Investigating the cause of increased tetracycline-resistant Neisseria gonorrhoeae in England, 2016-20.

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 (r = 0.97, P = 0.01) and antimicrobial treatment (r = 0.87, P = 0.05). 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.

Attribution of nosocomial seeding to long-term care facility COVID-19 outbreaks.

Residents of long-term care facilities (LTCFs) were disproportionately affected by the COVID-19 pandemic. We assessed the extent to which hospital-associated infections contributed to COVID-19 LTCF outbreaks in England. We matched addresses of cases between March 2020 and June 2021 to reference databases to identify LTCF residents. Linkage to health service records identified hospital-associated infections, with the number of days spent in hospital before positive specimen date used to classify these as definite or probable. Of 149,129 cases in LTCF residents during the study period, 3,748 (2.5%) were definite or probable hospital-associated and discharged to an LTCF. Overall, 431 (0.3%) were identified as index cases of potentially nosocomial-seeded outbreaks (2.7% (431/15,797) of all identified LTCF outbreaks). These outbreaks involved 4,521 resident cases and 1,335 deaths, representing 3.0% and 3.6% of all cases and deaths in LTCF residents, respectively. The proportion of outbreaks that were potentially nosocomial-seeded peaked in late June 2020, early December 2020, mid-January 2021, and mid-April 2021. Nosocomial seeding contributed to COVID-19 LTCF outbreaks but is unlikely to have accounted for a substantial proportion. The continued identification of such outbreaks after the implementation of preventative policies highlights the challenges of preventing their occurrence.

Is there an association between previous infection with Neisseria gonorrhoeae and gonococcal AMR? A cross-sectional analysis of national and sentinel surveillance data in England, 2015-2019.

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.

Differential impact of quarantine policies for recovered COVID-19 cases in England: a case cohort study of surveillance data, June to December 2020.

BACKGROUND: From 12th March 2020, individuals in England were advised to quarantine in their home if a household member tested positive for SARS-CoV-2. A mandatory isolation period of 10 days was introduced on 28th September 2020 and applied to all individuals with COVID-19. We assessed the frequency, timing, and characteristics of recovered COVID-19 cases requiring subsequent quarantine episodes due to household re-exposure. METHODS: In this case cohort study, all laboratory-confirmed COVID-19 cases notified in England (29th June to 28th December 2020) were analysed to identify consecutive household case(s). Multivariable logistic regression was used to determine associations between case characteristics and need to quarantine following recent infection (within 28 days of diagnosis). RESULTS: Among 1,651,550 cases resident in private dwellings and Houses of Multiple Occupancy (HMOs), 744,548 (45.1%) were the only case in their home and 56,179 (3.4%) were succeeded by further household cases diagnosed within 11-28 days of their diagnosis. Of 1,641,412 cases arising in private homes, the likelihood of further household cases was highest for Bangladeshi (aOR = 2.20, 95% CI = 2.10-2.31) and Pakistani (aOR = 2.15, 95% CI = 2.08-2.22) individuals compared to White British, as well as among young people (17-24y vs. 25-64y; aOR = 1.19, 95% CI = 1.16-1.22), men (vs. women; aOR = 1.06, 95% CI = 1.04-1.08), London residents (vs. Yorkshire and Humber; aOR = 1.57, 95% CI = 1.52-1.63) and areas of high deprivation (IMD 1 vs. 10; aOR = 1.13, 95% CI = 1.09-1.19). CONCLUSION: Policies requiring quarantine on re-exposure differentially impact some of the most disadvantaged populations. Quarantine exemption for recently recovered individuals could mitigate the socioeconomic impact of responses to COVID-19 or similar infectious disease outbreaks.

Antimicrobial-resistant gonorrhoea: the national public health response, England, 2013 to 2020.

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 > 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.

A cross-sectional national investigation of COVID-19 outbreaks in nurseries during rapid spread of the Alpha (B.1.1.7) variant of SARS-CoV-2 in England.

