Overdiagnosis in
Sexually Transmitted Infections Dr David Barlow Emeritus Consultant Physician Guy’s and St Thomas’ Hospitals London 19th Academic Sessions Sri Lanka College of Venereologists Colombo, September 2014 19th Academic sessions SLCV 2014
Declaration of interest I report no conflicts of interest in the contents of this talk.
19th Academic sessions SLCV 2014
Overdiagnosis by Screening • • • • • •
Breast cancer Prostate cancer Chronic kidney disease Pulmonary embolism Depression Bone density
19th Academic sessions SLCV 2014
Overdiagnosis by Screening • • • • • •
NAATs (false positives) Gonorrhoea, chlamydia, others? Contamination (NAATs) NGU (microscopy) Herpes (serology) Cervical cancer (HPV-based) Syphilis
19th Academic sessions SLCV 2014
‘Widening’ of disease definition • Creation of ‘pre-disease’ (e.g. ‘pre-diabetes’), • Lowering the threshold for a diagnosis (hypertension now starts at a lower blood pressure than before), • Change of (“earlier or different”) diagnostic criteria (a new definition of kidney failure that meant a majority of over-60s in USA had this ‘condition’). 19th Academic sessions SLCV 2014
Overdiagnosis by Screening • Increased sensitivity may reflect early detection rather than overdiagnosis • Long term duration of protective effect for HPV negative women: follow-up of primary HPV screening randomised trial • After 13 years’ follow-up the cumulative incidence of CIN2+ was the same from HPV screening as for cytology • Is it more expensive? • Who benefits? Patient? Diagnostic Company? BMJ 2014;348:g130 doi:10.1136/bmj.g1340
19th Academic sessions SLCV 2014
Initiation of ART in asymptomatics: BHIVA guidelines CD4 counts (cells/μl)
1997 <300 2003 between 201 and 350 2005 between 201 and 350 2008 <350. “in a small number of patients, treatment may be started or considered before the CD4 count <350” (consider 301-500) • 2012 ≤350 (≤500 if co-infection HepB/C) • 2013 “WHO is currently revising its treatment guidelines and considering recommending ART initiation at CD4 counts <500 cells/μl*.” • • • •
*Geffen N. S Afr J HIV Med 2013;14(1):6-7. DOI:10.7196/SAJHIVMED.906
19th Academic sessions SLCV 2014
Initiation of ART in asymptomatics: BHIVA guidelines CD4 counts (cells/μl)
• • • •
Earlier treatment with ART may increase lifespan Earlier treatment may increase quality of life Earlier treatment may reduce incidence of associated disease Earlier treatment may reduce transmission of HIV
• Q: How many of those involved in formulating/writing guidelines or recommendations on initiation of ART have no links whatsoever with commercial pharma? • Q: Do any of those involved in formulating/writing guidelines or recommendations on initiation of ART have no links whatsoever with commercial pharma? 19th Academic sessions SLCV 2014
Fig 1 Prevalence of chronic kidney disease in the US by 2012 classification Prevalence of chronic kidney disease in the US by 2012 classification. Data on 18 â&#x20AC;&#x2030;026 adults from National Health and Nutrition Examination Survey 1999-2006.. Green=low risk (if no other markers of kidney disease, no CKD), yellow=moderately increased risk, orange=high risk, red=very high risk.
Moynihan R et al. BMJ 2013;347:bmj.f4298
19th Academic sessions SLCV 2014 Š2013 by British Medical Journal Publishing Group
Fig 2 Median eGFR rates for healthy white men and women by age.
Moynihan R et al. BMJ 2013;347:bmj.f4298
19th Academic sessions SLCV 2014 Š2013 by British Medical Journal Publishing Group
Has everyone got chronic kidney disease? Kidney Disease Outcomes Quality Initiative 2002 – 2012 •
“Chronic kidney disease if eGFR < 60 ml/min/1.73 m2” irrespective of age, sex, or albuminuria
•
14% of unselected adults in USA have CKD (!!)
•
50% of adults aged >70 have CKD (!!)
•
But, <1% adults (median age 49) with stage 3A went on to develop kidney disease after 8 years
•
This gives number needed to treat of 3200
•
If the persistence of abnormality for diagnosis were 12 months rather than 3, there would be a 37% reduction in numbers with CKD
No possibility of conflict of interest? •
2002 guidelines supported by a pharmaceutical company
•
2012 guidelines: Nine of 16 working party members had financial ties with industry
•
The body responsible for developing the guidelines has disclosed funding from a consortium of pharmaceutical or device manufacturers, though not for the “development of specific guidelines.”
