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OBJECTIVES: Since June 2022, there has been a rise in the number of ceftriaxone-resistant Neisseria gonorrhoeae cases detected in England (nâ=â15), of which a third were XDR. We describe the demographic and clinical details of the recent cases and investigate the phenotypic and molecular characteristics of the isolates. For a comprehensive overview, we also reviewed 16 ceftriaxone-resistant cases previously identified in England since December 2015 and performed a global genomic comparison of all publicly available ceftriaxone-resistant N. gonorrhoeae strains with mosaic penA alleles. METHODS: All N. gonorrhoeae isolates resistant to ceftriaxone (MICâ>â0.125â mg/L) were whole-genome sequenced and compared with 142 global sequences of ceftriaxone-resistant N. gonorrhoeae. Demographic, behavioural and clinical data were collected. RESULTS: All cases were heterosexual, and most infections were associated with travel from the Asia-Pacific region. However, some had not travelled outside England within the previous few months. There were no ceftriaxone genital treatment failures, but three of five pharyngeal infections and the only rectal infection failed treatment. The isolates represented 13 different MLST STs, and most had the mosaic penA-60.001 allele. The global genomes clustered into eight major phylogroups, with regional associations. All XDR isolates belonged to the same phylogroup, represented by MLST ST16406. CONCLUSIONS: Most cases of ceftriaxone-resistant N. gonorrhoeae detected in England were associated with travel from the Asia-Pacific region. All genital infections were successfully treated with ceftriaxone, but there were extragenital treatment failures. Ceftriaxone resistance continues to be associated with the penA-60.001 allele within multiple genetic backgrounds and with widespread dissemination in the Asia-Pacific region.
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The 2024 UK guidelines for the management of syphilis are in line with current evidence and practice within the UK. Key updates are detailed at the start of the article. These guidelines are accompanied by the first UK guidelines for the management of syphilis in pregnant people and children, 2024.
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This new guideline details the specific management of syphilis in pregnancy and in children. It is to be used in clinical practice alongside the BASHH UK guidelines for the management of syphilis 2024.
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OBJECTIVES: This study aimed to validate and implement a rapid screening assay for molecular detection of the penA-60 allele that is associated with ceftriaxone resistance in Neisseria gonorrhoeae for use on both isolate lysates and clinical specimen DNA extracts. METHODS: A N.â¯gonorrhoeae penA real-time (RT)-PCR was adapted to include a species-specific pap confirmation target and a commercially available internal control to monitor for PCR inhibition.The modified assay was validated using N.â¯gonorrhoeae-positive (n=24) and N.â¯gonorrhoeae-negative (n=42) clinical specimens and isolate lysates. The panel included seven samples with resistance conferred by penA alleles targeted by the assay and four samples with different penA alleles. The feasibility of using the penA RT-PCR for molecular surveillance was assessed using clinical specimens from 54 individuals attending a London sexual health clinic who also had a N.â¯gonorrhoeae isolate included in the 2020 Gonococcal Resistance to Antimicrobials Surveillance Programme (GRASP). RESULTS: The assay correctly identified N.â¯gonorrhoeae specimens (n=7) with penA-60/64 alleles targeted by the assay. No penA false negatives/positives were detected, giving the penA target of the assay a sensitivity, specificity, positive and negative predicted values (PPV, NPV) of 100% (95% CIs; sensitivity; 56.1-100%, specificity; 93.6-100%, PPV; 56.1-100%, NPV; 93.6-100%).No cross-reactivity with other Neisseria species or other urogenital pathogens was detected. The N.â¯gonorrhoeae target (pap) was detected in 73 out of 78 of the N.â¯gonorrhoeae-positive specimens, resulting in 92.6% sensitivity (95% CI 83.0% to 97.3%), 100% specificity (95% CI 75.9% to 100%) and PPV, and a NPV of 89.4% (95% CI 52.5% to 90.9%). No penA-59/60/64 alleles were detected within the clinical specimens from the GRASP 2020 feasibility molecular surveillance study (n=54 individuals). CONCLUSION: The implementation of this PCR assay for patient management, public health and surveillance purposes enables the rapid detection of gonococcal ceftriaxone resistance conferred by the most widely circulating penA alleles.
