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Increased incidence of adult gonococcal keratoconjunctivitis at two tertiary eye hospitals in Western Europe: clinical features, complications and antimicrobial susceptibility
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  1. Alice L Milligan1,
  2. Anna C Randag2,
  3. Sybren Lekkerkerk3,
  4. Helen Fifer4
  1. 1 Corneal and External Diseases Department and Emergency Department, Moorfields Eye Hospital NHS Foundation Trust, London, UK
  2. 2 Corneal and External Diseases Department, Eye Hospital Rotterdam, Rotterdam, The Netherlands
  3. 3 Department of Medical Microbiology, Maasstad Hospital, Rotterdam, The Netherlands
  4. 4 Blood Safety, Hepatitis, STI & HIV Division, UK Health Security Agency, London, UK
  1. Correspondence to Alice L Milligan, Corneal and External Diseases Department and Emergency Department, Moorfields Eye Hospital NHS Foundation Trust, London EC1V 2PD, UK; alice.milligan{at}nhs.net

Abstract

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.

  • Cornea
  • Infection
  • Public health

Data availability statement

All data relevant to the study are included in the article or uploaded as supplemental information.

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WHAT IS ALREADY KNOWN ON THIS TOPIC

  • Gonorrhoea, a sexually transmitted infection, is increasing in Western Europe, with concerns of antibiotic resistance. One of the possible complications, gonococcal keratoconjunctivitis, can lead to progressive corneal thinning and perforation, with poor visual outcomes.

WHAT THIS STUDY ADDS

  • A concurrent rise in the incidence of gonococcal keratoconjunctivitis is found in two tertiary eye hospitals in England and the Netherlands, with treatment delays of up to 17 days and over 50% complication rate. None of the isolates were resistant to ceftriaxone.

HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY

  • Reinforced awareness of gonococcal keratoconjunctivitis to promote prompt testing and treatment and prevent severe complications.

Background

Gonorrhoea is a sexually transmitted infection (STI), caused by the bacterium Neisseria gonorrhoeae. In 2020, there were 82.4 million new cases worldwide among individuals aged 15–49 years.1 Gonorrhoea is increasing in all ages, but predominantly in those aged 15–24 years. Although gay, bisexual or other men who have sex with men remain the largest group, gonorrhoea is increasing in heterosexual men and women. In 2022, there were 82 592 diagnoses in England, a 50.3% increase compared with 2021 (54 961), the highest number since records began.2 In the Netherlands, gonorrhoea infections rose by 33% between 2021 and 2022, from 7964 to 10 600.3

This increase coincides with a major public health concern; N. gonorrhoeae is evolving high levels of antimicrobial resistance, including to ceftriaxone, the last available option for empirical therapy.4 Between December 2021 and June 2022, 10 cases of ceftriaxone-resistant N. gonorrhoeae were detected in the UK, compared with 9 during the previous 6 years. Most cases were associated with travel from the Asia-Pacific region, where ceftriaxone-resistant N. gonorrhoeae is more prevalent. One of these cases presented to an eye clinic with conjunctivitis and was advised to attend a sexual health service (SHS) for STI screening, whereupon she was diagnosed with asymptomatic genital gonorrhoea.5 As yet, ceftriaxone-resistant N. gonorrhoeae has not been reported in the Netherlands.3 Novel drugs are in development to combat multidrug-resistant disease, notably zoliflodacin, a spiropyrimidinetrione, although its efficacy in ocular disease is not yet established.6