Moynihan R, et al (2013) Chronic kidney disease controversy: how expanding definitions are unnecessarily labelling people as diseased. BMJ 347:f4298
19th Academic sessions SLCV 2014
Nullius in Verba Motto of the Royal Society “Take no one's word for it”
19th Academic sessions SLCV 2014
Lies, Damned Lies and STItistics "There are three kinds of lies: lies, damned lies, and statistics." Mark Twain attributed the phrase to the 19th-century British Prime Minister Benjamin Disraeli (1804â&#x20AC;&#x201C;1881): Mark Twain
Benjamin Disraeli
19th Academic sessions SLCV 2014
Lies, Damned Lies and STItistics The purpose of this talk is to make you all THINK when you see a figure, a statement, a calculation or a conclusion. Be suspicious, even if the source is a trusted senior Consultant from St Thomas’. I base the talk on three experiences in 2011: 1. 2. 3.
4. 5.
An attempt to verify numbers in a new edition of my book An invitation to write a on-line posting for Nature A request to update 2010 gonorrhoea Chapter in Oxford Textbook of Medicine
For Instance, think about PID guidelines… …or the definition of cervicitis?
Question everything; believe nothing.
19th Academic sessions SLCV 2014
OVERDIAGNOSIS OF GONORRHOEA
IN TREATMENT GUIDELINES FOR PELVIC INFLAMMATORY DISEASE – A RECIPE FOR RESISTANCE? Dartmouth College Hanover, New Hampshire Sept 2013
Dr David Barlow St Thomas’ Hospital London SE1 7EH 19th Academic sessions SLCV 2014
Acknowledgements Thanks to the following for information and permission to use their data Professor Magnus Unemo Department of Microbiology, Orebro University Hospital, Sweden and WHO Collaborating Centre for gonorrhoea
Professor Carina Bjartling, Institute of Clinical Sciences, Skane University Hospital, Malmo, Sweden
Dr Gail Bolan Director, Division of STI and HIV prevention, CDC, Atlanta, Georgia
19th Academic sessions SLCV 2014
Abbreviations • • • •
PID BASHH MMWR CDC
Pelvic inflammatory disease British Association for Sexual Health and HIV Morbidity and mortality weekly report (USA) Centers for Disease Control
19th Academic sessions SLCV 2014
Sources referred to in presentation 1.
Practice. Easily missed? Pelvic inflammatory disease. EC Bartlett et al BMJ 2013;346:f3189 (online 23.05.13; print 10.08.13)
2.
Missing pelvic inflammatory disease? Substantial differences in the rate at which doctors diagnose PID. Doxanakis A, et al. Sex Transm Inf 2008;84:518-23.
3.
UK National Guideline for the Management of Pelvic Inflammatory Disease. J Ross & G McCarthy. BASHH guidelines 2011. http://www.bashh.org/documents/3572.pdf
4.
Sexually transmitted diseases treatment guidelines, 2010. Pelvic Inflammatory Disease KA Workowski & S Berman (MMWR). http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5912a1.htm
5.
*Antimicrobial resistance in Neisseria gonorrhoeae and possible emergence of untreatable gonorrhoea: how, when and essential actions? Magnus Unemo 2013 Plenary PL01.1
6.