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Antibacterianos , Ceftriaxona , Gonorrea , Neisseria gonorrhoeae , Neisseria gonorrhoeae/genética , Neisseria gonorrhoeae/efectos de los fármacos , Neisseria gonorrhoeae/aislamiento & purificación , Humanos , Ceftriaxona/farmacología , Gonorrea/microbiología , Gonorrea/diagnóstico , Antibacterianos/farmacología , Reacción en Cadena en Tiempo Real de la Polimerasa , Pruebas de Sensibilidad Microbiana , Alelos , Farmacorresistencia Bacteriana/genética , Salud Pública , Sensibilidad y Especificidad , MasculinoRESUMEN
BACKGROUND: Antimicrobial resistance in Neisseria gonorrhoeae is a global public health concern. Tetracycline resistance (TetR) increased from 39.4% to 75.2% between 2016 and 2021 in N. gonorrhoeae isolates collected through national surveillance in England, despite the absence of use of tetracyclines for the treatment of gonorrhoea. OBJECTIVES: We investigated whether there was correlation between bacterial sexually transmitted infection (STI) tests performed and treatment with antimicrobials, with increased TetR in N. gonorrhoeae. METHODS: We examined correlations between bacterial STI tests, antimicrobial treatment and TetR in N. gonorrhoeae, using national surveillance data from three large sexual health services (SHS) in London during 2016-20. Doxycycline prescribing data and antibiograms of a non-STI pathogen from distinct patient groups (sexual health, obstetric and paediatric), at a large London hospital, were analysed to identify if doxycycline use in SHS was associated with resistance in a non-STI organism. RESULTS: A substantial increase in TetR was observed, particularly in isolates from gay, bisexual and other MSM (GBMSM). Strong positive correlations were observed exclusively in GBMSM between N. gonorrhoeae TetR and both bacterial STI tests (râ=â0.97, Pâ=â0.01) and antimicrobial treatment (râ=â0.87, Pâ=â0.05). Doxycycline prescribing increased dramatically during the study period in SHS. Prevalence of TetR in Staphylococcus aureus was higher in isolates sourced from SHS attendees than those from other settings. CONCLUSIONS: Frequent screening of GBMSM at higher risk of STIs, such as those on pre-exposure prophylaxis (PrEP) leading to/and increased use of doxycycline for the treatment of diagnosed infections, may account for the increase in TetR in N. gonorrhoeae.
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Antibacterianos , Doxiciclina , Gonorrea , Pruebas de Sensibilidad Microbiana , Neisseria gonorrhoeae , Resistencia a la Tetraciclina , Neisseria gonorrhoeae/efectos de los fármacos , Neisseria gonorrhoeae/aislamiento & purificación , Humanos , Gonorrea/microbiología , Gonorrea/epidemiología , Gonorrea/tratamiento farmacológico , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Inglaterra/epidemiología , Masculino , Femenino , Doxiciclina/uso terapéutico , Doxiciclina/farmacología , Adulto , Londres/epidemiología , Tetraciclina/farmacología , Tetraciclina/uso terapéuticoRESUMEN
The meningococcal group B vaccine, 4CMenB, is a broad-spectrum, recombinant protein vaccine that is licensed for protection against meningococcal group B disease in children and adults. Over the past decade, several observational studies supported by laboratory studies have reported protection by 4CMenB against gonorrhoea, a sexually transmitted infection caused by Neisseria gonorrhoeae. Gonorrhoea is a major global public health problem, with rising numbers of diagnoses and increasing resistance to multiple antibiotics. In England, more than 82â000 cases of gonorrhoea were diagnosed in 2022, with nearly half of the cases diagnosed among gay, bisexual, and other men who have sex with men. There are currently no licensed vaccines against gonorrhoea but 4CMenB is estimated to provide 33-47% protection against gonorrhoea. On Nov 10, 2023, the UK Joint Scientific Committee on Vaccination and Immunisation agreed that a targeted programme should be initiated using 4CMenB to prevent gonorrhoea among individuals at higher risk of infection attending sexual health services in the UK. This decision was made after reviewing evidence from retrospective and prospective observational studies, laboratory and clinical data, national surveillance reports, and health economic analyses. In this Review, we summarise the epidemiology of invasive meningococcal disease and gonorrhoea in England, the evidence supporting the use of 4CMenB for protection against gonorrhoea, and the data needed to inform long-term programme planning and extension to the wider population.
