HPS Weekly Report. Current notes. Contents. 26 September 2017 Volume 51 No. 2017/38 ISSN (Online)

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1 HPS Weekly Report Volume 51 No. 2017/38 ISSN (Online) Contents Current notes Legionnaires disease, Dubai - ECDC risk assessment 331 Antibacterial agents in clinical development - WHO report 332 World Rabies Day - 28 September Bovine TB - disease control consultation 333 FSS advice on the sale of apricot kernels and bitter almonds 333 Lead in drinking water DWQR Project 334 Surveillance Report Genital chlamydia and gonorrhoea infection in Scotland: laboratory diagnoses Gonococcal antibiotic surveillance in Scotland (GASS): prevalence, patterns and trends in Current notes Legionnaires disease, Dubai - ECDC risk assessment 51/3801 Further to Current note 51/2503 (at nhs.uk/ewr/redirect.aspx?id=73639), the European Centre for Disease Prevention and Control (ECDC) issued an updated risk assessment on 21 September. ECDC observed a significant increase in the number of cases of travel-associated Legionnaires disease (TALD) in EU travellers returning from Dubai during the period October 2016 to May This increase, moreover, could not be accounted for by the increase in travel patterns from the EU. The return to the baseline level of TALD in the most recent two months suggests that the outbreak may have ended. However, in previous years October and November have been the months associated with the highest numbers of TALD notifications - particularly in and cases are therefore still expected to occur in the coming months. ECDC s ongoing monitoring of the situation will be based on the continued timely reporting of TALD cases by the EU member states through the ELDSNet surveillance scheme. There are also several options that EU members states may consider to assess and mitigate the risks in relation to TALD cases having travelled to areas that have experienced increased numbers of cases in the past: In addition to the standard reporting procedures, inform ELDSNet of TALD cases having stayed in private accommodation. Inform travellers particularly those over 50 years, smokers and immunocompromised persons to seek medical advice if they experience severe respiratory infection symptoms up to two weeks after travelling in order to ensure early and appropriate diagnosis and treatment. Remind clinicians to consider Legionnaires disease in patients presenting with community-acquired atypical pneumonia and a history of travel in the two weeks prior to disease onset. ECDC will be monitoring the epidemiological situation closely.

2 The full assessment can be accessed at Antibacterial agents in clinical development - WHO report 51/3802 On 20 September, the World Health Organization (WHO) published a report Antibacterial agents in clinical development - an analysis of the antibacterial clinical development pipeline, including tuberculosis which finds a serious lack of new antibiotics under development to combat the growing threat of antimicrobial resistance. Most of the drugs currently in the clinical pipeline are modifications of existing classes of antibiotics and are only short-term solutions. The report found very few potential treatment options for those antibiotic-resistant infections identified by WHO as posing the greatest threat to health, including drug-resistant tuberculosis which kills around 250,000 people each year. In addition to multidrug-resistant tuberculosis, WHO has identified 12 classes of priority pathogens - some of them causing common infections such as pneumonia or urinary tract infections - that are increasingly resistant to existing antibiotics and urgently in need of new treatments. The report identifies 51 new antibiotics and biologicals in clinical development to treat priority antibiotic-resistant pathogens, as well as tuberculosis and the sometimes deadly diarrhoeal infection Clostridium difficile. Among all these candidate medicines, however, only eight are classed by WHO as innovative treatments that will add value to the current antibiotic treatment arsenal. There is a serious lack of treatment options for multidrug- and extensively drug-resistant M. tuberculosis and gram-negative pathogens, including Acinetobacter and Enterobacteriaceae (such as Klebsiella and E. coli) which can cause severe and often deadly infections that pose a particular threat in hospitals and nursing homes. There are also very few oral antibiotics in the pipeline, yet these are essential formulations for treating infections outside hospitals or in resource-limited settings. To counter this threat, WHO and the Drugs for Neglected Diseases Initiative (DNDi) set up the Global Antibiotic Research and Development Partnership (known as GARDP). On 4 September 2017, Germany, Luxembourg, the Netherlands, South Africa, Switzerland, the UK and the Wellcome Trust pledged more than 56 million for this work. WHO concludes, however, that new treatments alone will not be sufficient to combat the threat of antimicrobial resistance. [Source: WHO News Release, 20 September mediacentre/news/releases/2017/running-out-antibiotics/en/] World Rabies Day - 28 September /3803 Created and coordinated annually by the Global Alliance for Rabies Control (GARC), World Rabies Day on September 28 focuses on rabies endemic countries, to increase community awareness of the disease and its prevention. World Rabies Day also raises the profile of national and local control programmes and acts as a springboard for year-round capacity building and awareness. At the global conference on rabies elimination in 2015, a common goal of zero human deaths from canine rabies by 2030 was agreed by the World Health Organization, World Organisation for Animal Health, UN Food and Agriculture Organization and GARC. In support of this goal, the 2017 World Rabies Day theme is Rabies: Zero by