*Mycoplasma genitalium and Chlamydia trachomatis in laparoscopically diagnosed pelvic inflammatory disease. Carina Bjartling 2013 Symposium S08.3 *STI & AIDS World Congress, July 14-17, 2013, Vienna
19th Academic sessions SLCV 2014
What are the problems? (1) •
•
•
•
Although gonorrhoea can undoubtedly cause pelvic infection, its prevalence in cases of ‘PID’ in UK (and possibly other countries) is low. = Problem of scarcity/shortage (?) of gonorrhoea In clinical settings, the diagnosis of ‘pelvic inflammatory disease’ (PID) is regarded as synonymous with a diagnosis of ‘pelvic infection’. = Problem of diagnosis = Problem of definition The gonococcus has proved itself hyper-efficient at developing resistance to each new antibiotic to which it is exposed; over-use of antibiotics has speeded development of resistance In spite of the fact that gonorrhoea can be diagnosed, and excluded, with great accuracy and rapidity, guidelines continue to recommend anti-gonococcal therapy before and/or without confirmation of gonorrhoea. = Problem of resistance 19th Academic sessions SLCV 2014
What are the problems? (2) •
Finally, since PID is used as a ‘blanket’ term by specialists in STIs, gynaecology (and family practitioners), the populations described in studies may not be comparable:
Young women seen with abdominal pain are more likely to: • Be treated with antibiotics in an STI clinic (see BMJ reference) • Be investigated by laparoscopy in gynae’ (see Bjartling ref’) • Treated how in general practice? Remember not to equate results from different populations! = Problem of definition
19th Academic sessions SLCV 2014
Problems of ‘shortage’ of gonorrhoea UK, European and USA guidelines all recommend anti-gonococcal therapy in cases of suspected ‘PID’. Where there is a high prevalence/incidence of gonorrhoea this may be reasonable. We have ‘good’ figures for UK (Health Protection Agency) and Sweden (Bjartling 2013, Vienna) – prevalence of gonorrhoea in cases of PID in both countries is low. Nucleic Acid Amplification Tests (NAATs) can diagnose and exclude gonorrhoea very quickly (<48 hours). [Numbers quoted when the abstract for this presentation was submitted have been changed (updated) by the Health Protection Agency.]
19th Academic sessions SLCV 2014
UK STI returns (updated)
19th Academic sessions SLCV 2014
Problems of ‘shortage’ of gonorrhoea PID figures UK 2011 (revised)
• Non-specific PID 15,768 • Chlamydial PID 1,763 • Gonococcal PID 298 2011 Total PID = 17,815
19th Academic sessions SLCV 2014
Problems of ‘shortage’ of gonorrhoea PID figures UK 2011 • “Neisseria gonorrhoeae and Chlamydia trachomatis have been identified as causative agents, but account for only a quarter of cases in the UK”. (PID guidelines 2011, BASHH) = 25% (claimed) • Neisseria gonorrhoeae and Chlamydia trachomatis 2011 actual figures : 298 + 1763 out of 17,815 (HPA 2013) = 11.56% (actual) • Gonorrhoea 298 cases out of 17,815 = 1.67% (actual) This is low !! http://www.hpa.org.uk/webc/HPAwebFile/HPAweb_C/1215589015024
19th Academic sessions SLCV 2014
Problem of definition ‘PID’ is caused by…? 1.
Authorities refer to, and accept that there is, a non-infectious differential diagnosis* for pelvic pain. a. b. c. d. e. f. g.
ectopic pregnancy – pregnancy should be excluded in all women suspected of having PID acute appendicitis – nausea and vomiting occurs in most patients with appendicitis but only 50% of those with PID. Cervical movement pain will occur in about a quarter of women with appendicitis endometriosis – the relationship between symptoms and the menstrual cycle may be helpful in establishing a diagnosis complications of an ovarian cyst e.g. torsion or rupture – often of sudden onset urinary tract infection – often associated with dysuria and/or urinary frequency functional pain – may be associated with longstanding symptoms adhesions from previous ‘infection’ (my addition)
*BASHH PID guideline 2011
19th Academic sessions SLCV 2014
Problem of definition ‘PID’ is caused by…? 1. 2.
Authorities accept that there is, and refer to, a non-infectious differential diagnosis for pelvic pain. Authorities discuss factors* that should influence management: a. b. c. d. e.
robust evidence on local antimicrobial sensitivity patterns robust evidence on the local epidemiology of specific infections in this setting cost patient preference and compliance severity of disease
*BASHH PID guideline 2011
19th Academic sessions SLCV 2014
Problem of definition ‘PID’ is caused by…?
1.
Authorities accept that there is (and refer to) a non-infectious differential diagnosis for pelvic pain.
2.
Authorities discuss factors that should influence management:
3.
In spite of the above, treatment guidelines take no account of this and always advise antibiotic therapy for ‘PID’.
19th Academic sessions SLCV 2014
A new take on the Emperor’s clothes 2013
The ‘Definition’ of ‘PID’ 19th Academic sessions SLCV 2014
PID (UK)
BASHH PID Guidelines 2011 www.bashh.org/documents/3205
Symptoms • lower abdominal pain which is typically bilateral • deep dyspareunia • abnormal vaginal bleeding, including post coital, inter-menstrual and menorrhagia • abnormal vaginal or cervical discharge which is often purulent
Signs • lower abdominal tenderness which is usually bilateral • adnexal tenderness on bimanual vaginal examination • cervical motion tenderness on bimanual vaginal examination • fever (>38°C) “A diagnosis of PID, and empirical antibiotic treatment, should be considered and usually offered in any young (under 25) sexually active woman who has recent onset, bilateral lower abdominal pain associated with local tenderness on bimanual vaginal examination, in whom pregnancy has been excluded.”