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Gonorrea , Infecciones Meningocócicas , Vacunas Meningococicas , Humanos , Gonorrea/epidemiología , Gonorrea/prevención & control , Vacunas Meningococicas/administración & dosificación , Vacunas Meningococicas/inmunología , Reino Unido/epidemiología , Masculino , Infecciones Meningocócicas/prevención & control , Infecciones Meningocócicas/epidemiología , Neisseria gonorrhoeae/inmunología , Femenino , Adulto , Neisseria meningitidis Serogrupo B/inmunologíaRESUMEN
BACKGROUND: Gonorrhoea is on the rise: between 2021 and 2022, a 50% and a 33% increase in diagnoses was seen, respectively, in England and the Netherlands. A concurrent rise in gonococcal keratoconjunctivitis (GKC) is a serious concern due to the potentially devastating visual complications. METHODS: This is a retrospective case series of adult GKC from two Western European tertiary ophthalmology centres between 2017 and July 2023. The clinical features, ocular complications and antimicrobial susceptibilities are reported within. RESULTS: An increased incidence was recorded at both centres, with 11 confirmed cases in the first 7 months of 2023, compared with ≤3 per year in 2017-2022. CONCLUSION: The notable increase of GKC cases in our centres in 2023 may indicate a rise across Western Europe. Enhanced, sustained, national surveillance of GKC is essential to establish incidence and antimicrobial susceptibility, to inform treatment guidelines and guide appropriate public health response.
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Antibacterianos , Infecciones Bacterianas del Ojo , Gonorrea , Queratoconjuntivitis , Pruebas de Sensibilidad Microbiana , Neisseria gonorrhoeae , Centros de Atención Terciaria , Humanos , Incidencia , Estudios Retrospectivos , Gonorrea/epidemiología , Gonorrea/tratamiento farmacológico , Gonorrea/microbiología , Masculino , Femenino , Neisseria gonorrhoeae/efectos de los fármacos , Neisseria gonorrhoeae/aislamiento & purificación , Adulto , Persona de Mediana Edad , Queratoconjuntivitis/epidemiología , Queratoconjuntivitis/microbiología , Queratoconjuntivitis/tratamiento farmacológico , Antibacterianos/uso terapéutico , Centros de Atención Terciaria/estadística & datos numéricos , Infecciones Bacterianas del Ojo/epidemiología , Infecciones Bacterianas del Ojo/microbiología , Infecciones Bacterianas del Ojo/tratamiento farmacológico , Anciano , Europa (Continente)/epidemiología , Adulto JovenRESUMEN
Due to the continued emergence of resistance to extended-spectrum cephalosporin antibiotics, clinicians are increasingly more likely to encounter cases of Neisseria gonorrhoeae treatment failure. The current international treatment guidelines offer few regimens for cases of N gonorrhoeae infection that do not respond to first-line therapy, and there are many complexities that should be considered with such regimens; these include regional variations in resistance to alternative agents, access to different antibiotics, and penetration of those antibiotics within different tissues. Further, such regimens do not account for the challenges of treating pharyngeal infections; many patients who have not responded to treatment with extended-spectrum cephalosporin antibiotics to date have had pharyngeal involvement. In addition, pharyngeal infections play a pivotal role in the emergence and spread of antimicrobial resistance in N gonorrhoeae and are more difficult to treat than urogenital infections because of the unfavourable pharmacokinetics of cephalosporins in pharyngeal tissues. Here, we summarise the current guidelines, provide additional approaches and considerations for clinicians, and highlight knowledge gaps that should be addressed to ensure appropriate therapy in cases of treatment failure.