3 The Partners for Rabies Prevention meeting held in August brought together over 40 representatives from 27 organizations to discuss international efforts to support countries as they move forward in their canine rabies elimination efforts. The delegates reflected a diverse range of stakeholders in rabies control, including International organizations, rabies experts, academics, vaccine manufacturers and non-governmental organizations. What emerged was a strong commitment from organisations at the international level to work together to provide concrete support to countries planning and implementing rabies elimination strategies, in the move towards an end to canine-transmitted human rabies by Attendees highlighted several recent international meetings involving rabies experts, and reported that coordinated revisions of both OIE and WHO guidance documents are currently being discussed. The OIE reported that its Rabies Vaccine Bank is now able to handle requests from any member country, and payments can be received through several different mechanisms, allowing for endemic country purchases as well as donations. A vaccine stockpile for human vaccine is being planned by WHO to fulfil a similar need on the human side. Recent modelling work presented the scope of what reaching zero human rabies deaths globally by 2030 would entail. It provided the canine vaccine forecasting data necessary and an appreciation of the scale of capacity building in terms of human resources that will be necessary to achieve this goal. [Source: Rabies Aliance News Releases, Bovine TB - disease control consultation 51/3804 A consultation which opened on 7 September sets out a number of proposed amendments to the Tuberculosis (Scotland) Order 2007 and seeks views on specific proposals to introduce changes to the way compensation for bovine TB in Scotland is paid. In 2009 Scotland achieved Officially Tuberculosis Free (OTF) status in recognition of the low and stable incidence of TB found in Scottish herds and the Scottish Government is committed to a comprehensive practical and proportionate programme of actions in order to maintain current low levels of TB and to safeguard Scotland s OTF status. Defra and the Welsh Government have already either introduced, or are consulting on, similar measures. This has highlighted the need to review the Tuberculosis (Scotland) Order 2007 and bovine TB compensation system to ensure it continues to incentivise compliance and best practice and remains financially sustainable for the future. The consultation closes on 30 November and can be accessed at animal-health-and-welfare/bovine-tb/. FSS advice on the sale of apricot kernels and bitter almonds 51/3805 Food Standards Scotland (FSS) has recently updated its advice to food business operators on the sale of apricot kernels and bitter almonds. FSS has previously advised that raw apricot kernels should not be consumed (see Current note 50/2005 at This is because they contain the naturally occurring substance amygdalin a cyanogenic glycoside which results in the release of cyanide during digestion of the kernels in the human gut. Following discussions with the European Commission and other member states, legislation has now been agreed to control the presence of cyanide in apricot kernels. A maximum level of 20 mg/kg has been established for hydrocyanic acid in raw, unprocessed apricot kernels both bitter 333

4 and sweet varieties, including milled, cracked or chopped raw products set out in Commission Regulation EU 2017/1237 amending section 8 of the Annex to Regulation (EC) No 1881/2006. The maximum limit of 20 mg/kg applies to raw, unprocessed apricot kernels including the milled, cracked or chopped forms placed on the market for the final consumer. If there are consignments of apricot kernel meant for further processing, e.g. persipan manufacture, the importer/food business operator (FBO) should provide clear evidence of intended use either on the label on each individual bag/box/etc. or in the original accompanying documents. In the absence of these evidence of compliance with the ML of 20 mg/kg should be provided. Bitter almonds which are also known to have high levels of cyanide are currently not included within the scope of the 20 mg/kg cyanide maxi mum level as it is understood that they are normally used only after further processing or home cooking and would not be eaten raw. However if it is evident that raw kernels are being sold for direct human consumption and there is an indication of risk to human health, enforcement action can be taken in accordance with general food law. The full advice from FSS can be accessed at update-on-apricot-kernels (21 September 2017). Lead in drinking water DWQR Project 51/3806 Over recent years, the Drinking Water Quality Regulator for Scotland (DWQR) has been pursuing a project to develop policy on achieving a reduction of exposure to lead in drinking water. The project seeks to identify enablers and strengthen or introduce mechanisms with a range of stakeholders and influencers for the removal of lead service pipes and plumbing. In drinking water quality legislation, the limit for lead in drinking water has progressively reduced over the past 30 years to 10µg/l (micrograms per litre). Over the same period however, concerns have developed within Scotland s health professional community that even this standard may be too high and there is an increasing view that we should strive to reduce lead levels in drinking water as far as is practicably possible. The specific aims of the project are to: ensure there is a clear and shared understanding of legislation as it relates to duties on drinking water suppliers; engage with health officials to identify common themes and to align drinking water quality policy with health policy; work with stakeholders to identify areas where policy can be aligned to ensure the risk of exposure to lead in the environment is minimised; investigate the various policy options available and work with our SG colleagues in determining the best way forward. A key sector of consumers at risk from lead in drinking water are children and babies. They absorb more lead than adults due to their growing bones and other organs within which lead can be deposited and accumulate as they develop. It is important therefore that we ensure that schools and nursery premises are free from lead. It is believed that attention to the removal of lead had been carried out in the past but in support of the project, local authorities have undertaken surveys of all their owned properties to ensure there is certainty around the issue. 334

5 A further survey is to be undertaken on behalf of DWQR to ensure a similar lead free status can be confidently claimed for all private schools and independent nursery premises. For further details of the project s progress, see the most DWQR s most recent newsletter (August 2017), available from 335