19th Academic sessions SLCV 2014
Problem of definition
PRACTICE: Easily missed? Pelvic Inflammatory Disease British Medical Journal, 10 August 2013, 34-5 BMJ 2013;346:f3189
Quotes: •
“What is PID?” “PID is due to infection in the upper female genital tract…”
•
“Why is PID missed” “The best recent data on easily missed PID comes from a retrospective audit*…”
*Doxanakis A, Hayes RD, Chen MY, Gurrin LC, Hocking J, Bradshaw CS, et al. Missing pelvic
inflammatory disease? Substantial differences in the rate at which doctors diagnose PID. Sex Transm Inf2008;84:518-23.
19th Academic sessions SLCV 2014
Problem of definition
BASHH PID Guidelines 2011 www.bashh.org/documents/3205
325 cases of PID (“Best recent data”) BMJ 10 August 2013 Symptoms • lower abdominal pain which is typically bilateral (any abdominal pain 238/325 = 73.2%) • deep dyspareunia (any dyspareunia 131/325 = 40.3%) • abnormal vaginal bleeding, including post coital, inter-menstrual and menorrhagia (post coital 13.5%; inter-menstrual 16.6%) • abnormal vaginal or cervical discharge which is often purulent (any vag dx 145/325 = 44.6%)
Signs • lower abdominal tenderness which is usually bilateral • adnexal tenderness on bimanual vaginal examination • cervical motion tenderness on bimanual vaginal examination • fever (>38°C)
19th Academic sessions SLCV 2014
N/A (bilateral 97/325 = 29.8%) (102/325 = 31.4%) (2/325 = 0.62%)
Problem of definition
PID (USA)
MMWR PID Guidelines 2010
http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5912a1.htm
Symptoms: One or more of: • Cervical motion tenderness • Uterine tenderness • Adnexal tenderness Specificity enhanced by one or more of: • oral temperature >101° F (>38.3° C); • abnormal cervical or vaginal mucopurulent discharge; • presence of abundant numbers of WBC on microscopy of vaginal fluid; • elevated erythrocyte sedimentation rate; • elevated C-reactive protein; • laboratory documentation of cervical infection with N. gonorrhoeae or C. trachomatis.
19th Academic sessions SLCV 2014
Problem of definition
PID (USA)
MMWR PID Guidelines 2010
http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5912a1.htm
325 cases of PID (“Best recent data”) BMJ 10 August 2013 Symptoms: One or more of: • Cervical motion tenderness (102/325 = 31.4%) • Uterine tenderness (123/325 = 37.8%) • Adnexal tenderness (bilateral 97/325 = 29.8%) Specificity enhanced by one or more of: • oral temperature >101° F (>38.3° C); (2/325 = 0.62%) • abnormal cervical or vaginal mucopurulent discharge; (any vag dx 145/325 = 44.6%) • presence of abundant numbers of WBC on microscopy of vaginal fluid; (212/325 = 65.2%) • elevated erythrocyte sedimentation rate; Not measured • elevated C-reactive protein; Not measured • laboratory documentation of cervical infection with N. gonorrhoeae or C. trachomatis. (no gonorrhoea; Chlamydia 62/325 = 19.1%)
19th Academic sessions SLCV 2014
Problem of diagnosis Carina Bjartling: STI and AIDS World Congress Vienna, July 2013 Laparoscopic (LAP) and microbiologic findings in 208 women with â&#x20AC;&#x2DC;PIDâ&#x20AC;&#x2122; Malmo Sweden (interim analysis to mid 2012) Laparoscopic diagnosis n=208
Chlamydia
M genitalium
CT & MG
Gonorrhoea
n=30
n=5
n=3
N=2
PID including salpingitis & endometritis
123 (59.1%)
29/123 (23.6%)
5/123 (4.1%)
3/123 (2.4%)
2/123 (1.6%)
Other diagnoses
85 (40.9%)
1
0
0
0
19th Academic sessions SLCV 2014
Problems of resistance 1. 2. 3. 4.