Gonorrhoea can present as urethritis, cervicitis or at extragenital sites (pharynx, rectum, conjunctiva) and rarely, systemically.7 Gonococcal keratoconjunctivitis (GKC) is a potentially blinding infection that typically presents with conjunctival injection, copious mucopurulent discharge and lid oedema. Neonatal GKC arises at birth from infected vaginal secretions. Adult infection occurs via inoculation or autoinoculation from infected bodily fluids. There is limited epidemiology on transmission, for example, specific sexual practices or hand-to-eye contact. N. gonorrhoeae can penetrate intact corneal epithelium and progress rapidly to invasive keratitis (illustrated in figure 1) and corneal perforation, necessitating emergency corneal transplantation with high risk of poor visual outcomes. Urgent empirical treatment is required with a single dose of systemic antibiotics, usually 500 mg–1 g intramuscular ceftriaxone and intensive topical antibiotics.8 Previously, a ‘rare’ condition predominantly described in neonates, recent limited, single-centre reports and case series indicate an increased incidence of adult GKC in Western Europe.9–11

Figure 1

Superior corneal thinning and conjunctivitis in 2023/1 (reproduced with patient permission).

Patients and methods

A descriptive, retrospective case series was conducted in two tertiary referral centres: Moorfields Eye Hospital (MEH), London, UK and Rotterdam Eye Hospital (REH), Rotterdam, the Netherlands. MEH has a walk-in emergency department open 24 hours a day, with approximately 64 000 new patients per year. The REH emergency department is open 24 hours a day but is referral only, with approximately 13 000 new patients per year. Inclusion criteria were laboratory-confirmed gonococcal eye infection (via molecular methods and/or culture) in any adult (≥16 years) between 1 January 2017 and 31 July 2023. At MEH, conjunctival nucleic acid amplification test (NAAT) samples were collected using Aptima swab collection kits (HOLOGIC, USA). NAAT for conjunctival specimens using the Aptima Combo 2 assay has been locally validated, although performance has not been evaluated by the manufacturer. Culture samples were collected using multipurpose culture swabs in transport medium (Transwab, UK), plated on chocolate agar and incubated for 48 hours at 35°C at 5% carbon dioxide (CO2). Organisms were identified using Maldi-ToF (Bruker, Germany) and confirmed with GonoCheck (E-Y Laboratories, USA) and API NH test (bioMérieux, France). At REH, eSwabs (COPAN, USA) were used to sample the conjunctiva, plated on chocolate agar with Vitox supplement (Oxoid, ThermoFisher, USA); the eSwab liquid was used for N. gonorrhoeae PCR (NeumoDX, Qiagen, Germany). Cultures were incubated on chocolate agar for 48 hours at 35°C at 5–7% CO2. Suspected N. gonorrhoeae colonies were identified using VITEK MS PRIME (bioMérieux, France). Antibiotic susceptibility testing was performed at MEH using MIC Test strips (Liofilchem, Italy) on agar base with 1% Isovitalex at 5% CO2, and at REH by Etest on Mueller Hinton agar (Xebios, Germany) at 5–7% CO2. Both centres interpreted susceptibility using breakpoint criteria derived from European Committee on Antimicrobial Susceptibility Testing guidance and in accordance with the manufacturer’s specifications, as previously described.12 13

Medical records were analysed for clinical presentation, treatment, complications and antibiotic susceptibility.

Results

There were 21 cases identified between 2019 and 2023. No cases were identified in 2017 and 2018. Figure 2 shows the GKC cases per year for both centres. In 2023, there is a sharp increase with 11 cases in the first 7 months, compared with ≤3 cases per year between 2019 and 2022. Table 1 shows clinical characteristics. N. gonorrhoeae NAAT was positive for all 21 cases. Culture was positive in 11 of 17 (64.7%) cases. Median age was 23.5 years (range 21–58) at MEH and 23 years (range 19–38) at REH. The population were majority male (16 of 21, 76.2%). In approximately half of cases (11 of 21, 52.4%), the clinical diagnosis was missed at first presentation, as non-gonococcal bacterial or viral infections were presumed and diagnostic samples not taken. None of the isolates from either centre were resistant to ceftriaxone. Systemic treatment was provided in 20 of 21 cases; 94.7% (18 of 19) received ceftriaxone. Topical treatment varied widely; agents used included moxifloxacin, ofloxacin, cefuroxime, cefazolin, azithromycin, gentamicin, benzylpenicillin, tetracycline and chloramphenicol. Complication rates were high (11 of 21, 52.4%) and included corneal thinning (6 of 21, 28.6%), pre-septal/orbital cellulitis (4 of 21, 19.0%) and symblepharon (1 of 21, 4.7%). Visual outcomes were good however, with 9 of 15 (60%) achieving 6 out of 7.5 or better on Snellen chart. There were no perforations. Despite the provision of ophthalmology appointments, one-third (4 of 12, 33.3%) in London did not attend so were lost to follow-up.