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Antibacterianos , Gonorrea , Neisseria gonorrhoeae , Guías de Práctica Clínica como Asunto , Insuficiencia del Tratamiento , Humanos , Gonorrea/tratamiento farmacológico , Antibacterianos/uso terapéutico , Neisseria gonorrhoeae/efectos de los fármacos , Cefalosporinas/uso terapéutico , Farmacorresistencia BacterianaRESUMEN
After lifting of all COVID-19 preventive measures in England in July 2021, marked, widespread increases in gonorrhea diagnoses, but not testing numbers, were observed, particularly in persons 15-24 years of age. Continued close surveillance and public health messaging to young persons are needed to control and prevent gonorrhea transmission.
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COVID-19 , Gonorrea , Humanos , COVID-19/prevención & control , Gonorrea/epidemiología , Gonorrea/prevención & control , SARS-CoV-2 , Salud Pública , Inglaterra/epidemiologíaRESUMEN
BACKGROUND: Syphilis is a sexually transmitted bacterial infection caused by Treponema pallidum subspecies pallidum. Since 2012, syphilis rates have risen dramatically in many high-income countries, including England. Although this increase in syphilis prevalence is known to be associated with high-risk sexual activity in gay, bisexual, and other men who have sex with men (GBMSM), cases are rising in heterosexual men and women. The transmission dynamics within and between sexual networks of GBMSM and heterosexual people are not well understood. We aimed to investigate if whole genome sequencing could be used to supplement or enhance epidemiological insights around syphilis transmission. METHODS: We linked national patient demographic, geospatial, and behavioural metadata to whole T pallidum genome sequences previously generated from patient samples collected from across England between Jan 1, 2012, and Oct 31, 2018, and performed detailed phylogenomic analyses. FINDINGS: Of 497 English samples submitted for sequencing, we recovered 240 genomes (198 from the UK Health Security Agency reference laboratory and 42 from other laboratories). Three duplicate samples (same patient and collection date) were included in the main phylogenies, but removed from further analyses of English populations, leaving 237 genomes. 220 (92·8%) of 237 samples were from men, nine (3·8%) were from women, and eight (3·4%) were of unknown gender. Samples were mostly from London (n=118 [49·8%]), followed by southeast England (n=29 [12·2%]), northeast England (n=24 [10·1%]), and southwest England (n=15 [6·3%]). 180 (76·0%) of 237 genomes came from GBMSM, compared with 25 (10·5%) from those identifying as men who have sex with women, 15 (6·3%) from men with unrecorded sexual orientation, nine (3·8%) from those identifying as women who have sex with men, and eight (3·4%) from people of unknown gender and sexual orientation. Phylogenomic analysis and clustering revealed two dominant T pallidum sublineages in England. Sublineage 1 was found throughout England and across all patient groups, whereas sublineage 14 occurred predominantly in GBMSM older than 34 years and was absent from samples sequenced from the north of England. These different spatiotemporal trends, linked to demography or behaviour in the dominant sublineages, suggest they represent different sexual networks. By focusing on different regions of England we were able to distinguish a local heterosexual transmission cluster from a background of transmission in GBMSM. INTERPRETATION: These findings show that, despite extremely close genetic relationships between T pallidum genomes globally, genomics can still be used to identify putative transmission clusters for epidemiological follow-up. This could be of value for deconvoluting putative outbreaks and for informing public health interventions. FUNDING: Wellcome funding to the Sanger Institute, UK Research and Innovation, National Institute for Health and Care Research, European and Developing Countries Clinical Trials Partnership, and UK Health Security Agency.