6 Surveillance report Genital chlamydia and gonorrhoea infection in Scotland: laboratory diagnoses Prepared by: KMA Trayner, LA Wallace, J Shepherd, K Templeton, DJ Goldberg Key points In 2016, diagnoses of genital chlamydia and gonorrhoea have remained at the same level as that reported in Young people, particularly women aged under 25, are the group most at risk of being diagnosed with an STI. Rectal gonorrhoea in men, a marker of condomless anal intercourse, has remained high. Introduction In this report, ten-year trend data are presented on two acute sexually transmitted infections (STIs): genital chlamydia and gonorrhoea. Data on genital chlamydia and gonorrhoea infection are extracted from the laboratory diagnoses database, the Electronic Communication of Surveillance in Scotland System (ECOSS). 1 This is an HPS surveillance system which is updated daily with positive test results from all Scottish diagnostic and reference laboratories. The universal use of ECOSS by testing laboratories in Scotland has resulted in a greater quantity and better quality of data which is subject to cleaning and refinement at HPS. Thus, the trends observed since 2009 and the implementation of ECOSS in all laboratories are not directly comparable to those prior to this date. The data associated with the laboratory-positive diagnoses are restricted to age, gender and the NHS board where the clinical specimen originated. Records of infection in those aged under 10 are not reported. Some numbers in this report have been suppressed as indicated with an asterisk (*) in instances where patient confidentiality might be compromised through deductive disclosure. Genital chlamydia In 2016, 15,147 diagnoses of genital chlamydial infection were reported to HPS, a similar number to that reported in 2015 (15,000). The total number of diagnoses has been reducing in recent years but appears to be stable at around 15,000 diagnoses annually during the past two years (Table 1). The improved data capture of laboratory test results via ECOSS means that the data since 2009 have been subject to more extensive validation, particularly with regard to removing repeat samples taken for the same episode of infection. The data presented in this report for genital (including extragenital) chlamydial infection indicate episodes of infection, where an episode is defined as a six-week period. Multiple laboratory-positive diagnoses made more than six weeks apart are classed as separate episodes of infection. 336

7 TABLE 1: Laboratory diagnoses of Chlamydia trachomatis infection in Scotland , by NHS board of report. NHS board AA BR DG FF FV GR GGC HG LN LO OR * 34 SH TY WI * 24 Total The majority of genital chlamydia diagnoses (60%) were made in women (Table 2), which has been the pattern observed over the past decade. Genital chlamydia is an infection which predominates in young people. In 2016, 68% of all diagnoses (75% and 58% of all female and male diagnoses, respectively) were made in those aged under 25 years (Table 3). The majority of diagnoses were made among women and men aged years. This has been a consistent finding for the past ten years (except for women in 2010, where more diagnoses were observed in those aged under 20). TABLE 2: Laboratory diagnoses of Chlamydia trachomatis infection in Scotland , by gender. Gender Women Men Unspecified Total

8 TABLE 3: Laboratory diagnoses of Chlamydia trachomatis infection in Scotland , by gender and age group. Women Age < Unknown Total Men Age < Unknown Total

9 In 2016, for women, the highest rates of diagnoses per 100,000 population were observed in NHS Tayside and NHS Lothian (over 600 diagnoses per 100,000 population) (Table 4). There was a similar observation for men with the highest rates in NHS Tayside and NHS Lothian (over 400 diagnoses per 100,000 population). Outside the island NHS boards, the lowest rates for men and women were observed in NHS Highland and NHS Lanarkshire. NHS Highland data are thought to reflect an under-representation of diagnoses, as Highland residents living in areas which were part of the former NHS Argyll & Clyde may have been diagnosed in, and reported from, NHS Greater Glasgow & Clyde. For those aged under 25 years, rates of diagnoses per 100,000 population are much higher than for the overall diagnosed population. Outside the island NHS boards, among young women aged under 25, the highest rates of diagnoses per 100,000 population were observed in NHS Tayside and NHS Lothian (greater that 2400 diagnoses per 100,000 population) (Table 4 and Figure 1). Among young men, the highest rates of diagnoses were recorded in NHS Tayside, NHS Borders and NHS Lothian (over 1200 diagnoses per 100,000 population). Outside the island NHS boards, the lowest rates were observed in NHS Lanarkshire for both men and women aged under 25 years. FIGURE 1: Rate (per 100,000) of diagnosis of Chlamydia trachomatis infection in those aged less than 25 years in Scotland in 2016, by gender and NHS board. Ayrshire & Arran Borders Dumfries & Galloway Fife Forth Valley Grampian Greater Glasgow & Clyde Highland Lanarkshire Lothian Orkney Shetland Tayside Western Isles Scotland * * * Women Men * Male rates for OR, SH and WI have been suppressed to prevent deductive disclosure. 339

10 TABLE 4: Chlamydia trachomatis infection, Scotland 2016: number and rate per 100,000 population by NHS board of report and gender. NHS board All ages Women Men Number Rate/100,000 1 Number Rate/100,000 1 AA BR DG FF FV GR GGC HG LN LO OR SH TY WI Scotland Less than 25 years NHS board Women Men Number Rate/100,000 2 Number Rate/100,000 2 AA BR DG FF FV GR GGC HG LN LO OR * * SH * * TY WI * * Scotland Rates based on population estimate as at 30 June 2016 using ages as denominator. 2 Rates based on population estimate as at 30 June 2016 using ages as denominator. 340