•
• •
Authorities accept that there is, and refer to, a non-infectious differential diagnosis for pelvic pain. Authorities discuss factors that should influence management: In spite of 1 and 2 above, treatment guidelines take no account of this and always advise antibiotic therapy for ‘PID’. Most recommended antibiotic regimens include anti-gonococcal agents that are usually inappropriate (>98% UK and Malmo). Ceftriaxone 500mg single dose followed by oral doxycycline 100mg twice daily plus metronidazole 400mg twice daily for 14 days (BASHH 2011) Cefotetan 2 g IV every 12 hours or Cefoxitin 2 g IV every 6 hours, plus Doxycycline 100 mg orally or IV every 12 hours (CDC 2010 parenteral Rx) Ceftriaxone 250 mg IM in a single dose plus Doxycycline 100 mg orally twice a day for 14 days with or without Metronidazole 500 mg orally twice a day for 14 days (CDC2010 oral Rx)
19th Academic sessions SLCV 2014
Problem of resistance How we use antibiotics makes a difference • Ideally, Treatment follows diagnosis, and considers antibiotic sensitivities. • Current practice promotes ‘epidemiologic’ treatment of index patient and partners (Treatment before or without diagnosis) “Male partners of women who have PID caused by C. trachomatis and/or N. gonorrhoeae frequently are asymptomatic. Sex partners should be treated empirically with regimens effective against both of these infections, regardless of the etiology of PID or pathogens isolated from the infected woman.” MMWR PID Guidelines 2010 “Once PID has been diagnosed all current sexual partners should be screened and offered empirical treatment,…” BMJ 10.08. 2013 Bartlett 2013;346:f3189 “Current male partners of women with PID should be contacted and offered health advice and screening for gonorrhoea and chlamydia.” BASHH PID Guidelines 2011 “If adequate screening for gonorrhoea and chlamydia in the sexual partner(s) is not possible, empirical therapy for gonorrhoea and chlamydia should be given.” IUSTI Europe Guidelines 2012
19th Academic sessions SLCV 2014
Epidemiological treatment Barlow Lancet 1978 604 women in 1976 diagnosed with gonorrhoea at St Thomasâ&#x20AC;&#x2122; Hospital In the 1970s we diagnosed before treatment! In the year of study, 16 culture-positive gonorrhoea cases defaulted from follow-up. Only four of these were gonorrhoea contacts Epidemiological treatment would have: identified these four gonorrhoea contacts and treated them, missed the other twelve who were not gonorrhoea contacts, and wrongly diagnosed and treated 128 women who did not have gonorrhoea Barlow D and Phillips I (1978) Lancet; i: 761-4 Gonorrhoea in Women - diagnostic, clinical and therapeutic aspects
19th Academic sessions SLCV 2014
Problem of resistance How we use antibiotics makes a difference • Ideally, Treatment follows diagnosis, and considers antibiotic sensitivities. • Current practice promotes ‘epidemiologic’ treatment of index patient and partners (Treatment before or without diagnosis) • Other practices include (have included) – Cluster treatment – Prophylactic treatment – Post hoc treatment ‘Vietnam Rose’ was a result of such practices
19th Academic sessions SLCV 2014
‘Vietnam Rose’
news.google.com/newspapers?nid=1955&dat=19690518&id.
19th Academic sessions SLCV 2014
Overtreatment of PID in general – resistance problems
Is it, are they, sensitive?
