Genome-based epidemiology and antimicrobial resistance of Neisseria gonorrhoeae in Spain: A prospective multicentre study.

BACKGROUND: Whole-genome sequencing (WGS) of Neisseria gonorrhoeae isolates combined with epidemiological and phenotypic data provides better understanding of population dynamics. AIM: The objective of this study was to investigate the molecular epidemiology of N. gonorrhoeae isolates from three centres in Spain and determine associations of antimicrobial resistance. METHODS: Genetic characterization was performed in 170 N. gonorrhoeae isolates. WGS was carried out with the HiSeq platform (Illumina). Genome assemblies were submitted to the PubMLST Neisseria database website to determine NG-MAST, MLST and NG-STAR. Antimicrobial resistance genes and point mutations were identified with PubMLST. Phylogenomic comparison was based on whole-genome single nucleotide polymorphism analysis. RESULTS: Twenty-six MLST, 49 NG-MAST and 41 NG-STAR sequence types were detected, the most prevalent being MLST-ST9363 (27.1%), NG-MAST ST569 (12.4%) and NG-STAR ST193 (14.7%). Phylogenetic analysis identified 13 clusters comprising 69% of the isolates, with two of note: one involved cefixime-resistant isolates from Barcelona presenting a mosaic penA X and belonging to MLST-ST7363 and the other involved azithromycin-resistant isolates from Mallorca that possessed the C2611T mutation in the four 23S rRNA alleles belonging to MLST-ST1901. CONCLUSION: The population of N. gonorrhoeae is quite heterogeneous in Spain. Our results agree with previous data published in Europe, albeit with some differences in distribution between regions. This study describes the circulation of two gonococcal populations with a specific resistance profile and sequence type in a specific geographic area. WGS is an effective tool for epidemiological surveillance of gonococcal infection and detection of resistance genes.

Emergence and dissemination of three mild outbreaks of Neisseria gonorrhoeae with high-level resistance to azithromycin in Barcelona, 2016-18.

BACKGROUND: Neisseria gonorrhoeae (NG) isolates with high-level azithromycin resistance (HL-AziR) have emerged worldwide in recent decades, threatening the sustainability of current dual-antimicrobial therapy. OBJECTIVES: This study aimed to characterize the first 16 NG isolates with HL-AziR in Barcelona between 2016 and 2018. METHODS: WGS was used to identify the mechanisms of antimicrobial resistance, to establish the MLST ST, NG multiantigen sequence typing (NG-MAST) ST and NG sequence typing for antimicrobial resistance (NG-STAR) ST and to identify the clonal relatedness of the isolates with other closely related NG previously described in other countries based on a whole-genome SNP analysis approach. The sociodemographic characteristics of the patients included in the study were collected by comprehensive review of their medical records. RESULTS: Twelve out of 16 HL-AziR isolates belonged to the MLST ST7823/NG-MAST ST5309 genotype and 4 to MLST ST9363/NG-MAST ST3935. All presented the A2059G mutation in all four alleles of the 23S rRNA gene. MLST ST7823/NG-MAST ST5309 isolates were only identified in men who have sex with women and MLST ST9363/NG-MAST ST3935 were found in MSM. Phylogenomic analysis revealed the presence of three transmission clusters of three different NG strains independently associated with sexual behaviour. CONCLUSIONS: Our findings support the first appearance of three mild outbreaks of NG with HL-AziR in Spain. These results highlight the continuous capacity of NG to develop antimicrobial resistance and spread among sexual networks. The enhanced resolution of WGS provides valuable information for outbreak investigation, complementing the implementation of public health measures focused on the prevention and dissemination of MDR NG.

The Jarisch-Herxheimer reaction in syphilis: could molecular typing help to understand it better?

