Scottish Bacterial Sexually Transmitted Infections Reference Laboratory (SBSTIRL) User Report for the period January - December 2011

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1 Scottish Bacterial Sexually Transmitted Infections Reference Laboratory (SBSTIRL) User Report for the period January - ember 211 Kirstine Eastick PhD FRCPath (Director) SBSTIRL, Microbiology Edinburgh Royal Infirmary 51 Little France Crescent, Edinburgh EH16 4SA Contact: kirstine.eastick@luht.scot.nhs.uk Telephone: /681 WWW: Our web page (hosted by HPS) is and is regularly updated. Our User Manual can be found there. We welcome requests for advice and comments on our service by post, and telephone throughout the year. 1

2 Episodes of gonorrhoea submitted to SBSTIRL: Total Male Female Unknown Episodes Year The increase in diagnoses of gonorrhoea in Scotland has continued to 211. Some of the increase reflects changes in testing methodology (introduction of NAATs and extension of their use to extra-genital samples), but this is unlikely to explain a rise of this extent. The epidemiology is explored further in later slides. 2

3 Episodes of gonorrhoea in males by age-group < >65 Episodes Year Gonorrhoea is most frequestly diagnosed in men aged between 2 and 24 years. Recent increases have been seen across all age-groups. 3

4 Episodes of gonorrhoea in females by age-group 2 < >65 15 Episodes Year Gonorrhoea is most frequently diagnosed n women aged less than 25 years. 4

5 Episodes of gonorrhoea (isolates and NAAT specimens) submitted to SBSTIRL by six month period: 26 to 211 N o of episodes Jan-June Jan-June 7 7 Jan-June 8 8 Jan-June 9 9 Jan-June 1 1 Jan-June Cultured isolates Confirmed GC NAAT Episodes of gonorrhoea diagnosed by GC NAAT have been included in the data since 28. These include clinical specimens confirmed at SBSTIRL, clinical specimens tested and confirmed by a second test elsewhere but sent to the laboratory for typing, and non-viable cultures. See later slide for details of supplemental GC NAAT testing. 5

6 N. gonorrhoeae isolation/detection by site Urogenital Rectal Pharyngeal Other Number of specimens Year There has been an increase in rectal and pharyngeal detections over time. This is proabably mainly due to the introduction of NAATs, which have a greater sensitivity at these sites. There has also been a marked increase in detection of urogenital N. gonorrhoeae, which may be due to use of NAATs or reflect a genuine increase in cases of gonorrhoea. 6

7 Gonorrhoea diagnosis by setting 1% 9% 8% 7% 6% 5% 4% Other Hosp GP SHS 3% 2% 1% % SHS - Sexual Health Service (includes Family Planning where specified) One fifth of gonorrhoea diagnoses are currently made in General Practice, and almost one quarter outside specialist Sexual Health Services. This figure is likely to be an under-estimate due to double-counting of those individuals diagnosed in primary care and referred to Sexual Health services for management. This presents challenges in terms of ensuring referral to specialist services for treatment and partner notification. It is intended to extend this slide in future years, in order to plot trends. 7

8 Episodes of gonorrhoea by NHS Board July -ember 211 compared with previous three six-month periods Jan-June 21 (n=638) Jan-June 211 (n=7) 21 (n=743) 211 (n=842) No of episodes AA BR DG FF FV GGC GR HG LN LO OR SH TY WI The majority of episodes of gonorrhoea in this period were diagnosed in Greater Glasgow & Clyde (37%) and Lothian (26%). The number of episodes increased in Dumfries and Galloway, Forth Valley, Lanarkshire, and Lothian, and marginally in Ayrshire and Arran and Fife. NAAT testing has been introduced in Dumfries and Galloway in the past year. The number of episodes decreased in Tayside and Highland (compared to the same period of the previous year) and was steady in Grampian. Users are reminded that cultures should be taken from symptomatic patients, those positive on Gram stain, contacts of gonorrhoea, those who have failed treatment and those who are positive by NAAT. All N. gonorrhoeae cultures and NAAT-positive specimens should be forwarded to SBSTIRL. Only numbers >4 are shown, due to potential disclosure concerns. 8

9 Episodes of gonorrhoeabynhsboard in the 5 years to No of episodes AA BR DG FF FV GGC GR HG LN LO TY Only numbers >4 are shown, due to potential disclosure concerns. 9