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Minorías Sexuales y de Género , Sífilis , Humanos , Masculino , Femenino , Sífilis/epidemiología , Homosexualidad Masculina , Inglaterra/epidemiología , GenómicaRESUMEN
OBJECTIVES: A global outbreak of mpox (monkeypox) has been ongoing since 2022, with most cases in the UK detected in gay, bisexual and other men who have sex with men (GBMSM). Asymptomatic and pauci-symptomatic mpox infection has been reported outside of the UK. We aimed to investigate whether mpox could be detected in specimens from GBMSM in England who were attending sexual health services (SHSs) for asymptomatic sexually transmitted infection screening. METHODS: Anonymised, residual clinical specimens from GBMSM undertaking routine asymptomatic screening for gonorrhoea (Neisseria gonorrhoeae (NG)) and chlamydia (Chlamydia trachomatis (CT)) infection were tested for the presence of mpox virus. Specimens were collected between 1 August and 7 October 2022 from three SHSs in high-mpox incidence areas in England. Testing was performed using a dual-clade, mpox virus-specific real-time PCR. RESULTS: During the collection period, 2927 clinical specimens (951 pharyngeal swabs, 1022 urine specimens and 954 rectal swabs) were obtained from 1159 GBMSM. Mpox virus was detected in four specimens from two participants who attended the same SHS at different times (the first during the week 8-12 of August, the second during the week 19-23 of September). One participant was positive in the urine specimen only, while the other tested positive at all three sites. CONCLUSIONS: A very low prevalence (2 of 1159, 0.17%) of mpox infection was detected in GBMSM attending SHS in England for asymptomatic NG/CT screening, suggesting that undetected infection in this population was unlikely to be a main driver of transmission. Confirmed mpox cases in the UK declined from over 1100 per month in June and July to 764 cumulatively during the collection period. These data give reassurance that the observed reduction in cases during the collection period was not due to undetected infection or changes in presentation among SHS attendees. Currently, there is insufficient evidence to support routine testing of asymptomatic GBMSM for mpox infection in England.
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Infecciones por Chlamydia , Gonorrea , Mpox , Minorías Sexuales y de Género , Masculino , Humanos , Homosexualidad Masculina , Monkeypox virus , Estudios Retrospectivos , Gonorrea/diagnóstico , Gonorrea/epidemiología , Neisseria gonorrhoeae , Infecciones por Chlamydia/diagnóstico , Infecciones por Chlamydia/epidemiología , Infecciones por Chlamydia/orina , Chlamydia trachomatis , Inglaterra/epidemiologíaRESUMEN
We report a case of gonococcal pericarditis, which was unexpected due to its extremely unusual occurrence. A 42-year-old man presented with fever, chest pain, dyspnea, and tachycardia. He was initially stable but rapidly deteriorated, developing pericardial effusion with tamponade requiring a pericardial window. Incompletely decolorized gram stain of the pericardial fluid initially suggested the presence of gram-positive diplococci, which wrongly directed treatment toward possible pneumococcal infection. Because cultures were negative, identification of the causative organism was attempted by molecular and genotyping analysis. These techniques identified Neisseria gonorrhoeae-multi-antigen sequence type 14994 (por 5136/tbpB 33) as the etiology, which has been associated with disseminated gonococcal disease. Real-time polymerase chain reaction showed no evidence of mutations within the N. gonorrhoeae penA gene responsible for causing ceftriaxone resistance. This was crucial in guiding antibiotic treatment, in light of the high prevalence of multi-drug-resistant N. gonorrhoeae. This case highlights the utility of diagnostic molecular techniques in identifying N. gonorrhoeae as the etiology of an exceedingly rare case of pericarditis.