•
Ceftriaxone resistance has now been reported in N.gonorrhoeae • = higher dose (1-2G) or multiple doses? • Gentamycin (+ doxy) works in Malawi • Solithromycin, a fluoroketolide or ertapenem (Unemo, IUSTI Europe 2012) • Gentamycin or gemifloxacin (both+ azithromycin) (Kircaldy, Vienna 2013)
•
Azithromycin resistance has now been reported in C.trachomatis • Rectal CT: 9/42 (21.2%) Rx failures in MSM; 0/40 Rx failures in women (Hathorn et al, Sex trans Infect, 2012) • Rectal CT: MSM Rx failures: 4/26 (15.4%) AZI 1G; 1/165 (0.6%) Doxy. (Elgalib et al, Int J STD & AIDS 2011)
•
Azithromycin resistance has now been reported in M.genitalium • NGU/CT : Sweden : when standard Rx= doxy, MG macrolide resistance < 2% Denmark: when standard Rx= AZI, MG macrolide resistance = 39% • MG macrolide resistance is induced by treatment in Sweden: 114 given AZI 1 G → 7 (6% developed resistance) 77 given AZI 1.5 G (extended dosage) → 0 developed resistance (Anagrius IUSTI Europe 2012)
19th Academic sessions SLCV 2014
(WHO 2012; Ndowa, Lustinarasimhan, Unemo. Global Plan. STI. 2012. Editorial)
A
ECDC for EU/EEA
19th Academic sessions SLCV 2014
CDC for USA
Sex Super Bug
Antimicrobial resistance in Neisseria gonorrhoeae and possible emergence of untreatable gonorrhoea: how, when and essential actions Magnus Unemo, Ph.D., Assoc. Professor
WHO CC for Gonorrhoea and other STIs Swedish Reference Laboratory for Pathogenic Neisseria Department of Laboratory Medicine, Microbiology
19th Academic Hospital, sessions SLCVSweden 2014 Ă&#x2013;rebro University
Ceftriaxone (parenteral, more potent) ď ¸
Cefixime
Ceftriaxone
Ceftriaxone treatment failures: Australia1, Sweden2, Slovenia3
ď ¸
Pharyngeal gonorrhoea, only MICs of 0.016-0.125 mg/L and most probably affected by pharmacokinetics/pharmacodynamics! 1Tapsall,
et al, J Med Microbiol. 2009 2Unemo, et al, Euro Surveill. 2011 3Unemo, 19th Academic sessions SLCV 2014 et al, Euro Surveill. 2012
Introduced treatment and emergence of resistance â&#x2021;&#x2019; only 1-2 decades for international spread
2021?
19th Academic sessions SLCV 2014 Unemo and Shafer. New York Acad Sci. 2011
Or go back to the pre-antimicrobial era?
-
Behandling av gonore før antibiotika
Ă&#x2013;rebro Hospital, Sweden 1921 - Patient with gonococcal arthritis, urethra stricture and epididymitis - Silver compounds and irrigations every or every second day?
Treatments
19th Academic sessions SLCV 2014
Overdiagnosis of PID - Summary • The label ‘Pelvic inflammatory disease’ is interpreted differently in different settings. It is assumed to be of infective aetiology. • In spite of universal acceptance of non-infective aetiologies, anti-microbial therapy is the ‘gold standard’ of treatment. • Overdiagnosis of ‘gonorrhoea’ may lead to more rapid loss of antibiotic sensitivity amongst gonococci. • Overdiagnosis of ‘pelvic infection’ (PID) may numerically and significantly dwarf overdiagnosis of gonorrhoea.
19th Academic sessions SLCV 2014
Sources referred to in presentation 1.
Practice. Easily missed? Pelvic inflammatory disease. EC Bartlett et al BMJ 2013;346:f3189 (online 23.05.13; print 10.08.13)
2.
Missing pelvic inflammatory disease? Substantial differences in the rate at which doctors diagnose PID. Doxanakis A, et al. Sex Transm Inf 2008;84:518-23.
3.
UK National Guideline for the Management of Pelvic Inflammatory Disease. J Ross & G McCarthy. BASHH guidelines 2011. http://www.bashh.org/documents/3572.pdf
4.
Sexually transmitted diseases treatment guidelines, 2010. Pelvic Inflammatory Disease KA Workowski & S Berman (MMWR). http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5912a1.htm
5.
*Antimicrobial resistance in Neisseria gonorrhoeae and possible emergence of untreatable gonorrhoea: how, when and essential actions? Magnus Unemo 2013 Plenary PL01.1
6.