10 Most common sequence types (STs) January-June 211 and their occurrence in previous three six-month periods 29 Jan-June Jan-June 211 No of isolates ST51 ST273 ST2992 ST2 ST995 ST352 ST482 ST26 ST147 ST25 Typing data is available to June 211, due to the lag in typing NAAT-positive specimens by Nested NG-MAST. Typing data is available for 624 of the 72 episodes of infection including 254 GC NAAT specimens. The ten STs in this list account for 56% of typed episodes. STs with larger numbers of isolates are associated with larger sexual networks. Seven of the ten top STs were also in the top STs for the previous six month period (ST51, ST273, ST2992, ST2, ST352, ST147 and ST25). Of note, ST147, which has been the most commonly-identified ST in every half-year since January 29, is now much less common. This ST, along with ST352, contributed to high rates of ciprofloxacin resistance in Scotland and appears to be at risk of developing resistance to cephalosporins, as reported elsewhere in the world. Of the ten most common STs in this half year, only ST352 and ST147 were associated with significant antibiotic resistance. 1

11 Distribution of Sequence Types by NHS Board: January -June 211 No of episodes AA DG FF FV GR GGC HG LN LO TY Other ST ST1241 ST384 ST47 ST4792 ST649 ST4758 ST1222 ST25 ST147 ST26 ST482 ST352 ST995 ST2 ST2992 ST273 ST51 Sequence types with 1 or more occurences in this half-year period are shown. There is a marked regional distribution of many of the common sequence types. Where there are many episodes of common STs, this may reflect large sexual networks. The presence of less common STs may indicate importation of strains either from other parts of the UK or internationally. Only HB with >4 episodes of gonorrhoea are shown, due to potential disclosure concerns. Not all episodes are able to be typed, so total numbers differ from those in Slide 8. 11

12 Distribution of common Sequence Types by patient gender: January-June 211 Male Female 6 5 No of episodes ST51 ST273 ST2992 ST2 ST995 ST352 ST482 ST26 ST147 ST25 ST1222 ST4758 ST649 ST4792 Examining the proportion of each ST found in women and men can suggest which STs are likely to be heterosexually or homosexually acquired. All STs representing 1 or more episodes are shown. ST2992, ST995, ST352, ST482, ST147, ST4758 and ST4792 were rarely detected in women suggesting that these STs are associated with sex between men. ST273, ST25, ST1222 and ST649 are found in more women than men, a pattern typical of heterosexual transmission. ST51, ST2 and ST26 fit neither of these patterns. This suggests that these strains may be co-circulating in both homosexual and heterosexual networks, or that their epidemilogy is shifting from one type of network to another. 12

13 Sequence Types in male rectal infection: January-June 211 No of episodes ST2992 ST995 ST482 ST352 ST4758 ST147 ST4792 Male - not rectal infection Male rectal infection Female SBSTIRL does not routinely receive information on patients sexual orientation. Male rectal infection can be used as a proxy to identify STs associated with homosexual transmission amongst men. Rectal infection was associated with 29% (144 episodes) of all male infections. Sequence types associated with >5 male rectal infections are shown, and are ordered by the number of male rectal infections identified. The 134 typed episodes represented 36 different STs. 13

14 Prevalence of antibiotic resistant* isolates 211 compared with previous three six-month periods Percent Jan-June 1 1 Jan-June PPNG TRNG PPNG/TRNG CipR Pen-Chromosomal *Includes reduced susceptibility (MIC >.5 mg/l in case of ciprofloxacin) Resistance data is available for 418 episodes of gonococcal infection in this half-year period. This represents 5% of all new episodes for which any sample was received, compared with 52% in the previous half year. The 29 PPNG and PPNG/TRNG strains in this period represented 18 different STs. 13 PPNG strains were STs that occurred only once (i.e. there was no detected onwards transmission). This is a lower proportion than has been seen in previous periods. Ciprofloxacin resistance was found in 2/4 (5%) PPNG isolates, 25/25 (1%) of PPNG/TRNG and 26/32 (81%) TRNG isolates. The rise in TRNG isolates is mainly due to the emergence of ST isolates were identified during ember 211, 5 of which were PPNG/TRNG and the remainder TRNG. All were ciprofloxacin-resistant. ST1582 isolates have been identified in Scotland since 26, but identified transmission has previously been limited. Rates of ciprofloxacin and chromosomal penicillin resistance have fallen sharply. This is likely to be associated with reduced transmission of strains such as ST147 and ST352, compared with previous years. The root cause of this is unknown. 14

