patients were HIV-infected, 5 were under HIV pre-exposure prophylaxis (PrEP), 6 had a history of HIV postexposure prophylaxis and 19 had a history of at least one STI. Only three patients had received HAV vaccine. Proportion of patients tested for syphilis, chlamydial and gonococcal infections was 75% (18/24) in those seen by sexual health specialists and 21% (6/29) in those seen by other specialists. At least one concomitant STI was diagnosed in 13 out of 24 tested patients (54%). RT-PCR sequencing was available for 38 cases and confirmed co-circulation of 3 different strains of subgenotype IA (VRD 521 2016: n=24, RIVM-HAV16-090: n=13, V16-25801: n=1), already identified in several European countries. CONCLUSIONS: We are facing an outbreak of AHA among MSM in the North of France with a high rate of hospitalisation. Analysis of cases highlighted missed opportunities of vaccination and lack of concomitant STI screening. Awareness among healthcare providers and MSM should be increased and HAV vaccination promoted.

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.

Risk factors for syphilis infection in men who have sex with men: results of a case-control study in Lille, France.

BACKGROUND: Substantial increases in syphilis have been reported since the early 2000s in northern countries, particularly among men who have sex with men (MSM). The authors aimed to identify risk factors for early syphilis in MSM in Lille, a large urban area of northern France. METHODS: A matched case-control study was conducted in MSM aged ≥ 18 years. Cases were diagnosed with primary, secondary or early latent syphilis between April 2008 and June 2010. Controls sought care in STIs clinics or were followed in an HIV clinic. Controls had no history of and no current syphilis. They were matched to cases for age and HIV status. Multivariate conditional logistic regression models were used to identify risk factors for early syphilis. RESULTS: 53 patients with early syphilis were enrolled. Average age was 37 years, and 47% were HIV-infected. For analysis, they were matched to 90 controls. Factors associated with syphilis were: low educational attainment (OR=5.38, 95% CI 1.94 to 14.94; p=0.001), receptive oral sex with casual male partners without a condom (OR=4.86, 95% CI 1.63 to 14.48; p=0.005) and anal sex toy use with casual male partners (OR=2.72, 95% CI 1.01 to 7.32; p=0.05). Seeking of sex partners online (OR=5.17, 95% CI 1.33 to 20.11), use of poppers (OR=2.2, 95% CI 1.1 to 4.3) and erectile dysfunction drugs (OR=1.9, 95% CI 1.0 to 13.2) were associated with syphilis only in the univariate analysis. CONCLUSIONS: Receptive oral sex without a condom and use of anal sex toys were identified as presenting a major risk of syphilis infection. Although these practices have been shown to present low risk of HIV transmission, the general public is unaware of their impact on transmission of other STIs.

Thymidine analogue mutations in antiretroviral-naive HIV-1 patients on triple therapy including either zidovudine or stavudine.

AIMS: The aims of this study were to: (i) determine the incidence of thymidine-associated mutations (TAMs) in an observational clinical cohort of naive HIV-1 patients who stopped first-line therapy including either zidovudine or stavudine; and (ii) assess the immunological and virological responses to subsequent second-line therapy in patients who switched from zidovudine to stavudine or conversely. PATIENTS AND METHODS: Plasma samples from 165 patients who stopped first-line antiretroviral therapy containing either zidovudine or stavudine were examined for the presence of drug-resistant genotypes. Subsequent second-line immunological and virological follow-up was performed in 136 patients who switched from zidovudine to stavudine and conversely. RESULTS: Among the 93 patients who stopped first-line therapy including zidovudine and the 72 who stopped first-line therapy including stavudine, genotypic resistance testing was available for 67 (72%) and 54 (75%), respectively. The presence of TAMs was significantly more frequent in the zidovudine than the stavudine group (23.8% versus 5.5; P = 0.006). The short- and long-term immunological and virological responses to second-line therapy were comparable in the zidovudine and stavudine groups, despite different baseline profiles of viral resistance (median increase in CD4 cells/mm3 at 1 year of therapy, 118 versus 119; viral load <400 copies/mL, 47% versus 47%). CONCLUSIONS: These results suggest that TAMs occur in more patients on antiretroviral regimens including zidovudine than on regimens including stavudine. Although the results from observational studies should be interpreted cautiously, these findings may be useful in determining the optimal sequencing of zidovudine and stavudine for the treatment of naive HIV-1-infected patients.