11 Lymphogranuloma venereum (LGV) infection, caused by a serovar of Chlamydia trachomatis, re-emerged during 2003/2004 when outbreaks were reported in many European cities. LGV infection occurs predominantly in men who have sex with men (MSM) and is associated with high levels of concurrent STIs, in particular HIV and with high risk sexual behaviour, including multiple anonymous partners. Since its re-emergence, over 4600 diagnoses have been reported in the UK to the end March 2016 (latest report available). 2 The UK now has the largest documented outbreak of LGV among MSM in Europe. 2,3 In Scotland during 2016, 45 LGV diagnoses were recorded, all of which were among men, compared to 15 in 2015, eight in 2014, 11 in 2013, 10 in 2012 and six in Provisional 2017 data indicate that the number may have returned to pre-2016 levels with 13 diagnoses recorded at the end of August Gonorrhoea In 2016, 2363 diagnoses of gonorrhoea were reported to HPS, a similar number to that reported in 2015 (2346). This follows a 28% increase between 2014 and Since 2012, nucleic acid amplification tests (NAATs) have been in routine use across Scotland. 4 During this time, there has been a concomitant increase in extragenital testing. Testing strategy has now stabilised and epidemiological trends since 2013 are more comparable than those in previous years. Furthermore, since 2015, confirmatory testing is now being performed by several testing laboratories and not exclusively by the Scottish Bacterial Sexually Transmitted Infection Reference Laboratory (SBSTIRL). As a consequence, the number of episodes reported here differ from those reported in the GASS 2016 report (HPS Weekly report, this issue). Thus, while a proportion of the increase in episodes during the past few years is due to more effective testing, it is likely that the incidence of infection has also increased. TABLE 5: Gonorrhoea, Scotland : laboratory reports (episodes) by gender Female Male Unspecified Total Note: one episode of gonorrhoea corresponds to an infected individual from whom more than one isolate could have been recovered. 341

12 Over the past decade, there has been annual variability in the number of episodes in each NHS board and, for some NHS boards, no clear trends in incidence are evident (Table 6, Figure 2). However, an increase in the number of episodes was noted in several NHS board areas in A continuing pattern remains of one third of episodes being diagnosed in NHS Greater Glasgow & Clyde and around one quarter being diagnosed in NHS Lothian. TABLE 6: Gonorrhoea, Scotland : laboratory reports (episodes) by NHS board of report. NHS board AA BR 0 6 * * DG * 9 * * FF FV GR GGC HG LN LO OR * * 0 0 * SH * 0 * * TY WI * 0 0 * 0 * * Total Note: one episode of gonorrhoea corresponds to an infected individual from whom more than one isolate could have been recovered. FIGURE 2: Episodes of gonorrhoea by NHS board, Scotland, Number Year Grampian Greater Glasgow & Clyde Lothian Tayside Rest of Scotland 342

13 In contrast to genital chlamydia, the majority of gonorrhoea diagnoses were made in men (Table 5). The male:female ratio was 2.9:1, which is lower than that observed in 2015 (4.2:1) but similar to the ratio in preceding years (3:1 male:female). In women, infection with gonorrhoea is associated predominantly with a younger age group, with 67% of female episodes occurring in those aged under 25 years (Table 7). For men, in 2016, 41% of episodes occurred in those aged under 25 years (Table 7). TABLE 7: Gonorrhoea, Scotland : laboratory reports (episodes) by gender and age group. Men Age < > Not given Total Women Age < * * * * * > Not given * Total The increase in gonorrhoea among men, is considered to be due, largely, to transmission among men who have sex with men (MSM). Rectal gonorrhoea is a key marker for condomless anal intercourse. In 2016, 37% of episodes in men were diagnosed from a rectal swab positive for gonorrhoea (Table 8). The number and proportion of episodes of male rectal gonorrhoea remains high and compares with 37% and 40% recorded in 2014 and 2015, respectively. 343

14 TABLE 8: Gonorrhoea, Scotland : number and proportion of rectal gonorrhoea in men. Year Men-all Men-Rectal % Rectal % % % % % % % % % % 1 Data based on 597 gonococcal isolates reported by SBSTIRL. 2 Includes only those cases for whom specimen type data available. In 2016, the highest rates of gonorrhoea infection for men (at over 160 per 100,000 population) were seen in NHS Greater Glasgow & Clyde and NHS Lothian and for women (at over 40 per 100,000 population) in NHS Lothian and NHS Grampian (Table 9). TABLE 9: Gonorrhoea, Scotland 2016: laboratory reports (episodes) by NHS board, gender and rate per 100,000 population. Men Women All NHS Board Number Rate/100,000 Number Rate/100,000 Number Rate/100,000 AA BR DG * * * * FF FV GR GGC HG LN LO OR * * 0 0 * * SH 0 0 * * * * TY WI * * 0 0 * * Scotland Note: rates based on population estimate as at 30 June 2016 using ages as denominator. 344