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Gonorrea , Derrame Pericárdico , Pericarditis , Masculino , Humanos , Adulto , Gonorrea/complicaciones , Gonorrea/diagnóstico , Gonorrea/tratamiento farmacológico , Antibacterianos/uso terapéutico , Ceftriaxona/uso terapéutico , Neisseria gonorrhoeae/genética , Pericarditis/diagnóstico , Pericarditis/tratamiento farmacológico , Pericarditis/genética , Derrame Pericárdico/diagnóstico , Antígenos Bacterianos , Pruebas de Sensibilidad MicrobianaRESUMEN
OBJECTIVES: Quarterly STI screening is recommended for high-risk gay, bisexual and other men who have sex with men (MSM) in the UK, but frequent antibiotic exposure could potentially increase the risk of antimicrobial resistance (AMR) developing in Neisseria gonorrhoeae. We investigated whether repeat diagnosis of gonorrhoea in those attending sexual health services (SHS) was associated with reduced antimicrobial susceptibility. METHODS: Antimicrobial susceptibility data relating to the most recent gonorrhoea diagnosis for each individual included in the Gonococcal Resistance to Antimicrobials Surveillance Programme (2015-2019) were matched to their historical records in the national GUMCAD STI surveillance data set (2012-2019). The number of gonorrhoea diagnoses in the previous 3 years was calculated for each SHS attendee. Logistic regression was used to examine the associations between the number of diagnoses and reduced susceptibility to ceftriaxone (minimum inhibitory concentration (MIC) >0.03 mg/L), cefixime (MIC >0.06 mg/L) and azithromycin (MIC >0.25 mg/L) at the time of the latest diagnosis. RESULTS: Of 6161 individuals included in the analysis, 3913 (63.5%) were MSM, 1220 (19.8%) were heterosexual men and 814 (13.2%) were women. Among MSM, 2476 (63.3%) had 1 past gonorrhoea diagnosis, 1295 (33.1%) had 2-4, 140 (3.6%) 5-9, and 2 (0.1%) ≥10. Most women and heterosexual men (91.7%) had one past gonorrhoea diagnosis; none had more than four. Reduced ceftriaxone and cefixime susceptibility was more common among MSM with two to four gonorrhoea diagnoses (3.8% and 5.8%, respectively) compared with those with one (2.2% and 3.9%, respectively). After adjusting for potential confounding, this association remained (adjusted OR: 1.59, 95% CI 1.07 to 2.37, p=0.02; adjusted OR: 1.54, 95% CI 1.11 to 2.14, p=0.01). No evidence was found for any other associations. CONCLUSIONS: Among MSM, repeat diagnosis of gonorrhoea may be associated with reduced ceftriaxone and cefixime susceptibility. As these are last-line therapies for gonorrhoea, further research is needed to assess the impact of intensive STI screening on AMR.
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Gonorrea , Minorías Sexuales y de Género , Masculino , Femenino , Humanos , Gonorrea/tratamiento farmacológico , Gonorrea/epidemiología , Gonorrea/diagnóstico , Neisseria gonorrhoeae , Ceftriaxona/uso terapéutico , Ceftriaxona/farmacología , Cefixima/farmacología , Cefixima/uso terapéutico , Homosexualidad Masculina , Estudios Transversales , Vigilancia de Guardia , Farmacorresistencia Bacteriana , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Inglaterra/epidemiología , Pruebas de Sensibilidad MicrobianaRESUMEN
Between December 2021 and June 2022, 10 cases of ceftriaxone-resistant Neisseria gonorrhoeae (ST8123;â¯nâ¯=â¯8) were detected in the United Kingdom, compared with nine cases during the previous 6 years. Most of these cases were associated with travel from the Asia-Pacific region; all were heterosexual people, with most in their 20s. Although all cases were successfully treated, not all partners of cases could be traced, and there is a risk of further transmission of ceftriaxone-resistant gonococcal infection within the UK.