Figure 2

Number of cases of GKC 2017–2023. GKC, gonococcal keratoconjunctivitis; MEH, Moorfields Eye Hospital; REH, Rotterdam Eye Hospital.

Table 1

Clinical characteristics of GKC cases: 1 January 2017–31 July 2023

Conclusion

There is a notable increase in the incidence of GKC cases in our centres in 2023, which may indicate a rise across Western Europe. More data are needed to determine if the rise in GKC is disproportionate to the overall rise in gonorrhoea diagnoses. The increase in GKC could be due to ophthalmologists being more aware of the condition and testing more frequently, or possibly a particular strain or strains of N. gonorrhoeae with a preponderance for causing GKC may be currently circulating. As GKC can result in severe vision loss if left untreated, emergency departments need a heightened awareness to identify and treat cases with hyperacute purulent keratoconjunctivitis at first presentation, even in individuals without identifiable risk factors. All suspected cases should have a swab taken for urgent N. gonorrhoeae NAAT, culture and susceptibility testing. Appropriate treatment protocols should be in place, based on national and/or local antimicrobial susceptibility data which vary between countries. It should be noted that clinical breakpoints are based on systemic rather than topical dosing regimens, so the results of susceptibility testing may not correlate clinically. There are limited trial data to support GKC management, particularly for topical treatment. The lack of data is a major concern and there is no consensus among experts. The use of topical adjunctive antibiotics is commonplace although not present in international guidance due to lack of evidence. Further research of optimal treatment strategies is required. Departments need robust links to SHS for STI screening, partner notification and follow-up for confirmation of cure. Similarly, SHS specialists should be aware of the potential for sight-threatening eye disease in gonococcal infection and refer all cases of suspected GKC for ophthalmic input.

This report has limitations in that it is retrospective and in two centres. Sexual history was not documented in ophthalmology notes so no conclusions could be drawn regarding risk factors or particular high-risk sexual practices. Patients with GKC may present to services other than eye hospitals, leading to underascertainment of cases. There is limited national epidemiology on GKC, including on antimicrobial susceptibility. From 2023, GKC surveillance has been incorporated into the STI surveillance system in England. Additionally, nationwide studies on GKC including antimicrobial susceptibility and whole-genome sequencing of gonococcal isolates are planned for 2024 in both countries. Enhanced, sustained, national surveillance of GKC is essential to inform treatment guidelines, aid investigation into cases of treatment failure and guide appropriate public health response. A multinational, European surveillance programme for GKC would be of benefit.

Data availability statement

All data relevant to the study are included in the article or uploaded as supplemental information.

Ethics statements

Patient consent for publication

Ethics approval

The study was approved by institutional review at both centres: the Clinical Audit Committee of Moorfields Eye Hospital (approval number 1297) and the Scientific Research Committee at Rotterdam Eye Hospital (approval number WCO-2023-11). The study was compliant with the Declaration of Helsinki.

References

Footnotes

  • ALM and ACR contributed equally.

  • Correction notice This paper has been corrected since it was first published. The second author's name has been updated.

  • Contributors ALM and AR conceived the idea for the report and prepared the first draft of the manuscript. All authors contributed to the analysis of the data and critical revisions of the manuscript. ALM was responsible for the overall content as the guarantor.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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