*Mycoplasma genitalium and Chlamydia trachomatis in laparoscopically diagnosed pelvic inflammatory disease. Carina Bjartling 2013 Symposium S08.3 *STI & AIDS World Congress, July 14-17, 2013, Vienna
19th Academic sessions SLCV 2014
PID correspondence in BMJ September 2013 Barlow D (2013)Pelvic inflammatory disease. BMJ rapid response (x3) http://www.bmj.com/content/346/bmj.f3189/rr /658573 (plus: rr/659424) and rr/662716)
19th Academic sessions SLCV 2014
Thank you for your attention
19th Academic sessions SLCV 2014
Andy Winter Plenary Session IUSTI Europe Sept’ 2014 Malta ‘The Known Unknowns’
19th Academic sessions SLCV 2014
19th Academic sessions SLCV 2014
Gonorrhoea in Lambeth, Southwark and Lewisham* Age
Ethnic group
Rate/100,000/year
15-19
White non-white
male 80.3 942.0
female 171.4 1221.8
20-24
White non-white
121.2 1258.1
90.7 731.1
25-29
White non-white
220.0 1632.1
37.5 435.5
30-59
White non-white
30.5 191.3
4.7 24.5
*Low, Daker-White, Barlow & Pozniak BMJ 1997; 3141715-18 19th Academic sessions SLCV 2014
Amplified DNA assay in St Thomas’ 2003 GC component (B-D SDA) • False positive rate 3/43 on 798 specimens • = 3.759 on 1,000 specimens • = 37.59 on 10,000 specimens • = 375.9 on 100,000 specimens
19th Academic sessions SLCV 2014
Gonorrhoea in Lambeth, Southwark and Lewisham* Age
Ethnic group
Rate/100,000/year
15-19
White non-white
male 80.3 942.0
female 171.4 1221.8
20-24
White non-white
121.2 1258.1
90.7 731.1
25-29
White non-white
220.0 1632.1
37.5 435.5
30-59
White non-white
30.5 191.3
4.7 24.5
*Low, Daker-White, Barlow & Pozniak BMJ 1997; 3141715-18 19th Academic sessions SLCV 2014
Gonorrhoea in Lambeth, Southwark and Lewisham*; add 375.9/100,000 Age
Ethnic group
Rate/100,000/year
15-19
White non-white
male 456.2 1317.9
female 547.3 1597.7
20-24
White non-white
497.1 1634
466.6 1107
25-29
White non-white
595.9 2008
413.4 811.4
30-59
White non-white
406.4 567.2
380.6 400.4
*Low, Daker-White, Barlow & Pozniak BMJ 1997; 3141715-18 19th Academic sessions SLCV 2014
Gonorrhoea in Lambeth, Southwark and Lewisham*; add 375.9/100,000 Age
Ethnic group
15-19
percentage false positives
White non-white
male 82.4% 28.5%
female 68.7% 23.5%
20-24
White non-white
75.6% 33.0%
80.6% 34.0%
25-29
White non-white
63.1% 18.7%
90.9% 46.3%
30-59
White non-white
92.5% 66.3%
98.8% 93.9%
*Low, Daker-White, Barlow & Pozniak BMJ 1997; 3141715-18 19th Academic sessions SLCV 2014
19th Academic sessions SLCV 2014
19th Academic sessions SLCV 2014
19th Academic sessions SLCV 2014
Recommendations for commissioners and providers (Health Protection England Aug 2014)
â&#x20AC;˘ Screening for gonorrhoea is recommended in any population or setting where gonorrhoea prevalence is â&#x2030;Ľ1%; â&#x20AC;˘ Below a prevalence of 1%, the majority of initial positive test results are likely to be false positives, suggesting unselected screening would be of limited public health benefit
(my italics) 19th Academic sessions SLCV 2014
‘Aerobic vaginosis’ Gilbert Donders, IUSTI Europe Malta 2014
19th Academic sessions SLCV 2014
‘Aerobic vaginosis’ “…The gynaecologist has been has been ordering a PCR test from a private, forprofit, laboratory (Medical Diagnostics laboratory) called the ‘aerobic vaginitis panel’, which purports to detect E.coli, Gp B strep, S. faecalis and S. aureus from a vaginal swab. Based on these results, she has had multiple courses of antibiotics…”: • Amoxicillin • Oral ampicillin • Ciprofloxacin • Clindamycin • Metronidazole • 4 weeks of ceftriaxone
!!??!! – (my emphasis) Gilbert Donders IUSTI Europe Malta 2014 19th Academic sessions SLCV 2014
Syphilis overdiagnosis • • • •
‘Reagin’ tests (BFPs) ‘Fast’ (unchanging) results Past treatment Non-venereal treponematoses (yaws, etc)
19th Academic sessions SLCV 2014
Contamination in clinic false-positive NAATs? • • • • •
20 of 154 (13%) clinic sites tested were positive by TMA 5 positive for CT; 11 positive for GC; 4 positive for CT and GC Patient toilets most likely sites Positive GC more likely from male than female side PCR and culture all negative • TMA – transcription mediated amplification
•
Lewis et al Chlamydia and gonorrhoea contamination of clinic surfaces Sex Transm Infect. 2012 Oct;88(6):418-21
19th Academic sessions SLCV 2014
Chlamydia and gonorrhoea screening Turner et al 2014 (1)
Model of clinic vs. POCT management
chlamydia
Infected symptomatics Rx’d
Uninfected symptomatics Rx’d
M 70% F 24%
M 33% F 8%
gonorrhoea M 90% F 50%
M 2% F 3%
Sex Transm Infect 2014;90:104-111
19th Academic sessions SLCV 2014
Chlamydia and gonorrhoea screening Turner et al 2014 (2)
Model of clinic vs. POCT management Probability* partner is infected chlamydia
M 0.4 F 0.4
gonorrhoea
M 0.4 F 0.4
* “Conservative assumption” Sex Transm Infect 2014;90:104-111 19th Academic sessions SLCV 2014
Chlamydia and gonorrhoea screening Turner et al 2014 (1) Quote from discussion The study highlights that many symptomatic men and women currently receive treatment using an antibiotic primarily intended for treating chlamydia when this infection may not be present, and for which better treatments may be available.â&#x20AC;? â&#x20AC;&#x153;
The hazards of epidemiological treatment seem much the same as in Barlow and Phillips 1978.