OBJECTIVES: The Jarisch-Herxheimer reaction (JHR) is a febrile inflammatory reaction that may occur in patients after treatment of syphilis. The overall rate is estimated to be 10-25% with broad variations over time. It appears to be related to factors like stage of the disease or reagin titres. In this study, we aimed to describe the incidence of and risk factors including strain typing for JHR among patients with syphilis. METHODS: From January through October 2015, 224 consecutive patients (82 of them with HIV) who were diagnosed with early syphilis were enrolled in this prospective observational study in a referral STI clinic in Barcelona. An appointment was offered to them after 10-14 days of treatment to inquire about the reaction with the use of a standardized form. Treponema pallidum molecular typing was made to detect a possible strain related to reaction. RESULTS: Overall, 28% of patients developed JHR. This varied from 56% in secondary, 37% in primary to 7% in early latent syphilis. The most frequent types of reaction were fever (57.5%) and worsening of the lesions (31%). The median time to development of JHR was 6 h [IQR 4-10 h] and lasted a median of 9 h [IQR 4-24 h]. The JHR was less probable in early latent compared to primary/secondary syphilis (P = 0.04) and in patients treated with doxycycline compared to those treated with penicillin (P = 0.01). No differences were seen regarding reagin titres or HIV status, and no association with a specific strain was found. CONCLUSIONS: In this study, JHR occurred in a similar frequency as in other contemporary studies. Symptomatic syphilis and treatment with penicillin were associated with an increased risk of JHR, whereas the previous episode of syphilis was associated with a low risk of it. We could not find associations with specific strains of T. pallidum.

Lymphogranuloma venereum in Barcelona, 2007-2012: the role of seroadaptation in men who have sex with men.

This study describes the incidence rate of reported lymphogranuloma venereum (LGV) in men who have sex with men (MSM) in Barcelona from 2007 to 2012. Epidemiological, clinical and sexual behaviour characteristics of LGV cases are described. Seroadaptive behaviours as a transmission risk factor were assessed by a telephone questionnaire during 2012. Data were handled on a strictly confidential basis. LGV annual rate ratios in MSM were compared with cases from 2007. Differences were statistically analysed with a Poisson test. The incidence rate of LGV in MSM aged 15-69 years ranged from 32·1/105 MSM per year in 2007 to 182·7/105 MSM per year in 2012. In 2012, 31/51 LGV cases (61%) answered the telephone questionnaire, of which 84% (26/31) were HIV positive, 39% (12/31) reported having sex according to their partners' serostatus and 7% (2/31) used strategic positioning. The incidence of LGV has increased since 2007 and mainly affects HIV-positive MSM. It is probable that seroadaptation has facilitated LGV transmission.

Lymphogranuloma venereum: a hidden emerging problem, Barcelona, 2011.

From the beginning of 2007 until the end of 2011, 146 cases of lymphogranuloma venereum (LGV) were notified to the Barcelona Public Health Agency. Some 49% of them were diagnosed and reported in 2011, mainly in men who have sex with men. Almost half of them, 32 cases, were reported between July and September. This cluster represents the largest since 2004. This article presents the ongoing outbreak of LGV in Barcelona.

The Epidemiological and Clinical Characteristics of the Epidemic of Syphilis in Barcelona. / Las características epidemiológicas y clínicas de la epidemia de sífilis en Barcelona.

BACKGROUND: Since 2000, substantial increases in syphilis have been reported in metropolitan areas of Western countries, with increases noted among men who have sex with men (MSM). Clinical manifestations of syphilis might be influenced by concomitant VIH infection and previous episodes of syphilis. The objectives of this study were to describe the epidemiological and clinical characteristics of the cases of syphilis diagnosed in Barcelona. METHODS: Retrospective study of cases with early syphilis diagnosed in the referral STI Unit of Barcelona from January 2003 to December 2013. Revision of medical records with structured collection of epidemiological and clinical data. Univariate and multivariate statistical analyses comparing the characteristics of MSM cases with and without VIH infection and with and without previous syphilis. RESULTS: A total of 1702 cases of syphilis (37% primary, 48% secondary and 14% early latent) were diagnosed, 93% of them in MSM. Among MSM 40% were coinfected with VIH, VIH-positive cases were associated with a previous syphilis (aOR, 5.2 [95% CI, 3.32-8.24]) and with unprotected anal intercourse (aOR, 1.75 [95%CI, 1.17-2.63]). Cases with a history of syphilis presented less often with primary syphilis compared to those without it (27.5% vs. 40%) (aOR, 0.58 [95% CI, 0.44-0.77]). One year after treatment, the clinical and serological evolution were similar between VIH-positive and VIH-negative cases. CONCLUSION: The epidemic of syphilis in Barcelona disproportionately affects MSM and is closelly linked to VIH infection. The presentation of syphilis is influenced by VIH infection and by previous history of syphilis, without significant differences in their evolution after one year of treatment.