15 Discussion Overall, the number of laboratory-positive diagnoses for genital chlamydial infection and gonorrhoea infection has remained similar between 2015 and Infection among heterosexual men and women Information about sexual orientation is not available from laboratory reports to SBSTIRL or through ECOSS. It is therefore not possible to identify whether infections in men are occurring among those who have sex with women or those who have sex with men. The analysis of STIs in women can however be used to provide an insight into heterosexual transmission. Testing for many STIs has increased since the start of the last decade due to a combination of improvements in access to sexual health clinics, sexual health promotion activities and, improvements in test technology. Testing for chlamydia infection, which is asymptomatic in up to 80% of individuals, also increased during this time, 5 initially as a result of the SIGN guideline 6 recommendations which included the provision of NAAT testing platforms which enable samples to be tested for both chlamydia and gonorrhoea. It is also likely that this change in testing practice has resulted in an increase in gonorrhoea diagnoses. Prior to 2011, annual increases in the number of chlamydia diagnoses were recorded, due in part to a combination of increased opportunistic testing, 5,6 the use of more sensitive diagnostic tests, 6 increased awareness through health promotion campaigns, and latterly, improvements in data collection. Between 2011 and 2015, a reverse in the number of diagnoses has been observed with an 8% decrease between 2014 and 2015 resulting in the lowest annual total recorded over the past decade. In 2016, the number of positive chlamydial diagnoses has remained similar. Over the past few years, genital chlamydia diagnoses have decreased and it is, as yet, unclear whether this reflects a true decrease in incidence or a decrease in opportunistic testing with a more targeted approach. In recent years, there has been discussion about the extent of opportunistic testing and testing of asymptomatic individuals as a result of the initial findings of the CMO Expert Advisory Group on Chlamydia trachomatis testing. HPS is unable to measure the extent of opportunistic testing with our current data collection systems, but it may be that levels of testing have decreased resulting in the lower numbers of diagnoses. Nevertheless, there is no doubt that very large numbers of people are infected, particularly those in the younger age groups. The discrepancy between the numbers of male and female chlamydial infections is almost certainly due to more women than men undergoing testing. Trends in gonorrhoea diagnoses among women could be considered true reflections of any changes in high-risk sexual behaviour among heterosexual populations. During the past five years, the number of annual diagnoses in women has fluctuated between 450 and 600. However, in 2016, we observed over 600 episodes, a 36% increase on that reported since 2015 and the highest number for several years. The majority of gonorrhoea infections in women occur in those under 25 years of age. The data continue to indicate that young people, in particular women, are acquiring STIs at an early age. Thus, it is essential that efforts to effect behavioural change in this group, through positive sexual health messages, are continued while encouraging individuals to undergo testing when at risk of infection and so receive appropriate treatment. 345

16 Infections among men who have sex with men (MSM) As laboratory data contain no information on sexual orientation, rectal gonococcal infection may be used as a surrogate marker for sex between men. The incidence of rectal gonorrhoea, an indicator of condomless anal intercourse between men, accounted for 37% of male gonorrhoea diagnoses. This is similar to that reported in 2015, when 40% of male gonorrhoea diagnoses included a rectal infection. Nevertheless, it is encouraging that the incidence of rectal gonorrhoea in 2016, while still high at 650 episodes, decreased by 14% when compared to the 758 figure for The likelihood of HIV transmission is increased in the presence of another STI, particularly rectal gonorrhoea. HPS reported a decrease in the overall number of reports of HIV among MSM, including new, first time reports in The data available on newly acquired or recent HIV infection (i.e. acquired within the preceding three to four months) also indicate a change: in 2015, over one third of MSM tested (35%) had evidence of a recent infection; while both the number and proportion decreased in 2016 with around one fifth (22%) of MSM recently infected. While this is encouraging and is likely to be related in part to the high levels of individuals on treatment (and therefore a reduction in overall community viral load), it is not yet clear whether this decrease in HIV diagnoses will be sustained in It is too early to observe an effect on HIV incidence based on the use of HIV pre-exposure prophylaxis (PrEP) which, following the SMC decision in April 2017, has been provided by the NHS in Scotland since the beginning of July. The introduction of PrEP may have an effect on sexual behaviour, and thus on STI incidence. Plans are being put in place to monitor the impact of PrEP use. There are a number of additional sexual health concerns in this population; the annual incidence of infectious syphilis among MSM having increased in recent years and diagnoses in men overall having reached the highest level recorded for over 60 years. 8 The sexual transmission of Shigella infection is also a concern, and has been associated with a high number of sexual partners, increased rates of HIV and chemsex. 9,10 In recent years, along with the rest of the UK, Scotland has seen an increase in rectal STIs such as Lymphogranuloma venereum (LGV). Since June 2016, there has been an outbreak of hepatitis A throughout Europe 11 including in England where there have been almost 300 diagnoses with at least 74% of these among MSM at April However, there is no evidence to suggest that hepatitis A is being widely transmitted among MSM in Scotland. This may be due, in part, to levels of immunity as a result of continued efforts to vaccinate MSM against hepatitis B, which has, in many clinics, involved the use of the combined hepatitis A/hepatitis B vaccine. BASHH guidance changed in 2017 to advise that all MSM attending sexual and reproductive health services should receive hepatitis A vaccine. 13 In summary, information from the infection data (particularly the high level of rectal gonorrhoea) suggest that condomless sexual intercourse and risk of STI infection among MSM continue. There are ongoing challenges for the control and prevention of STIs in MSM. References 1. Health Protection Scotland. ECOSS (The Electronic Communication of Surveillance in Scotland). Available from: aspx?id=248. (accessed 21 September 2017). 2. Public Health England. Lymphogranuloma venereum (LGV): guidance, data and analysis. Available from: (accessed 21 September 2017). 346