Sex Transm Infect 2014;90:104-111 19th Academic sessions SLCV 2014
Herpes serology • 4-5% false positives for HSV2 serology (Raj Patel IUSTI Malta 2014, personal communication) • USA (CDC 2010) 16.2% (black 39.2%; white 12.3%) • Serology on black US gives 44% positive (40 + 4) • 9% will be false positives… • Serology on white US gives 16% positive (12 + 4) • 25% will be false-positives in USA… • UK prevalence (Kinghorn 2009) 8% • Serology on UK resident gives 12% positive (8 + 4) • 33% will be false-positives in UK…
19th Academic sessions SLCV 2014
NSU Over/under-diagnosis? But, how reliable is microscopy? Or, what will happen to Mr Jonesâ&#x20AC;&#x2122; marriage?
report -
pc/hpf
marriage okay??
0
+/1-9 ----------------------------------------------------------------------------------+ 10-19 ++ 20-29 +++ 30-39
David Barlow 16th Annual Sessions 2011
yes yes no no no
Variation in slide reading: same observer 4 observers - 52 slides
â&#x20AC;˘ Some difference â&#x20AC;˘ Significant difference
33.0% 16.8%
Willcox et al (1981) BJVD; 57: 134-6
David Barlow 16th Annual Sessions 2011
Variation in slide reading: different observer 4 observers - 52 slides â&#x20AC;˘ Some difference â&#x20AC;˘ Significant difference
61.0 36.5%
Willcox et al (1981) BJVD; 57: 134-6
David Barlow 16th Annual Sessions 2011
Guideline ‘opinion’ index..... (Andy Winter plenary ‘The known unknowns’, IUSTI Europe, Malta 2014) Proportion of statements 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0%
C: opinion B: study A: RCT
IUSTI Europe Guidelines 2014 (Andy Winter plenary ‘The known unknowns’, IUSTI Europe, Malta 2014) Statements
100 226
A: RCT B: study C: opinion
186
Nullius in Verba Motto of the Royal Society “Take no one's word for it”
19th Academic sessions SLCV 2014
Horseradish (Armoracia rusticana) The root fresh from the ground
The root fresh from the larder
19th Academic sessions SLCV 2014
Horseradish sauce (have you ever made it?)
Cookery sources •
•
•
• •
Modern Cookery for Private Families, Eliza Acton, Southover Press, 1845, p116; Mrs Beeton’s book of Household Management, Chancellor Press 1861, p214 Sociable Cook’s Book, ‘Bon Viveur’ (Fanny Cradock) Daily Telegraph 1967, p67 The Cookery Year, Reader’s Digest, 1973, p312 Larousse Gastronomique (English edition), Hamlyn 2001, p611
Instructions •
“wash and wipe a stick of young horseradish, scrape off the outer skin, grate it as small as possible with a fine grater, then…”
•
“Grate the horseradish and mix it well with sugar, salt, pepper, and mustard”
•
“This should be…simply washed, peeled horseradish root, grated and mixed with cream and freshly milled black pepper.”
•
”Peel and coarsely grate the horseradish.”
•
“Wear rubber gloves and hold the root submerged in a bowl of cold water while scrubbing and peeling it to reduce the irritation it causes to skin and eyes.”
19th Academic sessions SLCV 2014
Scandinavian a language lesson (1) Water • Swedish (SE)
‘vatten’
• Danish (DK)
‘vand’
• Norwegian (NO)
‘vann’
Scandinavian a language lesson (2) Cooking instructions ‘koktid’ • Swedish (SE) • Danish (DK)
‘kogetid’
• Norwegian (NO)
‘koketid’