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Gonorrea , Neisseria gonorrhoeae , Humanos , Neisseria gonorrhoeae/genética , Ceftriaxona/farmacología , Ceftriaxona/uso terapéutico , Pruebas de Sensibilidad Microbiana , Gonorrea/diagnóstico , Gonorrea/tratamiento farmacológico , Gonorrea/epidemiología , Reino Unido/epidemiologíaRESUMEN
Neisseria gonorrhoeae has developed resistance to all antimicrobials used to treat gonorrhoea, and the emergence of ceftriaxone-resistant strains threatens the last-line option for empirical treatment. The 2013 Gonococcal Resistance to Antimicrobials Surveillance Programme (GRASP) Action Plan recommended measures to delay the spread of antimicrobial resistance (AMR) in N. gonorrhoeae in England. We reviewed trends in gonococcal AMR since then and the experience of implementing the Action Plan's recommendations to respond to incidents of resistant N. gonorrhoeae. Between 2013 and 2019, diagnoses of gonorrhoea in England rose by 128% to 70,922, the largest annual number ever reported. Over this period, N. gonorrhoeae isolates have become less susceptible to azithromycin (minimum inhibitory concentration >â¯0.5 mg/L), increasing from 4.7% in 2016 to 8.7% in 2020; this led to a change in first-line treatment for gonorrhoea in the United Kingdom (UK) from dual therapy (ceftriaxone/azithromycin) to ceftriaxone monotherapy in 2019. We also detected the first global treatment failure for pharyngeal gonorrhoea with a dual-therapy regimen (ceftriaxone/azithromycin), followed by an additional six ceftriaxone-resistant strains. Continued engagement of sexual health clinicians and laboratories with the UK Health Security Agency (UKHSA) is essential for the timely detection of N. gonorrhoeae strains with ceftriaxone resistance and to rapidly contain transmission of these strains within England.
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Antiinfecciosos , Gonorrea , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Azitromicina/farmacología , Azitromicina/uso terapéutico , Ceftriaxona/farmacología , Ceftriaxona/uso terapéutico , Farmacorresistencia Bacteriana , Inglaterra/epidemiología , Gonorrea/diagnóstico , Gonorrea/tratamiento farmacológico , Gonorrea/epidemiología , Humanos , Pruebas de Sensibilidad Microbiana , Neisseria gonorrhoeae , Salud PúblicaRESUMEN
BACKGROUND: Shigellosis, traditionally a foodborne and waterborne infection, causes substantial morbidity globally. It is now a leading cause of sexually transmitted gastroenteritis among gay, bisexual, and other men who have sex with men (MSM). We describe an ongoing outbreak of extensively drug-resistant (XDR) Shigella sonnei in the UK. METHODS: Routine laboratory surveillance (Second Generation Surveillance System, Gastrointestinal Data Warehouse) identified an exceedance of S sonnei clade 5 in England, first detected in September, 2021. Cases within this clade were subsequently reported from Scotland, Wales, and Northern Ireland. Confirmed cases in this outbreak were defined as individuals diagnosed with S sonnei clade 5 in the UK, with a specimen date between Sept 1, 2021, and Feb 9, 2022, who were genomically confirmed as part of a ten-single nucleotide polymorphism (SNP) linkage cluster. We used whole-genome sequencing with SNP typing to identify genomic clusters and antimicrobial-resistance determinants, analysing cases across the UK. We collected demographic, epidemiological, and clinical data from people infected with S sonnei clade 5 in England using questionnaires (standard and bespoke outbreak questionnaires). We used descriptive summary statistics to characterise cases. FINDINGS: 72 cases (70 [97%] male, median age 34 years [IQR 27-39]) belonging to the ten-SNP single linkage cluster of S sonnei clade 5 were identified between Sept 4, 2021, and Feb 9, 2022. Isolates were predominantly XDR, with 66 (92%) of 72 harbouring blaCTX-M-27, a plasmid-mediated gene for production of extended-spectrum ß-lactamases (ESBLs). Of 33 cases with clinical data, 19 (58%) received antibiotics and eight (24%) were hospitalised. 21 (78%) of 27 cases with completed bespoke outbreak questionnaires were HIV-negative MSM taking HIV pre-exposure prophylaxis (PrEP) who reported sexual contacts in the UK and Europe within the incubation period. INTERPRETATION: We highlight the rapid dissemination of XDR ESBL-producing S sonnei in sexual networks of MSM. We recommend strengthening shigella testing where clinically indicated, antimicrobial-resistance surveillance, and integrated health promotion messaging among all MSM, including PrEP users, to reduce the burden of shigellosis. FUNDING: National Institute for Health Research Health Protection Research Unit in Gastrointestinal Infections at the University of Liverpool in partnership with the UK Health Security Agency.