17 3. Childs T, Simms I, Alexander S et al. Rapid increase in lymphogranuloma venereum in men who have sex with men, United Kingdom, 2003 to September Euro Surveill. 2015;20(48):pii= Available from: aspx?articleid= (accessed 21 September 2017). 4. Scottish Microbiology Forum, British Association of Sexual Health and HIV, Health Protection Scotland. Guidance on the use of molecular testing for Neisseria gonorrhoeae in diagnostic laboratories Available from: (accessed 21 September 2017). 5. Health Protection Scotland. Key Clinical Indicators for Sexual Health Report Available from: (accessed 21 Septemmber 2017). 6. Scottish Intercollegiate Guidelines Network. Management of genital Chlamydia trachomatis infection. No.109. Edinburgh: SIGN, March Available from: management-of-genital-chlamydia-trachomatis-infection.html. (accessed September 2017). 7. Health Protection Scotland. ANSWER HIV infection and AIDS: quarterly report to 30 June HPS Weekly Report 2017; 51(36): Available from: ewr/redirect.aspx?id= (accessed 21 September 2017). 8. Health Protection Scotland. Syphilis in Scotland 2016: update. HPS Weekly Report 2017:51(33): Available from: 9accessed 21 September 2017). 9. Simms I, Field N, Jenkins C et al. Rapid communication: Intensified shigellosis epidemic associated with sexual transmission in MSM - Shigella flexneri and S. sonnei in England, 2004 to end of February Euro surveill. 2015;20(15):pii= Available from: eurosurveillance.org/viewarticle.aspx?articleid= (accessed 21 September 2017). 10. Gilbart VL, Simms I, Jenkins C et al. Sex, drugs and smart phone applications: findings from semi-structured interviews with MSM diagnosed with Shigella flexneri 3a in England and Wales. Sexually Transmitted Infections 2015;91(8): Available from: content/91/8/598. (accessed 21 September 2017). 11. European Centre for Disease Control and Prevention. Rapid risk assessment: Hepatitis A outbreak in the EU/EEA mostly affecting me who have sex with men, 3rd update, 28 June Available from: (accessed 21 September 2017). 12. Public Health England. Hepatitis A outbreak in England under investigation. Health Protection Report. 2017;11(17). Available from: (accessed 21 September 2017). 13. Public Health England. Hepatitis A vaccination in adults temporary recommendations. Available from: (accessed 21 September 2017). Acknowledgements HPS wishes to thank consultant microbiologists, consultant virologists and their staff who supply data to the SBSTIRL and to HPS. 347

18 Gonococcal antibiotic surveillance in Scotland (GASS): prevalence, patterns and trends in 2016 Prepared by: Jill Shepherd Summary The number of episodes of gonorrhoea submitted to SBSTIRL remained steady between 2015 and Around half of episodes were diagnosed by nucleic acid amplification only. The resistance surveillance in 2016 was therefore based on 50% of gonococcal infections in Scotland. No resistance was observed to ceftriaxone, the recommended first-line therapy along with azithromycin, or to spectinomycin. No treatment failures were formally reported. Decreased susceptibility to azithromycin has fallen to 0.9% of isolates. A small number of isolates (two) demonstrated high-level resistance to azithromycin. The percentage of isolates resistant to cefixime has remained steady at 0.5%. The rate of resistance to ciprofloxacin has also remained steady (34.9%). Continued surveillance for antibiotic resistance is essential for guiding the choice of effective therapeutic regimens for gonorrhoea and every effort should be made to maintain culture from a high proportion of gonococcal episodes of infection to avoid compromising the accuracy of surveillance data. This is particularly important in view of the outbreak of high-level azithromycin-resistant gonorrhoea seen in England. Methodology The Scottish Bacterial Sexually Transmitted Infections Reference Laboratory (SBSTIRL) provides surveillance data on antimicrobial resistance for all gonococci isolated in Scotland. All cultured organisms are tested against seven antibiotics using the agar dilution method, 1 and by E-tests (biomérieux) when the minimum inhibitory concentration (MIC) exceeds the dilution series. Neisseria gonorrhoeae multi-antigen sequence typing (NG-MAST) 2 is performed on a proportion isolates and specimens positive by N. gonorrhoeae nucleic acid amplification tests (NAAT) submitted to SBSTIRL where a culture is not available. Episodes of gonorrhoea in Scotland The number of episodes of gonorrhoea is obtained by the manual removal from the database of duplicate samples from the same patient taken within a six-week period, and presumed duplicate patients who appear to have been tested both in primary care and at sexual health services. A total of 2193 episodes of gonococcal infection were reported by SBSTIRL in Of these, 17 were cultures non-recoverable on receipt in the laboratory and 1092 were diagnosed by NAAT with no culture available. Antibiotic susceptibility testing was therefore performed on isolates from 1087 episodes (50%). Since April 2015, NG-MAST has only been performed on a proportion of samples, NG-MAST data being available for 727 episodes (33%). NG-MAST data can be a useful predictor of antibiotic susceptibility profile for those sequence types (STs) that occur commonly and for which no cultured isolate exists. 3 Table 1 shows gonorrhoea episodes and trends by gender. Total gonorrhoea episodes show no change in comparison with Males accounted for 76.0% of episodes in As has been the case for every year for which such data have been available, a larger proportion (51.5%) of diagnoses in women were by NAAT only, compared with 49.2% in men and 49.8% overall. 348