BACKGROUND: In England, the emergence the more transmissible SARS-CoV-2 variant Alpha (B.1.1.7) led to a third national lockdown from December 2020, including restricted attendance at schools. Nurseries, however, remained fully open. COVID-19 outbreaks (≥ 2 laboratory-confirmed cases within 14 days) in nurseries were investigated to assess the risk of SARS-CoV-2 infection and cumulative incidence in staff and children over a three-month period when community SARS-CoV-2 infections rates were high and the Alpha variant was spreading rapidly across England. METHODS: This was a cross-sectional national investigation of COVID-19 outbreaks in nurseries across England. Nurseries reporting a COVID-19 outbreak to PHE between November 2020 and January 2021 were requested to complete a questionnaire about their outbreak. RESULTS: Three hundred and twenty-four nurseries, comprising 1% (324/32,852) of nurseries in England, reported a COVID-19 outbreak. Of the 315 (97%) nurseries contacted, 173 (55%) reported 1,657 SARS-CoV-2 cases, including 510 (31%) children and 1,147 (69%) staff. A child was the index case in 45 outbreaks (26%) and staff in 125 (72%) outbreaks. Overall, children had an incidence rate of 3.50% (95%CI, 3.21-3.81%) and was similar irrespective of whether the index case was a child (3.55%; 95%CI, 3.01-4.19%) or staff (3.44%; 95%CI, 3.10-3.82%). Among staff, cumulative incidence was lower if the index case was a child (26.28%; 95%CI, 23.54-29.21%%) compared to a staff member (32.98%; 95%CI, 31.19-34.82%), with the highest cumulative incidence when the index case was also a staff member (37.52%; 95%CI, 35.39-39.70%). Compared to November 2020, outbreak sizes and cumulative incidence was higher in January 2021, when the Alpha variant predominated. Nationally, SARS-CoV-2 infection rates in < 5 year-olds remained low and followed trends in older age-groups, increasing during December 2020 and declining thereafter. CONCLUSIONS: In this cross-sectional study of COVID-19 outbreaks in nurseries, one in three staff were affected compared to one in thirty children. There was some evidence of increased transmissibility and higher cumulative incidence associated with the Alpha variant, highlighting the importance of maintaining a low level of community infections.

What is the role of sexual health services in the delivery of primary prevention of sexually transmitted infections? A narrative review.

Sexually transmitted infections (STIs) affect hundreds of millions of people globally. The resulting impact on quality of life and the economy for health systems is huge. Specialist sexual health services (SHS) play a key role in the provision of primary prevention interventions targeted against STIs. We conducted a narrative review to explore the role of SHSs in delivering primary prevention interventions for STIs. Established interventions include education and awareness building, condom promotion, and the provision of vaccines. Nascent interventions such as the use of antibiotics as pre- and post-exposure prophylaxis are not currently recommended, but have already been adopted by some key population groups. The shift to delivering SHS through digital health technologies may help to reduce barriers to access for some individuals, but creates challenges for the delivery of primary prevention and may inadvertently increase health inequities. Intervention development will need to consider carefully these shifting models of service delivery so that existing primary prevention options are not side-lined and that new interventions reach those who can benefit most.

Frequency and Correlates of Mycoplasma genitalium Antimicrobial Resistance Mutations and Their Association With Treatment Outcomes: Findings From a National Sentinel Surveillance Pilot in England.

BACKGROUND: Mycoplasma genitalium infection is a public health concern due to extensive antimicrobial resistance. Using data from a pilot of M. genitalium antimicrobial resistance surveillance, we determined the prevalence and risk factors for resistance among specimens from sexual health clinic attendees and assessed treatment outcomes. METHODS: Seventeen sexual health clinics in England sent consecutive M. genitalium-positive specimens to the national reference laboratory from January to March 2019. Regions of the 23S rRNA, parC, and gyrA genes associated with macrolide and fluoroquinolone resistance, respectively, were amplified and sequenced where appropriate. Fisher exact tests, and univariate and multivariable logistic regression models were used to determine associations between demographic, clinical, and behavioral factors and resistance-associated mutations. RESULTS: More than two-thirds (173 of 249 [69%]) of M. genitalium specimens had mutations associated with macrolide resistance, whereas predicted fluoroquinolone (21 of 251 [8%]) and dual-drug (12 of 237 [5%]) resistance were less prevalent. No specimens had both gyrA and parC resistance-associated mutations. Macrolide resistance was more common in specimens from men who have sex with men compared with heterosexual men (adjusted odds ratio, 2.64; 95% confidence interval, 1.09-6.38; P = 0.03). There was an association between both macrolide and fluoroquinolone resistance and having a previous sexually transmitted infection (P = 0.06).Only 19% of individuals returned for a test of cure. Of those infected with a macrolide-resistant genotype who were given azithromycin, 57 of 78 (73%) were known or assumed to be clinically cured; however, 43 of these 57 (75%) also received doxycycline. Of the 21 with a macrolide-resistant genotype who failed treatment, 18 of 21 (86%) also received doxycycline. CONCLUSIONS: Although macrolide resistance was widespread, particularly among specimens from men who have sex with men and those with a previous sexually transmitted infection diagnosis in the past year, resistance-associated mutations in M. genitalium did not seem to be unequivocally predictive of treatment failure.