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Disentería Bacilar , Infecciones por VIH , Minorías Sexuales y de Género , Adulto , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Brotes de Enfermedades , Disentería Bacilar/epidemiología , Femenino , Infecciones por VIH/epidemiología , Homosexualidad Masculina , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Shigella sonnei/genética , Reino Unido/epidemiología , beta-Lactamasas/genéticaRESUMEN
Introduction. Due to the complex nature of treponemal serology interpretation, testing algorithms vary across the UK.Gap statement. There is currently no gold standard method for interpretation of discordant serology results.Aim. To analyse serological response in early infection and to determine the best approach for discordant total antibody EIA and TPPA samples.Methodology. National reference laboratory serology and PCR (genital ulcer swabs) results from 2010 to 2017 were extracted from an electronic laboratory database.Results. A total of 24149 sera underwent analysis. Of syphilis PCR positive cases with contemporaneous sera, 33% (17/52) were IgM positive/equivocal, whilst all were EIA and TPPA positive. No sera with isolated IgM positivity (0/90) demonstrated seroconversion consistent with early treponemal infection, in contrast to 17% (2/12) of sera with isolated TPPA positivity. Isolated EIA positivity was observed in 6.2% (1499/24149) samples with the same result on repeat testing in 73% (154/211). In 100 samples with discordant EIA/TPPA results, IgG Immunoblot was more commonly positive (12/41, 29%) or equivocal (24/41, 59%), in those with a higher EIA antibody index, compared to those with a low antibody index, of which none tested positive and 2/3 (67 %) were equivocal.Conclusion. Isolated IgM positivity was not helpful in identifying early infection; isolated total antibody EIA positivity is unlikely to be a significant finding. IgG immunoblot testing was unable to determine clear treponemal antibody status in nearly half of all EIA/TPPA discordant samples.
Asunto(s)
Sífilis , Algoritmos , Anticuerpos Antibacterianos , Humanos , Inmunoglobulina G , Inmunoglobulina M , Sífilis/diagnóstico , Treponema pallidum , Reino UnidoRESUMEN
OBJECTIVES: A Finnish Chlamydia trachomatis (CT) new variant was detected in 2019 that escaped detection in the Hologic Aptima Combo 2 (AC2) assay due to a C1515T mutation in the CT 23S rRNA target region. Reflex testing of CT-negative/CT-equivocal specimens as well as those positive for Neisseria gonorrhoeae (NG) with the Hologic Aptima CT (ACT) assay was recommended to identify any CT variants. METHODS: From June to October 2019, specimens with discrepant AC2/ACT CT results were submitted to Public Health England and screened for detectable CT DNA using an inhouse real-time (RT)-PCR. When enough DNA was present, partial CT 23S rRNA gene sequencing was performed. Analysis of available relative light units and interpretative data was performed. RESULTS: A total of 317 discordant AC2/ACT specimens were collected from 315 patients. Three hundred were tested on the RT-PCR; 53.3% (n=160) were negative and 46.7% (n=140) were positive. Due to low DNA load in most specimens, sequencing was successful for only 36 specimens. The CT 23S rRNA wild-type sequence was present in 32 specimens, and two variants with C1514T or G1523A mutation were detected in four specimens from three patients. Of the discordant specimens with NG interpretation, 36.6% of NG-negative/CT-negative AC2 specimens had detectable CT DNA on the inhouse RT-PCR vs 53.3% of NG-positive/CT-negative specimens. CONCLUSIONS: No widespread dissemination of AC2 diagnostic-escape CT variants has occurred in England. We however identified the impact of NG positivity on the discordant AC2/ACT specimens; a proportion appeared due to NG positivity and the associated NG signal, rather than any diagnostic-escape variants or low DNA load. Several patients with gonorrhoea may therefore receive false-negative AC2 CT results. Single diagnostic targets and multiplex diagnostic assays have their limitations such as providing selection pressure for escape mutants and potentially reduced sensitivity, respectively. These limitations must be considered when establishing diagnostic pathways.