19 TABLE 1: Episodes of gonorrhoea: isolates and NAAT specimens sent to SBSTIRL over the last five years Culture positive NAAT positive Total Culture positive NAAT positive Total Culture positive NAAT positive Total Culture positive NAAT positive Total Culture positive NAAT positive Total Total Male Female Unknown General antibiotic susceptibility trends Table 2 and Figure 1 provide resistance trends for the antibiotics tested over the last five years and Table 3 gives the pattern of resistance for isolates in TABLE 2: Gonococcal antibiotic resistance trends over the last five years. Antimicrobial resistance PPNG (b-lactamase positive) TRNG (plasmid mediated tetracycline resistance tetracycline MIC 16 mg/l) PenR (chromosomally mediated resistance to penicillin - MIC 2mg/l but b-lactamase negative) TetR (chromosomally mediated resistance to tetracycline - MIC 2 to 8 mg/l) Ciprofloxacin intermediate resistance (MIC mg/l) Ciprofloxacin resistant (MIC 1mg/l) Azithromycin decreased susceptibility (MIC 1 mg/l) Spectinomycin resistance (MIC 128 mg/l) Ceftriaxone resistance (MIC >0.125 mg/l) Cefixime resistance (MIC >0.125 mg/l) Resistant to one or more antibiotics 2012 (n=951) 2013 (n=827) 2014 (n=929) 2015 (n=1101) 2016 (n=1087) 6.5% (62) 7.1% (59) 11.3% (105) 11.6% (128) 7.4% (80) 10.4% (99) 8.6% (71) 14.9% (138) 6.4% (71) 7.6% (83) 7.8% (74) 3.9% (32) 7.8% (72) 7.2% (79) 1.2% (13) 18.3% (174) 19.9% (164) 19% (176) 25.8% (284) 15.7% (171) 0.5% (5) 1.2% (10) 1.1% (10) 0.3% (3) 2.6%(28) 33.8% (321) 30.7% (254) 27.2% (253) 34.2% (376) 32.3% (351) 1.1% (10) 0.5% (4) 1.3% (12) 2.4% (26) 0.9% (10) 0% 0% 0% 0% 0% 0% 0% 0% 0% 0% 0% 0.7% (6) 1.4% (13) 0.2% (2) 0.5% (5) 39.1% (372) 37.5% (301) 42.7% (397) 50.1% (552) 42.4% (461) 349

20 FIGURE 1: Five-year trends in gonococcal resistance PPNG TRNG Pen MIC 2 mg/l, Tet MIC 2 and <16 mg/l Ciprofloxacin MIC 1 mg/l Azithromycin MIC 1 mg/l Cefixime MIC mg/l Resistant to 1 antibiotics TABLE 3: Antibiotic resistance patterns in isolates from 1087 episodes of infection, Scotland Total 2015 Plasmid resistance Chromosomal resistance PPNGa TRNGb Penicillin Tetracycline Ciprofloxacin Azithromycin Cefixime Total 2 mg/l 2 mg/l mg/l 1.0 mg/l >0.125 mg/l (7.4%) 128 (11.6%) 83 (7.6%) 71 (6.4%) a b-lactamase positive. 13 (1.2%) 79 (7.2%) 171 (15.7%) 284 (25.8%) 379 (34.9%) 379 (34.4%) b Plasmid mediated tetracycline resistance tetracycline MIC 16 mg/l. 10 (0.9%) 26 (2.4%) 5 (0.5%) 2 (0.2%) 461 (42.4%) 552 (50.1%) 350