15 Trends in azithromycin resistance: SBSTIRL MIC =>1 and <256 MIC =>256 Percent % In 27 the percentage of isolates of N. gonorrhoeae with decreased susceptibility (MIC > 1mg/L) or high level resistance (MIC >256mg/L) exceeded 5% (3.9% had MIC >256mg/L). In 28 there was a decrease in isolates with high level resistance (1.4% versus 3.9% in 27. This was mainly attributable to a decrease in the number of isolates of ST649 and the proportion of these that exhibited high level resistance (21/74, 23% in 27 versus 4/5, 8% in 28). In 29 there were only two isolates with high level resistance, both ST174. In 21 and 211, no isolates were found with high level resistance. 15

16 Cefixime MICs (percentages) 1% 9% 8% 7% 6% 5% 4% 3% MIC > <=.15 2% 1% % The first N. gonorrhoeae isolate in Scotland with cefixime MIC >.12 mg/l (the EUCAST clinical breakpoint) was identified in May 21, and was ST3638. The actual MIC was.19 mg/l by Etest (confirmed by HPA). The patient was successfully treated with a cephalosporin. No further isolates with decreased susceptibility to cephalosporins have been identified. In some antibiotic/organism combinations resistance is developed stepwise through the accumulation of mutations. This is thought to be the case with thirdgeneration cephalosporins and N. gonorrhoeae, so changes in the MIC distribution can indicate whether genetic determinants of resistance are accumulating in a population, which may herald the emergence of future resistance. MIC distribution appears to fluctuate according to prevalent strains (sequence types). 16

17 Ceftriaxone MICs (percentages) 1% 8% 6% 4% MIC <=.15 2% % To 21, N. gonorrhoeae MICs for ceftriaxone had shown a clearer pattern of increase year on year than those for cefixime. However, in 211 the proportion of isolates with MIC.12mg/L decreased compared with the previous two years. 17

18 SBSTIRL supplemental testing ember 211 compared with previous six-month periods Jan- June Jan- June Jan- June SBSTIRL confirmed positive Negative Indeterminate All specimens sent to the reference laboratory for supplemental GCNAAT testing are tested by an in-house real time PCR targeting the PorA pseudogene, any that did not confirm the initial positive result were also then tested by another GCNAAT (the Aptima GC assay (Gen-probe)). The PorA pseudogene real time PCR is a sensitive assay with an internal control, which is suitable for problematic specimens (e.g. a proportion of those in BD Probetec collection media). The introduction of this test has contributed to an increase in the proportion of reactive specimens which are confirmed. This proportion is also influenced by the initial test used, as some screening NAATs may cross-react with commensal Neisseria species. SBSTIRL will provide supplemental NAAT testing for gonorrhoea for any NHS laboratory in Scotland free of charge. We will also type (by NG-MAST) any confirmed GC NAAT positive specimen where no culture exists for the episode. Confirmed NAAT specimens are an important specimen for typing in the absence of any cultured isolate. Please send both unconfirmed and confirmed GC NAAT specimens indicating which test is needed on the request form. 18

19 SBSTIRL T. pallidumpcr testing on ulcer specimens to ember T. pallidum Positive T. pallidum negative Jan- June Jan- June Jan- June Jan- June Positive specimens in the past half-year period were observed from Grampian and Lothian. Specimens were also received from Borders, Fife and Tayside. SBSTIRL is no longer funded by HPS to provide T. palllidum PCR. However, we continue to offer the test as a Specialist Service at a cost of 25 per test. A T. pallidum PCR result may be useful in the following ways: To confirm initial serology To help define the stage of disease In cases of reinfection, where some serological markers are already positive. 19

20 SBSTIRL LGV PCR testing to ember LGV Positive LGV Negative Six cases of LGV have been observed in this 6-month period. This reflects an increase in diagnoses in the UK as a whole since mid-21. Specimens for testing were received from Ayrshire and Arran, Dumfries and Galloway, Fife, Forth Valley, Greater Glasgow and Clyde, Grampian, Lanarkshire and Lothian. SBSTIRL encourages laboratories to send specimens from HIV-positive MSM with rectal chlamydia, and from any symptomatic patient or known contact of LGV. 2

21 Summary Diagnoses of gonorrhoea in Scotland have continued to increase over the past year. Rates of chromosomal resistance to ciprofloxacin and penicillin have fallen, due to a shift in the predominant circulating strains ofn. gonorrhoeae Reports of gonorrhoea treatment failures and reduced-susceptibility N. gonorrhoeae isolates continue to accumulate in the international literature and elsewhere in the UK. A robust programme of culture and susceptibility testing is essential. LGV continues to be detected in Scotland, against a background of a marked increase in cases in England and Wales Please send specimens from HIV-positive MSM with rectal chlamydia, and from any symptomatic patient or known contact of LGV 21

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