21 In total, 461 (42.4%) of the 1087 episodes for which susceptibility data were available exhibited decreased susceptibility to one or more antibiotics tested, down from the 50.1% seen in There were no isolates with decreased susceptibility to ceftriaxone or resistance to spectinomycin in This GASS report continues to report with the same antibiotic breakpoints used in previous years, although SBSTIRL now use EUCAST (European Committee on Antimicrobial Susceptibility Testing) v7.1 breakpoints to report antibiotic susceptibility. 4 Cephalosporin resistance Resistance to cefixime (MIC >0.125 mg/l) was found in two isolates in 2015 (0.2%), similar to previous years. In 2016 five isolates (0.5%) were cefixime-resistant. All isolates remained susceptible to ceftriaxone. Azithromycin decreased susceptibility Decreased susceptibility to azithromycin exceeded 5% in 2007 (44 of 845 episodes, 5.2%), reduced by 2009 to 1.6% (11 episodes), and fell gradually to a low of 0.5% in In 2015 Public Health England (PHE) reported an outbreak of high-level azithromycin resistance (HiL-AziR; MIC >256 mg/l). 5 SBSTIRL detected 10 isolates with decreased susceptility to azithromycin (0.9%), down from 2015 (2.4%), with two being HiL-AziR. Penicillin and tetracycline resistance Overall resistance to penicillin and tetracycline (plasmid and chromosomal) was found in 8.6% and 23.4% of culture episodes respectively. Penicillin resistance, both chromosome- and plasmidmediated, has decreased considerably this year. Ciprofloxacin resistance Ciprofloxacin resistance (MIC 1mg/l) has remained steady in comparison with 2015, with 351 of 1087 episodes (32.3%) resistant. Prior to 2015, the percentage of isolates demonstrating resistance to ciprofloxacin was declining. Sequence type and antibiotic resistance NG-MAST is a highly discriminatory typing scheme that differentiates between isolates on the basis of the sequence variation observed in two genes, coding for the por protein and transferrin binding protein b (tbpb). Each sequence type (ST) is unique and differs from any other by at least one nucleotide. Clusters of isolates sharing the same ST can be observed and both phenotypic and demographic data support the validity of the clusters as containing related isolates. Sequence types represented by five or more antibiotic resistant episodes are given in Table 4, plus STs associated with azithromycin and cefixime resistance. 351

22 TABLE 4: Antibiotic resistance and commonly occurring sequence types PPNG TRNG Resistance category Tetracycline (chromosomal) Ciprofloxacin Azithromycin Cefixime Sequence type a Therefore no antibiotic resistance data available. No. resistant isolates No. non-resistant isolates No. identified by NAAT only a Total No episodes in Plasmid-mediated resistance has previously been associated with infection outside the UK 6 and limited onward transmission in Scotland. However, in 2016 as seen in previous years, PPNG and TRNG appeared to be associated with multiple isolations of the same ST, giving a likely indication of clusters of infection. 352

23 A number of STs were associated with more than one resistance category. ST is associated with ciprofloxacin resistance, with some isolates also showing chromosomally-mediated tetracycline resistance. It has previously been associated with an elevated cefixime MIC (0.12 mg/l) and in 2016 three isolates were resistant. The 2014 data indicated that ST 1407 was associated with cefixime resistance in around a third of isolates. In 2016, none of the five isolates were cefixime-resistant, although all had elevated MICs of 0.12 (mg/l). Acknowledgements I would like to acknowledge all microbiologists who have submitted isolates and specimens to SBSTIRL throughout the year, and all sexual health clinicians for their support. Thanks are also due to staff at SBSTIRL for performing susceptibility testing and NG-MAST typing and particularly to Anne-Marie Logue for maintaining the SBSTIRL databases. References 1. Young H, Moyes A, Robertson DHH et al. Gonococcal infection within Scotland: antigenic heterogeneity and antibiotic susceptibility of infecting strains. European Journal of Epidemiology. 1990;6: Martin IMC, Ison CA, Aanensen DM et al. Rapid sequence-based identification of gonococcal transmission clusters in a large metropolitan area. Journal of Infectious Diseases. 2004;189: Available from: Rapid-Sequence-Based-Identification-of-Gonococcal. (accessed 21 September 2017). 3. Palmer HM, Young H, Graham C, Dave J. Prediction of antibiotic resistance using Neisseria gonorrhoeae multi-antigen sequence typing. Sexually Transmitted Infections. 2008;84(4): Available from: (accessed 21 September 2017). 4. European Committee on Antimicrobial Susceptibility Testing. Clinical breakpoints. Available from: (accessed 21 September 2017) 5. Public Health England. Outbreak of high-level azithromycin resistant gonorrhoea in England: an update. Health Protection Report. 2016;10(30). Available from: publications/high-level-azithromycin-resistant-gonorrhoea-in-england. (accessed 21 September 2017). 6. Young H, Moyes A, Noone A. Epidemiology and treatment outcome of infection with antibiotic resistant strains of Neisseria gonorrhoeae in Scotland. Communicable Disease and Public Health. 1999;2(3): Available from: uk/ / (accessed 21 September 2017). Jill Shepherd, Scottish Bacterial Sexually Transmitted Infections Reference Laboratory Royal Infirmary of Edinburgh, 51 Little France Crescent, Edinburgh EH16 4SA NHS board abbreviations AA Ayrshire & Arran BR Borders DG Dumfries & Galloway GGC Greater Glasgow & Clyde FF Fife FV Forth Valley GR Grampian HG Highland LO Lothian LN Lanarkshire OR Orkney SH Shetland TY Tayside WI Western Isles Correspondence to: The Editor, HPS Weekly Report, Health Protection Scotland, Meridian Court, 5 Cadogan Street, Glasgow, G2 6QE, Scotland T F E NSS.HPSWReditor@nhs.net W Printed in the UK. HPS is a division of the NHS National Services Scotland. Registered as a newspaper at the Post Office. Health Protection Scotland 2017